Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Cancer of the lung lung neoplasm NSCLC - non-small cell lung cancer Nonsquamou squamous squamous NSCLC Tumor locally advanced NSCLC metastatic NSCLC advanced lung cancer metastatic lung cancer non-squamous NSCLC lung cancer Abraxane ABI-007 nab-paclitaxel albumin-bound paclitaxel taxanes CC-486 oral azacitidine azacitidine second line treatment of lung cancer second line treatment Celgene abound.2L third line treatment durvalumab immunotherapy MEDI4736
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 240
Healthy volunteers: no

Brief summary:
This is a Phase 2, open-label, multicenter study to assess the efficacy and safety of second/third-line treatment with nab-paclitaxel in combination with the epigenetic modifying therapy of CC-486 or immunotherapy of durvalumab, and nab-paclitaxel monotherapy in subjects with advanced non-small cell lung cancer (NSCLC).

Detailed description:
This Phase 2 study will test the hypothesis that epigenetic modifying therapy of CC-486 or immunotherapy of durvalumab can improve the anti-tumor activity of nab-paclitaxel in subjects with advanced non-small cell lung cancer (NSCLC) who have received no more than one prior chemotherapy regimen for their advanced disease. It will further assess efficacy and safety of nab-paclitaxel monotherapy in this setting. Each subject will receive study therapy as second- or third-line of treatment. Approximately 240 male and female subjects with advanced NSCLC will be assigned to one of the following treatment arms (approximately 80 subjects per group): nab-paclitaxel /CC-486 combination therapy, nab-paclitaxel/durvalumab combination therapy or nab-paclitaxel monotherapy prior to receiving first dose of Investigational Product. A permuted-block randomization method will be employed to assign the subjects among the treatment arms that are enrolling simultaneously, when applicable, stratified by the following baseline factors: ECOG performance status (0 versus 1), gender (males versus females), and smoker (yes versus no). Treatment assignments of subjects to the nab-paclitaxel/CC-486 combination therapy and nab-paclitaxel monotherapy arms will be conducted completely in a randomized fashion.

Arms:
arm 1: Subjects in the combination arm will receive nab-paclitaxel 100 mg\^/m2 intravenous (IV) infusion over 30 minutes on Days 8 and 15 and CC-486 200 mg orally daily (QD) on Days 1 to14 of each 21-day treatment cycle arm 2: Subjects in the monotherapy arm will receive nab-Paclitaxel 100 mg/m\^2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day treatment cycle arm 3: subjects in the nab-Paclitaxel/durvalumab combination arm will receive nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15 of each 21-day treatment cycle

Interventions: intervention 1: nab-paclitaxel IV intervention 2: CC-486 intervention 3: Duravalumab
Intervention descriptions: intervention 1: nab-Paclitaxel intravenous (IV) infusion intervention 2: Oral CC-486 intervention 3: None

Protocol document:
Prot_003.pdf: 
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
TITLE PAGE
A PHASE 2, OPEN-LABEL, MULTICENTER STUDY TO 
ASSESS SAFETY AND EFFICACY OF SECOND/THIRD-
LINE TREATMENT WITH NAB®-PACLITAXEL (ABI-
007) IN COMBINATION WITH EPIGENETIC 
MODIFYING THERAPY OF CC-486, OR 
IMMUNOTHERAPY OF DURVALUMAB (MEDI4736), 
OR AS MONOTHERAPY IN SUBJECTS WITH 
ADVANCED NON-SMALL CELL LUNG CANCER 
(NSCLC): ABOUND.2L+
INVESTIGATIONAL PRODUCTS:
CC-486, nab-Paclitaxel (ABI-007), 
durvalumab (MEDI4736)
PROTOCOL NUMBER:
ABI-007-NSCL-006
DATE FINAL:
29 May 2014
AMENDMENT 1.0 FINAL:
24 Jun 2014
AMENDMENT 2.0 FINAL:
18 Jul 2014
AMENDMENT 3.0 FINAL:
14 Apr 2016
EudraCT NUMBER
2014-001105-41
IND NUMBER
123160
SPONSOR NAME / ADDRESS:
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
United States
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board. The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations.
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them.
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information:
Name:
Title:
Address: 
86 Morris Avenue
Summit, NJ 07901
United States
Phone:
E-mail:
Contact Information:
Name:
Title:
Address: 
86 Morris Avenue
Summit, NJ 07901
United States
Phone:
E-mail:
Note: The back-up 24 hour global emergency contact call center should only be used if you 
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emergency calls.
Back-up 24 Hour Global Emergency Contact Call Center: 
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Confidential and Proprietary
3
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}.
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:_______________________________________
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
PROTOCOL SUMMARY
Study Title
A Phase 2, Open-label, Multicenter Study to Assess Safety and Efficacy of Second/Third-line 
Treatment with nab®-Paclitaxel1 (ABI-007) in Combination with Epigenetic Modifying Therapy 
of CC-486, or Immunotherapy of Durvalumab (MEDI4736), or as Monotherapy in Subjects with
Advanced Non-small Cell Lung Cancer (NSCLC): ABOUND.2L+
Indication
Second/third-line treatment of advanced NSCLC.
Objectives
Primary
!
To estimate the efficacy of nab-paclitaxel administered intravenously (IV) on Days 8 
and 15 with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 
14 every 21 days or nab-paclitaxel administered intravenously (IV) on Days 1 and 8
with immunotherapy of durvalumab administered IV on Day 15 every 21 days, and 
nab-paclitaxel monotherapy administered IV on Days 1 and 8 every 21 days as 
second/third-line treatment for advanced NSCLC.
Secondary 
!
To estimate the relative efficacy of each of the combination therapy arms to the 
monotherapy arm.
!
To evaluate the safety and tolerability of nab-paclitaxel administered intravenously 
(IV) on Days 8 and 15 with epigenetic modifying therapy of CC-486 once daily 
(QD) on Days 1 to 14 every 21 days, or nab-paclitaxel administered intravenously 
(IV) on Days 1 and 8 with immunotherapy of durvalumab administered IV on Day 
15 every 21 days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 
every 21 days as second/third-line treatment for advanced NSCLC.
Exploratory 
!
To assess healthcare resource utilization for the treatment arms.
!
To assess the quality of life (QoL) for the treatment arms.
!
To determine baseline tumor characteristics which predict response to nab-paclitaxel 
as a single agent and in combination with epigenetic modifying therapy of CC-486 or 
in combination with immunotherapy of durvalumab. 
!
To evaluate genomic correlates of response to nab-paclitaxel as a single agent and in 
combination with epigenetic modifying therapy of CC-486 or in combination with 
immunotherapy of durvalumab. 
                                               
1 nab® is a registered trademark of Celgene Corporation.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
!
To evaluate anti-tumor activity of nab-paclitaxel/durvalumab combination therapy 
using Investigator assessment according to immune related response criteria updated 
with RECIST 1.1 (irRECIST), and its association with PD-L1 expression.
Study Design
This is a Phase 2, open-label, multicenter study to assess efficacy and safety of:
o
nab-paclitaxel in combination with epigenetic modifying therapy of CC-486,
o
nab-paclitaxel in combination with immunotherapy of durvalumab, 
o
and nab-paclitaxel monotherapy 
as second/third-line treatment in subjects with advanced NSCLC who have received no more 
than one prior chemotherapy regimen. Approximately 240 subjects with advanced NSCLC will 
be assigned 1:1:1 into one of the following treatment arms: nab-paclitaxel /CC-486 combination 
therapy, nab-paclitaxel /durvalumab combination therapy or nab-paclitaxel monotherapy prior to 
receiving the first dose of investigational product (IP). Randomization/treatment assignment 
strategy of subjects to the three treatment arms is described in the Overview of Statistical 
Methods below and in Section 10.1. 
The study will consist of up to a 28-day Screening Period, a Treatment Period and a Follow-up 
Period.
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of IP.
The Treatment Period begins with the first dose of IP as described in Section 8.  Subjects will 
receive one of the following treatments based on the randomization/treatment assignment:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days  1 to 14 of each 21-day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 
durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15 of each 21-
day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the Investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, withdrawal of 
consent, or termination of the study by the Sponsor. Subjects in the nab-paclitaxel/durvalumab 
arm may continue treatment beyond disease progression per Response Evaluation Criteria in 
Solid Tumors (RECIST) guidelines, Version 1.1 as described in Section 4.1.2.1.
Tumor evaluations will be assessed by the investigative sites and response will be determined 
according to RECIST guidelines, Version 1.1 (Eisenhauer, 2009), and immune-related RECIST 
criteria (irRECIST) when applicable.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an adverse event (AE)/serious adverse event (SAE) and also recorded on the 
laboratory electronic Case Report Form (eCRF) (see Section 11.3).
All subjects who discontinue from treatment for any reason other than withdrawal of consent, 
lost to follow-up, death, or termination of the study by the sponsor will enter the Follow-up 
Period. It will consist of a visit 28 days after the last dose of IP or End of Treatment Visit, 
whichever is later. Thereafter, subjects in the nab-paclitaxel/CC-486 combination and nab-
paclitaxel monotherapy arms will be followed for survival by phone call contact approximately 
every 90 days (+/- 14 days) for at least 12 months after the last subject is randomized/assigned in 
either arm or 120 progression-free survival (PFS) events have been observed between these two 
arms, whichever comes later. Subjects in the nab-paclitaxel/durvalumab arm will be followed for 
survival in a similar manner for at least 12 months after the last subject is assigned to this arm.
During the study, subjects will have computed tomography (CT) scans every 42 days (-3/+7 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the Sponsor. Subjects in the nab-paclitaxel/durvalumab arm who 
continue beyond disease progression per RECIST 1.1 will continue to have CT scans every 42 
days (-3/+7) until progression per immune-related RECIST criteria (irRECIST 1.1) (Nishino, 
2013). Those subjects entering the Follow-up Period without documented progression will 
continue to have CT scans in accordance with local standard of care (or approximately every 90 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the Sponsor. All post-treatment anticancer therapies will be 
recorded during the Follow-up Period.  
Study Population
Male and female subjects with advanced NSCLC who have received no more than one prior
chemotherapy regimen for their advanced disease will be eligible for this study (immunotherapy 
in prior line of treatment is allowed, including platinum doublet combination). Subjects will 
receive study therapy as second or third line of treatment for advanced disease.
Length of Study
The enrollment of 240 subjects on this study will take approximately 28 months. The total length 
of this Phase 2 study with follow-up for survival is estimated to be approximately 40 months.
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, 
whichever is the later date.
Study Treatments
Subjects will receive nab-paclitaxel in combination with CC-486 or durvalumab, or nab-
paclitaxel monotherapy during the study. The CC-486, nab-paclitaxel, and durvalumab are
designated as IP and will be packaged and supplied by the Study Sponsor.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
9
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Overview of Statistical Methods
The primary objective of this study is to estimate the efficacy of the CC-486 and nab-paclitaxel 
combination therapy, that of the durvalumab and nab-paclitaxel combination therapy, and that of 
the nab-paclitaxel monotherapy. The secondary efficacy objective is to estimate the relative 
efficacy of each of the combination regimens to the monotherapy regimen and the tolerability of 
each of the 3 treatment regimens.  
Approximately 240 subjects will be assigned to one of the three treatment arms (approximately 
80 subjects per group).  A permuted-block randomization method will be employed to assign the 
subjects among the treatment arms that are enrolling simultaneously, stratified by the following 
baseline factors: ECOG performance status (0 versus 1), gender (males versus females), and 
smoker (yes versus no). Randomization/treatment assignment of subjects will be carried out 
centrally using an Interactive Response Technology (IRT) system. Prior to the time of Protocol 
Amendment 3.0, all subjects will be randomized 1:1 to the nab-paclitaxel/CC-486 combination 
therapy and nab-paclitaxel monotherapy arms. Once Protocol Amendment 3.0 is in effect, 
subjects from sites that are ready to implement the said amendment will be randomized 1:1:1 to 
the nab-paclitaxel/CC-486 combination therapy, nab-paclitaxel monotherapy, and nab-
paclitaxel/durvalumab combination therapy arms, respectively. Subjects from the remaining sites 
will continue to be randomized 1:1 to the nab-paclitaxel/CC-486 combination therapy and nab-
paclitaxel monotherapy arms.  Once approximately 80 subjects have been randomized to each of 
the nab-paclitaxel/CC-486 combination therapy and the nab-paclitaxel monotherapy arms, all 
incoming subjects will be assigned to the nab-paclitaxel/durvalumab combination therapy arm 
until approximately 80 subjects have been enrolled to receive the IP in that arm. Hence, 
treatment assignments of subjects to the nab-paclitaxel/CC-486 combination therapy and nab-
paclitaxel monotherapy arms will be in effect conducted completely in a randomized fashion. If 
the nab-paclitaxel/CC-486 arm stops after the interim analysis, incoming subjects will be 
randomized 2:1 to the nab-paclitaxel/durvalumab combination therapy and nab-paclitaxel 
monotherapy arms, respectively, until enrollment to the monotherapy arm is complete.  
Thereafter, subjects will be assigned to the nab-paclitaxel/durvalumab combination therapy arm 
until approximately 80 subjects have been enrolled in this arm.  
Evaluations of the study endpoints will be based primarily on the point estimates and the 
associated 95% confidence intervals of the within- and between-treatment differences (each 
combination therapy vs. monotherapy).
An independent Data Monitoring Committee (DMC) will be established to review the interim 
safety and efficacy data.  
Efficacy Analyses
The intent-to-treat population, which includes all randomized (or assigned) subjects regardless of 
whether the subject receives any IP or has any efficacy assessments performed, will be used for 
all efficacy analyses. The primary efficacy endpoint is PFS, which is defined as the time from the 
date of randomization/treatment assignment to the date of disease progression or death (from any 
cause) on or prior to the data cutoff date for analyses, whichever occurs first, based on the 
Investigator’s assessment of the data from CT scans using RECIST 1.1 guidelines. Baseline 
tumor measurements will be determined from the radiologic evaluation performed within 28 
days before the start of study therapy. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
10
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% confidence interval [CI]) for each treatment arm.  The relative 
treatment effect between each of the combination therapy and monotherapy arms with respect to 
PFS will be estimated by the hazard ratio (HR) and the associated two-sided 95% CIs using the 
stratified Cox proportional hazard model with ECOG performance status (0 versus 1), gender
(males versus females), and smoker (yes versus no) as the stratification factors. No statistical 
inferential tests will be performed. To explore the effect of treatment post initial progression, 
PFS defined by irRECIST criteria may be estimated for those subjects in the nab-
paclitaxel/durvalumab combination arm.  
The secondary endpoints include disease control rate (DCR), overall response rate (ORR), and 
overall survival (OS). Disease control rate and ORR will be summarized within each treatment 
arm by the observed rates and the associated 95% CIs. The relative treatment effect of each of 
the combination therapy arms to the monotherapy arm will be summarized by the ratio of the 
observed rates. Overall survival will be analyzed using similar statistical methods as that for the 
PFS endpoint.
Safety Analyses
The treated population, which includes all subjects who receive at least one dose of IP, will be 
the analysis population for all safety analyses. 
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AE or SAE occurring or worsening on or after the day of the first dose of the IP
through 28 days after the last dose of the last IP administration.  
In addition, any SAE with an onset date more than 28 days after the last dose of IP that is 
assessed by the Investigator as related to IP will be considered a TEAE. For the nab-
paclitaxel/durvalumab arm, AEs with an onset from 29 days up to 90 days after the last dose of 
any IP will be summarized separately.
Treatment-emergent adverse events, Grade 3 or higher TEAEs, SAEs, TEAEs leading to dose 
reduction, and dose interruption, TEAEs leading to treatment discontinuation, and TEAEs with 
an outcome of death will be summarized by treatment arms using MedDRA system organ class 
and preferred terms.
Sample Size
This study is designed primarily to estimate the treatment effect within each of the combination 
and monotherapy arms and secondarily the relative effect between each of the combination 
therapy and the monotherapy arms with respect to the primary and secondary efficacy endpoints. 
The sample size was chosen to support the estimation of the within- and between-treatment 
effects with reasonable precision. Table 1 below summarizes the precisions that can be achieved 
given different scenarios of hypothetical observed hazard ratios between the two treatment arms 
for PFS events, assuming a total of approximately 120 events are observed between two
treatment arms, and the time to PFS has an exponential distribution. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
11
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Table 1:
Progression-Free Survival – Two-sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms
Hypothetical Number of 
Events Observed
Hypothetical Observed Hazard 
Ratio of PFS Events
95% Confidence Interval of 
Hazard Ratioa
120
0.60
(0.42, 0.86)
0.65
(0.45, 0.93)
0.70
(0.49, 1.00)
a Assuming a standard error of 0.18 for the log hazard ratio.
Assuming the median times of PFS are 4.17, 4.25 and 2.5 months, respectively, for the nab-
paclitaxel/CC-486 combination therapy, the nab-paclitaxel/durvalumab combination therapy and 
nab-paclitaxel monotherapy arms, and an approximate 28 months accrual period for a total of 
approximately 240 subjects, it is estimated that an approximate total of 170 PFS events among 
the three arms will be observed by approximately 3 months after the last subject is assigned to 
the nab-paclitaxel/durvalumab arm, assuming an exponential distribution for PFS. 
One nonbinding interim analysis for PFS with early stopping rule for futility will be conducted 
when approximately 60 events have been observed between the nab-paclitaxel/CC-486 
combination and nab-paclitaxel monotherapy arms. An additional non-binding interim analysis 
for futility with early stopping rule with the PFS endpoint between the nab-
paclitaxel/durvalumab combination and nab-paclitaxel monotherapy arms will be conducted 
when approximately 30 PFS events have been observed in the nab-paclitaxel/durvalumab arm 
(60 or more events are expected to have occurred in the monotherapy arm at that point).
Data Monitoring Committee
An independent Data Monitoring Committee (DMC) will be established with the responsibilities 
for safeguarding the interests of study participants and monitoring the overall conduct of the 
study. Final recommendations of the DMC will reflect the judgment of the DMC members and 
will be considered advisory in nature to the Sponsor. The decision to implement the 
recommendations of the DMC will be made by the Sponsor, following consultation with the trial 
Coordinating Investigator and Steering Committee. A DMC charter will be established.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
12
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
1.
INTRODUCTION..................................................................................................19
1.1.
Non-small Cell Lung Cancer ..................................................................................19
1.2.
nab-Paclitaxel in NSCLC .......................................................................................20
1.3.
Rationale for nab-Paclitaxel as Second/Third-line Treatment in Subjects 
with Advanced NSCLC ..........................................................................................22
1.4.
Rationale for nab-Paclitaxel in Combination With Epigenetic Modifying 
Therapy of CC-486 as Second/Third-line Treatment in Subjects with 
Advanced NSCLC ..................................................................................................23
1.5.
Rationale for nab-Paclitaxel in Combination With Immunotherapy of 
Durvalumab as Second/Third-line Treatment in Subjects with Advanced 
NSCLC...................................................................................................................26
2.
STUDY OBJECTIVES...........................................................................................31
2.1.
Primary Objective...................................................................................................31
2.2.
Secondary Objective...............................................................................................31
2.3.
Exploratory Objectives ...........................................................................................31
3.
STUDY ENDPOINTS............................................................................................32
3.1.
Primary Endpoint....................................................................................................32
3.2.
Secondary Endpoints ..............................................................................................32
3.2.1.
Efficacy..................................................................................................................32
3.2.2.
Safety.....................................................................................................................32
3.3.
Exploratory Endpoints............................................................................................32
4.
OVERALL STUDY DESIGN ................................................................................33
4.1.
Study Design ..........................................................................................................33
4.1.1.
Screening Period.....................................................................................................33
4.1.2.
Treatment Period ....................................................................................................33
4.1.2.1.
Treatment Beyond Progression for Subjects in the nab-
Paclitaxel/Durvalumab Arm....................................................................................34
4.1.3.
End-of-Treatment Visit...........................................................................................34
4.1.4.
Follow-up Period....................................................................................................34
4.2.
Study Design Rationale ..........................................................................................35
4.3.
Study Duration .......................................................................................................38
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4.1.3
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1 4


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
13
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
4.4.
End of Trial ............................................................................................................38
5.
TABLE OF EVENTS.............................................................................................39
6.
PROCEDURES......................................................................................................43
6.1.
Medical History......................................................................................................43
6.2.
Prior and Concomitant Medications and Procedures ...............................................43
6.3.
Pregnancy Testing ..................................................................................................44
6.4.
Complete Chest Computed Tomography (CT) Scan................................................44
6.5.
Weight and Height..................................................................................................44
6.6.
ECOG Performance Score ......................................................................................44
6.7.
Peripheral Neuropathy Assessment.........................................................................45
6.8.
Adverse Event Reporting........................................................................................45
6.9.
Quality of Life Questionnaires................................................................................45
6.10.
Healthcare Resource Utilization Questionnaire .......................................................45
6.11.
Laboratory Assessments .........................................................................................45
6.12.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) .....................................................................................46
6.13.
Electrocardiogram ..................................................................................................47
6.14.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI) .......................47
6.15.
Bone Scans and X-rays...........................................................................................47
6.16.
Physical Examinations............................................................................................48
6.17.
Vital Signs..............................................................................................................48
6.18.
Survival..................................................................................................................48
7.
STUDY POPULATION.........................................................................................49
7.1.
Number of Subjects and Sites .................................................................................49
7.2.
Inclusion Criteria....................................................................................................49
7.3.
Exclusion Criteria...................................................................................................50
8.
DESCRIPTION OF STUDY TREATMENTS........................................................54
8.1.
Description of Investigational Products...................................................................54
8.1.1.
nab-Paclitaxel.........................................................................................................54
8.1.2.
CC-486 (Azacitidine for Oral Administration) ........................................................54
8.1.3.
Durvalumab (MEDI4736).......................................................................................54
8.1.4.
Monitoring During/After Durvalumab Infusion ......................................................55
8.2.
Treatment Administration and Schedule .................................................................56
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3


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
14
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
8.3.
Dose Omissions and Modifications.........................................................................56
8.3.1.
Rules for Dose Omissions and Modified Schedules ................................................56
8.3.2.
Rules for Dose Modifications .................................................................................58
8.4.
Method of Treatment Assignment...........................................................................62
8.5.
Packaging and Labeling..........................................................................................62
8.6.
Investigational Product Accountability and Disposal ..............................................62
8.7.
Investigational Product Compliance........................................................................63
8.8.
Overdose ................................................................................................................63
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................64
9.1.
Permitted Concomitant Medications and Procedures...............................................64
9.2.
Prohibited Concomitant Medications and Procedures..............................................65
9.3.
Required Concomitant Medications and Procedures for Subjects Receiving 
CC-486...................................................................................................................65
9.3.1.
Description of G-CSF.............................................................................................66
9.3.2.
Administration of G-CSF........................................................................................66
10.
STATISTICAL ANALYSES..................................................................................67
10.1.
Overview................................................................................................................67
10.2.
Study Population Definitions ..................................................................................68
10.2.1.
Intent-to-treat Population........................................................................................68
10.2.2.
Per-protocol (PP) Population ..................................................................................68
10.2.3.
Treated Population..................................................................................................68
10.3.
Sample Size and Power Considerations...................................................................68
10.4.
Background and Demographic Characteristics........................................................71
10.5.
Subject Disposition.................................................................................................71
10.6.
Efficacy Analysis....................................................................................................72
10.6.1.
Primary Efficacy Endpoints....................................................................................72
10.6.2.
Secondary Efficacy Endpoints ................................................................................73
10.6.2.1.
Disease Control Rate ..............................................................................................73
10.6.2.2.
Overall Survival .....................................................................................................73
10.6.2.3.
Overall Response Rate............................................................................................73
10.6.3.
Exploratory Endpoints............................................................................................73
10.6.3.1.
HealthCare Utilization............................................................................................73
10.6.3.2.
Quality of Life Questionnaires................................................................................73
2
.......63
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6


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
15
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
10.6.3.3.
Biomarker, Tumor Characteristics, and Genomic Analyses.....................................73
10.6.3.4.
Anti-tumor Activity and PD-L1 Expression (nab-Paclitaxel/Durvalumab 
Arm).......................................................................................................................73
10.7.
Safety Analysis.......................................................................................................74
10.7.1.
Adverse Events.......................................................................................................74
10.7.2.
Laboratory Assessments .........................................................................................74
10.7.3.
IP Exposure............................................................................................................74
10.8.
Study Therapy Termination ....................................................................................75
10.9.
Deaths ....................................................................................................................75
10.10.
Interim Analysis .....................................................................................................75
10.11.
Data Monitoring Committee ...................................................................................75
10.12.
Scientific Steering Committee ................................................................................75
11.
ADVERSE EVENTS..............................................................................................76
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................76
11.2.
Evaluation of Adverse Events.................................................................................77
11.2.1.
Seriousness.............................................................................................................77
11.2.2.
Severity / Intensity..................................................................................................78
11.2.3.
Causality ................................................................................................................78
11.2.4.
Duration .................................................................................................................79
11.2.5.
Action Taken..........................................................................................................79
11.2.6.
Outcome.................................................................................................................79
11.3.
Abnormal Laboratory Values..................................................................................79
11.4.
Pregnancy...............................................................................................................80
11.4.1.
Females of Childbearing Potential ..........................................................................80
11.4.2.
Male Subjects.........................................................................................................80
11.5.
Reporting of Serious Adverse Events......................................................................80
11.5.1.
Safety Queries ........................................................................................................81
11.6.
Expedited Reporting of Adverse Events..................................................................81
11.7.
Definition of Adverse Events of Special Interest .....................................................82
12.
DISCONTINUATIONS .........................................................................................83
12.1.
Study Treatment Discontinuation............................................................................83
12.2.
Study Discontinuation ............................................................................................83
12.3.
Subject Replacement ..............................................................................................84
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
16
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
13.
EMERGENCY PROCEDURES.............................................................................85
13.1.
Emergency Contact.................................................................................................85
13.2.
Emergency Identification of Investigational Products .............................................85
14.
REGULATORY CONSIDERATIONS...................................................................86
14.1.
Good Clinical Practice............................................................................................86
14.2.
Investigator Responsibilities ...................................................................................86
14.3.
Subject Information and Informed Consent.............................................................87
14.4.
Confidentiality........................................................................................................87
14.5.
Protocol Amendments.............................................................................................87
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................87
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................88
14.8.
Closure of the Study ...............................................................................................88
15.
DATA HANDLING AND RECORDKEEPING.....................................................89
15.1.
Data/Documents .....................................................................................................89
15.2.
Data Management...................................................................................................89
15.3.
Record Retention....................................................................................................89
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................91
16.1.
Study Monitoring and Source Data Verification......................................................91
16.2.
Audits and Inspections............................................................................................91
17.
PUBLICATIONS ...................................................................................................92
18.
REFERENCES.......................................................................................................93
19.
APPENDICES........................................................................................................98
Appendix A:
ECOG Performance Status Score.......................................................................98
Appendix B:
Recommendations for Management of Treatment-Induced Diarrhea..................99
Appendix C:
Treatment Modification and Toxicity Management for nab-Paclitaxel 
/Durvalumab arm..................................................................................................100
&(/*(1(35235,(7$5<,1)250$7,21
6
.......87
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
17
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
LIST OF TABLES
Table 1:
Progression-Free Survival – Two-sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms..............................11
Table 2:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat 
Population).............................................................................................................21
Table 3:
Data for Control Arms using Taxanes from Phase II and III Studies Blinded ..........36
Table 4:
Table of Events.......................................................................................................39
Table 5:
Requirements for Collection Based on Archival Tumor Sample Type.....................46
Table 6:
Permanent Dose Reductions for Hematologic and Nonhematologic 
Toxicities and Dosing on the Study.........................................................................61
Table 7:
Disease Control Rate –Two-Sided 95% Confidence Interval of Hypothetical 
Disease Control Rate with a Sample Size of 80 Subjects in a Treatment Arm .........69
Table 8:
Progression-Free Survival – Two-Sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms..............................69
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
18
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
LIST OF FIGURES
Figure 1:
Anti-PD-L1 in Combination with Platinum-Based Doublets ...................................29
Figure 2:
Overall Study Design..............................................................................................37
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
19
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer
Lung cancer is the leading cause of cancer-related deaths among men and women worldwide, 
with 1.2 million new cases diagnosed each year. Non-small cell lung cancer (NSCLC) is the 
most common type of lung cancer, accounting for 80% of all new cases. There are an estimated 
1.1 million lives lost per year (approximately 500,000 in the United States [US] and European 
Union [EU] alone) due to NSCLC. Smoking is the causative factor for up to 85% of cases 
(http://www.lungcancercoalition.org/en/pages/about/awareness).
The majority of patients are not diagnosed until the tumor has progressed beyond the primary 
site. Despite step-wise advances in patient selection, targeted agents, and optimizing
chemotherapy regimens, patients with advanced NSCLC continue to have an unmet medical 
need (Schiller, 2013).
Platinum-containing chemotherapy regimens remain (eg, platinum-based agents with taxanes) 
the standard first-line treatment in the US and Japan. In the EU, a third-generation 
chemotherapeutic agent (docetaxel, gemcitabine, paclitaxel, or vinorelbine), most commonly 
gemcitabine or vinorelbine, plus a platinum drug is used for advanced NSCLC (NICE, 2011). 
For first-line therapy in patients with Stage IV NSCLC and good performance status, the 
American Society of Clinical Oncology (ASCO) clinical practice guideline recommends 
treatment with a platinum-based two-drug combination of cytotoxic drugs (Azzoli, 2009). For 
patients without disease progression, the option of maintenance monotherapy with pemetrexed or 
erlotinib could also be considered (Gerber, 2013; Schiller, 2013). A trend that is becoming more 
prevalent is personalized NSCLC treatment based on tumor histology (squamous versus
nonsquamous), on molecular characteristics of the tumor, and on the patient’s clinical status 
using agents targeting specific receptors, kinases and pathways (ie, epidermal growth factor 
receptor [EGFR], echinoderm microtubule-associated protein-like 4 [EML4] and anaplastic 
lymphoma kinase [ALK] fusion protein).
Single agent chemotherapy (pemetrexed, EGFR-inhibitors and taxanes) are standards of care for 
second-line treatment of patients with locally advanced or metastatic NSCLC after failure of 
prior platinum-based chemotherapy. Docetaxel has been widely evaluated in this setting, and is 
currently approved by the US Food and Drug Administration (FDA) and the European 
Medicines Agency (EMA) as a single agent for the treatment of patients with locally advanced or 
metastatic NSCLC after failure of prior chemotherapy  (the US label specifies prior platinum-
based chemotherapy). For patients with a good performance status at the time of disease 
progression following first-line chemotherapy, docetaxel, despite a low response rate, was
associated with a 10% to 20% prolongation of 1-year survival and an improved quality of life 
when compared with ifosfamide, vinorelbine, or best supportive care (BSC) alone (Hanna, 
2004). Erlotinib is indicated in the US and EU for the treatment of patients with locally advanced 
or metastatic NSCLC after failure of at least one prior chemotherapy regimen, although no 
survival benefit has been demonstrated in patients with EGFR-IHC negative tumors.  
Pemetrexed is indicated in the US and EU as a single agent for the treatment of patients with 
locally advanced or metastatic nonsquamous NSCLC after prior chemotherapy. However, the 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
20
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
approval and subsequent increased use of pemetrexed and erlotinib in the first-line setting poses 
an unmet need in the second-line setting, whereby new therapeutic options are needed.
Recently, nintedanib, a triple angiokinase inhibitor, was approved in the European Union (EU) in 
combination with docetaxel as second-line therapy for NSCLC. The results showed that 
compared to docetaxel alone, nintedanib plus docetaxel significantly extended the median OS 
from 10.3 to 12.6 months for patients with advanced adenocarcinoma, after first-line 
chemotherapy (p = 0.0359; hazard ratio [HR]: 0.83) (Reck, 2014a). In addition, ramucirumab 
was approved in the US in combination with docetaxel as second-line therapy. The Phase 3 
REVEL trial compared ramucirumab, a vascular endothelial growth factor (VEGFR)-2 
antagonist, plus docetaxel with placebo plus docetaxel in NSCLC patients who experienced 
disease progression after treatment with platinum-based chemotherapy for locally advanced or 
metastatic disease. Median OS was better in the ramucirumab group than in the placebo group 
(10.5 vs 9.1 months; HR, 0.857; p = .0235), as was median progression-free survival (PFS) (4.5 
vs 3.0 months; HR, 0.762; p < .0001) (Garon, 2014).
More recently, advances in immunotherapy have seen approvals of nivolumab (US and EU) and 
pembrolizumab (US) in the advanced NSCLC setting after prior chemotherapy. In this setting,
nivolumab has shown benefit in overall survival with 9.2 months (95% CI, 7.3 to13.3) versus 6.0 
months (95% CI, 5.1 to 7.3) with docetaxel in advanced squamous NSCLC (Checkmate 017 
study) (Brahmer, 2015), and 12.2 months (95% CI, 9.7 to 15.0) versus 9.4 months (95% CI, 8.1 
to 10.7) with docetaxel (HR 0.73; 95% CI, 0.59 to 0.89; p = 0.002) in nonsquamous disease
(Checkmate 057 study) (Borghaei, 2015). However, PFS benefit was modest (3.5 months with 
nivolumab versus 2.8 months with docetaxel (HR 0.62; 95% CI, 0.47 to 0.81; p <0.001) or did 
not favor nivolumab in these populations. Regarding its safety profile, nivolumab is most 
commonly associated with immune-related adverse reactions. Most of these including severe 
reactions resolved following initiation of appropriate medical therapy, or withdrawal of 
nivolumab. In the pooled dataset of two studies in squamous NSCLC, the most frequent adverse 
reactions were fatigue (33%), decreased appetite (15%), and nausea (12%). The majority of 
adverse reactions were mild to moderate (Grades 1 or 2) (Opdivo® Prescribing Information). In
comparison, the efficacy of pembrolizumab was investigated in a sub-group of a cohort of 280 
patients enrolled in a multicenter, open-label multi-cohort, activity-estimating study which 
showed an overall response rate (ORR) of 41% (95% CI, 29 to 54) in both squamous and 
nonsquamous subjects. Serious adverse reactions occurred in 38% of patients receiving 
pembrolizumab and the most frequent reported in at least 2% of patients were pleural effusion, 
pneumonia, dyspnea, pulmonary embolism, and pneumonitis (Keytruda® Prescribing 
Information).
Similarly and as will be described below, the PD-L1 inhibitor durvalumab has demonstrated 
encouraging clinical activity both as a monotherapy and in combination with other agents 
including standard chemotherapies in metastatic melanoma, NSCLC and other advanced solid 
tumors, with acceptable and manageable reported toxicities.
1.2.
nab-Paclitaxel in NSCLC
nab-Paclitaxel is approved in the first-line setting in combination with carboplatin for patients 
with NSCLC in the US, EU, Japan, Argentina, Australia, New Zealand and other countries.  The 
approval was based on the evaluation of Phase I and II data (Belani, 2008; Rizvi, 2008; Socinski, 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
21
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
2010), as well as the pivotal Phase 3 study (CA031), (Socinski, 2012). The pivotal Phase 3 study 
was a multicenter, randomized, open-label study conducted in 1052 chemo-naïve subjects with 
Stage IIIB/IV NSCLC to compare nab-paclitaxel in combination with carboplatin to paclitaxel 
injection in combination with carboplatin as first-line treatment in patients with advanced 
NSCLC. nab-Paclitaxel was administered as an IV infusion over 30 minutes at a dose of 
100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel injection was administered as 
an IV infusion over 3 hours at a dose of 200 mg/m2, following premedication. In both treatment 
arms carboplatin at a dose of area under the curve (AUC) = 6 mg*min/mL was administered IV
on Day 1 of each 21-day cycle after completion of nab-paclitaxel/paclitaxel infusion. Treatment 
was administered until disease progression, development of an unacceptable toxicity or patient 
withdrawal. The primary efficacy outcome measure was overall response rate (ORR) as
determined by a central independent review committee using RECIST guidelines (Version 1.0).
In the intent-to-treat (all-randomized) population, the median age was 60 years, 75% were men, 
81% were white, 49% had carcinoma/adenocarcinoma, 43% had squamous cell lung cancer, 76% 
were ECOG performance status (PS) 1, 15% were ≥70 years of age and 73% were current or 
former smokers. Patients received a median of 6 cycles of treatment in both study arms. Patients 
in the nab-paclitaxel/carboplatin arm had a statistically significantly higher overall response rate 
compared to patients in the paclitaxel injection/carboplatin arm [(33% versus 25%;response rate 
ratio, 1.313; 95% CI, 1.082 to 1.593; p = 0.005), see Table 2].
Non-inferiority analysis of overall survival (OS) demonstrated that nab-paclitaxel/carboplatin
(nab-p/C) treatment is not inferior to paclitaxel/carboplatin (P/C) treatment. Overall survival in 
the nab-paclitaxel arm was 12.1 months versus 11.2 months in the control arm (p = 0.271; HR = 
0.922). There was an approximately 10% increase in PFS in the nab-p/C versus P/C arm and PFS 
in the nab-p/C arm was noninferior to PFS in the P/C arm (HRnab-p/C/P/C 95% CI upper bound, 
1.086).
Table 2:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat
Population)
Variable
Category/Statistic
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carboplatin
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Response Rate 
Ratio
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p-value
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132 (25%)
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170 (33%)
131 (25%)
PA/PT: response rate of nab-paclitaxel/response rate of paclitaxel.
a 95% CI of response rate and 95.1% CI of response rate ratio.
* Indicates p-value < 0.049.
Note: p-value is based on a chi-square test.
Source: Data on File.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
22
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Adverse events (AEs) were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. The following common (≥ 10% incidence) AEs
were observed at a similar incidence in nab-paclitaxel/carboplatin and paclitaxel/carboplatin
arms: alopecia 56%, nausea 27%, fatigue 25%, decreased appetite 17%, asthenia 16%, 
constipation 16%, diarrhea 15%, vomiting 12%, dyspnea 12%, and rash 10% (incidence rates are 
for the nab-paclitaxel plus carboplatin treatment group). Toxicities, particularly neuropathy and 
Grade 3/4 neutropenia were less pronounced using nab-paclitaxel in the dose and schedule 
employed. Laboratory-detected abnormalities which occurred with a difference ≥5% for nab-
paclitaxel plus carboplatin versus paclitaxel injection plus carboplatin (Grades 1 to 4 [and Grade 
3/4]) were: anemia (98% vs 91% [28% vs 7%]), neutropenia (85% vs 83% [47% vs 58%]) and 
thrombocytopenia (68% vs 55% [18% vs 9%]).  
1.3.
Rationale for nab-Paclitaxel as Second/Third-line Treatment in
Subjects with Advanced NSCLC
Patients who fail first-line chemotherapy are eligible for second-line treatment with single agent 
docetaxel, pemetrexed or erlotinib. In patients with good performance (eg, ECOG PS 0 or 1) and 
general health status, further treatment with chemotherapy is an important consideration that has 
been shown to extend overall survival. Despite the availability of second-line therapy, the trend 
of increased use of pemetrexed, as well as erlotinib (in selected patients) in the first-line and 
maintenance settings, potentially limits the number of available second-line treatment options for 
many patients. Furthermore, the tolerability issues associated with the administration of 
docetaxel once every 3 weeks (q3w) has prompted active research in the past decade to evaluate 
whether weekly regimens of taxanes could be optimized to improve the toxicity profile. The 
availability of an effective second-line cytotoxic chemotherapy with an improved efficacy/safety
profile over current available options would be a valuable addition for both the patient and the 
treating physician. Paclitaxel has also demonstrated potential activity in second-line NSCLC in a 
few studies (Socinski, 1999; Juan, 2002; Socinski, 2002; Sculier, 2002; Buccheri, 2004; Ceresoli, 
2004; Yasuda, 2004). More recently, advances in immunotherapy have seen increased use of 
immune checkpoint inhibitors (eg, nivolumab, pembrolizumab) in the first and/or second-line 
setting for advanced NSCLC disease. 
nab-Paclitaxel exhibits 10-fold higher mean Cmax of free paclitaxel, delivers 33% higher drug 
concentration to tumors in preclinical xenograft models, and demonstrates enhanced transport 
across endothelial cell monolayers, when compared with paclitaxel (Desai, 2006; Gardner, 
2008). Distribution of nab-paclitaxel to peripheral tissues as demonstrated in a recent study was 
4-fold faster and 10-fold more extensive than of Cremophor EL-paclitaxel micelles, which 
results in a unique and distinct profile of paclitaxel in tissues (Li, 2015). The Cremophor EL-free 
medium enables nab-paclitaxel to be given over a shorter duration without the need for 
premedication to prevent solvent-related hypersensitivity reactions, thus also avoiding negative 
impact of steroids on paclitaxel induced apoptosis and decreased antitumoral activity of 
chemotherapeutic agents as reported in pre-clinical models glucocorticoids (Abraxane®
Prescribing Information; Zavodovskaya, 2015; Herr, 2003; Sui, 2006; Khan, 2013; Pang, 2006).
When administered with carboplatin in the first-line setting, weekly nab-paclitaxel has 
demonstrated a more favorable efficacy:safety profile compared to the every 3 weeks schedule.  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
23
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
This weekly schedule of nab-paclitaxel allows the opportunity for closer (ie, shorter interval)
monitoring of side effects and optimizing dose-intensity through timely adjustments.  
Finally, recently published data has demonstrated efficacy of nab-paclitaxel as monotherapy in 
the second line setting in advanced NSCLC with ORR ranging from 16.1% to 33% and a median 
PFS of up to 5 months (Chen, 2012; Saxena, 2012; Yuan, 2012).  
Rationale for dose and schedule
As previously noted, nab-paclitaxel 100 mg/m2 weekly (Days 1, 8 and 15) in combination with 
carboplatin (21 day cycle) is approved in the US, EU, Japan, Argentina, Australia, New Zealand 
and other countries for the treatment of locally advanced or metastatic NSCLC in the first-line 
setting.  However, there is limited data of monotherapy nab-paclitaxel in the second or third-line 
setting; hence, this study will assess the efficacy and tolerability of weekly nab-paclitaxel, when 
administered on Days 1 and 8 of each 21-day cycle.  The allowance of a one week rest period in 
this study (ie, no treatment on Day 15), takes into account research findings from other taxanes, 
whereby patients in the second-line setting are unlikely to tolerate the same dose-intensity 
compared to chemo-naïve patients (eg, sharper dose reduction in the second-line setting). 
Therefore, the proposed nab-paclitaxel schedule (2 weeks treatment, 1 week rest) could offer the 
option of maintaining consistent dose-intensity for NSCLC patients in this setting.
1.4.
Rationale for nab-Paclitaxel in Combination With Epigenetic 
Modifying Therapy of CC-486 as Second/Third-line Treatment in 
Subjects with Advanced NSCLC
CC-486 is an orally bioavailable formulation of the nucleoside analog 5-azacitidine (AZA).  
After its incorporation into a cell’s DNA during the S-phase of the cell cycle, CC-486 forms 
covalent adducts with DNA Methyltransferase 1 (DNMT1) and depletes this enzyme required for 
the maintenance of DNA methylation patterns, thereby altering the epigenetic status of the cell. 
Epigenetic changes are covalent modifications of chromatin (DNA and histone proteins) that 
mediate the stable transmission of a gene’s transcriptional status through cell division.  One of 
the first recognized epigenetic alterations in cancer was DNA methylation.  The addition of a 
methyl group to cytosine in the dinucleotide CpG is catalyzed by DNA methyltransferases 
(DNMTs) and is associated with transcriptional repression of genes with high density of CpGs 
(CpG islands) in the vicinity of their promoters (Jones, 2007).  Genomic methylation patterns are 
precisely regulated during normal embryonic development and differentiation and have been 
found to be altered in specific ways in cancer. Specifically, cancer cell genomes are typified by 
reduced methylation globally with focal areas of aberrant hypermethylation in the CpG islands of 
genes encoding known tumor suppressors such as PTEN and BRCA1 as well as genes encoding 
proteins required for apoptosis, including caspase 8, DAPK and Apaf-1.  DNA methylation-
based silencing can thus contribute to the establishment and maintenance of the transformed state 
and limit the effectiveness of anti-cancer therapies.  The recognition of the role of aberrant 
methylation in carcinogenesis and its reversibility has led to the development of DNMT 
inhibitors for cancer. Subcutaneous (SC) AZA was the first DNMT inhibitor to be approved in 
myelodysplastic syndromes (MDS) in 2004 (Kaminskas, 2005).
The notion that sequential treatment with an epigenetic modifying agent followed by a cytotoxic
agent can result in improved response to the latter is supported by numerous preclinical 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
24
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
experiments and now by early clinical results.  In breast cancer cell lines, restoring expression of 
the aberrantly methylated pro-apoptotic gene TMS1 with azacitidine can restore taxane 
sensitivity (Gordian, 2009).  In a model of platinum resistant ovarian cancer, azacitidine reversed 
resistance to carboplatin (Li, 2009).  This effect required pretreatment of the cells with 
noncytotoxic levels of azacitidine for 24 hours before the addition of carboplatin and was not 
observed with concurrent exposure to both agents.  More recently, Juergens and colleagues 
observed an unusually high ORR of approximately 20% in multiple-relapsed NSCLC patients 
treated with a variety of regimens after being treated with a combination of SC AZA and another 
epigenetic agent, entinostat, a histone deacetylase inhibitor (Juergens, 2011).  In one case, a 
patient who had previously progressed on a regimen of paclitaxel, carboplatin and bevacizumab 
responded to the same triplet after treatment with SC AZA and entinostat, suggesting that the 
epigenetic modifying agents had reversed acquired resistance to the cytotoxic/anti-angiogenic 
regimen.  In a Phase 1/2 study of SC AZA with nab-paclitaxel in subjects with advanced 
metastatic solid tumors and breast cancer (Dumlao, 2011), escalating doses of SC AZA (75 to
100 mg/m2) were administered on Days 1 through 5, followed by nab-paclitaxel (100 mg/m2) 
intravenous (IV) on Days 8, 15, and 22 of a 28-day cycle.  Of 16 subjects treated at the time of 
publication, clinical activity has included 3 complete responses (CR, 1 Diffuse Large B-cell 
Lymphoma [DLBCL], 2 ovarian), 4 partial responses (PR) in ovarian and endometrial cancer 
and 4 stable diseases (SD, 2 lung, 1 pancreatic, and 1 sarcoma).  
CC-486 entered clinical testing in 2006 in subjects with MDS, chronic myelomonocytic 
leukemia [CMML], and acute myeloid leukemia [AML], with daily extended dosing schedules 
of 14 and 21 out of 28 days in a non-crossover fashion.  Daily doses of 300 mg CC-486 have 
proven to be tolerated on both the 14 and 21 out of 28-day schedules with myelosuppression, 
gastrointestinal symptoms, and fatigue being the most common toxicities (Garcia-Manero, 
2011).  Subjects treated with CC-486 for 14 or 21 days had DNA hypomethylation that persisted 
through the end of cycle.  This contrasts with the lack of persistent hypomethylation at the end of 
cycle when subjects were treated with SC AZA for 7 out of 28 days. 
 
 
 
  
 
 
 
 
 
 
 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
25
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
 
  
 
 
 
 
 
 
 
This Phase 2 study will test the hypothesis that epigenetic modifying therapy with CC-486 can 
improve the anti-tumor activity of nab-paclitaxel in second/third-line NSCLC patients (see 
Section 4.2 for study rationale). Although docetaxel has been assessed in other randomized 
studies as a chemotherapy backbone, the considerable neutropenia-related toxicity could 
potentially pose safety concerns if combined with CC-486, and the steroid premedication could 
confound the epigenetic impact of CC-486.  In addition, the q3w dosing schedule of docetaxel 
restricts dose adjustment options, thus potentially yielding lower chemotherapy dose-intensity.
Please refer to the Investigator’s Brochures (IBs) of CC-486 and nab-paclitaxel (ABI-007) for 
detailed information concerning the available pharmacology, toxicology, drug metabolism, 
clinical studies, and adverse event profile of the IPs.
 
 
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
26
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
1.5.
Rationale for nab-Paclitaxel in Combination With Immunotherapy 
of Durvalumab as Second/Third-line Treatment in Subjects with 
Advanced NSCLC
Durvalumab 
Durvalumab is a human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa 
subclass that inhibits binding of PD-L1 to PD-1 and CD80 and is being developed by 
AstraZeneca/MedImmune for use in the treatment of cancer.  (MedImmune is a wholly owned 
subsidiary of AstraZeneca; AstraZeneca/MedImmune will be referred to as AstraZeneca 
throughout this document.)  As durvalumab is an engineered mAb, it does not induce antibody-
dependent cellular cytotoxicity or complement-dependent cytotoxicity.  The proposed 
mechanism of action for durvalumab is interference of the interaction of PD-L1 with PD-1 and 
CD80.
To date durvalumab has been given to more than 1900 patients as part of ongoing studies either 
as monotherapy or in combination with other anti-cancer agents.  Refer to the current 
durvalumab Investigator’s Brochure for a complete summary of non-clinical and clinical 
information including safety, efficacy and pharmacokinetics.  
A Phase 2 trial of durvalumab is currently ongoing to assess efficacy and safety of the immune 
checkpoint inhibitor (dose of 10 mg/kg once every two weeks [q2w]) in patients with locally 
advanced or metastatic NSCLC in the third-line setting (Rizvi, 2014) (ATLANTIC trial, 
NCT02087423). 
 
 
 
Preliminary data of an open-label Phase 1b study of durvalumab 20 mg/kg every 4 weeks plus 
tremelimumab 1 mg/kg in immunonaive patients with advanced or metastatic squamous or non-
squamous NSCLC showed a manageable tolerability profile, with antitumor activity irrespective 
of PD-L1 status (ORR 22%, 95% CI 9-44) (Antonia, 2016).  
 
 
 
 
 
 
 
 
 
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
27
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
nab-Paclitaxel in combination with immune checkpoint inhibitors
Tumor lysis as a consequence of chemotherapy treatment leads to release of tumor antigens, 
which in turn are recognized by the immune system, thus priming the immune system for 
checkpoint inhibitor activity (Bracci, 2014; Chen, 2013; Mellman, 2011). Accumulating 
evidence suggests that immune activation plays an important role in chemotherapy efficacy
(Zitvogel, 2013). In addition to increasing tumor antigenicity, chemotherapy also reduces tumor 
burden and acts directly on immune cell populations, activating dendritic cells, depleting 
immunosuppressive regulatory T cells at low doses, depleting myeloid-derived suppressor cells, 
and increasing tumor-infiltrating lymphocytes (Tanaka, 2009; Banissi, 2009; Kodumudi, 2010; 
Dieci, 2014). Taxanes have been shown to facilitate dendritic cell maturation and cytokine 
secretion (Chen, 2013a). In patients with lung cancer, paclitaxel was associated with generation
of pro-inflammatory markers, including interleukin 2 and interferon gamma, and the expression 
of T cell activation markers (Zhang, 2008). Taxanes have been demonstrated to modulate the 
immune system by impairing regulatory T cells, which are drivers of peripheral tolerance, but 
not effector T cells, which are drivers of tumor-cell killing (Tanaka, 2009). Taxanes are also 
known to act on myeloid cells such as myeloid-derived suppressor cells and alternatively 
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
28
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
differentiated (M2) macrophages to decrease their immunosuppressive functions (Kodumudi, 
2010).
The data above suggest a potential for synergistic activity of cytotoxic therapy, such as taxanes, 
with checkpoint inhibitors, including those that target PD-1 or PD-L1.  nab-Paclitaxel has 
demonstrated cytotoxic activity in non-small cell lung cancer (overall response rate = 33% vs 
25% with paclitaxel in a Phase III trial) (Socinski, 2012) and, as stated above, does not require 
steroid pretreatment, which may make it a logical choice for combination with immune 
checkpoint inhibitor.
Therefore, this Phase 2 study will further assess the potential synergistic activity of nab-
paclitaxel, a cytotoxic agent, in combination with the anti-PD-L1 checkpoint inhibitor 
durvalumab in second/third-line treatment for advanced NSCLC, from an efficacy and safety 
standpoint.  The current study will allow patients who progress on prior checkpoint inhibitor 
therapy (eg, as their first-line or second-line therapy) as it is hypothesized that the companion 
chemotherapy of nab-paclitaxel may re-sensitize the disease to allow patient to respond to 
checkpoint inhibitors.
!
nab-Paclitaxel in combination with anti-PD-L1
More recently, preliminary results of an ongoing Phase 1b trial in first line metastatic NSCLC of
another immune checkpoint anti-PD-L1 inhibitor, atezolizumab, showed high response rates in 
combination with the following platinum-based doublets: 60 % (95% CI: 15-95) in the 
carboplatin/paclitaxel cohort (Arm C; n = 5), 75% (95% CI: 43-95) in the 
carboplatin/pemetrexed arm (Arm D; n=14), and 62 % (95% CI: 32-86) with four patients 
experiencing complete response when atezolizumab was combined with carboplatin/nab-
paclitaxel regimen (Arm E; n=13) (Liu, 2015). The most frequent AEs included nausea (Arms C 
and D, 50%; Arm E, 73%), fatigue (Arm C, 38%; Arm D, 36%; Arm E, 73%) and constipation 
(Arm C, 25%; Arm D, 71%; Arm E, 27%). The most common MPDL3280A-related Grades 3 to 
4 AEs included anemia (Arms D and E, 7%), neutropenia (Arm C, 13%; Arm D, 7%) and 
thrombocytopenia (Arms D and E, 7%). No pneumonitis was seen. One MPDL3280A-related 
Grade 5 AE due to candidemia after prolonged neutropenia was seen in Arm D. Thirty patients
were efficacy evaluable (Arm C, 5; Arm D, 12; Arm E, 13). Overall, treatment with 
atezolizumab plus chemotherapy (including maintenance therapy) was well tolerated, without 
apparent exacerbation of chemotherapy-associated adverse events.
 
 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
29
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Figure 1:
Anti-PD-L1 in Combination with Platinum-Based Doublets
Liu et al. ASCO- June 2015. Abstract 8030
!
nab-Paclitaxel in combination with anti-PD-1
An ongoing Celgene-sponsored Phase 1 trial (NCT02309177) in solid tumors is assessing the 
safety and efficacy of the anti-PD-1 agent nivolumab in combination with nab-paclitaxel and
carboplatin in a cohort of subjects with advanced NSCLC patients in the first-line setting (nab-
paclitaxel 100 mg/m2 on Days 1, 8 and 15 and carboplatin AUC 6 on Day 1 of each 21-day cycle 
(Cycles 1 to 4 only); nivolumab 5 mg/kg on Day 15 of each 21-day cycle starting in Cycle 1). 
Preliminary results show that amongst the 9 subjects having received study treatment including 
nivolumab, 6 had partial responses and 3 stable disease. No dose limiting toxicities were 
observed. Most common AEs were low grade vomiting, diarrhea, alopecia, peripheral 
neuropathy and neutropenia (data on file). These results are consistent with another Phase 1 trial 
comparing anti-PD-1 antibody nivolumab (10 mg/kg IV q3w) combined with three different 
platinum-doublet regimens in 52 patients with chemotherapy-naïve advanced NSCLC, with a
reported ORR of 33% with gemcitabine/cisplatin, 47% with pemetrexed/cisplatin, as well as with 
paclitaxel/carboplatin, while stable disease was reported in 58%, 47%, and 27% of subjects, 
respectively (Checkmate 012; NCT01454102); (Antonia, 2014). Grades 3 to 4 treatment-related 
adverse events were reported in 45% of patients (25% to 73% across arms), including 
pneumonitis (4 patients, 7%; managed by protocol algorithm), and fatigue and acute renal failure 
(3 patients, 5% each).
Rationale for fixed dose and schedule 
 
 
 
 
 
 
 
 
 
  Similarly, a population PK model 
was developed for tremelimumab using data from Phase 1 through Phase 3 (N=654; doses= 0.01 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
30
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
to 15 mg/kg q4w or once every 90 days (Q90D); metastatic melanoma) (Wang, 2014). A 
population PK model indicated minor impact of body WT on the PK of tremelimumab 
(coefficient of ≤ 0.5). The WT-based (1 mg/kg q4w) and fixed dosing (75 mg/kg q4w; based on 
median body WT of ~75 kg) regimens were compared using predicted PK concentrations (5th, 
median and 95th percentiles) using a population PK model in a simulated population of 1000 
patients with body WT distribution of 40 to 120 kg. Similar to durvalumab, simulations indicated 
that both body WT-based and fixed dosing regimens of tremelimumab yield similar median 
steady state PK concentrations with slightly less between-subject variability with fixed dosing 
regimen.
Similar findings have been reported by others (Ng, 2006; Wang, 2009; Zhang, 2012; Narwal,
2013). Wang and colleagues investigated 12 monoclonal antibodies and found that fixed and 
body size-based dosing perform similarly, with fixed dosing being better for 7 of 12 antibodies 
(Wang, 2009). In addition, they investigated 18 therapeutic proteins and peptides and showed 
that fixed dosing performed better for 12 of 18 in terms of reducing the between-subject 
variability in PK/PD parameters (Zhang, 2012). 
A fixed dosing approach is preferred by the prescribing community due to ease of use and 
reduced dosing errors. Given the expectation of similar PK exposure and variability, it is 
considered feasible to switch to fixed dosing regimens.
Sequential administration of chemotherapy and checkpoint inhibitor will allow for limitation of 
potential interactions and better management of toxicities.
Please refer to the Investigator’s Brochures (IBs) of durvalumab and nab-paclitaxel (ABI-007) 
for detailed information concerning the available pharmacology, toxicology, drug metabolism, 
clinical studies, and adverse event profile of the investigational products (IPs).
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
31
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
2.
STUDY OBJECTIVES
2.1.
Primary Objective 
The primary objective of the study is:
!
To estimate the efficacy of nab-paclitaxel administered intravenously (IV) on Days 8 
and 15 with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 
14 every 21 days, or nab-paclitaxel administered intravenously (IV) on Days 1 and 8
with immunotherapy of durvalumab administered IV on Day 15 every 21 days, and 
nab-paclitaxel monotherapy administered IV on Days 1 and 8 every 21 days as 
second/third-line treatment for advanced NSCLC.
2.2.
Secondary Objective
The secondary objective of the study is:
!
To estimate the relative efficacy of each of the combination therapy arms to the 
monotherapy arm.
!
To evaluate the safety and tolerability of nab-paclitaxel administered IV on Days 8 
and 15 with epigenetic modifying therapy of CC-486 QD on Days 1 to 14 every 21 
days, or nab-paclitaxel administered intravenously (IV) on Days 1 and 8 with 
immunotherapy of durvalumab administered IV on Day 15 every 21 days, and nab-
paclitaxel monotherapy administered IV on Days 1 and 8 every 21 days as 
second/third-line treatment for advanced NSCLC.
2.3.
Exploratory Objectives
The exploratory objectives of the study are:
!
To assess healthcare resource utilization for the treatment arms.
!
To assess the quality of life (QoL) for the treatment arms.
!
To determine baseline tumor characteristics which predict response to nab-paclitaxel 
as a single agent and with epigenetic modifying therapy of CC-486 or immunotherapy 
of durvalumab. 
!
To evaluate genomic correlates of response to nab-paclitaxel as a single agent and 
with epigenetic modifying therapy of CC-486 or immunotherapy of durvalumab.
!
To evaluate anti-tumor activity of nab-paclitaxel/durvalumab combination therapy 
using investigator assessment according to immune related response criteria updated 
with RECIST 1.1 (irRECIST), and its association with PD-L1 expression.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
32
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
3.
STUDY ENDPOINTS
Study efficacy endpoints will be assessed by the Investigator using RECIST 1.1 guidelines.
3.1.
Primary Endpoint
The primary endpoint is:
!
Progression free survival.
3.2.
Secondary Endpoints
The secondary endpoints are: 
3.2.1.
Efficacy
!
Disease control rate.
!
Overall response rate.
!
Overall survival.
3.2.2.
Safety
!
The type, frequency, and severity of AEs and SAEs graded using National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, 
Version 4.0). 
!
Discontinuation rate.
!
The median dose intensity.
!
The incidence of dose reduction.
3.3.
Exploratory Endpoints
!
Healthcare resource utilization during the study via patient feedback.
!
Changes in the Lung Cancer Symptom Scale (LCSS), European Organisation for 
Research and Treatment of Cancer (EORTC) QLQ C30, and EuroQoL 5D-5L (EQ-
5D-5L).
!
The correlation between pretreatment tumor characteristics and response to the study 
treatment determined using next-generation sequencing methods, 
immunohistochemistry, or other analysis methods.
!
Analysis of PFS and DCR and their association with PD-L1 expression using 
Investigator’s assessments according to irRECIST. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
33
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is a Phase 2, open-label, multicenter study to assess safety and efficacy of:
!
nab-paclitaxel in combination with epigenetic modifying therapy of CC-486,
!
nab-paclitaxel in combination with immunotherapy of durvalumab, 
!
and nab-paclitaxel monotherapy 
as second/third-line treatment in subjects with advanced NSCLC who have received no more 
than one prior chemotherapy regimen. Approximately 240 subjects with advanced NSCLC will 
be assigned 1:1:1 into one of the following treatment arms: nab-paclitaxel/CC-486, nab-
paclitaxel/durvalumab combination therapy or nab-paclitaxel monotherapy prior to receiving the 
first dose of investigational product (IP). Randomization (details in Section 10.1), when 
conducted, will be centralized and stratified by ECOG performance status (0 versus 1, see 
Appendix A), gender (males versus females), and smoker (yes versus no).
The study will consist of up to a 28-day Screening Period, a Treatment Period and a Follow-up 
Period.  
4.1.1.
Screening Period 
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of IP.
4.1.2.
Treatment Period 
The Treatment Period begins with the first dose of IP as described in Section 8.  Subjects will 
receive one of the following treatments based on the randomization/treatment assignment:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 
durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15 of each 21-
day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle.
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the Investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, withdrawal of 
consent, or termination of the study by the Sponsor.
During the study, subjects will have computed tomography (CT) scans every 42 days (-3/+7 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
34
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
or termination of the study by the Sponsor. Tumor evaluations will be assessed by the 
investigative sites and response will be determined according to RECIST 1.1 guidelines, and 
immune-related RECIST criteria (irRECIST) when applicable. All scheduled laboratory samples 
will be sent to a central laboratory for analysis. Local hematology and chemistry tests may be 
performed as required for subject management/treatment decisions. Local laboratory values that 
are considered abnormal and clinically significant will be recorded as an AE/SAE and also 
recorded on the laboratory eCRF (see Section 11.3).
4.1.2.1.
Treatment Beyond Progression for Subjects in the nab-Paclitaxel/Durvalumab 
Arm
Subjects in the nab-paclitaxel/durvalumab arm may be permitted to continue treatment beyond 
initial RECIST 1.1 defined progressive disease as long as they meet the following criteria:
!
Continue to meet all other study protocol eligibility criteria
!
Investigator assessed clinical benefit and absence of rapid disease progression or 
clinical deterioration
!
Stable performance status
!
Tolerance to IP
!
Treatment beyond progression will not delay an imminent intervention to prevent
serious complications of disease progression (eg, brain metastases)
Subjects will be re-consented with an informed consent document describing any reasonably 
foreseeable risks or discomforts and other alternative treatment options.
Response assessment should continue every 42 days (-3/+7 days) as per Table of Events
(Table 4). The assessment of clinical benefit should be balanced by clinical judgment as to 
whether the subject is clinically deteriorating and unlikely to receive any benefit from continued 
treatment with nab-paclitaxel/durvalumab. If the Investigator feels that the subject continues to 
achieve clinical benefit by continuing treatment and the subject consents, the subject may remain 
on the trial and will continue to receive monitoring according to the schedule in the Table of 
Events. The decision to continue treatment should be discussed with the Sponsor’s Medical 
Monitor and documented in the study source documents.
Study therapy should be discontinued if further progression is documented by irRECIST. 
4.1.3.
End-of-Treatment Visit
The End-of-Treatment Visit is defined as the visit when decision for treatment discontinuation is 
made. 
4.1.4.
Follow-up Period
All subjects who discontinue from treatment for reasons other than withdrawal of consent, lost to 
follow-up, death, or termination of the study by the Sponsor will enter the Follow-up Period. It 
will consist of a visit 28 days after last dose of IP or End-of-Treatment Visit, whichever is later,
followed by phone follow-up for survival approximately every 90 days (+/- 14 days) for at least
12 months after the last subject is randomized or 120 PFS events have been observed, whichever 
b 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
35
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
comes later, between the nab-paclitaxel/CC-486 combination and nab-paclitaxel monotherapy 
arms. Subjects in the nab-paclitaxel/durvalumab arm will also attend a follow-up visit 90 days 
after the last dose of IP, and will be followed for survival in a similar manner for at least 12 
months after the last subject is assigned to this arm. Those subjects entering the Follow-up 
Period without documented progression will continue to have CT scans in accordance with local 
standard of care (or approximately every 90 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death, or termination of the study by the Sponsor. All 
post-treatment anticancer therapies will be recorded during the Follow-up Period.  
4.2.
Study Design Rationale
This is an open-label study designed to estimate the effects of adding CC-486 or durvalumab to 
nab-paclitaxel and nab-paclitaxel monotherapy in second/third-line NSCLC. A placebo-
controlled study would not be feasible for this population as blinding would be difficult and 
would need a double dummy design.  
A key objective in this study is to determine the chemo-priming effect of CC-486 and to estimate 
the effect of the combination of nab-paclitaxel with PD-L1 checkpoint inhibitor. Second/third-
line NSCLC enables a unique setting to evaluate epigenetics: 
a) It is currently unknown whether patients in second or later lines of treatment have 
optimal immune function/reserve which is critical for safety and activation of immune 
cells that target cancer cells,
b) Due to the overlapping (and dose-limiting) toxicities of doublet/triplet chemotherapy 
regimens in the first-line setting, it would be very challenging to combine epigenetic 
therapy at a dose level to elicit clinically meaningful benefit.
Although docetaxel has been assessed in other randomized studies as a chemotherapy backbone
as shown in Table 3, the considerable neutropenia-related toxicity could potentially pose safety 
concerns if combined with CC-486, and the steroid premedication could confound the epigenetic 
impact of CC-486.  In addition, the q3w dosing schedule of docetaxel restricts dose adjustment 
options, thus potentially yielding lower chemotherapy dose-intensity. As mentioned above, nab-
paclitaxel has shown benefit for both squamous and nonsquamous histologies. Furthermore, 
recent data with immune checkpoint inhibitors (eg, nivolumab) have shown greater efficacy in 
subjects with squamous histology versus nonsquamous histology with manageable toxicities. 
Hence it will be important in the current study to assess the efficacy and safety of nab-paclitaxel 
either as monotherapy or in combination treatment in subjects with squamous and nonsquamous 
NSCLC histologies.
For patients with NSCLC whose disease progressed after initial chemotherapy, the goal of 
therapy is to delay further progression for as long as possible; hence, the use of PFS as the 
primary endpoint for efficacy evaluation.  
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CC-48
-486 an
inhibitor
inhibitor
ter lines of
er line
r safet
safe y y and
an
xixicicities of
ties o
i
d
f
be ver
be ve y y cha
cha
y meaningf
meaning
her random
her random
eutropenia
utropeni
and the ster
nd the s
e q3w dosin
e q3w dosin
ng l
g lower ch
ower ch
for both sq
for both sq
checkpo
checkpoint
s histol
s hist ogy
gy
portant in th
rtant in t
erapy
erapy o
y r in 
r in
logies
gies.
ts wi
with
th
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mary
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endpo


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
36
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Table 3:
Data for Control Arms using Taxanes from Phase II and III Studies Blinded
Study compound
(year)
Doce
(Shepherd, 
2000)
Doce
(Hanna, 
2004)
nab-Pac
(Chen  
2012, 
Saxena, 
2012, 
Yuan 
2012)
Doce
(Reck, 
2014a)
LUME-1
Doce
(Garon, 
2014)
Doce
(Brahmer, 
2015)
Checkmate 
017 
Doce
(Borghaei, 
2015)
Checkmate 
057
Doce 
(Vansteenkiste, 
2015)
POPLAR
Phase
III
III
II
III
III
III
III
II
N
55 + 48
288
16 (x2) -  
33
272
625
137
290
143
Efficacy
ORR (%)
7.1
8.8
18 - 33
3.3
14
9
12
15
SD rate (or DCR)
(%)
42.7
46.4
31  -  42
37.9
53
34
33
n/a
PFS (TTP)
(median, in 
months)
na
2.9
2.1 – 5.0
2.7
3.0
2.8
4.2
3.0
OS (median, in 
months)
7.0
7.9
n/a
9.1
9.1
6.0
9.4
9.7
Toxicity
Neutropenia (%)
Neutrophils 
decreased (%)
67.3
40.2
n/a
12.1
29.9
39
33
31
n/a
Febrile 
neutropenia
1.8
12.7
n/a
4.7
10
11
10
n/a
Thrombocytopenia 
(%)
0
0.4
3
NR
1
n/a
n/a
n/a
Anemia (%)
5.5
4.3
3
3.5
6
22
20
n/a
Peripheral 
Neuropathy (%)
1.8
1.1
3
NR
2
12
n/a
n/a
Fatigue / Asthenia 
(%)
18.2
5.4
3
5.1
10*
46.5
46.6
n/a
DCR = disease control rate; Doce = docetaxel; nab-Pac = nab-paclitaxel; N = number of subjects randomized; n/a = not 
available; ORR = overall response rate; OS = overall survival; PFS = progression free survival; SD = standard deviation; TTP =
time to progression; *Grade ≥ 3
Furthermore, maintaining quality of life during this period, especially in reducing/managing 
toxicity is also an important consideration.  Therefore, the proposed study is designed to 
optimize the evaluation of efficacy with a tolerable dose/schedule of chemotherapy, and its 
combination with an epigenetic modifying therapy or with an immune checkpoint inhibitor.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
37
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Figure 2:
Overall Study Design
IP = investigational product; IV = intravenous; OS = overall survival; PFS = progression-free survival; QD = once daily.
nab-paclitaxel 100 mg/m2 IV 
infusion over 30 minutes on 
Days 1 and 8 of each 21-day 
cycle until disease progression
(n = 80)
o
nab-paclitaxel 100 mg/m2 IV 
infusion over 30 minutes on Days 
1 and 8 of each 21-day cycle 
o
durvalumab 1125 mg IV over 
approximately 1 hour on Day15 
of each 21-day cycle
until disease progression
(n = 80)
Follow-up Period: 28-day Follow-up Visit (after last dose of IP or End-of-Treatment Visit, whichever is later)
Monotherapy or CC-486 combination arms: followed for OS by phone approximately every 90 days for at least 12 months after last subject is randomized 
in either the monotherapy arm or the CC-486 combination arm or 120 PFS events have been observed, whichever is later
nab-paclitaxel/durvalumab arm: 90-Day Follow-up Visit and  consequent follow-up for OS by phone approximately every 90 days for at least 12 months 
after last subject is allocated to this arm
o
nab-paclitaxel 100 mg/m2  IV 
infusion over 30 minutes on Days 
8 and 15 of each 21-day cycle
o
CC-486 200 mg orally QD
     Days 1 to 14 of each 21-day
cycle
until disease progression
(n = 80)
Screening for Eligibility (up to 28 days)
(n=240)
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
38
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
4.3.
Study Duration 
Recruitment is expected to take approximately 28 months, and the final analysis of PFS between 
the nab-paclitaxel/CC-486 combination and nab-paclitaxel monotherapy arms will be performed 
when approximately 120 PFS events have occurred, estimated as approximately 25 months from 
first subject randomized. The final analysis for the nab-paclitaxel/durvalumab arm will be 
conducted when approximately 50 events have occurred in this arm. The total length of this 
Phase 2 study with follow-up is estimated to last approximately 40 months.
4.4.
End of Trial
The End of Trial is defined as either the:
!
date of the last visit of the last subject to complete the post-treatment follow-up, or 
!
date of receipt of the last data point from the last subject that is required for primary, 
secondary and/or exploratory analysis, as prespecified in the protocol, whichever is 
the later date.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
5.
TABLE OF EVENTS
Table 4:
Table of Events
Screening/ 
Baseline
Treatment Period
Every 21-day Cycle
Follow-Up Period
Assessment
Day -28 to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu
-ation Visit
28-day Follow-up 
Visit (after last 
dose of IP)
90-day Follow-up 
Visit for subjects in 
the nab-paclitaxel/ 
durvalumab arm
(after last dose of IP)
Survival Follow-upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
Informed Consent
X
-
-
-
-
-
-
-
-
Medical History (including Tobacco 
Exposure History), Prior Medication 
and Procedures
X
-
-
-
-
-
-
-
-
Serum β-hCG b
X
-
-
-
-
-
-
-
-
Urine Pregnancy Testb
-
X
-
-
-
X
X
(nab-paclitaxel/ 
durvalumab arm)
X
(nab-paclitaxel/ 
durvalumab arm)
-
Reminder to Avoid Pregnancyb
X
-
-
-
X
X
X
-
Complete Chest CT Scan and Any 
Other Studies Required for Tumor 
Imagingc
X
-
-
-
X
Xc
-
-
X
Weight and Heightd
X
X
X
X
-
-
-
-
-
ECOG Status
X
X
-
-
-
X
X
X
-
Concomitant Medication/Procedures
-
X
X
X
-
X
X
X
X
Peripheral Neuropathy Assessmente
X
X
-
-
-
X
X
-
-
Healthcare Resource Utilization 
Questionnaire
-
X
-
-
-
X
X
-
-
LCSS, EORTC QLQ C30 and EQ-
5D-5L
-
X
-
-
-
X
X
-
-
Hematologyf,g
X
X
X
X
-
X
X
Xk
-
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
40
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Table 4:
Table of Events (Continued)
Screening/ 
Baseline
Treatment Period
Every 21-day Cycle
Follow-Up Period
Assessment
Day -28 to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu
-ation Visit
28-day Follow-up 
Visit (after last 
dose of IP)
90-day Follow-up 
Visit for subjects in 
the nab-paclitaxel/ 
durvalumab arm 
(after last dose of IP)
Survival Follow-upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
Serum Chemistryf,h
X
X
-
-
-
X
X
Xk
-
Archived Tumor Tissue Sample for 
Biomarker (biopsy, surgical 
specimen, or other diagnostic tumor 
sample)
-
X
(C1D1 
only)
-
-
-
-
-
-
-
Plasma for Biomarker Analyses
-
X
(C1D1 only 
predose)
-
-
-
-
-
-
-
Blood for Pharmacogenomic 
Analyses
-
X
(C1D1 only 
predose)
-
-
-
-
-
-
-
Adverse Event Evaluation in the 
Monotherapy or nab-Paclitaxel/CC-
486 Combination Arm
After signing ICF and until 28 days after the last dose of IP
-
-
Adverse Event Evaluation in the nab-
Paclitaxel/Durvalumab combination
Arm
After signing ICF and until 90 days after the last dose of IP
X
-
nab-PaclitaxelMonotherapy Arm and   
nab-Paclitaxel/Durvalumab
Combination Arm
nab-Paclitaxel Administration/
Accountabilityi
-
X
X
-
-
-
-
-
nab-Paclitaxel/CC-486 Combination 
Arm
nab-Paclitaxel Administration/
Accountabilityi
-
-
X
X
-
-
-
-
-
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
41
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Table 4:
Table of Events (Continued)
Screening/ 
Baseline
Treatment Period
Every 21-day Cycle
Follow-Up Period
Assessment
Day -28 to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu
-ation Visit
28-day Follow-up 
Visit (after last 
dose of IP)
90-day Follow-up 
Visit for subjects in 
the nab-paclitaxel/ 
durvalumab arm 
(after last dose of IP)
Survival Follow-upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
nab-Paclitaxel/CC-486 Combination 
arm
CC-486 Administration/
Accountabilityi
-
X
-
-
-
-
-
nab-Paclitaxel/Durvalumab
Combination Arm
Durvalumab Administration/
Accountabilityi
-
-
-
X
-
-
-
-
-
Survival Phone Call
-
-
-
-
-
-
-
-
Xa
Physical Examinationj
X
X
-
-
-
X
-
-
-
Vital Signsj
X
X
X
X
-
X
-
-
-
Electrocardiogram (ECG)
X
Will be done as per standard of care during the Treatment Period and as clinically indicated; however, results will not be routinely 
collected in the eCRFs. If CT/bone scans show lesions pertinent for RECIST 1.1 or irRECIST criteria evaluation, data will be 
collected on the pertinent tumor evaluation eCRFs. If ECGs are abnormal and clinically significant, the data will be recorded on the 
AE/SAE eCRF.
Bone Scan (X-rays if needed)
If clinically 
indicated
CT Scan of the Head or Brain 
Magnetic Resonance Imaging (MRI)
If clinically 
indicated 
(mandatory if 
symptomatic)
AE = adverse event; β-HCG = beta human chorionic gonadotropin; C1D1 = Cycle 1 Day 1; CT = computed tomography; ECOG = Eastern Cooperative Oncology Group; eCRF =
electronic Case Report Form; EORTC QLQ C30 = European Organisation for Research and Treatment of Cancer QLQ C30; EQ-5D-5L = EuroQol 5D-5L; ICF = informed 
consent form; IP = investigational product; irRECIST = immune-related Response Evaluation Criteria in Solid Tumors; IV = intravenous; LCSS = Lung Cancer Symptom Scale;
QD = once daily; RECIST = Response Evaluation Criteria in Solid Tumors; SAE = serious adverse event.
a Every 90 (+/-14) days (from 28-day Follow-up Visit ) for at least 12 months after the last subject is randomized in either the monotherapy or the CC-486 combination arms or 
120 PFS events have been observed whichever comes later. Subjects in the nab-paclitaxel/durvalumab arm will be followed for survival in a similar manner for at least 12 
months after the last subject is assigned to this arm.
b All males and all women of child-bearing potential must be reminded to avoid pregnancy prior to administration of IP before beginning each new cycle, at the End-of-Treatment 
Visit and at the Follow-up Visits. A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a serum β-hCG pregnancy test 
must be performed to assess eligibility at Screening/Baseline. Note: the screening serum pregnancy test can be used as the Cycle 1 Day 1 test prior to study therapy if it is 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
42
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
performed within the 72-hour timeframe.  A urine pregnancy test must be performed prior to administration of IP before beginning each new cycle and at the End-of-Treatment 
Visit for all subjects, and at the Follow-up Visits for subjects in the nab-paclitaxel/durvalumab arm.
c All subjects must have a radiographically documented measurable tumor(s) by RECIST 1.1 criteria: Complete chest CT scan (including base of neck and adrenal gland) will be 
performed at Screening, every 42 days (-3/+7 days) (starting from Cycle 1 Day 1) until disease progression, withdrawal of consent, lost to follow-up, death, or termination of the 
study by the Sponsor. The results of a complete chest CT scan (including base of neck and adrenal gland) performed per standard of care may be accepted and not repeated 
during Screening provided it was performed within 28 days of the first dose of IP (Cycle 1 Day 1). The methods of assessment chosen at baseline to follow tumors are to remain 
consistent throughout study duration. Those subjects entering the Follow-up Period without documented progression will continue to have CT scans in accordance with local 
standard of care (or approximately every 90 days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, or termination of the study by the 
Sponsor.  If the CT scan was performed within 2 weeks of the End-of-Treatment Visit, this End-of-Treatment Visit CT scan will not need to be repeated. Subjects in the nab-
paclitaxel/durvalumab arm who continue beyond disease progression per RECIST 1.1 will continue to have CT scans every 42 days (-3/+7) until progression per immune-related 
RECIST criteria (irRECIST) version 1.1 (Nishino, 2013).
d Height will only be obtained at Screening Visit. Weight will be obtained at Screening and every visit during the Treatment Period before administration of IP.
e The occurrence of peripheral neuropathy will be reported by the Investigator per protocol as an AE or SAE.
f All scheduled laboratory samples will be sent to a central laboratory for analysis. Local hematology and chemistry tests may be performed as required for subject 
management/treatment decisions. Local laboratory values that are considered abnormal and clinically significant will be recorded as an AE/SAE and also recorded on the 
laboratory eCRF (see Section 11.3).
g Hematology panel: hemoglobin, hematocrit, red blood cell count and morphology, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin 
concentration, white blood cell count with absolute and differential and percent (neutrophils, lymphocytes, monocytes, eosinophils, basophils, bands), platelet count, 
reticulocytes, erythrocyte sedimentation rate, international normalized ratio, prothrombin time, partial thromboplastin time, and fibrinogen. Additional laboratory samples for 
safety may be collected as clinically indicated.
h Serum chemistry panel: sodium, potassium, bicarbonate, calcium, magnesium, phosphorus, blood urea nitrogen, serum creatinine and clearance, uric acid, glucose, lactic
dehydrogenase, total protein, albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, total, direct and indirect 
bilirubin, ferritin, amylase, lipase, thyroid stimulating hormone (TSH), T4, free T3, and free T4. Additional laboratory samples for safety may be collected as clinically indicated.
i nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 200 mg orally QD on Days 1 to14 of each 21-day treatment cycle; nab-paclitaxel 
100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day treatment cycle; or nab-paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and
durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15.
j Physical examination and vital signs assessment should be performed prior to IP administration at these visits. Additional physical examination and vital signs assessments may 
be performed throughout the study as clinically indicated. Only abnormal and clinically significant physical examination data and/or vital signs will be recorded as an AE/SAE 
on the eCRF. Vital signs will be (at a minimum): blood pressure, heart rate, respiratory rate, body temperature.
k Hematology panel, serum chemistry will be performed at the 90-day Follow-up Visit for subjects in the nab-paclitaxel/durvalumab arm if applicable following AEs or abnormal 
assessments findings during the 28-day Follow-up Visit.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
43
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
6.
PROCEDURES
Subjects will be provided with a written Informed Consent Form (ICF), given the opportunity to 
ask any questions concerning the study and will sign an ICF prior to participating in any study 
procedures. After giving written informed consent, subjects will undergo a Screening Period to 
be assessed for eligibility. All subjects who sign an ICF must be entered into the Integrated 
Response Technology (IRT) immediately upon signature on the document. Subjects who do not 
meet the eligibility criteria will be considered screening failures and will not be eligible for the 
study. Subjects who fail initial screening may undergo re-screening up to 2 times at any time 
and an ICF will need to be resigned, as well as all screening procedures repeated (some 
procedures may not need to be done if previously done within 28 days prior to screening again).
Subjects that have met all eligibility criteria after the Screening Period will be eligible for
randomization /treatment assignment. 
6.1.
Medical History
A complete medical history including, but not limited to, evaluation for past (up to 5 years) or
present cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine,
lymphatic, hematological, immunologic, dermatological, psychiatric, genitourinary, obstetrical, 
surgical history or any other diseases or disorders will be performed at Screening. All NSCLC-
related medical history should be recorded regardless of time. Smoking status/tobacco exposure 
history will be captured on the eCRF.
6.2.
Prior and Concomitant Medications and Procedures
Prior medications are defined as any medications started before randomization/treatment
assignment. All NSCLC-related prior medications/procedures should be recorded regardless of 
time.
Concomitant medications are defined as any medication that was either initiated before 
randomization/treatment assignment and continued during the study treatment, or initiated 
on/after the date of randomization/treatment assignment and within 28 days after the last dose of 
IP for the monotherapy arm and the nab-paclitaxel/CC-486 combination arms, or 90 days after 
last dose of IP in the nab-paclitaxel/durvalumab combination arm. 
All subjects will have concomitant medications and procedures (including radiation therapy) 
recorded at each visit from the time of signature on the ICF until the 28-day Follow-up Visit for 
the monotherapy arm and the nab-paclitaxel/CC-486 combination arms or 90 days after last dose 
of IP in the nab-paclitaxel/durvalumab combination arm, for conditions that are clinically 
significant or ongoing. During the Follow-up Period only NSCLC-associated concomitant 
medications/procedures (including radiation therapy) will be recorded, ie, subsequent-line(s) of 
anti-cancer therapy. Additionally, for laboratory procedures performed per standard of care 
during follow-up, laboratory values that are considered abnormal and clinically significant will 
be recorded as an AE/SAE and also recorded on the laboratory eCRF.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
44
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
6.3.
Pregnancy Testing
All males and all women of child-bearing potential must be reminded to avoid pregnancy prior to 
administration of IP before beginning each new cycle, at the End-of-Treatment Visit and at the 
Follow-up Visits. A pregnancy test is required for women of child-bearing potential only. For 
women of child-bearing potential a serum β-hCG pregnancy test with sensitivity of at least 25
mIU/mL must be performed to assess eligibility at Screening/Baseline. Note: the screening 
serum pregnancy test can be used as the Cycle 1 Day 1 test prior to study therapy if it is 
performed within the 72-hour timeframe.  A urine pregnancy test must be performed prior to 
administration of IP before beginning each new cycle and at the End-of-Treatment Visit for all 
subjects, and at the Follow-up Visits for subjects in the nab-paclitaxel/durvalumab arm. The 
subject may not receive treatment until the Investigator has verified that the result of the 
pregnancy test is negative. See inclusion criteria for pregnancy testing requirements. Any 
pregnancies that occur in women who have received IP must be immediately reported to Celgene 
Drug Safety (See Section 11.4).
6.4.
Complete Chest Computed Tomography (CT) Scan
A complete chest CT scan (including base of neck and adrenal gland) and any other studies 
required for tumor imaging will be done at Screening, every 42 days (-3/+7 days) (starting from 
Day 1 Cycle 1), and End-of-Treatment, until documented progression of disease, withdrawal of 
consent, lost to follow-up, death, or termination of the study by the Sponsor. The results of a 
complete chest CT scan (including base of neck and adrenal gland) performed per standard of 
care may be accepted and not repeated during Screening provided it was performed within 28 
days of the first dose of IP (Cycle 1 Day 1). Those subjects entering the Follow-up Period 
without documented progression will continue to have CT scans in accordance with local 
standard of care (or approximately every 90 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death, or termination of the study by the Sponsor. If the 
CT scan was performed within 2 weeks of End-of-Treatment Visit, this End-of-Treatment CT 
scan will not need to be repeated. Additional CT scans may be done at any time during the study 
if clinically indicated. All CT scans and reports should be archived at the site according to site 
regulations and copies provided to the Sponsor if requested. All post-treatment anticancer 
therapies will be recorded during the Follow-up Period.  
6.5.
Weight and Height
Weight will be obtained at Screening and at every visit during the Treatment Period before 
administration of IP. Additional measurements of weight may be collected per local standards at 
any time during the study as needed. Height will only be collected at Screening. All weight and 
height data will be collected on eCRFs.
6.6.
ECOG Performance Score
Eastern Cooperative Oncology Group performance status score will be collected at Screening, 
Day 1 of every treatment cycle, at the End-of-Treatment Visit and at the Follow-up Visits. 
Additional ECOG assessments may be performed at any time during the study as clinically 
indicated.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
45
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
6.7.
Peripheral Neuropathy Assessment
Peripheral neuropathy (sensory or motor) assessment will be done at Screening, Day 1 of every 
treatment cycle, at the End-of-Treatment Visit and at the 28-day Follow-up Visit. Changes in 
neuropathy grade from baseline will be reported as an AE as per Section 11. Additional 
peripheral neuropathy assessments may be done at any time during the study as clinically 
indicated.
6.8.
Adverse Event Reporting
Adverse events will be recorded from time of signature on the ICF until 28 days after the last 
dose of IP for the monotherapy and the nab-paclitaxel/CC-486 combination arms and until 90 
days after the last dose of IP for the nab-paclitaxel/durvalumab combination arm during the 
Follow-up Visits, including any unscheduled visits. See Section 11 for details. 
6.9.
Quality of Life Questionnaires
The LCSS, EORTC QLQ C30 and EQ-5D-5L questionnaires will be used to measure quality of 
life (QoL) for subjects in the study. The LCSS is comprised of 9 questions to be completed by 
the subject using a visual analogue scale (VAS) to denote intensity of a symptom. The EQ-5D-
5L comprises 5 questions on mobility, self-care, usual activities, pain/discomfort, 
anxiety/depression and a VAS for overall QoL. These questionnaires will be completed by the 
subject prior to interaction with study personnel, at Day 1 of every Cycle, at the End-of-
Treatment Visit and at the 28-day Follow-up Visit.
6.10.
Healthcare Resource Utilization Questionnaire
A healthcare resource utilization questionnaire will be used to capture the additional use of 
healthcare resources, including hospitalizations, emergency room visits, doctor or nurse visits, 
procedures, and/or additional medication during the study period. The assessment will be 
completed on Day 1 of every treatment cycle, at the End-of-Treatment Visit and at the 28-day
Follow-up Visit. 
6.11.
Laboratory Assessments
Blood for hematology and chemistry evaluation will be collected as per Table 4, Table of Events. 
Blood for hematology will be collected at Screening, Days 1, 8, and 15 of every treatment cycle, 
at the End-of-Treatment Visit and at the 28-day Follow-up Visit. Blood for serum chemistry will 
be collected at Screening, Day 1 of every treatment cycle, at the End-of-Treatment Visit and at 
the 28-day Follow-up Visit. Hematology panel and serum chemistry will be performed at the 90-
day Follow-up Visit for subjects in the nab-paclitaxel/durvalumab arm if applicable following 
AEs or abnormal assessments findings during the 28-day Follow-up Visit. Hematology panel 
will consist of: hemoglobin, hematocrit, red blood cell count and morphology, mean corpuscular 
volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, white 
blood cell count with absolute and differential and percent (neutrophils, lymphocytes, 
monocytes, eosinophils, basophils, bands), platelet count, reticulocytes, erythrocyte 
sedimentation rate, international normalized ratio, prothrombin time, partial thromboplastin time
and fibrinogen. Serum chemistry panel includes: sodium, potassium, bicarbonate, calcium, 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
46
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
magnesium, phosphorus, blood urea nitrogen, serum creatinine and clearance, uric acid, glucose, 
lactic dehydrogenase, total protein, albumin, alkaline phosphatase, aspartate aminotransferase, 
alanine aminotransferase, gamma glutamyl transferase, total, direct and indirect bilirubin,
ferritin, amylase, lipase, thyroid stimulating hormone (TSH), T4, free T3, and free T4. 
Additional laboratory samples for safety may be collected as clinically indicated. 
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an AE/SAE and also recorded on the laboratory eCRF (see Section 11.3).
Abnormal and clinically significant laboratory assessments at Screening will be recorded as 
medical history, and after Screening, as AE or SAE (clinically significant laboratory 
abnormalities at Screening may result in a subject being ineligible for the study and should not 
be captured as an AE). 
Any abnormal values that persist should be followed at the discretion of the Investigator. The 
Investigator should file all copies of the reports, including faxes with the subject’s medical chart.
6.12.
Tumor Tissue Sample Collection and Peripheral Blood Collection
(Exploratory Assessments) 
Histologically or cytologically confirmed advanced NSCLC is a required inclusion criteria for 
entry into this study.  If a subject’s previously collected tumor tissue (also known as archival 
tumor) is available, these samples will be collected for biomarker testing as detailed below at 
Cycle 1 Day 1.  If such samples do not exist, have been depleted, or do not contain sufficient 
tumor material to be analyzed, this will not preclude participation in the study and a new biopsy 
or other procedure to collect tumor tissue will not be required. Table 5 delineates the specific 
requirements for commonly encountered archival tumor types.
Table 5:
Requirements for Collection Based on Archival Tumor Sample Type
Sample Type
Amount to Collect
Collection 
Requirement for 
Biomarkers
Comments/ Exceptions
Core biopsy or surgical 
specimen
10 slides ≥4 ∀M 
thickness. If a block is 
provided, a core of 
viable tumor will also 
be collected.
Mandatory if the sample 
exists. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Fine needle aspirates 
(FNA)
10 slides ≥4 ∀M. If a 
block is provided, a 
core of viable tumor 
will also be collected. 
Mandatory if the sample 
exists, unless a core 
biopsy or surgical 
sample was provided. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Transbronchial 
endoscopy samples
10 slides ≥4 ∀M. If a 
block is provided, a 
core of viable tumor 
will also be collected.
Mandatory if the sample 
exists, unless a core 
biopsy or surgical 
sample was provided. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
47
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Table 5:
Requirements for Collection Based on Archival Tumor Sample Type 
(Continued)
Sample Type
Amount to Collect
Collection 
Requirement for 
Biomarkers
Comments/ Exceptions
Bronchial lavage, 
sputum, or other 
sample types
Slides or blocks 
representing >100,000 
tumor cells
Collection is strongly 
encouraged when these 
samples contain 
sufficient material.
Collection is strongly 
encouraged when these 
samples contain sufficient 
material.
In addition, test results for tumor mutational status of genes, including but not limited to EGFR,
ALK, KRAS and PD-L1 will be collected, if available from prior testing, and recorded on eCRF 
if these tests have been performed.
Plasma for cell-free nucleic acids analyses will be collected on Cycle 1 Day 1 prior to first dose 
of IP, as will a sample of whole blood or peripheral blood mononuclear cells for a germ-line 
reference comparison. Types of techniques planned to be used for tumor and plasma analyses 
include:
!
Gene expression by RNA sequencing
!
Immunohistochemistry 
!
DNA sequencing
!
DNA methylation profiling
Details regarding the collection, storage, and shipment of the samples are given in the Laboratory 
Manual.
6.13.
Electrocardiogram
Electrocardiograms (ECGs) will be done at Screening and as per standard of care during the 
Treatment Period, and as clinically indicated. Results will be collected in the eCRFs as AE or 
SAE only if results are abnormal, changed and clinically significant, unless the finding is already 
documented in medical history.
6.14.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI)
A CT scan of the head, or preferably brain MRI, will be done as per standard of care at 
Screening (mandatory if symptomatic), during the Treatment Period, and as clinically indicated.
If CT scans show lesions pertinent for RECIST 1.1 criteria evaluation, data will be collected on 
the pertinent tumor evaluation eCRFs.
6.15.
Bone Scans and X-rays
Bone scans and x-rays will be done as per standard of care at Screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs. If bone scans or X-
rays show lesions pertinent for RECIST 1.1 criteria evaluation, data will be collected on the 
pertinent tumor evaluation eCRFs.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
48
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
6.16.
Physical Examinations
Physical examinations will be done at Screening, on Day 1 of every treatment cycle, at the End-
of-Treatment Visit, and as clinically indicated. Results will be collected in the eCRFs as AE or 
SAE only if results are abnormal and clinically significant.
6.17.
Vital Signs
Vital signs (at a minimum blood pressure, heart rate, respiratory rate and body temperature) will 
be done at Screening, prior to IP administration on Days 1, 8, and 15 of every treatment cycle, at 
the End-of-Treatment Visit, and as clinically indicated. Results will be collected in the eCRFs as 
AE or SAE only if results are abnormal and clinically significant.
6.18.
Survival 
After the End-of-Treatment Visit, the subjects will have a 28-day Follow-up Visit followed by a 
phone call approximately every 90 days (+/- 14 days) for at least 12 months after the last subject 
is randomized in either the nab-paclitaxel/CC-486 combination therapy and nab-paclitaxel 
monotherapy arm or 120 PFS events have been observed between these two arms, whichever 
comes later. Subjects in the nab-paclitaxel/durvalumab arm will be followed for survival in a 
similar manner for at least 12 months after the last subject is assigned to this arm.
The subjects will also be asked questions about other medications they may be taking for their 
NSCLC. Those subjects entering the Follow-up Period without documented progression will 
continue to have CT scans in accordance with local standard of care (or approximately every 90 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the Sponsor.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
49
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Male and female subjects with advanced NSCLC who have received no more than one prior
chemotherapy regimen for their advanced disease will be eligible for this study (immunotherapy 
in prior line of treatment is allowed, including platinum doublet combination). Subjects will 
receive study therapy as second or third line of treatment for advanced disease. The study will 
randomize/assign a maximum of approximately 240 subjects if all 3 arms proceed to the end of 
the study. The study will be conducted at approximately 40 sites in the US, Canada, and Europe.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be randomized/assigned in the study:
1. Age ≥ 18 years at the time of signing the ICF.
2. Understand and voluntarily provide written informed consent prior to the conduct of any 
study related assessments/procedures.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Histologically or cytologically confirmed advanced NSCLC who will receive study 
therapy as second- or third-line of treatment for advanced disease.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease (defined by the presence of 
≥1 radiographically documented measurable lesion).
7. No more than one prior line of chemotherapy (immunotherapy in prior line of treatment 
is allowed, including platinum doublet combination).
8. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
9. Platelets ≥ 100,000 cells/mm3.
10. Hemoglobin (Hgb) ≥ 9 g/dL.
11. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and 
alanine transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper 
limit of normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
12. Total bilirubin ≤ 1.5 ULN (unless there is a known history of Gilberts Syndrome).
13. Serum creatinine ≤1.5 x ULN, or calculated creatinine clearance ≥60 mL/min (if renal 
impairment is suspected 24-hour urine collection for measurement is required).
14. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
15. Females of childbearing potential [defined as a sexually mature woman who (1) have not 
undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy 
(the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
50
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
at least 24 consecutive months (ie, has had menses at any time during the preceding 24 
consecutive months)] must:
a.
Have a negative pregnancy test (ß-hCG) as verified by the study doctor within 72 
hours prior to starting study therapy. She must agree to ongoing pregnancy testing 
during the course of the study, and after end of study therapy. This applies even if the 
subject practices true abstinence* from heterosexual contact.
b. Either commit to true abstinence* from heterosexual contact or agree to use, and be 
able to comply with, effective contraception without interruption, 28 days prior to 
starting IP, during the study therapy (including dose interruptions), and for 3 months 
after discontinuation of study therapy. 
Male subjects must:
a.
Practice true abstinence* or agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the study, 
during dose interruptions and for at least 6 months following IP discontinuation, even 
if he has undergone a successful vasectomy. 
b. Refrain from semen or sperm donation while taking durvalumab and for at least 3 
months after the last dose of durvalumab.
16. Females must abstain from breastfeeding during study participation and 3 months after IP 
discontinuation. 
7.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. Refractory to prior taxane therapy for advanced disease. Prior taxane used in the adjuvant 
setting does not exclude eligibility, provided there is no disease recurrence within 12 
months upon completion of chemotherapy in that setting.
2. Evidence of active brain metastases, including leptomeningeal involvement (prior 
evidence of brain metastasis are permitted only if asymptomatic and clinically stable for 
at least 8 weeks following completion of therapy). MRI of the brain (or CT scan 
w/contrast) is preferred.
3. Only evidence of disease is non-measurable at study entry.
4. Patients with known activating mutations in EGFR (such as exon 19 deletions or L858R).
5. Patients with known activating mutations in EML4-ALK.
6. Preexisting peripheral neuropathy of Grade > 2 (per NCI CTCAE v4.0).
7. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with 
the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion 
criteria.
                                               
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic 
abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception].
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
51
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
8. Venous thromboembolism within 1 month prior to Cycle 1 Day 1.
9. Current congestive heart failure (New York Heart Association Class II-IV).
10. History of the following within 6 months prior to Cycle 1 Day 1: a myocardial infarction, 
severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart 
Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically 
significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG)
abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder.
11. Known hepatitis B or C virus (HBV/HCV) infection, known history of human 
immunodeficiency virus (HIV) infection, or receiving immunosuppressive or 
myelosuppressive medications that would in the opinion of the Investigator, increase the 
risk of serious neutropenic complications, history of active primary immunodeficiency, 
active tuberculosis (clinical evaluation that includes clinical history, physical examination 
and radiographic findings, and TB testing in line with local practice).
12. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, 
defined as ongoing signs/symptoms related to the infection without improvement despite 
appropriate antibiotics, antiviral therapy, and/or other treatment.
13. Subject has a history of interstitial lung disease, history of slowly progressive dyspnea 
and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary 
hypersensitivity pneumonitis or multiple allergies. Any lung disease that may interfere 
with the detection or management of suspected drug-related pulmonary toxicity. 
14. Subject has a clinically significant malabsorption syndrome, persistent diarrhea, or 
known sub-acute bowel obstruction > NCI CTCAE Grade 2, despite medical 
management.
15. Treatment with any chemotherapy, investigational product, biologic or hormonal therapy 
for cancer treatment within 28 days prior to signing the ICF. Concurrent use of hormonal 
therapy for non-cancer-related conditions (eg, hormone replacement therapy) is 
acceptable.
16. History of or suspected allergy to any IP or their excipients.
17. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first 
dose of IP.  Note: Local surgery of isolated lesions for palliative intent is acceptable.
18. Currently enrolled in any other clinical protocol or investigational trial that involves
administration of experimental therapy and/or therapeutic devices.
19. Any other clinically significant medical condition, psychiatric illness, and/or organ 
dysfunction that will interfere with the administration of the therapy according to this 
protocol or which, in the views of Investigator, preclude combination chemotherapy.
20. Any other malignancy within 5 years prior to randomization/treatment assignment, or 
advanced malignant hepatic tumors, with the exception of adequately treated squamous 
cell carcinoma of the skin, in-situ carcinoma of the cervix, uteri, non-melanomatous skin 
cancer, carcinoma in situ of the breast, or incidental histological finding of prostate 
cancer (TNM Classification of Malignant Tumours (TNM) stage of T1a or T1b). (All 
treatment of which should have been completed 6 months prior to signing ICF).
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
52
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
21. Radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting 
IP, and/or from whom ≥ 30% of the bone marrow was irradiated. Prior radiation therapy 
to a target lesion is permitted only if there has been clear progression of the lesion since 
radiation was completed.
22. Any condition including the presence of laboratory abnormalities, which places the 
subject at unacceptable risk if he/she were to participate in the study.
23. Any medical condition that confounds the ability to interpret data from the study.
24. Female patients who are pregnant or breastfeeding or female patients of reproductive 
potential who are not willing to employ effective birth control from screening to 90 days 
after the last dose of durvalumab.  
25. Male patients of reproductive potential who are not willing to employ effective birth 
control from screening to 90 days after the last dose of durvalumab and from screening to 
6 months after the last dose of nab-paclitaxel.
26. History of allogenic organ transplantation.
27. Active or prior documented autoimmune or inflammatory disorders (including 
inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the 
exception of diverticulosis], celiac disease, irritable bowel disease, or other serious 
gastrointestinal chronic conditions associated with diarrhea, systemic lupus 
erythematosus, sarcoidosis syndrome, or Wegener’s syndrome [granulomatosis with 
polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]) within the 
past 3 years prior to the start of treatment.  The following are exceptions to this criterion:
-
Patients with vitiligo or alopecia
-
Patients with hypothyroidism (eg, following Hashimoto’s syndrome) stable on 
hormone replacement 
-
Any chronic skin condition that does not require systemic therapy
-
Patients without active disease in the last 5 years may be included but only after 
consultation with the study physician
28. Current or prior use of immunosuppressive medication within 14 days before the first 
dose of durvalumab.  The following are exceptions to this criterion:
-
Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular 
injection)
-
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of 
prednisone or its equivalent
-
Steroids as premedication for hypersensitivity reactions (eg, CT scan 
premedication)
29. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.  Note: 
Patients, if enrolled, should not receive live vaccine during the study and up to 30 days 
after the last dose of IP.
30. Prior enrollment and treatment in a previous durvalumab clinical study. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
53
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
31. Patients who have received prior anti-PD-1 or anti PD-L1 :
# Must not have experienced a toxicity that led to permanent discontinuation of prior 
immunotherapy. 
# All AEs while receiving prior immunotherapy must have completely resolved or 
resolved to baseline prior to screening for this study.
# Must not have experienced a ≥ Grade 3 immune related AE or an immune related 
neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: 
Subjects with endocrine AE of ≤ Grade 2 are permitted to enroll if they are stably 
maintained on appropriate replacement therapy and are asymptomatic.
# Must not have required the use of additional immunosuppression other than 
corticosteroids for the management of an AE, not have experienced recurrence of 
an AE if re-challenged, and not currently require maintenance doses of > 10 mg 
prednisone or equivalent per day.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
54
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Investigational Products
Subjects will receive open-label nab-paclitaxel / CC-486, nab-paclitaxel /durvalumab or nab-
paclitaxel monotherapy during the Treatment Period of the study. nab-paclitaxel, durvalumab
and CC-486 are designated as IP and will be packaged and supplied by the study Sponsor.
The reconstitution and IV administration of nab-paclitaxel should follow the local Prescribing 
Information for Abraxane®.
8.1.1.
nab-Paclitaxel
nab-Paclitaxel will be supplied by the Sponsor in single-use vials in single count cartons. Each 
single-use 50 mL vial will contain paclitaxel (100 mg) and human albumin as a stabilizer.
Please see local prescribing information for Abraxane® for detailed instructions on the 
reconstitution, storage conditions and IV administration of nab-paclitaxel. Reconstituted nab-
paclitaxel should be stored in an area accessible only to study personnel.
Temperature records for nab-paclitaxel must be made available to the Sponsor or other Sponsor-
nominated monitoring teams for verification of proper IP storage.
8.1.2.
CC-486 (Azacitidine for Oral Administration)
The Sponsor will supply azacitidine 100 mg tablets for oral administration. Each tablet is 
formulated using excipients that are generally regarded as safe and are used in marketed drug 
products.
All tablets will be packaged in blister cards. Only sufficient IP for one cycle of treatment will be 
provided to each subject at the start of each treatment cycle. All tablets should be swallowed 
whole, and should not be broken or chewed. CC-486 may be taken on an empty stomach or with 
food. Subjects should drink 8 ounces (240 mL) of room temperature water with each dose. It is 
strongly recommended that all subjects receive a dose of a prophylactic antiemetic, preferably a 
5-HT3 antagonist, approximately 30 minutes prior to each dose of CC-486.
The IP must be stored as directed on package label at controlled temperature and a temperature 
log must be maintained in the source documents. The storage area should be secure and have 
access limited to study personnel. 
8.1.3.
Durvalumab (MEDI4736)
Durvalumab will be supplied by the Sponsor in single use vials in single count cartons. Each 10R 
(10 mL) vial will be supplied as a liquid solution containing 500 mg (nominal) of IP at a 
concentration of 50 mg/mL. Durvalumab should be stored in accordance with the product label. 
The study site is to supply the following:
!
IV infusion bags of normal saline (0.9% [w/v] sodium chloride injection, 250 mL 
size). Saline bags must be latex-free and can be made of polypropylene, polyethylene, 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
55
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
polyolefin copolymers, or polyvinyl chloride. Infusion lines should contain a 0.2-μm 
in-line filter.  
!
Since the compatibility of durvalumab with other IV medications and solutions, other 
than normal saline, is not known, the durvalumab solution should not be infused 
through an IV line in which other solutions or medications are being administered.
Durvalumab will be administered using an IV bag containing 0.9% (w/v) saline or 5% (w/v) 
dextrose, with a final durvalumab concentration ranging from 1 to 20 mg/mL, and delivered 
through an IV administration set with a 0.2- or 0.22-μm in-line filter.
The dose of durvalumab for administration must be prepared by the Investigator’s or site’s 
designated IP manager using aseptic technique. Total time from needle puncture of the 
MEDI4736 vial to the start of administration should not exceed:
!
24 hours at 2°C to 8°C (36°F to 46°F)
!
4 hours at room temperature
Standard infusion time is 1 hour. However, if there are interruptions during infusion, the total 
allowed time should not exceed 8 hours at room temperature. In the event that either preparation 
time or infusion time exceeds the time limits outlined above, a new dose must be prepared from 
new vials. Durvalumab does not contain preservatives, and any unused portion must be 
discarded.
For additional information on preparation and storage please refer to the pharmacy manual.
8.1.4.
Monitoring During/After Durvalumab Infusion 
First durvalumab infusion
On the first infusion day, subjects in the nab-paclitaxel/durvalumab combination arm will be 
monitored, and assessments collected/recorded in the eCRF prior to, during and after infusion of 
IP as presented in the bulleted list below.
Blood pressure (BP) and pulse will be collected from subjects before, during, and after each 
infusion at the following times (based on a 60-minute infusion):
!
Prior to the beginning of the infusion (measured once from approximately 30 minutes 
before up to 0 minutes [ie, the beginning of the infusion])
!
Approximately 30 minutes during the infusion (halfway through infusion) 
!
At the end of the infusion ( approximately 60 minutes ±5 minutes)
!
If the infusion takes longer than 60 minutes, then BP and pulse measurements should 
follow the principles as described above or be taken more frequently if clinically 
indicated.  A 1-hour observation period is recommended after the first infusion of 
durvalumab.
Subsequent durvalumab infusions
BP, pulse and other vital signs should be measured, collected/recorded in eCRF prior to the start 
of the infusion. Subjects should be carefully monitored and BP and other vital signs should be 
measured during and post infusion as per institution standard and as clinically indicated. Any 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
56
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
clinically significant changes in vital signs should be entered onto an unscheduled vital signs 
CRF page.
For all infusions
In the event of a ≤ Grade 2 infusion-related reaction, the infusion rate of IP may be decreased by 
50% or interrupted until resolution of the event (up to 4 hours) and re-initiated at 50% of the 
initial rate until completion of the infusion. For subjects with a ≤ Grade 2 infusion-related 
reaction, subsequent infusions may be administered at 50% of the initial rate. 
Acetaminophen/paracetamol and/or an antihistamine (eg, diphenhydramine) or equivalent 
medications per institutional standard may be administered at the discretion of the investigator. If 
the infusion-related reaction is ≥ Grade 3 or higher in severity, IP will be discontinued. 
As with any antibody, allergic reactions to dose administration are possible. Appropriate drugs 
and medical equipment to treat acute anaphylactic reactions must be immediately available, and
study personnel must be trained to recognize and treat anaphylaxis. The study site must have 
immediate access to emergency resuscitation teams and equipment in addition to the ability to 
admit subjects to an intensive care unit if necessary.
8.2.
Treatment Administration and Schedule
Following administration of nab-paclitaxel, the intravenous line should be flushed with sodium
chloride 9 mg/mL (0.9%) solution for injection to ensure administration of the complete dose, 
according to local practice.
Once randomized (or assigned), subjects will be treated with nab-paclitaxel / CC-486, nab-
paclitaxel / durvalumab or nab-paclitaxel monotherapy until disease progression, development of 
an unacceptable toxicity, death, lost to follow-up, withdrawal of consent, or termination of the 
study by the Sponsor:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment cycle, or
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 
durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15 of each 21-
day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle
8.3.
Dose Omissions and Modifications
8.3.1.
Rules for Dose Omissions and Modified Schedules
nab-Paclitaxel Monotherapy Arm
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
!
Day 1 Dose Missed
If nab-paclitaxel cannot be administered on Day 1 within the 2 days allowable window,
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
57
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
 nab-paclitaxel may not be skipped but only delayed 
 Delay of Day 1 will automatically shift the following visit for this cycle 
!
Day 8 Dose Missed
If the nab-paclitaxel dose for Day 8 is given >9 days from Day 1, the Day 8 dose, when 
administered, can be either considered as delayed or skipped, depending on the intention of the 
Investigator.
 nab-paclitaxel may be delayed up to Day 15: this dose will be considered as delayed 
Day 8; the next visit will be the planned Day 1 of the next cycle which will not be 
automatically pushed back
 nab-paclitaxel may be skipped: if the second nab-paclitaxel dose cannot be given in a 
cycle it may be skipped; the next dose would be administered as the Day 1 dose 
nab-Paclitaxel/CC-486 Combination Arm
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
If any doses of CC-486 are missed, skip that day and resume as appropriate, do not double up on 
subsequent days.
!
Day 1 Dose Missed
If CC-486 cannot be administered on Day 1 within the 2 days allowable window,
 The nab-paclitaxel Day 8 dose would not necessarily be pushed back / delayed
 Doses of CC-486 would be skipped (exposure to CC-486 would be reduced on that 
cycle). 
For hematologic toxicity, dosing should be reassessed at the next visit on Day 8.
!
Day 8 Dose Missed
If nab-paclitaxel cannot be administered on Day 8 within the 2 days allowable window,
 nab-paclitaxel may be delayed (eg, for neuropathy): this dose will be considered as 
delayed Day 8; the next dose (Day 15) may also be delayed up to the original Day 1 of 
the next cycle (approximately 20 days from Day 1 of this cycle) to maintain the protocol 
specified visit gap
 nab-paclitaxel may be skipped (eg, hematotoxicity); the next dose would be administered 
as the Day 15 dose 
If the dose for Day 8 is given > 9 days from Day 1, the Day 8 dose, when administered, can be 
either considered as delayed or skipped, depending on the intention of the Investigator.
Upon resuming treatment after stopping both IPs on adjusted Day 8, consideration for nab-
paclitaxel resumption should take priority.
!
Day 15 Dose Missed
If nab-paclitaxel cannot be administered on Day 15 within the 2 days allowable window,
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
58
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
 nab-paclitaxel may be delayed: this dose will be considered as delayed Day 15 (up to 
Day 1 of the next cycle); CC-486 may be started on Day 1 as planned
 If the nab-paclitaxel dose cannot be administered within 14 days from the last dose, it 
will be considered as skipped
nab-Paclitaxel/Durvalumab Combination Arm
No dose reductions of durvalumab are allowed. In case of doubt, the Investigator should consult 
with the Study Physician.
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
!
Day 1 Dose Missed
If nab-paclitaxel cannot be administered on Day 1 within the 2 days allowable window,
 nab-paclitaxel may not be skipped but only delayed 
 Delay of Day 1 will automatically shift the following visit for this cycle 
!
Day 8 Dose Missed
If the nab-paclitaxel dose for Day 8 is given > 9 days from Day 1, the Day 8 nab-paclitaxel dose 
should be skipped
!
Day 15 Dose Missed
If durvalumab cannot be administered on Day 15 within the 2 days allowable window,
 Durvalumab may be delayed: this dose will be considered as delayed Day 15 
 If the durvalumab dose cannot be administered within 14 days from the last dose, it will 
be considered as skipped
8.3.2.
Rules for Dose Modifications
Subjects who experience any of the adverse drug reactions in Table 6 will be dose reduced as per 
Table 6 during treatment. 
nab-Paclitaxel Monotherapy Arm
!
Do not administer nab-paclitaxel on Day 1 of a cycle until ANC is at least 
1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment until 
counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and platelet 
count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil count of at least 
500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Day 8 of the cycle. 
Upon resumption of dosing, permanently reduce nab-paclitaxel doses as outlined in 
Table 6.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-paclitaxel 
at reduced doses (Table 6) when peripheral neuropathy improves to Grade 1 or 
completely resolves.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
59
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to 
the guidelines in Table 6. For any other Grade 3 or 4 nonhematologic toxicity or other 
Investigator defined unacceptable toxicity, interrupt treatment until the toxicity 
improves to ≤Grade 2, then restart treatment according to the guidelines in Table 6.
Re-escalation is not permitted at any time. 
nab-Paclitaxel/CC-486 Combination Arm
!
Do not administer nab-paclitaxel on Day 8 or CC-486 on Day 1 or 8 of a cycle until ANC 
is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe thrombocytopenia, withhold treatment until counts 
recover to a platelet count of at least 100,000 cells/mm3 on Days 1 and 8 for CC-486 and 
Day 8 for nab-paclitaxel or to a platelet count of at least 50,000 cells/mm3 on Day 15 of 
the cycle for nab-paclitaxel. Upon resumption of dosing, permanently reduce nab-
paclitaxel and/or CC-486 doses as outlined in Table 6.
!
In subjects who experience Grade ≥3 neutropenia, withhold treatment and start G-CSF 
treatment daily until the ANC ≥ 2000/mm3 (please refer to Section 9.3 for G-CSF 
administration). Upon resumption, permanently reduce nab-paclitaxel and/or CC-486 
dose as outlined in Table 6.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy (CC-486 does not need 
to be withheld). Resume nab-paclitaxel at reduced doses (Table 6) when peripheral 
neuropathy improves to Grade 1 or completely resolves. 
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to the 
guidelines in Table 6. For any other Grade 3 or 4 nonhematologic toxicity or other 
Investigator defined unacceptable toxicity, interrupt treatment until the toxicity improves 
to ≤Grade 2, then restart treatment according to the guidelines in Table 6.
Re-escalation is not permitted at any time. 
nab-Paclitaxel/Durvalumab Combination Arm
Guidelines for the management of toxicities for durvalumab and nab-paclitaxel are provided in 
Appendix C.
In addition:
!
Do not administer nab-paclitaxel on Day 1 of a cycle until ANC is at least 
1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment until 
counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and platelet 
count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil count of at least 
500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Day 8 of the cycle. 
Upon resumption of dosing, permanently reduce nab-paclitaxel doses as outlined in 
Table 6.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
60
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-paclitaxel 
at reduced doses (Table 6) when peripheral neuropathy improves to Grade 1 or 
completely resolves. 
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to the 
guidelines in Table 6. For any other Grade 3 or 4 nonhematologic toxicity or other 
Investigator defined unacceptable toxicity, interrupt treatment until the toxicity improves 
to ≤Grade 2, then restart treatment according to the guidelines in Table 6.
Following the first dose of IP, subsequent administration of durvalumab can be modified based 
on toxicities observed as described in the Dosing Modification and Toxicity Management 
Guidelines.  These guidelines have been prepared by the Sponsor to assist the Investigator in the 
exercise of his/her clinical judgment in treating these types of toxicities.  These guidelines apply 
to AEs considered causally related to the durvalumab containing regimen by the reporting 
Investigator.
Treatment modifications referring to ‘study regimen or treatment’ would apply to both nab-
paclitaxel and durvalumab unless AEs are not considered causally related to nab-paclitaxel by 
the reporting Investigator. In that case nab-paclitaxel or durvalumab treatment may be continued 
alone if deemed beneficial to the patient per Investigator’s assessment.
Re-escalation is not permitted at any time. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
61
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Table 6:
Permanent Dose Reductions for Hematologic and Nonhematologic Toxicities and Dosing on the Study
Dose Modification During Treatment
Adverse Drug Reaction
Occurrence
Monotherapy Arm: nab-
paclitaxel Dose (mg/m2)
Combination Arm: nab-
paclitaxel Dose (mg/m2) / 
CC-486 Dose (mg)
Neutropenic Fever (ANC < 500/mm3 with fever >38°C)
OR
Delay of next cycle by > 7 days for ANC < 1500/mm3
OR
ANC < 500/mm3 for > 7 days
First
75
100/100
Second
50
75/100
Third
Discontinue Treatment*
50/100
Fourth
NA
Discontinue Treatment*
Platelet count < 50,000/mm3
First
75
100/100
Second
Discontinue Treatment*
75/100
Third
NA
Discontinue Treatment*
Peripheral Neuropathy Grade ≥3
First
75
75/200
Second
50
50/200
Third
Discontinue Treatment*
Grade 2 or 3 Cutaneous toxicity
Grade 3 Diarrhea
Grade 3 Mucositis
Any other Grade 3 or 4 nonhematologic toxicity or other 
Investigator defined unacceptable toxicity
First
75
100/100
Second
50
75/100
Third
Discontinue Treatment*
50/100
Fourth
NA
Discontinue Treatment*
Grade 4 Cutaneous toxicity, Diarrhea or Mucositis
First
Discontinue Treatment*
ANC = absolute neutrophil count; AUC = area under the curve; NA = not applicable.
* If an adverse event that requires dose reduction recurs after the dose has been reduced according to the table above, the subject should generally have treatment 
discontinued unless, at the discretion of the Investigator, there is evidence of continuing benefit to the subject that outweighs the risk of recurrent toxicity.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
62
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
8.4.
Method of Treatment Assignment
The Treatment Period of the study is open-label. Randomization/treatment assignment has been 
and will be carried out centrally using an IRT system.
8.5.
Packaging and Labeling
The label(s) for all IP will include Sponsor name, address and telephone number, the protocol 
number, IP name, dosage form and strength (where applicable), amount of IP per container, lot 
number, expiry date (where applicable), medication identification/kit number, dosing 
instructions, storage conditions, and required caution statements and/or regulatory statements as 
applicable. Additional information may be included on the label as applicable per local 
regulations.
8.6.
Investigational Product Accountability and Disposal
The Sponsor (or its designee) will review with the Investigator and relevant site personnel the 
process for IP return, disposal, and/or destruction including responsibilities for the site versus the 
responsibilities of the Sponsor (or designee).
The Sponsor will instruct the Investigator on the return, disposal and/or destruction of IP. Only 
completely unused IP vials should be retained by the site until a representative from the Sponsor
or other Sponsor-designated personnel have completed an inventory. Partially used and
completely used vials should be destroyed according to local guidelines, and disposition should 
be recorded on the Investigational Drug Accountability Record Form.
The Investigator(s) or designee(s) is responsible for accounting for all IP that is issued to and
returned by the subject during the course of the study according to applicable regulatory
requirements. Any unused CC-486 must be returned by a study subject and retained by the
investigative site for accountability to be conducted by a Sponsor representative (or its designee). 
If any IP is lost or damaged, its disposition should be documented. At the periodic monitoring
visits, a Sponsor representative (or its designee) will conduct IP accountability and address any
discrepancies. Upon satisfactory reconciliation of all IP, returned IP may be destroyed. At the
conclusion of the study, all remaining IP will be counted, reconciled with dispensing records, 
documented, and destroyed at the clinic site or allocated drug destruction location after
completion of drug accountability by a Sponsor representative (or its designee). The Sponsor
representative (or its designee) will ensure that a final report of drug accountability to the unit 
dose level (ie, tablet) is prepared and placed in both the Investigator study file and the central 
clinical study file.
Investigational product will not be loaned or dispensed by the Investigator to another 
Investigator or site. Under certain circumstances, and with Sponsor permission, cooperative 
groups may manage IP between locations within their network as clinical trial agreement and 
local guidelines permit.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
63
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
8.7.
Investigational Product Compliance
All IP will be administered only by study site personnel and accurate recording of all IP 
administration will be made in the appropriate section of the subject’s eCRF and source 
documents.
8.8.
Overdose
Overdose, as defined for this protocol, refers to nab-paclitaxel, CC-486, or durvalumab dosing.
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel, durvalumab or CC-486 to a given subject, regardless of any associated adverse events 
or sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate. For nab-paclitaxel, an infusion completed in less than 25 minutes may increase Cmax by 
approximately 20%, therefore a nab-paclitaxel infusion completed in less than 25 minutes will 
meet the infusion rate criterion for an overdose.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the AE case report form. See 
Section 11.1 for the reporting of adverse events associated with overdose.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
64
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
Over the course of this study, additional medications may be required to manage aspects of the 
disease state of the subjects, including side effects from study treatments or disease recurrence. 
All supportive care (including but not limited to growth factors, antiemetics, analgesics, 
zolendronic acid, denosumab) is permitted as per the Investigator’s discretion and should be 
administered according to local institutional practice. All concomitant treatments, including 
blood and blood products, must be reported on the eCRF.
!
Antiemetics are not required during the study; however, it is strongly recommended 
that all subjects receive a dose of a prophylactic antiemetic, preferably a 5-HT3 
antagonist, approximately 30 minutes prior to each dose of CC-486.
!
Stable, therapeutic doses of anticoagulants are permitted; however, subjects on 
warfarin should have prothrombin time (PT) or international normalized ratio (INR)
and partial thromboplastin time (PTT) monitored as clinically indicated.
!
Subjects on erythropoietin or darbepoetin alfa for at least 4 weeks prior to starting the 
IP may continue their pretreatment doses throughout the study.
#
Note: If the subject is not on a stable dose of an erythropoiesis-stimulating agents 
(ESA) prior to study entry, the subject may not start an ESA during Cycle 1. 
However, medications such as ESAs, granulocyte colony-stimulating factors (G-
CSFs), etc., may be administered according to standard of care after Cycle 1.
!
Use of white blood cell growth factors (eg, filgrastim, G-CSF for the treatment of 
subjects with neutropenic fever is permitted at the Investigator’s discretion. Use of 
filgrastim rather than pegylated-filgrastim is indicated, because of the 14 day delay of 
the next cycle following treatment with peg-filgrastim.
!
Use of white blood cell growth factors (eg, filgrastim, G-CSF) for secondary
prophylaxis in subjects who experienced a neutropenic complication from a prior
cycle of chemotherapy (for which primary prophylaxis was not received) is permitted.
!
Flu vaccination with inactivated virus is permitted.
!
Routine infectious disease prophylaxis is not recommended, however, antibiotic,
antiviral, antipneumocystis, antifungal, or other prophylaxis may be implemented
during the study at the discretion of the Investigator.
!
Treatments with bisphosphonates (eg, pamidronate, zolendronate), or other agents
(eg, denosumab) to prevent or delay progression of bone metastases are permitted.
Maintenance of a stable dosing regimen throughout the study is recommended.
!
Subjects may receive physiologic replacement doses of glucocorticoids as
maintenance therapy for adrenal insufficiency. Glucocorticoids may be administered
as an antiemetic with IV chemotherapy, if directed by local standard of care. Use of 
immunosuppressive medications for the management of durvalumab-related AEs, or 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
65
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
in subjects with contrast allergies is acceptable.  In addition, use of inhaled, topical, 
and intranasal corticosteroids is permitted.
!
Treatment with antidiarrheal medications is recommended at the first sign of diarrhea
as per the guidelines in Appendix B. Pre-medication with antidiarrheal medication for 
subsequent doses of CC-486 may be appropriate.
!
The potential drug-drug interactions precautions contained in the nab-paclitaxel 
prescribing information will be applied to this study, unless otherwise specified in the 
protocol. Specifically, the metabolism of paclitaxel is catalyzed by cytochrome P450 
isozymes CYP2C8 and CYP3A4. Caution is recommended when administering nab-
paclitaxel concomitantly with medicines known to inhibit (eg, ketoconazole and other 
imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, 
saquinavir, indinavir, and nelfinavir) or induce (eg, rifampicin, carbamazepine, 
phenytoin, efavirenz, nevirapine) either CYP2C8 or CYP3A4. For information 
regarding other drugs that may interact with either nab-paclitaxel or durvalumab and 
affect their metabolism, pharmacokinetics, or excretion, please see the respective IP 
product information (refer to Prescribing Information and/or IB).
9.2.
Prohibited Concomitant Medications and Procedures
Other investigational therapies must not be used while the subject is enrolled in the study.
Anticancer therapy (chemotherapy, biologic or investigational therapy, and surgery) other than
the study treatments must not be given to subjects during the study. If such treatment is required,
the subject must be discontinued from the study. Focal palliative radiotherapy for treatment of
cancer-related symptoms is allowed during study treatment at the discretion of the Investigator.
The administration of either α-interferon and/or ribavirin, or drugs with known renal toxicity is
prohibited during study treatment. Monoclonal antibodies against CTLA-4, PD-1 or PD-L1 
should not be given concomitantly.
Immunosuppressive medications including, but not limited to, systemic corticosteroids at doses 
exceeding 10 mg/day of prednisone or equivalent, methotrexate, azathioprine, and tumor 
necrosis factor-α blockers should not be given during the study unless required for management 
of immune-related toxicities (Appendix C).
Live attenuated vaccines should not be given through 30 days after the last dose of IP.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) EGFR TKIs should 
not be given concomitantly with durvalumab, and should be used with caution in the 90 days 
post last dose of durvalumab. Increased incidences of pneumonitis (with third generation EGFR 
TKIs) and increased incidence of transaminase increases (with first generation EGFR TKIs) has 
been reported when durvalumab has been given concomitantly.
9.3.
Required Concomitant Medications and Procedures for Subjects 
Receiving CC-486
Data regarding G-CSF administration should be recorded on the eCRF provided for G-CSF 
administration.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
66
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
9.3.1.
Description of G-CSF
This medication stimulates the blood system (bone marrow) to make white blood cells, helping
fight infections. This medication is given to those whose ability to make white blood cells has
been reduced. Filgrastim (also known as G-CSF, or granulocyte colony stimulating factor) is a
man-made version of a certain natural substance found in the body. It is produced using a certain
bacteria. It will be obtained commercially and relabeled as clinical supplies. It should be stored,
and administered according to the manufacturer’s recommendation.
9.3.2.
Administration of G-CSF
For subjects who experience Grade ≥3 neutropenia, G-CSF 5 ∀g/kg daily will be administered
subcutaneously. During any cycle when Grade ≥3 neutropenia occurs, CC-486 and other 
cytotoxic agents will be held, and G-CSF will begin immediately (a minimum of 24 hours after 
the last dose of CC-486 and chemotherapy). In subsequent cycles, G-CSF will begin on Day 16. 
G-CSF will continue daily until the ANC ≥2000/mm3. In subjects receiving G-CSF, the next 
cycle should begin no sooner than 48 hours after discontinuation of G-CSF. 
For complete details on drug administration, storage, clinical pharmacology, and the human PK 
of G-CSF (filgrastim), please see the G-CSF (filgrastim) package insert.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
67
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the study are described 
below.  Additional analyses of these endpoints as well as exploratory endpoints or subgroup 
analyses will be described in detail in the statistical analysis plan (SAP).  The SAP supersedes 
the analyses described in the protocol should there be differences between the two.
Evaluations of the study endpoints will be based primarily on the point estimates and the 
associated 95% confidence intervals of the within- and between-treatment differences. 
10.1.
Overview
Approximately 240 subjects will be assigned 1:1:1 to one of the three treatment arms 
(approximately 80 subjects per group). The combination arms will receive nab-paclitaxel with 
epigenetic modifying therapy of CC-486 or nab-paclitaxel with immunotherapy of durvalumab,
and the monotherapy arm will receive nab-paclitaxel alone.  All regimens will be administered 
in 21-day cycles. All subjects will receive the assigned study treatment until disease progression, 
unacceptable toxicity, death, lost to follow-up, withdrawal of consent, or termination of the 
study by the Sponsor, in accordance with local standard of care. Treatment beyond progression 
defined by RECIST 1.1 will be permitted per irRECIST criteria for those subjects in the nab-
paclitaxel/durvalumab arm (see Section 4.1.2.1).
Prior to the time of implementation of Protocol Amendment 3.0, subjects will be assigned to 
either the nab-paclitaxel/CC-486 combination or nab-paclitaxel monotherapy arms in a 1:1 
fashion based on a permuted-block randomization method with the following baseline 
stratification factors: 
!
ECOG performance status (0 versus 1)
!
Gender (males versus females)
!
Smoker (yes versus no)
Randomization will be carried out centrally using an IRT system. Once Protocol Amendment 3.0 
is in effect, subjects from sites that are ready to implement the said amendment will be 
randomized 1:1:1 to the nab-paclitaxel/CC-486 combination therapy, nab-paclitaxel 
monotherapy, and nab-paclitaxel/durvalumab combination therapy arms, respectively. Subjects 
from the remaining sites will continue to be randomized 1:1 to the nab-paclitaxel/CC-486 
combination therapy and nab-paclitaxel monotherapy arms, respectively. When approximately 
80 subjects have been randomized to each of the nab-paclitaxel/CC-486 combination therapy and 
nab-paclitaxel monotherapy arms, all incoming subjects will be assigned to the nab-
paclitaxel/durvalumab combination therapy arm until approximately 80 subjects have been 
enrolled to receive the IP in that arm. Hence, treatment assignments of subjects to the nab-
paclitaxel/CC-486 combination therapy and nab-paclitaxel monotherapy arms will be in effect 
conducted completely in a randomized fashion.
If the nab-paclitaxel/CC-486 arm stops after the interim analysis, incoming subjects will be 
randomized 2:1 to the nab-paclitaxel/durvalumab combination therapy and nab-paclitaxel 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
68
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
monotherapy arms, respectively, until enrollment to the monotherapy arm is complete.  
Thereafter, subjects will be assigned to the nab-paclitaxel/durvalumab combination therapy arm 
until approximately 80 subjects have been enrolled in this arm.
A data monitoring committee (DMC) will be used to review the safety and efficacy data during 
the study.
10.2.
Study Population Definitions
10.2.1.
Intent-to-treat Population
The primary efficacy analysis will be performed on the intent-to-treat (ITT) population, which 
includes all randomized (assigned) subjects regardless of whether the subject receives any IP or 
has any efficacy assessments performed. 
10.2.2.
Per-protocol (PP) Population
The PP population is defined as all eligible subjects randomized/assigned who receive at least 
one dose of the IP, have been treated in the arm they were assigned and meet the major eligibility
criteria of the protocol.  Additional analyses utilizing the PP population will be described in the 
SAP.
10.2.3.
Treated Population
The treated population will consist of all randomized/assigned subjects who receive at least one 
dose of IP. The safety analyses will be based on the treatment as received if different from the 
assigned treatment by randomization/treatment assignment.
10.3.
Sample Size and Power Considerations
The primary objective of this study is to estimate the efficacy of the nab-paclitaxel/CC-486 
combination therapy, that of the nab-paclitaxel/durvalumab combination therapy, and that of the 
nab-paclitaxel monotherapy.
A secondary efficacy objective is to estimate the relative efficacy of each of the combination 
regimens to the nab-paclitaxel monotherapy regimen. 
The effect of the treatment regimens with respect to the efficacy endpoints will be based on the 
point estimates and the associated 95% confidence intervals. The sample size was chosen to 
support the estimation of the within- treatment effects with reasonable precision. In the 
durvalumab arm, a sample size of 80 subjects will further allow the estimation of the treatment 
effect with reasonable precision when stratification by prior checkpoint inhibitor exposure 
(checkpoint naïve and prior exposure to checkpoint inhibitors) is performed. 
No inferential statistical tests will be performed and no multiplicity adjustments are planned for 
the statistical analyses.
Table 7 below summarizes the two-sided 95% confidence intervals for a range of hypothetical 
observed disease control rates given a sample size of 80 subjects in a treatment arm. If the 
observed disease control rate is 0.30, then the actual width of the 2-sided 95% confidence 
interval is 0.21 (95% CI is [0.20, 0.41]).
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
69
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Table 7:
Disease Control Rate –Two-Sided 95% Confidence Interval of Hypothetical 
Disease Control Rate with a Sample Size of 80 Subjects in a Treatment Arm
Hypothetical Observed Disease 
Control Rate
Actual Width of 95% 
Confidence Interval
95% Confidence Intervala
0.20
0.186
(0.119, 0.304)
0.25
0.199
(0.16, 0.359)
0.30
0.21
(0.203, 0.413)
0.35
0.218
(0.247, 0.465
0.40
0.224
(0.292, 0.516)
0.45
0.227
(0.338, 0.565)
0.50
0.228
(0.386, 0.614)
a Based on the Clopper-Pearson exact method.
The between-treatment effect with respect to PFS can be estimated based on the point estimate of 
the hazard ratio and the associated 95% confidence interval. Table 8 below summarizes the 
precision that can be achieved given different scenarios of hypothetical observed hazard ratios 
between the treatment arms for PFS events, assuming a total of 120 events are observed. 
Table 8:
Progression-Free Survival – Two-Sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms
Hypothetical Number of Events 
Observed
Hypothetical Observed Hazard 
Ratio of PFS Events
95% Confidence Interval of 
Hazard Ratioa
120
0.60
(0.42, 0.86)
0.65
(0.45, 0.93)
0.70
(0.49, 1.00)
a Assuming a standard error of 0.18 [estimated based on (4/120)1/2] for the log hazard ratio.
Assuming the median times of PFS are 4.17 and 2.5 months, respectively, for the nab-
paclitaxel/CC-486 combination therapy and nab-paclitaxel monotherapy arms, and an 
approximate 23 months accrual period for a total of 160 subjects, it is estimated that a total of 
120 PFS events will have been observed approximately 2 months after the last subject is 
randomized to these 2 arms, assuming an exponential distribution for PFS. The final analysis of 
the nab-paclitaxel/CC-486 combination and nab-paclitaxel monotherapy arms will be performed 
when a total of approximately 120 PFS events have been observed between these two arms.
While there is published data demonstrating efficacy of nab-paclitaxel as monotherapy in a 
second line setting in advanced NSCLC with ORR ranging from 16.1 to 33% and a median PFS 
of up to 5 months, it is difficult to place an assumed treatment effect on nab-paclitaxel as a 
monotherapy (Chen, 2012; Saxena, 2012; Yuan, 2012).  The assumption of 2.5 months PFS in 
the monotherapy arm is in line with this data and other efficacy data previously observed 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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following monotherapy treatment of advanced disease with other agents (Shepherd, 2000; 
Hanna, 2004; Reck, 2014; Garon, 2014).
[Of note, with 120 PFS events, this study has an 80% power (1-sided, Type-1 error of 2.5%) to 
detect a HR of 0.60 for PFS between two treatment arms.]
Assuming the median time of PFS is 4.25 months for the nab-paclitaxel/durvalumab 
combination therapy, and an approximate 13 months accrual period for a total of approximately
80 subjects, it is estimated that a total of approximate 50 PFS events will have been observed at 
approximately 3 months after the last subject is assigned to this arm, assuming an exponential
distribution for PFS. The final analysis for PFS for the nab-paclitaxel/durvalumab arm will be 
performed when approximately 50 PFS events have been observed in this arm.
One nonbinding interim analysis for PFS with an early stopping rule for futility between the nab-
paclitaxel/CC-486 combination and nab-paclitaxel monotherapy arms will be conducted when 
approximately 60 events have been observed. The nab-paclitaxel/CC-486 combination arm may 
be stopped early for futility if the observed HR is > 1.10, and/or if recommended by the DMC 
based on the safety profile of this combination regimen. A HR> 1.10 when half of the target 
events of 120 have occurred signals a low probability for observing a meaningful difference in 
favor of the nab-paclitaxel/CC-486 combination therapy should the study continue to the end. 
With the assumptions stated above, it will take approximately 15 months from the first subject 
randomized to observe approximately 60 PFS events for the interim analysis.
An additional interim analysis for futility with the PFS endpoint between the nab-
paclitaxel/durvalumab combination therapy and nab-paclitaxel monotherapy arms will be 
conducted when approximately 30 PFS events have been observed in the nab-paclitaxel/
durvalumab combination arm. It is projected that 60 or more PFS events will have been observed 
in the nab-paclitaxel monotherapy arm at that point. The nab-paclitaxel/durvalumab combination 
arm may be stopped early for futility if the observed HR is ≥ 1.10, and/or if recommended by the 
DMC based on the safety profile of this combination regimen. With the assumptions stated 
above, it will take approximately 13 months from the first subject randomized to the nab-
paclitaxel/durvalumab arm to observe the events needed for this interim analysis.
Disease control rate, OS, and ORR within and the difference between the nab-paclitaxel/CC-486 
combination and nab-paclitaxel monotherapy treatment arms will be estimated at the time of the 
final analysis of the PFS endpoint when approximately 120 PFS events have been observed
between these two arms. The same endpoints will be estimated within the nab-
paclitaxel/durvalumab arm and between this and the nab-paclitaxel monotherapy arms when 
approximately 50 PFS events have been observed in the nab-paclitaxel/durvalumab arm. 
All subjects in the nab-paclitaxel/CC-486 combination and nab-paclitaxel monotherapy arms 
will continue to be followed for OS for at least 12 months after the last subject is randomized to
either of these two arms or 120 PFS events have been observed between these two arms, 
whichever comes later. All subjects in the nab-paclitaxel/durvalumab arm will be followed for 
OS for at least 12 months after the last subject is assigned to this arm.
The study milestones for the scenario that all 3 arms proceed to the end of the study are
summarized in the table below:
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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Study Milestone
Time from First Subject 
Randomized (Day 1)
First subject randomized to either the nab-paclitaxel/CC-486 and nab-
paclitaxel monotherapy arms (1:1 randomization ratio)
Day 1
Interim analysis for nab-paclitaxel/CC-486 vs. nab-paclitaxel 
monotherapy (~60 PFS events total)
~ 15 months
Addition of the nab-paclitaxel/durvalumab arm to the study; 
randomization in a 1:1:1 ratio to the nab-paclitaxel/CC-486, nab-
paclitaxel/durvalumab, and nab-paclitaxel arms begins.
~ 15 months
Last subject randomized to the nab-paclitaxel/CC-486 and nab-paclitaxel 
arms
~ 23 months
Assignment of all incoming subjects to the durvalumab arm begins.
~ 24 months
Final analysis for nab-paclitaxel/CC-486 vs. nab-paclitaxel (~120 PFS 
events total)
~25 months
Last subject assigned to the nab-paclitaxel/durvalumab arm
~ 28 months
Interim analysis for nab-paclitaxel/durvalumab vs. nab-paclitaxel (~30 
PFS events from nab-paclitaxel/durvalumab, ≥60 from nab-paclitaxel 
monotherapy)
~28 months
Final analysis for nab-paclitaxel/durvalumab vs. nab-paclitaxel (~50 PFS 
events have been observed in the nab-paclitaxel/durvalumab arm)
~ 31 months
End of OS Follow-up for subjects in nab-paclitaxel/CC-486 and nab-
paclitaxel arms
~ 35 months
End of OS Follow-up for durvalumab subjects
~40 months
10.4.
Background and Demographic Characteristics
The baseline characteristics of all randomized/assigned subjects will be summarized. Subject’s 
age, height, weight, and baseline characteristics will be summarized using descriptive statistics, 
while gender, race and other categorical variables will be provided using frequency tabulations. 
Selected medical history data will be summarized using frequency tabulations by system organ 
class and preferred term.
10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both Treatment 
and Follow-up Periods. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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10.6.
Efficacy Analysis
10.6.1.
Primary Efficacy Endpoints 
The primary efficacy endpoint is progression-free survival, which is defined as the time from the 
date of randomization/treatment assignment to the date of disease progression or death (any 
cause) on or prior to the data cutoff date for analyses, whichever occurs first, based on the 
Investigator’s assessment of the data from CT scans using RECIST 1.1 guidelines. Baseline 
tumor measurements will be determined from the radiologic evaluation performed within 28 
days before the start of study therapy. 
Subjects who do not have disease progression and are alive as of the data cutoff date for the 
statistical analysis will be censored at the date of the last radiologic assessment prior to the data 
cutoff date.  Similarly, subjects who discontinue from the study prior to disease progression or 
death will be censored at the date of the last radiologic assessment prior to the data cutoff date.  
In the event that a new anticancer treatment occurs prior to documented progression, the subject 
will be censored at the date of the last radiologic assessment where the subject was documented 
to be progression-free prior to the new anticancer treatment. Subjects with a single missing 
radiologic assessment prior to a visit with documented disease progression (or death) will be 
analyzed as a PFS event at the date of the radiologic assessment that shows progression or death 
(whichever is earlier). Subjects with two or more missing radiologic assessments prior to a visit 
with documented disease progression (or death) will be censored at the date of the last radiologic 
assessment where the subject was documented to be progression-free prior to the first of the two 
missing visits.  Subjects who are alive and drop out early without any post baseline radiologic 
tumor assessment will be censored on the date of randomization/treatment assignment. 
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% CI) for each treatment arm. The Kaplan-Meier curve for PFS will 
be presented graphically for each treatment arm. The relative treatment effect between the 
combination and monotherapy arms on PFS will be estimated by the hazard ratio (HR) and the 
associated two-sided 95% CIs using the stratified Cox proportional hazard model with ECOG 
performance status (0 versus 1), gender (males versus females), and smoker (yes versus no) as 
the stratification factors, given the number of events in each cell is adequate. No statistical 
inferential tests will be performed.
To assess the impact on PFS of radiologic assessments not occurring at the regularly scheduled 
assessment times, the frequency of these unscheduled/off-scheduled assessments will be 
presented for each treatment arm. In addition, confirmatory and sensitivity analyses may be 
performed to further assess the impact of missed radiologic assessments. An additional analysis 
of PFS, where death or new treatment will be considered as an event, will be conducted to 
address the impact of next line therapy. 
To explore the effect of treatment post initial progression, PFS defined by irRECIST criteria may 
be estimated for the subjects in the nab-paclitaxel/durvalumab arm.  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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10.6.2.
Secondary Efficacy Endpoints
10.6.2.1.
Disease Control Rate
Disease control rate is defined as the percent of subjects who have a radiologic complete 
response, partial response, or stable disease according to RECIST 1.1 guidelines, as determined 
by the Investigator.
Disease control rate for each treatment arm will be summarized by the observed DCR rate and 
the associated two-sided 95% CI. The relative treatment effect will be summarized by the 
absolute difference and ratio of the response rates and the associated two-sided 95% CI.
10.6.2.2.
Overall Survival
Overall survival is defined as the time between randomization/treatment assignment and death. 
All deaths, regardless of the cause of death, will be included. All subjects who are lost to follow-
up prior to the end of the study or who are withdrawn from the study will be censored at the time 
of last contact. Subjects who are still receiving treatment as of the data cutoff date will be 
censored at the cutoff date. Overall survival will be analyzed in a similar manner as that for PFS.
10.6.2.3.
Overall Response Rate 
Overall response rate is defined as the percent of subjects who have a radiologic complete or 
partial response according to RECIST 1.1 guidelines determined by the Investigator.  
Overall response rate will be assessed using the same statistical methods as those for the DCR 
endpoint.
10.6.3.
Exploratory Endpoints
10.6.3.1.
HealthCare Utilization 
Healthcare utilization will be summarized by treatment. Additional analyses will be described in 
detail in the SAP.
10.6.3.2.
Quality of Life Questionnaires
The score or VAS value and the corresponding change from baseline at each timepoint will be 
summarized by treatment for the EQ-5D-5L, EORTC QLQ C30 and LCSS questionnaires. 
Additional analyses will be described in detail in the SAP. 
10.6.3.3.
Biomarker, Tumor Characteristics, and Genomic Analyses 
Statistical analysis of the biomarkers, tumor characteristics, and genomic correlates will be 
described in a SAP separate from that described above.
10.6.3.4.
Anti-tumor Activity and PD-L1 Expression (nab-Paclitaxel/Durvalumab Arm)
An exploratory analysis of PFS and DCR using investigator’s assessments based according to 
irRECIST criteria, and their association with PD-L1 expression will be performed for subjects in 
the nab-paclitaxel/durvalumab arm.  
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entnt and dea
and dea
are lost to 
are lost to
censored a
censored
utoff date w
toff da
lar 
ar ma
manner
nne
ho ha
ho have
v a ra
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rmined by
statist
statistical
ical
marized by t
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Questionn
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ment f
ent for th
or t
f
ses will be
ses will be
Biomarker
Biomarker
cal analysis
cal analysis
ribed in a S
ribed in a 
10.6.3.4.
0.6.3.4.
n ex


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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10.7.
Safety Analysis
The treated population, which includes all subjects who receive at least one dose of IP, will be 
the analysis population for all safety analyses.
The safety/tolerability of the treatment arms will be monitored through continuous reporting and 
evaluated by adverse events and serious adverse events, and incidence of subjects experiencing 
dose modifications, dose interruptions, and/or premature discontinuation of IP.
10.7.1.
Adverse Events
TEAEs will be defined as any AE or SAE occurring or worsening on or after the day of the first 
dose of the IP through 28 days after the last dose of IP for the monotherapy arm and the nab-
paclitaxel/CC-486 combination arms, or 90 days after last dose of IP in the nab-
paclitaxel/durvalumab combination arm.  In addition, any serious AE with an onset date more 
than 28 days after the last dose of IP that is assessed by the Investigator as related to IP will be 
considered a TEAE. TEAEs occurring up to 28 days after the last dose of IP will be summarized. 
In addition, for the nab-paclitaxel/durvalumab arm, AEs with an onset from 29 days up to 90 
days after the last dose of IP will be summarized separately.
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA). The severity of AEs will be graded based on NCI CTCAE, Version 4.0; 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Treatment-emergent adverse events, Grade 3 or higher TEAEs, serious AEs, TEAEs leading to 
dose reduction, and dose interruption, TEAEs leading to treatment discontinuation, and TEAEs 
with an outcome of death will be summarized per treatment arms by MedDRA system organ 
class and preferred terms. 
Adverse events of special interest relevant to the nab-paclitaxel/CC-486 combination, nab-
paclitaxel/durvalumab combination, and nab-paclitaxel monotherapy regimens observed in 
previous studies in a similar population may be identified and summarized by worst NCI 
CTCAE grade, and MedDRA preferred terms.
By-subject listings will be provided for all relevant safety data. Graphical displays and figures 
will be provided where useful to assist in the interpretation of results.
10.7.2.
Laboratory Assessments
Treatment group differences in each laboratory parameter with respect to the NCI CTCAE 
grades will be summarized by the frequency distribution of subjects with the AE grades.  
All laboratory parameters will be summarized by descriptive statistics within each treatment arm, 
as appropriate. 
10.7.3.
IP Exposure
The extent of exposure to the IPs will be assessed based on the descriptive statistics on the 
number of cycles and IP doses administered, cumulative dose, average dose intensity, and 
percentage of protocol dose administered.  The incidences of CC-486, nab-paclitaxel, and 
durvalumab dose reductions (although not expected for durvalumab) and dose interruptions will 
be summarized by treatment arm.  
he firstst
e nab-
nab-
set date mo
set date mo
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IP
P will be su
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rom 29 day
29 d
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or Regu
f
CTCAE, V
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TEAEs, se
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0.7.3.
0.7.3.
I
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b


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
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Confidential and Proprietary
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10.8.
Study Therapy Termination
Reasons for stopping study therapy will be presented in listings and summarized by frequency of 
occurrence and corresponding percentage of occurrence.
10.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the IP
through 28 days post last dose of the IP will be summarized by frequency of occurrence and 
corresponding percentage by cause of death per period (during treatment or follow-up). In 
addition, deaths that occur from 29 to 90 days post last dose will be summarized in a similar 
manner for the nab-paclitaxel/durvalumab combination therapy arm.
10.10.
Interim Analysis
One nonbinding interim analysis for PFS with an early stopping rule for futility will be 
conducted when approximately 60 events have been observed between the nab-paclitaxel/CC-
486 combination and nab-paclitaxel monotherapy arms. The nab-paclitaxel/CC-486 combination 
arm may be stopped early for futility if the observed HR is ≥1.10 given the assumed number of 
PFS events above, and/or if recommended by the DMC based on the safety profile of this 
combination regimen.   
An additional interim analysis for futility with the PFS endpoint between the nab-
paclitaxel/durvalumab combination therapy and nab-paclitaxel monotherapy arms will be 
conducted when approximately 30 PFS have been observed in the nab-paclitaxel/durvalumab 
combination arm. This is similar to approximately half of the number of events that are planned 
for the interim analysis between the nab-paclitaxel/CC-486 combination and nab-paclitaxel 
monotherapy arms mentioned above. At this time point, it is projected that approximately ≥ 60 
PFS events will have been observed in the nab-paclitaxel monotherapy arm. The nab-
paclitaxel/durvalumab combination therapy arm may be stopped early for futility if the observed 
HR is ≥ 1.10, and/or if recommended by the DMC based on the safety profile of this 
combination regimen. Should this occur, enrollment in the study may discontinue.   
10.11.
Data Monitoring Committee
An independent DMC will be established with the responsibilities for safeguarding the interests 
of study subjects and monitoring the overall conduct of the study. Final recommendations of the 
DMC will reflect the judgment of the DMC members and will be considered advisory in nature 
to the Sponsor. The decision to implement the recommendations of the DMC will be made by 
the Sponsor, following consultation with the coordinating Investigator and Steering Committee.
Operational details for the DMC will be detailed in the DMC charter. 
10.12.
Scientific Steering Committee
The conduct of this study will be overseen by a Steering Committee. The Steering Committee 
will serve in an advisory capacity to the Sponsor.
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0.12.
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-006
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Confidential and Proprietary
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11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the eCRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of NSCLC will not require reporting as 
an adverse event. However, signs and symptoms (events) related to disease progression may be 
reported as adverse events. If reported, events of disease progression for NSCLC (including 
deaths due to disease progression for indications that are considered to be fatal) will be assessed 
as expected adverse events and will not be reported as expedited safety reports to regulatory 
authorities.
Abuse, withdrawal, sensitivity or toxicity to an investigational product should be reported as an 
AE. Overdose, accidental or intentional, whether or not it is associated with an AE should be 
reported as an AE. (See Section 8.8 for the definition of overdose.) Any sequela of an accidental 
or intentional overdose of an investigational product should be reported as an AE on the AE 
CRF. If the sequela of an overdose is an SAE, then the sequela must be reported on an SAE 
report form and on the AE CRF. The overdose resulting in the SAE should be identified as the 
cause of the event on the SAE report form and CRF but should not be reported as an SAE itself.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for nab-paclitaxel,
CC-486 or durvalumab overdose. Actual treatment should depend on the severity of the clinical 
situation and the judgment and experience of the treating physician.
All subjects will be monitored for AEs during the study. Assessments may include monitoring of 
any or all of the following parameters: the subject’s clinical symptoms, laboratory, pathological, 
radiological or surgical findings, physical examination findings, or findings from other 
appropriate tests and procedures.
All AEs will be recorded by the Investigator from the time the subject signs informed consent to
28 days after the last dose of IP for the monotherapy and CC-486 combination arms or to 90 days 
for the durvalumab combination arm, and those SAEs made known to the Investigator at any 
time thereafter that are suspected of being related to IP. AEs and serious adverse events (SAEs) 
will be recorded on the AE page of the eCRF and in the subject’s source documents. All SAEs 
must be reported to Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the 
event by facsimile, or other appropriate method, using the SAE Report Form, or approved 
equivalent form.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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11.2.
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to: 
11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
!
Results in death;
!
Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the eCRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
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Celgene Corporation
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ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
!
An elective treatment of or an elective procedure for a pre-existing condition 
unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to IP, action taken regarding IP, and outcome.
11.2.2.
Severity / Intensity
For both AEs and SAEs, the Investigator must assess the severity/intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current active minor version of NCI CTCAE, Version 4.0
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Adverse events that are not defined in the NCI CTCAE should be evaluated for severity/intensity 
according to the following scale:
!
Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required
!
Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required
!
Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible
!
Grade 4 = Life threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable
!
Grade 5 = Death – the event results in death
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.
Seriousness, not severity, serves as a guide for defining regulatory obligations.
11.2.3.
Causality 
The Investigator must determine the relationship between the administration of IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
Means a causal relationship of the adverse event to IP
administration is unlikely or remote, or other medications, 
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therapeutic interventions, or underlying conditions provide a 
sufficient explanation for the observed event.
Suspected:
Means there is a reasonable possibility that the administration 
of IP caused the adverse event.  ‘Reasonable possibility’ means 
there is evidence to suggest a causal relationship between the IP
and the adverse event.
Causality should be assessed and provided for every AE/SAE based on currently available 
information.  Causality is to be reassessed and provided as additional information becomes 
available.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP
that has not been manufactured or provided by the Sponsor, please provide the name of the 
manufacturer when reporting the event.
11.2.4.
Duration
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event.
11.2.5.
Action Taken
The Investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(eg, discontinuation or reduction of IP, as appropriate) and report if concomitant and/or 
additional treatments were given for the event. 
11.2.6.
Outcome
The Investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered or death (due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or
!
is judged to be of significant clinical importance by the Investigator.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF. If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE.
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
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Confidential and Proprietary
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11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
11.4.1.
Females of Childbearing Potential
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on IP, or within 3 months of the 
subject’s last dose of IP, are considered immediately reportable events. IP is to be discontinued 
immediately. The pregnancy, suspected pregnancy, or positive pregnancy test must be reported 
to Celgene Drug Safety immediately by facsimile, or other appropriate method, using the 
Pregnancy Initial Report Form, or approved equivalent form. The female subject should be 
referred to an obstetrician-gynecologist or another appropriate healthcare professional for further 
evaluation.
The Investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the Investigator
should report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate 
method, within 24 hours of the Investigator’s knowledge of the event using the SAE Report 
Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the Investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the Investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving IP or within 
6 months of the last dose of IP, the male subject taking IP should notify the Investigator, and the 
pregnant female partner should be advised to call her healthcare provider immediately. If the 
male subject is receiving IP, the IP may need to be discontinued in the male subject, but may be 
resumed later at the discretion of the Investigator and medical monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The Investigator is required to ensure that the data on these forms are accurate and consistent.
This requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent to at least 28 days after the last dose of IP for 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
81
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the monotherapy and CC-486 combination arms or 90 days after the last dose of IP for the 
durvalumab combination arm) and those made known to the Investigator at any time thereafter 
that are suspected of being related to IP. SAEs occurring prior to treatment (after signing the 
ICF) will be captured.
The SAE report should provide a detailed description of the SAE and include a concise summary
of hospital records and other relevant documents. If a subject died and an autopsy has been 
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available. Any follow-up data will be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety.
Where required by local legislation, the Investigator is responsible for informing the Independent 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The Investigator must keep copies of all SAE 
information on file including correspondence with the Sponsor and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than five (5) business 
days. Urgent queries (eg, missing causality assessment) may be handled by phone.
11.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to nab-paclitaxel, CC-486 or durvalumab based on the
Investigator Brochures of the respective IPs.
In the US, all suspected unexpected serious adverse reactions (SUSARs) will be reported in an 
expedited manner in accordance with 21 CFR 312.32.
For countries within the European Economic Area (EEA), the Sponsor or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 
presentation of adverse reaction reports arising from clinical trials on investigational products for 
human use (ENTR/CT3) and also in accordance with country-specific requirements.
The Sponsor or its authorized representative shall notify the Investigator of the following 
information: 
!
Any AE suspected of being related to the use of IP in this study or in other studies
that is both serious and unexpected (ie, SUSAR);
!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
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Celgene Corporation
Confidential and Proprietary
82
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with the Sponsor and the IRB/EC. (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form/Completion Guidelines or to the Pregnancy Report Form/Completion Guidelines.
11.7.
Definition of Adverse Events of Special Interest
An adverse event of special interest (AESI) is one of scientific and medical interest specific to 
the understanding of the IP and may require close monitoring and rapid communication by the 
Investigator to the Sponsor. An AESI may be serious or nonserious. The rapid reporting of 
AESIs allows ongoing surveillance of these events in order to characterize and understand them 
in association with the use of this IP. Further information on risks (eg, presenting symptoms) can 
be found in the current version of the Investigator Brochure, including guidelines for their 
evaluation and treatment.
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Celgene Corporation
Confidential and Proprietary
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12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the IP:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent
!
Death
!
Lost to follow-up
!
Protocol violation
The reason for discontinuation should be recorded in the eCRF and in the source documents.
The decision to discontinue a subject remains the responsibility of the treating physician, which
will not be delayed or refused by the Sponsor. However, prior to discontinuing a subject, the
Investigator may contact the Medical Monitor and forward appropriate supporting documents for 
review and discussion.
All subjects discontinued from IP for any reason will have a treatment discontinuation visit at the 
time of discontinuation and should undergo treatment discontinuation procedures.
All subjects discontinued from IP will be followed for a period of 28 days after last dose of IP
for the monotherapy and CC-486 combination arms or 90 days after the last dose of IP for the 
durvalumab combination arm for the collection of AEs.
Additionally subjects who withdraw from or discontinue treatment should be followed for 
progressive disease (if applicable), survival and any new anticancer therapy given.
12.2.
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
study:
!
Withdrawal of consent
!
Death
!
Lost to follow-up
The following events may be considered sufficient reasons for discontinuing a subject from the 
study:
!
Adverse events(s)
!
Protocol violation
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. The Investigator must notify the Medical Monitor immediately when a subject has 
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Celgene Corporation
Confidential and Proprietary
84
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been discontinued/withdrawn due to an AE (any unacceptable toxicity). All subjects who are 
withdrawn from the study should complete all protocol-required evaluations scheduled for early 
termination at the time of withdrawal.
Since follow-up of subjects who discontinue prematurely is of particular importance, every 
attempt should be made to collect all survival information and NSCLC treatment/therapy, unless 
the subject has specifically withdrawn consent from further follow-up. The Investigator must 
make every effort to obtain minimal information regarding the subject’s survival status before 
determining that the subject is lost to follow-up.
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.
&(/*(1(35235,(7$5<,1)250$7,21


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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
85
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13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page). This global 
Emergency Call Center is available 24 hours a day and 7 days a week. The representatives are 
responsible for obtaining your call-back information and contacting the on call Sponsor/Contract 
Research Organization (CRO) Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
13.2.
Emergency Identification of Investigational Products
This is an open-label study; therefore, IP will be identified on the package labeling. 
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-006
Celgene Corporation
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ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that the Sponsor, its authorized 
representative, and Investigator abide by Good Clinical Practice (GCP), as described in 
International Conference on Harmonization (ICH) Guideline E6 and in accordance with the 
general ethical principles outlined in the Declaration of Helsinki. The study will receive approval 
from an IRB/EC prior to commencement. The Investigator will conduct all aspects of this study 
in accordance with applicable national, state, and local laws of the pertinent regulatory 
authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. The Sponsor staff or its authorized representative will evaluate and approve 
all Investigators who in turn will select their staff.
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions. 
The Investigator should maintain a list of sub-Investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The Investigator is responsible for keeping a record of all subjects who sign an ICF and are 
screened for entry into the study. Subjects who fail screening must have the reason(s) recorded in 
the subject’s source documents.
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The Investigator must ensure timely and accurate completion of eCRFs and queries.
The information contained in the protocol and amendments (with the exception of the 
information provided by the Sponsor on public registry websites) is considered the Sponsor’s 
confidential information. Only information that is previously disclosed by the Sponsor on a 
public registry website may be freely disclosed by the Investigator or its institution, or as 
outlined in the Clinical Trial Agreement. The Sponsor’s protocol, amendment and IB 
information is not to be made publicly available (for example on the Investigator’s or their 
institution’s website) without express written approval from the Sponsor. Information proposed 
for posting on the Investigator’s or their institution’s website must be submitted to the Sponsor
for review and approval, providing at least 5 business days for review. 
At the time results of this study are made available to the public the Sponsor will provide 
Investigators with a summary of the results that is written for the lay person. The Investigator is 
responsible for sharing these results with the subject and/or their caregiver as agreed by the 
subject.
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14.3.
Subject Information and Informed Consent
The Investigator must obtain informed consent of the subject and/or the subject’s legal 
representative prior to any study-related procedures.
Documentation that informed consent occurred prior to the subject’s entry into the study and of 
the informed consent process should be recorded in the subject’s source documents including the 
date. The original ICF signed and dated by the subject and by the person consenting the subject
prior to the subject’s entry into the study, must be maintained in the Investigator’s study files and 
a copy given to the subject. In addition, if a protocol is amended and it impacts the content of the 
informed consent, the ICF must be revised. Subjects participating in the study when the amended 
protocol is implemented must be re-consented with the revised version of the ICF. The revised 
ICF signed and dated by the subject and by the person consenting the subject must be maintained 
in the Investigator’s study files and a copy given to the subject. Subjects in the nab-
paclitaxel/durvalumab arm who continue treatment beyond disease progression per RECIST 1.1 
will be requested to sign a consent form at time of progression and prior to treatment 
continuation.
14.4.
Confidentiality
The Sponsor affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). The Sponsor
requires the Investigator to permit the Sponsor's representatives and, when necessary, 
representatives from regulatory authorities, to review and/or copy any medical records relevant 
to the study in accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the Investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Sponsor’s Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the Investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
88
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
IP can only be supplied to an Investigator by the Sponsor or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
the Sponsor or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB/EC should mention the protocol title, number, amendment number 
(if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by the Sponsor and 
the IRB/EC prior to use.
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
The Sponsor reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the Investigator or the Sponsor has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
89
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and distribution of the IP are complete, accurate, filed and retained. Examples of source 
documents include: hospital records; clinic and office charts; laboratory notes; memoranda; 
subject’s diaries or evaluation checklists; dispensing records; recorded data from automated 
instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy and the laboratories, as well 
as copies of CRFs or CD-ROM.
15.2.
Data Management
Data will be collected via eCRF and entered into the clinical database per the Sponsor’s Standard 
Operating Procedures (SOPs). This data will be electronically verified through use of 
programmed edit checks specified by the clinical team. Discrepancies in the data will be brought 
to the attention of the clinical team, and investigational site personnel, if necessary. Resolutions 
to these issues will be reflected in the database. An audit trail within the system will track all 
changes made to the data.
15.3.
Record Retention
Essential documents must be retained by the Investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IP. The Investigator must retain these 
documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the Investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the Investigator, Sponsor, and their authorized 
representative(s);
!
List of sub-Investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of CRFs (if paper) and of documentation of corrections for all subjects;
!
IP accountability records;
!
Record of any body fluids or tissue samples retained;
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
90
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
!
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The Investigator must notify the Sponsor if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.
The Investigator must obtain approval in writing from the Sponsor prior to destruction of any 
records. If the Investigator is unable to meet this obligation, the Investigator must ask the 
Sponsor for permission to make alternative arrangements. Details of these arrangements should 
be documented. 
All study documents should be made available if required by relevant health authorities. The 
Investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
91
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
16.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by the Sponsor or its authorized 
representative for compliance with applicable government regulations with respect to current 
GCP and standard operating procedures.
16.1.
Study Monitoring and Source Data Verification
The Sponsor ensures that appropriate monitoring procedures are performed before, during and 
after the study. All aspects of the study are reviewed with the Investigator and the staff at a study 
initiation visit and/or at an Investigator meeting. Prior to enrolling subjects into the study, a 
Sponsor representative or designee will review the protocol, eCRFs, procedures for obtaining 
informed consent, record keeping, and reporting of AEs/SAEs with the Investigator. Monitoring 
will include on-site visits with the Investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, IP 
storage area, eCRFs, subject’s source documents, and all other study documentation will be
inspected/reviewed by the Sponsor representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the eCRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff. Any necessary 
corrections will be made directly to the eCRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within the Sponsor. Representatives of this unit will conduct audits of clinical 
research activities in accordance with the Sponsor’s SOPs to evaluate compliance with Good 
Clinical Practice guidelines and regulations.
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, eCRFs and applicable supporting records of subject participation for audits 
and inspections by IRB/IECs, regulatory authorities (eg, FDA, European Medicines Agency 
[EMA], Health Canada) and company authorized representatives. The Investigator should make 
every effort to be available for the audits and/or inspections. If the Investigator is contacted by 
any regulatory authority regarding an inspection, he/she should contact the Sponsor immediately.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
92
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
17.
PUBLICATIONS
As described in Section 14.2, all protocol- and amendment-related information, with the 
exception of the information provided by the Sponsor on public registry websites, is considered 
Sponsor’s confidential information and is not to be used in any publications. The Sponsor
protocol-related information proposed for use in a publication must be submitted to the Sponsor
for review and approval, and should not be utilized in a publication without express written 
approval from the Sponsor, or as described in the Clinical Trial Agreement. 
The Sponsor will ensure sponsored studies are considered for publication in the scientific 
literature in a peer-reviewed journal, irrespective of the results. At a minimum, this applies to 
results from all Phase 3 clinical studies, and any other study results of significant medical 
importance. This also includes results relating to investigational medicines whose development 
programs have been discontinued. 
Study results may also be presented at one or more medical congresses, and may be used for 
scientific exchange and teaching purposes. Additionally, this study and its results may be 
submitted for inclusion in all appropriate health authority study registries, as well as publication 
on health authority study registry websites, as required by local health authority regulations. 
Eligibility for external authorship, as well as selection of first authorship, will be based on  
several considerations, including, but not limited to, contribution to protocol development, study 
recruitment, data quality, participation in data analysis, participation in study steering committee 
(when applicable) and contribution to abstract, presentation and/or publication development.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
93
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
18.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
95
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
96
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
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Reck M, Popat S, Reinmuth N, De Ruysscher D, Kerr KM, Peters S; ESMO Guidelines Working 
Group. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for 
diagnosis, treatment and follow-up. Ann Oncol. 2014 Sep;25 Suppl 3:iii27-39 doi: 
10.1093/annonc/mdu199. Epub 2014 Aug 11.
Rizvi NA, Riely GJ, Azzoli CG, Miller VA, Ng KK, Fiore J, et al. Phase I/II trial of weekly 
intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with Stage IV 
non-small-cell lung cancer. J Clin Oncol 2008;26(4):639-43.
Rizvi N, Gray J, Ballas M, Jayawardene D, Stockman P, Powderly JD. A Phase 2, non-
comparative, open-label, multicenter, international study of MEDI4736 in patients with locally 
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Saxena A, Christos PJ, Cagney JM, et al. Nanoparticle albumin-bound paclitaxel (NabP) as a 
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Schiller JH, Gandara DR, Goss GD, Vokes EE.  Non-small-cell lung cancer: then and now. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
97
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Socinski MA, Schell MJ, Bakri K, Peterman A, Lee JH, Unger P, et al. Second-line, low-dose, 
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carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final 
results of a phase III trial. J Clin Oncol 2012 Jun 10;30(17):2055-62.
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Pharmacol. 2014 Oct 1;54(10):1108-16.
Yasuda K, Igishi T, Kawasaki Y, Kato K, Matsumoto S, Katayama S, et al. Phase II study of 
weekly paclitaxel in patients with non-small cell lung cancer who have failed previous 
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Yuan DM, Lv YL, Yao YW, Miao XH, Wang Q, Xiao XW, et al. Efficacy and safety of 
Abraxane in treatment of progressive and recurrent non-small cell lung cancer patients: a 
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Zhang L, Dermawan K, Jin M, Liu R, Zheng H, Xu L, et al. Differential impairment of 
regulatory T cells rather than effector T cells by paclitaxel-based chemotherapy. Clin Immunol. 
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Zhang S, Shi R, Li C, Parivar K, Wang DD. Fixed dosing versus body size-based dosing of 
therapeutic peptides and proteins in adults. J Clin Pharmacol. 2012 Jan 1;52(1):18-28. 
Zavodovskaya M, Brachmann C, DiMartino J, Pierce D. Dexamethasone interrupts paclitaxel-
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Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G. Mechanism of action of conventional and 
targeted anticancer therapies: reinstating immunosurveillance. Immunity 2013;39(1),74-88.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
98
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
19.
APPENDICES
Appendix A: ECOG Performance Status Score
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5
Dead
Oken, 1982.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
99
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Appendix B: Recommendations for Management of Treatment-Induced 
Diarrhea
The following published guidelines (Benson, 2004) were modified in order to be consistent with 
the clinical study protocol.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
100
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Appendix C: Treatment Modification and Toxicity Management for nab-
Paclitaxel /Durvalumab arm
General guidelines regarding treatment modification for MEDI4736 and/or nab-paclitaxel are 
provided below for immune-related AEs (Table C1), infusion-related reactions (Table C2), and
non-immune-mediated reactions (Table C3).
These guidelines apply to AEs considered causally related to the durvalumab containing regimen 
by the reporting Investigator. Treatment modifications referring to “study regimen” would apply 
to both nab-paclitaxel and durvalumab unless AEs are not considered causally related to nab-
paclitaxel by the reporting Investigator. In that case nab-paclitaxel treatment may be continued 
alone if deemed beneficial to the subject per Investigator’s assessment.
Table C1:
Treatment Modification and Toxicity Management Guidelines for Immune-
related Adverse Events
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
Immune-related AEs 
(overall 
management for 
toxicities not noted 
below)
Drug administration modifications 
of IP/study regimen will be made 
to manage potential immune-
related AEs based on severity of 
treatment-emergent toxicities 
graded per NCI CTCAE v4.03.
In addition to the criteria for 
permanent discontinuation of 
IP/regimen based on CTC 
Grade/severity (table below),
permanently discontinue IP/study 
regimen for the following 
conditions:
• Inability to reduce corticosteroid 
to a dose of ≤10 mg of prednisone 
per day (or equivalent) within 12 
weeks after last dose of IP/regimen
• Recurrence of a previously 
experienced Grade 3 treatment-
related AE following resumption 
of dosing.
It is recommended that 
management of ir AEs follow the 
guidelines presented in this table
- Subjects should be thoroughly 
evaluated to rule out any 
alternative etiology (eg,, disease 
progression, concomitant 
medications, infections, etc.)
- In the absence of a clear 
alternative etiology, all events 
should be considered potentially 
immune related.
- Symptomatic and topical 
therapy should be considered for 
low-grade (Grade 1 or 2, unless 
otherwise specified)
events
- For persistent (greater than 3 to 
5 days) low-grade (Grade 2) or 
severe (Grade ≥3) events 
promptly start prednisone
PO 1-2mg/kg/day or IV 
equivalent
- If symptoms recur or worsen 
during corticosteroid tapering 28 
days of taper), increase the 
corticosteroid dose (prednisone 
dose [eg, up to 2-4mg/kg/day or 
IV
equivalent]) until stabilization or 
improvement of symptoms, then 
resume corticosteroid tapering at 
a slower rate (> 28 days of taper)
- More potent 
Grade 1
No dose modification
Grade 2
Hold IP/study regimen dose until
Grade 2 resolution to ≤ Grade 1
• If toxicity worsens then treat as 
Grade 3 or Grade 4
• If toxicity improves to baseline 
then treat at next scheduled 
treatment date IP/study treatment 
can be resumed at the next 
scheduled dose once event  
stabilizes to Grade ≤1 and 5-7 days 
have passed after completion of 
steroid taper
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
101
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
Subjects with endocrinopathies 
who may require prolonged or 
continued steroid replacement can 
be retreated with IP/study regimen 
on the following conditions: 
1) the event stabilizes and is
controlled, 
2) the subject is clinically stable as 
per Investigator or treating 
physician’s clinical judgment, and 
3) doses of prednisone are at less 
than or equal to 10mg/day or 
equivalent.
immunosuppressives such as 
TNF inhibitors (eg, infliximab) 
– (also refer to the individual 
sections of the immune related 
adverse event for specific type 
of
immunosuppressive) should be 
considered for events not 
responding to systemic 
steroids.
- Discontinuation of IP is not 
mandated for Grade 3 / 4 
inflammatory reactions attributed 
to local tumor response (eg,
inflammatory reaction at sites of
metastatic disease, lymph nodes 
etc.). Continuation of IP in this 
situation should be based upon a 
benefit/risk analysis for that 
subject
Grade 3
Depending on the individual 
toxicity, may permanently 
discontinue IP/study regimen. 
Please refer to guidelines below
Grade 4
Permanently discontinue IP/study
regimen
Note: For Grade 3 and above asymptomatic amylase or 
lipase levels hold IP/regimen and if complete work up 
shows no evidence of pancreatitis, may continue or 
resume IP/regimen
Pneumonitis/ILD
Any grade
- Monitor subjects for signs and 
symptoms of pneumonitis
or ILD (new onset or worsening 
shortness of breath or cough). 
Subjects should be evaluated 
with imaging and pulmonary 
function tests including other 
diagnostic procedures as 
described below
- Initial work-up may include 
clinical evaluation,
monitoring of oxygenation via 
pulse oximetry (resting
and exertion), laboratory work-
up and high-resolution
CT scan.
Grade 1 
(asymptomatic,
clinical or
diagnostic
observations only,
intervention not 
indicated)
No dose modification required. 
However,
consider holding IP/study regimen 
dosing as clinically appropriate and 
during diagnostic work-up for 
other etiologies
For Grade 1 (radiographic 
changes only)
- Monitor and closely follow up 
in 2-4 days for clinical
symptoms, pulse oximetry 
(resting and exertion) and
laboratory work-up and then as 
clinically indicated
- Consider pulmonary and 
infectious disease consult
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
102
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
Grade 2
(symptomatic,
medical
intervention
indicated, limiting
instrumental 
ADL)
• Hold IP/study regimen dose until 
Grade 2 resolution to ≤ Grade 1
• If toxicity worsens then treat as 
Grade 3 or Grade 4
• If toxicity improves to baseline 
then the decision to reinitiate 
IP/regimen at next scheduled 
treatment date will be based upon 
treating physician’s clinical
judgment.
• IP/study treatment can be 
resumed at the next scheduled dose 
once event stabilizes to Grade ≤1 
and 5-7 days have passed after 
completion of steroid taper
For Grade 2 (mild to moderate 
new symptoms)
- Monitor symptoms daily and 
consider hospitalization
- Promptly start systemic steroids 
(eg, prednisone 1-
2 mg/kg/day or IV equivalent)
- Reimaging as clinically 
indicated
- If no improvement within 3-5 
days, additional workup
should be considered and prompt 
treatment with IV
methylprednisolone 2-4 
mg/kg/day started
- If still no improvement within 
3-5 days despite IV
methylprednisone at 2-
4/g/kg/day, promptly start
immunosuppressive therapy such 
as TNF inhibitors (eg,
infliximab at 5mg/kg every 2 
weeks). Caution: Important to 
rule out sepsis and refer to 
infliximab label for general
guidance before using infliximab
- Once improving, gradually 
taper steroids over ≥4 weeks
and consider prophylactic 
antibiotics, antifungal or anti
PCP treatment (refer to current 
NCCN guidelines for treatment 
of cancer-related infections 
(Category 2B recommendation)2
- Consider pulmonary and 
infectious disease consult
- Consider as necessary 
discussing with study physician
Grade 3 or 4 
(Grade 3: severe
symptoms; 
limiting
self-care ADL;
oxygen indicated;
Grade 4: life
threatening
Permanently discontinue IP/study
regimen
For Grade 3 or 4 (severe or new 
symptoms, new/worsening
hypoxia, life threatening
- Promptly initiate empiric IV 
methylprednisolone 1 to
4 mg/kg/day or equivalent
- Obtain pulmonary and 
infectious disease consult
- Hospitalize the subject
2 ASCO Educational Book 2015. Michael Postow MD. “Managing Immune Checkpoint Blocking Antibody Side 
Effects”
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
103
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
respiratory
compromise, 
urgent
intervention
indicated [eg,
tracheostomy or 
intubation])
- Supportive Care (oxygen, etc.)
- If no improvement within 3-5 
days, additional workup should 
be considered and prompt 
treatment with additional 
immunosuppressive therapy such 
as TNF inhibitors (eg, infliximab 
at 5mg/kg every 2 weeks dose)
started. Caution: rule out sepsis 
and refer to infliximab label for 
general guidance before using 
infliximab
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and in 
particular, anti PCP treatment 
(please refer to current NCCN 
guidelines for treatment of 
cancer-related infections 
(Category 2B recommendation)3
Diarrhea/
enterocolitis
Any grade
- Monitor for symptoms that may 
be related to diarrhea/
enterocolitis (abdominal pain, 
cramping, or changes in bowel 
habits such as increased 
frequency over baseline or blood 
in stool) or related to bowel 
perforation (such as sepsis, 
peritoneal signs and ileus)
- Subjects should be thoroughly 
evaluated to rule out any
alternative etiology (eg, disease 
progression, other medications, 
infections including testing for 
clostridium difficile toxin, etc.)
- Steroids should be considered 
in the absence of clear
alternative etiology, even for low 
grade events, in order to prevent 
potential progression to higher 
grade event
- Use analgesics carefully; they 
can mask symptoms of
perforation and peritonitis
3 ASCO Educational Book 2015. Michael Postow MD. “Managing Immune Checkpoint Blocking Antibody Side 
Effects”
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
104
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
Grade 1 diarrhea
(stool frequency 
of <4 over 
baseline per day)
No dose modification
For Grade 1 diarrhea :
- Close monitoring for worsening 
symptoms
- Consider symptomatic 
treatment including hydration,
electrolyte replacement, dietary 
changes (eg, American
Dietetic Association colitis diet), 
and loperamide. Use of
probiotics as per treating 
physician’s clinical judgment.
Grade 2 diarrhea
(stool frequency 
of 4-6 over 
baseline per day)
• Hold IP/study regimen until 
resolution to ≤ Grade 1
• If toxicity worsens then treat as 
Grade 3 or Grade 4
• If toxicity improves to baseline 
then treat at next scheduled 
treatment date
• IP/study regimen can be resumed
at the next scheduled dose once 
event stabilizes to Grade ≤1 and 5-
7 days have passed after 
completion of steroid taper
For Grade 2 diarrhea:
- Consider symptomatic 
treatment including hydration,
electrolyte replacement, dietary 
changes (eg,eg, American
Dietetic Association colitis diet), 
and loperamide and/or
budesonide
- Promptly start prednisone 1 to 
2 mg/kg/day or IV equivalent
- If event is not responsive 
within 3-5 days or worsens
despite prednisone at 1-2 
mg/kg/day or IV equivalent, GI
consult should be obtained for 
consideration of further
workup such as imaging and/or 
colonoscopy to confirm
colitis and rule out perforation, 
and prompt treatment
with IV methylprednisolone 2-
4mg/kg/day started.
- If still no improvement within 
3-5 days despite 2 to
4 mg/kg IV methylprednisolone, 
promptly start 
immunosuppressives such as 
(infliximab at 5mg/kg once
every 2 weeks). Caution: 
important to rule out bowel
perforation and refer to 
infliximab label for general
guidance before using infliximab
- Consult study physician if no 
resolution to ≤ Grade 1 in
3-4 days
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
105
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
to current NCCN
guidelines for treatment of 
cancer-related infections
[Category 2B recommendation])4
Grade 3 or 4
Diarrhea
(Grade 3: stool
frequency of ≥7
over baseline per
day;
Grade 4: life
threatening
consequences)
Permanently discontinue IP/study
regimen
For Grade 3 or 4 diarrhea:
- Promptly initiate empiric IV 
methylprednisolone 2 to 4
mg/kg/day or equivalent
- Monitor stool frequency and 
volume and maintain hydration
- Urgent GI consult and imaging 
and/or colonoscopy as
appropriate
- If still no improvement within 
3-5 days of IV 
methylprednisolone 2 to 
4mg/kg/day or equivalent,
promptly start further 
immunosuppressives (eg,
infliximab at 5mg/kg once every 
2 weeks).
- Caution: ensure GI consult to 
rule out bowel perforation
and refer to infliximab label for 
general guidance before
using infliximab.
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN
guidelines for treatment of 
cancer-related infections
[Category 2B recommendation])
Hepatitis
(elevated LFTs)
Infliximab
should not be
used for
management of
immune related
hepatitis
Grade of liver
function test
elevation 
(CTCAE
version 4.03)
Any grade
Grade 1
(AST or ALT 
>ULN
to 3 times ULN
and/or TB > ULN 
to
No dose modification
If it worsens, treat as Grade 2 event
- Monitor and evaluate liver 
function test: AST, ALT, ALP
and total bilirubin
- Evaluate for alternative 
etiologies (eg, viral hepatitis,
disease progression, concomitant 
medications)
For Grade 1 AST or ALT and/or 
TB elevation
- Continue LFT monitoring per 
protocol
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Effects”
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
106
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
1.5 times ULN)
Grade 2
(AST or ALT > 3 
to 5 times ULN 
and/or TB >1.5-
3.0 times ULN)
Hold IP/study regimen dose until
Grade 2 resolution to ≤ Grade 1
• If toxicity worsens then treat as 
Grade 3 or Grade 4
• If improves to baseline then treat 
at next scheduled treatment date
IP/study regimen can be resumed 
at the next scheduled dose once 
event stabilizes to Grade ≤1 and 5-
7 days have passed after
completion of steroid taper
For Grade 2 AST or ALT and or 
TB elevation:
- Regular and frequent checking 
of LFTs (eg, every 1-2 days) 
until elevations of these are 
improving or resolved.
- If no resolution to ≤ Grade 1 in 
1-2 days, discuss with study 
physician.
- If event is persistent (> 3-5 
days) or worsens, promptly
start prednisone 1-2mg/kg/day or 
IV equivalent.
- If still no improvement within 
3-5 days despite 1- 2mg/kg/day 
of prednisone or IV equivalent, 
consider additional workup and 
prompt treatment with IV
methylprednisolone 2-
4mg/kg/day started.
- If still no improvement within 
3-5 days despite 2-
4mg/kg/day of IV 
methylprednisolone, promptly 
start immunosuppressives 
(mycophenolate mofetil). 
Discuss with study physician if 
mycophenolate mofetil is not
available. Infliximab should 
NOT be used.
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN guidelines for 
treatment of cancer-related 
infections [Category 2B 
recommendation])
Grade 3
(AST or ALT >5-
20 times ULN 
and/or TB > 3.0-
10
times ULN
For elevations in transaminases ≤ 8 
× ULN, or elevations in bilirubin ≤ 
5 × ULN:
• Hold IP/study regimen dose until 
resolution to ≤ Grade 1 or baseline
• Resume IP/study regimen 
administration at the next 
scheduled dose if elevations 
downgrade ≤ Grade 1 or baseline
within 14 days
• Permanently discontinue IP/study 
regimen if the elevations do not 
For Grade 3 or 4 AST or ALT 
and/or TB elevation:
- Promptly initiate empiric IV 
methylprednisolone at 1 to 4
mg/kg/day or equivalent
- If still no improvement within 
3-5 days despite 1 to
4 mg/kg/day methylprednisolone 
IV or equivalent, promptly start 
treatment with 
immunosuppressive
therapy (mycophenolate 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
107
ABI-007-NSCL-006 Amendment 3.0 Final: 14Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
downgrade
to ≤Grade 1 or baseline within 14 
days
• For elevations in transaminases > 
8 × ULN or elevations in bilirubin 
> 5 × ULN, discontinue IP/study 
regimen
• Permanently discontinue IP/study 
regimen for any case meeting Hy’s 
law criteria (ALT > 3x ULN + 
bilirubin > 2x
ULN without initial findings of 
cholestasis (ie,elevated alkaline 
P04) and in the absence of any 
alternative cause
5
mofetil). Discuss with study
physician if mycophenolate is 
not available. Infliximab
should NOT be used.
-Hepatology consult, abdominal 
workup, and imaging as
appropriate.
-Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN
guidelines for treatment of 
cancer-related infections
[Category 2B recommendation])
Grade 4
(AST or ALT > 
20 times ULN 
and/or TB > 10 
times ULN)
Permanently discontinue IP/study
regimen
Nephritis or renal
dysfunction
(elevated serum
creatinine)
Grade of elevated
serum creatinine
(CTCAE version
4.03)
Any grade
-Consult with nephrologist
-Monitor for signs and 
symptoms that may be related to
changes in renal function (eg,
routine urinalysis, elevated 
serum BUN and creatinine, 
decreased creatinine clearance, 
electrolyte imbalance, decrease 
in urine output, proteinuria, etc.)
-Subjects should be thoroughly 
evaluated to rule out any
alternative etiology (eg,disease 
progression, infections etc.)
-Steroids should be considered 
in the absence of clear
alternative etiology even for low 
grade events (Grade 2), in order 
to prevent potential progression 
to higher grade event
Grade 1 [serum
creatinine > 1-
1.5X baseline; > 
ULN to 1.5X  
ULN]
No dose modification
For Grade 1 elevated creatinine:
-Monitor serum creatinine 
weekly and any accompanying
symptom
If creatinine returns to 
baseline, resume its
regular monitoring per study 
protocol.
                                               
5FDA Liver Guidance Document 2009 Guidance for Industry: Drug Induced Liver Injury –Premarketing Clinical 
Evaluation
CELGENE PROPRIETARY INFORMATION


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
108
ABI-007-NSCL-006 Amendment 3.0 Final: 14Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
If it worsens, depending on the 
severity , treat as Grade 2 or 
Grade 3 or 4
-Consider symptomatic 
treatment including hydration,
electrolyte replacement, 
diuretics, etc.
Grade 2 [serum
creatinine>1.5-
3.0X baseline; 
>1.5X-
3.0XULN]
Hold IP/study regimen until 
resolution to ≤ Grade 1
• If toxicity worsens then treat as 
Grade 3 or Grade 4
• If toxicity improves to baseline 
then treat at next scheduled 
treatment date IP/study regimen 
can be resumed at
the next scheduled dose once event 
stabilizes to Grade ≤1 for 5-7 days 
have passed after completion of 
steroid taper
For Grade 2 elevated creatinine:
-Consider symptomatic 
treatment including hydration,
electrolyte replacement, 
diuretics, etc.
-Carefully monitor serum 
creatinine every 2-3 days and as
clinically warranted
-Consult nephrologist and 
consider renal biopsy if
clinically indicated
-If event is persistent (> 3-5 
days) or worsens, promptly
start prednisone 1 to 2 
mg/kg/day or IV equivalent
-If event is not responsive 
within 3-5 days or worsens
despite prednisone at 1-2 
mg/kg/day or IV equivalent,
additional workup should be 
considered and prompt
treatment with IV 
methylprednisolone at 2-
4mg/kg/day started.
-Once improving gradually taper 
steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN guidelines for 
treatment of cancer-related 
infections [Category 2B 
recommendation]).
-When event returns to baseline, 
resume IP/study
regimen and routine serum 
creatinine monitoring per
study protocol.
Grade 3 or 4
(Grade 3: serum
creatinine > 3.0 X
baseline; >3.0-6.0
X ULN
Permanently discontinue IP/study 
regimen
-Carefully monitor serum 
creatinine on daily basis
-Consult Nephrologist and 
consider renal biopsy if
clinically indicated
-Promptly startprednisone 1 to 
2 mg/kg/day or IV equivalent
CELGENE PROPRIETARY INFORMATION


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
109
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
- If event is not responsive 
within 3-5 days or worsens
despite prednisone at 1-2 
mg/kg/day or IV equivalent,
additional workup should be 
considered and prompt
treatment with IV 
methylprednisolone 2-
4mg/kg/day started.
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN guidelines for 
treatment of cancer-related 
infections [Category 2B 
recommendation]
Rash (excluding
bullous skin
formations)
Any grade
• Monitor for signs and 
symptoms of dermatitis (rash and
pruritus)
• **IF THERE IS ANY 
BULLOUS FORMATION, THE
STUDY PHYSICIAN SHOULD 
BE CONTACTED AND
IP DISCONTINUED**
Grade 1
No dose modification
For Grade 1:
- Consider symptomatic 
treatment including oral
antipruritics (eg,
diphenhydramine or 
hydroxyzine) and topical therapy 
(eg, urea cream)
Grade 2
For persistent (> 1- 2 weeks) 
Grade 2 events, hold scheduled 
IP/study regimen until
resolution to ≤ Grade 1 or baseline
• If toxicity worsens then treat as 
Grade 3
• If toxicity improves then resume
administration at next scheduled 
dose
• IP/study regimen can be resumed 
at the next scheduled dose once 
event stabilizes to Grade ≤1 and 5-
7 days have passed after 
completion of steroid taper
For Grade 2 :
- Obtain dermatology consult
- Consider symptomatic 
treatment including oral
antipruritics (eg,
diphenhydramine or 
hydroxyzine) and
topical therapy (eg, urea cream)
- Consider moderate-strength 
topical steroid
- If no improvement of rash/skin 
lesions occurs within 3-5
days or is worsening despite 
symptomatic treatment
and/or use of moderate strength 
topical steroid, discuss
with study physician and 
promptly start systemic steroids
prednisone 1-2 mg/kg/day or IV 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
110
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
equivalent
- Consider skin biopsy if 
persistent for >1-2 weeks or
recurs
Grade 3
• Hold IP/study regimen until 
resolution to ≤ Grade 1 or baseline
• If temporarily holding the study
drug/study regimen does not 
provide improvement of the Grade 
3 skin rash to ≤ Grade 1 or baseline 
within 30 days, then permanently 
discontinue IP/study regimen
For Grade 3 or 4:
- Consult dermatology
- Promptly initiate empiric IV 
methylprednisolone 1 to
4 mg/kg/day or equivalent
- Consider hospitalization
- Monitor extent of rash [Rule of 
Nines]
- Consider skin biopsy 
(preferably more than 1) as
clinically feasible.
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN guidelines for 
treatment of cancer-related 
infections [Category 2B 
recommendation])
- Discuss with study physician
Grade 4
Permanently discontinue IP/study 
regimen
Endocrinopathy
(eg,
hyperthyroidism,
hypothyroidism,
hypopituitarism,
adrenal
insufficiency,
etc.)
Any grade
- Consult Endocrinologist
- Monitor subjects for signs and 
symptoms of endocrinopathies. 
Non-specific symptoms include
headache, fatigue, behavior 
changes, changed mental
status, vertigo, abdominal pain, 
unusual bowel habits, 
hypotension and weakness.
- Subjects should be thoroughly 
evaluated to rule out any
alternative etiology (eg, disease 
progression including
brain metastases, infections, etc.)
- Monitor and evaluate thyroid 
function tests: TSH, free T3
and free T4 and other relevant 
endocrine labs depending
on suspected endocrinopathy.
- If a subject experiences an AE 
that is thought to be possibly of 
autoimmune nature (eg,
thyroiditis, pancreatitis, 
hypophysitis, diabetes insipidus), 
the investigator should send a 
blood sample for appropriate
autoimmune antibody testing
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
111
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
Grade 1
(depending on the
type of
endocrinopathy,
refer to NCI
CTCAE version
4.03 for defining
the CTC Grade 1)
No dose modification
For Grade 1: (including those 
with asymptomatic TSH
elevation)
- Monitor subject with 
appropriate endocrine function 
tests
- If TSH < 0.5X LLN, or TSH 
>2X ULN or consistently
out of range in 2 subsequent 
measurements, include FT4
at subsequent cycles as clinically 
indicated and consider
endocrinology consult.
Grade 2
(depending on the
type of
endocrinopathy,
refer to NCI
CTCAE version
4.03 for defining
the CTC 
Grade/severity 2)
For Grade 2 endocrinopathy other 
than hypothyroidism, hold IP/study 
regimen dose until subject is 
clinically stable
• If toxicity worsens then treat as 
Grade 3 or Grade 4
• If toxicity improves to baseline 
then treat at next scheduled 
treatment date IP/study regimen 
can be resumed at
the next scheduled dose once event 
stabilizes to Grade ≤1 and 5-7 days 
have passed after completion of 
steroid taper
Subjects with endocrinopathies 
who may require prolonged or 
continued steroid replacement can 
be retreated with IP/study regimen 
on the following
conditions: 
1) the event stabilizes and is
controlled ,
2) the subject is clinically stable as
per Investigator or treating 
physician’s clinical judgement, and 
3) doses of prednisone are at
less than or equal to 10mg/day or 
equivalent.
For Grade 2: (including those 
with symptomatic
endocrinopathy)
- Isolated hypothyroidism may 
be treated with replacement
therapy without treatment 
interruption and without
corticosteroids
- Initiate hormone replacement 
as needed for management
- Evaluate endocrine function, 
and as clinically indicated,
consider pituitary scan
- For subjects with abnormal 
endocrine work up, except
for those with isolated 
hypothyroidism, consider
short-term, corticosteroids (eg,
1-2 mg/kg/day
methylprednisolone or IV 
equivalent) and prompt
initiation of treatment with 
relevant hormone
replacement (eg, Levothyroxine, 
hydrocortisone, or sex
hormones). 
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN
guidelines for treatment of 
cancer-related infections
[Category 2B recommendation])
- For subjects with normal 
endocrine work up (lab or MRI
scans), repeat labs/MRI as 
clinically indicated.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
112
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
Grade 3 or 4
(depending on the
type of
endocrinopathy,
refer to NCI
CTCAE version
4.03 for defining
the CTC Grade/
severity 3 or 4)
• For Grade 3 or 4 endocrinopathy 
other than hypothyroidism, hold 
IP/study regimen dose until 
endocrinopathy symptom(s) are 
controlled
• Resume IP/study regimen 
administration if controlled at the 
next scheduled dose
• IP/study regimen can be resumed 
at the next scheduled dose once 
event stabilizes to Grade ≤1 and 5-
7 days have passed after 
completion of steroid taper.
For Grade 3 or 4:
- Consult endocrinologist
- Isolated hypothyroidism may 
be treated with replacement
therapy without treatment 
interruption and without
corticosteroids
- Promptly initiate empiric IV 
methylprednisolone 1 to 2
mg/kg/day or equivalent
- Administer hormone 
replacement therapy as 
necessary.
- For adrenal crisis, severe 
dehydration, hypotension, or
shock: immediately initiate 
intravenous corticosteroids
with mineralocorticoid activity
- Once improving, gradually 
taper immunosuppressive
steroids over ≥4 weeks and 
consider prophylactic
antibiotics, antifungals and anti 
PCP treatment (please
refer to current NCCN guidelines 
for treatment of cancer related
infections [Category 2B 
recommendation])
- Discuss with study physician
Immune mediated
neurotoxicity (to
include but not
limited to limbic
encephalitis .
autonomic
neuropathy,
excluding
myasthenia gravis
and Guillain-Barre)
Any grade
- Subjects should be evaluated to 
rule out any alternative etiology 
(eg, disease progression, 
infections, metabolic syndromes 
and medications, etc.)
- Monitor subject for general 
symptoms (headache, nausea,
vertigo, behavior change, or 
weakness)
- Consider appropriate diagnostic 
testing (eg, electromyogram and 
nerve conduction investigations)
- Symptomatic treatment with 
neurological consult as
appropriate
Grade 1
No dose modifications
See “Any Grade” 
recommendations above.
Grade 2
• For acute motor neuropathies or
neurotoxicity, hold study rug/study
regimen dose until resolution to ≤ 
Grade 1
• For sensory neuropathy/ 
neuropathic pain, consider holding 
For Grade 2:
- Discuss with the study 
physician
- Obtain Neurology Consult
- Sensory neuropathy/ 
neuropathic pain may be 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
113
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
IP/study regimen dose until 
resolution to ≤ Grade 1
- If toxicity worsens then treat as
Grade 3 or Grade 4
- If toxicity improves to baseline 
then treat at next scheduled 
treatment date
• IP/study regimen can be resumed 
at the next scheduled dose once 
event stabilizes to Grade ≤1 and 5-
7 days have passed after 
completion of steroid taper
managed by appropriate 
medications (eg, gabapentin, 
duloxetine, etc.)
- Promptly start systemic steroids 
prednisone 1-
2mg/kg/day or IV equivalent
- If no improvement within 3-5 
days despite 1-2mg/kg/day
prednisone or IV equivalent 
consider additional workup
and promptly treat with 
additional immunosuppressive
therapy (eg, IVIG)
Grade 3
• Hold IP/study regimen dose until
resolution to ≤ Grade 1
• Permanently discontinue Study
drug/study regimen if Grade 3 
irAE does not resolve to ≤ Grade 1 
within 30 days.
For Grade 3 or 4:
- Discuss with study physician
- Obtain Neurology Consult
- Consider hospitalization
- Promptly initiate empiric IV 
methylprednisolone 1 to 2
mg/kg/day or equivalent
- If no improvement within 3-5 
days despite IV corticosteroids, 
consider additional workup and 
promptly treat with additional 
immunosuppressants (eg, IVIG)
- Once stable, gradually taper 
steroids over ≥4 weeks
Grade 4
Permanently discontinue IP/study 
regimen
Immunemediated
peripheral
neuromotor
syndromes, such
as Guillain-Barre
and myasthenia
gravis
Any grade
- The prompt diagnosis of 
immune-mediated peripheral
neuromotor syndromes is 
important, since certain
subjects may unpredictably 
experience acute
decompensations which can 
result in substantial morbidity or 
in the worst case, death. Special 
care should be taken for certain 
sentinel symptoms which may
predict a more severe outcome, 
such as prominent dysphagia, 
rapidly progressive weakness, 
and signs of respiratory 
insufficiency or autonomic 
instability
- Subjects should be evaluated to 
rule out any alternative etiology 
(eg, disease progression, 
infections, metabolic syndromes 
and medications, etc.). It should 
be noted that the diagnosis of 
immune-mediated peripheral 
neuromotor syndromes can be 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
114
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
particularly challenging in 
subjects with underlying cancer, 
due to the multiple potential
confounding effects of cancer 
(and its treatments) throughout 
the neuraxis. Given the 
importance of prompt and 
accurate diagnosis, it is essential 
to have a low threshold to obtain 
a neurological consult
- Neurophysiologic diagnostic 
testing (eg, electromyogram and 
nerve conduction  investigations, 
and “repetitive stimulation” if 
myasthenia is suspected) are 
routinely indicated upon 
suspicion of such conditions and 
may be best facilitated by means 
of a neurology consultation
Important to consider that the 
use of steroids as the primary 
treatment of Guillain-Barre is not 
typically considered effective. 
Subjects requiring treatment 
should be started with IVIG and 
followed by plasmapheresis if
not responsive to IVIG
Grade 1
No dose modification
For Grade 1:
- Discuss with the study 
physician
- Care should be taken to 
monitor subjects for sentinel
symptoms of a potential 
decompensation as described
above
- Obtain a neurology consult 
unless the symptoms are very
minor and stable
Grade 2
• Hold IP/study regimen dose until 
resolution to ≤ Grade 1
• Permanently discontinue IP/study 
regimen if it does not resolve to ≤ 
Grade 1 within 30 days or if there 
are signs of
respiratory insufficiency or 
autonomic instability
For Grade 2:
- Discuss with the study 
physician
- Care should be taken to 
monitor subjects for sentinel
symptoms of a potential 
decompensation as described
above
- Obtain a Neurology Consult
- Sensory neuropathy/ 
neuropathic pain may be 
managed by appropriate 
medications (eg, gabapentin, 
duloxetine, etc.)
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
115
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
MYASTHENIA GRAVIS
o Steroids may be successfully 
used to treat Myasthenia Gravis. 
Important to consider that
steroid therapy (especially with 
high doses) may result in 
transient worsening of 
myasthenia and should typically 
be administered in a monitored
setting under supervision of a 
consulting neurologist.
o Subjects unable to tolerate 
steroids may be candidates for 
treatment with plasmapheresis or
IVIG. Such decisions are best 
made in consultation with a 
neurologist, taking into account 
the unique needs of each subject.
o If Myasthenia Gravis-like 
neurotoxicity present,
consider starting AChE inhibitor 
therapy in addition to steroids. 
Such therapy, if successful,
can also serve to reinforce the 
diagnosis.
GUILLAIN-BARRE:
o Important to consider here that 
the use of steroids as the primary 
treatment of Guillain-Barre is not 
typically considered effective.
Subjects requiring treatment 
should be started with IVIG and 
followed by plasmapheresis if
not responsive to IVIG.
Grade 3
• Hold IP/study regimen dose until 
resolution to ≤ Grade 1
• Permanently discontinue IP/study 
regimen if Grade 3 irAE does not 
resolve to ≤ Grade 1 within 30 
days or if there are
signs of respiratory insufficiency 
or autonomic instability
For severe or life threatening 
(Grade 3 or 4) events:
- Discuss with study physician
- Recommend hospitalization
- Monitor symptoms and obtain 
neurological consult
MYASTHENIA GRAVIS
o Steroids may be successfully 
used to treat Myasthenia Gravis. 
It should typically be
administered in a monitored 
setting under supervision of a 
consulting neurologist.
o Subjects unable to tolerate 
steroids may be candidates for 
Grade 4
Permanently discontinue IP/study
regimen
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
116
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
treatment with plasmapheresis or
IVIG.
o If Myasthenia Gravis-like 
neurotoxicity present, consider 
starting AChE inhibitor therapy 
in addition to steroids. Such 
therapy, if successful, can also 
serve to reinforce the diagnosis.
GUILLAIN-BARRE:
◦ Important to consider here that 
the use of steroids as the primary 
treatment of Guillain-Barre is not
typically considered effective. 
Subjects requiring treatment 
should be started with IVIG and
followed by plasmapheresis if 
not responsive to IVIG
AChE = acetylcholine esterase; ADL = activities of daily living; AE = adverse event; ALP = alkaline phosphatase; ALT = 
alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CT = computed tomography; CTC = 
Common Terminology Criteria; FT4 = free thyroxine; GI = gastrointestinal; ILD = interstitial lung disease; irAE = immune-
related adverse event; IV = intravenous; IVIG = intravenous immunoglobulin; LFT = liver function test; LLN = lower limit of 
normal; MRI = magnetic resonance imaging; NCCN = National  Comprehensive Cancer Network; NCI CTCAE = National 
Cancer Institute Common Terminology Criteria for Adverse Events; PCP = pneumocystis pneumonia; PO = oral; TB = total 
bilirubin; TNF = tumor necrosis factor; TSH = thyroid-stimulating hormone; ULN = upper limit of normal.
Table C2:
Treatment Modification and Toxicity Management Guidelines for Infusion-
related Adverse Events
CTC 
Grade/Severity
Dose Modifications
Toxicity Management
Any grade
- Management per institutional standard at the 
discretion of investigator
- Monitor subjects for signs and symptoms of infusion-
related reactions (eg, fever and/or shaking chills, 
flushing and/or itching, alterations in
heart rate and blood pressure, dyspnea or chest 
discomfort, skin rashes etc.) and anaphylaxis (eg,
generalized urticaria, angioedema, wheezing, 
hypotension, tachycardia, etc.)
Grade 1
The infusion rate of IP/study 
regimen may be
decreased by 50% or temporarily 
interrupted until resolution of the 
event
For Grade 1 or Grade 2:
- Acetaminophen and/or antihistamines may be 
administered per institutional standard at the discretion 
of the investigator
- Consider premedication per institutional standard 
prior to subsequent doses
Grade 2 
The infusion rate of IP/study 
regimen may be
decreased 50% or temporarily 
interrupted until resolution of the 
event
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
117
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
CTC 
Grade/Severity
Dose Modifications
Toxicity Management
Subsequent infusions may be given 
at 50% of the initial infusion rate
Grade 3 or 4 
Permanently discontinue IP/study 
regimen
For Grade 3 or 4:
Manage severe infusion-related reactions per 
institutional standards
(eg, IM epinephrine, followed by IV diphenhydramine 
and ranitidine,
and IV glucocorticoid) 
IM = intramuscular; IV = intravenous.
Table C3:
Treatment Modification and Toxicity Management Guidelines for Non-
immune-mediated Reactions
CTC 
Grade/Severity
Dose Modifications
Toxicity Management
Any grade
Note: dose modifications are not required for 
adverse events not deemed to be related to study 
treatment (ie, events due to underlying disease) or 
for laboratory abnormalities not deemed to be 
clinically significant.
Treat accordingly as per institutional 
standard
Treat accordingly as per institutional 
standard
Grade 1
No dose adjustment 
Grade 2 
Hold IP/study regimen until resolution to ≤ Grade 1 
or baseline
Grade 3
Hold IP/study regimen until resolution to ≤ Grade 1 
or baseline
For AEs that downgrade to ≤ Grade 2 within 7 days 
or resolve to ≤ Grade 1 or baseline within
14 days, resume IP/study regimen administration at 
next scheduled dose. Otherwise,
discontinue IP/study regimen
Grade 4
Discontinue IP/study regimen (Note for Grade 4 
labs, decision to discontinue would be
based on accompanying clinical signs/symptoms 
and as per Investigator’s clinical judgment and
in consultation with the sponsor)
AE = adverse event; CTC = Common Terminology Criteria.
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('06'RF1XPEHU
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This is a representation of an electronic record that was signed electronically in Livelink.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
TITLE PAGE
A PHASE 2, RANDOMIZED, OPEN-LABEL, 
MULTICENTER STUDY TO ASSESS SAFETY AND 
EFFICACY OF NAB®-PACLITAXEL (ABI-007) WITH 
EPIGENETIC MODIFYING THERAPY OF
CC-486, AND NAB®-PACLITAXEL MONOTHERAPY AS 
SECOND-LINE TREATMENT IN SUBJECTS WITH 
ADVANCED NONSQUAMOUS NON-SMALL CELL 
LUNG CANCER (NSCLC): ABOUND.2L
INVESTIGATIONAL PRODUCTS:
CC-486, nab-Paclitaxel (ABI-007)
PROTOCOL NUMBER:
ABI-007-NSCL-006
DATE FINAL:
29 May 2014
AMENDMENT 1 FINAL:
24 June 2014
EudraCT NUMBER
2014-001105-41
IND NUMBER
123160
SPONSOR NAME / ADDRESS:
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
United States
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board. The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations.
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them.
&(/*(1(
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20
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, your staff, a
document is r
cument is r
may no
may no
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information:
Name:
Title:
Address: 
86 Morris Avenue
Summit, NJ 07901
United States
Phone:
E-mail:
Contact Information:
Name:
Title:
Address: 
86 Morris Avenue
Summit, NJ 07901
United States
Phone:
E-mail:
Note: The back-up 24 hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls.
Back-up 24 Hour Global Emergency Contact Call Center: 
&(/*(1(
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}.
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
 
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.
&(/*(1(35235,(7$5<,1)250$7,21
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:_______________________________________
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
PROTOCOL SUMMARY
Study Title
A Phase 2, randomized, open-label, multicenter study to assess safety and efficacy of nab-
paclitaxel (ABI-007) with epigenetic modifying therapy of CC-486, and nab-paclitaxel 
monotherapy as second-line treatment in subjects with advanced nonsquamous non-small cell
lung cancer (NSCLC): ABOUND.2L
Indication
Second-line treatment of advanced nonsquamous NSCLC.
Objectives
Primary
!
To assess the efficacy of nab-paclitaxel1 administered intravenously (IV) on Days 8 
and 15 with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 
14 every 21 days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 
every 21 days as second-line treatment for advanced nonsquamous NSCLC, and the 
relative efficacy of these two treatment regimens.
Secondary 
!
To evaluate the safety and tolerability of nab-paclitaxel administered IV on Days 8 
and 15 in combination with epigenetic modifying therapy of CC-486 once daily (QD) 
on Days 1 to 14 every 21 days, and nab-paclitaxel monotherapy administered IV on 
Days 1 and 8 every 21 days as second-line treatment for advanced nonsquamous 
NSCLC.
Exploratory 
!
To assess healthcare resource utilization for the two treatment arms.
!
To assess the quality of life (QoL) for the two treatment arms.
!
To determine baseline tumor characteristics which predict response to nab-paclitaxel 
as a single agent and in combination with epigenetic modifying therapy of CC-486. 
!
To evaluate genomic correlates of response to nab-paclitaxel as a single agent and in 
combination with epigenetic modifying therapy of CC-486.
Study Design
This is a Phase 2, randomized, open-label, multicenter study to assess efficacy and safety of  
nab-paclitaxel in combination with epigenetic modifying therapy of CC-486, and nab-paclitaxel 
monotherapy as second-line treatment in subjects with advanced nonsquamous NSCLC who 
have received one platinum-containing chemotherapy regimen. Approximately 160 subjects with 
advanced nonsquamous NSCLC will be randomized 1:1 into one of the two treatment arms: nab-
paclitaxel / CC-486 combination therapy or nab-paclitaxel monotherapy prior to receiving first 
1 nab® is a registered trademark of Celgene Corporation.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
dose of investigational product (IP). Randomization will be centralized and stratified by Eastern 
Cooperative Oncology Group (ECOG) performance status (0 versus 1, see Appendix A), gender
(males versus females), and smoker (yes versus no).
The study will consist of up to a 28-day Screening Period, a Treatment Period and a Follow-up 
Period.  
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of IP.
The Treatment Period begins with the first dose of IP as described in Section 8.  Subjects will 
receive one of the following treatments based on the randomization assignment:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days  1 to 14 of each 21-day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment  cycle
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, withdrawal of 
consent, or termination of the study by the sponsor.
Tumor evaluations will be assessed by the investigative sites and response will be determined 
according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, Version 1.1
(Eisenhauer, 2009).
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an adverse event (AE)/serious adverse event (SAE) and also recorded on the 
laboratory electronic Case Report Form (eCRF) (see Section 11.3).
All subjects who discontinue from treatment for any reason other than withdrawal of consent, 
lost to follow-up, death, or termination of the study by the sponsor will enter the Follow-up 
Period. It will consist of a visit 28 days after treatment discontinuation. Thereafter, subjects will 
be followed for survival by phone call contact approximately every 90 days (+/- 14 days) for 12
months after the last subject is randomized or 120 progression-free survival (PFS) events have 
been observed, whichever comes later.
During the study, subjects will have computed tomography (CT) scans every 42 days (-3/+7 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the sponsor. Those subjects entering the Follow-up Period without 
documented progression will continue to have CT scans in accordance with local standard of 
care (or approximately every 90 days) until documented progression of disease, withdrawal of
consent, lost to follow-up, death, or termination of the study by the sponsor. All posttreatment 
anticancer therapies will be recorded during the Follow-up Period.  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
Study Population
Male and female subjects with advanced nonsquamous NSCLC who have received one 
platinum-containing chemotherapy regimen for their advanced disease will be eligible for this 
study.
Length of Study
The enrollment of 160 subjects on this study will take approximately 24 months. The total length 
of this Phase 2 study with follow-up is estimated to be approximately 3 years.
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
study, or the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol and/or the 
Statistical Analysis Plan, whichever is the later date.
Study Treatments
Subjects will receive nab-paclitaxel in combination with CC-486 or nab-paclitaxel monotherapy 
during the study. The CC-486 and nab-paclitaxel for both arms are designated as IP and will be 
packaged and supplied by Celgene Corporation.
Overview of Statistical Methods
The primary objective of this study is to evaluate the efficacy of the CC-486 and nab-paclitaxel 
combination therapy and that of the nab-paclitaxel monotherapy, and the relative efficacy of 
these two treatment regimens.  
Approximately 160 subjects will be randomized to the two treatment arms in a 1:1 ratio.  A 
permuted-block randomization method will be employed, and the randomization will be carried 
out centrally using an Interactive Response Technology (IRT) system. The randomization will be 
stratified based on the following baseline factors: ECOG performance status (0 versus 1), gender 
(males versus females), and smoker (yes versus no).
Evaluations of the study endpoints will be based primarily on the point estimates and the 
associated 95%  confidence intervals of the within- and between-treatment differences. However, 
nominal p-values from statistical tests may be provided in the clinical study report to indicate the 
strength of the treatment differences evaluated. 
An independent Data Monitoring Committee (DMC) will be established to review the interim 
safety and efficacy data.  
Efficacy Analyses
The intent-to-treat population, which includes all randomized subjects regardless of whether the 
subject receives any IP or has any efficacy assessments performed, will be used for all efficacy 
analyses. The primary efficacy endpoint is PFS, which is defined as the time from the date of 
randomization to the date of disease progression or death (from any cause) on or prior to the data 
cutoff date for analyses, whichever occurs first, based on the investigator’s assessment of the 
data from CT scans using RECIST 1.1 guidelines. Baseline tumor measurements will be 
determined from the radiologic evaluation performed within 28 days before the start of study 
therapy. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
9
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% confidence interval [CI]) for each treatment arm.  The relative 
treatment effect between the combination and monotherapy arms with respect to PFS will be 
estimated by the hazard ratio (HR) and the associated two-sided 95% CIs using the stratified Cox 
proportional hazard model with ECOG performance status (0 versus 1), gender (males versus 
females), and smoker (yes versus no) as the stratification factors. No statistical inferential tests 
will be performed. 
The secondary endpoints include disease control rate (DCR), overall response rate (ORR), and 
overall survival (OS). Disease control rate and ORR will be summarized within each treatment 
arm by the observed rates and the associated 95% CIs. The relative treatment effect will be 
summarized by the absolute difference and the  ratio of the observed rates. Overall survival will 
be analyzed using similar statistical method as that for the PFS endpoint.
Safety Analyses
The treated population, which includes all randomized subjects who receive at least one dose of 
IP, will be the analysis population for all safety analyses. 
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AE or SAE occurring or worsening on or after the day of the first dose of the IP
through 28 days after the last dose of IP.  In addition, any SAE with an onset date more than 28 
days after the last dose of IP that is assessed by the investigator as related to IP will be 
considered a TEAE.
Treatment-emergent adverse events, Grade 3 or higher TEAEs, SAEs, TEAEs leading to dose 
reduction, dose delay, and dose interruption, TEAEs leading to treatment discontinuation, and 
TEAEs with an outcome of death will be summarized by treatment arms using MedDRA system 
organ class and preferred terms.
Sample Size
This study is designed to estimate the treatment effect within each of the combination and 
monotherapy arms and the relative effect between the two arms with respect to the primary and 
secondary efficacy endpoints. The sample size was chosen to support the estimation of the 
within- and between-treatment effects with reasonable precision. Table 1 below summarizes the 
precisions that can be achieved given different scenarios of hypothetical observed hazard ratios 
between the two treatment arms for PFS events, assuming a total of 120 events are observed, and 
the time to PFS has an exponential distribution. 
Table 1:
Progression-Free Survival – Two-side 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms
Hypothetical Number of 
Events Observed
Hypothetical Observed Hazard 
Ratio of PFS Events
95% Confidence Interval of 
Hazard Ratioa
120
0.60
(0.42, 0.86)
0.65
(0.45, 0.93)
0.70
(0.49, 1.00)
a Assuming a standard error of 0.18 for the log hazard ratio.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
10
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
Assuming the median times of PFS are 4.17 and 2.5 months, respectively, for the nab-
paclitaxel/CC-486 combination therapy
and nab-paclitaxel
monotherapy arms, and an 
approximate 24 months accrual period for a total of 160 subjects, it is estimated that a total of 
120 PFS events will be observed approximately 2 months after the last subject is randomized, 
assuming an exponential distribution for PFS. 
One nonbinding interim analysis for PFS with early stopping rule for futility will be conducted 
when approximately 60 events are observed. 
Data Monitoring Committee
An independent Data Monitoring Committee (DMC) will be established with the responsibilities 
for safeguarding the interests of study participants and monitoring the overall conduct of the 
study. Final recommendations of the DMC will reflect the judgment of the DMC members and 
will be considered advisory in nature to the sponsor. The decision to implement the 
recommendations of the DMC will be made by the sponsor, following consultation with the trial 
Coordinating Investigator and Steering Committee. A DMC charter will be established.
ibilit
bilities
ies
of the
of the
embers and
embers an
the
the
tation wit
tation with
establishe
establishe


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
11
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
1.
INTRODUCTION..................................................................................................18
1.1.
Non-small Cell Lung Cancer ..................................................................................18
1.2.
nab-Paclitaxel in NSCLC .......................................................................................19
1.3.
Rationale for nab-Paclitaxel as Second-line Treatment in Subjects with 
Advanced Nonsquamous NSCLC ...........................................................................20
1.4.
Rationale for nab-Paclitaxel in Combination With Epigenetic Modifying 
Therapy of CC-486 as Second-line Treatment in Subjects with Advanced 
Nonsquamous NSCLC............................................................................................21
2.
STUDY OBJECTIVES...........................................................................................24
2.1.
Primary Objective...................................................................................................24
2.2.
Secondary Objective...............................................................................................24
2.3.
Exploratory Objectives ...........................................................................................24
3.
STUDY ENDPOINTS............................................................................................25
3.1.
Primary Endpoint....................................................................................................25
3.2.
Secondary Endpoints ..............................................................................................25
3.2.1.
Efficacy..................................................................................................................25
3.2.2.
Safety.....................................................................................................................25
3.3.
Exploratory Endpoints............................................................................................25
4.
OVERALL STUDY DESIGN ................................................................................26
4.1.
Study Design ..........................................................................................................26
4.1.1.
Screening Period.....................................................................................................26
4.1.2.
Treatment Period ....................................................................................................26
4.1.3.
Follow-up Period....................................................................................................27
4.2.
Study Design Rationale ..........................................................................................27
4.3.
Study Duration .......................................................................................................29
4.4.
End of Trial ............................................................................................................29
5.
TABLE OF EVENTS.............................................................................................30
6.
PROCEDURES......................................................................................................33
6.1.
Medical History......................................................................................................33
6.2.
Prior and Concomitant Medications and Procedures ...............................................33
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5.


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
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Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
6.3.
Pregnancy Testing ..................................................................................................33
6.4.
Complete Chest Computed Tomography (CT) Scan................................................34
6.5.
Weight and Height..................................................................................................34
6.6.
ECOG Performance Score ......................................................................................34
6.7.
Peripheral Neuropathy Assessment.........................................................................34
6.8.
Adverse Event Reporting........................................................................................34
6.9.
Quality of Life Questionnaires................................................................................35
6.10.
Healthcare Resource Utilization Questionnaire .......................................................35
6.11.
Laboratory Assessments .........................................................................................35
6.12.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) .....................................................................................35
6.13.
Electrocardiogram ..................................................................................................36
6.14.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI) .......................37
6.15.
Bone Scans and X-rays...........................................................................................37
6.16.
Physical Examinations............................................................................................37
6.17.
Vital Signs..............................................................................................................37
6.18.
Survival..................................................................................................................37
7.
STUDY POPULATION.........................................................................................38
7.1.
Number of Subjects and Sites .................................................................................38
7.2.
Inclusion Criteria....................................................................................................38
7.3.
Exclusion Criteria...................................................................................................39
8.
DESCRIPTION OF STUDY TREATMENTS........................................................41
8.1.
Description of Investigational Products...................................................................41
8.1.1.
nab-Paclitaxel.........................................................................................................41
8.1.2.
CC-486 (Azacitidine for Oral Administration) ........................................................41
8.2.
Treatment Administration and Schedule .................................................................41
8.3.
Dose Omissions and Modifications.........................................................................42
8.3.1.
Rules for Dose Omissions and Modified Schedules ................................................42
8.3.2.
Rules for Dose Modifications .................................................................................42
8.4.
Method of Treatment Assignment...........................................................................45
8.5.
Packaging and Labeling..........................................................................................45
8.6.
Investigational Product Accountability and Disposal ..............................................45
8.7.
Investigational Product Compliance........................................................................46
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.......35
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
13
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
8.8.
Overdose ................................................................................................................46
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................47
9.1.
Permitted Concomitant Medications and Procedures...............................................47
9.2.
Prohibited Concomitant Medications and Procedures..............................................48
9.3.
Required Concomitant Medications and Procedures for Patients Receiving 
CC-486...................................................................................................................48
9.3.1.
Description of G-CSF.............................................................................................48
9.3.2.
Administration of G-CSF........................................................................................48
10.
STATISTICAL ANALYSES..................................................................................49
10.1.
Overview................................................................................................................49
10.2.
Study Population Definitions ..................................................................................49
10.2.1.
Intent-to-treat Population........................................................................................49
10.2.2.
Per-protocol (PP) Population ..................................................................................49
10.2.3.
Treated Population..................................................................................................50
10.3.
Sample Size and Power Considerations...................................................................50
10.4.
Background and Demographic Characteristics........................................................51
10.5.
Subject Disposition.................................................................................................52
10.6.
Efficacy Analysis....................................................................................................52
10.6.1.
Primary Efficacy Endpoints....................................................................................52
10.6.2.
Secondary Efficacy Endpoints ................................................................................53
10.6.2.1.
Disease Control Rate ..............................................................................................53
10.6.2.2.
Overall Survival .....................................................................................................53
10.6.2.3.
Overall Response Rate............................................................................................53
10.6.3.
Exploratory Endpoints............................................................................................53
10.6.3.1.
HealthCare Utilization............................................................................................53
10.6.3.2.
Quality of Life Questionnaires................................................................................53
10.6.3.3.
Biomarker, Tumor Characteristics, and Genomic Analyses.....................................53
10.7.
Safety Analysis.......................................................................................................53
10.7.1.
Adverse Events.......................................................................................................54
10.7.2.
Laboratory Assessments .........................................................................................54
10.7.3.
Study Drug Exposure..............................................................................................54
10.8.
Study Therapy Termination ....................................................................................54
10.9.
Deaths ....................................................................................................................54
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7


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
14
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
10.10.
Interim Analysis .....................................................................................................55
10.11.
Data Monitoring Committee ...................................................................................55
10.12.
Scientific Steering Committee ................................................................................55
11.
ADVERSE EVENTS..............................................................................................56
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................56
11.2.
Evaluation of Adverse Events.................................................................................56
11.2.1.
Seriousness.............................................................................................................56
11.2.2.
Severity / Intensity..................................................................................................58
11.2.3.
Causality ................................................................................................................58
11.2.4.
Duration .................................................................................................................59
11.2.5.
Action Taken..........................................................................................................59
11.2.6.
Outcome.................................................................................................................59
11.3.
Abnormal Laboratory Values..................................................................................59
11.4.
Pregnancy...............................................................................................................59
11.4.1.
Females of Childbearing Potential ..........................................................................60
11.4.2.
Male Subjects.........................................................................................................60
11.5.
Reporting of Serious Adverse Events......................................................................60
11.5.1.
Safety Queries ........................................................................................................61
11.6.
Expedited Reporting of Adverse Events..................................................................61
12.
DISCONTINUATIONS .........................................................................................62
12.1.
Study Treatment Discontinuation............................................................................62
12.2.
Study Discontinuation ............................................................................................62
12.3.
Subject Replacement ..............................................................................................63
13.
EMERGENCY PROCEDURES.............................................................................64
13.1.
Emergency Contact.................................................................................................64
13.2.
Emergency Identification of Investigational Products .............................................64
14.
REGULATORY CONSIDERATIONS...................................................................65
14.1.
Good Clinical Practice............................................................................................65
14.2.
Investigator Responsibilities ...................................................................................65
14.3.
Subject Information and Informed Consent.............................................................65
14.4.
Confidentiality........................................................................................................66
14.5.
Protocol Amendments.............................................................................................66
6
.......56
5
..........
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4.3.


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
15
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................66
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................67
14.8.
Closure of the Study ...............................................................................................67
15.
DATA HANDLING AND RECORDKEEPING.....................................................68
15.1.
Data/Documents .....................................................................................................68
15.2.
Data Management...................................................................................................68
15.3.
Record Retention....................................................................................................68
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................70
16.1.
Study Monitoring and Source Data Verification......................................................70
16.2.
Audits and Inspections............................................................................................70
17.
PUBLICATIONS ...................................................................................................71
18.
REFERENCES.......................................................................................................72
19.
APPENDICES........................................................................................................75
Appendix A:
ECOG Performance Status Score.......................................................................75
Appendix B: Recommendations for Management of Treatment-Induced Diarrhea.....................76
&(/*(1(35235,(7$5<,1)250$7,21
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68
........
.......68
68
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
16
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
LIST OF TABLES
Table 1:
Progression-Free Survival – Two-side 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms................................9
Table 2:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat 
Population).............................................................................................................20
Table 3:
Table of Events.......................................................................................................30
Table 4:
Requirements for Collection Based on Archival Tumor Sample Type.....................36
Table 5:
Permanent Dose Reductions for Hematologic and Nonhematologic 
Toxicities and Dosing on the Study.........................................................................44
Table 6:
Disease Control Rate –Two-Sided 95% Confidence Interval of Hypothetical 
Disease Control Rate with a Sample Size of 80 Subjects in a Treatment Arm .........50
Table 7:
Progression-Free Survival – Two-Sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms..............................51
&(/*(1(35235,(7$5<,1)250$7,21
.36
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
17
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................28


('06'RF1XPEHU
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ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer
Lung cancer is the leading cause of cancer-related deaths among men and women worldwide, 
with 1.2 million new cases diagnosed each year. Non-small cell lung cancer (NSCLC) is the 
most common type of lung cancer, accounting for 80% of all new cases. There are an estimated 
1.1 million lives lost per year (approximately 500,000 in the United States [US] and European 
Union [EU] alone) due to NSCLC. Smoking is the causative factor for up to 85% of cases 
(http://www.lungcancercoalition.org/en/pages/about/awareness).
The majority of patients are not diagnosed until the tumor has progressed beyond the primary 
site. Despite step-wise advances in patient selection, targeted agents, and optimizing
chemotherapy regimens, patients with advanced NSCLC continue to have an unmet medical 
need (Schiller, 2013).
Platinum-containing chemotherapy regimens remain the standard first-line treatment in the 
majority of patients in the US and Japan. In the EU, a third-generation chemotherapeutic agent 
(docetaxel, gemcitabine, paclitaxel, or vinorelbine), most commonly gemcitabine or vinorelbine, 
plus a platinum drug is used for advanced NSCLC (NICE, 2011). For first-line therapy in 
patients with Stage IV NSCLC and good performance status, the American Society of Clinical 
Oncology (ASCO) clinical practice guideline recommends treatment with a platinum-based 
two-drug combination of cytotoxic drugs (Azzoli, 2009). For patients without disease 
progression, the option of maintenance monotherapy with pemetrexed or erlotinib could also be 
considered (Gerber, 2013; Schiller, 2013). A trend that is becoming more prevalent is 
personalized NSCLC treatment based on tumor histology (squamous versus nonsquamous), on 
molecular characteristics of the tumor, and on the patient’s clinical status using agents targeting 
specific receptors, kinases and pathways (ie, epidermal growth factor receptor [EGFR], 
echinoderm microtubule-associated protein-like 4 [EML4] and anaplastic lymphoma kinase 
[ALK] fusion protein).
Single agent chemotherapy (pemetrexed, EGFR-inhibitors and taxanes) are standards of care for 
second-line treatment of patients with locally advanced or metastatic NSCLC after failure of 
prior platinum-based chemotherapy. Docetaxel has been widely evaluated in this setting, and is 
currently approved by the US Food and Drug Administration (FDA) and the European 
Medicines Agency (EMA) as a single agent for the treatment of patients with locally advanced or 
metastatic NSCLC after failure of prior chemotherapy  (the US label specifies prior platinum-
based chemotherapy). For patients with a good performance status at the time of disease 
progression following first-line chemotherapy, docetaxel, despite a low response rate, was
associated with a 10% to 20% prolongation of 1-year survival and an improved quality of life 
when compared with ifosfamide, vinorelbine, or best supportive care (BSC) alone (Hanna, 
2004). Erlotinib is indicated in the US and EU for the treatment of patients with locally advanced 
or metastatic NSCLC after failure of at least one prior chemotherapy regimen, although no 
survival benefit has been demonstrated in patients with EGFR-IHC negative tumors. 
Pemetrexed is indicated in the US and EU as a single agent for the treatment of patients with 
locally advanced or metastatic nonsquamous NSCLC after prior chemotherapy. However, the 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
19
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
approval and subsequent increased use of pemetrexed and erlotinib in the first-line setting poses 
an unmet need in the second-line setting, whereby new therapeutic options are needed.
1.2.
nab-Paclitaxel in NSCLC
nab-Paclitaxel is approved in the first-line setting in combination with carboplatin for patients 
with NSCLC in the US, Japan, Argentina, Australia, and New Zealand.  The approval  was based 
on the evaluation of Phase I and II data (Belani, 2008; Rizvi, 2008; Socinski, 2010), as well as 
the pivotal Phase 3 study (CA031), (Socinski, 2012). The pivotal Phase 3 study was a 
multicenter, randomized, open-label study conducted in 1052 chemo-naïve subjects with Stage 
IIIB/IV NSCLC to compare nab-paclitaxel in combination with carboplatin to paclitaxel 
injection in combination with carboplatin as first-line treatment in patients with advanced 
NSCLC. nab-Paclitaxel was administered as an IV infusion over 30 minutes at a dose of 
100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel injection was administered as 
an IV infusion over 3 hours at a dose of 200 mg/m2, following premedication. In both treatment 
arms carboplatin at a dose of area under the curve (AUC) = 6 mg*min/mL was administered IV
on Day 1 of each 21-day cycle after completion of nab-paclitaxel/paclitaxel infusion. Treatment 
was administered until disease progression, development of an unacceptable toxicity or patient 
withdrawal. The primary efficacy outcome measure was overall response rate (ORR) as
determined by a central independent review committee using RECIST guidelines (Version 1.0).
In the intent-to-treat (all-randomized) population, the median age was 60 years, 75% were men, 
81% were white, 49% had carcinoma/adenocarcinoma, 43% had squamous cell lung cancer, 76% 
were ECOG performance status (PS) 1, 15% were ≥70 years of age and 73% were current or 
former smokers. Patients received a median of 6 cycles of treatment in both study arms. Patients 
in the nab-paclitaxel/carboplatin arm had a statistically significantly higher overall response rate 
compared to patients in the paclitaxel injection/carboplatin arm [(33% versus 25%; response rate 
ratio, 1.313; 95% CI, 1.082 to 1.593; p=0.005), see Table 2].
Non-inferiority analysis of overall survival (OS) demonstrated that nab-paclitaxel/carboplatin
(nab-p/C) treatment is not inferior to paclitaxel/carboplatin (P/C) treatment. Overall survival in 
the nab-paclitaxel arm was 12.1 months versus 11.2 months in the control arm (p = 0.271; HR = 
0.922). There was an approximately 10% increase in PFS in the nab-p/C versus P/C arm and PFS 
in the nab-p/C arm was noninferior to PFS in the P/C arm (HRnab-p/C/P/C 95% CI upper bound, 
1.086).
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
Table 2:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat
Population)
Variable
Category/Statistic
nab-Paclitaxel/
carboplatin
(N=521)
Paclitaxel/
carboplatin
(N=531)
Response Rate 
Ratio
(pA/pT)
p-value
Patients with Confirmed Complete or Partial Overall Response
n (%)
170 (33%)
132 (25%)
1.313
0.005*
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28.6, 36.7
21.2, 28.5
1.082, 1.593
Complete Response, n (%)
0
1 (< 1%)
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170 (33%)
131 (25%)
PA/PT: response rate of nab-paclitaxel/response rate of paclitaxel.
a 95% CI of response rate and 95.1% CI of response rate ratio.
* Indicates p-value < 0.049.
Note: p-value is based on a chi-square test.
Source: Data on File.
Adverse events (AEs) were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. The following common (≥ 10% incidence) AEs
were observed at a similar incidence in nab-paclitaxel/carboplatin and paclitaxel/carboplatin
arms: alopecia 56%, nausea 27%, fatigue 25%, decreased appetite 17%, asthenia 16%, 
constipation 16%, diarrhea 15%, vomiting 12%, dyspnea 12%, and rash 10% (incidence rates are 
for the nab-paclitaxel plus carboplatin treatment group). Toxicities, particularly neuropathy and 
Grade 3/4 neutropenia were less pronounced using nab-paclitaxel in the dose and schedule 
employed. Laboratory-detected abnormalities which occurred with a difference ≥5% for nab-
paclitaxel plus carboplatin versus paclitaxel injection plus carboplatin (Grades 1 to 4 [and Grade 
3/4]) were: anemia (98% vs 91% [28% vs 7%]), neutropenia (85% vs 83% [47% vs 58%]) and 
thrombocytopenia (68% vs 55% [18% vs 9%]).  
1.3.
Rationale for nab-Paclitaxel as Second-line Treatment in Subjects 
with Advanced Nonsquamous NSCLC
Patients who fail first-line chemotherapy are eligible for second-line treatment with single agent 
docetaxel, pemetrexed or erlotinib. In patients with good performance (eg, ECOG PS 0 or 1) and 
general health status, further treatment with chemotherapy is an important consideration that has 
been shown to extend overall survival. Despite the availability of second-line therapy, the trend 
of increased use of pemetrexed, as well as erlotinib (in selected patients) in the first-line and 
maintenance settings, potentially limits the number of available second-line treatment options for 
many patients. Furthermore, the tolerability issues associated with the administration  of 
docetaxel once every 3 weeks (q3w) has prompted active research in the past decade to evaluate 
whether weekly regimens of taxanes could be optimized to improve the toxicity profile. The 
availability of an effective second-line cytotoxic chemotherapy with an improved efficacy/safety
profile over current available options would be a valuable addition for both the patient and the 
treating physician. Paclitaxel has also demonstrated potential activity in second-line NSCLC in a 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
21
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
few studies (Socinski, 1999; Juan, 2002; Socinski, 2002; Sculier, 2002; Buccheri, 2004; Ceresoli, 
2004; Yasuda, 2004).
nab-Paclitaxel exhibits 10-fold higher mean Cmax of free paclitaxel, delivers 33% higher drug 
concentration to tumors in preclinical xenograft models, and demonstrates enhanced transport 
across endothelial cell monolayers, when compared with paclitaxel (Desai, 2006; Gardner, 
2008). The Cremophor EL-free medium enables nab-paclitaxel to be given over a shorter 
duration without the need for premedication to prevent solvent-related hypersensitivity reactions.
When administered with carboplatin in the first-line setting, weekly nab-paclitaxel has 
demonstrated a more favorable efficacy:safety profile compared to the every 3 weeks schedule.  
This weekly schedule schedule of nab-paclitaxel allows the opportunity for closer (ie, shorter 
interval) monitoring of side effects and optimizing dose-intensity through timely adjustments.  
As previously noted, nab-paclitaxel 100 mg/m2 weekly (Days 1, 8 and 15) in combination with 
carboplatin (21 day cycle) is approved in the US, Japan, Argentina, Australia, and New Zealand 
for the treatment of locally advanced or metastatic NSCLC in the first-line setting.  However, 
there is limited data of monotherapy nab-paclitaxel in the second-line setting; hence, this study 
will  assess the efficacy and tolerability of weekly nab-paclitaxel, when administered on Days 1 
and 8 of each 21-day cycle.  The allowance of a one week rest period in this study (ie, no 
treatment on Day 15), takes into account research findings from other taxanes, whereby patients 
in the second-line setting are unlikely to tolerate the same dose-intensity compared to chemo-
naïve patients (eg, sharper dose reduction in the second-line setting). Therefore, the proposed 
nab-paclitaxel schedule (2 weeks treatment, 1 week rest) could offer the option of maintaining 
consistent dose-intensity for NSCLC patients in this setting.
1.4.
Rationale for nab-Paclitaxel in Combination With Epigenetic 
Modifying Therapy of CC-486 as Second-line Treatment in Subjects 
with Advanced Nonsquamous NSCLC
CC-486 is an orally bioavailable formulation of the nucleoside analog 5-azacitidine (AZA).  
After its incorporation into a cell’s DNA during the S-phase of the cell cycle, CC-486 forms 
covalent adducts with DNA Methyltransferase 1 (DNMT1) and depletes this enzyme required for 
the maintenance of DNA methylation patterns, thereby altering the epigenetic status of the cell. 
Epigenetic changes are covalent modifications of chromatin (DNA and histone proteins) that 
mediate the stable transmission of a gene’s transcriptional status through cell division.  One of 
the first recognized epigenetic alterations in cancer was DNA methylation.  The addition of a 
methyl group to cytosine in the dinucleotide CpG is catalyzed by DNA methyltransferases 
(DNMTs) and is associated with transcriptional repression of genes with high density of CpGs 
(CpG islands) in the vicinity of their promoters (Jones, 2007).  Genomic methylation patterns are 
precisely regulated during normal embryonic development and differentiation and have been 
found to be altered in specific ways in cancer. Specifically, cancer cell genomes are typified by 
reduced methylation globally with focal areas of aberrant hypermethylation in the CpG islands of 
genes encoding known tumor suppressors such as PTEN and BRCA1 as well as genes encoding 
proteins required for apoptosis, including caspase 8, DAPK and Apaf-1.  DNA methylation-
based silencing can thus contribute to the establishment and maintenance of the transformed state 
and limit the effectiveness of anti-cancer therapies.  The recognition of the role of aberrant 
methylation in carcinogenesis and its reversibility has led to the development of DNMT 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
22
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
inhibitors for cancer. Subcutaneous (SC) AZA was the first DNMT inhibitor to be approved in 
myelodysplastic syndromes (MDS) in 2004 (Kaminskas, 2005).
The notion that sequential treatment with an epigenetic modifying agent followed by a cytotoxic
agent can result in improved response to the latter is supported by numerous preclinical 
experiments and now by early clinical results.  In breast cancer cell lines, restoring expression of 
the aberrantly methylated pro-apoptotic gene TMS1 with azacitidine can restore taxane 
sensitivity (Gordian, 2009).  In a model of platinum resistant ovarian cancer, azacitidine reversed 
resistance to carboplatin (Li, 2009).  This effect required pretreatment of the cells with 
noncytotoxic levels of azacitidine for 24 hours before the addition of carboplatin and was not 
observed with concurrent exposure to both agents.  More recently, Juergens and colleagues 
observed an unusually high ORR of approximately 20% in multiple-relapsed NSCLC patients 
treated with a variety of regimens after being treated with a combination of SC AZA and another 
epigenetic agent, entinostat, a histone deacetylase inhibitor (Juergens, 2011).  In one case, a 
patient who had previously progressed on a regimen of paclitaxel, carboplatin and bevacizumab 
responded to the same triplet after treatment with SC AZA and entinostat, suggesting that the 
epigenetic modifying agents had reversed acquired resistance to the cytotoxic/anti-angiogenic 
regimen.  In a Phase 1/2 study of SC AZA with nab-paclitaxel in subjects with advanced 
metastatic solid tumors and breast cancer (Dumlao, 2011), escalating doses of SC AZA (75 to
100 mg/m2) were administered on Days 1 through 5, followed by nab-paclitaxel (100 mg/m2) 
intravenous (IV) on Days 8, 15, and 22 of a 28-day cycle.  Of 16 subjects treated at the time of 
publication, clinical activity has included 3 complete responses (CR, 1 Diffuse Large B-cell 
Lymphoma [DLBCL], 2 ovarian), 4 partial responses (PR) in ovarian and endometrial cancer 
and 4 stable diseases (SD, 2 lung, 1 pancreatic, and 1 sarcoma).  
CC-486 entered clinical testing in 2006 in subjects with MDS, chronic myelomonocytic 
leukemia [CMML], and acute myeloid leukemia [AML], with daily extended dosing schedules 
of 14 and 21 out of 28 days in a non-crossover fashion.  Daily doses of 300 mg CC-486 have 
proven to be tolerated on both the 14 and 21 out of 28-day schedules with myelosuppression, 
gastrointestinal symptoms, and fatigue being the most common toxicities (Garcia-Manero, 
2011).  Subjects treated with CC-486 for 14 or 21 days had DNA hypomethylation that persisted 
through the end of cycle.  This contrasts with the lack of persistent hypomethylation at the end of 
cycle when subjects were treated with SC AZA for 7 out of 28 days. 
 
 
 
 
  
 
 
 
 
 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
23
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
  
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
This Phase 2 study will test the hypothesis that epigenetic modifying therapy with CC-486 can 
improve the anti-tumor activity of nab-paclitaxel in second-line NSCLC patients (see Section 4.2
for study rationale). Although docetaxel has been assessed in other randomized studies as a 
chemotherapy backbone, the considerable neutropenia-related toxicity could potentially pose 
safety concerns if combined with CC-486, and the steroid premedication could confound the 
epigenetic impact of CC-486.  In addition, the q3w dosing schedule of docetaxel restricts dose 
adjustment options, thus potentially yielding lower chemotherapy dose-intensity.
Please refer to the Investigator’s Brochures (IBs) of CC-486 and nab-paclitaxel (ABI-007) for 
detailed information concerning the available pharmacology, toxicology, drug metabolism, 
clinical studies, and adverse event profile of the IPs.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
24
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
2.
STUDY OBJECTIVES
2.1.
Primary Objective 
The primary objective of the study is:
!
To assess the efficacy of nab-paclitaxel administered intravenously (IV) on Days 8 
and 15 with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 
14 every 21 days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 
every 21 days as second-line treatment for advanced nonsquamous NSCLC, and the 
relative efficacy of these two treatment regimens.
2.2.
Secondary Objective
The secondary objective of the study is:
!
To evaluate the safety and tolerability of nab-paclitaxel administered IV on Days 8 
and 15 with epigenetic modifying therapy of CC-486 QD on Days 1 to 14 every 21 
days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 every 21 
days as second-line treatment for advanced nonsquamous NSCLC.
2.3.
Exploratory Objectives
The exploratory objectives of the study are:
!
To assess healthcare resource utilization for the two treatment arms.
!
To assess the QoL for the two treatment arms.
!
To determine baseline tumor characteristics which predict response to nab-paclitaxel 
as a single agent and with epigenetic modifying therapy of CC-486. 
!
To evaluate genomic correlates of response to nab-paclitaxel as a single agent and 
with epigenetic modifying therapy of CC-486.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
25
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
3.
STUDY ENDPOINTS
Study efficacy endpoints will be assessed by the investigator using RECIST 1.1 guidelines.
3.1.
Primary Endpoint
The primary endpoint is:
!
Progression free survival.
3.2.
Secondary Endpoints
The secondary endpoints are: 
3.2.1.
Efficacy
!
Disease control rate.
!
Overall response rate.
!
Overall survival.
3.2.2.
Safety
!
The type, frequency, and severity of AEs and SAEs graded using National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, 
Version 4.0). 
!
Discontinuation rate.
!
The median dose intensity.
!
The incidence of dose reduction.
3.3.
Exploratory Endpoints
!
Healthcare resource utilization during the study using a questionnaire.
!
Changes in the Lung Cancer Symptom Scale (LCSS), European Organisation for 
Research and Treatment of Cancer (EORTC) QLQ C30, and EuroQoL 5D-5L (EQ-
5D-5L).
!
The correlation between pretreatment tumor characteristics and response to the study 
treatment determined using next-generation sequencing methods, 
immunohistochemistry, or other analysis methods.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
4.
OVERALL STUDY DESIGN 
4.1.
Study Design
This is a Phase 2, randomized, open-label, multicenter study to assess safety and efficacy of  
nab-paclitaxel in combination with epigenetic modifying therapy of CC-486, and nab-paclitaxel 
monotherapy as second-line treatment in subjects with advanced nonsquamous NSCLC who 
have received one platinum-containing chemotherapy regimen. Approximately 160 subjects with 
advanced nonsquamous NSCLC will be randomized 1:1 into one of the two treatment arms: nab-
paclitaxel / CC-486 or nab-paclitaxel monotherapy prior to receiving first dose of investigational 
product (IP). Randomization will be centralized and stratified by ECOG performance status (0 
versus 1), gender (males versus females), and smoker (yes versus no).
The study will consist of up to a 28-day Screening Period, a Treatment Period and a Follow-up 
Period.  
4.1.1.
Screening Period 
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of IP.
4.1.2.
Treatment Period 
The Treatment Period begins with the first dose of IP as described in Section 8. Subjects will 
receive one of the following treatments based on the randomization assignment:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment  cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment  cycle.
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, withdrawal of 
consent, or termination of the study by the sponsor.
During the study, subjects will have computed tomography (CT) scans every 42 days (-3/+7 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the sponsor. Tumor evaluations will be assessed by the 
investigative sites and response will be determined according to RECIST 1.1 guidelines.
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an AE/SAE and also recorded on the laboratory eCRF (see Section 11.3).   
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
27
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
4.1.3.
Follow-up Period
All subjects who discontinue from treatment for reasons other than withdrawal of consent, lost to 
follow-up, death, or termination of the study by the sponsor will enter the Follow-up Period. It 
will consist of a visit 28 days after treatment discontinuation followed by phone follow-up for 
survival approximately every 90 days (+/- 14 days) for up to 12 months after the last subject is 
randomized or 120 PFS events have been observed whichever comes later.
Those subjects entering the Follow-up Period without documented progression will continue to 
have CT scans in accordance with local standard of care (or approximately every 90 days) until 
documented progression of disease, withdrawal of consent, lost to follow-up, death, or 
termination of the study by the sponsor. All posttreatment anticancer therapies will be recorded 
during the Follow-up Period.  
4.2.
Study Design Rationale
This is an open-label, randomized study designed to evaluate the effects of adding CC-486 to 
nab-paclitaxel and nab-paclitaxel monotherapy in second-line NSCLC. A placebo-controlled 
study would not be feasible for this population as blinding would be difficult and would need a 
double dummy design.  A key objective in this study is to determine the chemo-priming effect of
CC-486. The inclusion of only patients with nonsquamous NSCLC histology allows for a more 
homogenous population, hence, reducing the impact of potential confounding factors. Second-
line NSCLC enables a unique setting to evaluate epigenetics: 
a) compared to more heavily treated patients, patients eligible for second-line treatment
have better immune function/reserve which is critical for safety and activation of immune 
cells that target cancer cells,
b) due to the overlapping (and dose-limiting) toxicities of doublet/triplet chemotherapy 
regimens in the first-line setting, it would be very challenging to combine epigenetic 
therapy at a dose level to elicit clinically meaningful benefit.  
Although docetaxel has been assessed in other randomized studies as a chemotherapy backbone, 
the considerable neutropenia-related toxicity could potentially pose safety concerns if combined 
with CC-486, and the steroid premedication could confound the epigenetic impact of CC-486.  In 
addition, the q3w dosing schedule of docetaxel restricts dose adjustment options, thus potentially 
yielding lower chemotherapy dose-intensity.
For patients with NSCLC whose disease progressed after initial platinum-based chemotherapy, 
the goal of therapy is to delay further progression for as long as possible; hence, the use of PFS 
as the primary endpoint for efficacy evaluation.  Furthermore, maintaining quality of life during 
this period, especially in reducing/managing toxicity is also an important consideration.  
Therefore, the proposed study is designed to optimize the evaluation of efficacy with a tolerable 
dose/schedule of chemotherapy, and its combination with an epigenetic modifying therapy.  
  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
28
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
Figure 1:
Overall Study Design
IP = investigational product; PFS = progression-free survival; QD = once daily; OS = overall survival
Screening for Eligibility  (up to 28 days)
(n=160)
Follow-up Period
28-day Follow-up visit (after last dose of IP)
Followed for OS by phone approximately every 90 days for up o 12 months after last subject is randomized or 120 
PFS events have been observed, whichever is later
nab-paclitaxel 100 mg/m2  IV infusion over 30 
minutes on Days 1 and 8 of each 21-day cycle 
until disease progression
(n = 80)
-
nab-paclitaxel 100 mg/m2  IV infusion over 30 
minutes on Days 8 and 15 of each 21-day cycle 
until disease progression
-
CC-486 200 mg orally QD Days 1 to 14 of each 
21-day cycle until disease progression
(n = 80)
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
29
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
4.3.
Study Duration 
Recruitment is expected to take approximately 24 months, and the analysis of PFS will be 
performed when approximately 120 PFS events have occurred, estimated as approximately 26
months from first subject randomized. The total length of this Phase 2 study with follow-up is 
estimated to last approximately 3 years.
4.4.
End of Trial
The End of Trial is defined as either the:
!
date of the last visit of the last subject to complete the study, or 
!
the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol
and/or the Statistical Analysis Plan (SAP), whichever is the later date.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
30
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
5.
TABLE OF EVENTS
Table 3:
Table of Events
Screening
/ Baseline
Treatment Period
Every 21-day Cycle
Follow-up Period
Assessment
Day -28 
to
Day -1
Day 1
( ±2 
days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu
ation Visit 
28-day Follow-up 
Visit (after last 
dose of IP)
Survival Follow-upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
Informed Consent
X
-
-
-
-
-
-
-
Medical History (including Tobacco Exposure History), 
Prior Medication and Procedures
X
-
-
-
-
-
-
-
Serum β-hCG b
X
-
-
-
-
-
-
-
Urine Pregnancy Test b
-
X
-
-
-
X
-
-
Complete Chest CT Scan and Any Other Studies 
Required for Tumor Imagingc
X
-
-
-
X
X
-
X
Weight and Heightd
X
X
X
X
-
-
-
-
ECOG Status
X
X
-
-
-
X
X
-
Concomitant Medication/Procedures
-
X
X
X
-
X
X
X
Peripheral Neuropathy Assessmente
X
X
-
-
-
X
X
-
Healthcare Resource Utilization Questionnaire
-
X
-
-
-
X
X
-
Hematologyf
X
X
X
X
-
X
X
-
Serum Chemistryf
X
X
-
-
-
X
X
-
Archived Tumor Tissue Sample for Biomarker (biopsy, 
surgical specimen, or other diagnostic tumor sample)
-
X
(C1D1 
only)
-
-
-
-
-
-
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
31
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
Table 3:
Table of Events (Continued)
Screening/ 
Baseline
Treatment Period
Every 21-day Cycle
Follow-Up Period
Assessment
Day -28 to
Day -1
Day 1
( ±2 
days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu-
ation Visit 
28-day Follow-up 
Visit (after last 
dose of IP)
Survival Follow-Upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
Plasma for Biomarker Analyses
-
X
(C1D1 
only
predose)
-
-
-
-
-
-
Blood for Pharmacogenomic Analyses
-
X
(C1D1 
only 
predose)
-
-
-
-
-
-
Adverse Event Evaluation
After signing ICF and until 28 days after the last dose of IP
-
nab-PaclitaxelMonotherapy 
Administration/Accountabilityg
-
X
X
-
-
-
-
nab-Paclitaxel Combination 
Administration/Accountabilityg
-
-
X
X
-
-
-
-
CC-486 Administration/Accountabilityg
-
X
-
-
-
-
LCSS, EORTC QLQ C30 and EQ-5D-5L
-
X
-
-
-
X
X
-
Survival Phone Call
-
-
-
-
-
-
-
Xa
Electrocardiogram (ECG)
X
Will be done as per standard of care during the Treatment Period and as clinically indicated; however, results 
will not be routinely collected in the eCRFs. If CT/bone scans show lesions pertinent for RECIST 1.1 criteria 
evaluation, data will be collected on the pertinent tumor evaluation eCRFs. If ECGs, physical examinations, 
and/or vital signs are abnormal and clinically significant, the data will be recorded on the AE/SAE eCRF.
Vital Signs
X
Physical Examination
X
Bone Scan (X-rays if needed)
If clinically 
indicated
CT Scan of the Head or Brain Magnetic Resonance 
Imaging (MRI)
If clinically 
indicated
(mandatory if 
symptomatic)
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
32
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
AE = Adverse Event; β-HCG = beta human chorionic gonadotropin; C1D1 = Cycle 1 Day 1; CT = Computed Tomography; ECOG = Eastern Cooperative Oncology Group; eCRF
= electronic Case Report Form; EORTC QLQ C30 = European Organisation for Research and Treatment of Cancer QLQ C30; EQ-5D-5L = EuroQol 5D-5L; ICF = informed 
consent form; IP = investigational product; LCSS = Lung Cancer Symptom Scale; QD = once daily; RECIST = Response Evaluation Criteria in Solid Tumors; SAE = Serious 
Adverse Event.
a Every 90 (+/-14) days (from 28-day Follow-up Visit ) for up 12 months after the last subject is randomized or 120 PFS events have been observed whichever comes later.
b A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a Serum β-hCG pregnancy test must be performed to assess 
eligibility at Screening/Baseline. Note: the screening serum pregnancy test can be used as the Cycle 1 Day 1 test prior to study therapy if it is performed within the 72-hour 
timeframe.  A urine pregnancy test must be performed prior to administration of IP before beginning each new cycle and at the End-of-Treatment Visit.
c All subjects must have a radiographically documented measurable tumor(s) by RECIST 1.1 criteria: Complete chest CT scan (including base of neck and adrenal gland) will be 
performed at Screening, every 42 days (-3/+7 days) (starting from Day 1 Cycle 1) until disease progression, withdrawal of consent, lost to follow-up, death, or termination of the 
study by the sponsor. The results of a complete chest CT scan (including base of neck and adrenal gland) performed per Standard of Care may be accepted and not repeated 
during Screening provided it was performed within 28 days of the first dose of study drug (Cycle 1 Day 1). The methods of assessment chosen at baseline to follow tumors are to 
remain consistent throughout study duration. Those subjects entering the Follow-up Period without documented progression will continue to have CT scans in accordance with 
local standard of care (or approximately every 90 days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, or termination of the study by 
the sponsor.
d Height will only be obtained at screening visit. Weight will be obtained at Screening and every visit during the Treatment Period before administration of IP.
e The occurrence of peripheral neuropathy will be reported by the investigator per protocol as an AE or SAE.
f All scheduled laboratory samples will be sent to a central laboratory for analysis. Local hematology and chemistry tests may be performed as required for subject 
management/treatment decisions. Local laboratory values that are considered abnormal and clinically significant will be recorded as an AE/SAE and also recorded on the 
laboratory eCRF (see Section 11.3).
g nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 200 mg orally QD on Days 1 to14 of each 21-day treatment cycle or nab-paclitaxel 
100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day treatment cycle.
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ICF = 
d Tumors;
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
33
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
6.
PROCEDURES
Subjects will be provided with a written Informed Consent Form (ICF), given the opportunity to 
ask any questions concerning the study and will sign an ICF prior to participating in any study 
procedures. After giving written informed consent, subjects will undergo a Screening Period to 
be assessed for eligibility. All subjects who sign an ICF must be entered into the Integrated 
Response Technology (IRT) immediately upon signature on the document. Subjects who do not 
meet the eligibility criteria will be considered screening failures and will not be eligible for the 
study. Subjects who fail initial screening may undergo re-screening up to 2 times at any time 
and an ICF will need to be resigned, as well as all screening procedures repeated (some 
procedures may not need to be done if previously done within 28 days prior to screening again).
Subjects that have met all eligibility criteria after the Screening Period will be eligible for
randomization. 
6.1.
Medical History
A complete medical history including, but not limited to, evaluation for past (up to 5 years) or
present cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine,
lymphatic, hematological, immunologic, dermatological, psychiatric, genitourinary, obstetrical, 
surgical history or any other diseases or disorders will be performed at Screening. All NSCLC-
related medical history should be recorded regardless of time. Smoking status/tobacco exposure 
history will be captured on the eCRF.
6.2.
Prior and Concomitant Medications and Procedures
Prior medications are defined as any medications started before the first dose of IP and stopped 
either prior to the date of the first dose of IP or continued after study treatment. All prior 
medications/procedures of clinically significant or ongoing medical conditions taken up to 28 
days of time of signature on the ICF should be recorded. All NSCLC-related prior 
medications/procedures should be recorded regardless of time.
Concomitant medication is defined as the medication that was either initiated before the first 
dose of IP and continued during the study treatment, or initiated on/after the date of the first dose 
of IP but on or before 28 days after the last dose of IP. All subjects will have concomitant 
medications and procedures (including radiation therapy) recorded at each visit from the time of 
signature on the ICF until the 28-day Follow-up Visit, for conditions that are clinically 
significant or ongoing. During the Follow-up Period only NSCLC-associated concomitant 
medications/procedures (including radiation therapy) will be recorded, ie, subsequent-line(s) of 
anti-cancer therapy.
6.3.
Pregnancy Testing
A pregnancy test is required for women of child-bearing potential only. For women of child-
bearing potential a serum β-hCG pregnancy test with sensitivity of at least 25 mIU/mL must be 
performed to assess eligibility at Screening/Baseline. Note: the screening serum pregnancy test 
can be used as the Cycle 1 Day 1 test prior to study therapy if it is performed within the 72-hour 
timeframe.  A urine pregnancy test must be performed prior to administration of IP before 
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tions
ons sta
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IP or conti
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should be
should b
be recorded
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efined as th
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during the 
during t
28 days afte
28 days aft
ocedures 
edures (in
(in
ICF
ICF unt
until th
il th
ongoing. D
ngoing. D
s/procedur
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
34
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
beginning each new cycle and at the End-of-Treatment Visit. The subject may not receive 
treatment until the investigator has verified that the result of the pregnancy test is negative. See 
inclusion criteria for pregnancy testing requirements. Any pregnancies that occur in women who 
have received IP must be immediately reported to Celgene Drug Safety (See Section 11.4).
6.4.
Complete Chest Computed Tomography (CT) Scan
A complete chest CT scan (including base of neck and adrenal gland) and any other studies 
required for tumor imaging will be done at Screening, every 42 days (-3/+7 days) (starting from 
Day 1 Cycle 1), and End-of-Treatment, until documented progression of disease, withdrawal of 
consent, lost to follow-up, death, or termination of the study by the sponsor. The results of a 
complete chest CT scan (including base of neck and adrenal gland) performed per Standard of 
Care may be accepted and not repeated during Screening provided it was performed within 28 
days of the first dose of study drug (Cycle 1 Day 1). Those subjects entering the Follow-up 
Period without documented progression will continue to have CT scans in accordance with local 
standard of care (or approximately every 90 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death, or termination of the study by the sponsor. 
Additional CT scans may be done at any time during the study if clinically indicated. All CT
scans and reports should be archived at the site according to site regulations and copies provided 
to sponsor if requested. All posttreatment anticancer therapies will be recorded during the 
Follow-up Period.  
6.5.
Weight and Height
Weight will be obtained at Screening and at every visit during the Treatment Period before 
administration of IP. Additional measurements of weight may be collected per local standards at 
any time during the study as needed. Height will only be collected at Screening. All weight and 
height data will be collected on eCRFs.
6.6.
ECOG Performance Score
Eastern Cooperative Oncology Group performance status score will be collected at Screening, 
Day 1 of every treatment cycle, at the End-of-Treatment Visit and at the 28-day Follow-up Visit. 
Additional ECOG assessments may be performed at any time during the study as clinically 
indicated.
6.7.
Peripheral Neuropathy Assessment
Peripheral neuropathy (sensory or motor) assessment will be done at Screening, Day 1 of every 
treatment cycle, at the End-of-Treatment Visit and at the 28-day Follow-up Visit. Changes in 
neuropathy grade from baseline will be reported as an AE as per Section 11. Additional 
peripheral neuropathy assessments may be done at any time during the study as clinically 
indicated.
6.8.
Adverse Event Reporting
Adverse events will be recorded from time of signature on the ICF until 28 days after the last 
dose of IP, including any unscheduled visits. See Section 11 for details. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
35
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
6.9.
Quality of Life Questionnaires
The LCSS, EORTC QLQ C30 and EQ-5D-5L questionnaires will be used to measure quality of 
life (QoL) for subjects in the study. The LCSS is comprised of 9 questions to be completed by 
the subject using a visual analogue scale (VAS) to denote intensity of a symptom. The EQ-5D-
5L comprises 5 questions on mobility, self-care, usual activities, pain/discomfort, 
anxiety/depression and a VAS for overall QoL. These questionnaires will be completed by the 
subject prior to interaction with study personnel, at Day 1 of every Cycle, at the End-of-
Treatment Visit and at the 28-day Follow-up Visit.
6.10.
Healthcare Resource Utilization Questionnaire
A healthcare resource utilization questionnaire will be used to capture the additional use of 
healthcare resources, including hospitalizations, emergency room visits, doctor or nurse visits, 
procedures, and/or additional medication during the study period. The assessment will be 
completed on Day 1 of every treatment cycle, at the End-of-Treatment Visit and at the 28-day
Follow-up Visit. 
6.11.
Laboratory Assessments
Blood for hematology and chemistry evaluation will be collected as per Table 3, Table of Events. 
Blood for hematology will be collected at Screening, Days 1, 8, and 15 of every treatment cycle, 
at the End-of-Treatment Visit and at the 28-day Follow-up Visit. Blood for serum chemistry will 
be collected at Screening, Day 1 of every treatment cycle, at the End-of-Treatment Visit and at 
the 28-day Follow-up Visit. Additional laboratory samples for safety may be collected as 
clinically indicated. 
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an AE/SAE and also recorded on the laboratory eCRF (see Section 11.3).   
Abnormal and clinically significant laboratory assessments at Screening will be recorded as 
medical history, and after Screening, as AE or SAE (clinically significant laboratory 
abnormalities at Screening may result in a subject being ineligible for the study and should not 
be captured as an AE). 
Any abnormal values that persist should be followed at the discretion of the investigator. The 
investigator should file all copies of the reports, including faxes with the subject’s medical chart.
6.12.
Tumor Tissue Sample Collection and Peripheral Blood Collection
(Exploratory Assessments) 
Histologically or cytologically confirmed advanced nonsquamous NSCLC is a required inclusion 
criteria for entry into this study.  If a subject’s previously collected tumor tissue (also known as 
archival tumor) is available, these samples will be collected for biomarker testing as detailed 
below at Cycle 1 Day 1.  If such samples do not exist, have been depleted, or do not contain 
sufficient tumor material to be analyzed, this will not preclude participation in the study and a 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
36
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
new biopsy or other procedure to collect tumor tissue will not be required.  Table 4 delineates the 
specific requirements for commonly encountered  archival tumor types.
Table 4:
Requirements for Collection Based on Archival Tumor Sample Type
Sample Type
Amount to Collect
Collection 
Requirement for 
Biomarkers
Comments/ Exceptions
Core biopsy or surgical 
specimen
10 slides ≥4 ∀M 
thickness. If a block is 
provided, a core of 
viable tumor will also 
be collected.
Mandatory if the sample 
exists. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Fine needle aspirates 
(FNA)
10 slides ≥4 ∀M. If a 
block is provided, a 
core of viable tumor 
will also be collected. 
Mandatory if the sample 
exists, unless a core 
biopsy or surgical 
sample was provided. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Transbronchial 
endoscopy samples
10 slides ≥4 ∀M. If a 
block is provided, a 
core of viable tumor 
will also be collected.
Mandatory if the sample 
exists, unless a core 
biopsy or surgical 
sample was provided. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Bronchial lavage, 
sputum, or other 
sample types
Slides or blocks 
representing >100,000 
tumor cells
Collection is strongly 
encouraged when these 
samples contain 
sufficient material.
Collection is strongly 
encouraged when these 
samples contain sufficient 
material.
In addition, test results for tumor mutational status of genes, including but not limited to EGFR,
ALK, and KRAS will be collected and recorded on eCRF if these tests have been performed.
Plasma for cell-free nucleic acids analyses will be collected on Cycle 1 Day 1 prior to first dose 
of IP, as will a sample of whole blood or peripheral blood mononuclear cells for a germ-line 
reference comparison. Types of techniques planned to be used for tumor and plasma analyses 
include:
!
Gene expression by RNA sequencing
!
Immunohistochemistry 
!
DNA sequencing
!
DNA methylation profiling
Details regarding the collection, storage, and shipment of the samples are given in the Laboratory 
Manual.
6.13.
Electrocardiogram
Electrocardiograms (ECGs) will be done at Screening and as per standard of care during the 
Treatment Period, and as clinically indicated. Results will be collected in the eCRFs as AE or 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
37
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
SAE only if results are abnormal, changed and clinically significant, unless the finding is already 
documented in medical history.
6.14.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI)
A CT scan of the head, or preferably brain MRI, will be done as per standard of care at 
Screening, during the Treatment Period, and as clinically indicated. If CT scans show lesions 
pertinent for RECIST 1.1 criteria evaluation, data will be collected on the pertinent tumor 
evaluation eCRFs.
6.15.
Bone Scans and X-rays
Bone scans and x-rays will be done as per standard of care at Screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs. If bone scans or X-
rays show lesions pertinent for RECIST 1.1 criteria evaluation, data will be collected on the 
pertinent tumor evaluation eCRFs.
6.16.
Physical Examinations
Physical examinations will be done at Screening and as per standard of care during the 
Treatment Period, and as clinically indicated. Results will be collected in the eCRFs as AE or 
SAE only if results are abnormal and clinically significant.
6.17.
Vital Signs
Vital signs will be done at Screening and as per standard of care during the Treatment Period, 
and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if results 
are abnormal and clinically significant.
6.18.
Survival 
After the End-of-Treatment Visit, the subjects will have a 28-day Follow-up Visit followed by a 
phone call approximately every 90 days (+/- 14 days) for at least 12 months after the last subject 
is randomized or 120 PFS events have been observed whichever comes later. The subjects will 
also be asked questions about other medications they may be taking for their NSCLC. Those 
subjects entering the Follow-up Period without documented progression will continue to have 
CT scans in accordance with local standard of care (or approximately every 90 days) until 
documented progression of disease, withdrawal of consent, lost to follow-up, death, or 
termination of the study by the sponsor.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
38
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Male and female subjects with advanced nonsquamous NSCLC who have received one 
platinum-containing chemotherapy regimen for their advanced disease will be eligible for this 
study. The study will randomize approximately 160 subjects. The study will be conducted at 
approximately 30 to 60 sites in the United States, Canada, and Europe.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be randomized in the study:
1. Age ≥ 18 years at the time of signing the ICF.
2. Understand and voluntarily provide written informed consent prior to the conduct of any 
study related assessments/procedures.  
3. Able to adhere to the study visit schedule and other protocol requirements
4. Histologically or cytologically confirmed advanced nonsquamous NSCLC.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease (defined by the presence of 
≥1 radiographically documented measurable lesion).
7. One prior platinum-containing chemotherapy for the treatment of advanced disease.
8. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
9. Platelets ≥ 100,000 cells/mm3.
10. Hemoglobin (Hgb) ≥ 9 g/dL.
11. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and 
alanine transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper 
limit of normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
12. Total bilirubin ≤ 1.5 ULN  (unless there is a known history of Gilberts Syndrome).
13. Serum creatinine ≤1.5 x ULN, or calculated creatinine clearance ≥60 mL/min (if renal 
impairment is suspected 24-hour urine collection for measurement is required).
14. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
15. Females of childbearing potential [defined as a sexually mature woman who (1) have not 
undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy 
(the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for 
at least 24 consecutive months (ie, has had menses at any time during the preceding 24 
consecutive months)] must:
a.
Have a negative pregnancy test (ß-hCG) as verified by the study doctor within 72 
hours prior to starting study therapy. She must agree to ongoing pregnancy testing 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
during the course of the study, and after end of study therapy. This applies even if the 
subject practices true abstinence* from heterosexual contact.
b. Either commit to true abstinence* from heterosexual contact (which must be reviewed 
on a monthly basis) or agree to use, and be able to comply with, effective 
contraception without interruption, 28 days prior to starting IP, during the study 
therapy (including dose interruptions), and for 3 months after discontinuation of study 
therapy. 
Male subjects must:
a.
Practice true abstinence* or agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the study, 
during dose interruptions and for at least 6 months following IP discontinuation, even 
if he has undergone a successful vasectomy. 
16. Females must abstain from breastfeeding during study participation and 3 months after IP 
discontinuation. 
7.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. Squamous cell NSCLC.
2. Prior taxane therapy.
3. Evidence of active brain metastases, including leptomeningeal involvement (prior 
evidence of brain metastasis are permitted only if asymptomatic and clinically stable for 
at least 8 weeks following completion of therapy). MRI of the brain (or CT scan 
w/contrast) is preferred.
4. Only evidence of disease is non-measurable.
5. Known EGFR mutation.
6. Known EML4-ALK mutation.
7. Preexisting peripheral neuropathy of Grade > 2 (per NCI CTCAE v4.0).
8. Venous thromboembolism within 1 month prior to Cycle 1 Day 1.
9. Current congestive heart failure (New York Heart Association Class II-IV).
10. History of the following within 6 months prior to Cycle 1 Day 1: a myocardial infarction, 
severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart 
Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically 
significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG)
abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder.
11. Known hepatitis B or C virus (HBV/HCV) infection, known history of human 
immunodeficiency virus (HIV) infection, or receiving immunosuppressive or 
                                               
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic 
abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception].
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
40
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
myelosuppressive medications that would in the opinion of the investigator, increase the 
risk of serious neutropenic complications.
12. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, 
defined as ongoing signs/symptoms related to the infection without improvement despite 
appropriate antibiotics, antiviral therapy, and/or other treatment.
13. History of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or 
pulmonary hypersensitivity pneumonitis.
14. Subject has a clinically significant malabsorption syndrome, persistent diarrhea, or 
known sub-acute bowel obstruction > NCI CTCAE Grade 2, despite medical 
management.
15. Treatment with any investigational product within 28 days prior to signing the ICF.
16. History of or suspected allergy to nab-paclitaxel, azacitidine, human albumin or 
mannitol.
17. Currently enrolled in any other clinical protocol or investigational trial that involves
administration of experimental therapy and/or therapeutic devices.
18. Any other clinically significant medical condition, psychiatric illness, and/or organ 
dysfunction that will interfere with the administration of the therapy according to this 
protocol or which, in the views of investigator, preclude combination chemotherapy.
19. Any other malignancy within 5 years prior to randomization, or advanced malignant 
hepatic tumors, with the exception of adequately treated squamous cell carcinoma of the 
skin, in-situ carcinoma of the cervix, uteri, non-melanomatous skin cancer, carcinoma in 
situ of the breast, or incidental histological finding of prostate cancer (TNM 
Classification of Malignant Tumours (TNM) stage of T1a or T1b). (All treatment of 
which should have been completed 6 months prior to signing ICF).
20. Any condition including the presence of laboratory abnormalities, which places the 
subject at unacceptable risk if he/she were to participate in the study.
21. Any medical condition that confounds the ability to interpret data from the study.
22. Pregnant or breastfeeding females.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
41
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Investigational Products
Subjects will receive open-label nab-paclitaxel / CC-486 or nab-paclitaxel monotherapy during 
the Treatment Period of the study. The nab-paclitaxel and CC-486 are designated as IP and will 
be packaged and supplied by Celgene Corporation.
The reconstitution and IV administration of nab-paclitaxel should follow the local Prescribing 
Information for Abraxane.
8.1.1.
nab-Paclitaxel
nab-Paclitaxel will be supplied by the sponsor, Celgene Corporation, in single-use vials in single 
count cartons. Each single-use 50 mL vial will contain paclitaxel (100 mg) and human albumin 
as a stabilizer.
Please see local prescribing information for Abraxane for detailed instructions on the 
reconstitution, storage conditions and IV administration of nab-paclitaxel. Reconstituted nab-
paclitaxel should be stored in an area accessible only to study personnel.
Temperature records for nab-paclitaxel must be made available to Celgene or other sponsor-
nominated monitoring teams for verification of proper IP storage.
8.1.2.
CC-486 (Azacitidine for Oral Administration)
Celgene Corporation will supply azacitidine 100 mg tablets for oral administration. Each tablet is 
formulated using excipients that are generally regarded as safe and are used in marketed drug 
products.
All tablets will be packaged in blister cards. Only sufficient IP for one cycle of treatment will be 
provided to each subject at the start of each treatment cycle. All tablets should be swallowed 
whole, and should not be broken or chewed. CC-486 may be taken on an empty stomach or with 
food. Subjects should drink 8 ounces (240 mL) of room temperature water with each dose. It is 
strongly recommended that all subjects receive a dose of a prophylactic antiemetic, preferably a 
5-HT3 antagonist, approximately 30 minutes prior to each dose of CC-486.
The IP must be stored as directed on package label at controlled temperature and a temperature 
log must be maintained in the source documents The storage area should be secure and have 
access limited to study personnel. 
8.2.
Treatment Administration and Schedule
Approximately 160 subjects will be treated with nab-paclitaxel / CC-486 or nab-paclitaxel
monotherapy until disease progression, development of an unacceptable toxicity, death, lost to 
follow-up, withdrawal of consent, or termination of the study by the sponsor:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment  cycle  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
42
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment  cycle
8.3.
Dose Omissions and Modifications
8.3.1.
Rules for Dose Omissions and Modified Schedules
nab-Paclitaxel Monotherapy Arm
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
!
Day 1 Dose Missed
If the dose held or missed was to be given on Day 1 of the next cycle, that next cycle will 
not be considered to start until the day the first dose is actually administered to the 
subject (ie, D1-D8-Rest, X-D1-D8-Rest, etc).
!
Day 8 Dose Missed
That dose will be skipped.  Next dose (if laboratory results permit) will be Day 1 of the 
next scheduled cycle (ie, D1-X-Rest, D1-D8-Rest, etc).
nab-Paclitaxel/CC-486 Combination Arm
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
If any doses of CC-486 are missed, skip that day and resume as appropriate, do not double up on
subsequent days.
For nab-paclitaxel: 
!
Day 8 Dose Missed
That dose will be skipped. Next dose (if laboratory results permit) will be at Day 15 (ie, 
Rest-X-D15, Rest-D8-D15, etc).
!
Day 15 Dose Missed
That dose will be skipped.  Next dose (if laboratory results permit) will be Day 8 of the 
next scheduled cycle (ie, Rest-D8-X, Rest-D8-D15, etc).
8.3.2.
Rules for Dose Modifications
Subjects who experience any of the adverse drug reactions in Table 5 will be dose reduced as per 
Table 5 during treatment. 
nab-Paclitaxel Monotherapy Arm
!
Do not administer nab-paclitaxel on Day 1 of a cycle until ANC is at least 
1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment until 
counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and platelet 
count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil count of at least 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
43
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Day 8 of the cycle. 
Upon resumption of dosing, permanently reduce nab-paclitaxel doses as outlined in 
Table 5.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-paclitaxel 
at reduced doses (Table 5) when peripheral neuropathy improves to Grade 1 or 
completely resolves.
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to 
the guidelines in Table 5. For any other Grade 3 or 4 nonhematologic toxicity or other 
investigator defined unacceptable toxicity, interrupt treatment until the toxicity 
improves to ≤Grade 2, then restart treatment according to the guidelines in Table 5.
Re-escalation is not permitted at any time. 
nab-Paclitaxel/CC-486 Combination Arm
!
Do not administer nab-paclitaxel on Day 8 or CC-486 on Day 1 or 8 of a cycle until ANC 
is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment until 
counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and platelet 
count of at least 100,000 cells/mm3 on Day 1 and 8 for CC-486 and Day 8 for nab-
paclitaxel or to an absolute neutrophil count of at least 500 cells/mm3 and platelet count 
of at least 50,000 cells/mm3 on Day 15 of the cycle for nab-paclitaxel. Upon resumption 
of dosing, permanently reduce nab-paclitaxel and/or CC-486 doses as outlined in Table 5.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy (CC-486 does not need 
to be withheld). Resume nab-paclitaxel at reduced doses (Table 5) when peripheral 
neuropathy improves to Grade 1 or completely resolves. 
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to 
the guidelines in Table 5. For any other Grade 3 or 4 nonhematologic toxicity or 
other investigator defined unacceptable toxicity, interrupt treatment until the toxicity 
improves to ≤Grade 2, then restart treatment according to the guidelines in Table 5.
Re-escalation is not permitted at any time. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
44
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
Table 5:
Permanent Dose Reductions for Hematologic and Nonhematologic Toxicities and Dosing on the Study
Dose Modification During Treatment
Adverse Drug Reaction
Occurrence
Monotherapy Arm: nab-
paclitaxel Dose (mg/m2)
Combination Arm: nab-
paclitaxel Dose (mg/m2) / 
CC-486 Dose (mg)
Neutropenic Fever (ANC < 500/mm3 with fever >38°C)
OR
Delay of next cycle by > 7 days for ANC < 1500/mm3
OR
ANC < 500/mm3 for > 7 days
First
75
100/100
Second
50
75/100
Third
Discontinue Treatment*
50/100
Fourth
NA
Discontinue Treatment*
Platelet count < 50,000/mm3
First
75
100/100
Second
Discontinue Treatment*
75/100
Third
NA
Discontinue Treatment*
Peripheral Neuropathy Grade ≥3
First
75
75/200
Second
50
50/200
Third
Discontinue Treatment*
Grade 2 or 3 Cutaneous toxicity
Grade 3 Diarrhea
Grade 3 Mucositis
Any other Grade 3 or 4 nonhematologic toxicity or other 
investigator defined unacceptable toxicity
First
75
100/100
Second
50
75/100
Third
Discontinue Treatment*
50/100
Fourth
NA
Discontinue Treatment*
Grade 4 Cutaneous toxicity, Diarrhea or Mucositis
First
Discontinue Treatment*
ANC = absolute neutrophil count; AUC = area under the curve; NA = not applicable.
* If an adverse event that requires dose reduction recurs after the dose has been reduced according to the table  above , the subject should generally have 
treatment discontinued unless, at the discretion of the investigator, there is evidence of continuing benefit to the subject that outweighs the risk of recurrent 
toxicity.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
45
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
8.4.
Method of Treatment Assignment
The Treatment Period of the study is open-label. Enrollment/randomization will occur 1:1 via 
IRT. 
8.5.
Packaging and Labeling
The label(s) for all IP will include sponsor name, address and telephone number, the protocol 
number, IP name, dosage form and strength (where applicable), amount of IP per container, lot 
number, expiry date (where applicable), medication identification/kit number, dosing 
instructions, storage conditions, and required caution statements and/or regulatory statements as 
applicable. Additional information may be included on the label as applicable per local 
regulations.
8.6.
Investigational Product Accountability and Disposal
Celgene (or designee) will review with the investigator and relevant site personnel the process 
for IP return, disposal, and/or destruction including responsibilities for the site versus the 
responsibilities of Celgene (or designee).
Celgene will instruct the investigator on the return, disposal and/or destruction of IP. Only 
completely unused IP vials should be retained by the site until a representative from Celgene or 
other Celgene-designated personnel have completed an inventory. Partially used and completely 
used vials should be destroyed according to local guidelines, and disposition should be recorded 
on the Investigational Drug Accountability Record Form.
The investigator(s) or designee(s) is responsible for accounting for all IP that is issued to and
returned by the subject during the course of the study according to applicable regulatory
requirements. Any unused CC-486 must be returned by a study subject and retained by the
investigative site for accountability to be conducted by a Celgene representative (or designee). If
any IP is lost or damaged, its disposition should be documented. At the periodic monitoring
visits, a Celgene representative (or designee) will conduct IP accountability and address any
discrepancies. Upon unsatisfactory reconciliation of all IP, returned IP may be destroyed. At the
conclusion of the study, all remaining IP will be counted, reconciled with dispensing records, 
documented, and destroyed at the clinic site or allocated drug destruction location after
completion of drug accountability by a Celgene representative (or designee). The Celgene
representative (or designee) will ensure that a final report of drug accountability to the unit dose
level (ie, tablet) is prepared and placed in both the investigator study file and the central clinical
study file.
Investigational product will not be loaned or dispensed by the investigator to another investigator 
or site. Under certain circumstances, and with sponsor permission, cooperative groups may 
manage IP between locations within their network as clinical trial agreement and local guidelines 
permit.
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ot 
ments as
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nd/or destru
nd/or des
ntil a repres
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delines, and
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Fo
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le for accou
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f the study
the study a
y
be
be returned
returned
be conduc
be conduc
sititi
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on shou
(or 
(or desi
designe
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ed at the
accountabil
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designee) 
designee) 
t) is prepare
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gat
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e. Under c
anage
anage IP
IP be
b
permit
permit.


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
46
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
8.7.
Investigational Product Compliance
All IP will be administered only by study site personnel and accurate recording of all IP 
administration will be made in the appropriate section of the subject’s eCRF and source 
documents.
8.8.
Overdose
Overdose, as defined for this protocol, refers to nab-paclitaxel and CC-486 dosing.
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel or CC-486 to a given subject, regardless of any associated adverse events or sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. See 
Section 11.1 for the reporting of adverse events associated with overdose.
&(/*(1(35235,(7$5<,1)250$7,21
quelae.
uelae.
tha
han the
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otocol
otoc -spec
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ardl
rdless of w
ess of 
se report fo
report fo
overdose.
erdose.


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
47
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
Over the course of this study, additional medications may be required to manage aspects of the 
disease state of the subjects, including side effects from study treatments or disease recurrence. 
All supportive care (including but not limited to growth factors, antiemetics, analgesics, 
zolendronic acid, denosumab) is permitted as per the investigator’s discretion and should be 
administered according to local institutional practice. All concomitant treatments, including 
blood and blood products, must be reported on the eCRF.
!
Antiemetics are not required during the study; however, it is strongly recommended 
that all subjects receive a dose of a prophylactic antiemetic, preferably a 5-HT3 
antagonist, approximately 30 minutes prior to each dose of CC-486.
!
Stable, therapeutic doses of anticoagulants are permitted; however, subjects on 
warfarin should have prothrombin time (PT) or international normalized ratio (INR)
and partial thromboplastin time (PTT) monitored as clinically indicated.
!
Subjects on erythropoietin or darbepoetin alfa for at least 4 weeks prior to starting the 
IP may continue their pretreatment doses throughout the study.
#
Note: If the subject is not on a stable dose of an erythropoiesis-stimulating agents 
(ESA) prior to study entry, the subject may not start an ESA during Cycle 1. 
However, medications such as ESAs, granulocyte colony-stimulating factors (G-
CSFs), etc., may be administered according to standard of care after Cycle 1.
!
Use of white blood cell growth factors (eg, filgrastim, G-CSF for the treatment of 
subjects with neutropenic fever is permitted at the investigator’s discretion. Use of 
filgrastim rather than pegylated-filgrastim is indicated, because of the 14 day delay 
of the next cycle following treatment with peg-filgrastim.
!
Use of white blood cell growth factors (eg, filgrastim, G-CSF) for secondary
prophylaxis in subjects who experienced a neutropenic complication from a prior
cycle of chemotherapy (for which primary prophylaxis was not received) is permitted.
!
Flu vaccination is permitted.
!
Suppressive antiviral therapy (eg, entecavir, tenofovir, or lamivudine) is
recommended for subjects with chronic HBV infection (eg, those who are HBsAg
positive).
!
Routine infectious disease prophylaxis is not recommended, however, antibiotic,
antiviral, antipneumocystis, antifungal, or other prophylaxis may be implemented
during the study at the discretion of the investigator.
!
Treatments with bisphosphonates (eg, pamidronate, zolendronate), or other agents
(eg, denosumab) to prevent or delay progression of bone metastases are permitted.
Maintenance of a stable dosing regimen throughout the study is recommended.
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g
commended
commende
y a 5
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HT3
6.
ever, subje
ever, subje
l norm
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ically indic
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s, granuloc
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
48
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
!
Subjects may receive physiologic replacement doses of glucocorticoids as
maintenance therapy for adrenal insufficiency. Glucocorticoids may be administered
as an antiemetic with IV chemotherapy, if directed by local standard of care.
!
Treatment with antidiarrheal medications is recommended at the first sign of diarrhea
as per the guidelines in Appendix B. Pre-medication with antidiarrheal medication for 
subsequent doses of CC-486 may be appropriate.
9.2.
Prohibited Concomitant Medications and Procedures
Other investigational therapies must not be used while the subject is enrolled in the study.
Anticancer therapy (chemotherapy, biologic or investigational therapy, and surgery) other than
the study treatments must not be given to subjects during the study. If such treatment is required,
the subject must be discontinued from the study. Focal palliative radiotherapy for treatment of
cancer-related symptoms is allowed during study treatment at the discretion of the investigator.
The administration of either α-interferon and/or ribavirin, or drugs with known renal toxicity is
prohibited during study treatment.
9.3.
Required Concomitant Medications and Procedures for Patients 
Receiving CC-486
If a subject experiences ≥Grade 3 neutropenia, that subject will be treated with G-CSF 5 ∀g/kg 
daily until the ANC ≥2000/mm3. In subsequent cycles, that subject should receive G-CSF 
5∀g/kg daily beginning on Day 16 and continuing until the ANC ≥2000/mm3. In subjects
receiving G-CSF, the next cycle should begin no sooner than 48 hours after discontinuation of G-
CSF. Data regarding G-CSF administration should be recorded on the eCRF provided for G-CSF 
administration.
9.3.1.
Description of G-CSF
This medication stimulates the blood system (bone marrow) to make white blood cells, helping
fight infections. This medication is given to those whose ability to make white blood cells has
been reduced. Filgrastim (also known as G-CSF, or granulocyte colony stimulating factor) is a
man-made version of a certain natural substance found in the body. It is produced using a certain
bacteria. It will be obtained commercially and relabeled as clinical supplies. It should be stored,
and administered according to the manufacturer’s recommendation.
9.3.2.
Administration of G-CSF
For subjects who experience Grade ≥3 neutropenia, G-CSF 5 ∀g/kg daily will be administered
subcutaneously. During any cycle when Grade ≥3 neutropenia occurs, CC-486 and other 
cytotoxic agents will be held, and G-CSF will begin immediately (a minimum of 24 hours after 
the last dose of CC-486 and chemotherapy). In subsequent cycles, G-CSF will begin on Day 16. 
G-CSF will continue daily until the ANC ≥2000/mm3. For complete details on drug
administration, storage, clinical pharmacology, and the human PK of G-CSF (filgrastim), please
see the G-CSF(filgrastim) package insert.
&(/*(1(35235,(7$5<,1)250$7,21
er than
than
s requi
required,
red
i
reatment of
reatment o
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for
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subject 
he ANC 
e ANC ≥
ner than 48
ner than 48
be recorde
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CSF will c
administra
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ee the


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
49
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the study are described 
below.  Additional analyses of these endpoints as well as exploratory endpoints or subgroup 
analyses will be described in detail in the SAP.  The SAP supersedes the analyses described in 
the protocol should there be differences between the two.
Evaluations of the study endpoints will be based primarily on the point estimates and the 
associated 95% confidence intervals of the within- and between-treatment differences. However, 
statistical tests may be conducted and the nominal p-values may be provided in the clinical study 
report to indicate the strength of the treatment differences evaluated.
10.1.
Overview
Approximately 160 subjects will be randomized in a 1:1 ratio to two treatment arms (80 subjects 
per group). Arm A will receive nab-paclitaxel with epigenetic modifying therapy of CC-486 and 
Arm B will receive nab-paclitaxel as a monotherapy.  Both regimens will be administered in 21-
day cycles. All subjects will receive the assigned study treatment until disease progression, 
unacceptable toxicity, death, lost to follow-up, withdrawal of consent, or termination of the 
study by the sponsor, in accordance with local standard of care.  A permuted-block 
randomization method will be employed, and the randomization will be carried out centrally 
using an IRT system. The randomization will be stratified based on the following baseline
factors: 
!
ECOG performance status (0 versus 1)
!
Gender (males versus females)
!
Smoker (yes versus no)
A DMC will be used to review the safety and efficacy data during the study.   
10.2.
Study Population Definitions
10.2.1.
Intent-to-treat Population
The primary efficacy analysis will be performed on the intent-to-treat (ITT) population, which 
includes all randomized subjects regardless of whether the subject receives any IP or has any 
efficacy assessments performed. 
10.2.2.
Per-protocol (PP) Population
The PP population is defined as all eligible subjects randomized who receive at least one dose of 
the IP and have been treated in the arm they were assigned.  Additional analyses utilizing the PP 
population will be described in the SAP.
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ever,
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therap o
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will be adm
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1)
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e PP popul
PP popul
the IP
IP and 
and 
popul
opulata


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
50
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
10.2.3.
Treated Population
The treated population will consist of all randomized subjects who receive at least one dose of 
IP. The safety analyses will be based on the treatment as received if different from the assigned 
treatment by randomization.
10.3.
Sample Size and Power Considerations
The primary objective of this study is to evaluate the efficacy of the CC-486/nab-paclitaxel 
combination therapy and that of the nab-paclitaxel monotherapy, and the relative efficacy of 
these two treatment regimens. 
The effect of the two treatment regimens with respect to the efficacy endpoints will be based on 
the point estimates and the associated 95% confidence intervals. The sample size was chosen to 
support the estimation of the within- and between-treatment effects with reasonable precision. 
Table 6 below summarizes the two-sided 95% confidence intervals for a range of hypothetical
observed disease control rates given a sample size of 80 subjects in a treatment arm. If the 
observed disease control rate is 0.30, then the actual width of the 2-sided 95% confidence 
interval is 0.21 (95% CI is [0.20, 0.41]).
Table 6:
Disease Control Rate –Two-Sided 95% Confidence Interval of Hypothetical 
Disease Control Rate with a Sample Size of 80 Subjects in a Treatment Arm
Hypothetical Observed Disease 
Control Rate
Half Width of 95% Confidence 
Interval
95% Confidence Intervala
0.20
0.186
(0.119, 0.304)
0.25
0.199
(0.16, 0.359)
0.30
0.21
(0.203, 0.413)
0.35
0.218
(0.247, 0.465
0.40
0.224
(0.292, 0.516)
0.45
0.227
(0.338, 0.565)
0.50
0.228
(0.386, 0.614)
a Based on the Clopper-Pearson exact method.
Table 7 below summarizes the precision that can be achieved given different scenarios of 
hypothetical observed hazard ratios between the two treatment arms for PFS events, assuming a 
total of 120 events are observed. 
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based on
based on
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as chosen 
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2-
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idence
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86
86
(7$
0.199
0.199
,(
0.21
0.21
5,
0
35
23
52
35
35
35
( 35
earson exact 
earson exa
summarize
summari
observed 
observed h
20 eve
eventnts a
s a


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
51
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
Table 7:
Progression-Free Survival – Two-Sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms
Hypothetical Number of Events 
Observed
Hypothetical Observed Hazard 
Ratio of PFS Events
95% Confidence Interval of 
Hazard Ratioa
120
0.60
(0.42, 0.86)
0.65
(0.45, 0.93)
0.70
(0.49, 1.00)
a Assuming a standard error of 0.18 for the log hazard ratio.
Assuming the median times of PFS are 4.17 and 2.5 months, respectively, for the nab-
paclitaxel/CC-486
combination therapy
and nab-paclitaxel monotherapy arms, and an 
approximate 24 months accrual period for a total of 160 subjects, it is estimated that a total of 
120 PFS events will have been observed approximately 2 months after the last subject is 
randomized, assuming an exponential distribution for PFS. 
Of note, with 120 PFS events, this study has an 80% power (1-sided, Type-1 error of 2.5%)  to 
detect a HR of 0.60 for PFS improvement with the nab-paclitaxel/CC-486 arm over the nab-
paclitaxel monotherapy arm.    
One nonbinding interim analysis for PFS with an early stopping rule for futility will be 
conducted when approximately 60 events are observed. The nab-paclitaxel/CC-486 combination 
arm of the study may be stopped early for futility if the observed HR is > 1.10 given an 
approximate 60 PFS events have occurred at the time of the interim analysis. A HR> 1.10 when 
half of the target events of 120 have occurred signals a low probability for observing a 
meaningful difference in favor of the nab-paclitaxel/CC-486 combination therapy should the 
study continue to the end. With the assumptions stated above, it will take approximately 16 
months from the first subject randomized to observe approximately 60 PFS events for the interim 
analysis.    
If futility is declared, enrollment in the monotherapy nab-paclitaxel arm will continue up to a 
total of 80 subjects. 
Disease control rate, OS, and ORR will be evaluated within each treatment arm and between the 
treatment arms at the time of the final analysis of the PFS endpoint when approximately 120 PFS 
events have been observed.  
All subjects will continue to be followed for OS up to 12 months after the last subject is 
randomized or 120 PFS events have been observed, whichever comes later.
10.4.
Background and Demographic Characteristics
The baseline characteristics of all randomized subjects will be summarized. Subject’s age, 
height, weight, and baseline characteristics will be summarized using descriptive statistics, while 
gender, race and other categorical variables will be provided using frequency tabulations. 
Selected medical history data will be summarized using frequency tabulations by system organ 
class and preferred term.
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time of the 
ime of the
signals a lo
signals a lo
aclitaxel/C
aclitaxel/C
mptions sta
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ized to obse
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ent in the m
nt in the m
S, and ORR
S, and OR
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time of th
observed
observed
will cont
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inu
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or 120 P
.
Bac
Ba
The baselin
The baselin
height, w
height,
nde


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
52
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both Treatment 
and Follow-up Periods. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
10.6.
Efficacy Analysis
10.6.1.
Primary Efficacy Endpoints 
The primary efficacy endpoint is progression-free survival, which is defined as the time from the 
date of randomization to the date of disease progression or death (any cause) on or prior to the 
data cutoff date for analyses, whichever occurs first, based on the investigator’s assessment of 
the data from CT scans using RECIST 1.1 guidelines. Baseline tumor measurements will be 
determined from the radiologic evaluation performed within 28 days before the start of study 
therapy. 
Subjects who do not have disease progression and are alive as of the data cutoff date for the 
statistical analysis will be censored at the date of the last radiologic assessment prior to the data 
cutoff date.  Similarly, subjects who discontinue from the study prior to disease progression or 
death will be censored at the date of the last radiologic assessment prior to the data cutoff date.  
In the event that a new anticancer treatment occurs prior to documented progression, the subject 
will be censored at the date of the last radiologic assessment where the subject was documented 
to be progression-free prior to the new anticancer treatment. Subjects with a single missing 
radiologic assessment prior to a visit with documented disease progression (or death) will be 
analyzed as a PFS event at the date of the radiologic assessment that shows progression or death 
(whichever is earlier). Subjects with two or more missing radiologic assessments prior to a visit 
with documented disease progression (or death) will be censored at the date of the last radiologic 
assessment where the subject was documented to be progression-free prior to the first of the two 
missing visits.  Subjects who drop out early or die without any postbaseline radiologic tumor 
assessment will be censored on the date of randomization. 
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% CI) for each treatment arm. The Kaplan-Meier curve for PFS will 
be presented graphically for each treatment arm. The relative treatment effect between the 
combination and monotherapy arms on PFS will be estimated by the hazard ratio (HR) and the 
associated two-sided 95% CIs using the stratified Cox proportional hazard model with ECOG 
performance status (0 versus 1), gender (males versus females), and smoker (yes versus no) as 
the stratification factors, given the number of events in each cell is adequate.  No statistical 
inferential tests will be performed.
To assess the impact on PFS of radiologic assessments not occurring at the regularly scheduled 
assessment times, the frequency of these unscheduled/off-scheduled assessments will be 
presented for each treatment arm. In addition, confirmatory and sensitivity analyses will be 
performed to further assess the impact of missed radiologic assessments. An additional analysis 
of PFS, where death or new treatment will be considered as an event, will be conducted to 
address the impact of next line therapy. 
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from the
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data cutof
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to documen
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more mis
or death) wi
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cumented t
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the date of
the date o
will
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be sum
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ed 95% C
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assessme
ssessme
esen
esen


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
53
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
10.6.2.
Secondary Efficacy Endpoints
10.6.2.1.
Disease Control Rate
Disease control rate is defined as the percent of subjects who have a radiologic complete 
response, partial response, or stable disease according to RECIST 1.1 guidelines, as determined 
by the investigator.
Disease control rate for each treatment arm will be summarized by the observed DCR rate and 
the associated two-sided 95% CI. The relative treatment effect will be summarized by the 
absolute difference and ratio of the response rates and the associated two-sided 95% CI.    
10.6.2.2.
Overall Survival
Overall survival is defined as the time between randomization and death. All deaths, regardless 
of the cause of death, will be included. All subjects who are lost to follow-up prior to the end of
the study or who are withdrawn from the study will be censored at the time of last contact. 
Subjects who are still receiving treatment as of the data cutoff date will be censored at the cutoff 
date. Overall survival will be analyzed in a similar manner as that for PFS.
10.6.2.3.
Overall Response Rate 
Overall response rate is defined as the percent of subjects who have a radiologic complete or 
partial response according to RECIST 1.1 guidelines determined by the investigator.  
Overall response rate will be assessed using the same statistical methods as those for the DCR 
endpoint.    
10.6.3.
Exploratory Endpoints
10.6.3.1.
HealthCare Utilization 
Healthcare utilization will be summarized by treatment. Additional analyses will be described in 
detail in the SAP.
10.6.3.2.
Quality of Life Questionnaires
The score or VAS value and the corresponding change from baseline at each timepoint will be 
summarized by treatment for the EQ-5D-5L, EORTC QLQ C30 and LCSS questionnaires. 
Additional analyses will be described in detail in the SAP. 
10.6.3.3.
Biomarker, Tumor Characteristics, and Genomic Analyses 
Statistical analysis of the biomarkers, tumor characteristics, and genomic correlates will be 
described in a SAP separate from that described above.
10.7.
Safety Analysis
The treated population, which includes all randomized subjects who receive at least one dose of 
IP, will be the analysis population for all safety analyses.
&(/*(1(35235,(7$5<,1)250$7,21
hs, regardle
s, regardl
pririor to the 
or to th
of last cont
of last con
e censored
e censo
PFS.
FS.
ho ha
ho have
v a ra
a r
rmined by
rmined by
statist
statistical
ical
marized by t
rized by 
Questio
Questionn
n
e and the c
e and the c
ment f
ent for th
or t
f
ses will be
ses will be
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10.7.
10
e tr


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Celgene Corporation
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The safety/tolerability of the two treatment arms will be monitored through continuous reporting 
and evaluated by adverse events and serious adverse events, and incidence of subjects 
experiencing dose modifications, dose interruptions, and/or premature discontinuation of IP.
10.7.1.
Adverse Events
Adverse events will be analyzed in terms of TEAEs, defined as any AE or SAE occurring or 
worsening on or after the day of the first dose of the IP through 28 days after the last dose of IP.  
In addition, any serious AE with an onset date more than 28 days after the last dose of IP that is 
assessed by the investigator as related to IP will be considered a TEAE. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA). The severity of AEs will be graded based on NCI CTCAE, Version 4.0; 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Treatment-emergent adverse events, Grade 3 or higher TEAEs, serious AEs, TEAEs leading to 
dose reduction, dose delay, and dose interruption, TEAEs leading to treatment discontinuation, 
and TEAEs with an outcome of death will be summarized per treatment arms by MedDRA 
system organ class and preferred terms. 
Adverse events of special interest of the nab-paclitaxel/CC-486 combination and nab-paclitaxel 
monotherapy regimens identified in previous studies in a similar population may be identified 
and summarized by worst NCI CTCAE grade, System Organ Class (SOC) and MedDRA
preferred terms.
By-subject listings will be provided for all relevant safety data. Graphical displays and figures 
will be provided where useful to assist in the interpretation of results.
10.7.2.
Laboratory Assessments
Treatment group differences in each laboratory parameter with respect to the NCI CTCAE 
grades will be summarized by the frequency distribution of subjects with the AE grades.  
All laboratory parameters will be summarized by descriptive statistics within each treatment arm, 
as appropriate. 
10.7.3.
Study Drug Exposure
The extent of exposure to the IPs will be assessed based on the descriptive statistics on the 
number of cycles and IP doses administered, cumulative dose, average dose intensity, and 
percentage of protocol dose administered.  The incidences of CC-486 and nab-paclitaxel dose 
reductions, dose interruptions, and dose delays will be summarized by treatment arm.  
10.8.
Study Therapy Termination
Reasons for stopping study therapy will be presented in listings and summarized by frequency of 
occurrence and corresponding percentage of occurrence.
10.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the IP
through 28 days post last dose of the IP) and deaths that occur during the Follow-up Period will 
&(/*(1(35235,(7$5<,1)250$7,21
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occurrenc
occurrenc


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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
55
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
be summarized by frequency of occurrence and corresponding percentage by cause of death per 
period (during treatment or follow-up). 
10.10.
Interim Analysis
One nonbinding interim analysis for PFS with an early stopping rule for futility will be 
conducted when approximately 60 events are observed. The nab-paclitaxel/CC-486 combination 
arm of the study may be stopped early for futility if the observed HR is ≥1.10 given an 
approximate 60 PFS events have occurred at the time of the interim analysis. Should this occur, 
enrollment in the monotherapy nab-paclitaxel arm will continue up to a total of 80 subjects.  
10.11.
Data Monitoring Committee
An independent DMC will be established with the responsibilities for safeguarding the interests 
of study participants and monitoring the overall conduct of the study. Final recommendations of 
the DMC will reflect the judgment of the DMC members and will be considered advisory in 
nature to the sponsor. The decision to implement the recommendations of the DMC will be made 
by the sponsor, following consultation with the coordinating investigator and Steering 
Committee.
Operational details for the DMC will be detailed in the DMC charter. 
10.12.
Scientific Steering Committee
The conduct of this study will be overseen by a Steering Committee. The Steering Committee 
will serve in an advisory capacity to the sponsor.
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the eCRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of NSCLC will not require reporting as 
an adverse event.
An overdose, accidental or intentional, whether or not it is associated with an AE, or abuse, 
withdrawal, sensitivity or toxicity to an investigational product should be reported as an AE.  If 
an overdose is associated with an AE, the overdose and adverse event should be reported as 
separate terms.  See Section 8.8 for the definition of overdose.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for nab-paclitaxel or   
CC-486 overdose. Actual treatment should depend on the severity of the clinical situation and 
the judgment and experience of the treating physician.
All subjects will be monitored for AEs during the study. Assessments may include monitoring of 
any or all of the following parameters: the subject’s clinical symptoms, laboratory, pathological, 
radiological or surgical findings, physical examination findings, or findings from other 
appropriate tests and procedures.
All AEs will be recorded by the investigator from the time the subject signs informed consent to
28 days after the last dose of IP, and those SAEs made known to the investigator at any time 
thereafter that are suspected of being related to IP. AEs and serious adverse events (SAEs) will 
be recorded on the AE page of the eCRF and in the subject’s source documents. All SAEs must 
be reported to Celgene Drug Safety within 24 hours of the investigator’s knowledge of the event 
by facsimile, or other appropriate method, using the SAE Report Form, or approved equivalent 
form.
11.2.
Evaluation of Adverse Events
A qualified investigator will evaluate all adverse events as to: 
11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
!
Results in death;
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subject’s c
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11.2.1.
1.2.1.
ser


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Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
!
Is life-threatening (ie, in the opinion of the investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the eCRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of or an elective procedure for a pre-existing condition 
unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
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y life
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absence of
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E


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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
58
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
For each SAE, the investigator will provide information on severity, start and stop dates, 
relationship to IP, action taken regarding IP, and outcome.
11.2.2.
Severity / Intensity
For both AEs and SAEs, the investigator must assess the severity/intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current active minor version of NCI CTCAE, Version 4.0
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Adverse events that are not defined in the NCI CTCAE should be evaluated for severity/intensity 
according to the following scale:
!
Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required
!
Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required
!
Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible
!
Grade 4 = Life threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable
!
Grade 5 = Death – the event results in death
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.
Seriousness, not severity, serves as a guide for defining regulatory obligations.
11.2.3.
Causality 
The investigator must determine the relationship between the administration of IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
Means a causal relationship of the adverse event to IP
administration is unlikely or remote, or other medications, 
therapeutic interventions, or underlying conditions provide a 
sufficient explanation for the observed event.
Suspected:
Means there is a reasonable possibility that the administration 
of IP caused the adverse event.  ‘Reasonable possibility’ means 
there is evidence to suggest a causal relationship between the IP
and the adverse event.
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Su


('06'RF1XPEHU
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
59
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
Causality should be assessed and provided for every AE/SAE based on currently available 
information.  Causality is to be reassessed and provided as additional information becomes 
available.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP
that has not been manufactured or provided by Celgene, please provide the name of the 
manufacturer when reporting the event.
11.2.4.
Duration
For both AEs and SAEs, the investigator will provide a record of the start and stop dates of the 
event.
11.2.5.
Action Taken
The investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(eg, discontinuation or reduction of IP, as appropriate) and report if concomitant and/or 
additional treatments were given for the event. 
11.2.6.
Outcome
The investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered or death (due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or
!
is judged to be of significant clinical importance.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF. If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE.
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
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Celgene Corporation
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11.4.1.
Females of Childbearing Potential
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on IP, or within 3 months of the 
subject’s last dose of IP, are considered immediately reportable events. IP is to be discontinued 
immediately. The pregnancy, suspected pregnancy, or positive pregnancy test must be reported 
to Celgene Drug Safety immediately by facsimile, or other appropriate method, using the 
Pregnancy Initial Report Form, or approved equivalent form. The female subject should be 
referred to an obstetrician-gynecologist or another appropriate healthcare professional for further 
evaluation.
The investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the investigator
should report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate 
method, within 24 hours of the investigator’s knowledge of the event using the SAE Report 
Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving IP or within 
6 months of the last dose of IP, the male subject taking IP should notify the investigator, and the 
pregnant female partner should be advised to call her healthcare provider immediately. If the 
male subject is receiving IP, the IP may need to be discontinued in the male subject, but may be 
resumed later at the discretion of the investigator and medical monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The investigator is required to ensure that the data on these forms are accurate and consistent.
This requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent to at least 28 days after the last dose of IP) and 
those made known to the investigator at anytime thereafter that are suspected of being related to 
IP. SAEs occurring prior to treatment (after signing the ICF) will be captured.
The SAE report should provide a detailed description of the SAE and include a concise summary
of hospital records and other relevant documents. If a subject died and an autopsy has been 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
61
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available. Any follow-up data will be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety.
Where required by local legislation, the investigator is responsible for informing the Independent 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The investigator must keep copies of all SAE 
information on file including correspondence with Celgene and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via
facsimile or electronic mail. The response time is expected to be no more than five (5) business 
days. Urgent queries (eg, missing causality assessment) may be handled by phone.
11.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to nab-paclitaxel and CC-486 based on the Investigator
Brochures.
In the United States, all suspected unexpected serious adverse reactions (SUSARs) will be 
reported in an expedited manner in accordance with 21 CFR 312.32.
For countries within the European Economic Area (EEA), Celgene or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 
presentation of adverse reaction reports arising from clinical trials on investigational products for 
human use (ENTR/CT3) and also in accordance with country-specific requirements.
Celgene or its authorized representative shall notify the investigator of the following 
information: 
!
Any AE suspected of being related to the use of IP in this study or in other studies
that is both serious and unexpected (ie, SUSAR);
!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
The investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC. (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form/Completion Guidelines or to the Pregnancy Report Form/Completion Guidelines.
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
62
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the IP:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent
!
Death
!
Lost to follow-up
!
Protocol violation
The reason for discontinuation should be recorded in the eCRF and in the source documents.
The decision to discontinue a subject remains the responsibility of the treating physician, which
will not be delayed or refused by the sponsor. However, prior to discontinuing a subject, the
investigator may contact the Medical Monitor and forward appropriate supporting documents for 
review and discussion.
All subjects discontinued from IP for any reason will have a treatment discontinuation visit at the 
time of discontinuation and should undergo treatment discontinuation procedures.
All subjects discontinued from IP will be followed for a period of 28 days after last dose of IP
for the collection of AEs.
Additionally subjects who withdraw from or discontinue treatment should be followed for 
progressive disease (if applicable), survival and any new anticancer therapy given.
12.2.
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
study:
!
Withdrawal of consent
!
Death
!
Lost to follow-up
The following events may be considered sufficient reasons for discontinuing a subject from the 
study:
!
Adverse events(s)
!
Protocol violation
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. The investigator must notify the Medical Monitor immediately when a subject has 
been discontinued/withdrawn due to an AE (any unacceptable toxicity). All subjects who are 
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!
A


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Celgene Corporation
Confidential and Proprietary
63
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
withdrawn from the study should complete all protocol-required evaluations scheduled for early 
termination at the time of withdrawal.
Since follow-up of subjects who discontinue prematurely is of particular importance, every 
attempt should be made to collect all survival information and NSCLC treatment/therapy, unless 
the subject has specifically withdrawn consent from further follow-up. The investigator must 
make every effort to obtain minimal information regarding the subject’s survival status before 
determining that the subject is lost to follow-up.
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.
&(/*(1(35235,(7$5<,1)250$7,21


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64
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the investigator should contact the responsible Clinical Research
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page). This global 
Emergency Call Center is available 24 hours a day and 7 days a week. The representatives are 
responsible for obtaining your call-back information and contacting the on call Celgene/Contract 
Research Organization (CRO) Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
13.2.
Emergency Identification of Investigational Products
This is an open-label study; therefore, IP will be indentified on the package labeling. 
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
65
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative,
and investigator abide by Good Clinical Practice (GCP), as described in International Conference 
on Harmonization (ICH) Guideline E6 and in accordance with the general ethical principles 
outlined in the Declaration of Helsinki. The study will receive approval from an IRB/EC prior to 
commencement. The investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. Celgene staff or an authorized representative will evaluate and approve all 
investigators who in turn will select their staff.
The investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions. 
The investigator should maintain a list of sub-investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The investigator is responsible for keeping a record of all subjects who sign an ICF and are 
screened for entry into the study. Subjects who fail screening must have the reason(s) recorded in 
the subject’s source documents.
The investigator, or a designated member of the investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The investigator must ensure timely and accurate completion of eCRFs and queries.
14.3.
Subject Information and Informed Consent
The investigator must obtain informed consent of the subject and/or the subject’s legal 
representative prior to any study-related procedures.
Documentation that informed consent occurred prior to the subject’s entry into the study and of 
the informed consent process should be recorded in the subject’s source documents including the 
date. The original ICF signed and dated by the subject and by the person consenting the subject
prior to the subject’s entry into the study, must be maintained in the investigator’s study files and 
a copy given to the subject. In addition, if a protocol is amended and it impacts the content of the 
informed consent, the ICF must be revised. Subjects participating in the study when the amended 
protocol is implemented must be re-consented with the revised version of the ICF. The revised 
ICF signed and dated by the subject and by the person consenting the subject must be maintained 
in the investigator’s study files and a copy given to the subject.
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Celgene Corporation
Confidential and Proprietary
66
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The
written signed approval from the IRB/EC should specifically reference the investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
IP can only be supplied to an Investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
Celgene or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB/EC should mention the protocol title, number, amendment number 
(if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
67
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
The investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating investigator and the IRB/EC. This statement also applies to any 
communication between the investigator (or coordinating investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
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Celgene Corporation
Confidential and Proprietary
68
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The investigator must ensure that the records and documents pertaining to the conduct of the 
study and distribution of the IP are complete, accurate, filed and retained. Examples of source 
documents include: hospital records; clinic and office charts; laboratory notes; memoranda; 
subject’s diaries or evaluation checklists; dispensing records; recorded data from automated 
instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy and the laboratories, as well 
as copies of CRFs or CD-ROM.
15.2.
Data Management
Data will be collected via eCRF and entered into the clinical database per Celgene Standard 
Operating Procedures (SOPs). This data will be electronically verified through use of 
programmed edit checks specified by the clinical team. Discrepancies in the data will be brought 
to the attention of the clinical team, and investigational site personnel, if necessary. Resolutions 
to these issues will be reflected in the database. An audit trail within the system will track all 
changes made to the data.
15.3.
Record Retention
Essential documents must be retained by the investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IP. The investigator must retain these 
documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the investigator, Celgene, and their authorized 
representative(s);
!
List of sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of CRFs (if paper) and of documentation of corrections for all subjects;
!
IP accountability records;
!
Record of any body fluids or tissue samples retained;
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
69
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
!
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.
The investigator must obtain approval in writing from Celgene prior to destruction of any 
records. If the investigator is unable to meet this obligation, the investigator must ask Celgene 
for permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
70
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
16.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative
for compliance with applicable government regulations with respect to current GCP and standard 
operating procedures.
16.1.
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study. All aspects of the study are reviewed with the investigator and the staff at a study 
initiation visit and/or at an investigator meeting. Prior to enrolling subjects into the study, a 
Celgene representative or designee will review the protocol, eCRFs, procedures for obtaining 
informed consent, record keeping, and reporting of AEs/SAEs with the investigator. Monitoring 
will include on-site visits with the investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, IP 
storage area, eCRFs, subject’s source documents, and all other study documentation will be
inspected/reviewed by the Celgene representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the eCRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the investigator and/or his/her staff. Any necessary 
corrections will be made directly to the eCRFs or via queries by the investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene. Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The investigator is required to permit direct access to the facilities where the study took place, 
source documents, eCRFs and applicable supporting records of subject participation for audits 
and inspections by IRB/IECs, regulatory authorities (eg, FDA, European Medicines Agency 
[EMA], Health Canada) and company authorized representatives. The investigator should make 
every effort to be available for the audits and/or inspections. If the investigator is contacted by 
any regulatory authority regarding an inspection, he/she should contact Celgene immediately.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
71
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
17.
PUBLICATIONS
The results of this study may be published in a medical publication, journal, or may be used for 
teaching purposes. Additionally, this study and its results may be submitted for inclusion in all 
appropriate health authority study registries, as well as publication on health authority study 
registry websites, as required by local health authority regulations. Selection of first authorship 
will be based on several considerations, including, but not limited to study participation, 
contribution to the protocol development, and analysis and input into the manuscript, related 
abstracts, and presentations in a study.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
72
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
18.
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eated 
ated
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r, et al.
Clin Onco
Clin Onc
perable non
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arini C, e
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ed paclita
HT. A phase
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bound pacl
bound pac
Clin Onco
lin Oncol
gaerts J, Sch
gaerts J, Sc
n so
solid tum
lid tum
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47. 
re SD, Cog
e SD, Cog
odysplast
odysplasticic
Onco
Oncol 201
20
, Dahut WL
, Dahut WL
r pharmaco
harmaco
14(13):4200
4(13):4200
rber DE
ber DE, S
new life fo
new life fo
ordi
ordi


('06'RF1XPEHU
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non–Small-Cell Lung Cancer 
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non-small-cell lung cancer. J Clin Oncol 2008;26(4):639-43.
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J Clin Oncol 2013;31(8):981-3.
Sculier JP, Berghmans T, Lafitte JJ, Richez M, Recloux P, Van Cutsem O, et al. A phase II study 
testing paclitaxel as second-line single agent treatment for patients with advanced non-small cell 
lung cancer failing after a first-line chemotherapy. Lung Cancer 2002;37:73–7.
Socinski MA, Manikhas GM, Stroyakovsky DL, Makhson AN, Cheporov SV, Orlov SV, et al. A 
dose finding study of weekly and every-3-week nab-paclitaxel followed by carboplatin as 
first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol 
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Socinski MA, Schell MJ, Bakri K, Peterman A, Lee JH, Unger P, et al. Second-line, low-dose, 
weekly paclitaxel in patients with stage IIIB/IV nonsmall cell lung carcinoma who fail first-line 
chemotherapy with carboplatin plus paclitaxel. Cancer 2002;95:1265–73. 
Socinski MA, Steagall A, Gillenwater H. Second-line chemotherapy with 96-hour infusional 
paclitaxel in refractory non-small cell lung cancer: report of a phase II trial. Cancer Invest 
1999;17:181–8. 
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rapy
apy i
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52-61.
-61.
nski MA, S
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eekly paclit
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
74
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, et al. 
Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus 
carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final 
results of a phase III trial. J Clin Oncol 2012 Jun 10;30(17):2055-62.
Yasuda K, Igishi T, Kawasaki Y, Kato K, Matsumoto S, Katayama S, et al. Phase II study of 
weekly paclitaxel in patients with non-small cell lung cancer who have failed previous 
treatments. Oncology 2004;66:347–52.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
75
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
19.
APPENDICES
Appendix A: ECOG Performance Status Score
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5
Dead
Oken, 1982.
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
76
ABI-007-NSCL-006 Amendment 1.0 Final: 24 June 2014
Appendix B: Recommendations for Management of Treatment-Induced 
Diarrhea
The following published guidelines (Benson, 2004) were modified in order to be consistent with 
the clinical study protocol.
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Celgene Signing Page
This is a representation of an electronic record that was signed electronically in Livelink.
This page is the manifestation of the electronic signature(s) used in compliance with
the organizations electronic signature policies and procedures.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
TITLE PAGE
A PHASE 2, OPEN-LABEL, MULTICENTER STUDY TO 
ASSESS SAFETY AND EFFICACY OF SECOND/THIRD-
LINE TREATMENT WITH NAB®-PACLITAXEL (ABI-
007) IN COMBINATION WITH EPIGENETIC 
MODIFYING THERAPY OF CC-486, OR 
IMMUNOTHERAPY OF DURVALUMAB (MEDI4736), 
OR AS MONOTHERAPY IN SUBJECTS WITH 
ADVANCED NON-SMALL CELL LUNG CANCER 
(NSCLC): ABOUND.2L+
INVESTIGATIONAL PRODUCTS:
CC-486, nab-Paclitaxel (ABI-007), 
durvalumab (MEDI4736)
PROTOCOL NUMBER:
ABI-007-NSCL-006
DATE FINAL:
29 May 2014
AMENDMENT 1.0 FINAL:
24 Jun 2014
AMENDMENT 2.0 FINAL:
18 Jul 2014
AMENDMENT 3.0 FINAL:
14 Apr 2016
AMENDMENT 4.0 FINAL:
31 May 2016
EudraCT NUMBER
2014-001105-41
IND NUMBER
123160
SPONSOR NAME / ADDRESS:
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
United States
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board. The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations.
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information:
Name:
Title:
Address: 
86 Morris Avenue
Summit, NJ 07901
United States
Phone:
E-mail:
Contact Information:
Name:
Title:
Address: 
86 Morris Avenue
Summit, NJ 07901
United States
Phone:
E-mail:
Note: The back-up 24 hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls.
Back-up 24 Hour Global Emergency Contact Call Center: 
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}.
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:_______________________________________
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
PROTOCOL SUMMARY
Study Title
A Phase 2, Open-label, Multicenter Study to Assess Safety and Efficacy of Second/Third-line 
Treatment with nab®-Paclitaxel1 (ABI-007) in Combination with Epigenetic Modifying Therapy 
of CC-486, or Immunotherapy of Durvalumab (MEDI4736), or as Monotherapy in Subjects with 
Advanced Non-small Cell Lung Cancer (NSCLC): ABOUND.2L+
Indication
Second/third-line treatment of advanced NSCLC.
Objectives
Primary
!
To estimate the efficacy of nab-paclitaxel administered intravenously (IV) on Days 8 
and 15 with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 
14 every 21 days or nab-paclitaxel administered intravenously (IV) on Days 1 and 8
with immunotherapy of durvalumab administered IV on Day 15 every 21 days, and 
nab-paclitaxel monotherapy administered IV on Days 1 and 8 every 21 days as 
second/third-line treatment for advanced NSCLC.
Secondary 
!
To estimate the relative efficacy of each of the combination therapy arms to the 
monotherapy arm.
!
To evaluate the safety and tolerability of nab-paclitaxel administered intravenously 
(IV) on Days 8 and 15 with epigenetic modifying therapy of CC-486 once daily 
(QD) on Days 1 to 14 every 21 days, or nab-paclitaxel administered intravenously 
(IV) on Days 1 and 8 with immunotherapy of durvalumab administered IV on Day 
15 every 21 days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 
every 21 days as second/third-line treatment for advanced NSCLC.
Exploratory 
!
To assess healthcare resource utilization for the treatment arms.
!
To assess the quality of life (QoL) for the treatment arms.
!
To determine baseline tumor characteristics which predict response to nab-paclitaxel 
as a single agent and in combination with epigenetic modifying therapy of CC-486 or 
in combination with immunotherapy of durvalumab. 
!
To evaluate genomic correlates of response to nab-paclitaxel as a single agent and in 
combination with epigenetic modifying therapy of CC-486 or in combination with 
immunotherapy of durvalumab. 
                                               
1 nab® is a registered trademark of Celgene Corporation.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
!
To evaluate anti-tumor activity of nab-paclitaxel/durvalumab combination therapy 
using Investigator assessment according to immune related response criteria updated 
with RECIST 1.1 (irRECIST), and its association with PD-L1 expression.
Study Design
This is a Phase 2, open-label, multicenter study to assess efficacy and safety of:
o
nab-paclitaxel in combination with epigenetic modifying therapy of CC-486,
o
nab-paclitaxel in combination with immunotherapy of durvalumab, 
o
and nab-paclitaxel monotherapy 
as second/third-line treatment in subjects with advanced NSCLC who have received no more 
than one prior chemotherapy regimen. Approximately 240 subjects with advanced NSCLC will 
be assigned 1:1:1 into one of the following treatment arms: nab-paclitaxel /CC-486 combination 
therapy, nab-paclitaxel /durvalumab combination therapy or nab-paclitaxel monotherapy prior to 
receiving the first dose of investigational product (IP). Randomization/treatment assignment 
strategy of subjects to the three treatment arms is described in the Overview of Statistical 
Methods below and in Section 10.1. 
The study will consist of up to a 28-day Screening Period, a Treatment Period and a Follow-up 
Period.
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of IP.
The Treatment Period begins with the first dose of IP as described in Section 8.  Subjects will 
receive one of the following treatments based on the randomization/treatment assignment:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days  1 to 14 of each 21-day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 
durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15 of each 21-
day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the Investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, withdrawal of 
consent, or termination of the study by the Sponsor. Subjects in the nab-paclitaxel/durvalumab 
arm may continue treatment beyond disease progression per Response Evaluation Criteria in 
Solid Tumors (RECIST) guidelines, Version 1.1 as described in Section 4.1.2.1.
Tumor evaluations will be assessed by the investigative sites and response will be determined 
according to RECIST guidelines, Version 1.1 (Eisenhauer, 2009), and immune-related RECIST 
criteria (irRECIST) when applicable.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an adverse event (AE)/serious adverse event (SAE) and also recorded on the 
laboratory electronic Case Report Form (eCRF) (see Section 11.3).
All subjects who discontinue from treatment for any reason other than withdrawal of consent, 
lost to follow-up, death, or termination of the study by the sponsor will enter the Follow-up 
Period. It will consist of a visit 28 days after the last dose of IP or End of Treatment Visit, 
whichever is later. Thereafter, subjects in the nab-paclitaxel/CC-486 combination and nab-
paclitaxel monotherapy arms will be followed for survival by phone call contact approximately 
every 90 days (+/- 14 days) for at least 12 months after the last subject is randomized/assigned in 
either arm or 120 progression-free survival (PFS) events have been observed between these two 
arms, whichever comes later. Subjects in the nab-paclitaxel/durvalumab arm will be followed for 
survival in a similar manner for at least 12 months after the last subject is assigned to this arm.
During the study, subjects will have computed tomography (CT) scans every 42 days (-3/+7
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the Sponsor. Subjects in the nab-paclitaxel/durvalumab arm who 
continue beyond disease progression per RECIST 1.1 will continue to have CT scans every 42 
days (-3/+7) until progression per immune-related RECIST criteria (irRECIST 1.1) (Nishino, 
2013). Those subjects entering the Follow-up Period without documented progression will 
continue to have CT scans in accordance with local standard of care (or approximately every 90 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the Sponsor. All post-treatment anticancer therapies will be 
recorded during the Follow-up Period.  
Study Population
Male and female subjects with advanced NSCLC who have received no more than one prior
chemotherapy regimen for their advanced disease will be eligible for this study (immunotherapy 
in prior line of treatment is allowed, including platinum doublet combination). Subjects will 
receive study therapy as second or third line of treatment for advanced disease.
Length of Study
The enrollment of 240 subjects on this study will take approximately 28 months. The total length 
of this Phase 2 study with follow-up for survival is estimated to be approximately 40 months.
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, 
whichever is the later date.
Study Treatments
Subjects will receive nab-paclitaxel in combination with CC-486 or durvalumab, or nab-
paclitaxel monotherapy during the study. The CC-486, nab-paclitaxel, and durvalumab are
designated as IP and will be packaged and supplied by the Study Sponsor.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
9
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Overview of Statistical Methods
The primary objective of this study is to estimate the efficacy of the CC-486 and nab-paclitaxel 
combination therapy, that of the durvalumab and nab-paclitaxel combination therapy, and that of 
the nab-paclitaxel monotherapy. The secondary efficacy objective is to estimate the relative 
efficacy of each of the combination regimens to the monotherapy regimen and the tolerability of 
each of the 3 treatment regimens.  
Approximately 240 subjects will be assigned to one of the three treatment arms (approximately 
80 subjects per group).  A permuted-block randomization method will be employed to assign the 
subjects among the treatment arms that are enrolling simultaneously, stratified by the following 
baseline factors: ECOG performance status (0 versus 1), gender (males versus females), and 
smoker (yes versus no). Randomization/treatment assignment of subjects will be carried out 
centrally using an Interactive Response Technology (IRT) system. Prior to the time of Protocol 
Amendment 3.0, all subjects will be randomized 1:1 to the nab-paclitaxel/CC-486 combination 
therapy and nab-paclitaxel monotherapy arms. Once Protocol Amendment 3.0 is in effect, 
subjects from sites that are ready to implement the said amendment will be randomized 1:1:1 to 
the nab-paclitaxel/CC-486 combination therapy, nab-paclitaxel monotherapy, and nab-
paclitaxel/durvalumab combination therapy arms, respectively. Subjects from the remaining sites 
will continue to be randomized 1:1 to the nab-paclitaxel/CC-486 combination therapy and nab-
paclitaxel monotherapy arms.  Once approximately 80 subjects have been randomized to each of 
the nab-paclitaxel/CC-486 combination therapy and the nab-paclitaxel monotherapy arms, all 
incoming subjects will be assigned to the nab-paclitaxel/durvalumab combination therapy arm 
until approximately 80 subjects have been enrolled to receive the IP in that arm. Hence, 
treatment assignments of subjects to the nab-paclitaxel/CC-486 combination therapy and nab-
paclitaxel monotherapy arms will be in effect conducted completely in a randomized fashion. If 
the nab-paclitaxel/CC-486 arm stops after the interim analysis, incoming subjects will be 
randomized 2:1 to the nab-paclitaxel/durvalumab combination therapy and nab-paclitaxel 
monotherapy arms, respectively, until enrollment to the monotherapy arm is complete.  
Thereafter, subjects will be assigned to the nab-paclitaxel/durvalumab combination therapy arm 
until approximately 80 subjects have been enrolled in this arm.  
Evaluations of the study endpoints will be based primarily on the point estimates and the 
associated 95% confidence intervals of the within- and between-treatment differences (each 
combination therapy vs. monotherapy).
An independent Data Monitoring Committee (DMC) will be established to review the interim 
safety and efficacy data.  
Efficacy Analyses
The intent-to-treat population, which includes all randomized (or assigned) subjects regardless of 
whether the subject receives any IP or has any efficacy assessments performed, will be used for 
all efficacy analyses. The primary efficacy endpoint is PFS, which is defined as the time from the 
date of randomization/treatment assignment to the date of disease progression or death (from any 
cause) on or prior to the data cutoff date for analyses, whichever occurs first, based on the 
Investigator’s assessment of the data from CT scans using RECIST 1.1 guidelines. Baseline 
tumor measurements will be determined from the radiologic evaluation performed within 28 
days before the start of study therapy. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
10
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% confidence interval [CI]) for each treatment arm.  The relative 
treatment effect between each of the combination therapy and monotherapy arms with respect to 
PFS will be estimated by the hazard ratio (HR) and the associated two-sided 95% CIs using the 
stratified Cox proportional hazard model with ECOG performance status (0 versus 1), gender
(males versus females), and smoker (yes versus no) as the stratification factors. No statistical 
inferential tests will be performed. To explore the effect of treatment post initial progression, 
PFS defined by irRECIST criteria may be estimated for those subjects in the nab-
paclitaxel/durvalumab combination arm.  
The secondary endpoints include disease control rate (DCR), overall response rate (ORR), and 
overall survival (OS). Disease control rate and ORR will be summarized within each treatment 
arm by the observed rates and the associated 95% CIs. The relative treatment effect of each of 
the combination therapy arms to the monotherapy arm will be summarized by the ratio of the 
observed rates. Overall survival will be analyzed using similar statistical methods as that for the 
PFS endpoint.
Safety Analyses
The treated population, which includes all subjects who receive at least one dose of IP, will be 
the analysis population for all safety analyses. 
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AE or SAE occurring or worsening on or after the day of the first dose of the IP
through 28 days after the last dose of the last IP administration.  
In addition, any SAE with an onset date more than 28 days after the last dose of IP that is 
assessed by the Investigator as related to IP will be considered a TEAE. For the nab-
paclitaxel/durvalumab arm, AEs with an onset from 29 days up to 90 days after the last dose of 
any IP will be summarized separately.
Treatment-emergent adverse events, Grade 3 or higher TEAEs, SAEs, TEAEs leading to dose 
reduction, and dose interruption, TEAEs leading to treatment discontinuation, and TEAEs with 
an outcome of death will be summarized by treatment arms using MedDRA system organ class 
and preferred terms.
Sample Size
This study is designed primarily to estimate the treatment effect within each of the combination 
and monotherapy arms and secondarily the relative effect between each of the combination 
therapy and the monotherapy arms with respect to the primary and secondary efficacy endpoints. 
The sample size was chosen to support the estimation of the within- and between-treatment 
effects with reasonable precision. Table 1 below summarizes the precisions that can be achieved 
given different scenarios of hypothetical observed hazard ratios between the two treatment arms 
for PFS events, assuming a total of approximately 120 events are observed between two
treatment arms, and the time to PFS has an exponential distribution. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
11
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Table 1:
Progression-Free Survival – Two-sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms
Hypothetical Number of 
Events Observed
Hypothetical Observed Hazard 
Ratio of PFS Events
95% Confidence Interval of 
Hazard Ratioa
120
0.60
(0.42, 0.86)
0.65
(0.45, 0.93)
0.70
(0.49, 1.00)
a Assuming a standard error of 0.18 for the log hazard ratio.
Assuming the median times of PFS are 4.17, 4.25 and 2.5 months, respectively, for the nab-
paclitaxel/CC-486 combination therapy, the nab-paclitaxel/durvalumab combination therapy and 
nab-paclitaxel monotherapy arms, and an approximate 28 months accrual period for a total of 
approximately 240 subjects, it is estimated that an approximate total of 170 PFS events among 
the three arms will be observed by approximately 3 months after the last subject is assigned to 
the nab-paclitaxel/durvalumab arm, assuming an exponential distribution for PFS. 
One nonbinding interim analysis for PFS with early stopping rule for futility will be conducted 
when approximately 60 events have been observed between the nab-paclitaxel/CC-486 
combination and nab-paclitaxel monotherapy arms. An additional non-binding interim analysis 
for futility with early stopping rule with the PFS endpoint between the nab-
paclitaxel/durvalumab combination and nab-paclitaxel monotherapy arms will be conducted 
when approximately 30 PFS events have been observed in the nab-paclitaxel/durvalumab arm 
(60 or more events are expected to have occurred in the monotherapy arm at that point).
Data Monitoring Committee
An independent Data Monitoring Committee (DMC) will be established with the responsibilities 
for safeguarding the interests of study participants and monitoring the overall conduct of the 
study. Final recommendations of the DMC will reflect the judgment of the DMC members and 
will be considered advisory in nature to the Sponsor. The decision to implement the 
recommendations of the DMC will be made by the Sponsor, following consultation with the trial 
Coordinating Investigator and Steering Committee. A DMC charter will be established.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
12
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
1.
INTRODUCTION..................................................................................................19
1.1.
Non-small Cell Lung Cancer ..................................................................................19
1.2.
nab-Paclitaxel in NSCLC .......................................................................................20
1.3.
Rationale for nab-Paclitaxel as Second/Third-line Treatment in Subjects 
with Advanced NSCLC ..........................................................................................22
1.4.
Rationale for nab-Paclitaxel in Combination With Epigenetic Modifying 
Therapy of CC-486 as Second/Third-line Treatment in Subjects with 
Advanced NSCLC ..................................................................................................23
1.5.
Rationale for nab-Paclitaxel in Combination With Immunotherapy of 
Durvalumab as Second/Third-line Treatment in Subjects with Advanced 
NSCLC...................................................................................................................26
2.
STUDY OBJECTIVES...........................................................................................31
2.1.
Primary Objective...................................................................................................31
2.2.
Secondary Objective...............................................................................................31
2.3.
Exploratory Objectives ...........................................................................................31
3.
STUDY ENDPOINTS............................................................................................32
3.1.
Primary Endpoint....................................................................................................32
3.2.
Secondary Endpoints ..............................................................................................32
3.2.1.
Efficacy..................................................................................................................32
3.2.2.
Safety.....................................................................................................................32
3.3.
Exploratory Endpoints............................................................................................32
4.
OVERALL STUDY DESIGN ................................................................................33
4.1.
Study Design ..........................................................................................................33
4.1.1.
Screening Period.....................................................................................................33
4.1.2.
Treatment Period ....................................................................................................33
4.1.2.1.
Treatment Beyond Progression for Subjects in the nab-
Paclitaxel/Durvalumab Arm....................................................................................34
4.1.3.
End-of-Treatment Visit...........................................................................................34
4.1.4.
Follow-up Period....................................................................................................34
4.2.
Study Design Rationale ..........................................................................................35
4.3.
Study Duration .......................................................................................................38
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4.1.3
1.4.
1 4


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
13
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
4.4.
End of Trial ............................................................................................................38
5.
TABLE OF EVENTS.............................................................................................39
6.
PROCEDURES......................................................................................................43
6.1.
Medical History......................................................................................................43
6.2.
Prior and Concomitant Medications and Procedures ...............................................43
6.3.
Pregnancy Testing ..................................................................................................44
6.4.
Complete Chest Computed Tomography (CT) Scan................................................44
6.5.
Weight and Height..................................................................................................44
6.6.
ECOG Performance Score ......................................................................................44
6.7.
Peripheral Neuropathy Assessment.........................................................................45
6.8.
Adverse Event Reporting........................................................................................45
6.9.
Quality of Life Questionnaires................................................................................45
6.10.
Healthcare Resource Utilization Questionnaire .......................................................45
6.11.
Laboratory Assessments .........................................................................................45
6.12.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) .....................................................................................46
6.13.
Electrocardiogram ..................................................................................................47
6.14.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI) .......................47
6.15.
Bone Scans and X-rays...........................................................................................47
6.16.
Physical Examinations............................................................................................48
6.17.
Vital Signs..............................................................................................................48
6.18.
Survival..................................................................................................................48
7.
STUDY POPULATION.........................................................................................49
7.1.
Number of Subjects and Sites .................................................................................49
7.2.
Inclusion Criteria....................................................................................................49
7.3.
Exclusion Criteria...................................................................................................50
8.
DESCRIPTION OF STUDY TREATMENTS........................................................54
8.1.
Description of Investigational Products...................................................................54
8.1.1.
nab-Paclitaxel.........................................................................................................54
8.1.2.
CC-486 (Azacitidine for Oral Administration) ........................................................54
8.1.3.
Durvalumab (MEDI4736).......................................................................................54
8.1.4.
Monitoring During/After Durvalumab Infusion ......................................................55
8.2.
Treatment Administration and Schedule .................................................................56
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3


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
14
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
8.3.
Dose Omissions and Modifications.........................................................................56
8.3.1.
Rules for Dose Omissions and Modified Schedules ................................................56
8.3.2.
Rules for Dose Modifications .................................................................................58
8.4.
Method of Treatment Assignment...........................................................................62
8.5.
Packaging and Labeling..........................................................................................62
8.6.
Investigational Product Accountability and Disposal ..............................................62
8.7.
Investigational Product Compliance........................................................................63
8.8.
Overdose ................................................................................................................63
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................64
9.1.
Permitted Concomitant Medications and Procedures...............................................64
9.2.
Prohibited Concomitant Medications and Procedures..............................................65
9.3.
Required Concomitant Medications and Procedures for Subjects Receiving 
CC-486...................................................................................................................65
9.3.1.
Description of G-CSF.............................................................................................66
9.3.2.
Administration of G-CSF........................................................................................66
10.
STATISTICAL ANALYSES..................................................................................67
10.1.
Overview................................................................................................................67
10.2.
Study Population Definitions ..................................................................................68
10.2.1.
Intent-to-treat Population........................................................................................68
10.2.2.
Per-protocol (PP) Population ..................................................................................68
10.2.3.
Treated Population..................................................................................................68
10.3.
Sample Size and Power Considerations...................................................................68
10.4.
Background and Demographic Characteristics........................................................71
10.5.
Subject Disposition.................................................................................................71
10.6.
Efficacy Analysis....................................................................................................72
10.6.1.
Primary Efficacy Endpoints....................................................................................72
10.6.2.
Secondary Efficacy Endpoints ................................................................................73
10.6.2.1.
Disease Control Rate ..............................................................................................73
10.6.2.2.
Overall Survival .....................................................................................................73
10.6.2.3.
Overall Response Rate............................................................................................73
10.6.3.
Exploratory Endpoints............................................................................................73
10.6.3.1.
HealthCare Utilization............................................................................................73
10.6.3.2.
Quality of Life Questionnaires................................................................................73
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10.6.2.3.
0.6.2.3.
6


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
15
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
10.6.3.3.
Biomarker, Tumor Characteristics, and Genomic Analyses.....................................73
10.6.3.4.
Anti-tumor Activity and PD-L1 Expression (nab-Paclitaxel/Durvalumab 
Arm).......................................................................................................................73
10.7.
Safety Analysis.......................................................................................................74
10.7.1.
Adverse Events.......................................................................................................74
10.7.2.
Laboratory Assessments .........................................................................................74
10.7.3.
IP Exposure............................................................................................................74
10.8.
Study Therapy Termination ....................................................................................75
10.9.
Deaths ....................................................................................................................75
10.10.
Interim Analysis .....................................................................................................75
10.11.
Data Monitoring Committee ...................................................................................75
10.12.
Scientific Steering Committee ................................................................................75
11.
ADVERSE EVENTS..............................................................................................76
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................76
11.2.
Evaluation of Adverse Events.................................................................................77
11.2.1.
Seriousness.............................................................................................................77
11.2.2.
Severity / Intensity..................................................................................................78
11.2.3.
Causality ................................................................................................................78
11.2.4.
Duration .................................................................................................................79
11.2.5.
Action Taken..........................................................................................................79
11.2.6.
Outcome.................................................................................................................79
11.3.
Abnormal Laboratory Values..................................................................................79
11.4.
Pregnancy...............................................................................................................80
11.4.1.
Females of Childbearing Potential ..........................................................................80
11.4.2.
Male Subjects.........................................................................................................80
11.5.
Reporting of Serious Adverse Events......................................................................80
11.5.1.
Safety Queries ........................................................................................................81
11.6.
Expedited Reporting of Adverse Events..................................................................81
11.7.
Definition of Adverse Events of Special Interest .....................................................82
12.
DISCONTINUATIONS .........................................................................................83
12.1.
Study Treatment Discontinuation............................................................................83
12.2.
Study Discontinuation ............................................................................................83
12.3.
Subject Replacement ..............................................................................................84
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
16
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
13.
EMERGENCY PROCEDURES.............................................................................85
13.1.
Emergency Contact.................................................................................................85
13.2.
Emergency Identification of Investigational Products .............................................85
14.
REGULATORY CONSIDERATIONS...................................................................86
14.1.
Good Clinical Practice............................................................................................86
14.2.
Investigator Responsibilities ...................................................................................86
14.3.
Subject Information and Informed Consent.............................................................87
14.4.
Confidentiality........................................................................................................87
14.5.
Protocol Amendments.............................................................................................87
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................87
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................88
14.8.
Closure of the Study ...............................................................................................88
15.
DATA HANDLING AND RECORDKEEPING.....................................................89
15.1.
Data/Documents .....................................................................................................89
15.2.
Data Management...................................................................................................89
15.3.
Record Retention....................................................................................................89
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................91
16.1.
Study Monitoring and Source Data Verification......................................................91
16.2.
Audits and Inspections............................................................................................91
17.
PUBLICATIONS ...................................................................................................92
18.
REFERENCES.......................................................................................................93
19.
APPENDICES........................................................................................................98
Appendix A:
ECOG Performance Status Score.......................................................................98
Appendix B:
Recommendations for Management of Treatment-Induced Diarrhea..................99
Appendix C:
Treatment Modification and Toxicity Management for nab-Paclitaxel 
/Durvalumab arm..................................................................................................100
&(/*(1(35235,(7$5<,1)250$7,21
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.......87
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/Durvalum


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
17
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
LIST OF TABLES
Table 1:
Progression-Free Survival – Two-sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms..............................11
Table 2:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat 
Population).............................................................................................................21
Table 3:
Data for Control Arms using Taxanes from Phase II and III Studies Blinded ..........36
Table 4:
Table of Events.......................................................................................................39
Table 5:
Requirements for Collection Based on Archival Tumor Sample Type.....................46
Table 6:
Permanent Dose Reductions for Hematologic and Nonhematologic 
Toxicities and Dosing on the Study.........................................................................61
Table 7:
Disease Control Rate –Two-Sided 95% Confidence Interval of Hypothetical 
Disease Control Rate with a Sample Size of 80 Subjects in a Treatment Arm .........69
Table 8:
Progression-Free Survival – Two-Sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms..............................69
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Protocol ABI-007-NSCL-006
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ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
LIST OF FIGURES
Figure 1:
Anti-PD-L1 in Combination with Platinum-Based Doublets ...................................29
Figure 2:
Overall Study Design..............................................................................................37
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer
Lung cancer is the leading cause of cancer-related deaths among men and women worldwide, 
with 1.2 million new cases diagnosed each year. Non-small cell lung cancer (NSCLC) is the 
most common type of lung cancer, accounting for 80% of all new cases. There are an estimated 
1.1 million lives lost per year (approximately 500,000 in the United States [US] and European 
Union [EU] alone) due to NSCLC. Smoking is the causative factor for up to 85% of cases 
(http://www.lungcancercoalition.org/en/pages/about/awareness).
The majority of patients are not diagnosed until the tumor has progressed beyond the primary 
site. Despite step-wise advances in patient selection, targeted agents, and optimizing
chemotherapy regimens, patients with advanced NSCLC continue to have an unmet medical 
need (Schiller, 2013).
Platinum-containing chemotherapy regimens remain (eg, platinum-based agents with taxanes) 
the standard first-line treatment in the US and Japan. In the EU, a third-generation 
chemotherapeutic agent (docetaxel, gemcitabine, paclitaxel, or vinorelbine), most commonly 
gemcitabine or vinorelbine, plus a platinum drug is used for advanced NSCLC (NICE, 2011). 
For first-line therapy in patients with Stage IV NSCLC and good performance status, the 
American Society of Clinical Oncology (ASCO) clinical practice guideline recommends 
treatment with a platinum-based two-drug combination of cytotoxic drugs (Azzoli, 2009). For 
patients without disease progression, the option of maintenance monotherapy with pemetrexed or 
erlotinib could also be considered (Gerber, 2013; Schiller, 2013). A trend that is becoming more 
prevalent is personalized NSCLC treatment based on tumor histology (squamous versus
nonsquamous), on molecular characteristics of the tumor, and on the patient’s clinical status 
using agents targeting specific receptors, kinases and pathways (ie, epidermal growth factor 
receptor [EGFR], echinoderm microtubule-associated protein-like 4 [EML4] and anaplastic 
lymphoma kinase [ALK] fusion protein).
Single agent chemotherapy (pemetrexed, EGFR-inhibitors and taxanes) are standards of care for 
second-line treatment of patients with locally advanced or metastatic NSCLC after failure of 
prior platinum-based chemotherapy. Docetaxel has been widely evaluated in this setting, and is 
currently approved by the US Food and Drug Administration (FDA) and the European 
Medicines Agency (EMA) as a single agent for the treatment of patients with locally advanced or 
metastatic NSCLC after failure of prior chemotherapy  (the US label specifies prior platinum-
based chemotherapy). For patients with a good performance status at the time of disease 
progression following first-line chemotherapy, docetaxel, despite a low response rate, was
associated with a 10% to 20% prolongation of 1-year survival and an improved quality of life 
when compared with ifosfamide, vinorelbine, or best supportive care (BSC) alone (Hanna, 
2004). Erlotinib is indicated in the US and EU for the treatment of patients with locally advanced 
or metastatic NSCLC after failure of at least one prior chemotherapy regimen, although no 
survival benefit has been demonstrated in patients with EGFR-IHC negative tumors.  
Pemetrexed is indicated in the US and EU as a single agent for the treatment of patients with 
locally advanced or metastatic nonsquamous NSCLC after prior chemotherapy. However, the 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
approval and subsequent increased use of pemetrexed and erlotinib in the first-line setting poses 
an unmet need in the second-line setting, whereby new therapeutic options are needed.
Recently, nintedanib, a triple angiokinase inhibitor, was approved in the European Union (EU) in 
combination with docetaxel as second-line therapy for NSCLC. The results showed that 
compared to docetaxel alone, nintedanib plus docetaxel significantly extended the median OS 
from 10.3 to 12.6 months for patients with advanced adenocarcinoma, after first-line 
chemotherapy (p = 0.0359; hazard ratio [HR]: 0.83) (Reck, 2014a). In addition, ramucirumab 
was approved in the US in combination with docetaxel as second-line therapy. The Phase 3 
REVEL trial compared ramucirumab, a vascular endothelial growth factor (VEGFR)-2 
antagonist, plus docetaxel with placebo plus docetaxel in NSCLC patients who experienced 
disease progression after treatment with platinum-based chemotherapy for locally advanced or 
metastatic disease. Median OS was better in the ramucirumab group than in the placebo group 
(10.5 vs 9.1 months; HR, 0.857; p = .0235), as was median progression-free survival (PFS) (4.5 
vs 3.0 months; HR, 0.762; p < .0001) (Garon, 2014).
More recently, advances in immunotherapy have seen approvals of nivolumab (US and EU) and 
pembrolizumab (US) in the advanced NSCLC setting after prior chemotherapy. In this setting,
nivolumab has shown benefit in overall survival with 9.2 months (95% CI, 7.3 to13.3) versus 6.0 
months (95% CI, 5.1 to 7.3) with docetaxel in advanced squamous NSCLC (Checkmate 017 
study) (Brahmer, 2015), and 12.2 months (95% CI, 9.7 to 15.0) versus 9.4 months (95% CI, 8.1 
to 10.7) with docetaxel (HR 0.73; 95% CI, 0.59 to 0.89; p = 0.002) in nonsquamous disease
(Checkmate 057 study) (Borghaei, 2015). However, PFS benefit was modest (3.5 months with 
nivolumab versus 2.8 months with docetaxel (HR 0.62; 95% CI, 0.47 to 0.81; p <0.001) or did 
not favor nivolumab in these populations. Regarding its safety profile, nivolumab is most 
commonly associated with immune-related adverse reactions. Most of these including severe 
reactions resolved following initiation of appropriate medical therapy, or withdrawal of 
nivolumab. In the pooled dataset of two studies in squamous NSCLC, the most frequent adverse 
reactions were fatigue (33%), decreased appetite (15%), and nausea (12%). The majority of 
adverse reactions were mild to moderate (Grades 1 or 2) (Opdivo® Prescribing Information). In
comparison, the efficacy of pembrolizumab was investigated in a sub-group of a cohort of 280 
patients enrolled in a multicenter, open-label multi-cohort, activity-estimating study which 
showed an overall response rate (ORR) of 41% (95% CI, 29 to 54) in both squamous and 
nonsquamous subjects. Serious adverse reactions occurred in 38% of patients receiving 
pembrolizumab and the most frequent reported in at least 2% of patients were pleural effusion, 
pneumonia, dyspnea, pulmonary embolism, and pneumonitis (Keytruda® Prescribing 
Information).
Similarly and as will be described below, the PD-L1 inhibitor durvalumab has demonstrated 
encouraging clinical activity both as a monotherapy and in combination with other agents 
including standard chemotherapies in metastatic melanoma, NSCLC and other advanced solid 
tumors, with acceptable and manageable reported toxicities.
1.2.
nab-Paclitaxel in NSCLC
nab-Paclitaxel is approved in the first-line setting in combination with carboplatin for patients 
with NSCLC in the US, EU, Japan, Argentina, Australia, New Zealand and other countries.  The 
approval was based on the evaluation of Phase I and II data (Belani, 2008; Rizvi, 2008; Socinski, 
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
2010), as well as the pivotal Phase 3 study (CA031), (Socinski, 2012). The pivotal Phase 3 study 
was a multicenter, randomized, open-label study conducted in 1052 chemo-naïve subjects with 
Stage IIIB/IV NSCLC to compare nab-paclitaxel in combination with carboplatin to paclitaxel 
injection in combination with carboplatin as first-line treatment in patients with advanced 
NSCLC. nab-Paclitaxel was administered as an IV infusion over 30 minutes at a dose of 
100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel injection was administered as 
an IV infusion over 3 hours at a dose of 200 mg/m2, following premedication. In both treatment 
arms carboplatin at a dose of area under the curve (AUC) = 6 mg*min/mL was administered IV
on Day 1 of each 21-day cycle after completion of nab-paclitaxel/paclitaxel infusion. Treatment 
was administered until disease progression, development of an unacceptable toxicity or patient 
withdrawal. The primary efficacy outcome measure was overall response rate (ORR) as
determined by a central independent review committee using RECIST guidelines (Version 1.0).
In the intent-to-treat (all-randomized) population, the median age was 60 years, 75% were men, 
81% were white, 49% had carcinoma/adenocarcinoma, 43% had squamous cell lung cancer, 76% 
were ECOG performance status (PS) 1, 15% were ≥70 years of age and 73% were current or 
former smokers. Patients received a median of 6 cycles of treatment in both study arms. Patients 
in the nab-paclitaxel/carboplatin arm had a statistically significantly higher overall response rate 
compared to patients in the paclitaxel injection/carboplatin arm [(33% versus 25%;response rate 
ratio, 1.313; 95% CI, 1.082 to 1.593; p = 0.005), see Table 2].
Non-inferiority analysis of overall survival (OS) demonstrated that nab-paclitaxel/carboplatin
(nab-p/C) treatment is not inferior to paclitaxel/carboplatin (P/C) treatment. Overall survival in 
the nab-paclitaxel arm was 12.1 months versus 11.2 months in the control arm (p = 0.271; HR = 
0.922). There was an approximately 10% increase in PFS in the nab-p/C versus P/C arm and PFS 
in the nab-p/C arm was noninferior to PFS in the P/C arm (HRnab-p/C/P/C 95% CI upper bound, 
1.086).
Table 2:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat
Population)
Variable
Category/Statistic
nab-Paclitaxel/
carboplatin
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Paclitaxel/
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Response Rate 
Ratio
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p-value
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n (%)
170 (33%)
132 (25%)
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1.082, 1.593
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170 (33%)
131 (25%)
PA/PT: response rate of nab-paclitaxel/response rate of paclitaxel.
a 95% CI of response rate and 95.1% CI of response rate ratio.
* Indicates p-value < 0.049.
Note: p-value is based on a chi-square test.
Source: Data on File.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Adverse events (AEs) were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. The following common (≥ 10% incidence) AEs
were observed at a similar incidence in nab-paclitaxel/carboplatin and paclitaxel/carboplatin
arms: alopecia 56%, nausea 27%, fatigue 25%, decreased appetite 17%, asthenia 16%, 
constipation 16%, diarrhea 15%, vomiting 12%, dyspnea 12%, and rash 10% (incidence rates are 
for the nab-paclitaxel plus carboplatin treatment group). Toxicities, particularly neuropathy and 
Grade 3/4 neutropenia were less pronounced using nab-paclitaxel in the dose and schedule 
employed. Laboratory-detected abnormalities which occurred with a difference ≥5% for nab-
paclitaxel plus carboplatin versus paclitaxel injection plus carboplatin (Grades 1 to 4 [and Grade 
3/4]) were: anemia (98% vs 91% [28% vs 7%]), neutropenia (85% vs 83% [47% vs 58%]) and 
thrombocytopenia (68% vs 55% [18% vs 9%]).  
1.3.
Rationale for nab-Paclitaxel as Second/Third-line Treatment in
Subjects with Advanced NSCLC
Patients who fail first-line chemotherapy are eligible for second-line treatment with single agent 
docetaxel, pemetrexed or erlotinib. In patients with good performance (eg, ECOG PS 0 or 1) and 
general health status, further treatment with chemotherapy is an important consideration that has 
been shown to extend overall survival. Despite the availability of second-line therapy, the trend 
of increased use of pemetrexed, as well as erlotinib (in selected patients) in the first-line and 
maintenance settings, potentially limits the number of available second-line treatment options for 
many patients. Furthermore, the tolerability issues associated with the administration of 
docetaxel once every 3 weeks (q3w) has prompted active research in the past decade to evaluate 
whether weekly regimens of taxanes could be optimized to improve the toxicity profile. The 
availability of an effective second-line cytotoxic chemotherapy with an improved efficacy/safety
profile over current available options would be a valuable addition for both the patient and the 
treating physician. Paclitaxel has also demonstrated potential activity in second-line NSCLC in a 
few studies (Socinski, 1999; Juan, 2002; Socinski, 2002; Sculier, 2002; Buccheri, 2004; Ceresoli, 
2004; Yasuda, 2004). More recently, advances in immunotherapy have seen increased use of 
immune checkpoint inhibitors (eg, nivolumab, pembrolizumab) in the first and/or second-line 
setting for advanced NSCLC disease. 
nab-Paclitaxel exhibits 10-fold higher mean Cmax of free paclitaxel, delivers 33% higher drug 
concentration to tumors in preclinical xenograft models, and demonstrates enhanced transport 
across endothelial cell monolayers, when compared with paclitaxel (Desai, 2006; Gardner, 
2008). Distribution of nab-paclitaxel to peripheral tissues as demonstrated in a recent study was 
4-fold faster and 10-fold more extensive than of Cremophor EL-paclitaxel micelles, which 
results in a unique and distinct profile of paclitaxel in tissues (Li, 2015). The Cremophor EL-free 
medium enables nab-paclitaxel to be given over a shorter duration without the need for 
premedication to prevent solvent-related hypersensitivity reactions, thus also avoiding negative 
impact of steroids on paclitaxel induced apoptosis and decreased antitumoral activity of 
chemotherapeutic agents as reported in pre-clinical models glucocorticoids (Abraxane®
Prescribing Information; Zavodovskaya, 2015; Herr, 2003; Sui, 2006; Khan, 2013; Pang, 2006).
When administered with carboplatin in the first-line setting, weekly nab-paclitaxel has 
demonstrated a more favorable efficacy:safety profile compared to the every 3 weeks schedule.  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
This weekly schedule of nab-paclitaxel allows the opportunity for closer (ie, shorter interval)
monitoring of side effects and optimizing dose-intensity through timely adjustments.  
Finally, recently published data has demonstrated efficacy of nab-paclitaxel as monotherapy in 
the second line setting in advanced NSCLC with ORR ranging from 16.1% to 33% and a median 
PFS of up to 5 months (Chen, 2012; Saxena, 2012; Yuan, 2012).  
Rationale for dose and schedule
As previously noted, nab-paclitaxel 100 mg/m2 weekly (Days 1, 8 and 15) in combination with 
carboplatin (21 day cycle) is approved in the US, EU, Japan, Argentina, Australia, New Zealand 
and other countries for the treatment of locally advanced or metastatic NSCLC in the first-line 
setting.  However, there is limited data of monotherapy nab-paclitaxel in the second or third-line 
setting; hence, this study will assess the efficacy and tolerability of weekly nab-paclitaxel, when 
administered on Days 1 and 8 of each 21-day cycle.  The allowance of a one week rest period in 
this study (ie, no treatment on Day 15), takes into account research findings from other taxanes, 
whereby patients in the second-line setting are unlikely to tolerate the same dose-intensity 
compared to chemo-naïve patients (eg, sharper dose reduction in the second-line setting). 
Therefore, the proposed nab-paclitaxel schedule (2 weeks treatment, 1 week rest) could offer the 
option of maintaining consistent dose-intensity for NSCLC patients in this setting.
1.4.
Rationale for nab-Paclitaxel in Combination With Epigenetic 
Modifying Therapy of CC-486 as Second/Third-line Treatment in 
Subjects with Advanced NSCLC
CC-486 is an orally bioavailable formulation of the nucleoside analog 5-azacitidine (AZA).  
After its incorporation into a cell’s DNA during the S-phase of the cell cycle, CC-486 forms 
covalent adducts with DNA Methyltransferase 1 (DNMT1) and depletes this enzyme required for 
the maintenance of DNA methylation patterns, thereby altering the epigenetic status of the cell. 
Epigenetic changes are covalent modifications of chromatin (DNA and histone proteins) that 
mediate the stable transmission of a gene’s transcriptional status through cell division.  One of 
the first recognized epigenetic alterations in cancer was DNA methylation.  The addition of a 
methyl group to cytosine in the dinucleotide CpG is catalyzed by DNA methyltransferases 
(DNMTs) and is associated with transcriptional repression of genes with high density of CpGs 
(CpG islands) in the vicinity of their promoters (Jones, 2007).  Genomic methylation patterns are 
precisely regulated during normal embryonic development and differentiation and have been 
found to be altered in specific ways in cancer. Specifically, cancer cell genomes are typified by 
reduced methylation globally with focal areas of aberrant hypermethylation in the CpG islands of 
genes encoding known tumor suppressors such as PTEN and BRCA1 as well as genes encoding 
proteins required for apoptosis, including caspase 8, DAPK and Apaf-1.  DNA methylation-
based silencing can thus contribute to the establishment and maintenance of the transformed state 
and limit the effectiveness of anti-cancer therapies.  The recognition of the role of aberrant 
methylation in carcinogenesis and its reversibility has led to the development of DNMT 
inhibitors for cancer. Subcutaneous (SC) AZA was the first DNMT inhibitor to be approved in 
myelodysplastic syndromes (MDS) in 2004 (Kaminskas, 2005).
The notion that sequential treatment with an epigenetic modifying agent followed by a cytotoxic
agent can result in improved response to the latter is supported by numerous preclinical 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
experiments and now by early clinical results.  In breast cancer cell lines, restoring expression of 
the aberrantly methylated pro-apoptotic gene TMS1 with azacitidine can restore taxane 
sensitivity (Gordian, 2009).  In a model of platinum resistant ovarian cancer, azacitidine reversed 
resistance to carboplatin (Li, 2009).  This effect required pretreatment of the cells with 
noncytotoxic levels of azacitidine for 24 hours before the addition of carboplatin and was not 
observed with concurrent exposure to both agents.  More recently, Juergens and colleagues 
observed an unusually high ORR of approximately 20% in multiple-relapsed NSCLC patients 
treated with a variety of regimens after being treated with a combination of SC AZA and another 
epigenetic agent, entinostat, a histone deacetylase inhibitor (Juergens, 2011).  In one case, a 
patient who had previously progressed on a regimen of paclitaxel, carboplatin and bevacizumab 
responded to the same triplet after treatment with SC AZA and entinostat, suggesting that the 
epigenetic modifying agents had reversed acquired resistance to the cytotoxic/anti-angiogenic 
regimen.  In a Phase 1/2 study of SC AZA with nab-paclitaxel in subjects with advanced 
metastatic solid tumors and breast cancer (Dumlao, 2011), escalating doses of SC AZA (75 to
100 mg/m2) were administered on Days 1 through 5, followed by nab-paclitaxel (100 mg/m2) 
intravenous (IV) on Days 8, 15, and 22 of a 28-day cycle.  Of 16 subjects treated at the time of 
publication, clinical activity has included 3 complete responses (CR, 1 Diffuse Large B-cell 
Lymphoma [DLBCL], 2 ovarian), 4 partial responses (PR) in ovarian and endometrial cancer 
and 4 stable diseases (SD, 2 lung, 1 pancreatic, and 1 sarcoma).  
CC-486 entered clinical testing in 2006 in subjects with MDS, chronic myelomonocytic 
leukemia [CMML], and acute myeloid leukemia [AML], with daily extended dosing schedules 
of 14 and 21 out of 28 days in a non-crossover fashion.  Daily doses of 300 mg CC-486 have 
proven to be tolerated on both the 14 and 21 out of 28-day schedules with myelosuppression, 
gastrointestinal symptoms, and fatigue being the most common toxicities (Garcia-Manero, 
2011).  Subjects treated with CC-486 for 14 or 21 days had DNA hypomethylation that persisted 
through the end of cycle.  This contrasts with the lack of persistent hypomethylation at the end of 
cycle when subjects were treated with SC AZA for 7 out of 28 days. 
 
 
 
  
 
 
 
 
 
 
 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
 
  
 
 
 
 
 
 
 
This Phase 2 study will test the hypothesis that epigenetic modifying therapy with CC-486 can 
improve the anti-tumor activity of nab-paclitaxel in second/third-line NSCLC patients (see 
Section 4.2 for study rationale). Although docetaxel has been assessed in other randomized 
studies as a chemotherapy backbone, the considerable neutropenia-related toxicity could 
potentially pose safety concerns if combined with CC-486, and the steroid premedication could 
confound the epigenetic impact of CC-486.  In addition, the q3w dosing schedule of docetaxel 
restricts dose adjustment options, thus potentially yielding lower chemotherapy dose-intensity.
Please refer to the Investigator’s Brochures (IBs) of CC-486 and nab-paclitaxel (ABI-007) for 
detailed information concerning the available pharmacology, toxicology, drug metabolism, 
clinical studies, and adverse event profile of the IPs.
 
 
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
26
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
1.5.
Rationale for nab-Paclitaxel in Combination With Immunotherapy 
of Durvalumab as Second/Third-line Treatment in Subjects with 
Advanced NSCLC
Durvalumab 
Durvalumab is a human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa 
subclass that inhibits binding of PD-L1 to PD-1 and CD80 and is being developed by 
AstraZeneca/MedImmune for use in the treatment of cancer.  (MedImmune is a wholly owned 
subsidiary of AstraZeneca; AstraZeneca/MedImmune will be referred to as AstraZeneca 
throughout this document.)  As durvalumab is an engineered mAb, it does not induce antibody-
dependent cellular cytotoxicity or complement-dependent cytotoxicity.  The proposed 
mechanism of action for durvalumab is interference of the interaction of PD-L1 with PD-1 and 
CD80.
To date durvalumab has been given to more than 1900 patients as part of ongoing studies either 
as monotherapy or in combination with other anti-cancer agents.  Refer to the current 
durvalumab Investigator’s Brochure for a complete summary of non-clinical and clinical 
information including safety, efficacy and pharmacokinetics.  
A Phase 2 trial of durvalumab is currently ongoing to assess efficacy and safety of the immune 
checkpoint inhibitor (dose of 10 mg/kg once every two weeks [q2w]) in patients with locally 
advanced or metastatic NSCLC in the third-line setting (Rizvi, 2014) (ATLANTIC trial, 
NCT02087423). 
 
 
 
Preliminary data of an open-label Phase 1b study of durvalumab 20 mg/kg every 4 weeks plus 
tremelimumab 1 mg/kg in immunonaive patients with advanced or metastatic squamous or non-
squamous NSCLC showed a manageable tolerability profile, with antitumor activity irrespective 
of PD-L1 status (ORR 22%, 95% CI 9-44) (Antonia, 2016).  
 
 
 
 
 
 
 
 
 
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
27
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
nab-Paclitaxel in combination with immune checkpoint inhibitors
Tumor lysis as a consequence of chemotherapy treatment leads to release of tumor antigens, 
which in turn are recognized by the immune system, thus priming the immune system for 
checkpoint inhibitor activity (Bracci, 2014; Chen, 2013; Mellman, 2011). Accumulating 
evidence suggests that immune activation plays an important role in chemotherapy efficacy
(Zitvogel, 2013). In addition to increasing tumor antigenicity, chemotherapy also reduces tumor 
burden and acts directly on immune cell populations, activating dendritic cells, depleting 
immunosuppressive regulatory T cells at low doses, depleting myeloid-derived suppressor cells, 
and increasing tumor-infiltrating lymphocytes (Tanaka, 2009; Banissi, 2009; Kodumudi, 2010; 
Dieci, 2014). Taxanes have been shown to facilitate dendritic cell maturation and cytokine 
secretion (Chen, 2013a). In patients with lung cancer, paclitaxel was associated with generation
of pro-inflammatory markers, including interleukin 2 and interferon gamma, and the expression 
of T cell activation markers (Zhang, 2008). Taxanes have been demonstrated to modulate the 
immune system by impairing regulatory T cells, which are drivers of peripheral tolerance, but 
not effector T cells, which are drivers of tumor-cell killing (Tanaka, 2009). Taxanes are also 
known to act on myeloid cells such as myeloid-derived suppressor cells and alternatively 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
28
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
differentiated (M2) macrophages to decrease their immunosuppressive functions (Kodumudi, 
2010).
The data above suggest a potential for synergistic activity of cytotoxic therapy, such as taxanes, 
with checkpoint inhibitors, including those that target PD-1 or PD-L1.  nab-Paclitaxel has 
demonstrated cytotoxic activity in non-small cell lung cancer (overall response rate = 33% vs 
25% with paclitaxel in a Phase III trial) (Socinski, 2012) and, as stated above, does not require 
steroid pretreatment, which may make it a logical choice for combination with immune 
checkpoint inhibitor.
Therefore, this Phase 2 study will further assess the potential synergistic activity of nab-
paclitaxel, a cytotoxic agent, in combination with the anti-PD-L1 checkpoint inhibitor 
durvalumab in second/third-line treatment for advanced NSCLC, from an efficacy and safety 
standpoint.  The current study will allow patients who progress on prior checkpoint inhibitor 
therapy (eg, as their first-line or second-line therapy) as it is hypothesized that the companion 
chemotherapy of nab-paclitaxel may re-sensitize the disease to allow patient to respond to 
checkpoint inhibitors.
!
nab-Paclitaxel in combination with anti-PD-L1
More recently, preliminary results of an ongoing Phase 1b trial in first line metastatic NSCLC of
another immune checkpoint anti-PD-L1 inhibitor, atezolizumab, showed high response rates in 
combination with the following platinum-based doublets: 60 % (95% CI: 15-95) in the 
carboplatin/paclitaxel cohort (Arm C; n = 5), 75% (95% CI: 43-95) in the 
carboplatin/pemetrexed arm (Arm D; n=14), and 62 % (95% CI: 32-86) with four patients 
experiencing complete response when atezolizumab was combined with carboplatin/nab-
paclitaxel regimen (Arm E; n=13) (Liu, 2015). The most frequent AEs included nausea (Arms C 
and D, 50%; Arm E, 73%), fatigue (Arm C, 38%; Arm D, 36%; Arm E, 73%) and constipation 
(Arm C, 25%; Arm D, 71%; Arm E, 27%). The most common MPDL3280A-related Grades 3 to 
4 AEs included anemia (Arms D and E, 7%), neutropenia (Arm C, 13%; Arm D, 7%) and 
thrombocytopenia (Arms D and E, 7%). No pneumonitis was seen. One MPDL3280A-related 
Grade 5 AE due to candidemia after prolonged neutropenia was seen in Arm D. Thirty patients
were efficacy evaluable (Arm C, 5; Arm D, 12; Arm E, 13). Overall, treatment with 
atezolizumab plus chemotherapy (including maintenance therapy) was well tolerated, without 
apparent exacerbation of chemotherapy-associated adverse events.
 
 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
29
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Figure 1:
Anti-PD-L1 in Combination with Platinum-Based Doublets
Liu et al. ASCO- June 2015. Abstract 8030
!
nab-Paclitaxel in combination with anti-PD-1
An ongoing Celgene-sponsored Phase 1 trial (NCT02309177) in solid tumors is assessing the 
safety and efficacy of the anti-PD-1 agent nivolumab in combination with nab-paclitaxel and
carboplatin in a cohort of subjects with advanced NSCLC patients in the first-line setting (nab-
paclitaxel 100 mg/m2 on Days 1, 8 and 15 and carboplatin AUC 6 on Day 1 of each 21-day cycle 
(Cycles 1 to 4 only); nivolumab 5 mg/kg on Day 15 of each 21-day cycle starting in Cycle 1). 
Preliminary results show that amongst the 9 subjects having received study treatment including 
nivolumab, 6 had partial responses and 3 stable disease. No dose limiting toxicities were 
observed. Most common AEs were low grade vomiting, diarrhea, alopecia, peripheral 
neuropathy and neutropenia (data on file). These results are consistent with another Phase 1 trial 
comparing anti-PD-1 antibody nivolumab (10 mg/kg IV q3w) combined with three different 
platinum-doublet regimens in 52 patients with chemotherapy-naïve advanced NSCLC, with a
reported ORR of 33% with gemcitabine/cisplatin, 47% with pemetrexed/cisplatin, as well as with 
paclitaxel/carboplatin, while stable disease was reported in 58%, 47%, and 27% of subjects, 
respectively (Checkmate 012; NCT01454102); (Antonia, 2014). Grades 3 to 4 treatment-related 
adverse events were reported in 45% of patients (25% to 73% across arms), including 
pneumonitis (4 patients, 7%; managed by protocol algorithm), and fatigue and acute renal failure 
(3 patients, 5% each).
Rationale for fixed dose and schedule 
 
 
 
 
 
 
 
 
 
  Similarly, a population PK model 
was developed for tremelimumab using data from Phase 1 through Phase 3 (N=654; doses= 0.01 
( 35235,(7$5<,1)250$7,21
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
30
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
to 15 mg/kg q4w or once every 90 days (Q90D); metastatic melanoma) (Wang, 2014). A 
population PK model indicated minor impact of body WT on the PK of tremelimumab 
(coefficient of ≤ 0.5). The WT-based (1 mg/kg q4w) and fixed dosing (75 mg/kg q4w; based on 
median body WT of ~75 kg) regimens were compared using predicted PK concentrations (5th, 
median and 95th percentiles) using a population PK model in a simulated population of 1000 
patients with body WT distribution of 40 to 120 kg. Similar to durvalumab, simulations indicated 
that both body WT-based and fixed dosing regimens of tremelimumab yield similar median 
steady state PK concentrations with slightly less between-subject variability with fixed dosing 
regimen.
Similar findings have been reported by others (Ng, 2006; Wang, 2009; Zhang, 2012; Narwal,
2013). Wang and colleagues investigated 12 monoclonal antibodies and found that fixed and 
body size-based dosing perform similarly, with fixed dosing being better for 7 of 12 antibodies 
(Wang, 2009). In addition, they investigated 18 therapeutic proteins and peptides and showed 
that fixed dosing performed better for 12 of 18 in terms of reducing the between-subject 
variability in PK/PD parameters (Zhang, 2012). 
A fixed dosing approach is preferred by the prescribing community due to ease of use and 
reduced dosing errors. Given the expectation of similar PK exposure and variability, it is 
considered feasible to switch to fixed dosing regimens.
Sequential administration of chemotherapy and checkpoint inhibitor will allow for limitation of 
potential interactions and better management of toxicities.
Please refer to the Investigator’s Brochures (IBs) of durvalumab and nab-paclitaxel (ABI-007) 
for detailed information concerning the available pharmacology, toxicology, drug metabolism, 
clinical studies, and adverse event profile of the investigational products (IPs).
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
31
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
2.
STUDY OBJECTIVES
2.1.
Primary Objective 
The primary objective of the study is:
!
To estimate the efficacy of nab-paclitaxel administered intravenously (IV) on Days 8 
and 15 with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 
14 every 21 days, or nab-paclitaxel administered intravenously (IV) on Days 1 and 8
with immunotherapy of durvalumab administered IV on Day 15 every 21 days, and 
nab-paclitaxel monotherapy administered IV on Days 1 and 8 every 21 days as 
second/third-line treatment for advanced NSCLC.
2.2.
Secondary Objective
The secondary objective of the study is:
!
To estimate the relative efficacy of each of the combination therapy arms to the 
monotherapy arm.
!
To evaluate the safety and tolerability of nab-paclitaxel administered IV on Days 8 
and 15 with epigenetic modifying therapy of CC-486 QD on Days 1 to 14 every 21 
days, or nab-paclitaxel administered intravenously (IV) on Days 1 and 8 with 
immunotherapy of durvalumab administered IV on Day 15 every 21 days, and nab-
paclitaxel monotherapy administered IV on Days 1 and 8 every 21 days as 
second/third-line treatment for advanced NSCLC.
2.3.
Exploratory Objectives
The exploratory objectives of the study are:
!
To assess healthcare resource utilization for the treatment arms.
!
To assess the quality of life (QoL) for the treatment arms.
!
To determine baseline tumor characteristics which predict response to nab-paclitaxel 
as a single agent and with epigenetic modifying therapy of CC-486 or immunotherapy 
of durvalumab. 
!
To evaluate genomic correlates of response to nab-paclitaxel as a single agent and 
with epigenetic modifying therapy of CC-486 or immunotherapy of durvalumab.
!
To evaluate anti-tumor activity of nab-paclitaxel/durvalumab combination therapy 
using investigator assessment according to immune related response criteria updated 
with RECIST 1.1 (irRECIST), and its association with PD-L1 expression.
&(/*(1(35235,(7$5<,1)250$7,21
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
32
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
3.
STUDY ENDPOINTS
Study efficacy endpoints will be assessed by the Investigator using RECIST 1.1 guidelines.
3.1.
Primary Endpoint
The primary endpoint is:
!
Progression free survival.
3.2.
Secondary Endpoints
The secondary endpoints are: 
3.2.1.
Efficacy
!
Disease control rate.
!
Overall response rate.
!
Overall survival.
3.2.2.
Safety
!
The type, frequency, and severity of AEs and SAEs graded using National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, 
Version 4.0). 
!
Discontinuation rate.
!
The median dose intensity.
!
The incidence of dose reduction.
3.3.
Exploratory Endpoints
!
Healthcare resource utilization during the study via patient feedback.
!
Changes in the Lung Cancer Symptom Scale (LCSS), European Organisation for 
Research and Treatment of Cancer (EORTC) QLQ C30, and EuroQoL 5D-5L (EQ-
5D-5L).
!
The correlation between pretreatment tumor characteristics and response to the study 
treatment determined using next-generation sequencing methods, 
immunohistochemistry, or other analysis methods.
!
Analysis of PFS and DCR and their association with PD-L1 expression using 
Investigator’s assessments according to irRECIST. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
33
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is a Phase 2, open-label, multicenter study to assess safety and efficacy of:
!
nab-paclitaxel in combination with epigenetic modifying therapy of CC-486,
!
nab-paclitaxel in combination with immunotherapy of durvalumab, 
!
and nab-paclitaxel monotherapy 
as second/third-line treatment in subjects with advanced NSCLC who have received no more 
than one prior chemotherapy regimen. Approximately 240 subjects with advanced NSCLC will 
be assigned 1:1:1 into one of the following treatment arms: nab-paclitaxel/CC-486, nab-
paclitaxel/durvalumab combination therapy or nab-paclitaxel monotherapy prior to receiving the 
first dose of investigational product (IP). Randomization (details in Section 10.1), when 
conducted, will be centralized and stratified by ECOG performance status (0 versus 1, see 
Appendix A), gender (males versus females), and smoker (yes versus no).
The study will consist of up to a 28-day Screening Period, a Treatment Period and a Follow-up 
Period.  
4.1.1.
Screening Period 
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of IP.
4.1.2.
Treatment Period 
The Treatment Period begins with the first dose of IP as described in Section 8.  Subjects will 
receive one of the following treatments based on the randomization/treatment assignment:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 
durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15 of each 21-
day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle.
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the Investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, withdrawal of 
consent, or termination of the study by the Sponsor.
During the study, subjects will have computed tomography (CT) scans every 42 days (-3/+7 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
34
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
or termination of the study by the Sponsor. Tumor evaluations will be assessed by the 
investigative sites and response will be determined according to RECIST 1.1 guidelines, and 
immune-related RECIST criteria (irRECIST) when applicable. All scheduled laboratory samples 
will be sent to a central laboratory for analysis. Local hematology and chemistry tests may be 
performed as required for subject management/treatment decisions. Local laboratory values that 
are considered abnormal and clinically significant will be recorded as an AE/SAE and also 
recorded on the laboratory eCRF (see Section 11.3).
4.1.2.1.
Treatment Beyond Progression for Subjects in the nab-Paclitaxel/Durvalumab 
Arm
Subjects in the nab-paclitaxel/durvalumab arm may be permitted to continue treatment beyond 
initial RECIST 1.1 defined progressive disease as long as they meet the following criteria:
!
Continue to meet all other study protocol eligibility criteria
!
Investigator assessed clinical benefit and absence of rapid disease progression or 
clinical deterioration
!
Stable performance status
!
Tolerance to IP
!
Treatment beyond progression will not delay an imminent intervention to prevent
serious complications of disease progression (eg, brain metastases)
Subjects will be re-consented with an informed consent document describing any reasonably 
foreseeable risks or discomforts and other alternative treatment options.
Response assessment should continue every 42 days (-3/+7 days) as per Table of Events
(Table 4). The assessment of clinical benefit should be balanced by clinical judgment as to 
whether the subject is clinically deteriorating and unlikely to receive any benefit from continued 
treatment with nab-paclitaxel/durvalumab. If the Investigator feels that the subject continues to 
achieve clinical benefit by continuing treatment and the subject consents, the subject may remain 
on the trial and will continue to receive monitoring according to the schedule in the Table of 
Events. The decision to continue treatment should be discussed with the Sponsor’s Medical 
Monitor and documented in the study source documents.
Study therapy should be discontinued if further progression is documented by irRECIST. 
4.1.3.
End-of-Treatment Visit
The End-of-Treatment Visit is defined as the visit when decision for treatment discontinuation is 
made. 
4.1.4.
Follow-up Period
All subjects who discontinue from treatment for reasons other than withdrawal of consent, lost to 
follow-up, death, or termination of the study by the Sponsor will enter the Follow-up Period. It 
will consist of a visit 28 days after last dose of IP or End-of-Treatment Visit, whichever is later,
followed by phone follow-up for survival approximately every 90 days (+/- 14 days) for at least
12 months after the last subject is randomized or 120 PFS events have been observed, whichever 
b 
t bey
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
35
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
comes later, between the nab-paclitaxel/CC-486 combination and nab-paclitaxel monotherapy 
arms. Subjects in the nab-paclitaxel/durvalumab arm will also attend a follow-up visit 90 days 
after the last dose of IP, and will be followed for survival in a similar manner for at least 12 
months after the last subject is assigned to this arm. Those subjects entering the Follow-up 
Period without documented progression will continue to have CT scans in accordance with local 
standard of care (or approximately every 90 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death, or termination of the study by the Sponsor. All 
post-treatment anticancer therapies will be recorded during the Follow-up Period.  
4.2.
Study Design Rationale
This is an open-label study designed to estimate the effects of adding CC-486 or durvalumab to 
nab-paclitaxel and nab-paclitaxel monotherapy in second/third-line NSCLC. A placebo-
controlled study would not be feasible for this population as blinding would be difficult and 
would need a double dummy design.  
A key objective in this study is to determine the chemo-priming effect of CC-486 and to estimate 
the effect of the combination of nab-paclitaxel with PD-L1 checkpoint inhibitor. Second/third-
line NSCLC enables a unique setting to evaluate epigenetics: 
a) It is currently unknown whether patients in second or later lines of treatment have 
optimal immune function/reserve which is critical for safety and activation of immune 
cells that target cancer cells,
b) Due to the overlapping (and dose-limiting) toxicities of doublet/triplet chemotherapy 
regimens in the first-line setting, it would be very challenging to combine epigenetic 
therapy at a dose level to elicit clinically meaningful benefit.
Although docetaxel has been assessed in other randomized studies as a chemotherapy backbone
as shown in Table 3, the considerable neutropenia-related toxicity could potentially pose safety 
concerns if combined with CC-486, and the steroid premedication could confound the epigenetic 
impact of CC-486.  In addition, the q3w dosing schedule of docetaxel restricts dose adjustment 
options, thus potentially yielding lower chemotherapy dose-intensity. As mentioned above, nab-
paclitaxel has shown benefit for both squamous and nonsquamous histologies. Furthermore, 
recent data with immune checkpoint inhibitors (eg, nivolumab) have shown greater efficacy in 
subjects with squamous histology versus nonsquamous histology with manageable toxicities. 
Hence it will be important in the current study to assess the efficacy and safety of nab-paclitaxel 
either as monotherapy or in combination treatment in subjects with squamous and nonsquamous 
NSCLC histologies.
For patients with NSCLC whose disease progressed after initial chemotherapy, the goal of 
therapy is to delay further progression for as long as possible; hence, the use of PFS as the 
primary endpoint for efficacy evaluation.  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
36
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Table 3:
Data for Control Arms using Taxanes from Phase II and III Studies Blinded
Study compound
(year)
Doce
(Shepherd, 
2000)
Doce
(Hanna, 
2004)
nab-Pac
(Chen  
2012, 
Saxena, 
2012, 
Yuan 
2012)
Doce
(Reck, 
2014a)
LUME-1
Doce
(Garon, 
2014)
Doce
(Brahmer, 
2015)
Checkmate 
017 
Doce
(Borghaei, 
2015)
Checkmate 
057
Doce 
(Vansteenkiste, 
2015)
POPLAR
Phase
III
III
II
III
III
III
III
II
N
55 + 48
288
16 (x2) -  
33
272
625
137
290
143
Efficacy
ORR (%)
7.1
8.8
18 - 33
3.3
14
9
12
15
SD rate (or DCR)
(%)
42.7
46.4
31  -  42
37.9
53
34
33
n/a
PFS (TTP)
(median, in 
months)
na
2.9
2.1 – 5.0
2.7
3.0
2.8
4.2
3.0
OS (median, in 
months)
7.0
7.9
n/a
9.1
9.1
6.0
9.4
9.7
Toxicity
Neutropenia (%)
Neutrophils 
decreased (%)
67.3
40.2
n/a
12.1
29.9
39
33
31
n/a
Febrile 
neutropenia
1.8
12.7
n/a
4.7
10
11
10
n/a
Thrombocytopenia 
(%)
0
0.4
3
NR
1
n/a
n/a
n/a
Anemia (%)
5.5
4.3
3
3.5
6
22
20
n/a
Peripheral 
Neuropathy (%)
1.8
1.1
3
NR
2
12
n/a
n/a
Fatigue / Asthenia 
(%)
18.2
5.4
3
5.1
10*
46.5
46.6
n/a
DCR = disease control rate; Doce = docetaxel; nab-Pac = nab-paclitaxel; N = number of subjects randomized; n/a = not 
available; ORR = overall response rate; OS = overall survival; PFS = progression free survival; SD = standard deviation; TTP =
time to progression; *Grade ≥ 3
Furthermore, maintaining quality of life during this period, especially in reducing/managing 
toxicity is also an important consideration.  Therefore, the proposed study is designed to 
optimize the evaluation of efficacy with a tolerable dose/schedule of chemotherapy, and its 
combination with an epigenetic modifying therapy or with an immune checkpoint inhibitor.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
37
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Figure 2:
Overall Study Design
IP = investigational product; IV = intravenous; OS = overall survival; PFS = progression-free survival; QD = once daily.
nab-paclitaxel 100 mg/m2 IV 
infusion over 30 minutes on 
Days 1 and 8 of each 21-day 
cycle until disease progression
(n = 80)
o
nab-paclitaxel 100 mg/m2 IV 
infusion over 30 minutes on Days 
1 and 8 of each 21-day cycle 
o
durvalumab 1125 mg IV over 
approximately 1 hour on Day15 
of each 21-day cycle
until disease progression
(n = 80)
Follow-up Period: 28-day Follow-up Visit (after last dose of IP or End-of-Treatment Visit, whichever is later)
Monotherapy or CC-486 combination arms: followed for OS by phone approximately every 90 days for at least 12 months after last subject is randomized 
in either the monotherapy arm or the CC-486 combination arm or 120 PFS events have been observed, whichever is later
nab-paclitaxel/durvalumab arm: 90-Day Follow-up Visit and  consequent follow-up for OS by phone approximately every 90 days for at least 12 months 
after last subject is allocated to this arm
o
nab-paclitaxel 100 mg/m2  IV 
infusion over 30 minutes on Days 
8 and 15 of each 21-day cycle
o
CC-486 200 mg orally QD
     Days 1 to 14 of each 21-day
cycle
until disease progression
(n = 80)
Screening for Eligibility (up to 28 days)
(n=240)
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
38
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
4.3.
Study Duration 
Recruitment is expected to take approximately 28 months, and the final analysis of PFS between 
the nab-paclitaxel/CC-486 combination and nab-paclitaxel monotherapy arms will be performed 
when approximately 120 PFS events have occurred, estimated as approximately 25 months from 
first subject randomized. The final analysis for the nab-paclitaxel/durvalumab arm will be 
conducted when approximately 50 events have occurred in this arm. The total length of this 
Phase 2 study with follow-up is estimated to last approximately 40 months.
4.4.
End of Trial
The End of Trial is defined as either the:
!
date of the last visit of the last subject to complete the post-treatment follow-up, or 
!
date of receipt of the last data point from the last subject that is required for primary, 
secondary and/or exploratory analysis, as prespecified in the protocol, whichever is 
the later date.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
5.
TABLE OF EVENTS
Table 4:
Table of Events
Screening/ 
Baseline
Treatment Period
Every 21-day Cycle
Follow-Up Period
Assessment
Day -28 to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu
-ation Visit
28-day Follow-up 
Visit (after last 
dose of IP)
90-day Follow-up 
Visit for subjects in 
the nab-paclitaxel/ 
durvalumab arm
(after last dose of IP)
Survival Follow-upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
Informed Consent
X
-
-
-
-
-
-
-
-
Medical History (including Tobacco 
Exposure History), Prior Medication 
and Procedures
X
-
-
-
-
-
-
-
-
Serum β-hCG b
X
-
-
-
-
-
-
-
-
Urine Pregnancy Testb
-
X
-
-
-
X
X
(nab-paclitaxel/ 
durvalumab arm)
X
(nab-paclitaxel/ 
durvalumab arm)
-
Reminder to Avoid Pregnancyb
X
-
-
-
X
X
X
-
Complete Chest CT Scan and Any 
Other Studies Required for Tumor 
Imagingc
X
-
-
-
X
Xc
-
-
X
Weight and Heightd
X
X
X
X
-
-
-
-
-
ECOG Status
X
X
-
-
-
X
X
X
-
Concomitant Medication/Procedures
-
X
X
X
-
X
X
X
X
Peripheral Neuropathy Assessmente
X
X
-
-
-
X
X
-
-
Healthcare Resource Utilization 
Questionnaire
-
X
-
-
-
X
X
-
-
LCSS, EORTC QLQ C30 and EQ-
5D-5L
-
X
-
-
-
X
X
-
-
Hematologyf,g
X
X
X
X
-
X
X
Xk
-
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
40
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Table 4:
Table of Events (Continued)
Screening/ 
Baseline
Treatment Period
Every 21-day Cycle
Follow-Up Period
Assessment
Day -28 to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu
-ation Visit
28-day Follow-up 
Visit (after last 
dose of IP)
90-day Follow-up 
Visit for subjects in 
the nab-paclitaxel/ 
durvalumab arm 
(after last dose of IP)
Survival Follow-upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
Serum Chemistryf,h
X
X
-
-
-
X
X
Xk
-
Archived Tumor Tissue Sample for 
Biomarker (biopsy, surgical 
specimen, or other diagnostic tumor 
sample)
-
X
(C1D1 
only)
-
-
-
-
-
-
-
Plasma for Biomarker Analyses
-
X
(C1D1 only 
predose)
-
-
-
-
-
-
-
Blood for Pharmacogenomic 
Analyses
-
X
(C1D1 only 
predose)
-
-
-
-
-
-
-
Adverse Event Evaluation in the 
Monotherapy or nab-Paclitaxel/CC-
486 Combination Arm
After signing ICF and until 28 days after the last dose of IP
-
-
Adverse Event Evaluation in the nab-
Paclitaxel/Durvalumab combination
Arm
After signing ICF and until 90 days after the last dose of IP
X
-
nab-PaclitaxelMonotherapy Arm and   
nab-Paclitaxel/Durvalumab
Combination Arm
nab-Paclitaxel Administration/
Accountabilityi
-
X
X
-
-
-
-
-
nab-Paclitaxel/CC-486 Combination 
Arm
nab-Paclitaxel Administration/
Accountabilityi
-
-
X
X
-
-
-
-
-
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
41
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Table 4:
Table of Events (Continued)
Screening/ 
Baseline
Treatment Period
Every 21-day Cycle
Follow-Up Period
Assessment
Day -28 to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu
-ation Visit
28-day Follow-up 
Visit (after last 
dose of IP)
90-day Follow-up 
Visit for subjects in 
the nab-paclitaxel/ 
durvalumab arm 
(after last dose of IP)
Survival Follow-upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
nab-Paclitaxel/CC-486 Combination 
arm
CC-486 Administration/
Accountabilityi
-
X
-
-
-
-
-
nab-Paclitaxel/Durvalumab
Combination Arm
Durvalumab Administration/
Accountabilityi
-
-
-
X
-
-
-
-
-
Survival Phone Call
-
-
-
-
-
-
-
-
Xa
Physical Examinationj
X
X
-
-
-
X
-
-
-
Vital Signsj
X
X
X
X
-
X
-
-
-
Electrocardiogram (ECG)
X
Will be done as per standard of care during the Treatment Period and as clinically indicated; however, results will not be routinely 
collected in the eCRFs. If CT/bone scans show lesions pertinent for RECIST 1.1 or irRECIST criteria evaluation, data will be 
collected on the pertinent tumor evaluation eCRFs. If ECGs are abnormal and clinically significant, the data will be recorded on the 
AE/SAE eCRF.
Bone Scan (X-rays if needed)
If clinically 
indicated
CT Scan of the Head or Brain 
Magnetic Resonance Imaging (MRI)
If clinically 
indicated 
(mandatory if 
symptomatic)
AE = adverse event; β-HCG = beta human chorionic gonadotropin; C1D1 = Cycle 1 Day 1; CT = computed tomography; ECOG = Eastern Cooperative Oncology Group; eCRF =
electronic Case Report Form; EORTC QLQ C30 = European Organisation for Research and Treatment of Cancer QLQ C30; EQ-5D-5L = EuroQol 5D-5L; ICF = informed 
consent form; IP = investigational product; irRECIST = immune-related Response Evaluation Criteria in Solid Tumors; IV = intravenous; LCSS = Lung Cancer Symptom Scale;
QD = once daily; RECIST = Response Evaluation Criteria in Solid Tumors; SAE = serious adverse event.
a Every 90 (+/-14) days (from 28-day Follow-up Visit ) for at least 12 months after the last subject is randomized in either the monotherapy or the CC-486 combination arms or 
120 PFS events have been observed whichever comes later. Subjects in the nab-paclitaxel/durvalumab arm will be followed for survival in a similar manner for at least 12 
months after the last subject is assigned to this arm.
b All males and all women of child-bearing potential must be reminded to avoid pregnancy prior to administration of IP before beginning each new cycle, at the End-of-Treatment 
Visit and at the Follow-up Visits. A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a serum β-hCG pregnancy test 
must be performed to assess eligibility at Screening/Baseline. Note: the screening serum pregnancy test can be used as the Cycle 1 Day 1 test prior to study therapy if it is 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
42
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
performed within the 72-hour timeframe.  A urine pregnancy test must be performed prior to administration of IP before beginning each new cycle and at the End-of-Treatment 
Visit for all subjects, and at the Follow-up Visits for subjects in the nab-paclitaxel/durvalumab arm.
c All subjects must have a radiographically documented measurable tumor(s) by RECIST 1.1 criteria: Complete chest CT scan (including base of neck and adrenal gland) will be 
performed at Screening, every 42 days (-3/+7 days) (starting from Cycle 1 Day 1) until disease progression, withdrawal of consent, lost to follow-up, death, or termination of the 
study by the Sponsor. The results of a complete chest CT scan (including base of neck and adrenal gland) performed per standard of care may be accepted and not repeated 
during Screening provided it was performed within 28 days of the first dose of IP (Cycle 1 Day 1). The methods of assessment chosen at baseline to follow tumors are to remain 
consistent throughout study duration. Those subjects entering the Follow-up Period without documented progression will continue to have CT scans in accordance with local 
standard of care (or approximately every 90 days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, or termination of the study by the 
Sponsor.  If the CT scan was performed within 2 weeks of the End-of-Treatment Visit, this End-of-Treatment Visit CT scan will not need to be repeated. Subjects in the nab-
paclitaxel/durvalumab arm who continue beyond disease progression per RECIST 1.1 will continue to have CT scans every 42 days (-3/+7) until progression per immune-related 
RECIST criteria (irRECIST) version 1.1 (Nishino, 2013).
d Height will only be obtained at Screening Visit. Weight will be obtained at Screening and every visit during the Treatment Period before administration of IP.
e The occurrence of peripheral neuropathy will be reported by the Investigator per protocol as an AE or SAE.
f All scheduled laboratory samples will be sent to a central laboratory for analysis. Local hematology and chemistry tests may be performed as required for subject 
management/treatment decisions. Local laboratory values that are considered abnormal and clinically significant will be recorded as an AE/SAE and also recorded on the 
laboratory eCRF (see Section 11.3).
g Hematology panel: hemoglobin, hematocrit, red blood cell count and morphology, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin 
concentration, white blood cell count with absolute and differential and percent (neutrophils, lymphocytes, monocytes, eosinophils, basophils, bands), platelet count, 
reticulocytes, erythrocyte sedimentation rate, international normalized ratio, prothrombin time, partial thromboplastin time, and fibrinogen. Additional laboratory samples for 
safety may be collected as clinically indicated.
h Serum chemistry panel: sodium, potassium, bicarbonate, calcium, magnesium, phosphorus, blood urea nitrogen, serum creatinine and clearance, uric acid, glucose, lactic
dehydrogenase, total protein, albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, total, direct and indirect 
bilirubin, ferritin, amylase, lipase, thyroid stimulating hormone (TSH), T4, free T3, and free T4. Additional laboratory samples for safety may be collected as clinically indicated.
i nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 200 mg orally QD on Days 1 to14 of each 21-day treatment cycle; nab-paclitaxel 
100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day treatment cycle; or nab-paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and
durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15.
j Physical examination and vital signs assessment should be performed prior to IP administration at these visits. Additional physical examination and vital signs assessments may 
be performed throughout the study as clinically indicated. Only abnormal and clinically significant physical examination data and/or vital signs will be recorded as an AE/SAE 
on the eCRF. Vital signs will be (at a minimum): blood pressure, heart rate, respiratory rate, body temperature.
k Hematology panel, serum chemistry will be performed at the 90-day Follow-up Visit for subjects in the nab-paclitaxel/durvalumab arm if applicable following AEs or abnormal 
assessments findings during the 28-day Follow-up Visit.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
43
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
6.
PROCEDURES
Subjects will be provided with a written Informed Consent Form (ICF), given the opportunity to 
ask any questions concerning the study and will sign an ICF prior to participating in any study 
procedures. After giving written informed consent, subjects will undergo a Screening Period to 
be assessed for eligibility. All subjects who sign an ICF must be entered into the Integrated 
Response Technology (IRT) immediately upon signature on the document. Subjects who do not 
meet the eligibility criteria will be considered screening failures and will not be eligible for the 
study. Subjects who fail initial screening may undergo re-screening up to 2 times at any time 
and an ICF will need to be resigned, as well as all screening procedures repeated (some 
procedures may not need to be done if previously done within 28 days prior to screening again).
Subjects that have met all eligibility criteria after the Screening Period will be eligible for
randomization /treatment assignment. 
6.1.
Medical History
A complete medical history including, but not limited to, evaluation for past (up to 5 years) or
present cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine,
lymphatic, hematological, immunologic, dermatological, psychiatric, genitourinary, obstetrical, 
surgical history or any other diseases or disorders will be performed at Screening. All NSCLC-
related medical history should be recorded regardless of time. Smoking status/tobacco exposure 
history will be captured on the eCRF.
6.2.
Prior and Concomitant Medications and Procedures
Prior medications are defined as any medications started before randomization/treatment
assignment. All NSCLC-related prior medications/procedures should be recorded regardless of 
time.
Concomitant medications are defined as any medication that was either initiated before 
randomization/treatment assignment and continued during the study treatment, or initiated 
on/after the date of randomization/treatment assignment and within 28 days after the last dose of 
IP for the monotherapy arm and the nab-paclitaxel/CC-486 combination arms, or 90 days after 
last dose of IP in the nab-paclitaxel/durvalumab combination arm. 
All subjects will have concomitant medications and procedures (including radiation therapy) 
recorded at each visit from the time of signature on the ICF until the 28-day Follow-up Visit for 
the monotherapy arm and the nab-paclitaxel/CC-486 combination arms or 90 days after last dose 
of IP in the nab-paclitaxel/durvalumab combination arm, for conditions that are clinically 
significant or ongoing. During the Follow-up Period only NSCLC-associated concomitant 
medications/procedures (including radiation therapy) will be recorded, ie, subsequent-line(s) of 
anti-cancer therapy. Additionally, for laboratory procedures performed per standard of care 
during follow-up, laboratory values that are considered abnormal and clinically significant will 
be recorded as an AE/SAE and also recorded on the laboratory eCRF.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
44
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
6.3.
Pregnancy Testing
All males and all women of child-bearing potential must be reminded to avoid pregnancy prior to 
administration of IP before beginning each new cycle, at the End-of-Treatment Visit and at the 
Follow-up Visits. A pregnancy test is required for women of child-bearing potential only. For 
women of child-bearing potential a serum β-hCG pregnancy test with sensitivity of at least 25
mIU/mL must be performed to assess eligibility at Screening/Baseline. Note: the screening 
serum pregnancy test can be used as the Cycle 1 Day 1 test prior to study therapy if it is 
performed within the 72-hour timeframe.  A urine pregnancy test must be performed prior to 
administration of IP before beginning each new cycle and at the End-of-Treatment Visit for all 
subjects, and at the Follow-up Visits for subjects in the nab-paclitaxel/durvalumab arm. The 
subject may not receive treatment until the Investigator has verified that the result of the 
pregnancy test is negative. See inclusion criteria for pregnancy testing requirements. Any 
pregnancies that occur in women who have received IP must be immediately reported to Celgene 
Drug Safety (See Section 11.4).
6.4.
Complete Chest Computed Tomography (CT) Scan
A complete chest CT scan (including base of neck and adrenal gland) and any other studies 
required for tumor imaging will be done at Screening, every 42 days (-3/+7 days) (starting from 
Day 1 Cycle 1), and End-of-Treatment, until documented progression of disease, withdrawal of 
consent, lost to follow-up, death, or termination of the study by the Sponsor. The results of a 
complete chest CT scan (including base of neck and adrenal gland) performed per standard of 
care may be accepted and not repeated during Screening provided it was performed within 28 
days of the first dose of IP (Cycle 1 Day 1). Those subjects entering the Follow-up Period 
without documented progression will continue to have CT scans in accordance with local 
standard of care (or approximately every 90 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death, or termination of the study by the Sponsor. If the 
CT scan was performed within 2 weeks of End-of-Treatment Visit, this End-of-Treatment CT 
scan will not need to be repeated. Additional CT scans may be done at any time during the study 
if clinically indicated. All CT scans and reports should be archived at the site according to site 
regulations and copies provided to the Sponsor if requested. All post-treatment anticancer 
therapies will be recorded during the Follow-up Period.  
6.5.
Weight and Height
Weight will be obtained at Screening and at every visit during the Treatment Period before 
administration of IP. Additional measurements of weight may be collected per local standards at 
any time during the study as needed. Height will only be collected at Screening. All weight and 
height data will be collected on eCRFs.
6.6.
ECOG Performance Score
Eastern Cooperative Oncology Group performance status score will be collected at Screening, 
Day 1 of every treatment cycle, at the End-of-Treatment Visit and at the Follow-up Visits. 
Additional ECOG assessments may be performed at any time during the study as clinically 
indicated.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
45
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
6.7.
Peripheral Neuropathy Assessment
Peripheral neuropathy (sensory or motor) assessment will be done at Screening, Day 1 of every 
treatment cycle, at the End-of-Treatment Visit and at the 28-day Follow-up Visit. Changes in 
neuropathy grade from baseline will be reported as an AE as per Section 11. Additional 
peripheral neuropathy assessments may be done at any time during the study as clinically 
indicated.
6.8.
Adverse Event Reporting
Adverse events will be recorded from time of signature on the ICF until 28 days after the last 
dose of IP for the monotherapy and the nab-paclitaxel/CC-486 combination arms and until 90 
days after the last dose of IP for the nab-paclitaxel/durvalumab combination arm during the 
Follow-up Visits, including any unscheduled visits. See Section 11 for details. 
6.9.
Quality of Life Questionnaires
The LCSS, EORTC QLQ C30 and EQ-5D-5L questionnaires will be used to measure quality of 
life (QoL) for subjects in the study. The LCSS is comprised of 9 questions to be completed by 
the subject using a visual analogue scale (VAS) to denote intensity of a symptom. The EQ-5D-
5L comprises 5 questions on mobility, self-care, usual activities, pain/discomfort, 
anxiety/depression and a VAS for overall QoL. These questionnaires will be completed by the 
subject prior to interaction with study personnel, at Day 1 of every Cycle, at the End-of-
Treatment Visit and at the 28-day Follow-up Visit.
6.10.
Healthcare Resource Utilization Questionnaire
A healthcare resource utilization questionnaire will be used to capture the additional use of 
healthcare resources, including hospitalizations, emergency room visits, doctor or nurse visits, 
procedures, and/or additional medication during the study period. The assessment will be 
completed on Day 1 of every treatment cycle, at the End-of-Treatment Visit and at the 28-day
Follow-up Visit. 
6.11.
Laboratory Assessments
Blood for hematology and chemistry evaluation will be collected as per Table 4, Table of Events. 
Blood for hematology will be collected at Screening, Days 1, 8, and 15 of every treatment cycle, 
at the End-of-Treatment Visit and at the 28-day Follow-up Visit. Blood for serum chemistry will 
be collected at Screening, Day 1 of every treatment cycle, at the End-of-Treatment Visit and at 
the 28-day Follow-up Visit. Hematology panel and serum chemistry will be performed at the 90-
day Follow-up Visit for subjects in the nab-paclitaxel/durvalumab arm if applicable following 
AEs or abnormal assessments findings during the 28-day Follow-up Visit. Hematology panel 
will consist of: hemoglobin, hematocrit, red blood cell count and morphology, mean corpuscular 
volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, white 
blood cell count with absolute and differential and percent (neutrophils, lymphocytes, 
monocytes, eosinophils, basophils, bands), platelet count, reticulocytes, erythrocyte 
sedimentation rate, international normalized ratio, prothrombin time, partial thromboplastin time
and fibrinogen. Serum chemistry panel includes: sodium, potassium, bicarbonate, calcium, 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
46
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
magnesium, phosphorus, blood urea nitrogen, serum creatinine and clearance, uric acid, glucose, 
lactic dehydrogenase, total protein, albumin, alkaline phosphatase, aspartate aminotransferase, 
alanine aminotransferase, gamma glutamyl transferase, total, direct and indirect bilirubin,
ferritin, amylase, lipase, thyroid stimulating hormone (TSH), T4, free T3, and free T4. 
Additional laboratory samples for safety may be collected as clinically indicated. 
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an AE/SAE and also recorded on the laboratory eCRF (see Section 11.3).
Abnormal and clinically significant laboratory assessments at Screening will be recorded as 
medical history, and after Screening, as AE or SAE (clinically significant laboratory
abnormalities at Screening may result in a subject being ineligible for the study and should not 
be captured as an AE). 
Any abnormal values that persist should be followed at the discretion of the Investigator. The 
Investigator should file all copies of the reports, including faxes with the subject’s medical chart.
6.12.
Tumor Tissue Sample Collection and Peripheral Blood Collection
(Exploratory Assessments) 
Histologically or cytologically confirmed advanced NSCLC is a required inclusion criteria for 
entry into this study.  If a subject’s previously collected tumor tissue (also known as archival 
tumor) is available, these samples will be collected for biomarker testing as detailed below at 
Cycle 1 Day 1.  If such samples do not exist, have been depleted, or do not contain sufficient 
tumor material to be analyzed, this will not preclude participation in the study and a new biopsy 
or other procedure to collect tumor tissue will not be required. Table 5 delineates the specific 
requirements for commonly encountered archival tumor types.
Table 5:
Requirements for Collection Based on Archival Tumor Sample Type
Sample Type
Amount to Collect
Collection 
Requirement for 
Biomarkers
Comments/ Exceptions
Core biopsy or surgical 
specimen
10 slides ≥4 ∀M 
thickness. If a block is 
provided, a core of 
viable tumor will also 
be collected.
Mandatory if the sample 
exists. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Fine needle aspirates 
(FNA)
10 slides ≥4 ∀M. If a 
block is provided, a 
core of viable tumor 
will also be collected. 
Mandatory if the sample 
exists, unless a core 
biopsy or surgical 
sample was provided. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Transbronchial 
endoscopy samples
10 slides ≥4 ∀M. If a 
block is provided, a 
core of viable tumor 
will also be collected.
Mandatory if the sample 
exists, unless a core 
biopsy or surgical 
sample was provided. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
47
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Table 5:
Requirements for Collection Based on Archival Tumor Sample Type 
(Continued)
Sample Type
Amount to Collect
Collection 
Requirement for 
Biomarkers
Comments/ Exceptions
Bronchial lavage, 
sputum, or other 
sample types
Slides or blocks 
representing >100,000 
tumor cells
Collection is strongly 
encouraged when these 
samples contain 
sufficient material.
Collection is strongly 
encouraged when these 
samples contain sufficient 
material.
In addition, test results for tumor mutational status of genes, including but not limited to EGFR,
ALK, KRAS and PD-L1 will be collected, if available from prior testing, and recorded on eCRF 
if these tests have been performed.
Plasma for cell-free nucleic acids analyses will be collected on Cycle 1 Day 1 prior to first dose 
of IP, as will a sample of whole blood or peripheral blood mononuclear cells for a germ-line 
reference comparison. Types of techniques planned to be used for tumor and plasma analyses 
include:
!
Gene expression by RNA sequencing
!
Immunohistochemistry 
!
DNA sequencing
!
DNA methylation profiling
Details regarding the collection, storage, and shipment of the samples are given in the Laboratory 
Manual.
6.13.
Electrocardiogram
Electrocardiograms (ECGs) will be done at Screening and as per standard of care during the 
Treatment Period, and as clinically indicated. Results will be collected in the eCRFs as AE or 
SAE only if results are abnormal, changed and clinically significant, unless the finding is already 
documented in medical history.
6.14.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI)
A CT scan of the head, or preferably brain MRI, will be done as per standard of care at 
Screening (mandatory if symptomatic), during the Treatment Period, and as clinically indicated.
If CT scans show lesions pertinent for RECIST 1.1 criteria evaluation, data will be collected on 
the pertinent tumor evaluation eCRFs.
6.15.
Bone Scans and X-rays
Bone scans and x-rays will be done as per standard of care at Screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs. If bone scans or X-
rays show lesions pertinent for RECIST 1.1 criteria evaluation, data will be collected on the 
pertinent tumor evaluation eCRFs.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
48
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
6.16.
Physical Examinations
Physical examinations will be done at Screening, on Day 1 of every treatment cycle, at the End-
of-Treatment Visit, and as clinically indicated. Results will be collected in the eCRFs as AE or 
SAE only if results are abnormal and clinically significant.
6.17.
Vital Signs
Vital signs (at a minimum blood pressure, heart rate, respiratory rate and body temperature) will 
be done at Screening, prior to IP administration on Days 1, 8, and 15 of every treatment cycle, at 
the End-of-Treatment Visit, and as clinically indicated. Results will be collected in the eCRFs as 
AE or SAE only if results are abnormal and clinically significant.
6.18.
Survival 
After the End-of-Treatment Visit, the subjects will have a 28-day Follow-up Visit followed by a 
phone call approximately every 90 days (+/- 14 days) for at least 12 months after the last subject 
is randomized in either the nab-paclitaxel/CC-486 combination therapy and nab-paclitaxel 
monotherapy arm or 120 PFS events have been observed between these two arms, whichever 
comes later. Subjects in the nab-paclitaxel/durvalumab arm will be followed for survival in a 
similar manner for at least 12 months after the last subject is assigned to this arm.
The subjects will also be asked questions about other medications they may be taking for their 
NSCLC. Those subjects entering the Follow-up Period without documented progression will 
continue to have CT scans in accordance with local standard of care (or approximately every 90 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the Sponsor.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
49
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Male and female subjects with advanced NSCLC who have received no more than one prior
chemotherapy regimen for their advanced disease will be eligible for this study (immunotherapy 
in prior line of treatment is allowed, including platinum doublet combination). Subjects will 
receive study therapy as second or third line of treatment for advanced disease. The study will 
randomize/assign a maximum of approximately 240 subjects if all 3 arms proceed to the end of 
the study. The study will be conducted at approximately 40 sites in the US, Canada, and Europe.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be randomized/assigned in the study:
1. Age ≥ 18 years at the time of signing the ICF.
2. Understand and voluntarily provide written informed consent prior to the conduct of any 
study related assessments/procedures.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Histologically or cytologically confirmed advanced NSCLC who will receive study 
therapy as second- or third-line of treatment for advanced disease.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease (defined by the presence of 
≥1 radiographically documented measurable lesion).
7. One prior platinum-containing chemotherapy for metastatic or recurrent NSCLC unless 
patients are ineligible to receive it. Patients may have received no more than one line of 
chemotherapy; immunotherapy in prior line of treatment (first or second line) is allowed.
8. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
9. Platelets ≥ 100,000 cells/mm3.
10. Hemoglobin (Hgb) ≥ 9 g/dL.
11. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and 
alanine transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper 
limit of normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
12. Total bilirubin ≤ 1.5 ULN (unless there is a known history of Gilberts Syndrome).
13. Serum creatinine ≤1.5 x ULN, or calculated creatinine clearance ≥60 mL/min (if renal 
impairment is suspected 24-hour urine collection for measurement is required).
14. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
15. Females of childbearing potential [defined as a sexually mature woman who (1) have not 
undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy 
(the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
50
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
at least 24 consecutive months (ie, has had menses at any time during the preceding 24 
consecutive months)] must:
a.
Have a negative pregnancy test (ß-hCG) as verified by the study doctor within 72 
hours prior to starting study therapy. She must agree to ongoing pregnancy testing 
during the course of the study, and after end of study therapy. This applies even if the 
subject practices true abstinence* from heterosexual contact.
b. Either commit to true abstinence* from heterosexual contact or agree to use, and be 
able to comply with, effective contraception without interruption, 28 days prior to 
starting IP, during the study therapy (including dose interruptions), and for 3 months 
after discontinuation of study therapy. 
Male subjects must:
a.
Practice true abstinence* or agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the study, 
during dose interruptions and for at least 6 months following IP discontinuation, even 
if he has undergone a successful vasectomy. 
b. Refrain from semen or sperm donation while taking durvalumab and for at least 3 
months after the last dose of durvalumab.
16. Females must abstain from breastfeeding during study participation and 3 months after IP 
discontinuation. 
7.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. Refractory to prior taxane therapy for advanced disease. Prior taxane used in the adjuvant 
setting does not exclude eligibility, provided there is no disease recurrence within 12 
months upon completion of chemotherapy in that setting.
2. Evidence of active brain metastases, including leptomeningeal involvement (prior 
evidence of brain metastasis are permitted only if asymptomatic and clinically stable for 
at least 8 weeks following completion of therapy). MRI of the brain (or CT scan 
w/contrast) is preferred.
3. Only evidence of disease is non-measurable at study entry.
4. Patients with known activating mutations in EGFR (such as exon 19 deletions or L858R).
5. Patients with known activating mutations in EML4-ALK.
6. Preexisting peripheral neuropathy of Grade > 2 (per NCI CTCAE v4.0).
7. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with 
the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion 
criteria.
                                               
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic 
abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception].
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
51
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
8. Venous thromboembolism within 1 month prior to Cycle 1 Day 1.
9. Current congestive heart failure (New York Heart Association Class II-IV).
10. History of the following within 6 months prior to Cycle 1 Day 1: a myocardial infarction, 
severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart 
Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically 
significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG)
abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder.
11. Known hepatitis B or C virus (HBV/HCV) infection, known history of human 
immunodeficiency virus (HIV) infection, or receiving immunosuppressive or 
myelosuppressive medications that would in the opinion of the Investigator, increase the 
risk of serious neutropenic complications, history of active primary immunodeficiency, 
active tuberculosis (clinical evaluation that includes clinical history, physical examination 
and radiographic findings, and TB testing in line with local practice).
12. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, 
defined as ongoing signs/symptoms related to the infection without improvement despite 
appropriate antibiotics, antiviral therapy, and/or other treatment.
13. Subject has a history of interstitial lung disease, history of slowly progressive dyspnea 
and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary
hypersensitivity pneumonitis or multiple allergies. Any lung disease that may interfere 
with the detection or management of suspected drug-related pulmonary toxicity. 
14. Subject has a clinically significant malabsorption syndrome, persistent diarrhea, or 
known sub-acute bowel obstruction > NCI CTCAE Grade 2, despite medical 
management.
15. Treatment with any chemotherapy, investigational product, biologic or hormonal therapy 
for cancer treatment within 28 days prior to signing the ICF. Concurrent use of hormonal
therapy for non-cancer-related conditions (eg, hormone replacement therapy) is 
acceptable.
16. History of or suspected allergy to any IP or their excipients.
17. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first 
dose of IP.  Note: Local surgery of isolated lesions for palliative intent is acceptable.
18. Currently enrolled in any other clinical protocol or investigational trial that involves
administration of experimental therapy and/or therapeutic devices.
19. Any other clinically significant medical condition, psychiatric illness, and/or organ 
dysfunction that will interfere with the administration of the therapy according to this 
protocol or which, in the views of Investigator, preclude combination chemotherapy.
20. Any other malignancy within 5 years prior to randomization/treatment assignment, or 
advanced malignant hepatic tumors, with the exception of adequately treated squamous 
cell carcinoma of the skin, in-situ carcinoma of the cervix, uteri, non-melanomatous skin 
cancer, carcinoma in situ of the breast, or incidental histological finding of prostate 
cancer (TNM Classification of Malignant Tumours (TNM) stage of T1a or T1b). (All 
treatment of which should have been completed 6 months prior to signing ICF).
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
52
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
21. Radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting 
IP, and/or from whom ≥ 30% of the bone marrow was irradiated. Prior radiation therapy 
to a target lesion is permitted only if there has been clear progression of the lesion since 
radiation was completed.
22. Any condition including the presence of laboratory abnormalities, which places the 
subject at unacceptable risk if he/she were to participate in the study.
23. Any medical condition that confounds the ability to interpret data from the study.
24. Female patients who are pregnant or breastfeeding or female patients of reproductive 
potential who are not willing to employ effective birth control from screening to 90 days 
after the last dose of durvalumab.  
25. Male patients of reproductive potential who are not willing to employ effective birth 
control from screening to 90 days after the last dose of durvalumab and from screening to 
6 months after the last dose of nab-paclitaxel.
26. History of allogenic organ transplantation.
27. Active or prior documented autoimmune or inflammatory disorders (including 
inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the 
exception of diverticulosis], celiac disease, irritable bowel disease, or other serious 
gastrointestinal chronic conditions associated with diarrhea, systemic lupus 
erythematosus, sarcoidosis syndrome, or Wegener’s syndrome [granulomatosis with 
polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]) within the 
past 3 years prior to the start of treatment.  The following are exceptions to this criterion:
-
Patients with vitiligo or alopecia
-
Patients with hypothyroidism (eg, following Hashimoto’s syndrome) stable on 
hormone replacement 
-
Any chronic skin condition that does not require systemic therapy
-
Patients without active disease in the last 5 years may be included but only after 
consultation with the study physician
28. Current or prior use of immunosuppressive medication within 14 days before the first 
dose of durvalumab.  The following are exceptions to this criterion:
-
Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular 
injection)
-
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of 
prednisone or its equivalent
-
Steroids as premedication for hypersensitivity reactions (eg, CT scan 
premedication)
29. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.  Note: 
Patients, if enrolled, should not receive live vaccine during the study and up to 30 days 
after the last dose of IP.
30. Prior enrollment and treatment in a previous durvalumab clinical study. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
53
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
31. Patients who have received prior anti-PD-1 or anti PD-L1 :
# Must not have experienced a toxicity that led to permanent discontinuation of prior 
immunotherapy. 
# All AEs while receiving prior immunotherapy must have completely resolved or 
resolved to baseline prior to screening for this study.
# Must not have experienced a ≥ Grade 3 immune related AE or an immune related 
neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: 
Subjects with endocrine AE of ≤ Grade 2 are permitted to enroll if they are stably 
maintained on appropriate replacement therapy and are asymptomatic.
# Must not have required the use of additional immunosuppression other than 
corticosteroids for the management of an AE, not have experienced recurrence of 
an AE if re-challenged, and not currently require maintenance doses of > 10 mg 
prednisone or equivalent per day.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
54
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Investigational Products
Subjects will receive open-label nab-paclitaxel / CC-486, nab-paclitaxel /durvalumab or nab-
paclitaxel monotherapy during the Treatment Period of the study. nab-paclitaxel, durvalumab
and CC-486 are designated as IP and will be packaged and supplied by the study Sponsor.
The reconstitution and IV administration of nab-paclitaxel should follow the local Prescribing 
Information for Abraxane®.
8.1.1.
nab-Paclitaxel
nab-Paclitaxel will be supplied by the Sponsor in single-use vials in single count cartons. Each 
single-use 50 mL vial will contain paclitaxel (100 mg) and human albumin as a stabilizer.
Please see local prescribing information for Abraxane® for detailed instructions on the 
reconstitution, storage conditions and IV administration of nab-paclitaxel. Reconstituted nab-
paclitaxel should be stored in an area accessible only to study personnel.
Temperature records for nab-paclitaxel must be made available to the Sponsor or other Sponsor-
nominated monitoring teams for verification of proper IP storage.
8.1.2.
CC-486 (Azacitidine for Oral Administration)
The Sponsor will supply azacitidine 100 mg tablets for oral administration. Each tablet is 
formulated using excipients that are generally regarded as safe and are used in marketed drug 
products.
All tablets will be packaged in blister cards. Only sufficient IP for one cycle of treatment will be 
provided to each subject at the start of each treatment cycle. All tablets should be swallowed 
whole, and should not be broken or chewed. CC-486 may be taken on an empty stomach or with 
food. Subjects should drink 8 ounces (240 mL) of room temperature water with each dose. It is 
strongly recommended that all subjects receive a dose of a prophylactic antiemetic, preferably a 
5-HT3 antagonist, approximately 30 minutes prior to each dose of CC-486.
The IP must be stored as directed on package label at controlled temperature and a temperature 
log must be maintained in the source documents. The storage area should be secure and have 
access limited to study personnel. 
8.1.3.
Durvalumab (MEDI4736)
Durvalumab will be supplied by the Sponsor in single use vials in single count cartons. Each 10R 
(10 mL) vial will be supplied as a liquid solution containing 500 mg (nominal) of IP at a 
concentration of 50 mg/mL. Durvalumab should be stored in accordance with the product label. 
The study site is to supply the following:
!
IV infusion bags of normal saline (0.9% [w/v] sodium chloride injection, 250 mL 
size). Saline bags must be latex-free and can be made of polypropylene, polyethylene, 
ng
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
55
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
polyolefin copolymers, or polyvinyl chloride. Infusion lines should contain a 0.2-μm 
in-line filter.  
!
Since the compatibility of durvalumab with other IV medications and solutions, other 
than normal saline, is not known, the durvalumab solution should not be infused 
through an IV line in which other solutions or medications are being administered.
Durvalumab will be administered using an IV bag containing 0.9% (w/v) saline or 5% (w/v) 
dextrose, with a final durvalumab concentration ranging from 1 to 20 mg/mL, and delivered 
through an IV administration set with a 0.2- or 0.22-μm in-line filter.
The dose of durvalumab for administration must be prepared by the Investigator’s or site’s 
designated IP manager using aseptic technique. Total time from needle puncture of the 
MEDI4736 vial to the start of administration should not exceed:
!
24 hours at 2°C to 8°C (36°F to 46°F)
!
4 hours at room temperature
Standard infusion time is 1 hour. However, if there are interruptions during infusion, the total 
allowed time should not exceed 8 hours at room temperature. In the event that either preparation 
time or infusion time exceeds the time limits outlined above, a new dose must be prepared from 
new vials. Durvalumab does not contain preservatives, and any unused portion must be 
discarded.
For additional information on preparation and storage please refer to the pharmacy manual.
8.1.4.
Monitoring During/After Durvalumab Infusion 
First durvalumab infusion
On the first infusion day, subjects in the nab-paclitaxel/durvalumab combination arm will be 
monitored, and assessments collected/recorded in the eCRF prior to, during and after infusion of 
IP as presented in the bulleted list below.
Blood pressure (BP) and pulse will be collected from subjects before, during, and after each 
infusion at the following times (based on a 60-minute infusion):
!
Prior to the beginning of the infusion (measured once from approximately 30 minutes 
before up to 0 minutes [ie, the beginning of the infusion])
!
Approximately 30 minutes during the infusion (halfway through infusion) 
!
At the end of the infusion ( approximately 60 minutes ±5 minutes)
!
If the infusion takes longer than 60 minutes, then BP and pulse measurements should 
follow the principles as described above or be taken more frequently if clinically 
indicated.  A 1-hour observation period is recommended after the first infusion of 
durvalumab.
Subsequent durvalumab infusions
BP, pulse and other vital signs should be measured, collected/recorded in eCRF prior to the start 
of the infusion. Subjects should be carefully monitored and BP and other vital signs should be 
measured during and post infusion as per institution standard and as clinically indicated. Any 
s s 
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below.
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beginning o
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
56
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
clinically significant changes in vital signs should be entered onto an unscheduled vital signs 
CRF page.
For all infusions
In the event of a ≤ Grade 2 infusion-related reaction, the infusion rate of IP may be decreased by 
50% or interrupted until resolution of the event (up to 4 hours) and re-initiated at 50% of the 
initial rate until completion of the infusion. For subjects with a ≤ Grade 2 infusion-related 
reaction, subsequent infusions may be administered at 50% of the initial rate. 
Acetaminophen/paracetamol and/or an antihistamine (eg, diphenhydramine) or equivalent 
medications per institutional standard may be administered at the discretion of the investigator. If 
the infusion-related reaction is ≥ Grade 3 or higher in severity, IP will be discontinued. 
As with any antibody, allergic reactions to dose administration are possible. Appropriate drugs 
and medical equipment to treat acute anaphylactic reactions must be immediately available, and
study personnel must be trained to recognize and treat anaphylaxis. The study site must have 
immediate access to emergency resuscitation teams and equipment in addition to the ability to 
admit subjects to an intensive care unit if necessary.
8.2.
Treatment Administration and Schedule
Following administration of nab-paclitaxel, the intravenous line should be flushed with sodium
chloride 9 mg/mL (0.9%) solution for injection to ensure administration of the complete dose, 
according to local practice.
Once randomized (or assigned), subjects will be treated with nab-paclitaxel / CC-486, nab-
paclitaxel / durvalumab or nab-paclitaxel monotherapy until disease progression, development of 
an unacceptable toxicity, death, lost to follow-up, withdrawal of consent, or termination of the 
study by the Sponsor:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment cycle, or
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 
durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15 of each 21-
day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle
8.3.
Dose Omissions and Modifications
8.3.1.
Rules for Dose Omissions and Modified Schedules
nab-Paclitaxel Monotherapy Arm
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
!
Day 1 Dose Missed
If nab-paclitaxel cannot be administered on Day 1 within the 2 days allowable window,
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
57
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
 nab-paclitaxel may not be skipped but only delayed 
 Delay of Day 1 will automatically shift the following visit for this cycle 
!
Day 8 Dose Missed
If the nab-paclitaxel dose for Day 8 is given >9 days from Day 1, the Day 8 dose, when 
administered, can be either considered as delayed or skipped, depending on the intention of the 
Investigator.
 nab-paclitaxel may be delayed up to Day 15: this dose will be considered as delayed 
Day 8; the next visit will be the planned Day 1 of the next cycle which will not be 
automatically pushed back
 nab-paclitaxel may be skipped: if the second nab-paclitaxel dose cannot be given in a 
cycle it may be skipped; the next dose would be administered as the Day 1 dose 
nab-Paclitaxel/CC-486 Combination Arm
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
If any doses of CC-486 are missed, skip that day and resume as appropriate, do not double up on 
subsequent days.
!
Day 1 Dose Missed
If CC-486 cannot be administered on Day 1 within the 2 days allowable window,
 The nab-paclitaxel Day 8 dose would not necessarily be pushed back / delayed
 Doses of CC-486 would be skipped (exposure to CC-486 would be reduced on that 
cycle). 
For hematologic toxicity, dosing should be reassessed at the next visit on Day 8.
!
Day 8 Dose Missed
If nab-paclitaxel cannot be administered on Day 8 within the 2 days allowable window,
 nab-paclitaxel may be delayed (eg, for neuropathy): this dose will be considered as 
delayed Day 8; the next dose (Day 15) may also be delayed up to the original Day 1 of 
the next cycle (approximately 20 days from Day 1 of this cycle) to maintain the protocol 
specified visit gap
 nab-paclitaxel may be skipped (eg, hematotoxicity); the next dose would be administered 
as the Day 15 dose 
If the dose for Day 8 is given > 9 days from Day 1, the Day 8 dose, when administered, can be 
either considered as delayed or skipped, depending on the intention of the Investigator.
Upon resuming treatment after stopping both IPs on adjusted Day 8, consideration for nab-
paclitaxel resumption should take priority.
!
Day 15 Dose Missed
If nab-paclitaxel cannot be administered on Day 15 within the 2 days allowable window,
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
58
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
 nab-paclitaxel may be delayed: this dose will be considered as delayed Day 15 (up to 
Day 1 of the next cycle); CC-486 may be started on Day 1 as planned
 If the nab-paclitaxel dose cannot be administered within 14 days from the last dose, it 
will be considered as skipped
nab-Paclitaxel/Durvalumab Combination Arm
No dose reductions of durvalumab are allowed. In case of doubt, the Investigator should consult 
with the Study Physician.
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
!
Day 1 Dose Missed
If nab-paclitaxel cannot be administered on Day 1 within the 2 days allowable window,
 nab-paclitaxel may not be skipped but only delayed 
 Delay of Day 1 will automatically shift the following visit for this cycle 
!
Day 8 Dose Missed
If the nab-paclitaxel dose for Day 8 is given > 9 days from Day 1, the Day 8 nab-paclitaxel dose 
should be skipped
!
Day 15 Dose Missed
If durvalumab cannot be administered on Day 15 within the 2 days allowable window,
 Durvalumab may be delayed: this dose will be considered as delayed Day 15 
 If the durvalumab dose cannot be administered within 14 days from the last dose, it will 
be considered as skipped
8.3.2.
Rules for Dose Modifications
Subjects who experience any of the adverse drug reactions in Table 6 will be dose reduced as per 
Table 6 during treatment. 
nab-Paclitaxel Monotherapy Arm
!
Do not administer nab-paclitaxel on Day 1 of a cycle until ANC is at least 
1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment until 
counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and platelet 
count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil count of at least 
500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Day 8 of the cycle. 
Upon resumption of dosing, permanently reduce nab-paclitaxel doses as outlined in 
Table 6.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-paclitaxel 
at reduced doses (Table 6) when peripheral neuropathy improves to Grade 1 or 
completely resolves.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
59
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to 
the guidelines in Table 6. For any other Grade 3 or 4 nonhematologic toxicity or other 
Investigator defined unacceptable toxicity, interrupt treatment until the toxicity 
improves to ≤Grade 2, then restart treatment according to the guidelines in Table 6.
Re-escalation is not permitted at any time. 
nab-Paclitaxel/CC-486 Combination Arm
!
Do not administer nab-paclitaxel on Day 8 or CC-486 on Day 1 or 8 of a cycle until ANC 
is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe thrombocytopenia, withhold treatment until counts 
recover to a platelet count of at least 100,000 cells/mm3 on Days 1 and 8 for CC-486 and 
Day 8 for nab-paclitaxel or to a platelet count of at least 50,000 cells/mm3 on Day 15 of 
the cycle for nab-paclitaxel. Upon resumption of dosing, permanently reduce nab-
paclitaxel and/or CC-486 doses as outlined in Table 6.
!
In subjects who experience Grade ≥3 neutropenia, withhold treatment and start G-CSF 
treatment daily until the ANC ≥ 2000/mm3 (please refer to Section 9.3 for G-CSF 
administration). Upon resumption, permanently reduce nab-paclitaxel and/or CC-486 
dose as outlined in Table 6.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy (CC-486 does not need 
to be withheld). Resume nab-paclitaxel at reduced doses (Table 6) when peripheral 
neuropathy improves to Grade 1 or completely resolves. 
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to the 
guidelines in Table 6. For any other Grade 3 or 4 nonhematologic toxicity or other 
Investigator defined unacceptable toxicity, interrupt treatment until the toxicity improves 
to ≤Grade 2, then restart treatment according to the guidelines in Table 6.
Re-escalation is not permitted at any time. 
nab-Paclitaxel/Durvalumab Combination Arm
Guidelines for the management of toxicities for durvalumab and nab-paclitaxel are provided in 
Appendix C.
In addition:
!
Do not administer nab-paclitaxel on Day 1 of a cycle until ANC is at least 
1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment until 
counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and platelet 
count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil count of at least 
500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Day 8 of the cycle. 
Upon resumption of dosing, permanently reduce nab-paclitaxel doses as outlined in 
Table 6.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
60
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-paclitaxel 
at reduced doses (Table 6) when peripheral neuropathy improves to Grade 1 or 
completely resolves. 
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to the 
guidelines in Table 6. For any other Grade 3 or 4 nonhematologic toxicity or other 
Investigator defined unacceptable toxicity, interrupt treatment until the toxicity improves 
to ≤Grade 2, then restart treatment according to the guidelines in Table 6.
Following the first dose of IP, subsequent administration of durvalumab can be modified based 
on toxicities observed as described in the Dosing Modification and Toxicity Management 
Guidelines.  These guidelines have been prepared by the Sponsor to assist the Investigator in the 
exercise of his/her clinical judgment in treating these types of toxicities.  These guidelines apply 
to AEs considered causally related to the durvalumab containing regimen by the reporting 
Investigator.
Treatment modifications referring to ‘study regimen or treatment’ would apply to both nab-
paclitaxel and durvalumab unless AEs are not considered causally related to nab-paclitaxel by 
the reporting Investigator. In that case nab-paclitaxel or durvalumab treatment may be continued 
alone if deemed beneficial to the patient per Investigator’s assessment.
Re-escalation is not permitted at any time. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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61
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Table 6:
Permanent Dose Reductions for Hematologic and Nonhematologic Toxicities and Dosing on the Study
Dose Modification During Treatment
Adverse Drug Reaction
Occurrence
Monotherapy Arm: nab-
paclitaxel Dose (mg/m2)
Combination Arm: nab-
paclitaxel Dose (mg/m2) / 
CC-486 Dose (mg)
Neutropenic Fever (ANC < 500/mm3 with fever >38°C)
OR
Delay of next cycle by > 7 days for ANC < 1500/mm3
OR
ANC < 500/mm3 for > 7 days
First
75
100/100
Second
50
75/100
Third
Discontinue Treatment*
50/100
Fourth
NA
Discontinue Treatment*
Platelet count < 50,000/mm3
First
75
100/100
Second
Discontinue Treatment*
75/100
Third
NA
Discontinue Treatment*
Peripheral Neuropathy Grade ≥3
First
75
75/200
Second
50
50/200
Third
Discontinue Treatment*
Grade 2 or 3 Cutaneous toxicity
Grade 3 Diarrhea
Grade 3 Mucositis
Any other Grade 3 or 4 nonhematologic toxicity or other 
Investigator defined unacceptable toxicity
First
75
100/100
Second
50
75/100
Third
Discontinue Treatment*
50/100
Fourth
NA
Discontinue Treatment*
Grade 4 Cutaneous toxicity, Diarrhea or Mucositis
First
Discontinue Treatment*
ANC = absolute neutrophil count; AUC = area under the curve; NA = not applicable.
* If an adverse event that requires dose reduction recurs after the dose has been reduced according to the table above, the subject should generally have treatment 
discontinued unless, at the discretion of the Investigator, there is evidence of continuing benefit to the subject that outweighs the risk of recurrent toxicity.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
62
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
8.4.
Method of Treatment Assignment
The Treatment Period of the study is open-label. Randomization/treatment assignment has been 
and will be carried out centrally using an IRT system.
8.5.
Packaging and Labeling
The label(s) for all IP will include Sponsor name, address and telephone number, the protocol 
number, IP name, dosage form and strength (where applicable), amount of IP per container, lot 
number, expiry date (where applicable), medication identification/kit number, dosing 
instructions, storage conditions, and required caution statements and/or regulatory statements as 
applicable. Additional information may be included on the label as applicable per local 
regulations.
8.6.
Investigational Product Accountability and Disposal
The Sponsor (or its designee) will review with the Investigator and relevant site personnel the 
process for IP return, disposal, and/or destruction including responsibilities for the site versus the 
responsibilities of the Sponsor (or designee).
The Sponsor will instruct the Investigator on the return, disposal and/or destruction of IP. Only 
completely unused IP vials should be retained by the site until a representative from the Sponsor
or other Sponsor-designated personnel have completed an inventory. Partially used and
completely used vials should be destroyed according to local guidelines, and disposition should 
be recorded on the Investigational Drug Accountability Record Form.
The Investigator(s) or designee(s) is responsible for accounting for all IP that is issued to and
returned by the subject during the course of the study according to applicable regulatory
requirements. Any unused CC-486 must be returned by a study subject and retained by the
investigative site for accountability to be conducted by a Sponsor representative (or its designee). 
If any IP is lost or damaged, its disposition should be documented. At the periodic monitoring
visits, a Sponsor representative (or its designee) will conduct IP accountability and address any
discrepancies. Upon satisfactory reconciliation of all IP, returned IP may be destroyed. At the
conclusion of the study, all remaining IP will be counted, reconciled with dispensing records, 
documented, and destroyed at the clinic site or allocated drug destruction location after
completion of drug accountability by a Sponsor representative (or its designee). The Sponsor
representative (or its designee) will ensure that a final report of drug accountability to the unit 
dose level (ie, tablet) is prepared and placed in both the Investigator study file and the central 
clinical study file.
Investigational product will not be loaned or dispensed by the Investigator to another 
Investigator or site. Under certain circumstances, and with Sponsor permission, cooperative 
groups may manage IP between locations within their network as clinical trial agreement and 
local guidelines permit.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
63
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
8.7.
Investigational Product Compliance
All IP will be administered only by study site personnel and accurate recording of all IP 
administration will be made in the appropriate section of the subject’s eCRF and source 
documents.
8.8.
Overdose
Overdose, as defined for this protocol, refers to nab-paclitaxel, CC-486, or durvalumab dosing.
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel, durvalumab or CC-486 to a given subject, regardless of any associated adverse events 
or sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate. For nab-paclitaxel, an infusion completed in less than 25 minutes may increase Cmax by 
approximately 20%, therefore a nab-paclitaxel infusion completed in less than 25 minutes will 
meet the infusion rate criterion for an overdose.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the AE case report form. See 
Section 11.1 for the reporting of adverse events associated with overdose.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
64
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
Over the course of this study, additional medications may be required to manage aspects of the 
disease state of the subjects, including side effects from study treatments or disease recurrence. 
All supportive care (including but not limited to growth factors, antiemetics, analgesics, 
zolendronic acid, denosumab) is permitted as per the Investigator’s discretion and should be 
administered according to local institutional practice. All concomitant treatments, including 
blood and blood products, must be reported on the eCRF.
!
Antiemetics are not required during the study; however, it is strongly recommended 
that all subjects receive a dose of a prophylactic antiemetic, preferably a 5-HT3 
antagonist, approximately 30 minutes prior to each dose of CC-486.
!
Stable, therapeutic doses of anticoagulants are permitted; however, subjects on 
warfarin should have prothrombin time (PT) or international normalized ratio (INR)
and partial thromboplastin time (PTT) monitored as clinically indicated.
!
Subjects on erythropoietin or darbepoetin alfa for at least 4 weeks prior to starting the 
IP may continue their pretreatment doses throughout the study.
# Note: If the subject is not on a stable dose of an erythropoiesis-
stimulating agents (ESA) prior to study entry, the subject may not 
start an ESA during Cycle 1. However, medications such as ESAs, 
granulocyte colony-stimulating factors (G-CSFs), etc., may be
administered according to standard of care after Cycle 1.
!
Use of white blood cell growth factors (eg, filgrastim, G-CSF for the treatment of 
subjects with neutropenic fever is permitted at the Investigator’s discretion. Use of 
filgrastim rather than pegylated-filgrastim is indicated, because of the 14 day delay of 
the next cycle following treatment with peg-filgrastim.
!
Use of white blood cell growth factors (eg, filgrastim, G-CSF) for secondary
prophylaxis in subjects who experienced a neutropenic complication from a prior
cycle of chemotherapy (for which primary prophylaxis was not received) is permitted.
!
Flu vaccination with inactivated virus is permitted.
!
Routine infectious disease prophylaxis is not recommended, however, antibiotic,
antiviral, antipneumocystis, antifungal, or other prophylaxis may be implemented
during the study at the discretion of the Investigator.
!
Treatments with bisphosphonates (eg, pamidronate, zolendronate), or other agents
(eg, denosumab) to prevent or delay progression of bone metastases are permitted.
Maintenance of a stable dosing regimen throughout the study is recommended.
!
Subjects may receive physiologic replacement doses of glucocorticoids as
maintenance therapy for adrenal insufficiency. Glucocorticoids may be administered
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
65
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as an antiemetic with IV chemotherapy, if directed by local standard of care. Use of 
immunosuppressive medications for the management of durvalumab-related AEs, or 
in subjects with contrast allergies is acceptable.  In addition, use of inhaled, topical, 
and intranasal corticosteroids is permitted.
!
Treatment with antidiarrheal medications is recommended at the first sign of diarrhea
as per the guidelines in Appendix B. Pre-medication with antidiarrheal medication for 
subsequent doses of CC-486 may be appropriate.
!
The potential drug-drug interactions precautions contained in the nab-paclitaxel 
prescribing information will be applied to this study, unless otherwise specified in the 
protocol. Specifically, the metabolism of paclitaxel is catalyzed by cytochrome P450 
isozymes CYP2C8 and CYP3A4. Caution is recommended when administering nab-
paclitaxel concomitantly with medicines known to inhibit (eg, ketoconazole and other 
imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, 
saquinavir, indinavir, and nelfinavir) or induce (eg, rifampicin, carbamazepine,
phenytoin, efavirenz, nevirapine) either CYP2C8 or CYP3A4. For information 
regarding other drugs that may interact with either nab-paclitaxel or durvalumab and 
affect their metabolism, pharmacokinetics, or excretion, please see the respective IP 
product information (refer to Prescribing Information and/or IB).
9.2.
Prohibited Concomitant Medications and Procedures
Other investigational therapies must not be used while the subject is enrolled in the study.
Anticancer therapy (chemotherapy, biologic or investigational therapy, and surgery) other than
the study treatments must not be given to subjects during the study. If such treatment is required,
the subject must be discontinued from the study. Focal palliative radiotherapy for treatment of
cancer-related symptoms is allowed during study treatment at the discretion of the Investigator.
The administration of either α-interferon and/or ribavirin, or drugs with known renal toxicity is
prohibited during study treatment. Monoclonal antibodies against CTLA-4, PD-1 or PD-L1 
should not be given concomitantly.
Immunosuppressive medications including, but not limited to, systemic corticosteroids at doses 
exceeding 10 mg/day of prednisone or equivalent, methotrexate, azathioprine, and tumor 
necrosis factor-α blockers should not be given during the study unless required for management 
of immune-related toxicities (Appendix C).
Live attenuated vaccines should not be given through 30 days after the last dose of IP.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) EGFR TKIs should 
not be given concomitantly with durvalumab, and should be used with caution in the 90 days 
post last dose of durvalumab. Increased incidences of pneumonitis (with third generation EGFR 
TKIs) and increased incidence of transaminase increases (with first generation EGFR TKIs) has 
been reported when durvalumab has been given concomitantly.
9.3.
Required Concomitant Medications and Procedures for Subjects 
Receiving CC-486
Data regarding G-CSF administration should be recorded on the eCRF provided for G-CSF 
administration.
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('06'RF1XPEHU
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Celgene Corporation
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9.3.1.
Description of G-CSF
This medication stimulates the blood system (bone marrow) to make white blood cells, helping
fight infections. This medication is given to those whose ability to make white blood cells has
been reduced. Filgrastim (also known as G-CSF, or granulocyte colony stimulating factor) is a
man-made version of a certain natural substance found in the body. It is produced using a certain
bacteria. It will be obtained commercially and relabeled as clinical supplies. It should be stored,
and administered according to the manufacturer’s recommendation.
9.3.2.
Administration of G-CSF
For subjects who experience Grade ≥3 neutropenia, G-CSF 5 ∀g/kg daily will be administered
subcutaneously. During any cycle when Grade ≥3 neutropenia occurs, CC-486 and other 
cytotoxic agents will be held, and G-CSF will begin immediately (a minimum of 24 hours after 
the last dose of CC-486 and chemotherapy). In subsequent cycles, G-CSF will begin on Day 16. 
G-CSF will continue daily until the ANC ≥2000/mm3. In subjects receiving G-CSF, the next 
cycle should begin no sooner than 48 hours after discontinuation of G-CSF. 
For complete details on drug administration, storage, clinical pharmacology, and the human PK 
of G-CSF (filgrastim), please see the G-CSF (filgrastim) package insert.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
67
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10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the study are described 
below.  Additional analyses of these endpoints as well as exploratory endpoints or subgroup 
analyses will be described in detail in the statistical analysis plan (SAP).  The SAP supersedes 
the analyses described in the protocol should there be differences between the two.
Evaluations of the study endpoints will be based primarily on the point estimates and the 
associated 95% confidence intervals of the within- and between-treatment differences. 
10.1.
Overview
Approximately 240 subjects will be assigned 1:1:1 to one of the three treatment arms 
(approximately 80 subjects per group). The combination arms will receive nab-paclitaxel with 
epigenetic modifying therapy of CC-486 or nab-paclitaxel with immunotherapy of durvalumab,
and the monotherapy arm will receive nab-paclitaxel alone.  All regimens will be administered 
in 21-day cycles. All subjects will receive the assigned study treatment until disease progression, 
unacceptable toxicity, death, lost to follow-up, withdrawal of consent, or termination of the 
study by the Sponsor, in accordance with local standard of care. Treatment beyond progression 
defined by RECIST 1.1 will be permitted per irRECIST criteria for those subjects in the nab-
paclitaxel/durvalumab arm (see Section 4.1.2.1).
Prior to the time of implementation of Protocol Amendment 3.0, subjects will be assigned to 
either the nab-paclitaxel/CC-486 combination or nab-paclitaxel monotherapy arms in a 1:1 
fashion based on a permuted-block randomization method with the following baseline 
stratification factors: 
!
ECOG performance status (0 versus 1)
!
Gender (males versus females)
!
Smoker (yes versus no)
Randomization will be carried out centrally using an IRT system. Once Protocol Amendment 3.0 
is in effect, subjects from sites that are ready to implement the said amendment will be 
randomized 1:1:1 to the nab-paclitaxel/CC-486 combination therapy, nab-paclitaxel 
monotherapy, and nab-paclitaxel/durvalumab combination therapy arms, respectively. Subjects 
from the remaining sites will continue to be randomized 1:1 to the nab-paclitaxel/CC-486 
combination therapy and nab-paclitaxel monotherapy arms, respectively. When approximately 
80 subjects have been randomized to each of the nab-paclitaxel/CC-486 combination therapy and 
nab-paclitaxel monotherapy arms, all incoming subjects will be assigned to the nab-
paclitaxel/durvalumab combination therapy arm until approximately 80 subjects have been 
enrolled to receive the IP in that arm. Hence, treatment assignments of subjects to the nab-
paclitaxel/CC-486 combination therapy and nab-paclitaxel monotherapy arms will be in effect 
conducted completely in a randomized fashion.
If the nab-paclitaxel/CC-486 arm stops after the interim analysis, incoming subjects will be 
randomized 2:1 to the nab-paclitaxel/durvalumab combination therapy and nab-paclitaxel 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
68
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monotherapy arms, respectively, until enrollment to the monotherapy arm is complete.  
Thereafter, subjects will be assigned to the nab-paclitaxel/durvalumab combination therapy arm 
until approximately 80 subjects have been enrolled in this arm.
A data monitoring committee (DMC) will be used to review the safety and efficacy data during 
the study.
10.2.
Study Population Definitions
10.2.1.
Intent-to-treat Population
The primary efficacy analysis will be performed on the intent-to-treat (ITT) population, which 
includes all randomized (assigned) subjects regardless of whether the subject receives any IP or 
has any efficacy assessments performed. 
10.2.2.
Per-protocol (PP) Population
The PP population is defined as all eligible subjects randomized/assigned who receive at least 
one dose of the IP, have been treated in the arm they were assigned and meet the major eligibility
criteria of the protocol.  Additional analyses utilizing the PP population will be described in the 
SAP.
10.2.3.
Treated Population
The treated population will consist of all randomized/assigned subjects who receive at least one 
dose of IP. The safety analyses will be based on the treatment as received if different from the 
assigned treatment by randomization/treatment assignment.
10.3.
Sample Size and Power Considerations
The primary objective of this study is to estimate the efficacy of the nab-paclitaxel/CC-486 
combination therapy, that of the nab-paclitaxel/durvalumab combination therapy, and that of the 
nab-paclitaxel monotherapy.
A secondary efficacy objective is to estimate the relative efficacy of each of the combination 
regimens to the nab-paclitaxel monotherapy regimen. 
The effect of the treatment regimens with respect to the efficacy endpoints will be based on the 
point estimates and the associated 95% confidence intervals. The sample size was chosen to 
support the estimation of the within- treatment effects with reasonable precision. In the 
durvalumab arm, a sample size of 80 subjects will further allow the estimation of the treatment 
effect with reasonable precision when stratification by prior checkpoint inhibitor exposure 
(checkpoint naïve and prior exposure to checkpoint inhibitors) is performed. 
No inferential statistical tests will be performed and no multiplicity adjustments are planned for 
the statistical analyses.
Table 7 below summarizes the two-sided 95% confidence intervals for a range of hypothetical 
observed disease control rates given a sample size of 80 subjects in a treatment arm. If the 
observed disease control rate is 0.30, then the actual width of the 2-sided 95% confidence 
interval is 0.21 (95% CI is [0.20, 0.41]).
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
69
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Table 7:
Disease Control Rate –Two-Sided 95% Confidence Interval of Hypothetical 
Disease Control Rate with a Sample Size of 80 Subjects in a Treatment Arm
Hypothetical Observed Disease 
Control Rate
Actual Width of 95% 
Confidence Interval
95% Confidence Intervala
0.20
0.186
(0.119, 0.304)
0.25
0.199
(0.16, 0.359)
0.30
0.21
(0.203, 0.413)
0.35
0.218
(0.247, 0.465
0.40
0.224
(0.292, 0.516)
0.45
0.227
(0.338, 0.565)
0.50
0.228
(0.386, 0.614)
a Based on the Clopper-Pearson exact method.
The between-treatment effect with respect to PFS can be estimated based on the point estimate of 
the hazard ratio and the associated 95% confidence interval. Table 8 below summarizes the 
precision that can be achieved given different scenarios of hypothetical observed hazard ratios 
between the treatment arms for PFS events, assuming a total of 120 events are observed. 
Table 8:
Progression-Free Survival – Two-Sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms
Hypothetical Number of Events 
Observed
Hypothetical Observed Hazard 
Ratio of PFS Events
95% Confidence Interval of 
Hazard Ratioa
120
0.60
(0.42, 0.86)
0.65
(0.45, 0.93)
0.70
(0.49, 1.00)
a Assuming a standard error of 0.18 [estimated based on (4/120)1/2] for the log hazard ratio.
Assuming the median times of PFS are 4.17 and 2.5 months, respectively, for the nab-
paclitaxel/CC-486 combination therapy and nab-paclitaxel monotherapy arms, and an 
approximate 23 months accrual period for a total of 160 subjects, it is estimated that a total of 
120 PFS events will have been observed approximately 2 months after the last subject is 
randomized to these 2 arms, assuming an exponential distribution for PFS. The final analysis of 
the nab-paclitaxel/CC-486 combination and nab-paclitaxel monotherapy arms will be performed 
when a total of approximately 120 PFS events have been observed between these two arms.
While there is published data demonstrating efficacy of nab-paclitaxel as monotherapy in a 
second line setting in advanced NSCLC with ORR ranging from 16.1 to 33% and a median PFS 
of up to 5 months, it is difficult to place an assumed treatment effect on nab-paclitaxel as a 
monotherapy (Chen, 2012; Saxena, 2012; Yuan, 2012).  The assumption of 2.5 months PFS in 
the monotherapy arm is in line with this data and other efficacy data previously observed 
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up


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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following monotherapy treatment of advanced disease with other agents (Shepherd, 2000; 
Hanna, 2004; Reck, 2014; Garon, 2014).
[Of note, with 120 PFS events, this study has an 80% power (1-sided, Type-1 error of 2.5%) to 
detect a HR of 0.60 for PFS between two treatment arms.]
Assuming the median time of PFS is 4.25 months for the nab-paclitaxel/durvalumab 
combination therapy, and an approximate 13 months accrual period for a total of approximately
80 subjects, it is estimated that a total of approximate 50 PFS events will have been observed at 
approximately 3 months after the last subject is assigned to this arm, assuming an exponential
distribution for PFS. The final analysis for PFS for the nab-paclitaxel/durvalumab arm will be 
performed when approximately 50 PFS events have been observed in this arm.
One nonbinding interim analysis for PFS with an early stopping rule for futility between the nab-
paclitaxel/CC-486 combination and nab-paclitaxel monotherapy arms will be conducted when 
approximately 60 events have been observed. The nab-paclitaxel/CC-486 combination arm may 
be stopped early for futility if the observed HR is > 1.10, and/or if recommended by the DMC 
based on the safety profile of this combination regimen. A HR> 1.10 when half of the target 
events of 120 have occurred signals a low probability for observing a meaningful difference in 
favor of the nab-paclitaxel/CC-486 combination therapy should the study continue to the end. 
With the assumptions stated above, it will take approximately 15 months from the first subject 
randomized to observe approximately 60 PFS events for the interim analysis.
An additional interim analysis for futility with the PFS endpoint between the nab-
paclitaxel/durvalumab combination therapy and nab-paclitaxel monotherapy arms will be 
conducted when approximately 30 PFS events have been observed in the nab-paclitaxel/
durvalumab combination arm. It is projected that 60 or more PFS events will have been observed 
in the nab-paclitaxel monotherapy arm at that point. The nab-paclitaxel/durvalumab combination 
arm may be stopped early for futility if the observed HR is ≥ 1.10, and/or if recommended by the 
DMC based on the safety profile of this combination regimen. With the assumptions stated 
above, it will take approximately 13 months from the first subject randomized to the nab-
paclitaxel/durvalumab arm to observe the events needed for this interim analysis.
Disease control rate, OS, and ORR within and the difference between the nab-paclitaxel/CC-486 
combination and nab-paclitaxel monotherapy treatment arms will be estimated at the time of the 
final analysis of the PFS endpoint when approximately 120 PFS events have been observed
between these two arms. The same endpoints will be estimated within the nab-
paclitaxel/durvalumab arm and between this and the nab-paclitaxel monotherapy arms when 
approximately 50 PFS events have been observed in the nab-paclitaxel/durvalumab arm. 
All subjects in the nab-paclitaxel/CC-486 combination and nab-paclitaxel monotherapy arms 
will continue to be followed for OS for at least 12 months after the last subject is randomized to
either of these two arms or 120 PFS events have been observed between these two arms, 
whichever comes later. All subjects in the nab-paclitaxel/durvalumab arm will be followed for 
OS for at least 12 months after the last subject is assigned to this arm.
The study milestones for the scenario that all 3 arms proceed to the end of the study are
summarized in the table below:
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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Study Milestone
Time from First Subject 
Randomized (Day 1)
First subject randomized to either the nab-paclitaxel/CC-486 and nab-
paclitaxel monotherapy arms (1:1 randomization ratio)
Day 1
Interim analysis for nab-paclitaxel/CC-486 vs. nab-paclitaxel 
monotherapy (~60 PFS events total)
~ 15 months
Addition of the nab-paclitaxel/durvalumab arm to the study; 
randomization in a 1:1:1 ratio to the nab-paclitaxel/CC-486, nab-
paclitaxel/durvalumab, and nab-paclitaxel arms begins.
~ 15 months
Last subject randomized to the nab-paclitaxel/CC-486 and nab-paclitaxel 
arms
~ 23 months
Assignment of all incoming subjects to the durvalumab arm begins.
~ 24 months
Final analysis for nab-paclitaxel/CC-486 vs. nab-paclitaxel (~120 PFS 
events total)
~25 months
Last subject assigned to the nab-paclitaxel/durvalumab arm
~ 28 months
Interim analysis for nab-paclitaxel/durvalumab vs. nab-paclitaxel (~30 
PFS events from nab-paclitaxel/durvalumab, ≥60 from nab-paclitaxel 
monotherapy)
~28 months
Final analysis for nab-paclitaxel/durvalumab vs. nab-paclitaxel (~50 PFS 
events have been observed in the nab-paclitaxel/durvalumab arm)
~ 31 months
End of OS Follow-up for subjects in nab-paclitaxel/CC-486 and nab-
paclitaxel arms
~ 35 months
End of OS Follow-up for durvalumab subjects
~40 months
10.4.
Background and Demographic Characteristics
The baseline characteristics of all randomized/assigned subjects will be summarized. Subject’s 
age, height, weight, and baseline characteristics will be summarized using descriptive statistics, 
while gender, race and other categorical variables will be provided using frequency tabulations. 
Selected medical history data will be summarized using frequency tabulations by system organ 
class and preferred term.
10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both Treatment 
and Follow-up Periods. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
10.6.
Efficacy Analysis
10.6.1.
Primary Efficacy Endpoints 
The primary efficacy endpoint is progression-free survival, which is defined as the time from the 
date of randomization/treatment assignment to the date of disease progression or death (any 
cause) on or prior to the data cutoff date for analyses, whichever occurs first, based on the 
Investigator’s assessment of the data from CT scans using RECIST 1.1 guidelines. Baseline 
tumor measurements will be determined from the radiologic evaluation performed within 28 
days before the start of study therapy. 
Subjects who do not have disease progression and are alive as of the data cutoff date for the 
statistical analysis will be censored at the date of the last radiologic assessment prior to the data 
cutoff date.  Similarly, subjects who discontinue from the study prior to disease progression or 
death will be censored at the date of the last radiologic assessment prior to the data cutoff date.  
In the event that a new anticancer treatment occurs prior to documented progression, the subject 
will be censored at the date of the last radiologic assessment where the subject was documented 
to be progression-free prior to the new anticancer treatment. Subjects with a single missing 
radiologic assessment prior to a visit with documented disease progression (or death) will be 
analyzed as a PFS event at the date of the radiologic assessment that shows progression or death 
(whichever is earlier). Subjects with two or more missing radiologic assessments prior to a visit 
with documented disease progression (or death) will be censored at the date of the last radiologic 
assessment where the subject was documented to be progression-free prior to the first of the two 
missing visits.  Subjects who are alive and drop out early without any post baseline radiologic 
tumor assessment will be censored on the date of randomization/treatment assignment. 
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% CI) for each treatment arm. The Kaplan-Meier curve for PFS will 
be presented graphically for each treatment arm. The relative treatment effect between the 
combination and monotherapy arms on PFS will be estimated by the hazard ratio (HR) and the 
associated two-sided 95% CIs using the stratified Cox proportional hazard model with ECOG 
performance status (0 versus 1), gender (males versus females), and smoker (yes versus no) as 
the stratification factors, given the number of events in each cell is adequate. No statistical 
inferential tests will be performed.
To assess the impact on PFS of radiologic assessments not occurring at the regularly scheduled 
assessment times, the frequency of these unscheduled/off-scheduled assessments will be 
presented for each treatment arm. In addition, confirmatory and sensitivity analyses may be 
performed to further assess the impact of missed radiologic assessments. An additional analysis 
of PFS, where death or new treatment will be considered as an event, will be conducted to 
address the impact of next line therapy. 
To explore the effect of treatment post initial progression, PFS defined by irRECIST criteria may 
be estimated for the subjects in the nab-paclitaxel/durvalumab arm.  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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10.6.2.
Secondary Efficacy Endpoints
10.6.2.1.
Disease Control Rate
Disease control rate is defined as the percent of subjects who have a radiologic complete 
response, partial response, or stable disease according to RECIST 1.1 guidelines, as determined 
by the Investigator.
Disease control rate for each treatment arm will be summarized by the observed DCR rate and 
the associated two-sided 95% CI. The relative treatment effect will be summarized by the 
absolute difference and ratio of the response rates and the associated two-sided 95% CI.
10.6.2.2.
Overall Survival
Overall survival is defined as the time between randomization/treatment assignment and death. 
All deaths, regardless of the cause of death, will be included. All subjects who are lost to follow-
up prior to the end of the study or who are withdrawn from the study will be censored at the time 
of last contact. Subjects who are still receiving treatment as of the data cutoff date will be 
censored at the cutoff date. Overall survival will be analyzed in a similar manner as that for PFS.
10.6.2.3.
Overall Response Rate 
Overall response rate is defined as the percent of subjects who have a radiologic complete or 
partial response according to RECIST 1.1 guidelines determined by the Investigator.  
Overall response rate will be assessed using the same statistical methods as those for the DCR 
endpoint.
10.6.3.
Exploratory Endpoints
10.6.3.1.
HealthCare Utilization 
Healthcare utilization will be summarized by treatment. Additional analyses will be described in 
detail in the SAP.
10.6.3.2.
Quality of Life Questionnaires
The score or VAS value and the corresponding change from baseline at each timepoint will be 
summarized by treatment for the EQ-5D-5L, EORTC QLQ C30 and LCSS questionnaires. 
Additional analyses will be described in detail in the SAP. 
10.6.3.3.
Biomarker, Tumor Characteristics, and Genomic Analyses 
Statistical analysis of the biomarkers, tumor characteristics, and genomic correlates will be 
described in a SAP separate from that described above.
10.6.3.4.
Anti-tumor Activity and PD-L1 Expression (nab-Paclitaxel/Durvalumab Arm)
An exploratory analysis of PFS and DCR using investigator’s assessments based according to 
irRECIST criteria, and their association with PD-L1 expression will be performed for subjects in 
the nab-paclitaxel/durvalumab arm.  
&(/*(1(35235,(7$5<,1)250$7,21
entnt and dea
and dea
are lost to 
are lost to
censored a
censored
utoff date w
toff da
lar 
ar ma
manner
nne
ho ha
ho have
v a ra
a r
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rmined by
statist
statistical
ical
marized by t
rized by 
Questionn
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e and the c
e and the c
ment f
ent for th
or t
f
ses will be
ses will be
Biomarker
Biomarker
cal analysis
cal analysis
ribed in a S
ribed in a 
10.6.3.4.
0.6.3.4.
n ex


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
74
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
10.7.
Safety Analysis
The treated population, which includes all subjects who receive at least one dose of IP, will be 
the analysis population for all safety analyses.
The safety/tolerability of the treatment arms will be monitored through continuous reporting and 
evaluated by adverse events and serious adverse events, and incidence of subjects experiencing 
dose modifications, dose interruptions, and/or premature discontinuation of IP.
10.7.1.
Adverse Events
TEAEs will be defined as any AE or SAE occurring or worsening on or after the day of the first 
dose of the IP through 28 days after the last dose of IP for the monotherapy arm and the nab-
paclitaxel/CC-486 combination arms, or 90 days after last dose of IP in the nab-
paclitaxel/durvalumab combination arm.  In addition, any serious AE with an onset date more 
than 28 days after the last dose of IP that is assessed by the Investigator as related to IP will be 
considered a TEAE. TEAEs occurring up to 28 days after the last dose of IP will be summarized. 
In addition, for the nab-paclitaxel/durvalumab arm, AEs with an onset from 29 days up to 90 
days after the last dose of IP will be summarized separately.
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA). The severity of AEs will be graded based on NCI CTCAE, Version 4.0; 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Treatment-emergent adverse events, Grade 3 or higher TEAEs, serious AEs, TEAEs leading to 
dose reduction, and dose interruption, TEAEs leading to treatment discontinuation, and TEAEs 
with an outcome of death will be summarized per treatment arms by MedDRA system organ 
class and preferred terms. 
Adverse events of special interest relevant to the nab-paclitaxel/CC-486 combination, nab-
paclitaxel/durvalumab combination, and nab-paclitaxel monotherapy regimens observed in 
previous studies in a similar population may be identified and summarized by worst NCI 
CTCAE grade, and MedDRA preferred terms.
By-subject listings will be provided for all relevant safety data. Graphical displays and figures 
will be provided where useful to assist in the interpretation of results.
10.7.2.
Laboratory Assessments
Treatment group differences in each laboratory parameter with respect to the NCI CTCAE 
grades will be summarized by the frequency distribution of subjects with the AE grades.  
All laboratory parameters will be summarized by descriptive statistics within each treatment arm, 
as appropriate. 
10.7.3.
IP Exposure
The extent of exposure to the IPs will be assessed based on the descriptive statistics on the 
number of cycles and IP doses administered, cumulative dose, average dose intensity, and 
percentage of protocol dose administered.  The incidences of CC-486, nab-paclitaxel, and 
durvalumab dose reductions (although not expected for durvalumab) and dose interruptions will 
be summarized by treatment arm.  
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he firstst
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set date mo
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ed to IP
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rom 29 day
29 d
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or Regu
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CTCAE, V
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TEAEs, se
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0.7.3.
0.7.3.
I
The ext
The ex
b


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
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Confidential and Proprietary
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10.8.
Study Therapy Termination
Reasons for stopping study therapy will be presented in listings and summarized by frequency of 
occurrence and corresponding percentage of occurrence.
10.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the IP
through 28 days post last dose of the IP will be summarized by frequency of occurrence and 
corresponding percentage by cause of death per period (during treatment or follow-up). In 
addition, deaths that occur from 29 to 90 days post last dose will be summarized in a similar 
manner for the nab-paclitaxel/durvalumab combination therapy arm.
10.10.
Interim Analysis
One nonbinding interim analysis for PFS with an early stopping rule for futility will be 
conducted when approximately 60 events have been observed between the nab-paclitaxel/CC-
486 combination and nab-paclitaxel monotherapy arms. The nab-paclitaxel/CC-486 combination 
arm may be stopped early for futility if the observed HR is ≥1.10 given the assumed number of 
PFS events above, and/or if recommended by the DMC based on the safety profile of this 
combination regimen.   
An additional interim analysis for futility with the PFS endpoint between the nab-
paclitaxel/durvalumab combination therapy and nab-paclitaxel monotherapy arms will be 
conducted when approximately 30 PFS have been observed in the nab-paclitaxel/durvalumab 
combination arm. This is similar to approximately half of the number of events that are planned 
for the interim analysis between the nab-paclitaxel/CC-486 combination and nab-paclitaxel 
monotherapy arms mentioned above. At this time point, it is projected that approximately ≥ 60 
PFS events will have been observed in the nab-paclitaxel monotherapy arm. The nab-
paclitaxel/durvalumab combination therapy arm may be stopped early for futility if the observed 
HR is ≥ 1.10, and/or if recommended by the DMC based on the safety profile of this 
combination regimen. Should this occur, enrollment in the study may discontinue.   
10.11.
Data Monitoring Committee
An independent DMC will be established with the responsibilities for safeguarding the interests 
of study subjects and monitoring the overall conduct of the study. Final recommendations of the 
DMC will reflect the judgment of the DMC members and will be considered advisory in nature 
to the Sponsor. The decision to implement the recommendations of the DMC will be made by 
the Sponsor, following consultation with the coordinating Investigator and Steering Committee.
Operational details for the DMC will be detailed in the DMC charter. 
10.12.
Scientific Steering Committee
The conduct of this study will be overseen by a Steering Committee. The Steering Committee 
will serve in an advisory capacity to the Sponsor.
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0.12.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
76
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the eCRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of NSCLC will not require reporting as 
an adverse event. However, signs and symptoms (events) related to disease progression may be 
reported as adverse events. If reported, events of disease progression for NSCLC (including 
deaths due to disease progression for indications that are considered to be fatal) will be assessed 
as expected adverse events and will not be reported as expedited safety reports to regulatory 
authorities.
Abuse, withdrawal, sensitivity or toxicity to an investigational product should be reported as an 
AE. Overdose, accidental or intentional, whether or not it is associated with an AE should be 
reported as an AE. (See Section 8.8 for the definition of overdose.) Any sequela of an accidental 
or intentional overdose of an investigational product should be reported as an AE on the AE 
CRF. If the sequela of an overdose is an SAE, then the sequela must be reported on an SAE 
report form and on the AE CRF. The overdose resulting in the SAE should be identified as the 
cause of the event on the SAE report form and CRF but should not be reported as an SAE itself.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for nab-paclitaxel,
CC-486 or durvalumab overdose. Actual treatment should depend on the severity of the clinical 
situation and the judgment and experience of the treating physician.
All subjects will be monitored for AEs during the study. Assessments may include monitoring of 
any or all of the following parameters: the subject’s clinical symptoms, laboratory, pathological, 
radiological or surgical findings, physical examination findings, or findings from other 
appropriate tests and procedures.
All AEs will be recorded by the Investigator from the time the subject signs informed consent to
28 days after the last dose of IP for the monotherapy and CC-486 combination arms or to 90 days 
for the durvalumab combination arm, and those SAEs made known to the Investigator at any 
time thereafter that are suspected of being related to IP. AEs and serious adverse events (SAEs) 
will be recorded on the AE page of the eCRF and in the subject’s source documents. All SAEs 
must be reported to Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the 
event by facsimile, or other appropriate method, using the SAE Report Form, or approved 
equivalent form.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
77
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11.2.
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to: 
11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
!
Results in death;
!
Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the eCRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
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Celgene Corporation
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ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
!
An elective treatment of or an elective procedure for a pre-existing condition 
unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to IP, action taken regarding IP, and outcome.
11.2.2.
Severity / Intensity
For both AEs and SAEs, the Investigator must assess the severity/intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current active minor version of NCI CTCAE, Version 4.0
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Adverse events that are not defined in the NCI CTCAE should be evaluated for severity/intensity 
according to the following scale:
!
Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required
!
Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required
!
Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible
!
Grade 4 = Life threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable
!
Grade 5 = Death – the event results in death
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.
Seriousness, not severity, serves as a guide for defining regulatory obligations.
11.2.3.
Causality 
The Investigator must determine the relationship between the administration of IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
Means a causal relationship of the adverse event to IP
administration is unlikely or remote, or other medications, 
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therapeutic interventions, or underlying conditions provide a 
sufficient explanation for the observed event.
Suspected:
Means there is a reasonable possibility that the administration 
of IP caused the adverse event.  ‘Reasonable possibility’ means 
there is evidence to suggest a causal relationship between the IP
and the adverse event.
Causality should be assessed and provided for every AE/SAE based on currently available 
information.  Causality is to be reassessed and provided as additional information becomes 
available.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP
that has not been manufactured or provided by the Sponsor, please provide the name of the 
manufacturer when reporting the event.
11.2.4.
Duration
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event.
11.2.5.
Action Taken
The Investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(eg, discontinuation or reduction of IP, as appropriate) and report if concomitant and/or 
additional treatments were given for the event. 
11.2.6.
Outcome
The Investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered or death (due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or
!
is judged to be of significant clinical importance by the Investigator.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF. If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE.
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
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11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
11.4.1.
Females of Childbearing Potential
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on IP, or within 3 months of the 
subject’s last dose of IP, are considered immediately reportable events. IP is to be discontinued 
immediately. The pregnancy, suspected pregnancy, or positive pregnancy test must be reported 
to Celgene Drug Safety immediately by facsimile, or other appropriate method, using the 
Pregnancy Initial Report Form, or approved equivalent form. The female subject should be 
referred to an obstetrician-gynecologist or another appropriate healthcare professional for further 
evaluation.
The Investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the Investigator
should report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate 
method, within 24 hours of the Investigator’s knowledge of the event using the SAE Report 
Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the Investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the Investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving IP or within 
6 months of the last dose of IP, the male subject taking IP should notify the Investigator, and the 
pregnant female partner should be advised to call her healthcare provider immediately. If the 
male subject is receiving IP, the IP may need to be discontinued in the male subject, but may be 
resumed later at the discretion of the Investigator and medical monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The Investigator is required to ensure that the data on these forms are accurate and consistent.
This requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent to at least 28 days after the last dose of IP for 
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
81
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the monotherapy and CC-486 combination arms or 90 days after the last dose of IP for the 
durvalumab combination arm) and those made known to the Investigator at any time thereafter 
that are suspected of being related to IP. SAEs occurring prior to treatment (after signing the 
ICF) will be captured.
The SAE report should provide a detailed description of the SAE and include a concise summary
of hospital records and other relevant documents. If a subject died and an autopsy has been 
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available. Any follow-up data will be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety.
Where required by local legislation, the Investigator is responsible for informing the Independent 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The Investigator must keep copies of all SAE 
information on file including correspondence with the Sponsor and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than five (5) business 
days. Urgent queries (eg, missing causality assessment) may be handled by phone.
11.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to nab-paclitaxel, CC-486 or durvalumab based on the
Investigator Brochures of the respective IPs.
In the US, all suspected unexpected serious adverse reactions (SUSARs) will be reported in an 
expedited manner in accordance with 21 CFR 312.32.
For countries within the European Economic Area (EEA), the Sponsor or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 
presentation of adverse reaction reports arising from clinical trials on investigational products for 
human use (ENTR/CT3) and also in accordance with country-specific requirements.
The Sponsor or its authorized representative shall notify the Investigator of the following 
information: 
!
Any AE suspected of being related to the use of IP in this study or in other studies
that is both serious and unexpected (ie, SUSAR);
!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
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82
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with the Sponsor and the IRB/EC. (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form/Completion Guidelines or to the Pregnancy Report Form/Completion Guidelines.
11.7.
Definition of Adverse Events of Special Interest
An adverse event of special interest (AESI) is one of scientific and medical interest specific to 
the understanding of the IP and may require close monitoring and rapid communication by the 
Investigator to the Sponsor. An AESI may be serious or nonserious. The rapid reporting of 
AESIs allows ongoing surveillance of these events in order to characterize and understand them 
in association with the use of this IP. Further information on risks (eg, presenting symptoms) can 
be found in the current version of the Investigator Brochure, including guidelines for their 
evaluation and treatment.
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Celgene Corporation
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12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the IP:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent
!
Death
!
Lost to follow-up
!
Protocol violation
The reason for discontinuation should be recorded in the eCRF and in the source documents.
The decision to discontinue a subject remains the responsibility of the treating physician, which
will not be delayed or refused by the Sponsor. However, prior to discontinuing a subject, the
Investigator may contact the Medical Monitor and forward appropriate supporting documents for 
review and discussion.
All subjects discontinued from IP for any reason will have a treatment discontinuation visit at the 
time of discontinuation and should undergo treatment discontinuation procedures.
All subjects discontinued from IP will be followed for a period of 28 days after last dose of IP
for the monotherapy and CC-486 combination arms or 90 days after the last dose of IP for the 
durvalumab combination arm for the collection of AEs.
Additionally subjects who withdraw from or discontinue treatment should be followed for 
progressive disease (if applicable), survival and any new anticancer therapy given.
12.2.
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
study:
!
Withdrawal of consent
!
Death
!
Lost to follow-up
The following events may be considered sufficient reasons for discontinuing a subject from the 
study:
!
Adverse events(s)
!
Protocol violation
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. The Investigator must notify the Medical Monitor immediately when a subject has 
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Celgene Corporation
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84
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been discontinued/withdrawn due to an AE (any unacceptable toxicity). All subjects who are 
withdrawn from the study should complete all protocol-required evaluations scheduled for early 
termination at the time of withdrawal.
Since follow-up of subjects who discontinue prematurely is of particular importance, every 
attempt should be made to collect all survival information and NSCLC treatment/therapy, unless 
the subject has specifically withdrawn consent from further follow-up. The Investigator must 
make every effort to obtain minimal information regarding the subject’s survival status before 
determining that the subject is lost to follow-up.
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.
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Celgene Corporation
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85
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13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page). This global 
Emergency Call Center is available 24 hours a day and 7 days a week. The representatives are 
responsible for obtaining your call-back information and contacting the on call Sponsor/Contract 
Research Organization (CRO) Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
13.2.
Emergency Identification of Investigational Products
This is an open-label study; therefore, IP will be identified on the package labeling. 
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Protocol ABI-007-NSCL-006
Celgene Corporation
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ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that the Sponsor, its authorized 
representative, and Investigator abide by Good Clinical Practice (GCP), as described in 
International Conference on Harmonization (ICH) Guideline E6 and in accordance with the 
general ethical principles outlined in the Declaration of Helsinki. The study will receive approval 
from an IRB/EC prior to commencement. The Investigator will conduct all aspects of this study 
in accordance with applicable national, state, and local laws of the pertinent regulatory 
authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. The Sponsor staff or its authorized representative will evaluate and approve 
all Investigators who in turn will select their staff.
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions. 
The Investigator should maintain a list of sub-Investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The Investigator is responsible for keeping a record of all subjects who sign an ICF and are 
screened for entry into the study. Subjects who fail screening must have the reason(s) recorded in 
the subject’s source documents.
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The Investigator must ensure timely and accurate completion of eCRFs and queries.
The information contained in the protocol and amendments (with the exception of the 
information provided by the Sponsor on public registry websites) is considered the Sponsor’s 
confidential information. Only information that is previously disclosed by the Sponsor on a 
public registry website may be freely disclosed by the Investigator or its institution, or as 
outlined in the Clinical Trial Agreement. The Sponsor’s protocol, amendment and IB 
information is not to be made publicly available (for example on the Investigator’s or their 
institution’s website) without express written approval from the Sponsor. Information proposed 
for posting on the Investigator’s or their institution’s website must be submitted to the Sponsor
for review and approval, providing at least 5 business days for review. 
At the time results of this study are made available to the public the Sponsor will provide 
Investigators with a summary of the results that is written for the lay person. The Investigator is 
responsible for sharing these results with the subject and/or their caregiver as agreed by the 
subject.
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14.3.
Subject Information and Informed Consent
The Investigator must obtain informed consent of the subject and/or the subject’s legal 
representative prior to any study-related procedures.
Documentation that informed consent occurred prior to the subject’s entry into the study and of 
the informed consent process should be recorded in the subject’s source documents including the 
date. The original ICF signed and dated by the subject and by the person consenting the subject
prior to the subject’s entry into the study, must be maintained in the Investigator’s study files and 
a copy given to the subject. In addition, if a protocol is amended and it impacts the content of the 
informed consent, the ICF must be revised. Subjects participating in the study when the amended 
protocol is implemented must be re-consented with the revised version of the ICF. The revised 
ICF signed and dated by the subject and by the person consenting the subject must be maintained 
in the Investigator’s study files and a copy given to the subject. Subjects in the nab-
paclitaxel/durvalumab arm who continue treatment beyond disease progression per RECIST 1.1 
will be requested to sign a consent form at time of progression and prior to treatment 
continuation.
14.4.
Confidentiality
The Sponsor affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). The Sponsor
requires the Investigator to permit the Sponsor's representatives and, when necessary, 
representatives from regulatory authorities, to review and/or copy any medical records relevant 
to the study in accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the Investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Sponsor’s Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the Investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
88
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
IP can only be supplied to an Investigator by the Sponsor or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
the Sponsor or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB/EC should mention the protocol title, number, amendment number 
(if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by the Sponsor and 
the IRB/EC prior to use.
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
The Sponsor reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the Investigator or the Sponsor has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
89
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and distribution of the IP are complete, accurate, filed and retained. Examples of source 
documents include: hospital records; clinic and office charts; laboratory notes; memoranda; 
subject’s diaries or evaluation checklists; dispensing records; recorded data from automated 
instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy and the laboratories, as well 
as copies of CRFs or CD-ROM.
15.2.
Data Management
Data will be collected via eCRF and entered into the clinical database per the Sponsor’s Standard 
Operating Procedures (SOPs). This data will be electronically verified through use of 
programmed edit checks specified by the clinical team. Discrepancies in the data will be brought 
to the attention of the clinical team, and investigational site personnel, if necessary. Resolutions 
to these issues will be reflected in the database. An audit trail within the system will track all 
changes made to the data.
15.3.
Record Retention
Essential documents must be retained by the Investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IP. The Investigator must retain these 
documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the Investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the Investigator, Sponsor, and their authorized 
representative(s);
!
List of sub-Investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of CRFs (if paper) and of documentation of corrections for all subjects;
!
IP accountability records;
!
Record of any body fluids or tissue samples retained;
es, as well
s, as wel
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ubjects;
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
90
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
!
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The Investigator must notify the Sponsor if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.
The Investigator must obtain approval in writing from the Sponsor prior to destruction of any 
records. If the Investigator is unable to meet this obligation, the Investigator must ask the 
Sponsor for permission to make alternative arrangements. Details of these arrangements should 
be documented. 
All study documents should be made available if required by relevant health authorities. The 
Investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
91
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
16.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by the Sponsor or its authorized 
representative for compliance with applicable government regulations with respect to current 
GCP and standard operating procedures.
16.1.
Study Monitoring and Source Data Verification
The Sponsor ensures that appropriate monitoring procedures are performed before, during and 
after the study. All aspects of the study are reviewed with the Investigator and the staff at a study 
initiation visit and/or at an Investigator meeting. Prior to enrolling subjects into the study, a 
Sponsor representative or designee will review the protocol, eCRFs, procedures for obtaining 
informed consent, record keeping, and reporting of AEs/SAEs with the Investigator. Monitoring 
will include on-site visits with the Investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, IP 
storage area, eCRFs, subject’s source documents, and all other study documentation will be
inspected/reviewed by the Sponsor representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the eCRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff. Any necessary 
corrections will be made directly to the eCRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within the Sponsor. Representatives of this unit will conduct audits of clinical 
research activities in accordance with the Sponsor’s SOPs to evaluate compliance with Good 
Clinical Practice guidelines and regulations.
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, eCRFs and applicable supporting records of subject participation for audits 
and inspections by IRB/IECs, regulatory authorities (eg, FDA, European Medicines Agency 
[EMA], Health Canada) and company authorized representatives. The Investigator should make 
every effort to be available for the audits and/or inspections. If the Investigator is contacted by 
any regulatory authority regarding an inspection, he/she should contact the Sponsor immediately.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
92
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
17.
PUBLICATIONS
As described in Section 14.2, all protocol- and amendment-related information, with the 
exception of the information provided by the Sponsor on public registry websites, is considered 
Sponsor’s confidential information and is not to be used in any publications. The Sponsor
protocol-related information proposed for use in a publication must be submitted to the Sponsor
for review and approval, and should not be utilized in a publication without express written 
approval from the Sponsor, or as described in the Clinical Trial Agreement. 
The Sponsor will ensure sponsored studies are considered for publication in the scientific 
literature in a peer-reviewed journal, irrespective of the results. At a minimum, this applies to 
results from all Phase 3 clinical studies, and any other study results of significant medical 
importance. This also includes results relating to investigational medicines whose development 
programs have been discontinued. 
Study results may also be presented at one or more medical congresses, and may be used for 
scientific exchange and teaching purposes. Additionally, this study and its results may be 
submitted for inclusion in all appropriate health authority study registries, as well as publication 
on health authority study registry websites, as required by local health authority regulations. 
Eligibility for external authorship, as well as selection of first authorship, will be based on  
several considerations, including, but not limited to, contribution to protocol development, study 
recruitment, data quality, participation in data analysis, participation in study steering committee 
(when applicable) and contribution to abstract, presentation and/or publication development.
plies to
plies to
edical
edical
e developm
e developm
nd may
nd may be 
b
its resul
ts resul
i
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healt
alth autho
uth
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t authorsh
ibution to p
ibution to p
, participati
 participat
entation an
entation a


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
93
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
18.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
95
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
96
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
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Pang D, Kocherginsky M, Krausz T, Kim SY,  Conzen SD. Dexamethasone decreases xenograft 
response to Paclitaxel through inhibition of tumor cell apoptosis. Cancer Biol Ther. 
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Reck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowski M, et al. Docetaxel plus 
nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung 
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2014a Feb;15(2):143-55.
Reck M, Popat S, Reinmuth N, De Ruysscher D, Kerr KM, Peters S; ESMO Guidelines Working 
Group. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for 
diagnosis, treatment and follow-up. Ann Oncol. 2014 Sep;25 Suppl 3:iii27-39 doi: 
10.1093/annonc/mdu199. Epub 2014 Aug 11.
Rizvi NA, Riely GJ, Azzoli CG, Miller VA, Ng KK, Fiore J, et al. Phase I/II trial of weekly 
intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with Stage IV 
non-small-cell lung cancer. J Clin Oncol 2008;26(4):639-43.
Rizvi N, Gray J, Ballas M, Jayawardene D, Stockman P, Powderly JD. A Phase 2, non-
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Saxena A, Christos PJ, Cagney JM, et al. Nanoparticle albumin-bound paclitaxel (NabP) as a 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
97
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Socinski MA, Schell MJ, Bakri K, Peterman A, Lee JH, Unger P, et al. Second-line, low-dose, 
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Yasuda K, Igishi T, Kawasaki Y, Kato K, Matsumoto S, Katayama S, et al. Phase II study of 
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Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G. Mechanism of action of conventional and 
targeted anticancer therapies: reinstating immunosurveillance. Immunity 2013;39(1),74-88.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
98
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
19.
APPENDICES
Appendix A: ECOG Performance Status Score
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5
Dead
Oken, 1982.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
99
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Appendix B: Recommendations for Management of Treatment-Induced 
Diarrhea
The following published guidelines (Benson, 2004) were modified in order to be consistent with 
the clinical study protocol.


('06'RF1XPEHU
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Protocol ABI-007-NSCL-006
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ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Appendix C: Treatment Modification and Toxicity Management for nab-
Paclitaxel /Durvalumab arm
General guidelines regarding treatment modification for MEDI4736 and/or nab-paclitaxel are 
provided below for immune-related AEs (Table C1), infusion-related reactions (Table C2), and
non-immune-mediated reactions (Table C3).
These guidelines apply to AEs considered causally related to the durvalumab containing regimen 
by the reporting Investigator. Treatment modifications referring to “study regimen” would apply 
to both nab-paclitaxel and durvalumab unless AEs are not considered causally related to nab-
paclitaxel by the reporting Investigator. In that case nab-paclitaxel treatment may be continued 
alone if deemed beneficial to the subject per Investigator’s assessment.
Table C1:
Treatment Modification and Toxicity Management Guidelines for Immune-
related Adverse Events
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
Immune-related AEs 
(overall 
management for 
toxicities not noted 
below)
Drug administration modifications 
of IP/study regimen will be made 
to manage potential immune-
related AEs based on severity of 
treatment-emergent toxicities 
graded per NCI CTCAE v4.03.
In addition to the criteria for 
permanent discontinuation of 
IP/regimen based on CTC 
Grade/severity (table below),
permanently discontinue IP/study 
regimen for the following 
conditions:
• Inability to reduce corticosteroid 
to a dose of ≤10 mg of prednisone 
per day (or equivalent) within 12 
weeks after last dose of IP/regimen
• Recurrence of a previously 
experienced Grade 3 treatment-
related AE following resumption 
of dosing.
It is recommended that 
management of ir AEs follow the 
guidelines presented in this table
- Subjects should be thoroughly 
evaluated to rule out any 
alternative etiology (eg,, disease 
progression, concomitant 
medications, infections, etc.)
- In the absence of a clear 
alternative etiology, all events 
should be considered potentially 
immune related.
- Symptomatic and topical 
therapy should be considered for 
low-grade (Grade 1 or 2, unless 
otherwise specified)
events
- For persistent (greater than 3 to 
5 days) low-grade (Grade 2) or 
severe (Grade ≥3) events 
promptly start prednisone
PO 1-2mg/kg/day or IV 
equivalent
- If symptoms recur or worsen 
during corticosteroid tapering 28 
days of taper), increase the 
corticosteroid dose (prednisone 
dose [eg, up to 2-4mg/kg/day or 
IV
equivalent]) until stabilization or 
improvement of symptoms, then 
resume corticosteroid tapering at 
a slower rate (> 28 days of taper)
- More potent 
Grade 1
No dose modification
Grade 2
Hold IP/study regimen dose until
Grade 2 resolution to ≤ Grade 1
• If toxicity worsens then treat as 
Grade 3 or Grade 4
• If toxicity improves to baseline 
then treat at next scheduled 
treatment date IP/study treatment 
can be resumed at the next 
scheduled dose once event  
stabilizes to Grade ≤1 and 5-7 days 
have passed after completion of 
steroid taper
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
101
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
Subjects with endocrinopathies 
who may require prolonged or 
continued steroid replacement can 
be retreated with IP/study regimen 
on the following conditions: 
1) the event stabilizes and is
controlled, 
2) the subject is clinically stable as 
per Investigator or treating 
physician’s clinical judgment, and 
3) doses of prednisone are at less 
than or equal to 10mg/day or 
equivalent.
immunosuppressives such as 
TNF inhibitors (eg, infliximab) 
– (also refer to the individual 
sections of the immune related 
adverse event for specific type 
of
immunosuppressive) should be 
considered for events not 
responding to systemic 
steroids.
- Discontinuation of IP is not 
mandated for Grade 3 / 4 
inflammatory reactions attributed 
to local tumor response (eg,
inflammatory reaction at sites of
metastatic disease, lymph nodes 
etc.). Continuation of IP in this 
situation should be based upon a 
benefit/risk analysis for that 
subject
Grade 3
Depending on the individual 
toxicity, may permanently 
discontinue IP/study regimen. 
Please refer to guidelines below
Grade 4
Permanently discontinue IP/study
regimen
Note: For Grade 3 and above asymptomatic amylase or 
lipase levels hold IP/regimen and if complete work up 
shows no evidence of pancreatitis, may continue or 
resume IP/regimen
Pneumonitis/ILD
Any grade
- Monitor subjects for signs and 
symptoms of pneumonitis
or ILD (new onset or worsening 
shortness of breath or cough). 
Subjects should be evaluated 
with imaging and pulmonary 
function tests including other 
diagnostic procedures as 
described below
- Initial work-up may include 
clinical evaluation,
monitoring of oxygenation via 
pulse oximetry (resting
and exertion), laboratory work-
up and high-resolution
CT scan.
Grade 1 
(asymptomatic,
clinical or
diagnostic
observations only,
intervention not 
indicated)
No dose modification required. 
However,
consider holding IP/study regimen 
dosing as clinically appropriate and 
during diagnostic work-up for 
other etiologies
For Grade 1 (radiographic 
changes only)
- Monitor and closely follow up 
in 2-4 days for clinical
symptoms, pulse oximetry 
(resting and exertion) and
laboratory work-up and then as 
clinically indicated
- Consider pulmonary and 
infectious disease consult
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
102
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
Grade 2
(symptomatic,
medical
intervention
indicated, limiting
instrumental 
ADL)
• Hold IP/study regimen dose until 
Grade 2 resolution to ≤ Grade 1
• If toxicity worsens then treat as 
Grade 3 or Grade 4
• If toxicity improves to baseline 
then the decision to reinitiate 
IP/regimen at next scheduled 
treatment date will be based upon 
treating physician’s clinical
judgment.
• IP/study treatment can be 
resumed at the next scheduled dose 
once event stabilizes to Grade ≤1 
and 5-7 days have passed after 
completion of steroid taper
For Grade 2 (mild to moderate 
new symptoms)
- Monitor symptoms daily and 
consider hospitalization
- Promptly start systemic steroids 
(eg, prednisone 1-
2 mg/kg/day or IV equivalent)
- Reimaging as clinically 
indicated
- If no improvement within 3-5 
days, additional workup
should be considered and prompt 
treatment with IV
methylprednisolone 2-4 
mg/kg/day started
- If still no improvement within 
3-5 days despite IV
methylprednisone at 2-
4/g/kg/day, promptly start
immunosuppressive therapy such 
as TNF inhibitors (eg,
infliximab at 5mg/kg every 2 
weeks). Caution: Important to 
rule out sepsis and refer to 
infliximab label for general
guidance before using infliximab
- Once improving, gradually 
taper steroids over ≥4 weeks
and consider prophylactic 
antibiotics, antifungal or anti
PCP treatment (refer to current 
NCCN guidelines for treatment 
of cancer-related infections 
(Category 2B recommendation)2
- Consider pulmonary and 
infectious disease consult
- Consider as necessary 
discussing with study physician
Grade 3 or 4 
(Grade 3: severe
symptoms; 
limiting
self-care ADL;
oxygen indicated;
Grade 4: life
threatening
Permanently discontinue IP/study
regimen
For Grade 3 or 4 (severe or new 
symptoms, new/worsening
hypoxia, life threatening
- Promptly initiate empiric IV 
methylprednisolone 1 to
4 mg/kg/day or equivalent
- Obtain pulmonary and 
infectious disease consult
- Hospitalize the subject
2 ASCO Educational Book 2015. Michael Postow MD. “Managing Immune Checkpoint Blocking Antibody Side 
Effects”
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Grade 3
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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103
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
respiratory
compromise, 
urgent
intervention
indicated [eg,
tracheostomy or 
intubation])
- Supportive Care (oxygen, etc.)
- If no improvement within 3-5 
days, additional workup should 
be considered and prompt 
treatment with additional 
immunosuppressive therapy such 
as TNF inhibitors (eg, infliximab 
at 5mg/kg every 2 weeks dose)
started. Caution: rule out sepsis 
and refer to infliximab label for 
general guidance before using 
infliximab
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and in 
particular, anti PCP treatment 
(please refer to current NCCN 
guidelines for treatment of 
cancer-related infections 
(Category 2B recommendation)3
Diarrhea/
enterocolitis
Any grade
- Monitor for symptoms that may 
be related to diarrhea/
enterocolitis (abdominal pain, 
cramping, or changes in bowel 
habits such as increased 
frequency over baseline or blood 
in stool) or related to bowel 
perforation (such as sepsis, 
peritoneal signs and ileus)
- Subjects should be thoroughly 
evaluated to rule out any
alternative etiology (eg, disease 
progression, other medications, 
infections including testing for 
clostridium difficile toxin, etc.)
- Steroids should be considered 
in the absence of clear
alternative etiology, even for low 
grade events, in order to prevent 
potential progression to higher 
grade event
- Use analgesics carefully; they 
can mask symptoms of
perforation and peritonitis
3 ASCO Educational Book 2015. Michael Postow MD. “Managing Immune Checkpoint Blocking Antibody Side 
Effects”
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
104
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
Grade 1 diarrhea
(stool frequency 
of <4 over 
baseline per day)
No dose modification
For Grade 1 diarrhea :
- Close monitoring for worsening 
symptoms
- Consider symptomatic 
treatment including hydration,
electrolyte replacement, dietary 
changes (eg, American
Dietetic Association colitis diet), 
and loperamide. Use of
probiotics as per treating 
physician’s clinical judgment.
Grade 2 diarrhea
(stool frequency 
of 4-6 over 
baseline per day)
• Hold IP/study regimen until 
resolution to ≤ Grade 1
• If toxicity worsens then treat as 
Grade 3 or Grade 4
• If toxicity improves to baseline 
then treat at next scheduled 
treatment date
• IP/study regimen can be resumed
at the next scheduled dose once 
event stabilizes to Grade ≤1 and 5-
7 days have passed after 
completion of steroid taper
For Grade 2 diarrhea:
- Consider symptomatic 
treatment including hydration,
electrolyte replacement, dietary 
changes (eg,eg, American
Dietetic Association colitis diet), 
and loperamide and/or
budesonide
- Promptly start prednisone 1 to 
2 mg/kg/day or IV equivalent
- If event is not responsive 
within 3-5 days or worsens
despite prednisone at 1-2 
mg/kg/day or IV equivalent, GI
consult should be obtained for 
consideration of further
workup such as imaging and/or 
colonoscopy to confirm
colitis and rule out perforation, 
and prompt treatment
with IV methylprednisolone 2-
4mg/kg/day started.
- If still no improvement within 
3-5 days despite 2 to
4 mg/kg IV methylprednisolone, 
promptly start 
immunosuppressives such as 
(infliximab at 5mg/kg once
every 2 weeks). Caution: 
important to rule out bowel
perforation and refer to 
infliximab label for general
guidance before using infliximab
- Consult study physician if no 
resolution to ≤ Grade 1 in
3-4 days
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
105
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
to current NCCN
guidelines for treatment of 
cancer-related infections
[Category 2B recommendation])4
Grade 3 or 4
Diarrhea
(Grade 3: stool
frequency of ≥7
over baseline per
day;
Grade 4: life
threatening
consequences)
Permanently discontinue IP/study
regimen
For Grade 3 or 4 diarrhea:
- Promptly initiate empiric IV 
methylprednisolone 2 to 4
mg/kg/day or equivalent
- Monitor stool frequency and 
volume and maintain hydration
- Urgent GI consult and imaging 
and/or colonoscopy as
appropriate
- If still no improvement within 
3-5 days of IV 
methylprednisolone 2 to 
4mg/kg/day or equivalent,
promptly start further 
immunosuppressives (eg,
infliximab at 5mg/kg once every 
2 weeks).
- Caution: ensure GI consult to 
rule out bowel perforation
and refer to infliximab label for 
general guidance before
using infliximab.
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN
guidelines for treatment of 
cancer-related infections
[Category 2B recommendation])
Hepatitis
(elevated LFTs)
Infliximab
should not be
used for
management of
immune related
hepatitis
Grade of liver
function test
elevation 
(CTCAE
version 4.03)
Any grade
Grade 1
(AST or ALT 
>ULN
to 3 times ULN
and/or TB > ULN 
to
No dose modification
If it worsens, treat as Grade 2 event
- Monitor and evaluate liver 
function test: AST, ALT, ALP
and total bilirubin
- Evaluate for alternative 
etiologies (eg, viral hepatitis,
disease progression, concomitant 
medications)
For Grade 1 AST or ALT and/or 
TB elevation
- Continue LFT monitoring per 
protocol
4 ASCO Educational Book 2015. Michael Postow MD. “Managing Immune Checkpoint Blocking Antibody Side 
Effects”
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
106
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
1.5 times ULN)
Grade 2
(AST or ALT > 3 
to 5 times ULN 
and/or TB >1.5-
3.0 times ULN)
Hold IP/study regimen dose until
Grade 2 resolution to ≤ Grade 1
• If toxicity worsens then treat as 
Grade 3 or Grade 4
• If improves to baseline then treat 
at next scheduled treatment date
IP/study regimen can be resumed 
at the next scheduled dose once 
event stabilizes to Grade ≤1 and 5-
7 days have passed after
completion of steroid taper
For Grade 2 AST or ALT and or 
TB elevation:
- Regular and frequent checking 
of LFTs (eg, every 1-2 days) 
until elevations of these are 
improving or resolved.
- If no resolution to ≤ Grade 1 in 
1-2 days, discuss with study 
physician.
- If event is persistent (> 3-5 
days) or worsens, promptly
start prednisone 1-2mg/kg/day or 
IV equivalent.
- If still no improvement within 
3-5 days despite 1- 2mg/kg/day 
of prednisone or IV equivalent, 
consider additional workup and 
prompt treatment with IV
methylprednisolone 2-
4mg/kg/day started.
- If still no improvement within 
3-5 days despite 2-
4mg/kg/day of IV 
methylprednisolone, promptly 
start immunosuppressives 
(mycophenolate mofetil). 
Discuss with study physician if 
mycophenolate mofetil is not
available. Infliximab should 
NOT be used.
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN guidelines for 
treatment of cancer-related 
infections [Category 2B 
recommendation])
Grade 3
(AST or ALT >5-
20 times ULN 
and/or TB > 3.0-
10
times ULN
For elevations in transaminases ≤ 8 
× ULN, or elevations in bilirubin ≤ 
5 × ULN:
• Hold IP/study regimen dose until 
resolution to ≤ Grade 1 or baseline
• Resume IP/study regimen 
administration at the next 
scheduled dose if elevations 
downgrade ≤ Grade 1 or baseline
within 14 days
• Permanently discontinue IP/study 
regimen if the elevations do not 
For Grade 3 or 4 AST or ALT 
and/or TB elevation:
- Promptly initiate empiric IV 
methylprednisolone at 1 to 4
mg/kg/day or equivalent
- If still no improvement within 
3-5 days despite 1 to
4 mg/kg/day methylprednisolone 
IV or equivalent, promptly start 
treatment with 
immunosuppressive
therapy (mycophenolate 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
107
ABI-007-NSCL-006 Amendment 4.0Final: 31May2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
downgrade
to ≤Grade 1 or baseline within 14 
days
• For elevations in transaminases > 
8 × ULN or elevations in bilirubin 
> 5 × ULN, discontinue IP/study 
regimen
• Permanently discontinue IP/study 
regimen for any case meeting Hy’s 
law criteria (ALT > 3x ULN + 
bilirubin > 2x
ULN without initial findings of 
cholestasis (ie,elevated alkaline 
P04) and in the absence of any 
alternative cause
5
mofetil). Discuss with study
physician if mycophenolate is 
not available. Infliximab
should NOT be used.
-Hepatology consult, abdominal 
workup, and imaging as
appropriate.
-Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN
guidelines for treatment of 
cancer-related infections
[Category 2B recommendation])
Grade 4
(AST or ALT > 
20 times ULN 
and/or TB > 10 
times ULN)
Permanently discontinue IP/study
regimen
Nephritis or renal
dysfunction
(elevated serum
creatinine)
Grade of elevated
serum creatinine
(CTCAE version
4.03)
Any grade
-Consult with nephrologist
-Monitor for signs and 
symptoms that may be related to
changes in renal function (eg,
routine urinalysis, elevated 
serum BUN and creatinine, 
decreased creatinine clearance, 
electrolyte imbalance, decrease 
in urine output, proteinuria, etc.)
-Subjects should be thoroughly 
evaluated to rule out any
alternative etiology (eg,disease 
progression, infections etc.)
-Steroids should be considered 
in the absence of clear
alternative etiology even for low 
grade events (Grade 2), in order 
to prevent potential progression 
to higher grade event
Grade 1 [serum
creatinine > 1-
1.5X baseline; > 
ULN to 1.5X  
ULN]
No dose modification
For Grade 1 elevated creatinine:
-Monitor serum creatinine 
weekly and any accompanying
symptom
If creatinine returns to 
baseline, resume its
regular monitoring per study 
protocol.
                                               
5FDA Liver Guidance Document 2009 Guidance for Industry: Drug Induced Liver Injury –Premarketing Clinical 
Evaluation
CELGENE PROPRIETARY INFORMATION


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
108
ABI-007-NSCL-006 Amendment 4.0Final: 31May2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
If it worsens, depending on the 
severity , treat as Grade 2 or 
Grade 3 or 4
-Consider symptomatic 
treatment including hydration,
electrolyte replacement, 
diuretics, etc.
Grade 2 [serum
creatinine>1.5-
3.0X baseline; 
>1.5X-
3.0XULN]
Hold IP/study regimen until 
resolution to ≤ Grade 1
• If toxicity worsens then treat as 
Grade 3 or Grade 4
• If toxicity improves to baseline 
then treat at next scheduled 
treatment date IP/study regimen 
can be resumed at
the next scheduled dose once event 
stabilizes to Grade ≤1 for 5-7 days 
have passed after completion of 
steroid taper
For Grade 2 elevated creatinine:
-Consider symptomatic 
treatment including hydration,
electrolyte replacement, 
diuretics, etc.
-Carefully monitor serum 
creatinine every 2-3 days and as
clinically warranted
-Consult nephrologist and 
consider renal biopsy if
clinically indicated
-If event is persistent (> 3-5 
days) or worsens, promptly
start prednisone 1 to 2 
mg/kg/day or IV equivalent
-If event is not responsive 
within 3-5 days or worsens
despite prednisone at 1-2 
mg/kg/day or IV equivalent,
additional workup should be 
considered and prompt
treatment with IV 
methylprednisolone at 2-
4mg/kg/day started.
-Once improving gradually taper 
steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN guidelines for 
treatment of cancer-related 
infections [Category 2B 
recommendation]).
-When event returns to baseline, 
resume IP/study
regimen and routine serum 
creatinine monitoring per
study protocol.
Grade 3 or 4
(Grade 3: serum
creatinine > 3.0 X
baseline; >3.0-6.0
X ULN
Permanently discontinue IP/study 
regimen
-Carefully monitor serum 
creatinine on daily basis
-Consult Nephrologist and 
consider renal biopsy if
clinically indicated
-Promptly startprednisone 1 to 
2 mg/kg/day or IV equivalent
CELGENE PROPRIETARY INFORMATION


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
109
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
- If event is not responsive 
within 3-5 days or worsens
despite prednisone at 1-2 
mg/kg/day or IV equivalent,
additional workup should be 
considered and prompt
treatment with IV 
methylprednisolone 2-
4mg/kg/day started.
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN guidelines for 
treatment of cancer-related 
infections [Category 2B 
recommendation]
Rash (excluding
bullous skin
formations)
Any grade
• Monitor for signs and 
symptoms of dermatitis (rash and
pruritus)
• **IF THERE IS ANY 
BULLOUS FORMATION, THE
STUDY PHYSICIAN SHOULD 
BE CONTACTED AND
IP DISCONTINUED**
Grade 1
No dose modification
For Grade 1:
- Consider symptomatic 
treatment including oral
antipruritics (eg,
diphenhydramine or 
hydroxyzine) and topical therapy 
(eg, urea cream)
Grade 2
For persistent (> 1- 2 weeks) 
Grade 2 events, hold scheduled 
IP/study regimen until
resolution to ≤ Grade 1 or baseline
• If toxicity worsens then treat as 
Grade 3
• If toxicity improves then resume
administration at next scheduled 
dose
• IP/study regimen can be resumed 
at the next scheduled dose once 
event stabilizes to Grade ≤1 and 5-
7 days have passed after 
completion of steroid taper
For Grade 2 :
- Obtain dermatology consult
- Consider symptomatic 
treatment including oral
antipruritics (eg,
diphenhydramine or 
hydroxyzine) and
topical therapy (eg, urea cream)
- Consider moderate-strength 
topical steroid
- If no improvement of rash/skin 
lesions occurs within 3-5
days or is worsening despite 
symptomatic treatment
and/or use of moderate strength 
topical steroid, discuss
with study physician and 
promptly start systemic steroids
prednisone 1-2 mg/kg/day or IV 
gradually
adually
er 
er ≥28 days
≥28 days
prophylactic
prophylactic
 antifungals 
antifungal
P treatment (
P treatment 
rrent NCCN 
rrent NCCN
atment of ca
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
110
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
equivalent
- Consider skin biopsy if 
persistent for >1-2 weeks or
recurs
Grade 3
• Hold IP/study regimen until 
resolution to ≤ Grade 1 or baseline
• If temporarily holding the study
drug/study regimen does not 
provide improvement of the Grade 
3 skin rash to ≤ Grade 1 or baseline 
within 30 days, then permanently 
discontinue IP/study regimen
For Grade 3 or 4:
- Consult dermatology
- Promptly initiate empiric IV 
methylprednisolone 1 to
4 mg/kg/day or equivalent
- Consider hospitalization
- Monitor extent of rash [Rule of 
Nines]
- Consider skin biopsy 
(preferably more than 1) as
clinically feasible.
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN guidelines for 
treatment of cancer-related 
infections [Category 2B 
recommendation])
- Discuss with study physician
Grade 4
Permanently discontinue IP/study 
regimen
Endocrinopathy
(eg,
hyperthyroidism,
hypothyroidism,
hypopituitarism,
adrenal
insufficiency,
etc.)
Any grade
- Consult Endocrinologist
- Monitor subjects for signs and 
symptoms of endocrinopathies. 
Non-specific symptoms include
headache, fatigue, behavior 
changes, changed mental
status, vertigo, abdominal pain, 
unusual bowel habits, 
hypotension and weakness.
- Subjects should be thoroughly 
evaluated to rule out any
alternative etiology (eg, disease 
progression including
brain metastases, infections, etc.)
- Monitor and evaluate thyroid 
function tests: TSH, free T3
and free T4 and other relevant 
endocrine labs depending
on suspected endocrinopathy.
- If a subject experiences an AE 
that is thought to be possibly of 
autoimmune nature (eg,
thyroiditis, pancreatitis, 
hypophysitis, diabetes insipidus), 
the investigator should send a 
blood sample for appropriate
autoimmune antibody testing
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
111
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
Grade 1
(depending on the
type of
endocrinopathy,
refer to NCI
CTCAE version
4.03 for defining
the CTC Grade 1)
No dose modification
For Grade 1: (including those 
with asymptomatic TSH
elevation)
- Monitor subject with 
appropriate endocrine function 
tests
- If TSH < 0.5X LLN, or TSH 
>2X ULN or consistently
out of range in 2 subsequent 
measurements, include FT4
at subsequent cycles as clinically 
indicated and consider
endocrinology consult.
Grade 2
(depending on the
type of
endocrinopathy,
refer to NCI
CTCAE version
4.03 for defining
the CTC 
Grade/severity 2)
For Grade 2 endocrinopathy other 
than hypothyroidism, hold IP/study 
regimen dose until subject is 
clinically stable
• If toxicity worsens then treat as 
Grade 3 or Grade 4
• If toxicity improves to baseline 
then treat at next scheduled 
treatment date IP/study regimen 
can be resumed at
the next scheduled dose once event 
stabilizes to Grade ≤1 and 5-7 days 
have passed after completion of 
steroid taper
Subjects with endocrinopathies 
who may require prolonged or 
continued steroid replacement can 
be retreated with IP/study regimen 
on the following
conditions: 
1) the event stabilizes and is
controlled ,
2) the subject is clinically stable as
per Investigator or treating 
physician’s clinical judgement, and 
3) doses of prednisone are at
less than or equal to 10mg/day or 
equivalent.
For Grade 2: (including those 
with symptomatic
endocrinopathy)
- Isolated hypothyroidism may 
be treated with replacement
therapy without treatment 
interruption and without
corticosteroids
- Initiate hormone replacement 
as needed for management
- Evaluate endocrine function, 
and as clinically indicated,
consider pituitary scan
- For subjects with abnormal 
endocrine work up, except
for those with isolated 
hypothyroidism, consider
short-term, corticosteroids (eg,
1-2 mg/kg/day
methylprednisolone or IV 
equivalent) and prompt
initiation of treatment with 
relevant hormone
replacement (eg, Levothyroxine, 
hydrocortisone, or sex
hormones). 
- Once improving, gradually 
taper steroids over ≥28 days
and consider prophylactic 
antibiotics, antifungals and
anti PCP treatment (please refer 
to current NCCN
guidelines for treatment of 
cancer-related infections
[Category 2B recommendation])
- For subjects with normal 
endocrine work up (lab or MRI
scans), repeat labs/MRI as 
clinically indicated.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
112
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
Grade 3 or 4
(depending on the
type of
endocrinopathy,
refer to NCI
CTCAE version
4.03 for defining
the CTC Grade/
severity 3 or 4)
• For Grade 3 or 4 endocrinopathy 
other than hypothyroidism, hold 
IP/study regimen dose until 
endocrinopathy symptom(s) are 
controlled
• Resume IP/study regimen 
administration if controlled at the 
next scheduled dose
• IP/study regimen can be resumed 
at the next scheduled dose once 
event stabilizes to Grade ≤1 and 5-
7 days have passed after 
completion of steroid taper.
For Grade 3 or 4:
- Consult endocrinologist
- Isolated hypothyroidism may 
be treated with replacement
therapy without treatment 
interruption and without
corticosteroids
- Promptly initiate empiric IV 
methylprednisolone 1 to 2
mg/kg/day or equivalent
- Administer hormone 
replacement therapy as 
necessary.
- For adrenal crisis, severe 
dehydration, hypotension, or
shock: immediately initiate 
intravenous corticosteroids
with mineralocorticoid activity
- Once improving, gradually 
taper immunosuppressive
steroids over ≥4 weeks and 
consider prophylactic
antibiotics, antifungals and anti 
PCP treatment (please
refer to current NCCN guidelines 
for treatment of cancer related
infections [Category 2B 
recommendation])
- Discuss with study physician
Immune mediated
neurotoxicity (to
include but not
limited to limbic
encephalitis .
autonomic
neuropathy,
excluding
myasthenia gravis
and Guillain-Barre)
Any grade
- Subjects should be evaluated to 
rule out any alternative etiology 
(eg, disease progression, 
infections, metabolic syndromes 
and medications, etc.)
- Monitor subject for general 
symptoms (headache, nausea,
vertigo, behavior change, or 
weakness)
- Consider appropriate diagnostic 
testing (eg, electromyogram and 
nerve conduction investigations)
- Symptomatic treatment with 
neurological consult as
appropriate
Grade 1
No dose modifications
See “Any Grade” 
recommendations above.
Grade 2
• For acute motor neuropathies or
neurotoxicity, hold study rug/study
regimen dose until resolution to ≤ 
Grade 1
• For sensory neuropathy/ 
neuropathic pain, consider holding 
For Grade 2:
- Discuss with the study 
physician
- Obtain Neurology Consult
- Sensory neuropathy/ 
neuropathic pain may be 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
113
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
IP/study regimen dose until 
resolution to ≤ Grade 1
- If toxicity worsens then treat as
Grade 3 or Grade 4
- If toxicity improves to baseline 
then treat at next scheduled 
treatment date
• IP/study regimen can be resumed 
at the next scheduled dose once 
event stabilizes to Grade ≤1 and 5-
7 days have passed after 
completion of steroid taper
managed by appropriate 
medications (eg, gabapentin, 
duloxetine, etc.)
- Promptly start systemic steroids 
prednisone 1-
2mg/kg/day or IV equivalent
- If no improvement within 3-5 
days despite 1-2mg/kg/day
prednisone or IV equivalent 
consider additional workup
and promptly treat with 
additional immunosuppressive
therapy (eg, IVIG)
Grade 3
• Hold IP/study regimen dose until
resolution to ≤ Grade 1
• Permanently discontinue Study
drug/study regimen if Grade 3 
irAE does not resolve to ≤ Grade 1 
within 30 days.
For Grade 3 or 4:
- Discuss with study physician
- Obtain Neurology Consult
- Consider hospitalization
- Promptly initiate empiric IV 
methylprednisolone 1 to 2
mg/kg/day or equivalent
- If no improvement within 3-5 
days despite IV corticosteroids, 
consider additional workup and 
promptly treat with additional 
immunosuppressants (eg, IVIG)
- Once stable, gradually taper 
steroids over ≥4 weeks
Grade 4
Permanently discontinue IP/study 
regimen
Immunemediated
peripheral
neuromotor
syndromes, such
as Guillain-Barre
and myasthenia
gravis
Any grade
- The prompt diagnosis of 
immune-mediated peripheral
neuromotor syndromes is 
important, since certain
subjects may unpredictably 
experience acute
decompensations which can 
result in substantial morbidity or 
in the worst case, death. Special 
care should be taken for certain 
sentinel symptoms which may
predict a more severe outcome, 
such as prominent dysphagia, 
rapidly progressive weakness, 
and signs of respiratory 
insufficiency or autonomic 
instability
- Subjects should be evaluated to 
rule out any alternative etiology 
(eg, disease progression, 
infections, metabolic syndromes 
and medications, etc.). It should 
be noted that the diagnosis of 
immune-mediated peripheral 
neuromotor syndromes can be 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
114
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
particularly challenging in 
subjects with underlying cancer, 
due to the multiple potential
confounding effects of cancer 
(and its treatments) throughout 
the neuraxis. Given the 
importance of prompt and 
accurate diagnosis, it is essential 
to have a low threshold to obtain 
a neurological consult
- Neurophysiologic diagnostic 
testing (eg, electromyogram and 
nerve conduction  investigations, 
and “repetitive stimulation” if 
myasthenia is suspected) are 
routinely indicated upon 
suspicion of such conditions and 
may be best facilitated by means 
of a neurology consultation
Important to consider that the 
use of steroids as the primary 
treatment of Guillain-Barre is not 
typically considered effective. 
Subjects requiring treatment 
should be started with IVIG and 
followed by plasmapheresis if
not responsive to IVIG
Grade 1
No dose modification
For Grade 1:
- Discuss with the study 
physician
- Care should be taken to 
monitor subjects for sentinel
symptoms of a potential 
decompensation as described
above
- Obtain a neurology consult 
unless the symptoms are very
minor and stable
Grade 2
• Hold IP/study regimen dose until 
resolution to ≤ Grade 1
• Permanently discontinue IP/study 
regimen if it does not resolve to ≤ 
Grade 1 within 30 days or if there 
are signs of
respiratory insufficiency or 
autonomic instability
For Grade 2:
- Discuss with the study 
physician
- Care should be taken to 
monitor subjects for sentinel
symptoms of a potential 
decompensation as described
above
- Obtain a Neurology Consult
- Sensory neuropathy/ 
neuropathic pain may be 
managed by appropriate 
medications (eg, gabapentin, 
duloxetine, etc.)
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
115
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
MYASTHENIA GRAVIS
o Steroids may be successfully 
used to treat Myasthenia Gravis. 
Important to consider that
steroid therapy (especially with 
high doses) may result in 
transient worsening of 
myasthenia and should typically 
be administered in a monitored
setting under supervision of a 
consulting neurologist.
o Subjects unable to tolerate 
steroids may be candidates for 
treatment with plasmapheresis or
IVIG. Such decisions are best 
made in consultation with a 
neurologist, taking into account 
the unique needs of each subject.
o If Myasthenia Gravis-like 
neurotoxicity present,
consider starting AChE inhibitor 
therapy in addition to steroids. 
Such therapy, if successful,
can also serve to reinforce the 
diagnosis.
GUILLAIN-BARRE:
o Important to consider here that 
the use of steroids as the primary 
treatment of Guillain-Barre is not 
typically considered effective.
Subjects requiring treatment 
should be started with IVIG and 
followed by plasmapheresis if
not responsive to IVIG.
Grade 3
• Hold IP/study regimen dose until 
resolution to ≤ Grade 1
• Permanently discontinue IP/study 
regimen if Grade 3 irAE does not 
resolve to ≤ Grade 1 within 30 
days or if there are
signs of respiratory insufficiency 
or autonomic instability
For severe or life threatening 
(Grade 3 or 4) events:
- Discuss with study physician
- Recommend hospitalization
- Monitor symptoms and obtain 
neurological consult
MYASTHENIA GRAVIS
o Steroids may be successfully 
used to treat Myasthenia Gravis. 
It should typically be
administered in a monitored 
setting under supervision of a 
consulting neurologist.
o Subjects unable to tolerate 
steroids may be candidates for 
Grade 4
Permanently discontinue IP/study
regimen
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
116
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
Event
Grade of the 
Event (NCI 
CTCAE 4.0)
Dose Modifications
Toxicity Management
treatment with plasmapheresis or
IVIG.
o If Myasthenia Gravis-like 
neurotoxicity present, consider 
starting AChE inhibitor therapy 
in addition to steroids. Such 
therapy, if successful, can also 
serve to reinforce the diagnosis.
GUILLAIN-BARRE:
◦ Important to consider here that 
the use of steroids as the primary 
treatment of Guillain-Barre is not
typically considered effective. 
Subjects requiring treatment 
should be started with IVIG and
followed by plasmapheresis if 
not responsive to IVIG
AChE = acetylcholine esterase; ADL = activities of daily living; AE = adverse event; ALP = alkaline phosphatase; ALT = 
alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CT = computed tomography; CTC = 
Common Terminology Criteria; FT4 = free thyroxine; GI = gastrointestinal; ILD = interstitial lung disease; irAE = immune-
related adverse event; IV = intravenous; IVIG = intravenous immunoglobulin; LFT = liver function test; LLN = lower limit of 
normal; MRI = magnetic resonance imaging; NCCN = National  Comprehensive Cancer Network; NCI CTCAE = National 
Cancer Institute Common Terminology Criteria for Adverse Events; PCP = pneumocystis pneumonia; PO = oral; TB = total 
bilirubin; TNF = tumor necrosis factor; TSH = thyroid-stimulating hormone; ULN = upper limit of normal.
Table C2:
Treatment Modification and Toxicity Management Guidelines for Infusion-
related Adverse Events
CTC 
Grade/Severity
Dose Modifications
Toxicity Management
Any grade
- Management per institutional standard at the 
discretion of investigator
- Monitor subjects for signs and symptoms of infusion-
related reactions (eg, fever and/or shaking chills, 
flushing and/or itching, alterations in
heart rate and blood pressure, dyspnea or chest 
discomfort, skin rashes etc.) and anaphylaxis (eg,
generalized urticaria, angioedema, wheezing, 
hypotension, tachycardia, etc.)
Grade 1
The infusion rate of IP/study 
regimen may be
decreased by 50% or temporarily 
interrupted until resolution of the 
event
For Grade 1 or Grade 2:
- Acetaminophen and/or antihistamines may be 
administered per institutional standard at the discretion 
of the investigator
- Consider premedication per institutional standard 
prior to subsequent doses
Grade 2 
The infusion rate of IP/study 
regimen may be
decreased 50% or temporarily 
interrupted until resolution of the 
event
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
117
ABI-007-NSCL-006 Amendment 4.0 Final: 31 May 2016
CTC 
Grade/Severity
Dose Modifications
Toxicity Management
Subsequent infusions may be given 
at 50% of the initial infusion rate
Grade 3 or 4 
Permanently discontinue IP/study 
regimen
For Grade 3 or 4:
Manage severe infusion-related reactions per 
institutional standards
(eg, IM epinephrine, followed by IV diphenhydramine 
and ranitidine,
and IV glucocorticoid) 
IM = intramuscular; IV = intravenous.
Table C3:
Treatment Modification and Toxicity Management Guidelines for Non-
immune-mediated Reactions
CTC 
Grade/Severity
Dose Modifications
Toxicity Management
Any grade
Note: dose modifications are not required for 
adverse events not deemed to be related to study 
treatment (ie, events due to underlying disease) or 
for laboratory abnormalities not deemed to be 
clinically significant.
Treat accordingly as per institutional 
standard
Treat accordingly as per institutional 
standard
Grade 1
No dose adjustment 
Grade 2 
Hold IP/study regimen until resolution to ≤ Grade 1 
or baseline
Grade 3
Hold IP/study regimen until resolution to ≤ Grade 1 
or baseline
For AEs that downgrade to ≤ Grade 2 within 7 days 
or resolve to ≤ Grade 1 or baseline within
14 days, resume IP/study regimen administration at 
next scheduled dose. Otherwise,
discontinue IP/study regimen
Grade 4
Discontinue IP/study regimen (Note for Grade 4 
labs, decision to discontinue would be
based on accompanying clinical signs/symptoms 
and as per Investigator’s clinical judgment and
in consultation with the sponsor)
AE = adverse event; CTC = Common Terminology Criteria.
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This is a representation of an electronic record that was signed electronically in Livelink.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
TITLE PAGE
A PHASE 2, RANDOMIZED, OPEN-LABEL, 
MULTICENTER STUDY TO ASSESS SAFETY AND 
EFFICACY OF NAB®-PACLITAXEL (ABI-007) WITH 
EPIGENETIC MODIFYING THERAPY OF
CC-486, AND NAB®-PACLITAXEL MONOTHERAPY AS 
SECOND-LINE TREATMENT IN SUBJECTS WITH 
ADVANCED NONSQUAMOUS NON-SMALL CELL 
LUNG CANCER (NSCLC): ABOUND.2L
INVESTIGATIONAL PRODUCTS:
CC-486, nab-Paclitaxel (ABI-007)
PROTOCOL NUMBER:
ABI-007-NSCL-006
DATE FINAL:
29 May 2014
AMENDMENT 2 FINAL:
18 Jul 2014
EudraCT NUMBER
2014-001105-41
IND NUMBER
123160
SPONSOR NAME / ADDRESS:
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
United States
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board. The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations.
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them.
&(/*(1(
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20
u, your staff, a
, your staff, a
document is r
cument is r
may no
may no
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information:
Name:
Title:
Address: 
86 Morris Avenue
Summit, NJ 07901
United States
Phone:
E-mail:
Contact Information:
Name:
Title:
Address: 
86 Morris Avenue
Summit, NJ 07901
United States
Phone:
E-mail:
Note: The back-up 24 hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls.
Back-up 24 Hour Global Emergency Contact Call Center: 
&(/*(1(
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}.
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
 
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.
&(/*(1(35235,(7$5<,1)250$7,21
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:_______________________________________
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
PROTOCOL SUMMARY
Study Title
A Phase 2, randomized, open-label, multicenter study to assess safety and efficacy of nab-
paclitaxel (ABI-007) with epigenetic modifying therapy of CC-486, and nab-paclitaxel 
monotherapy as second-line treatment in subjects with advanced nonsquamous non-small cell
lung cancer (NSCLC): ABOUND.2L
Indication
Second-line treatment of advanced nonsquamous NSCLC.
Objectives
Primary
!
To assess the efficacy of nab-paclitaxel1 administered intravenously (IV) on Days 8 
and 15 with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 
14 every 21 days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 
every 21 days as second-line treatment for advanced nonsquamous NSCLC, and the 
relative efficacy of these two treatment regimens.
Secondary 
!
To evaluate the safety and tolerability of nab-paclitaxel administered IV on Days 8 
and 15 in combination with epigenetic modifying therapy of CC-486 once daily (QD) 
on Days 1 to 14 every 21 days, and nab-paclitaxel monotherapy administered IV on 
Days 1 and 8 every 21 days as second-line treatment for advanced nonsquamous 
NSCLC.
Exploratory 
!
To assess healthcare resource utilization for the two treatment arms.
!
To assess the quality of life (QoL) for the two treatment arms.
!
To determine baseline tumor characteristics which predict response to nab-paclitaxel 
as a single agent and in combination with epigenetic modifying therapy of CC-486. 
!
To evaluate genomic correlates of response to nab-paclitaxel as a single agent and in 
combination with epigenetic modifying therapy of CC-486.
Study Design
This is a Phase 2, randomized, open-label, multicenter study to assess efficacy and safety of  
nab-paclitaxel in combination with epigenetic modifying therapy of CC-486, and nab-paclitaxel 
monotherapy as second-line treatment in subjects with advanced nonsquamous NSCLC who 
have received one platinum-containing chemotherapy regimen. Approximately 160 subjects with 
advanced nonsquamous NSCLC will be randomized 1:1 into one of the two treatment arms: nab-
paclitaxel / CC-486 combination therapy or nab-paclitaxel monotherapy prior to receiving first 
1 nab® is a registered trademark of Celgene Corporation.
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nously (IV)
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ab-paclitax
aclitax
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ab-paclitax
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
dose of investigational product (IP). Randomization will be centralized and stratified by Eastern 
Cooperative Oncology Group (ECOG) performance status (0 versus 1, see Appendix A), gender
(males versus females), and smoker (yes versus no).
The study will consist of up to a 28-day Screening Period, a Treatment Period and a Follow-up 
Period.
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of IP.
The Treatment Period begins with the first dose of IP as described in Section 8.  Subjects will 
receive one of the following treatments based on the randomization assignment:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days  1 to 14 of each 21-day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, withdrawal of 
consent, or termination of the study by the sponsor.
Tumor evaluations will be assessed by the investigative sites and response will be determined 
according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, Version 1.1
(Eisenhauer, 2009).
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an adverse event (AE)/serious adverse event (SAE) and also recorded on the 
laboratory electronic Case Report Form (eCRF) (see Section 11.3).
All subjects who discontinue from treatment for any reason other than withdrawal of consent, 
lost to follow-up, death, or termination of the study by the sponsor will enter the Follow-up 
Period. It will consist of a visit 28 days after treatment discontinuation. Thereafter, subjects will 
be followed for survival by phone call contact approximately every 90 days (+/- 14 days) for 12
months after the last subject is randomized or 120 progression-free survival (PFS) events have 
been observed, whichever comes later.
During the study, subjects will have computed tomography (CT) scans every 42 days (-3/+7 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the sponsor. Those subjects entering the Follow-up Period without 
documented progression will continue to have CT scans in accordance with local standard of 
care (or approximately every 90 days) until documented progression of disease, withdrawal of
consent, lost to follow-up, death, or termination of the study by the sponsor. All posttreatment 
anticancer therapies will be recorded during the Follow-up Period.  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
Study Population
Male and female subjects with advanced nonsquamous NSCLC who have received one 
platinum-containing chemotherapy regimen for their advanced disease will be eligible for this 
study.
Length of Study
The enrollment of 160 subjects on this study will take approximately 24 months. The total length 
of this Phase 2 study with follow-up is estimated to be approximately 3 years.
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
study, or the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol and/or the 
Statistical Analysis Plan, whichever is the later date.
Study Treatments
Subjects will receive nab-paclitaxel in combination with CC-486 or nab-paclitaxel monotherapy 
during the study. The CC-486 and nab-paclitaxel for both arms are designated as IP and will be 
packaged and supplied by Celgene Corporation.
Overview of Statistical Methods
The primary objective of this study is to evaluate the efficacy of the CC-486 and nab-paclitaxel 
combination therapy and that of the nab-paclitaxel monotherapy, and the relative efficacy of 
these two treatment regimens.  
Approximately 160 subjects will be randomized to the two treatment arms in a 1:1 ratio.  A 
permuted-block randomization method will be employed, and the randomization will be carried 
out centrally using an Interactive Response Technology (IRT) system. The randomization will be 
stratified based on the following baseline factors: ECOG performance status (0 versus 1), gender 
(males versus females), and smoker (yes versus no).
Evaluations of the study endpoints will be based primarily on the point estimates and the 
associated 95%  confidence intervals of the within- and between-treatment differences. However, 
nominal p-values from statistical tests may be provided in the clinical study report to indicate the 
strength of the treatment differences evaluated. 
An independent Data Monitoring Committee (DMC) will be established to review the interim 
safety and efficacy data.  
Efficacy Analyses
The intent-to-treat population, which includes all randomized subjects regardless of whether the 
subject receives any IP or has any efficacy assessments performed, will be used for all efficacy 
analyses. The primary efficacy endpoint is PFS, which is defined as the time from the date of 
randomization to the date of disease progression or death (from any cause) on or prior to the data 
cutoff date for analyses, whichever occurs first, based on the investigator’s assessment of the 
data from CT scans using RECIST 1.1 guidelines. Baseline tumor measurements will be 
determined from the radiologic evaluation performed within 28 days before the start of study 
therapy. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
9
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% confidence interval [CI]) for each treatment arm.  The relative 
treatment effect between the combination and monotherapy arms with respect to PFS will be 
estimated by the hazard ratio (HR) and the associated two-sided 95% CIs using the stratified Cox 
proportional hazard model with ECOG performance status (0 versus 1), gender (males versus 
females), and smoker (yes versus no) as the stratification factors. No statistical inferential tests 
will be performed. 
The secondary endpoints include disease control rate (DCR), overall response rate (ORR), and 
overall survival (OS). Disease control rate and ORR will be summarized within each treatment 
arm by the observed rates and the associated 95% CIs. The relative treatment effect will be 
summarized by the absolute difference and the ratio of the observed rates. Overall survival will 
be analyzed using similar statistical method as that for the PFS endpoint.
Safety Analyses
The treated population, which includes all randomized subjects who receive at least one dose of 
IP, will be the analysis population for all safety analyses. 
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AE or SAE occurring or worsening on or after the day of the first dose of the IP
through 28 days after the last dose of IP.  In addition, any SAE with an onset date more than 28 
days after the last dose of IP that is assessed by the investigator as related to IP will be 
considered a TEAE.
Treatment-emergent adverse events, Grade 3 or higher TEAEs, SAEs, TEAEs leading to dose 
reduction, dose delay, and dose interruption, TEAEs leading to treatment discontinuation, and 
TEAEs with an outcome of death will be summarized by treatment arms using MedDRA system 
organ class and preferred terms.
Sample Size
This study is designed to estimate the treatment effect within each of the combination and 
monotherapy arms and the relative effect between the two arms with respect to the primary and 
secondary efficacy endpoints. The sample size was chosen to support the estimation of the 
within- and between-treatment effects with reasonable precision. Table 1 below summarizes the 
precisions that can be achieved given different scenarios of hypothetical observed hazard ratios 
between the two treatment arms for PFS events, assuming a total of 120 events are observed, and 
the time to PFS has an exponential distribution. 
Table 1:
Progression-Free Survival – Two-side 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms
Hypothetical Number of 
Events Observed
Hypothetical Observed Hazard 
Ratio of PFS Events
95% Confidence Interval of 
Hazard Ratioa
120
0.60
(0.42, 0.86)
0.65
(0.45, 0.93)
0.70
(0.49, 1.00)
a Assuming a standard error of 0.18 for the log hazard ratio.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
10
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
Assuming the median times of PFS are 4.17 and 2.5 months, respectively, for the nab-
paclitaxel/CC-486 combination therapy
and nab-paclitaxel
monotherapy arms, and an 
approximate 24 months accrual period for a total of 160 subjects, it is estimated that a total of 
120 PFS events will be observed approximately 2 months after the last subject is randomized, 
assuming an exponential distribution for PFS. 
One nonbinding interim analysis for PFS with early stopping rule for futility will be conducted 
when approximately 60 events are observed. 
Data Monitoring Committee
An independent Data Monitoring Committee (DMC) will be established with the responsibilities 
for safeguarding the interests of study participants and monitoring the overall conduct of the 
study. Final recommendations of the DMC will reflect the judgment of the DMC members and 
will be considered advisory in nature to the sponsor. The decision to implement the 
recommendations of the DMC will be made by the sponsor, following consultation with the trial 
Coordinating Investigator and Steering Committee. A DMC charter will be established.
&(/*(1(35235,(7$5<,1)250$7,21
ibilit
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
11
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
1.
INTRODUCTION..................................................................................................18
1.1.
Non-small Cell Lung Cancer ..................................................................................18
1.2.
nab-Paclitaxel in NSCLC .......................................................................................19
1.3.
Rationale for nab-Paclitaxel as Second-line Treatment in Subjects with 
Advanced Nonsquamous NSCLC ...........................................................................20
1.4.
Rationale for nab-Paclitaxel in Combination With Epigenetic Modifying 
Therapy of CC-486 as Second-line Treatment in Subjects with Advanced 
Nonsquamous NSCLC............................................................................................21
2.
STUDY OBJECTIVES...........................................................................................24
2.1.
Primary Objective...................................................................................................24
2.2.
Secondary Objective...............................................................................................24
2.3.
Exploratory Objectives ...........................................................................................24
3.
STUDY ENDPOINTS............................................................................................25
3.1.
Primary Endpoint....................................................................................................25
3.2.
Secondary Endpoints ..............................................................................................25
3.2.1.
Efficacy..................................................................................................................25
3.2.2.
Safety.....................................................................................................................25
3.3.
Exploratory Endpoints............................................................................................25
4.
OVERALL STUDY DESIGN ................................................................................26
4.1.
Study Design ..........................................................................................................26
4.1.1.
Screening Period.....................................................................................................26
4.1.2.
Treatment Period ....................................................................................................26
4.1.3.
Follow-up Period....................................................................................................27
4.2.
Study Design Rationale ..........................................................................................27
4.3.
Study Duration .......................................................................................................29
4.4.
End of Trial ............................................................................................................29
5.
TABLE OF EVENTS.............................................................................................30
6.
PROCEDURES......................................................................................................33
6.1.
Medical History......................................................................................................33
6.2.
Prior and Concomitant Medications and Procedures ...............................................33
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5.


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
12
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
6.3.
Pregnancy Testing ..................................................................................................33
6.4.
Complete Chest Computed Tomography (CT) Scan................................................34
6.5.
Weight and Height..................................................................................................34
6.6.
ECOG Performance Score ......................................................................................34
6.7.
Peripheral Neuropathy Assessment.........................................................................34
6.8.
Adverse Event Reporting........................................................................................35
6.9.
Quality of Life Questionnaires................................................................................35
6.10.
Healthcare Resource Utilization Questionnaire .......................................................35
6.11.
Laboratory Assessments .........................................................................................35
6.12.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) .....................................................................................36
6.13.
Electrocardiogram ..................................................................................................37
6.14.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI) .......................37
6.15.
Bone Scans and X-rays...........................................................................................37
6.16.
Physical Examinations............................................................................................37
6.17.
Vital Signs..............................................................................................................37
6.18.
Survival..................................................................................................................37
7.
STUDY POPULATION.........................................................................................39
7.1.
Number of Subjects and Sites .................................................................................39
7.2.
Inclusion Criteria....................................................................................................39
7.3.
Exclusion Criteria...................................................................................................40
8.
DESCRIPTION OF STUDY TREATMENTS........................................................42
8.1.
Description of Investigational Products...................................................................42
8.1.1.
nab-Paclitaxel.........................................................................................................42
8.1.2.
CC-486 (Azacitidine for Oral Administration) ........................................................42
8.2.
Treatment Administration and Schedule .................................................................42
8.3.
Dose Omissions and Modifications.........................................................................43
8.3.1.
Rules for Dose Omissions and Modified Schedules ................................................43
8.3.2.
Rules for Dose Modifications .................................................................................43
8.4.
Method of Treatment Assignment...........................................................................46
8.5.
Packaging and Labeling..........................................................................................46
8.6.
Investigational Product Accountability and Disposal ..............................................46
8.7.
Investigational Product Compliance........................................................................47
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
13
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
8.8.
Overdose ................................................................................................................47
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................48
9.1.
Permitted Concomitant Medications and Procedures...............................................48
9.2.
Prohibited Concomitant Medications and Procedures..............................................49
9.3.
Required Concomitant Medications and Procedures for Patients Receiving 
CC-486...................................................................................................................49
9.3.1.
Description of G-CSF.............................................................................................49
9.3.2.
Administration of G-CSF........................................................................................49
10.
STATISTICAL ANALYSES..................................................................................50
10.1.
Overview................................................................................................................50
10.2.
Study Population Definitions ..................................................................................50
10.2.1.
Intent-to-treat Population........................................................................................50
10.2.2.
Per-protocol (PP) Population ..................................................................................50
10.2.3.
Treated Population..................................................................................................51
10.3.
Sample Size and Power Considerations...................................................................51
10.4.
Background and Demographic Characteristics........................................................52
10.5.
Subject Disposition.................................................................................................53
10.6.
Efficacy Analysis....................................................................................................53
10.6.1.
Primary Efficacy Endpoints....................................................................................53
10.6.2.
Secondary Efficacy Endpoints ................................................................................54
10.6.2.1.
Disease Control Rate ..............................................................................................54
10.6.2.2.
Overall Survival .....................................................................................................54
10.6.2.3.
Overall Response Rate............................................................................................54
10.6.3.
Exploratory Endpoints............................................................................................54
10.6.3.1.
HealthCare Utilization............................................................................................54
10.6.3.2.
Quality of Life Questionnaires................................................................................54
10.6.3.3.
Biomarker, Tumor Characteristics, and Genomic Analyses.....................................54
10.7.
Safety Analysis.......................................................................................................54
10.7.1.
Adverse Events.......................................................................................................55
10.7.2.
Laboratory Assessments .........................................................................................55
10.7.3.
Study Drug Exposure..............................................................................................55
10.8.
Study Therapy Termination ....................................................................................55
10.9.
Deaths ....................................................................................................................55
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7


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
14
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
10.10.
Interim Analysis .....................................................................................................56
10.11.
Data Monitoring Committee ...................................................................................56
10.12.
Scientific Steering Committee ................................................................................56
11.
ADVERSE EVENTS..............................................................................................57
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................57
11.2.
Evaluation of Adverse Events.................................................................................57
11.2.1.
Seriousness.............................................................................................................57
11.2.2.
Severity / Intensity..................................................................................................59
11.2.3.
Causality ................................................................................................................59
11.2.4.
Duration .................................................................................................................60
11.2.5.
Action Taken..........................................................................................................60
11.2.6.
Outcome.................................................................................................................60
11.3.
Abnormal Laboratory Values..................................................................................60
11.4.
Pregnancy...............................................................................................................60
11.4.1.
Females of Childbearing Potential ..........................................................................61
11.4.2.
Male Subjects.........................................................................................................61
11.5.
Reporting of Serious Adverse Events......................................................................61
11.5.1.
Safety Queries ........................................................................................................62
11.6.
Expedited Reporting of Adverse Events..................................................................62
12.
DISCONTINUATIONS .........................................................................................63
12.1.
Study Treatment Discontinuation............................................................................63
12.2.
Study Discontinuation ............................................................................................63
12.3.
Subject Replacement ..............................................................................................64
13.
EMERGENCY PROCEDURES.............................................................................65
13.1.
Emergency Contact.................................................................................................65
13.2.
Emergency Identification of Investigational Products .............................................65
14.
REGULATORY CONSIDERATIONS...................................................................66
14.1.
Good Clinical Practice............................................................................................66
14.2.
Investigator Responsibilities ...................................................................................66
14.3.
Subject Information and Informed Consent.............................................................66
14.4.
Confidentiality........................................................................................................67
14.5.
Protocol Amendments.............................................................................................67
7
.......57
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4.3.


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
15
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................67
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................68
14.8.
Closure of the Study ...............................................................................................68
15.
DATA HANDLING AND RECORDKEEPING.....................................................69
15.1.
Data/Documents .....................................................................................................69
15.2.
Data Management...................................................................................................69
15.3.
Record Retention....................................................................................................69
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................71
16.1.
Study Monitoring and Source Data Verification......................................................71
16.2.
Audits and Inspections............................................................................................71
17.
PUBLICATIONS ...................................................................................................72
18.
REFERENCES.......................................................................................................73
19.
APPENDICES........................................................................................................76
Appendix A:
ECOG Performance Status Score.......................................................................76
Appendix B:
Recommendations for Management of Treatment-Induced Diarrhea..................77
&(/*(1(35235,(7$5<,1)250$7,21
..69
69
........
.......69
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
16
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
LIST OF TABLES
Table 1:
Progression-Free Survival – Two-side 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms................................9
Table 2:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat 
Population).............................................................................................................20
Table 3:
Table of Events.......................................................................................................30
Table 4:
Requirements for Collection Based on Archival Tumor Sample Type.....................36
Table 5:
Permanent Dose Reductions for Hematologic and Nonhematologic 
Toxicities and Dosing on the Study.........................................................................45
Table 6:
Disease Control Rate –Two-Sided 95% Confidence Interval of Hypothetical 
Disease Control Rate with a Sample Size of 80 Subjects in a Treatment Arm .........51
Table 7:
Progression-Free Survival – Two-Sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms..............................52
&(/*(1(35235,(7$5<,1)250$7,21
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
17
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................28
&(/*(1(35235,(7$5<,1)250$7,21


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Celgene Corporation
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18
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer
Lung cancer is the leading cause of cancer-related deaths among men and women worldwide, 
with 1.2 million new cases diagnosed each year. Non-small cell lung cancer (NSCLC) is the 
most common type of lung cancer, accounting for 80% of all new cases. There are an estimated 
1.1 million lives lost per year (approximately 500,000 in the United States [US] and European 
Union [EU] alone) due to NSCLC. Smoking is the causative factor for up to 85% of cases 
(http://www.lungcancercoalition.org/en/pages/about/awareness).
The majority of patients are not diagnosed until the tumor has progressed beyond the primary 
site. Despite step-wise advances in patient selection, targeted agents, and optimizing
chemotherapy regimens, patients with advanced NSCLC continue to have an unmet medical 
need (Schiller, 2013).
Platinum-containing chemotherapy regimens remain the standard first-line treatment in the 
majority of patients in the US and Japan. In the EU, a third-generation chemotherapeutic agent 
(docetaxel, gemcitabine, paclitaxel, or vinorelbine), most commonly gemcitabine or vinorelbine, 
plus a platinum drug is used for advanced NSCLC (NICE, 2011). For first-line therapy in 
patients with Stage IV NSCLC and good performance status, the American Society of Clinical 
Oncology (ASCO) clinical practice guideline recommends treatment with a platinum-based 
two-drug combination of cytotoxic drugs (Azzoli, 2009). For patients without disease 
progression, the option of maintenance monotherapy with pemetrexed or erlotinib could also be 
considered (Gerber, 2013; Schiller, 2013). A trend that is becoming more prevalent is 
personalized NSCLC treatment based on tumor histology (squamous versus nonsquamous), on 
molecular characteristics of the tumor, and on the patient’s clinical status using agents targeting 
specific receptors, kinases and pathways (ie, epidermal growth factor receptor [EGFR], 
echinoderm microtubule-associated protein-like 4 [EML4] and anaplastic lymphoma kinase 
[ALK] fusion protein).
Single agent chemotherapy (pemetrexed, EGFR-inhibitors and taxanes) are standards of care for 
second-line treatment of patients with locally advanced or metastatic NSCLC after failure of 
prior platinum-based chemotherapy. Docetaxel has been widely evaluated in this setting, and is 
currently approved by the US Food and Drug Administration (FDA) and the European 
Medicines Agency (EMA) as a single agent for the treatment of patients with locally advanced or 
metastatic NSCLC after failure of prior chemotherapy  (the US label specifies prior platinum-
based chemotherapy). For patients with a good performance status at the time of disease 
progression following first-line chemotherapy, docetaxel, despite a low response rate, was
associated with a 10% to 20% prolongation of 1-year survival and an improved quality of life 
when compared with ifosfamide, vinorelbine, or best supportive care (BSC) alone (Hanna, 
2004). Erlotinib is indicated in the US and EU for the treatment of patients with locally advanced 
or metastatic NSCLC after failure of at least one prior chemotherapy regimen, although no 
survival benefit has been demonstrated in patients with EGFR-IHC negative tumors.  
Pemetrexed is indicated in the US and EU as a single agent for the treatment of patients with 
locally advanced or metastatic nonsquamous NSCLC after prior chemotherapy. However, the 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
19
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
approval and subsequent increased use of pemetrexed and erlotinib in the first-line setting poses 
an unmet need in the second-line setting, whereby new therapeutic options are needed.
1.2.
nab-Paclitaxel in NSCLC
nab-Paclitaxel is approved in the first-line setting in combination with carboplatin for patients 
with NSCLC in the US, Japan, Argentina, Australia, and New Zealand.  The approval  was based 
on the evaluation of Phase I and II data (Belani, 2008; Rizvi, 2008; Socinski, 2010), as well as 
the pivotal Phase 3 study (CA031), (Socinski, 2012). The pivotal Phase 3 study was a 
multicenter, randomized, open-label study conducted in 1052 chemo-naïve subjects with Stage 
IIIB/IV NSCLC to compare nab-paclitaxel in combination with carboplatin to paclitaxel 
injection in combination with carboplatin as first-line treatment in patients with advanced 
NSCLC. nab-Paclitaxel was administered as an IV infusion over 30 minutes at a dose of 
100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel injection was administered as 
an IV infusion over 3 hours at a dose of 200 mg/m2, following premedication. In both treatment 
arms carboplatin at a dose of area under the curve (AUC) = 6 mg*min/mL was administered IV
on Day 1 of each 21-day cycle after completion of nab-paclitaxel/paclitaxel infusion. Treatment 
was administered until disease progression, development of an unacceptable toxicity or patient 
withdrawal. The primary efficacy outcome measure was overall response rate (ORR) as
determined by a central independent review committee using RECIST guidelines (Version 1.0).
In the intent-to-treat (all-randomized) population, the median age was 60 years, 75% were men, 
81% were white, 49% had carcinoma/adenocarcinoma, 43% had squamous cell lung cancer, 76% 
were ECOG performance status (PS) 1, 15% were ≥70 years of age and 73% were current or 
former smokers. Patients received a median of 6 cycles of treatment in both study arms. Patients 
in the nab-paclitaxel/carboplatin arm had a statistically significantly higher overall response rate 
compared to patients in the paclitaxel injection/carboplatin arm [(33% versus 25%; response rate 
ratio, 1.313; 95% CI, 1.082 to 1.593; p=0.005), see Table 2].
Non-inferiority analysis of overall survival (OS) demonstrated that nab-paclitaxel/carboplatin
(nab-p/C) treatment is not inferior to paclitaxel/carboplatin (P/C) treatment. Overall survival in 
the nab-paclitaxel arm was 12.1 months versus 11.2 months in the control arm (p = 0.271; HR = 
0.922). There was an approximately 10% increase in PFS in the nab-p/C versus P/C arm and PFS 
in the nab-p/C arm was noninferior to PFS in the P/C arm (HRnab-p/C/P/C 95% CI upper bound, 
1.086).
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
Table 2:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat
Population)
Variable
Category/Statistic
nab-Paclitaxel/
carboplatin
(N=521)
Paclitaxel/
carboplatin
(N=531)
Response Rate 
Ratio
(pA/pT)
p-value
Patients with Confirmed Complete or Partial Overall Response
n (%)
170 (33%)
132 (25%)
1.313
0.005*
Confidence Interval (CI) a
28.6, 36.7
21.2, 28.5
1.082, 1.593
Complete Response, n (%)
0
1 (< 1%)
Partial Response, n (%)
170 (33%)
131 (25%)
PA/PT: response rate of nab-paclitaxel/response rate of paclitaxel.
a 95% CI of response rate and 95.1% CI of response rate ratio.
* Indicates p-value < 0.049.
Note: p-value is based on a chi-square test.
Source: Data on File.
Adverse events (AEs) were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. The following common (≥ 10% incidence) AEs
were observed at a similar incidence in nab-paclitaxel/carboplatin and paclitaxel/carboplatin
arms: alopecia 56%, nausea 27%, fatigue 25%, decreased appetite 17%, asthenia 16%, 
constipation 16%, diarrhea 15%, vomiting 12%, dyspnea 12%, and rash 10% (incidence rates are 
for the nab-paclitaxel plus carboplatin treatment group). Toxicities, particularly neuropathy and 
Grade 3/4 neutropenia were less pronounced using nab-paclitaxel in the dose and schedule 
employed. Laboratory-detected abnormalities which occurred with a difference ≥5% for nab-
paclitaxel plus carboplatin versus paclitaxel injection plus carboplatin (Grades 1 to 4 [and Grade 
3/4]) were: anemia (98% vs 91% [28% vs 7%]), neutropenia (85% vs 83% [47% vs 58%]) and 
thrombocytopenia (68% vs 55% [18% vs 9%]).  
1.3.
Rationale for nab-Paclitaxel as Second-line Treatment in Subjects 
with Advanced Nonsquamous NSCLC
Patients who fail first-line chemotherapy are eligible for second-line treatment with single agent 
docetaxel, pemetrexed or erlotinib. In patients with good performance (eg, ECOG PS 0 or 1) and 
general health status, further treatment with chemotherapy is an important consideration that has 
been shown to extend overall survival. Despite the availability of second-line therapy, the trend 
of increased use of pemetrexed, as well as erlotinib (in selected patients) in the first-line and 
maintenance settings, potentially limits the number of available second-line treatment options for 
many patients. Furthermore, the tolerability issues associated with the administration of 
docetaxel once every 3 weeks (q3w) has prompted active research in the past decade to evaluate 
whether weekly regimens of taxanes could be optimized to improve the toxicity profile. The 
availability of an effective second-line cytotoxic chemotherapy with an improved efficacy/safety
profile over current available options would be a valuable addition for both the patient and the 
treating physician. Paclitaxel has also demonstrated potential activity in second-line NSCLC in a 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
21
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
few studies (Socinski, 1999; Juan, 2002; Socinski, 2002; Sculier, 2002; Buccheri, 2004; Ceresoli, 
2004; Yasuda, 2004).
nab-Paclitaxel exhibits 10-fold higher mean Cmax of free paclitaxel, delivers 33% higher drug 
concentration to tumors in preclinical xenograft models, and demonstrates enhanced transport 
across endothelial cell monolayers, when compared with paclitaxel (Desai, 2006; Gardner, 
2008). The Cremophor EL-free medium enables nab-paclitaxel to be given over a shorter 
duration without the need for premedication to prevent solvent-related hypersensitivity reactions.
When administered with carboplatin in the first-line setting, weekly nab-paclitaxel has 
demonstrated a more favorable efficacy:safety profile compared to the every 3 weeks schedule.  
This weekly schedule of nab-paclitaxel allows the opportunity for closer (ie, shorter interval)
monitoring of side effects and optimizing dose-intensity through timely adjustments.  
As previously noted, nab-paclitaxel 100 mg/m2 weekly (Days 1, 8 and 15) in combination with 
carboplatin (21 day cycle) is approved in the US, Japan, Argentina, Australia, and New Zealand 
for the treatment of locally advanced or metastatic NSCLC in the first-line setting.  However, 
there is limited data of monotherapy nab-paclitaxel in the second-line setting; hence, this study 
will  assess the efficacy and tolerability of weekly nab-paclitaxel, when administered on Days 1 
and 8 of each 21-day cycle.  The allowance of a one week rest period in this study (ie, no 
treatment on Day 15), takes into account research findings from other taxanes, whereby patients 
in the second-line setting are unlikely to tolerate the same dose-intensity compared to chemo-
naïve patients (eg, sharper dose reduction in the second-line setting). Therefore, the proposed 
nab-paclitaxel schedule (2 weeks treatment, 1 week rest) could offer the option of maintaining 
consistent dose-intensity for NSCLC patients in this setting.
1.4.
Rationale for nab-Paclitaxel in Combination With Epigenetic 
Modifying Therapy of CC-486 as Second-line Treatment in Subjects 
with Advanced Nonsquamous NSCLC
CC-486 is an orally bioavailable formulation of the nucleoside analog 5-azacitidine (AZA).  
After its incorporation into a cell’s DNA during the S-phase of the cell cycle, CC-486 forms 
covalent adducts with DNA Methyltransferase 1 (DNMT1) and depletes this enzyme required for 
the maintenance of DNA methylation patterns, thereby altering the epigenetic status of the cell. 
Epigenetic changes are covalent modifications of chromatin (DNA and histone proteins) that 
mediate the stable transmission of a gene’s transcriptional status through cell division.  One of 
the first recognized epigenetic alterations in cancer was DNA methylation.  The addition of a 
methyl group to cytosine in the dinucleotide CpG is catalyzed by DNA methyltransferases 
(DNMTs) and is associated with transcriptional repression of genes with high density of CpGs 
(CpG islands) in the vicinity of their promoters (Jones, 2007).  Genomic methylation patterns are 
precisely regulated during normal embryonic development and differentiation and have been 
found to be altered in specific ways in cancer. Specifically, cancer cell genomes are typified by 
reduced methylation globally with focal areas of aberrant hypermethylation in the CpG islands of 
genes encoding known tumor suppressors such as PTEN and BRCA1 as well as genes encoding 
proteins required for apoptosis, including caspase 8, DAPK and Apaf-1.  DNA methylation-
based silencing can thus contribute to the establishment and maintenance of the transformed state 
and limit the effectiveness of anti-cancer therapies.  The recognition of the role of aberrant 
methylation in carcinogenesis and its reversibility has led to the development of DNMT 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
22
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
inhibitors for cancer. Subcutaneous (SC) AZA was the first DNMT inhibitor to be approved in 
myelodysplastic syndromes (MDS) in 2004 (Kaminskas, 2005).
The notion that sequential treatment with an epigenetic modifying agent followed by a cytotoxic
agent can result in improved response to the latter is supported by numerous preclinical 
experiments and now by early clinical results.  In breast cancer cell lines, restoring expression of 
the aberrantly methylated pro-apoptotic gene TMS1 with azacitidine can restore taxane 
sensitivity (Gordian, 2009).  In a model of platinum resistant ovarian cancer, azacitidine reversed 
resistance to carboplatin (Li, 2009).  This effect required pretreatment of the cells with 
noncytotoxic levels of azacitidine for 24 hours before the addition of carboplatin and was not 
observed with concurrent exposure to both agents.  More recently, Juergens and colleagues 
observed an unusually high ORR of approximately 20% in multiple-relapsed NSCLC patients 
treated with a variety of regimens after being treated with a combination of SC AZA and another 
epigenetic agent, entinostat, a histone deacetylase inhibitor (Juergens, 2011).  In one case, a 
patient who had previously progressed on a regimen of paclitaxel, carboplatin and bevacizumab 
responded to the same triplet after treatment with SC AZA and entinostat, suggesting that the 
epigenetic modifying agents had reversed acquired resistance to the cytotoxic/anti-angiogenic 
regimen.  In a Phase 1/2 study of SC AZA with nab-paclitaxel in subjects with advanced 
metastatic solid tumors and breast cancer (Dumlao, 2011), escalating doses of SC AZA (75 to
100 mg/m2) were administered on Days 1 through 5, followed by nab-paclitaxel (100 mg/m2) 
intravenous (IV) on Days 8, 15, and 22 of a 28-day cycle.  Of 16 subjects treated at the time of 
publication, clinical activity has included 3 complete responses (CR, 1 Diffuse Large B-cell 
Lymphoma [DLBCL], 2 ovarian), 4 partial responses (PR) in ovarian and endometrial cancer 
and 4 stable diseases (SD, 2 lung, 1 pancreatic, and 1 sarcoma).  
CC-486 entered clinical testing in 2006 in subjects with MDS, chronic myelomonocytic 
leukemia [CMML], and acute myeloid leukemia [AML], with daily extended dosing schedules 
of 14 and 21 out of 28 days in a non-crossover fashion.  Daily doses of 300 mg CC-486 have 
proven to be tolerated on both the 14 and 21 out of 28-day schedules with myelosuppression, 
gastrointestinal symptoms, and fatigue being the most common toxicities (Garcia-Manero, 
2011).  Subjects treated with CC-486 for 14 or 21 days had DNA hypomethylation that persisted 
through the end of cycle.  This contrasts with the lack of persistent hypomethylation at the end of 
cycle when subjects were treated with SC AZA for 7 out of 28 days. 
 
 
 
 
  
 
 
 
 
 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
23
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
  
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
This Phase 2 study will test the hypothesis that epigenetic modifying therapy with CC-486 can 
improve the anti-tumor activity of nab-paclitaxel in second-line NSCLC patients (see Section 4.2
for study rationale). Although docetaxel has been assessed in other randomized studies as a 
chemotherapy backbone, the considerable neutropenia-related toxicity could potentially pose 
safety concerns if combined with CC-486, and the steroid premedication could confound the 
epigenetic impact of CC-486.  In addition, the q3w dosing schedule of docetaxel restricts dose 
adjustment options, thus potentially yielding lower chemotherapy dose-intensity.
Please refer to the Investigator’s Brochures (IBs) of CC-486 and nab-paclitaxel (ABI-007) for 
detailed information concerning the available pharmacology, toxicology, drug metabolism, 
clinical studies, and adverse event profile of the IPs.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
24
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
2.
STUDY OBJECTIVES
2.1.
Primary Objective 
The primary objective of the study is:
!
To assess the efficacy of nab-paclitaxel administered intravenously (IV) on Days 8 
and 15 with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 
14 every 21 days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 
every 21 days as second-line treatment for advanced nonsquamous NSCLC, and the 
relative efficacy of these two treatment regimens.
2.2.
Secondary Objective
The secondary objective of the study is:
!
To evaluate the safety and tolerability of nab-paclitaxel administered IV on Days 8 
and 15 with epigenetic modifying therapy of CC-486 QD on Days 1 to 14 every 21 
days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 every 21 
days as second-line treatment for advanced nonsquamous NSCLC.
2.3.
Exploratory Objectives
The exploratory objectives of the study are:
!
To assess healthcare resource utilization for the two treatment arms.
!
To assess the QoL for the two treatment arms.
!
To determine baseline tumor characteristics which predict response to nab-paclitaxel 
as a single agent and with epigenetic modifying therapy of CC-486. 
!
To evaluate genomic correlates of response to nab-paclitaxel as a single agent and 
with epigenetic modifying therapy of CC-486.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
25
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
3.
STUDY ENDPOINTS
Study efficacy endpoints will be assessed by the investigator using RECIST 1.1 guidelines.
3.1.
Primary Endpoint
The primary endpoint is:
!
Progression free survival.
3.2.
Secondary Endpoints
The secondary endpoints are: 
3.2.1.
Efficacy
!
Disease control rate.
!
Overall response rate.
!
Overall survival.
3.2.2.
Safety
!
The type, frequency, and severity of AEs and SAEs graded using National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, 
Version 4.0). 
!
Discontinuation rate.
!
The median dose intensity.
!
The incidence of dose reduction.
3.3.
Exploratory Endpoints
!
Healthcare resource utilization during the study using a questionnaire.
!
Changes in the Lung Cancer Symptom Scale (LCSS), European Organisation for 
Research and Treatment of Cancer (EORTC) QLQ C30, and EuroQoL 5D-5L (EQ-
5D-5L).
!
The correlation between pretreatment tumor characteristics and response to the study 
treatment determined using next-generation sequencing methods, 
immunohistochemistry, or other analysis methods.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
26
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
4.
OVERALL STUDY DESIGN 
4.1.
Study Design
This is a Phase 2, randomized, open-label, multicenter study to assess safety and efficacy of  
nab-paclitaxel in combination with epigenetic modifying therapy of CC-486, and nab-paclitaxel 
monotherapy as second-line treatment in subjects with advanced nonsquamous NSCLC who 
have received one platinum-containing chemotherapy regimen. Approximately 160 subjects with 
advanced nonsquamous NSCLC will be randomized 1:1 into one of the two treatment arms: nab-
paclitaxel / CC-486 or nab-paclitaxel monotherapy prior to receiving first dose of investigational 
product (IP). Randomization will be centralized and stratified by ECOG performance status (0 
versus 1), gender (males versus females), and smoker (yes versus no).
The study will consist of up to a 28-day Screening Period, a Treatment Period and a Follow-up 
Period.  
4.1.1.
Screening Period 
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of IP.
4.1.2.
Treatment Period 
The Treatment Period begins with the first dose of IP as described in Section 8. Subjects will 
receive one of the following treatments based on the randomization assignment:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle.
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, withdrawal of 
consent, or termination of the study by the sponsor.
During the study, subjects will have computed tomography (CT) scans every 42 days (-3/+7 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the sponsor. Tumor evaluations will be assessed by the 
investigative sites and response will be determined according to RECIST 1.1 guidelines.
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an AE/SAE and also recorded on the laboratory eCRF (see Section 11.3).  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
27
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
4.1.3.
Follow-up Period
All subjects who discontinue from treatment for reasons other than withdrawal of consent, lost to 
follow-up, death, or termination of the study by the sponsor will enter the Follow-up Period. It 
will consist of a visit 28 days after treatment discontinuation followed by phone follow-up for 
survival approximately every 90 days (+/- 14 days) for up to 12 months after the last subject is 
randomized or 120 PFS events have been observed whichever comes later.
Those subjects entering the Follow-up Period without documented progression will continue to 
have CT scans in accordance with local standard of care (or approximately every 90 days) until 
documented progression of disease, withdrawal of consent, lost to follow-up, death, or 
termination of the study by the sponsor. All posttreatment anticancer therapies will be recorded 
during the Follow-up Period.  
4.2.
Study Design Rationale
This is an open-label, randomized study designed to evaluate the effects of adding CC-486 to 
nab-paclitaxel and nab-paclitaxel monotherapy in second-line NSCLC. A placebo-controlled 
study would not be feasible for this population as blinding would be difficult and would need a 
double dummy design.  A key objective in this study is to determine the chemo-priming effect of
CC-486. The inclusion of only patients with nonsquamous NSCLC histology allows for a more 
homogenous population, hence, reducing the impact of potential confounding factors. Second-
line NSCLC enables a unique setting to evaluate epigenetics: 
a) compared to more heavily treated patients, patients eligible for second-line treatment
have better immune function/reserve which is critical for safety and activation of immune 
cells that target cancer cells,
b) due to the overlapping (and dose-limiting) toxicities of doublet/triplet chemotherapy 
regimens in the first-line setting, it would be very challenging to combine epigenetic 
therapy at a dose level to elicit clinically meaningful benefit.
Although docetaxel has been assessed in other randomized studies as a chemotherapy backbone, 
the considerable neutropenia-related toxicity could potentially pose safety concerns if combined 
with CC-486, and the steroid premedication could confound the epigenetic impact of CC-486.  In 
addition, the q3w dosing schedule of docetaxel restricts dose adjustment options, thus potentially 
yielding lower chemotherapy dose-intensity.
For patients with NSCLC whose disease progressed after initial platinum-based chemotherapy, 
the goal of therapy is to delay further progression for as long as possible; hence, the use of PFS 
as the primary endpoint for efficacy evaluation.  Furthermore, maintaining quality of life during 
this period, especially in reducing/managing toxicity is also an important consideration.  
Therefore, the proposed study is designed to optimize the evaluation of efficacy with a tolerable 
dose/schedule of chemotherapy, and its combination with an epigenetic modifying therapy.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
28
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
Figure 1:
Overall Study Design
IP = investigational product; PFS = progression-free survival; QD = once daily; OS = overall survival.
Screening for Eligibility  (up to 28 days)
(n=160)
Follow-up Period
28-day Follow-up visit (after last dose of IP)
Followed for OS by phone approximately every 90 days for up o 12 months after last subject is randomized or 120 
PFS events have been observed, whichever is later
nab-paclitaxel 100 mg/m2  IV infusion over 30 
minutes on Days 1 and 8 of each 21-day cycle 
until disease progression
(n = 80)
-
nab-paclitaxel 100 mg/m2  IV infusion over 30 
minutes on Days 8 and 15 of each 21-day cycle 
until disease progression
-
CC-486 200 mg orally QD Days 1 to 14 of each 
21-day cycle until disease progression
(n = 80)
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
29
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
4.3.
Study Duration 
Recruitment is expected to take approximately 24 months, and the analysis of PFS will be 
performed when approximately 120 PFS events have occurred, estimated as approximately 26
months from first subject randomized. The total length of this Phase 2 study with follow-up is 
estimated to last approximately 3 years.
4.4.
End of Trial
The End of Trial is defined as either the:
!
date of the last visit of the last subject to complete the study, or 
!
the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol
and/or the Statistical Analysis Plan (SAP), whichever is the later date.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
30
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
5.
TABLE OF EVENTS
Table 3:
Table of Events
Screening
/ Baseline
Treatment Period
Every 21-day Cycle
Follow-up Period
Assessment
Day -28 
to
Day -1
Day 1
( ±2 
days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu
ation Visit 
28-day Follow-up 
Visit (after last 
dose of IP)
Survival Follow-upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
Informed Consent
X
-
-
-
-
-
-
-
Medical History (including Tobacco Exposure History), 
Prior Medication and Procedures
X
-
-
-
-
-
-
-
Serum β-hCG b
X
-
-
-
-
-
-
-
Urine Pregnancy Test and Reminder to Avoid 
Pregnancyb
-
X
-
-
-
X
-
-
Complete Chest CT Scan and Any Other Studies 
Required for Tumor Imagingc
X
-
-
-
X
X
-
X
Weight and Heightd
X
X
X
X
-
-
-
-
ECOG Status
X
X
-
-
-
X
X
-
Concomitant Medication/Procedures
-
X
X
X
-
X
X
X
Peripheral Neuropathy Assessmente
X
X
-
-
-
X
X
-
Healthcare Resource Utilization Questionnaire
-
X
-
-
-
X
X
-
Hematologyf,g
X
X
X
X
-
X
X
-
Serum Chemistryf,h
X
X
-
-
-
X
X
-
Archived Tumor Tissue Sample for Biomarker (biopsy, 
surgical specimen, or other diagnostic tumor sample)
-
X
(C1D1 
only)
-
-
-
-
-
-
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
31
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
Table 3:
Table of Events (Continued)
Screening/ 
Baseline
Treatment Period
Every 21-day Cycle
Follow-Up Period
Assessment
Day -28 to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu-
ation Visit 
28-day Follow-up 
Visit (after last 
dose of IP)
Survival Follow-Upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
Plasma for Biomarker Analyses
-
X
(C1D1 
only
predose)
-
-
-
-
-
-
Blood for Pharmacogenomic Analyses
-
X
(C1D1 
only 
predose)
-
-
-
-
-
-
Adverse Event Evaluation
After signing ICF and until 28 days after the last dose of IP
-
nab-PaclitaxelMonotherapy 
Administration/Accountabilityi
-
X
X
-
-
-
-
nab-Paclitaxel Combination 
Administration/Accountabilityi
-
-
X
X
-
-
-
-
CC-486 Administration/Accountabilityi
-
X
-
-
-
-
LCSS, EORTC QLQ C30 and EQ-5D-5L
-
X
-
-
-
X
X
-
Survival Phone Call
-
-
-
-
-
-
-
Xa
Physical Examinationj
X
X
-
-
-
X
-
-
Vital Signsj
X
X
X
X
-
X
-
-
Electrocardiogram (ECG)
X
Will be done as per standard of care during the Treatment Period and as clinically indicated; however, results 
will not be routinely collected in the eCRFs. If CT/bone scans show lesions pertinent for RECIST 1.1 criteria 
evaluation, data will be collected on the pertinent tumor evaluation eCRFs. If ECGs are abnormal and
clinically significant, the data will be recorded on the AE/SAE eCRF.
Bone Scan (X-rays if needed)
If clinically 
indicated
CT Scan of the Head or Brain Magnetic Resonance 
Imaging (MRI)
If clinically 
indicated 
(mandatory if 
symptomatic)
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
32
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
AE = Adverse Event; β-HCG = beta human chorionic gonadotropin; C1D1 = Cycle 1 Day 1; CT = Computed Tomography; ECOG = Eastern Cooperative Oncology Group; eCRF
= electronic Case Report Form; EORTC QLQ C30 = European Organisation for Research and Treatment of Cancer QLQ C30; EQ-5D-5L = EuroQol 5D-5L; ICF = informed 
consent form; IP = investigational product; LCSS = Lung Cancer Symptom Scale; QD = once daily; RECIST = Response Evaluation Criteria in Solid Tumors; SAE = Serious 
Adverse Event.
a Every 90 (+/-14) days (from 28-day Follow-up Visit ) for up 12 months after the last subject is randomized or 120 PFS events have been observed whichever comes later.
b All males and all women of child-bearing potential must be reminded to avoid pregnancy prior to administration of IP before beginning each new cycle and at the End-of-
Treatment Visit. A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a Serum β-hCG pregnancy test must be performed 
to assess eligibility at Screening/Baseline. Note: the screening serum pregnancy test can be used as the Cycle 1 Day 1 test prior to study therapy if it is performed within the 72-
hour timeframe.  A urine pregnancy test must be performed prior to administration of IP before beginning each new cycle and at the End-of-Treatment Visit.
c All subjects must have a radiographically documented measurable tumor(s) by RECIST 1.1 criteria: Complete chest CT scan (including base of neck and adrenal gland) will be 
performed at Screening, every 42 days (-3/+7 days) (starting from Day 1 Cycle 1) until disease progression, withdrawal of consent, lost to follow-up, death, or termination of the 
study by the sponsor. The results of a complete chest CT scan (including base of neck and adrenal gland) performed per Standard of Care may be accepted and not repeated 
during Screening provided it was performed within 28 days of the first dose of study drug (Cycle 1 Day 1). The methods of assessment chosen at baseline to follow tumors are to 
remain consistent throughout study duration. Those subjects entering the Follow-up Period without documented progression will continue to have CT scans in accordance with 
local standard of care (or approximately every 90 days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, or termination of the study by 
the sponsor.
d Height will only be obtained at screening visit. Weight will be obtained at Screening and every visit during the Treatment Period before administration of IP.
e The occurrence of peripheral neuropathy will be reported by the investigator per protocol as an AE or SAE.
f All scheduled laboratory samples will be sent to a central laboratory for analysis. Local hematology and chemistry tests may be performed as required for subject 
management/treatment decisions. Local laboratory values that are considered abnormal and clinically significant will be recorded as an AE/SAE and also recorded on the 
laboratory eCRF (see Section 11.3).
g Hematology panel: hemoglobin, hematocrit, red blood cell count and morphology, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin 
concentration, white blood cell count with absolute and differential and percent (neutrophils, lymphocytes, monocytes, eosinophils, basophils, bands), platelet count, 
reticulocytes, erythrocyte sedimentation rate, international normalized ratio, prothrombin time, partial thromboplastin time. Additional laboratory samples for safety may be 
collected as clinically indicated.
h Serum chemistry panel: sodium, potassium, bicarbonate, calcium, magnesium, phosphorus, blood urea nitrogen, serum creatinine and clearance, uric acid, glucose, lactic
dehydrogenase, total protein, albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, total, direct and indirect 
bilirubin, fibrinogen, ferritin. Additional laboratory samples for safety may be collected as clinically indicated.
i nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 200 mg orally QD on Days 1 to14 of each 21-day treatment cycle or nab-paclitaxel 
100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day treatment cycle.
j Physical examination and vital signs assessment should be performed prior to IP administration at these visits. Additional physical examination and vital signs assessments may 
be performed throughout the study as clinically indicated. Only abnormal and clinically significant physical examination data and/or vital signs will be recorded as an AE/SAE 
on the eCRF. Vital signs will be (at a minimum): blood pressure, heart rate, respiratory rate, body temperature.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
33
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
6.
PROCEDURES
Subjects will be provided with a written Informed Consent Form (ICF), given the opportunity to 
ask any questions concerning the study and will sign an ICF prior to participating in any study 
procedures. After giving written informed consent, subjects will undergo a Screening Period to 
be assessed for eligibility. All subjects who sign an ICF must be entered into the Integrated 
Response Technology (IRT) immediately upon signature on the document. Subjects who do not 
meet the eligibility criteria will be considered screening failures and will not be eligible for the 
study. Subjects who fail initial screening may undergo re-screening up to 2 times at any time 
and an ICF will need to be resigned, as well as all screening procedures repeated (some 
procedures may not need to be done if previously done within 28 days prior to screening again).
Subjects that have met all eligibility criteria after the Screening Period will be eligible for
randomization. 
6.1.
Medical History
A complete medical history including, but not limited to, evaluation for past (up to 5 years) or
present cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine,
lymphatic, hematological, immunologic, dermatological, psychiatric, genitourinary, obstetrical, 
surgical history or any other diseases or disorders will be performed at Screening. All NSCLC-
related medical history should be recorded regardless of time. Smoking status/tobacco exposure 
history will be captured on the eCRF.
6.2.
Prior and Concomitant Medications and Procedures
Prior medications are defined as any medications started before the first dose of IP and stopped 
either prior to the date of the first dose of IP or continued after study treatment. All prior 
medications/procedures of clinically significant or ongoing medical conditions taken up to 28 
days of time of signature on the ICF should be recorded. All NSCLC-related prior 
medications/procedures should be recorded regardless of time.
Concomitant medication is defined as the medication that was either initiated before the first 
dose of IP and continued during the study treatment, or initiated on/after the date of the first dose 
of IP but on or before 28 days after the last dose of IP. All subjects will have concomitant 
medications and procedures (including radiation therapy) recorded at each visit from the time of 
signature on the ICF until the 28-day Follow-up Visit, for conditions that are clinically 
significant or ongoing. During the Follow-up Period only NSCLC-associated concomitant 
medications/procedures (including radiation therapy) will be recorded, ie, subsequent-line(s) of 
anti-cancer therapy.
6.3.
Pregnancy Testing
All males and all women of child-bearing potential must be reminded to avoid pregnancy prior to 
administration of IP before beginning each new cycle and at the End-of-Treatment Visit. A 
pregnancy test is required for women of child-bearing potential only. For women of child-
bearing potential a serum β-hCG pregnancy test with sensitivity of at least 25 mIU/mL must be 
performed to assess eligibility at Screening/Baseline. Note: the screening serum pregnancy test 
e
me
ning again)
ning again)
gible
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for
for past (up
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hiatric, geni
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rformed at
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ime. Sm
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an
tions
ons sta
starte
rte
IP
IP or conti
or cont
gnificant o
gnificant o
F should be
should b
be recorded
e recorded
efined as th
efined a
during th
during t e
28 days afte
28 days aft
ocedures 
edures (in
(in
ICF
ICF unt
until th
il th
ongoing. D
ngoing. D
s/procedur
/procedur
cer therapy
cer therap
3.
P
All
All male
male
mini


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
34
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
can be used as the Cycle 1 Day 1 test prior to study therapy if it is performed within the 72-hour 
timeframe.  A urine pregnancy test must be performed prior to administration of IP before 
beginning each new cycle and at the End-of-Treatment Visit. The subject may not receive 
treatment until the investigator has verified that the result of the pregnancy test is negative. See 
inclusion criteria for pregnancy testing requirements. Any pregnancies that occur in women who 
have received IP must be immediately reported to Celgene Drug Safety (See Section 11.4).
6.4.
Complete Chest Computed Tomography (CT) Scan
A complete chest CT scan (including base of neck and adrenal gland) and any other studies 
required for tumor imaging will be done at Screening, every 42 days (-3/+7 days) (starting from 
Day 1 Cycle 1), and End-of-Treatment, until documented progression of disease, withdrawal of 
consent, lost to follow-up, death, or termination of the study by the sponsor. The results of a 
complete chest CT scan (including base of neck and adrenal gland) performed per Standard of 
Care may be accepted and not repeated during Screening provided it was performed within 28 
days of the first dose of study drug (Cycle 1 Day 1). Those subjects entering the Follow-up 
Period without documented progression will continue to have CT scans in accordance with local 
standard of care (or approximately every 90 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death, or termination of the study by the sponsor. 
Additional CT scans may be done at any time during the study if clinically indicated. All CT
scans and reports should be archived at the site according to site regulations and copies provided 
to sponsor if requested. All posttreatment anticancer therapies will be recorded during the 
Follow-up Period.  
6.5.
Weight and Height
Weight will be obtained at Screening and at every visit during the Treatment Period before 
administration of IP. Additional measurements of weight may be collected per local standards at 
any time during the study as needed. Height will only be collected at Screening. All weight and 
height data will be collected on eCRFs.
6.6.
ECOG Performance Score
Eastern Cooperative Oncology Group performance status score will be collected at Screening, 
Day 1 of every treatment cycle, at the End-of-Treatment Visit and at the 28-day Follow-up Visit. 
Additional ECOG assessments may be performed at any time during the study as clinically 
indicated.
6.7.
Peripheral Neuropathy Assessment
Peripheral neuropathy (sensory or motor) assessment will be done at Screening, Day 1 of every 
treatment cycle, at the End-of-Treatment Visit and at the 28-day Follow-up Visit. Changes in 
neuropathy grade from baseline will be reported as an AE as per Section 11. Additional 
peripheral neuropathy assessments may be done at any time during the study as clinically 
indicated.
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ments of 
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cycle, a
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essment
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
35
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
6.8.
Adverse Event Reporting
Adverse events will be recorded from time of signature on the ICF until 28 days after the last 
dose of IP, including any unscheduled visits. See Section 11 for details. 
6.9.
Quality of Life Questionnaires
The LCSS, EORTC QLQ C30 and EQ-5D-5L questionnaires will be used to measure quality of 
life (QoL) for subjects in the study. The LCSS is comprised of 9 questions to be completed by 
the subject using a visual analogue scale (VAS) to denote intensity of a symptom. The EQ-5D-
5L comprises 5 questions on mobility, self-care, usual activities, pain/discomfort, 
anxiety/depression and a VAS for overall QoL. These questionnaires will be completed by the 
subject prior to interaction with study personnel, at Day 1 of every Cycle, at the End-of-
Treatment Visit and at the 28-day Follow-up Visit.
6.10.
Healthcare Resource Utilization Questionnaire
A healthcare resource utilization questionnaire will be used to capture the additional use of 
healthcare resources, including hospitalizations, emergency room visits, doctor or nurse visits, 
procedures, and/or additional medication during the study period. The assessment will be 
completed on Day 1 of every treatment cycle, at the End-of-Treatment Visit and at the 28-day
Follow-up Visit. 
6.11.
Laboratory Assessments
Blood for hematology and chemistry evaluation will be collected as per Table 3, Table of Events. 
Blood for hematology will be collected at Screening, Days 1, 8, and 15 of every treatment cycle, 
at the End-of-Treatment Visit and at the 28-day Follow-up Visit. Blood for serum chemistry will 
be collected at Screening, Day 1 of every treatment cycle, at the End-of-Treatment Visit and at 
the 28-day Follow-up Visit. Hematology panel will consist of: hemoglobin, hematocrit, red
blood cell count and morphology, mean corpuscular volume, mean corpuscular hemoglobin, 
mean corpuscular hemoglobin concentration, white blood cell count with absolute and 
differential and percent (neutrophils, lymphocytes, monocytes, eosinophils, basophils, bands), 
platelet count, reticulocytes, erythrocyte sedimentation rate, international normalized ratio, 
prothrombin time and partial thromboplastin time. Serum chemistry panel includes: sodium, 
potassium, bicarbonate, calcium, magnesium, phosphorus, blood urea nitrogen, serum creatinine 
and clearance, uric acid, glucose, lactic dehydrogenase, total protein, albumin, alkaline 
phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, 
total, direct and indirect bilirubin, fibrinogen and ferritin. Additional laboratory samples for 
safety may be collected as clinically indicated. 
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an AE/SAE and also recorded on the laboratory eCRF (see Section 11.3).
Abnormal and clinically significant laboratory assessments at Screening will be recorded as 
medical history, and after Screening, as AE or SAE (clinically significant laboratory 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
36
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
abnormalities at Screening may result in a subject being ineligible for the study and should not 
be captured as an AE). 
Any abnormal values that persist should be followed at the discretion of the investigator. The 
investigator should file all copies of the reports, including faxes with the subject’s medical chart.
6.12.
Tumor Tissue Sample Collection and Peripheral Blood Collection
(Exploratory Assessments) 
Histologically or cytologically confirmed advanced nonsquamous NSCLC is a required inclusion 
criteria for entry into this study.  If a subject’s previously collected tumor tissue (also known as 
archival tumor) is available, these samples will be collected for biomarker testing as detailed 
below at Cycle 1 Day 1.  If such samples do not exist, have been depleted, or do not contain 
sufficient tumor material to be analyzed, this will not preclude participation in the study and a 
new biopsy or other procedure to collect tumor tissue will not be required.  Table 4 delineates the 
specific requirements for commonly encountered archival tumor types.
Table 4:
Requirements for Collection Based on Archival Tumor Sample Type
Sample Type
Amount to Collect
Collection 
Requirement for 
Biomarkers
Comments/ Exceptions
Core biopsy or surgical 
specimen
10 slides ≥4 ∀M 
thickness. If a block is 
provided, a core of 
viable tumor will also 
be collected.
Mandatory if the sample 
exists. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Fine needle aspirates 
(FNA)
10 slides ≥4 ∀M. If a 
block is provided, a 
core of viable tumor 
will also be collected. 
Mandatory if the sample 
exists, unless a core 
biopsy or surgical 
sample was provided. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Transbronchial 
endoscopy samples
10 slides ≥4 ∀M. If a 
block is provided, a 
core of viable tumor 
will also be collected.
Mandatory if the sample 
exists, unless a core 
biopsy or surgical 
sample was provided. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Bronchial lavage, 
sputum, or other
sample types
Slides or blocks 
representing >100,000 
tumor cells
Collection is strongly 
encouraged when these 
samples contain 
sufficient material.
Collection is strongly 
encouraged when these 
samples contain sufficient 
material.
In addition, test results for tumor mutational status of genes, including but not limited to EGFR,
ALK, and KRAS will be collected and recorded on eCRF if these tests have been performed.
Plasma for cell-free nucleic acids analyses will be collected on Cycle 1 Day 1 prior to first dose 
of IP, as will a sample of whole blood or peripheral blood mononuclear cells for a germ-line 
reference comparison. Types of techniques planned to be used for tumor and plasma analyses 
include:
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
37
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
!
Gene expression by RNA sequencing
!
Immunohistochemistry 
!
DNA sequencing
!
DNA methylation profiling
Details regarding the collection, storage, and shipment of the samples are given in the Laboratory 
Manual.
6.13.
Electrocardiogram
Electrocardiograms (ECGs) will be done at Screening and as per standard of care during the 
Treatment Period, and as clinically indicated. Results will be collected in the eCRFs as AE or 
SAE only if results are abnormal, changed and clinically significant, unless the finding is already 
documented in medical history.
6.14.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI)
A CT scan of the head, or preferably brain MRI, will be done as per standard of care at 
Screening, during the Treatment Period, and as clinically indicated. If CT scans show lesions 
pertinent for RECIST 1.1 criteria evaluation, data will be collected on the pertinent tumor 
evaluation eCRFs.
6.15.
Bone Scans and X-rays
Bone scans and x-rays will be done as per standard of care at Screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs. If bone scans or X-
rays show lesions pertinent for RECIST 1.1 criteria evaluation, data will be collected on the 
pertinent tumor evaluation eCRFs.
6.16.
Physical Examinations
Physical examinations will be done at Screening, on Day 1 of every treatment cycle, at the End-
of-Treatment Visit, and as clinically indicated. Results will be collected in the eCRFs as AE or 
SAE only if results are abnormal and clinically significant.
6.17.
Vital Signs
Vital signs (at a minimum blood pressure, heart rate, respiratory rate and body temperature) will 
be done at Screening, prior to IP administration on Days 1, 8, and 15 of every treatment cycle, at 
the End-of-Treatment Visit, and as clinically indicated. Results will be collected in the eCRFs as 
AE or SAE only if results are abnormal and clinically significant.
6.18.
Survival 
After the End-of-Treatment Visit, the subjects will have a 28-day Follow-up Visit followed by a 
phone call approximately every 90 days (+/- 14 days) for at least 12 months after the last subject 
is randomized or 120 PFS events have been observed whichever comes later. The subjects will 
also be asked questions about other medications they may be taking for their NSCLC. Those 
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6.18
fter 
fter


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
38
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
subjects entering the Follow-up Period without documented progression will continue to have 
CT scans in accordance with local standard of care (or approximately every 90 days) until 
documented progression of disease, withdrawal of consent, lost to follow-up, death, or 
termination of the study by the sponsor.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Male and female subjects with advanced nonsquamous NSCLC who have received one 
platinum-containing chemotherapy regimen for their advanced disease will be eligible for this 
study. The study will randomize approximately 160 subjects. The study will be conducted at 
approximately 30 to 60 sites in the United States, Canada, and Europe.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be randomized in the study:
1. Age ≥ 18 years at the time of signing the ICF.
2. Understand and voluntarily provide written informed consent prior to the conduct of any 
study related assessments/procedures.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Histologically or cytologically confirmed advanced nonsquamous NSCLC.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease (defined by the presence of 
≥1 radiographically documented measurable lesion).
7. One prior platinum-containing chemotherapy for the treatment of advanced disease.
8. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
9. Platelets ≥ 100,000 cells/mm3.
10. Hemoglobin (Hgb) ≥ 9 g/dL.
11. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and 
alanine transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper 
limit of normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
12. Total bilirubin ≤ 1.5 ULN  (unless there is a known history of Gilberts Syndrome).
13. Serum creatinine ≤1.5 x ULN, or calculated creatinine clearance ≥60 mL/min (if renal 
impairment is suspected 24-hour urine collection for measurement is required).
14. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
15. Females of childbearing potential [defined as a sexually mature woman who (1) have not 
undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy 
(the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for 
at least 24 consecutive months (ie, has had menses at any time during the preceding 24 
consecutive months)] must:
a.
Have a negative pregnancy test (ß-hCG) as verified by the study doctor within 72 
hours prior to starting study therapy. She must agree to ongoing pregnancy testing 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
40
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
during the course of the study, and after end of study therapy. This applies even if the 
subject practices true abstinence* from heterosexual contact.
b. Either commit to true abstinence* from heterosexual contact or agree to use, and be 
able to comply with, effective contraception without interruption, 28 days prior to 
starting IP, during the study therapy (including dose interruptions), and for 3 months 
after discontinuation of study therapy. 
Male subjects must:
a.
Practice true abstinence* or agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the study, 
during dose interruptions and for at least 6 months following IP discontinuation, even 
if he has undergone a successful vasectomy. 
16. Females must abstain from breastfeeding during study participation and 3 months after IP 
discontinuation. 
7.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. Squamous cell NSCLC.
2. Prior taxane therapy.
3. Evidence of active brain metastases, including leptomeningeal involvement (prior 
evidence of brain metastasis are permitted only if asymptomatic and clinically stable for 
at least 8 weeks following completion of therapy). MRI of the brain (or CT scan 
w/contrast) is preferred.
4. Only evidence of disease is non-measurable.
5. Known EGFR mutation.
6. Known EML4-ALK mutation.
7. Preexisting peripheral neuropathy of Grade > 2 (per NCI CTCAE v4.0).
8. Venous thromboembolism within 1 month prior to Cycle 1 Day 1.
9. Current congestive heart failure (New York Heart Association Class II-IV).
10. History of the following within 6 months prior to Cycle 1 Day 1: a myocardial infarction, 
severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart 
Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically 
significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG)
abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder.
11. Known hepatitis B or C virus (HBV/HCV) infection, known history of human 
immunodeficiency virus (HIV) infection, or receiving immunosuppressive or 
                                               
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic 
abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception].
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
41
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
myelosuppressive medications that would in the opinion of the investigator, increase the 
risk of serious neutropenic complications.
12. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, 
defined as ongoing signs/symptoms related to the infection without improvement despite 
appropriate antibiotics, antiviral therapy, and/or other treatment.
13. History of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or 
pulmonary hypersensitivity pneumonitis.
14. Subject has a clinically significant malabsorption syndrome, persistent diarrhea, or 
known sub-acute bowel obstruction > NCI CTCAE Grade 2, despite medical 
management.
15. Treatment with any investigational product within 28 days prior to signing the ICF.
16. History of or suspected allergy to nab-paclitaxel, azacitidine, human albumin or 
mannitol.
17. Currently enrolled in any other clinical protocol or investigational trial that involves
administration of experimental therapy and/or therapeutic devices.
18. Any other clinically significant medical condition, psychiatric illness, and/or organ 
dysfunction that will interfere with the administration of the therapy according to this 
protocol or which, in the views of investigator, preclude combination chemotherapy.
19. Any other malignancy within 5 years prior to randomization, or advanced malignant 
hepatic tumors, with the exception of adequately treated squamous cell carcinoma of the 
skin, in-situ carcinoma of the cervix, uteri, non-melanomatous skin cancer, carcinoma in 
situ of the breast, or incidental histological finding of prostate cancer (TNM 
Classification of Malignant Tumours (TNM) stage of T1a or T1b). (All treatment of 
which should have been completed 6 months prior to signing ICF).
20. Any condition including the presence of laboratory abnormalities, which places the 
subject at unacceptable risk if he/she were to participate in the study.
21. Any medical condition that confounds the ability to interpret data from the study.
22. Pregnant or breastfeeding females.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
42
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Investigational Products
Subjects will receive open-label nab-paclitaxel / CC-486 or nab-paclitaxel monotherapy during 
the Treatment Period of the study. The nab-paclitaxel and CC-486 are designated as IP and will 
be packaged and supplied by Celgene Corporation.
The reconstitution and IV administration of nab-paclitaxel should follow the local Prescribing 
Information for Abraxane.
8.1.1.
nab-Paclitaxel
nab-Paclitaxel will be supplied by the sponsor, Celgene Corporation, in single-use vials in single 
count cartons. Each single-use 50 mL vial will contain paclitaxel (100 mg) and human albumin 
as a stabilizer.
Please see local prescribing information for Abraxane for detailed instructions on the 
reconstitution, storage conditions and IV administration of nab-paclitaxel. Reconstituted nab-
paclitaxel should be stored in an area accessible only to study personnel.
Temperature records for nab-paclitaxel must be made available to Celgene or other sponsor-
nominated monitoring teams for verification of proper IP storage.
8.1.2.
CC-486 (Azacitidine for Oral Administration)
Celgene Corporation will supply azacitidine 100 mg tablets for oral administration. Each tablet is 
formulated using excipients that are generally regarded as safe and are used in marketed drug 
products.
All tablets will be packaged in blister cards. Only sufficient IP for one cycle of treatment will be 
provided to each subject at the start of each treatment cycle. All tablets should be swallowed 
whole, and should not be broken or chewed. CC-486 may be taken on an empty stomach or with 
food. Subjects should drink 8 ounces (240 mL) of room temperature water with each dose. It is 
strongly recommended that all subjects receive a dose of a prophylactic antiemetic, preferably a 
5-HT3 antagonist, approximately 30 minutes prior to each dose of CC-486.
The IP must be stored as directed on package label at controlled temperature and a temperature 
log must be maintained in the source documents The storage area should be secure and have 
access limited to study personnel. 
8.2.
Treatment Administration and Schedule
Approximately 160 subjects will be treated with nab-paclitaxel / CC-486 or nab-paclitaxel
monotherapy until disease progression, development of an unacceptable toxicity, death, lost to 
follow-up, withdrawal of consent, or termination of the study by the sponsor:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment cycle
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
43
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle
8.3.
Dose Omissions and Modifications
8.3.1.
Rules for Dose Omissions and Modified Schedules
nab-Paclitaxel Monotherapy Arm
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
!
Day 1 Dose Missed
If the dose held or missed was to be given on Day 1 of the next cycle, that next cycle will 
not be considered to start until the day the first dose is actually administered to the 
subject (ie, D1-D8-Rest, X-D1-D8-Rest, etc).
!
Day 8 Dose Missed
That dose will be skipped.  Next dose (if laboratory results permit) will be Day 1 of the 
next scheduled cycle (ie, D1-X-Rest, D1-D8-Rest, etc).
nab-Paclitaxel/CC-486 Combination Arm
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
If any doses of CC-486 are missed, skip that day and resume as appropriate, do not double up on
subsequent days.
For nab-paclitaxel: 
!
Day 8 Dose Missed
That dose will be skipped. Next dose (if laboratory results permit) will be at Day 15 (ie, 
Rest-X-D15, Rest-D8-D15, etc).
!
Day 15 Dose Missed
That dose will be skipped.  Next dose (if laboratory results permit) will be Day 8 of the 
next scheduled cycle (ie, Rest-D8-X, Rest-D8-D15, etc).
8.3.2.
Rules for Dose Modifications
Subjects who experience any of the adverse drug reactions in Table 5 will be dose reduced as per 
Table 5 during treatment. 
nab-Paclitaxel Monotherapy Arm
!
Do not administer nab-paclitaxel on Day 1 of a cycle until ANC is at least 
1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment until 
counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and platelet 
count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil count of at least 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
44
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Day 8 of the cycle. 
Upon resumption of dosing, permanently reduce nab-paclitaxel doses as outlined in 
Table 5.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-paclitaxel 
at reduced doses (Table 5) when peripheral neuropathy improves to Grade 1 or 
completely resolves.
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to 
the guidelines in Table 5. For any other Grade 3 or 4 nonhematologic toxicity or other 
investigator defined unacceptable toxicity, interrupt treatment until the toxicity 
improves to ≤Grade 2, then restart treatment according to the guidelines in Table 5.
Re-escalation is not permitted at any time. 
nab-Paclitaxel/CC-486 Combination Arm
!
Do not administer nab-paclitaxel on Day 8 or CC-486 on Day 1 or 8 of a cycle until ANC 
is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment until 
counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and platelet 
count of at least 100,000 cells/mm3 on Day 1 and 8 for CC-486 and Day 8 for nab-
paclitaxel or to an absolute neutrophil count of at least 500 cells/mm3 and platelet count 
of at least 50,000 cells/mm3 on Day 15 of the cycle for nab-paclitaxel. Upon resumption 
of dosing, permanently reduce nab-paclitaxel and/or CC-486 doses as outlined in Table 5.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy (CC-486 does not need 
to be withheld). Resume nab-paclitaxel at reduced doses (Table 5) when peripheral 
neuropathy improves to Grade 1 or completely resolves. 
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to 
the guidelines in Table 5. For any other Grade 3 or 4 nonhematologic toxicity or 
other investigator defined unacceptable toxicity, interrupt treatment until the toxicity 
improves to ≤Grade 2, then restart treatment according to the guidelines in Table 5.
Re-escalation is not permitted at any time. 
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r 4 periphe
r 4 periphe
axel at redu
xel at red
or com
or complet
p
m
us toxicit
us toxicity
icit
icity y impro
impr
Table
able 5. Fo
Fo
or defined 
r defined
≤Grade 2,
Grade 2
permitted 
ermitted 


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
45
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
Table 5:
Permanent Dose Reductions for Hematologic and Nonhematologic Toxicities and Dosing on the Study
Dose Modification During Treatment
Adverse Drug Reaction
Occurrence
Monotherapy Arm: nab-
paclitaxel Dose (mg/m2)
Combination Arm: nab-
paclitaxel Dose (mg/m2) / 
CC-486 Dose (mg)
Neutropenic Fever (ANC < 500/mm3 with fever >38°C)
OR
Delay of next cycle by > 7 days for ANC < 1500/mm3
OR
ANC < 500/mm3 for > 7 days
First
75
100/100
Second
50
75/100
Third
Discontinue Treatment*
50/100
Fourth
NA
Discontinue Treatment*
Platelet count < 50,000/mm3
First
75
100/100
Second
Discontinue Treatment*
75/100
Third
NA
Discontinue Treatment*
Peripheral Neuropathy Grade ≥3
First
75
75/200
Second
50
50/200
Third
Discontinue Treatment*
Grade 2 or 3 Cutaneous toxicity
Grade 3 Diarrhea
Grade 3 Mucositis
Any other Grade 3 or 4 nonhematologic toxicity or other 
investigator defined unacceptable toxicity
First
75
100/100
Second
50
75/100
Third
Discontinue Treatment*
50/100
Fourth
NA
Discontinue Treatment*
Grade 4 Cutaneous toxicity, Diarrhea or Mucositis
First
Discontinue Treatment*
ANC = absolute neutrophil count; AUC = area under the curve; NA = not applicable.
* If an adverse event that requires dose reduction recurs after the dose has been reduced according to the table above, the subject should generally have treatment 
discontinued unless, at the discretion of the investigator, there is evidence of continuing benefit to the subject that outweighs the risk of recurrent toxicity.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
46
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
8.4.
Method of Treatment Assignment
The Treatment Period of the study is open-label. Enrollment/randomization will occur 1:1 via 
IRT. 
8.5.
Packaging and Labeling
The label(s) for all IP will include sponsor name, address and telephone number, the protocol 
number, IP name, dosage form and strength (where applicable), amount of IP per container, lot 
number, expiry date (where applicable), medication identification/kit number, dosing 
instructions, storage conditions, and required caution statements and/or regulatory statements as 
applicable. Additional information may be included on the label as applicable per local 
regulations.
8.6.
Investigational Product Accountability and Disposal
Celgene (or designee) will review with the investigator and relevant site personnel the process 
for IP return, disposal, and/or destruction including responsibilities for the site versus the 
responsibilities of Celgene (or designee).
Celgene will instruct the investigator on the return, disposal and/or destruction of IP. Only 
completely unused IP vials should be retained by the site until a representative from Celgene or 
other Celgene-designated personnel have completed an inventory. Partially used and completely 
used vials should be destroyed according to local guidelines, and disposition should be recorded 
on the Investigational Drug Accountability Record Form.
The investigator(s) or designee(s) is responsible for accounting for all IP that is issued to and
returned by the subject during the course of the study according to applicable regulatory
requirements. Any unused CC-486 must be returned by a study subject and retained by the
investigative site for accountability to be conducted by a Celgene representative (or designee). If
any IP is lost or damaged, its disposition should be documented. At the periodic monitoring
visits, a Celgene representative (or designee) will conduct IP accountability and address any
discrepancies. Upon unsatisfactory reconciliation of all IP, returned IP may be destroyed. At the
conclusion of the study, all remaining IP will be counted, reconciled with dispensing records, 
documented, and destroyed at the clinic site or allocated drug destruction location after
completion of drug accountability by a Celgene representative (or designee). The Celgene
representative (or designee) will ensure that a final report of drug accountability to the unit dose
level (ie, tablet) is prepared and placed in both the investigator study file and the central clinical
study file.
Investigational product will not be loaned or dispensed by the investigator to another investigator 
or site. Under certain circumstances, and with sponsor permission, cooperative groups may 
manage IP between locations within their network as clinical trial agreement and local guidelines 
permit.
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le for accou
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IP be
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permit
permit.


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
47
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
8.7.
Investigational Product Compliance
All IP will be administered only by study site personnel and accurate recording of all IP 
administration will be made in the appropriate section of the subject’s eCRF and source 
documents.
8.8.
Overdose
Overdose, as defined for this protocol, refers to nab-paclitaxel and CC-486 dosing.
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel or CC-486 to a given subject, regardless of any associated adverse events or sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. See 
Section 11.1 for the reporting of adverse events associated with overdose.
&(/*(1(35235,(7$5<,1)250$7,21
quelae.
uelae.
han the
han the
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se report fo
report fo
overdose.
erdose.


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
48
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
Over the course of this study, additional medications may be required to manage aspects of the 
disease state of the subjects, including side effects from study treatments or disease recurrence. 
All supportive care (including but not limited to growth factors, antiemetics, analgesics, 
zolendronic acid, denosumab) is permitted as per the investigator’s discretion and should be 
administered according to local institutional practice. All concomitant treatments, including 
blood and blood products, must be reported on the eCRF.
!
Antiemetics are not required during the study; however, it is strongly recommended 
that all subjects receive a dose of a prophylactic antiemetic, preferably a 5-HT3 
antagonist, approximately 30 minutes prior to each dose of CC-486.
!
Stable, therapeutic doses of anticoagulants are permitted; however, subjects on 
warfarin should have prothrombin time (PT) or international normalized ratio (INR)
and partial thromboplastin time (PTT) monitored as clinically indicated.
!
Subjects on erythropoietin or darbepoetin alfa for at least 4 weeks prior to starting the 
IP may continue their pretreatment doses throughout the study.
#
Note: If the subject is not on a stable dose of an erythropoiesis-stimulating agents 
(ESA) prior to study entry, the subject may not start an ESA during Cycle 1. 
However, medications such as ESAs, granulocyte colony-stimulating factors (G-
CSFs), etc., may be administered according to standard of care after Cycle 1.
!
Use of white blood cell growth factors (eg, filgrastim, G-CSF for the treatment of 
subjects with neutropenic fever is permitted at the investigator’s discretion. Use of 
filgrastim rather than pegylated-filgrastim is indicated, because of the 14 day delay 
of the next cycle following treatment with peg-filgrastim.
!
Use of white blood cell growth factors (eg, filgrastim, G-CSF) for secondary
prophylaxis in subjects who experienced a neutropenic complication from a prior
cycle of chemotherapy (for which primary prophylaxis was not received) is permitted.
!
Flu vaccination is permitted.
!
Routine infectious disease prophylaxis is not recommended, however, antibiotic,
antiviral, antipneumocystis, antifungal, or other prophylaxis may be implemented
during the study at the discretion of the investigator.
!
Treatments with bisphosphonates (eg, pamidronate, zolendronate), or other agents
(eg, denosumab) to prevent or delay progression of bone metastases are permitted.
Maintenance of a stable dosing regimen throughout the study is recommended.
!
Subjects may receive physiologic replacement doses of glucocorticoids as
maintenance therapy for adrenal insufficiency. Glucocorticoids may be administered
as an antiemetic with IV chemotherapy, if directed by local standard of care.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
49
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
!
Treatment with antidiarrheal medications is recommended at the first sign of diarrhea
as per the guidelines in Appendix B. Pre-medication with antidiarrheal medication for 
subsequent doses of CC-486 may be appropriate.
9.2.
Prohibited Concomitant Medications and Procedures
Other investigational therapies must not be used while the subject is enrolled in the study.
Anticancer therapy (chemotherapy, biologic or investigational therapy, and surgery) other than
the study treatments must not be given to subjects during the study. If such treatment is required,
the subject must be discontinued from the study. Focal palliative radiotherapy for treatment of
cancer-related symptoms is allowed during study treatment at the discretion of the investigator.
The administration of either α-interferon and/or ribavirin, or drugs with known renal toxicity is
prohibited during study treatment.
9.3.
Required Concomitant Medications and Procedures for Patients 
Receiving CC-486
If a subject experiences ≥Grade 3 neutropenia, that subject will be treated with G-CSF 5 ∀g/kg 
daily until the ANC ≥2000/mm3. In subsequent cycles, that subject should receive G-CSF 
5∀g/kg daily beginning on Day 16 and continuing until the ANC ≥2000/mm3. In subjects
receiving G-CSF, the next cycle should begin no sooner than 48 hours after discontinuation of G-
CSF. Data regarding G-CSF administration should be recorded on the eCRF provided for G-CSF 
administration.
9.3.1.
Description of G-CSF
This medication stimulates the blood system (bone marrow) to make white blood cells, helping
fight infections. This medication is given to those whose ability to make white blood cells has
been reduced. Filgrastim (also known as G-CSF, or granulocyte colony stimulating factor) is a
man-made version of a certain natural substance found in the body. It is produced using a certain
bacteria. It will be obtained commercially and relabeled as clinical supplies. It should be stored,
and administered according to the manufacturer’s recommendation.
9.3.2.
Administration of G-CSF
For subjects who experience Grade ≥3 neutropenia, G-CSF 5 ∀g/kg daily will be administered
subcutaneously. During any cycle when Grade ≥3 neutropenia occurs, CC-486 and other 
cytotoxic agents will be held, and G-CSF will begin immediately (a minimum of 24 hours after 
the last dose of CC-486 and chemotherapy). In subsequent cycles, G-CSF will begin on Day 16. 
G-CSF will continue daily until the ANC ≥2000/mm3. For complete details on drug
administration, storage, clinical pharmacology, and the human PK of G-CSF (filgrastim), please
see the G-CSF(filgrastim) package insert.
,
f
gator
gator.
xicit
xicity y isis
Patients
Patients
ed with
d with G-C
hould recei
hould recei
2000
2000/mm
/mm3
8 hours
hour afte
f
ed on the
ed on the
one marrow
ne marro
hose whose
hose whose
-CSF, or g
CSF, or g
substance fo
ubstance 
cially
cially and r
and
y
e manufactu
e manufac
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of G-CSF
CS
ience
ence Grade
ra
ing any
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y
will be held
will be held
CC
CC-486 an
486 
continue d
continue d
ration, stora
on, stora
 G-CSF(
CSF(fifi


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
50
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the study are described 
below.  Additional analyses of these endpoints as well as exploratory endpoints or subgroup 
analyses will be described in detail in the SAP.  The SAP supersedes the analyses described in 
the protocol should there be differences between the two.
Evaluations of the study endpoints will be based primarily on the point estimates and the 
associated 95% confidence intervals of the within- and between-treatment differences. However, 
statistical tests may be conducted and the nominal p-values may be provided in the clinical study 
report to indicate the strength of the treatment differences evaluated.
10.1.
Overview
Approximately 160 subjects will be randomized in a 1:1 ratio to two treatment arms (80 subjects 
per group). Arm A will receive nab-paclitaxel with epigenetic modifying therapy of CC-486 and 
Arm B will receive nab-paclitaxel as a monotherapy.  Both regimens will be administered in 21-
day cycles. All subjects will receive the assigned study treatment until disease progression, 
unacceptable toxicity, death, lost to follow-up, withdrawal of consent, or termination of the 
study by the sponsor, in accordance with local standard of care.  A permuted-block 
randomization method will be employed, and the randomization will be carried out centrally 
using an IRT system. The randomization will be stratified based on the following baseline
factors: 
!
ECOG performance status (0 versus 1)
!
Gender (males versus females)
!
Smoker (yes versus no)
A DMC will be used to review the safety and efficacy data during the study.
10.2.
Study Population Definitions
10.2.1.
Intent-to-treat Population
The primary efficacy analysis will be performed on the intent-to-treat (ITT) population, which 
includes all randomized subjects regardless of whether the subject receives any IP or has any 
efficacy assessments performed. 
10.2.2.
Per-protocol (PP) Population
The PP population is defined as all eligible subjects randomized who receive at least one dose of 
the IP and have been treated in the arm they were assigned.  Additional analyses utilizing the PP 
population will be described in the SAP.
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opulata


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
51
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
10.2.3.
Treated Population
The treated population will consist of all randomized subjects who receive at least one dose of 
IP. The safety analyses will be based on the treatment as received if different from the assigned 
treatment by randomization.
10.3.
Sample Size and Power Considerations
The primary objective of this study is to evaluate the efficacy of the CC-486/nab-paclitaxel 
combination therapy and that of the nab-paclitaxel monotherapy, and the relative efficacy of 
these two treatment regimens. 
The effect of the two treatment regimens with respect to the efficacy endpoints will be based on 
the point estimates and the associated 95% confidence intervals. The sample size was chosen to 
support the estimation of the within- and between-treatment effects with reasonable precision. 
Table 6 below summarizes the two-sided 95% confidence intervals for a range of hypothetical
observed disease control rates given a sample size of 80 subjects in a treatment arm. If the 
observed disease control rate is 0.30, then the actual width of the 2-sided 95% confidence 
interval is 0.21 (95% CI is [0.20, 0.41]).
Table 6:
Disease Control Rate –Two-Sided 95% Confidence Interval of Hypothetical 
Disease Control Rate with a Sample Size of 80 Subjects in a Treatment Arm
Hypothetical Observed Disease 
Control Rate
Half Width of 95% Confidence 
Interval
95% Confidence Intervala
0.20
0.186
(0.119, 0.304)
0.25
0.199
(0.16, 0.359)
0.30
0.21
(0.203, 0.413)
0.35
0.218
(0.247, 0.465
0.40
0.224
(0.292, 0.516)
0.45
0.227
(0.338, 0.565)
0.50
0.228
(0.386, 0.614)
a Based on the Clopper-Pearson exact method.
Table 7 below summarizes the precision that can be achieved given different scenarios of 
hypothetical observed hazard ratios between the two treatment arms for PFS events, assuming a 
total of 120 events are observed. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
52
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
Table 7:
Progression-Free Survival – Two-Sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms
Hypothetical Number of Events 
Observed
Hypothetical Observed Hazard 
Ratio of PFS Events
95% Confidence Interval of 
Hazard Ratioa
120
0.60
(0.42, 0.86)
0.65
(0.45, 0.93)
0.70
(0.49, 1.00)
a Assuming a standard error of 0.18 for the log hazard ratio.
Assuming the median times of PFS are 4.17 and 2.5 months, respectively, for the nab-
paclitaxel/CC-486
combination therapy
and nab-paclitaxel monotherapy arms, and an 
approximate 24 months accrual period for a total of 160 subjects, it is estimated that a total of 
120 PFS events will have been observed approximately 2 months after the last subject is 
randomized, assuming an exponential distribution for PFS. 
Of note, with 120 PFS events, this study has an 80% power (1-sided, Type-1 error of 2.5%)  to 
detect a HR of 0.60 for PFS improvement with the nab-paclitaxel/CC-486 arm over the nab-
paclitaxel monotherapy arm.
One nonbinding interim analysis for PFS with an early stopping rule for futility will be 
conducted when approximately 60 events are observed. The nab-paclitaxel/CC-486 combination 
arm of the study may be stopped early for futility if the observed HR is > 1.10 given an 
approximate 60 PFS events have occurred at the time of the interim analysis. A HR> 1.10 when 
half of the target events of 120 have occurred signals a low probability for observing a 
meaningful difference in favor of the nab-paclitaxel/CC-486 combination therapy should the 
study continue to the end. With the assumptions stated above, it will take approximately 16 
months from the first subject randomized to observe approximately 60 PFS events for the interim 
analysis.
If futility is declared, enrollment in the monotherapy nab-paclitaxel arm will continue up to a 
total of 80 subjects. 
Disease control rate, OS, and ORR will be evaluated within each treatment arm and between the 
treatment arms at the time of the final analysis of the PFS endpoint when approximately 120 PFS 
events have been observed.  
All subjects will continue to be followed for OS up to 12 months after the last subject is 
randomized or 120 PFS events have been observed, whichever comes later.
10.4.
Background and Demographic Characteristics
The baseline characteristics of all randomized subjects will be summarized. Subject’s age, 
height, weight, and baseline characteristics will be summarized using descriptive statistics, while 
gender, race and other categorical variables will be provided using frequency tabulations. 
Selected medical history data will be summarized using frequency tabulations by system organ 
class and preferred term.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
53
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both Treatment 
and Follow-up Periods. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
10.6.
Efficacy Analysis
10.6.1.
Primary Efficacy Endpoints 
The primary efficacy endpoint is progression-free survival, which is defined as the time from the 
date of randomization to the date of disease progression or death (any cause) on or prior to the 
data cutoff date for analyses, whichever occurs first, based on the investigator’s assessment of 
the data from CT scans using RECIST 1.1 guidelines. Baseline tumor measurements will be 
determined from the radiologic evaluation performed within 28 days before the start of study 
therapy. 
Subjects who do not have disease progression and are alive as of the data cutoff date for the 
statistical analysis will be censored at the date of the last radiologic assessment prior to the data 
cutoff date.  Similarly, subjects who discontinue from the study prior to disease progression or 
death will be censored at the date of the last radiologic assessment prior to the data cutoff date.  
In the event that a new anticancer treatment occurs prior to documented progression, the subject 
will be censored at the date of the last radiologic assessment where the subject was documented 
to be progression-free prior to the new anticancer treatment. Subjects with a single missing 
radiologic assessment prior to a visit with documented disease progression (or death) will be 
analyzed as a PFS event at the date of the radiologic assessment that shows progression or death 
(whichever is earlier). Subjects with two or more missing radiologic assessments prior to a visit 
with documented disease progression (or death) will be censored at the date of the last radiologic 
assessment where the subject was documented to be progression-free prior to the first of the two 
missing visits.  Subjects who drop out early or die without any postbaseline radiologic tumor 
assessment will be censored on the date of randomization. 
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% CI) for each treatment arm. The Kaplan-Meier curve for PFS will 
be presented graphically for each treatment arm. The relative treatment effect between the 
combination and monotherapy arms on PFS will be estimated by the hazard ratio (HR) and the 
associated two-sided 95% CIs using the stratified Cox proportional hazard model with ECOG 
performance status (0 versus 1), gender (males versus females), and smoker (yes versus no) as 
the stratification factors, given the number of events in each cell is adequate.  No statistical 
inferential tests will be performed.
To assess the impact on PFS of radiologic assessments not occurring at the regularly scheduled 
assessment times, the frequency of these unscheduled/off-scheduled assessments will be 
presented for each treatment arm. In addition, confirmatory and sensitivity analyses will be 
performed to further assess the impact of missed radiologic assessments. An additional analysis 
of PFS, where death or new treatment will be considered as an event, will be conducted to 
address the impact of next line therapy. 
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Celgene Corporation
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54
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
10.6.2.
Secondary Efficacy Endpoints
10.6.2.1.
Disease Control Rate
Disease control rate is defined as the percent of subjects who have a radiologic complete 
response, partial response, or stable disease according to RECIST 1.1 guidelines, as determined 
by the investigator.
Disease control rate for each treatment arm will be summarized by the observed DCR rate and 
the associated two-sided 95% CI. The relative treatment effect will be summarized by the 
absolute difference and ratio of the response rates and the associated two-sided 95% CI.
10.6.2.2.
Overall Survival
Overall survival is defined as the time between randomization and death. All deaths, regardless 
of the cause of death, will be included. All subjects who are lost to follow-up prior to the end of
the study or who are withdrawn from the study will be censored at the time of last contact. 
Subjects who are still receiving treatment as of the data cutoff date will be censored at the cutoff 
date. Overall survival will be analyzed in a similar manner as that for PFS.
10.6.2.3.
Overall Response Rate 
Overall response rate is defined as the percent of subjects who have a radiologic complete or 
partial response according to RECIST 1.1 guidelines determined by the investigator.  
Overall response rate will be assessed using the same statistical methods as those for the DCR 
endpoint.
10.6.3.
Exploratory Endpoints
10.6.3.1.
HealthCare Utilization 
Healthcare utilization will be summarized by treatment. Additional analyses will be described in 
detail in the SAP.
10.6.3.2.
Quality of Life Questionnaires
The score or VAS value and the corresponding change from baseline at each timepoint will be 
summarized by treatment for the EQ-5D-5L, EORTC QLQ C30 and LCSS questionnaires. 
Additional analyses will be described in detail in the SAP. 
10.6.3.3.
Biomarker, Tumor Characteristics, and Genomic Analyses 
Statistical analysis of the biomarkers, tumor characteristics, and genomic correlates will be 
described in a SAP separate from that described above.
10.7.
Safety Analysis
The treated population, which includes all randomized subjects who receive at least one dose of 
IP, will be the analysis population for all safety analyses.
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
55
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
The safety/tolerability of the two treatment arms will be monitored through continuous reporting 
and evaluated by adverse events and serious adverse events, and incidence of subjects 
experiencing dose modifications, dose interruptions, and/or premature discontinuation of IP.
10.7.1.
Adverse Events
Adverse events will be analyzed in terms of TEAEs, defined as any AE or SAE occurring or 
worsening on or after the day of the first dose of the IP through 28 days after the last dose of IP.  
In addition, any serious AE with an onset date more than 28 days after the last dose of IP that is 
assessed by the investigator as related to IP will be considered a TEAE. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA). The severity of AEs will be graded based on NCI CTCAE, Version 4.0; 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Treatment-emergent adverse events, Grade 3 or higher TEAEs, serious AEs, TEAEs leading to 
dose reduction, dose delay, and dose interruption, TEAEs leading to treatment discontinuation, 
and TEAEs with an outcome of death will be summarized per treatment arms by MedDRA 
system organ class and preferred terms. 
Adverse events of special interest of the nab-paclitaxel/CC-486 combination and nab-paclitaxel 
monotherapy regimens identified in previous studies in a similar population may be identified 
and summarized by worst NCI CTCAE grade, System Organ Class (SOC) and MedDRA
preferred terms.
By-subject listings will be provided for all relevant safety data. Graphical displays and figures 
will be provided where useful to assist in the interpretation of results.
10.7.2.
Laboratory Assessments
Treatment group differences in each laboratory parameter with respect to the NCI CTCAE 
grades will be summarized by the frequency distribution of subjects with the AE grades.  
All laboratory parameters will be summarized by descriptive statistics within each treatment arm, 
as appropriate. 
10.7.3.
Study Drug Exposure
The extent of exposure to the IPs will be assessed based on the descriptive statistics on the 
number of cycles and IP doses administered, cumulative dose, average dose intensity, and 
percentage of protocol dose administered.  The incidences of CC-486 and nab-paclitaxel dose 
reductions, dose interruptions, and dose delays will be summarized by treatment arm.  
10.8.
Study Therapy Termination
Reasons for stopping study therapy will be presented in listings and summarized by frequency of 
occurrence and corresponding percentage of occurrence.
10.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the IP
through 28 days post last dose of the IP) and deaths that occur during the Follow-up Period will 
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occurren


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Celgene Corporation
Confidential and Proprietary
56
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
be summarized by frequency of occurrence and corresponding percentage by cause of death per 
period (during treatment or follow-up). 
10.10.
Interim Analysis
One nonbinding interim analysis for PFS with an early stopping rule for futility will be 
conducted when approximately 60 events are observed. The nab-paclitaxel/CC-486 combination 
arm of the study may be stopped early for futility if the observed HR is ≥1.10 given an 
approximate 60 PFS events have occurred at the time of the interim analysis. Should this occur, 
enrollment in the monotherapy nab-paclitaxel arm will continue up to a total of 80 subjects.  
10.11.
Data Monitoring Committee
An independent DMC will be established with the responsibilities for safeguarding the interests 
of study participants and monitoring the overall conduct of the study. Final recommendations of 
the DMC will reflect the judgment of the DMC members and will be considered advisory in 
nature to the sponsor. The decision to implement the recommendations of the DMC will be made 
by the sponsor, following consultation with the coordinating investigator and Steering 
Committee.
Operational details for the DMC will be detailed in the DMC charter. 
10.12.
Scientific Steering Committee
The conduct of this study will be overseen by a Steering Committee. The Steering Committee 
will serve in an advisory capacity to the sponsor.
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the eCRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of NSCLC will not require reporting as 
an adverse event.
An overdose, accidental or intentional, whether or not it is associated with an AE, or abuse, 
withdrawal, sensitivity or toxicity to an investigational product should be reported as an AE.  If 
an overdose is associated with an AE, the overdose and adverse event should be reported as 
separate terms.  See Section 8.8 for the definition of overdose.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for nab-paclitaxel or 
CC-486 overdose. Actual treatment should depend on the severity of the clinical situation and 
the judgment and experience of the treating physician.
All subjects will be monitored for AEs during the study. Assessments may include monitoring of 
any or all of the following parameters: the subject’s clinical symptoms, laboratory, pathological, 
radiological or surgical findings, physical examination findings, or findings from other 
appropriate tests and procedures.
All AEs will be recorded by the investigator from the time the subject signs informed consent to
28 days after the last dose of IP, and those SAEs made known to the investigator at any time 
thereafter that are suspected of being related to IP. AEs and serious adverse events (SAEs) will 
be recorded on the AE page of the eCRF and in the subject’s source documents. All SAEs must 
be reported to Celgene Drug Safety within 24 hours of the investigator’s knowledge of the event 
by facsimile, or other appropriate method, using the SAE Report Form, or approved equivalent 
form.
11.2.
Evaluation of Adverse Events
A qualified investigator will evaluate all adverse events as to: 
11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
!
Results in death;
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11.2.1.
1.2.1.
ser


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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
!
Is life-threatening (ie, in the opinion of the investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the eCRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of or an elective procedure for a pre-existing condition 
unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
59
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
For each SAE, the investigator will provide information on severity, start and stop dates, 
relationship to IP, action taken regarding IP, and outcome.
11.2.2.
Severity / Intensity
For both AEs and SAEs, the investigator must assess the severity/intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current active minor version of NCI CTCAE, Version 4.0
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Adverse events that are not defined in the NCI CTCAE should be evaluated for severity/intensity 
according to the following scale:
!
Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required
!
Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required
!
Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible
!
Grade 4 = Life threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable
!
Grade 5 = Death – the event results in death
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.
Seriousness, not severity, serves as a guide for defining regulatory obligations.
11.2.3.
Causality 
The investigator must determine the relationship between the administration of IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
Means a causal relationship of the adverse event to IP
administration is unlikely or remote, or other medications, 
therapeutic interventions, or underlying conditions provide a 
sufficient explanation for the observed event.
Suspected:
Means there is a reasonable possibility that the administration 
of IP caused the adverse event.  ‘Reasonable possibility’ means 
there is evidence to suggest a causal relationship between the IP
and the adverse event.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
60
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
Causality should be assessed and provided for every AE/SAE based on currently available 
information.  Causality is to be reassessed and provided as additional information becomes 
available.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP
that has not been manufactured or provided by Celgene, please provide the name of the 
manufacturer when reporting the event.
11.2.4.
Duration
For both AEs and SAEs, the investigator will provide a record of the start and stop dates of the 
event.
11.2.5.
Action Taken
The investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(eg, discontinuation or reduction of IP, as appropriate) and report if concomitant and/or 
additional treatments were given for the event. 
11.2.6.
Outcome
The investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered or death (due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or
!
is judged to be of significant clinical importance.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF. If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE.
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
f the
he
E, as applic
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All pregn
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
61
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11.4.1.
Females of Childbearing Potential
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on IP, or within 3 months of the 
subject’s last dose of IP, are considered immediately reportable events. IP is to be discontinued 
immediately. The pregnancy, suspected pregnancy, or positive pregnancy test must be reported 
to Celgene Drug Safety immediately by facsimile, or other appropriate method, using the 
Pregnancy Initial Report Form, or approved equivalent form. The female subject should be 
referred to an obstetrician-gynecologist or another appropriate healthcare professional for further 
evaluation.
The investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the investigator
should report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate 
method, within 24 hours of the investigator’s knowledge of the event using the SAE Report 
Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving IP or within 
6 months of the last dose of IP, the male subject taking IP should notify the investigator, and the 
pregnant female partner should be advised to call her healthcare provider immediately. If the 
male subject is receiving IP, the IP may need to be discontinued in the male subject, but may be 
resumed later at the discretion of the investigator and medical monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The investigator is required to ensure that the data on these forms are accurate and consistent.
This requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent to at least 28 days after the last dose of IP) and 
those made known to the investigator at anytime thereafter that are suspected of being related to 
IP. SAEs occurring prior to treatment (after signing the ICF) will be captured.
The SAE report should provide a detailed description of the SAE and include a concise summary
of hospital records and other relevant documents. If a subject died and an autopsy has been 
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
62
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available. Any follow-up data will be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety.
Where required by local legislation, the investigator is responsible for informing the Independent 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The investigator must keep copies of all SAE 
information on file including correspondence with Celgene and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than five (5) business 
days. Urgent queries (eg, missing causality assessment) may be handled by phone.
11.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to nab-paclitaxel and CC-486 based on the Investigator
Brochures.
In the United States, all suspected unexpected serious adverse reactions (SUSARs) will be 
reported in an expedited manner in accordance with 21 CFR 312.32.
For countries within the European Economic Area (EEA), Celgene or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 
presentation of adverse reaction reports arising from clinical trials on investigational products for 
human use (ENTR/CT3) and also in accordance with country-specific requirements.
Celgene or its authorized representative shall notify the investigator of the following 
information: 
!
Any AE suspected of being related to the use of IP in this study or in other studies
that is both serious and unexpected (ie, SUSAR);
!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
The investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC. (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form/Completion Guidelines or to the Pregnancy Report Form/Completion Guidelines.
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ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the IP:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent
!
Death
!
Lost to follow-up
!
Protocol violation
The reason for discontinuation should be recorded in the eCRF and in the source documents.
The decision to discontinue a subject remains the responsibility of the treating physician, which
will not be delayed or refused by the sponsor. However, prior to discontinuing a subject, the
investigator may contact the Medical Monitor and forward appropriate supporting documents for 
review and discussion.
All subjects discontinued from IP for any reason will have a treatment discontinuation visit at the 
time of discontinuation and should undergo treatment discontinuation procedures.
All subjects discontinued from IP will be followed for a period of 28 days after last dose of IP
for the collection of AEs.
Additionally subjects who withdraw from or discontinue treatment should be followed for 
progressive disease (if applicable), survival and any new anticancer therapy given.
12.2.
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
study:
!
Withdrawal of consent
!
Death
!
Lost to follow-up
The following events may be considered sufficient reasons for discontinuing a subject from the 
study:
!
Adverse events(s)
!
Protocol violation
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. The investigator must notify the Medical Monitor immediately when a subject has 
been discontinued/withdrawn due to an AE (any unacceptable toxicity). All subjects who are 
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
64
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
withdrawn from the study should complete all protocol-required evaluations scheduled for early 
termination at the time of withdrawal.
Since follow-up of subjects who discontinue prematurely is of particular importance, every 
attempt should be made to collect all survival information and NSCLC treatment/therapy, unless 
the subject has specifically withdrawn consent from further follow-up. The investigator must 
make every effort to obtain minimal information regarding the subject’s survival status before 
determining that the subject is lost to follow-up.
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
65
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the investigator should contact the responsible Clinical Research
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page). This global 
Emergency Call Center is available 24 hours a day and 7 days a week. The representatives are 
responsible for obtaining your call-back information and contacting the on call Celgene/Contract 
Research Organization (CRO) Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
13.2.
Emergency Identification of Investigational Products
This is an open-label study; therefore, IP will be indentified on the package labeling. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
66
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative,
and investigator abide by Good Clinical Practice (GCP), as described in International Conference 
on Harmonization (ICH) Guideline E6 and in accordance with the general ethical principles 
outlined in the Declaration of Helsinki. The study will receive approval from an IRB/EC prior to 
commencement. The investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. Celgene staff or an authorized representative will evaluate and approve all 
investigators who in turn will select their staff.
The investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions. 
The investigator should maintain a list of sub-investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The investigator is responsible for keeping a record of all subjects who sign an ICF and are 
screened for entry into the study. Subjects who fail screening must have the reason(s) recorded in 
the subject’s source documents.
The investigator, or a designated member of the investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The investigator must ensure timely and accurate completion of eCRFs and queries.
14.3.
Subject Information and Informed Consent
The investigator must obtain informed consent of the subject and/or the subject’s legal 
representative prior to any study-related procedures.
Documentation that informed consent occurred prior to the subject’s entry into the study and of 
the informed consent process should be recorded in the subject’s source documents including the 
date. The original ICF signed and dated by the subject and by the person consenting the subject
prior to the subject’s entry into the study, must be maintained in the investigator’s study files and 
a copy given to the subject. In addition, if a protocol is amended and it impacts the content of the 
informed consent, the ICF must be revised. Subjects participating in the study when the amended 
protocol is implemented must be re-consented with the revised version of the ICF. The revised 
ICF signed and dated by the subject and by the person consenting the subject must be maintained 
in the investigator’s study files and a copy given to the subject.
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
67
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The
written signed approval from the IRB/EC should specifically reference the investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
IP can only be supplied to an Investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
Celgene or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB/EC should mention the protocol title, number, amendment number 
(if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
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Celgene Corporation
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68
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
The investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating investigator and the IRB/EC. This statement also applies to any 
communication between the investigator (or coordinating investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
69
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The investigator must ensure that the records and documents pertaining to the conduct of the 
study and distribution of the IP are complete, accurate, filed and retained. Examples of source 
documents include: hospital records; clinic and office charts; laboratory notes; memoranda; 
subject’s diaries or evaluation checklists; dispensing records; recorded data from automated 
instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy and the laboratories, as well 
as copies of CRFs or CD-ROM.
15.2.
Data Management
Data will be collected via eCRF and entered into the clinical database per Celgene Standard 
Operating Procedures (SOPs). This data will be electronically verified through use of 
programmed edit checks specified by the clinical team. Discrepancies in the data will be brought 
to the attention of the clinical team, and investigational site personnel, if necessary. Resolutions 
to these issues will be reflected in the database. An audit trail within the system will track all 
changes made to the data.
15.3.
Record Retention
Essential documents must be retained by the investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IP. The investigator must retain these 
documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the investigator, Celgene, and their authorized 
representative(s);
!
List of sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of CRFs (if paper) and of documentation of corrections for all subjects;
!
IP accountability records;
!
Record of any body fluids or tissue samples retained;
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nab-paclitaxel
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Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
!
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.
The investigator must obtain approval in writing from Celgene prior to destruction of any 
records. If the investigator is unable to meet this obligation, the investigator must ask Celgene 
for permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
71
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
16.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative
for compliance with applicable government regulations with respect to current GCP and standard 
operating procedures.
16.1.
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study. All aspects of the study are reviewed with the investigator and the staff at a study 
initiation visit and/or at an investigator meeting. Prior to enrolling subjects into the study, a 
Celgene representative or designee will review the protocol, eCRFs, procedures for obtaining 
informed consent, record keeping, and reporting of AEs/SAEs with the investigator. Monitoring 
will include on-site visits with the investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, IP 
storage area, eCRFs, subject’s source documents, and all other study documentation will be
inspected/reviewed by the Celgene representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the eCRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the investigator and/or his/her staff. Any necessary 
corrections will be made directly to the eCRFs or via queries by the investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene. Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The investigator is required to permit direct access to the facilities where the study took place, 
source documents, eCRFs and applicable supporting records of subject participation for audits 
and inspections by IRB/IECs, regulatory authorities (eg, FDA, European Medicines Agency 
[EMA], Health Canada) and company authorized representatives. The investigator should make 
every effort to be available for the audits and/or inspections. If the investigator is contacted by 
any regulatory authority regarding an inspection, he/she should contact Celgene immediately.
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
72
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
17.
PUBLICATIONS
The results of this study may be published in a medical publication, journal, or may be used for 
teaching purposes. Additionally, this study and its results may be submitted for inclusion in all 
appropriate health authority study registries, as well as publication on health authority study 
registry websites, as required by local health authority regulations. Selection of first authorship 
will be based on several considerations, including, but not limited to study participation, 
contribution to the protocol development, and analysis and input into the manuscript, related 
abstracts, and presentations in a study.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
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Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
18.
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Celgene Corporation
Confidential and Proprietary
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Cancer: Methods, Evidence & Guidance, 2011.
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and 
response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5(6):649-
55.
Rizvi NA, Riely GJ, Azzoli CG, Miller VA, Ng KK, Fiore J, et al. Phase I/II trial of weekly 
intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with Stage IV 
non-small-cell lung cancer. J Clin Oncol 2008;26(4):639-43.
Schiller JH, Gandara DR, Goss GD, Vokes EE.  Non-small-cell lung cancer: then and now. 
J Clin Oncol 2013;31(8):981-3.
Sculier JP, Berghmans T, Lafitte JJ, Richez M, Recloux P, Van Cutsem O, et al. A phase II study 
testing paclitaxel as second-line single agent treatment for patients with advanced non-small cell 
lung cancer failing after a first-line chemotherapy. Lung Cancer 2002;37:73–7.
Socinski MA, Manikhas GM, Stroyakovsky DL, Makhson AN, Cheporov SV, Orlov SV, et al. A 
dose finding study of weekly and every-3-week nab-paclitaxel followed by carboplatin as 
first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol 
2010;5(6):852-61.
Socinski MA, Schell MJ, Bakri K, Peterman A, Lee JH, Unger P, et al. Second-line, low-dose, 
weekly paclitaxel in patients with stage IIIB/IV nonsmall cell lung carcinoma who fail first-line 
chemotherapy with carboplatin plus paclitaxel. Cancer 2002;95:1265–73. 
Socinski MA, Steagall A, Gillenwater H. Second-line chemotherapy with 96-hour infusional 
paclitaxel in refractory non-small cell lung cancer: report of a phase II trial. Cancer Invest
1999;17:181–8. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
75
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, et al. 
Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus 
carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final 
results of a phase III trial. J Clin Oncol 2012 Jun 10;30(17):2055-62.
Yasuda K, Igishi T, Kawasaki Y, Kato K, Matsumoto S, Katayama S, et al. Phase II study of 
weekly paclitaxel in patients with non-small cell lung cancer who have failed previous 
treatments. Oncology 2004;66:347–52.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
76
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
19.
APPENDICES
Appendix A: ECOG Performance Status Score
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5
Dead
Oken, 1982.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
77
ABI-007-NSCL-006 Amendment 2.0 Final: 18 Jul 2014
Appendix B: Recommendations for Management of Treatment-Induced 
Diarrhea
The following published guidelines (Benson, 2004) were modified in order to be consistent with 
the clinical study protocol.
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Celgene Signing Page
This is a representation of an electronic record that was signed electronically in Livelink.
This page is the manifestation of the electronic signature(s) used in compliance with
the organizations electronic signature policies and procedures.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
TITLE PAGE
A PHASE 2, OPEN-LABEL, MULTICENTER STUDY TO 
ASSESS SAFETY AND EFFICACY OF SECOND/THIRD-
LINE TREATMENT WITH NAB®-PACLITAXEL (ABI-
007) IN COMBINATION WITH EPIGENETIC 
MODIFYING THERAPY OF CC-486, OR 
IMMUNOTHERAPY OF DURVALUMAB (MEDI4736), 
OR AS MONOTHERAPY IN SUBJECTS WITH 
ADVANCED NON-SMALL CELL LUNG CANCER 
(NSCLC): ABOUND.2L+
INVESTIGATIONAL PRODUCTS:
CC-486, nab-Paclitaxel (ABI-007), 
durvalumab (MEDI4736)
PROTOCOL NUMBER:
ABI-007-NSCL-006
DATE FINAL:
29 May 2014
AMENDMENT 1.0 FINAL:
24 Jun 2014
AMENDMENT 2.0 FINAL:
18 Jul 2014
AMENDMENT 3.0 FINAL:
14 Apr 2016
AMENDMENT 4.0 FINAL:
31 May 2016
AMENDMENT 5.0 FINAL:
09 Dec 2016
EudraCT NUMBER
2014-001105-41
IND NUMBER
123160
SPONSOR NAME / ADDRESS:
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
United States
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board. The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations.
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information:
Name:
Title:
Address: 
86 Morris Avenue
Summit, NJ 07901
United States
Phone:
E-mail:
Contact Information:
Name:
Title:
Address: 
86 Morris Avenue
Summit, NJ 07901
United States
Phone:
E-mail:
Note: The back-up 24 hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls.
Back-up 24 Hour Global Emergency Contact Call Center: 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}.
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:_______________________________________
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
PROTOCOL SUMMARY
Study Title
A Phase 2, Open-label, Multicenter Study to Assess Safety and Efficacy of Second/Third-line 
Treatment with nab®-Paclitaxel1 (ABI-007) in Combination with Epigenetic Modifying Therapy 
of CC-486, or Immunotherapy of Durvalumab (MEDI4736), or as Monotherapy in Subjects with 
Advanced Non-small Cell Lung Cancer (NSCLC): ABOUND.2L+
Indication
Second/third-line treatment of advanced NSCLC.
Objectives
Primary
!
To estimate the efficacy of nab-paclitaxel administered intravenously (IV) on Days 8 
and 15 with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 
14 every 21 days or nab-paclitaxel administered intravenously (IV) on Days 1 and 8
with immunotherapy of durvalumab administered IV on Day 15 every 21 days, and 
nab-paclitaxel monotherapy administered IV on Days 1 and 8 every 21 days as 
second/third-line treatment for advanced NSCLC.
Secondary 
!
To estimate the relative efficacy of each of the combination therapy arms to the 
monotherapy arm.
!
To evaluate the safety and tolerability of nab-paclitaxel administered intravenously 
(IV) on Days 8 and 15 with epigenetic modifying therapy of CC-486 once daily 
(QD) on Days 1 to 14 every 21 days, or nab-paclitaxel administered intravenously 
(IV) on Days 1 and 8 with immunotherapy of durvalumab administered IV on Day 
15 every 21 days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 
every 21 days as second/third-line treatment for advanced NSCLC.
Exploratory 
!
To assess healthcare resource utilization for the treatment arms.
!
To assess the quality of life (QoL) for the treatment arms.
!
To determine baseline tumor characteristics which predict response to nab-paclitaxel 
as a single agent and in combination with epigenetic modifying therapy of CC-486 or 
in combination with immunotherapy of durvalumab. 
!
To evaluate genomic correlates of response to nab-paclitaxel as a single agent and in 
combination with epigenetic modifying therapy of CC-486 or in combination with 
immunotherapy of durvalumab. 
                                               
1 nab® is a registered trademark of Celgene Corporation.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
!
To evaluate anti-tumor activity of nab-paclitaxel/durvalumab combination therapy 
using Investigator assessment according to immune related response criteria updated 
with RECIST 1.1 (irRECIST), and its association with PD-L1 expression.
Study Design
This is a Phase 2, open-label, multicenter study to assess efficacy and safety of:
o
nab-paclitaxel in combination with epigenetic modifying therapy of CC-486,
o
nab-paclitaxel in combination with immunotherapy of durvalumab, 
o
and nab-paclitaxel monotherapy 
as second/third-line treatment in subjects with advanced NSCLC who have received no more 
than one prior chemotherapy regimen. Approximately 240 subjects with advanced NSCLC will 
be assigned 1:1:1 into one of the following treatment arms: nab-paclitaxel /CC-486 combination 
therapy, nab-paclitaxel /durvalumab combination therapy or nab-paclitaxel monotherapy prior to 
receiving the first dose of investigational product (IP). Randomization/treatment assignment 
strategy of subjects to the three treatment arms is described in the Overview of Statistical 
Methods below and in Section 10.1. 
The study will consist of up to a 28-day Screening Period, a Treatment Period and a Follow-up 
Period.
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of IP.
The Treatment Period begins with the first dose of IP as described in Section 8.  Subjects will 
receive one of the following treatments based on the randomization/treatment assignment:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 
durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15 of each 21-
day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zoledronic acid, 
denosumab) is permitted as per the Investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, withdrawal of 
consent, or termination of the study by the Sponsor. Subjects in the nab-paclitaxel/durvalumab 
arm may continue treatment beyond disease progression per Response Evaluation Criteria in 
Solid Tumors (RECIST) guidelines, Version 1.1 as described in Section 4.1.2.1.
Tumor evaluations will be assessed by the investigative sites and response will be determined 
according to RECIST guidelines, Version 1.1 (Eisenhauer, 2009), and immune-related RECIST 
criteria (irRECIST) when applicable.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an adverse event (AE)/serious adverse event (SAE) and also recorded on the 
laboratory electronic Case Report Form (eCRF) (see Section 11.3).
All subjects who discontinue from treatment for any reason other than withdrawal of consent, 
lost to follow-up, death, or termination of the study by the sponsor will enter the Follow-up 
Period. It will consist of a visit 28 days after the last dose of IP or End of Treatment Visit, 
whichever is later. Thereafter, subjects in the nab-paclitaxel/CC-486 combination and nab-
paclitaxel monotherapy arms will be followed for survival by phone call contact approximately 
every 90 days (+/- 14 days) for at least 12 months after the last subject is randomized/assigned in 
either arm or 120 progression-free survival (PFS) events have been observed between these two 
arms, whichever comes later. Subjects in the nab-paclitaxel/durvalumab arm will be followed for 
survival in a similar manner for at least 12 months after the last subject is assigned to this arm.
During the study, subjects will have computed tomography (CT) scans every 42 days (-3/+7 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the Sponsor. Subjects in the nab-paclitaxel/durvalumab arm who 
continue beyond disease progression per RECIST 1.1 will continue to have CT scans every 42 
days (-3/+7) until progression per immune-related RECIST criteria (irRECIST 1.1) (Nishino, 
2013). Those subjects entering the Follow-up Period without documented progression will 
continue to have CT scans in accordance with local standard of care (or approximately every 90 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the Sponsor. All post-treatment anticancer therapies will be 
recorded during the Follow-up Period.  
Study Population
Male and female subjects with advanced NSCLC who have received no more than one prior
chemotherapy regimen for their advanced disease will be eligible for this study (immunotherapy 
in prior line of treatment is allowed, including platinum doublet combination). Subjects will 
receive study therapy as second or third line of treatment for advanced disease.
Length of Study
The enrollment of 240 subjects on this study will take approximately 28 months. The total length 
of this Phase 2 study with follow-up for survival is estimated to be approximately 40 months.
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, 
whichever is the later date.
Study Treatments
Subjects will receive nab-paclitaxel in combination with CC-486 or durvalumab, or nab-
paclitaxel monotherapy during the study. The CC-486, nab-paclitaxel, and durvalumab are
designated as IP and will be packaged and supplied by the Study Sponsor.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
9
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Overview of Statistical Methods
The primary objective of this study is to estimate the efficacy of the CC-486 and nab-paclitaxel 
combination therapy, that of the durvalumab and nab-paclitaxel combination therapy, and that of 
the nab-paclitaxel monotherapy. The secondary efficacy objective is to estimate the relative 
efficacy of each of the combination regimens to the monotherapy regimen and the tolerability of 
each of the 3 treatment regimens.  
Approximately 240 subjects will be assigned to one of the three treatment arms (approximately 
80 subjects per group).  A permuted-block randomization method will be employed to assign the 
subjects among the treatment arms that are enrolling simultaneously, stratified by the following 
baseline factors: ECOG performance status (0 versus 1), gender (males versus females), and 
smoker (yes versus no). Randomization/treatment assignment of subjects will be carried out 
centrally using an Interactive Response Technology (IRT) system. Prior to Protocol Amendment 
4.0, all subjects were randomized 1:1 to the nab-paclitaxel/CC-486 combination therapy and 
nab-paclitaxel monotherapy arms. As Protocol Amendment 4.0 implementation was in effect 
after enrollment in the nab-paclitaxel/CC-486 combination therapy and nab-paclitaxel 
monotherapy arms completed with each reaching approximately 80 subjects, all subjects enrolled 
while Protocol Amendment 4.0 is in effect and at the time of Protocol Amendment 5.0 
implementation will be assigned to the nab-paclitaxel/durvalumab combination therapy arm until 
approximately 80 subjects have been enrolled in that arm. Hence, treatment assignment of 
subjects to the nab-paclitaxel/CC-486 combination therapy and nab-paclitaxel monotherapy 
arms was in effect conducted completely in a randomized fashion and randomization between
the nab-paclitaxel/durvalumab combination and nab-paclitaxel monotherapy arms will not apply.  
Evaluations of the study endpoints will be based primarily on the point estimates and the 
associated 95% confidence intervals of the within- and between-treatment differences (each 
combination therapy vs. monotherapy).
An independent Data Monitoring Committee (DMC) will be established to review the interim 
safety and efficacy data.  
Efficacy Analyses
The intent-to-treat population, which includes all randomized (or assigned) subjects regardless of 
whether the subject receives any IP or has any efficacy assessments performed, will be used for 
all efficacy analyses. The primary efficacy endpoint is PFS, which is defined as the time from the 
date of randomization/treatment assignment to the date of disease progression or death (from any 
cause) on or prior to the data cutoff date for analyses, whichever occurs first, based on the 
Investigator’s assessment of the data from CT scans using RECIST 1.1 guidelines. Baseline 
tumor measurements will be determined from the radiologic evaluation performed within 28 
days before the start of study therapy. 
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% confidence interval [CI]) for each treatment arm.  The relative 
treatment effect between each of the combination therapy and monotherapy arms with respect to 
PFS will be estimated by the hazard ratio (HR) and the associated two-sided 95% CIs using the 
stratified Cox proportional hazard model with ECOG performance status (0 versus 1), gender
(males versus females), and smoker (yes versus no) as the stratification factors. No statistical 
inferential tests will be performed. To explore the effect of treatment post initial progression, 
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reatm
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S


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
10
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
PFS defined by irRECIST criteria may be estimated for those subjects in the nab-
paclitaxel/durvalumab combination arm.
The secondary endpoints include disease control rate (DCR), overall response rate (ORR), and 
overall survival (OS). Disease control rate and ORR will be summarized within each treatment 
arm by the observed rates and the associated 95% CIs. The relative treatment effect of each of 
the combination therapy arms to the monotherapy arm will be summarized by the ratio of the 
observed rates. Overall survival will be analyzed using similar statistical methods as that for the 
PFS endpoint.
Safety Analyses
The treated population, which includes all subjects who receive at least one dose of IP, will be 
the analysis population for all safety analyses. 
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AE or SAE occurring or worsening on or after the day of the first dose of the IP
through 28 days after the last dose of the last IP administration.  
In addition, any SAE with an onset date more than 28 days after the last dose of IP that is 
assessed by the Investigator as related to IP will be considered a TEAE. For the nab-
paclitaxel/durvalumab arm, AEs with an onset from 29 days up to 90 days after the last dose of 
any IP will be summarized separately.
Treatment-emergent adverse events, Grade 3 or higher TEAEs, SAEs, TEAEs leading to dose 
reduction, and dose interruption, TEAEs leading to treatment discontinuation, and TEAEs with 
an outcome of death will be summarized by treatment arms using MedDRA system organ class 
and preferred terms.
Sample Size
This study is designed primarily to estimate the treatment effect within each of the combination 
and monotherapy arms and secondarily the relative effect between each of the combination 
therapy and the monotherapy arms with respect to the primary and secondary efficacy endpoints. 
The sample size was chosen to support the estimation of the within- and between-treatment 
effects with reasonable precision. Table 1 below summarizes the precisions that can be achieved 
given different scenarios of hypothetical observed hazard ratios between the two treatment arms 
for PFS events, assuming a total of approximately 120 events are observed between two
treatment arms, and the time to PFS has an exponential distribution. 
Table 1:
Progression-Free Survival – Two-sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms
Hypothetical Number of 
Events Observed
Hypothetical Observed Hazard 
Ratio of PFS Events
95% Confidence Interval of 
Hazard Ratioa
120
0.60
(0.42, 0.86)
0.65
(0.45, 0.93)
0.70
(0.49, 1.00)
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*
(/


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
11
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Assuming the median times of PFS are 4.17, 4.25 and 2.5 months, respectively, for the nab-
paclitaxel/CC-486 combination therapy, the nab-paclitaxel/durvalumab combination therapy and 
nab-paclitaxel monotherapy arms, and an approximate 28 months accrual period for a total of 
approximately 240 subjects, it is estimated that an approximate total of 170 PFS events among the 
three arms will be observed by approximately 3 months after the last subject is assigned to the 
nab-paclitaxel/durvalumab arm, assuming an exponential distribution for PFS. 
One nonbinding interim analysis for PFS with early stopping rule for futility will be conducted 
when approximately 60 events have been observed between the nab-paclitaxel/CC-486 
combination and nab-paclitaxel monotherapy arms. An additional non-binding interim analysis 
for futility with early stopping rule with the PFS endpoint between the nab-
paclitaxel/durvalumab combination and nab-paclitaxel monotherapy arms will be conducted 
when approximately 30 PFS events have been observed in the nab-paclitaxel/durvalumab arm 
(60 or more events are expected to have occurred in the monotherapy arm at that point).
At the interim analysis data review on 
, based on the recommendation of the DMC, 
treatment with CC-486 will be discontinued in the nab-paclitaxel/CC-486 combination arm; 
subjects in this arm may be allowed to continue on nab-paclitaxel single agent, at the 
Investigator’s discretion.  
Similarly, following the outcome of the interim analysis between nab-paclitaxel/durvalumab 
combination and nab-paclitaxel monotherapy arms, and taking into account the DMC 
recommendations, subjects may be allowed to remain on either nab-paclitaxel or durvalumab as 
a single agent or both agents, at the Investigator’s discretion.
Data Monitoring Committee
An independent Data Monitoring Committee (DMC) will be established with the responsibilities 
for safeguarding the interests of study participants and monitoring the overall conduct of the 
study. Final recommendations of the DMC will reflect the judgment of the DMC members and 
will be considered advisory in nature to the Sponsor. The decision to implement the 
recommendations of the DMC will be made by the Sponsor, following consultation with the trial 
Coordinating Investigator and Steering Committee. A DMC charter will be established.
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Steering Co
teering Co


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
12
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
TABLE OF CONTENTS
TITLE PAGE.................................................................................................................1
PROTOCOL SUMMARY .............................................................................................6
1.
INTRODUCTION..................................................................................... 19
1.1.
Non-small Cell Lung Cancer ..................................................................... 19
1.2.
nab-Paclitaxel in NSCLC .......................................................................... 20
1.3.
Rationale for nab-Paclitaxel as Second/Third-line Treatment in Subjects 
with Advanced NSCLC ............................................................................. 22
1.4.
Rationale for nab-Paclitaxel in Combination With Epigenetic Modifying 
Therapy of CC-486 as Second/Third-line Treatment in Subjects with 
Advanced NSCLC ..................................................................................... 23
1.5.
Rationale for nab-Paclitaxel in Combination With Immunotherapy of 
Durvalumab as Second/Third-line Treatment in Subjects with Advanced 
NSCLC...................................................................................................... 26
2.
STUDY OBJECTIVES.............................................................................. 31
2.1.
Primary Objective...................................................................................... 31
2.2.
Secondary Objective.................................................................................. 31
2.3.
Exploratory Objectives .............................................................................. 31
3.
STUDY ENDPOINTS............................................................................... 32
3.1.
Primary Endpoint....................................................................................... 32
3.2.
Secondary Endpoints ................................................................................. 32
3.2.1.
Efficacy..................................................................................................... 32
3.2.2.
Safety........................................................................................................32
3.3.
Exploratory Endpoints............................................................................... 32
4.
OVERALL STUDY DESIGN ................................................................... 33
4.1.
Study Design ............................................................................................. 33
4.1.1.
Screening Period........................................................................................ 33
4.1.2.
Treatment Period ....................................................................................... 33
4.1.2.1.
Treatment Beyond Progression for Subjects in the nab-
Paclitaxel/Durvalumab Arm....................................................................... 34
4.1.3.
End-of-Treatment Visit.............................................................................. 34
4.1.4.
Follow-up Period....................................................................................... 34
4.2.
Study Design Rationale ............................................................................. 35
4.3.
Study Duration .......................................................................................... 38
&(/*(1(35235,(7$5<,1)250$7,21
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4.1.3.
4.1.3
1.4.
1 4


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
13
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
4.4.
End of Trial ............................................................................................... 38
5.
TABLE OF EVENTS................................................................................ 39
6.
PROCEDURES......................................................................................... 43
6.1.
Medical History......................................................................................... 43
6.2.
Prior and Concomitant Medications and Procedures .................................. 43
6.3.
Pregnancy Testing ..................................................................................... 44
6.4.
Complete Chest Computed Tomography (CT) Scan................................... 44
6.5.
Weight and Height..................................................................................... 44
6.6.
ECOG Performance Score ......................................................................... 44
6.7.
Peripheral Neuropathy Assessment............................................................ 45
6.8.
Adverse Event Reporting........................................................................... 45
6.9.
Quality of Life Questionnaires................................................................... 45
6.10.
Healthcare Resource Utilization Questionnaire .......................................... 45
6.11.
Laboratory Assessments ............................................................................ 45
6.12.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) ........................................................................ 46
6.13.
Electrocardiogram ..................................................................................... 47
6.14.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI) ..........47
6.15.
Bone Scans and X-rays.............................................................................. 47
6.16.
Physical Examinations............................................................................... 48
6.17.
Vital Signs.................................................................................................48
6.18.
Survival..................................................................................................... 48
7.
STUDY POPULATION............................................................................ 49
7.1.
Number of Subjects and Sites .................................................................... 49
7.2.
Inclusion Criteria....................................................................................... 49
7.3.
Exclusion Criteria...................................................................................... 50
8.
DESCRIPTION OF STUDY TREATMENTS........................................... 54
8.1.
Description of Investigational Products...................................................... 54
8.1.1.
nab-Paclitaxel............................................................................................ 54
8.1.2.
CC-486 (Azacitidine for Oral Administration) ........................................... 54
8.1.3.
Durvalumab (MEDI4736).......................................................................... 54
8.1.4.
Monitoring During/After Durvalumab Infusion ......................................... 55
8.2.
Treatment Administration and Schedule .................................................... 56
&(/*(1(35235,(7$5<,1)250$7,21
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...... 44
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&
8.1.2.
.1
3


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
14
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
8.3.
Dose Omissions and Modifications............................................................ 56
8.3.1.
Rules for Dose Omissions and Modified Schedules ................................... 56
8.3.2.
Rules for Dose Modifications .................................................................... 58
8.4.
Method of Treatment Assignment.............................................................. 62
8.5.
Packaging and Labeling............................................................................. 62
8.6.
Investigational Product Accountability and Disposal .................................62
8.7.
Investigational Product Compliance........................................................... 63
8.8.
Overdose ................................................................................................... 63
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................... 64
9.1.
Permitted Concomitant Medications and Procedures.................................. 64
9.2.
Prohibited Concomitant Medications and Procedures.................................65
9.3.
Required Concomitant Medications and Procedures for Subjects Receiving 
CC-486...................................................................................................... 66
9.3.1.
Description of G-CSF................................................................................ 66
9.3.2.
Administration of G-CSF........................................................................... 66
10.
STATISTICAL ANALYSES..................................................................... 67
10.1.
Overview................................................................................................... 67
10.2.
Study Population Definitions ..................................................................... 68
10.2.1.
Intent-to-treat Population........................................................................... 68
10.2.2.
Per-protocol (PP) Population ..................................................................... 68
10.2.3.
Treated Population..................................................................................... 68
10.3.
Sample Size and Power Considerations...................................................... 68
10.4.
Background and Demographic Characteristics........................................... 71
10.5.
Subject Disposition.................................................................................... 72
10.6.
Efficacy Analysis....................................................................................... 72
10.6.1.
Primary Efficacy Endpoints....................................................................... 72
10.6.2.
Secondary Efficacy Endpoints ................................................................... 73
10.6.2.1.
Disease Control Rate ................................................................................. 73
10.6.2.2.
Overall Survival ........................................................................................ 73
10.6.2.3.
Overall Response Rate............................................................................... 73
10.6.3.
Exploratory Endpoints............................................................................... 73
10.6.3.1.
HealthCare Utilization............................................................................... 73
10.6.3.2.
Quality of Life Questionnaires................................................................... 73
&(/*(1(35235,(7$5<,1)250$7,21
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0.6.2.3.
6


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
15
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
10.6.3.3.
Biomarker, Tumor Characteristics, and Genomic Analyses........................ 73
10.6.3.4.
Anti-tumor Activity and PD-L1 Expression (nab-Paclitaxel/Durvalumab 
Arm).......................................................................................................... 74
10.7.
Safety Analysis.......................................................................................... 74
10.7.1.
Adverse Events.......................................................................................... 74
10.7.2.
Laboratory Assessments ............................................................................ 74
10.7.3.
IP Exposure............................................................................................... 75
10.8.
Study Therapy Termination ....................................................................... 75
10.9.
Deaths ....................................................................................................... 75
10.10.
Interim Analysis ........................................................................................ 75
10.11.
Data Monitoring Committee ...................................................................... 76
10.12.
Scientific Steering Committee ................................................................... 76
11.
ADVERSE EVENTS................................................................................. 77
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................... 77
11.2.
Evaluation of Adverse Events.................................................................... 77
11.2.1.
Seriousness................................................................................................ 78
11.2.2.
Severity / Intensity..................................................................................... 79
11.2.3.
Causality ................................................................................................... 79
11.2.4.
Duration .................................................................................................... 80
11.2.5.
Action Taken............................................................................................. 80
11.2.6.
Outcome.................................................................................................... 80
11.3.
Abnormal Laboratory Values..................................................................... 80
11.4.
Pregnancy.................................................................................................. 80
11.4.1.
Females of Childbearing Potential ............................................................. 81
11.4.2.
Male Subjects............................................................................................ 81
11.5.
Reporting of Serious Adverse Events......................................................... 81
11.5.1.
Safety Queries ........................................................................................... 82
11.6.
Expedited Reporting of Adverse Events..................................................... 82
11.7.
Definition of Adverse Events of Special Interest ........................................ 83
12.
DISCONTINUATIONS ............................................................................ 84
12.1.
Study Treatment Discontinuation............................................................... 84
12.2.
Study Discontinuation ............................................................................... 84
12.3.
Subject Replacement ................................................................................. 85
&(/*(1(35235,(7$5<,1)250$7,21
.. 75
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12.2
1


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
16
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
13.
EMERGENCY PROCEDURES................................................................ 86
13.1.
Emergency Contact.................................................................................... 86
13.2.
Emergency Identification of Investigational Products ................................ 86
14.
REGULATORY CONSIDERATIONS...................................................... 87
14.1.
Good Clinical Practice............................................................................... 87
14.2.
Investigator Responsibilities ...................................................................... 87
14.3.
Subject Information and Informed Consent................................................ 88
14.4.
Confidentiality........................................................................................... 88
14.5.
Protocol Amendments................................................................................ 88
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................... 88
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee...89
14.8.
Closure of the Study .................................................................................. 89
15.
DATA HANDLING AND RECORDKEEPING........................................ 90
15.1.
Data/Documents........................................................................................ 90
15.2.
Data Management...................................................................................... 90
15.3.
Record Retention....................................................................................... 90
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................... 92
16.1.
Study Monitoring and Source Data Verification......................................... 92
16.2.
Audits and Inspections............................................................................... 92
17.
PUBLICATIONS ...................................................................................... 93
18.
REFERENCES.......................................................................................... 94
19.
APPENDICES........................................................................................... 99
Appendix A:
ECOG Performance Status Score.......................................................... 99
Appendix B:
Recommendations for Management of Treatment-Induced Diarrhea... 100
Appendix C:
Treatment Modification and Toxicity Management for nab-Paclitaxel 
/Durvalumab arm..................................................................................... 101
8
...... 88
88
and 
and 
.............
............. 8
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Committe
mm
.............
.......
.............
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..............
........
.............
..........
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LITY ASS
LITY AS
Data Verific
ata Verific
..............
.............
..............
.........
.............
...........
..............
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Performanc
Performan
ommendat
mmendat
Treatment
Treatmen
/Durvalum
/Durvalum


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
LIST OF TABLES
Table 1:
Progression-Free Survival – Two-sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms................. 10
Table 2:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat 
Population)................................................................................................ 21
Table 3:
Data for Control Arms using Taxanes from Phase II and III Studies 
Blinded...................................................................................................... 36
Table 4:
Table of Events.......................................................................................... 39
Table 5:
Requirements for Collection Based on Archival Tumor Sample Type........46
Table 6:
Permanent Dose Reductions for Hematologic and Nonhematologic 
Toxicities and Dosing on the Study............................................................ 61
Table 7:
Disease Control Rate –Two-Sided 95% Confidence Interval of Hypothetical 
Disease Control Rate with a Sample Size of 80 Subjects in a Treatment 
Arm........................................................................................................... 69
Table 8:
Progression-Free Survival – Two-Sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms................. 69
&(/*(1(35235,(7$5<,1)250$7,21
46
46
..........
.......... 61
6
Hypothetic
Hypothetic
Treatment
Treatm
.............
.............
nce Interva
ce Interv
atment Arm
tment A


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
LIST OF FIGURES
Figure 1:
Anti-PD-L1 in Combination with Platinum-Based Doublets ...................... 29
Figure 2:
Overall Study Design................................................................................. 37
&(/*(1(35235,(7$5<,1)250$7,21


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
19
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer
Lung cancer is the leading cause of cancer-related deaths among men and women worldwide, 
with 1.2 million new cases diagnosed each year. Non-small cell lung cancer (NSCLC) is the 
most common type of lung cancer, accounting for 80% of all new cases. There are an estimated 
1.1 million lives lost per year (approximately 500,000 in the United States [US] and European 
Union [EU] alone) due to NSCLC. Smoking is the causative factor for up to 85% of cases 
(http://www.lungcancercoalition.org/en/pages/about/awareness).
The majority of patients are not diagnosed until the tumor has progressed beyond the primary 
site. Despite step-wise advances in patient selection, targeted agents, and optimizing
chemotherapy regimens, patients with advanced NSCLC continue to have an unmet medical 
need (Schiller, 2013).
Platinum-containing chemotherapy regimens remain (eg, platinum-based agents with taxanes) 
the standard first-line treatment in the US and Japan. In the EU, a third-generation 
chemotherapeutic agent (docetaxel, gemcitabine, paclitaxel, or vinorelbine), most commonly 
gemcitabine or vinorelbine, plus a platinum drug is used for advanced NSCLC (NICE, 2011). 
For first-line therapy in patients with Stage IV NSCLC and good performance status, the 
American Society of Clinical Oncology (ASCO) clinical practice guideline recommends 
treatment with a platinum-based two-drug combination of cytotoxic drugs (Azzoli, 2009). For 
patients without disease progression, the option of maintenance monotherapy with pemetrexed or 
erlotinib could also be considered (Gerber, 2013; Schiller, 2013). A trend that is becoming more 
prevalent is personalized NSCLC treatment based on tumor histology (squamous versus
nonsquamous), on molecular characteristics of the tumor, and on the patient’s clinical status 
using agents targeting specific receptors, kinases and pathways (ie, epidermal growth factor 
receptor [EGFR], echinoderm microtubule-associated protein-like 4 [EML4] and anaplastic 
lymphoma kinase [ALK] fusion protein).
Single agent chemotherapy (pemetrexed, EGFR-inhibitors and taxanes) are standards of care for 
second-line treatment of patients with locally advanced or metastatic NSCLC after failure of 
prior platinum-based chemotherapy. Docetaxel has been widely evaluated in this setting, and is 
currently approved by the US Food and Drug Administration (FDA) and the European 
Medicines Agency (EMA) as a single agent for the treatment of patients with locally advanced or 
metastatic NSCLC after failure of prior chemotherapy  (the US label specifies prior platinum-
based chemotherapy). For patients with a good performance status at the time of disease 
progression following first-line chemotherapy, docetaxel, despite a low response rate, was
associated with a 10% to 20% prolongation of 1-year survival and an improved quality of life 
when compared with ifosfamide, vinorelbine, or best supportive care (BSC) alone (Hanna, 
2004). Erlotinib is indicated in the US and EU for the treatment of patients with locally advanced 
or metastatic NSCLC after failure of at least one prior chemotherapy regimen, although no 
survival benefit has been demonstrated in patients with EGFR-IHC negative tumors.  
Pemetrexed is indicated in the US and EU as a single agent for the treatment of patients with 
locally advanced or metastatic nonsquamous NSCLC after prior chemotherapy. However, the 
approval and subsequent increased use of pemetrexed and erlotinib in the first-line setting poses 
an unmet need in the second-line setting, whereby new therapeutic options are needed.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Recently, nintedanib, a triple angiokinase inhibitor, was approved in the European Union (EU) in
combination with docetaxel as second-line therapy for NSCLC. The results showed that 
compared to docetaxel alone, nintedanib plus docetaxel significantly extended the median OS 
from 10.3 to 12.6 months for patients with advanced adenocarcinoma, after first-line 
chemotherapy (p = 0.0359; hazard ratio [HR]: 0.83) (Reck, 2014a). In addition, ramucirumab 
was approved in the US in combination with docetaxel as second-line therapy. The Phase 3 
REVEL trial compared ramucirumab, a vascular endothelial growth factor (VEGFR)-2 
antagonist, plus docetaxel with placebo plus docetaxel in NSCLC patients who experienced 
disease progression after treatment with platinum-based chemotherapy for locally advanced or 
metastatic disease. Median OS was better in the ramucirumab group than in the placebo group 
(10.5 vs 9.1 months; HR, 0.857; p = .0235), as was median progression-free survival (PFS) (4.5 
vs 3.0 months; HR, 0.762; p < .0001) (Garon, 2014).
More recently, advances in immunotherapy have seen approvals of nivolumab (US and EU) and 
pembrolizumab (US) in the advanced NSCLC setting after prior chemotherapy. In this setting,
nivolumab has shown benefit in overall survival with 9.2 months (95% CI, 7.3 to 13.3) versus 
6.0 months (95% CI, 5.1 to 7.3) with docetaxel in advanced squamous NSCLC (Checkmate 017 
study) (Brahmer, 2015), and 12.2 months (95% CI, 9.7 to 15.0) versus 9.4 months (95% CI, 8.1 
to 10.7) with docetaxel (HR 0.73; 95% CI, 0.59 to 0.89; p = 0.002) in nonsquamous disease
(Checkmate 057 study) (Borghaei, 2015). However, PFS benefit was modest (3.5 months with 
nivolumab versus 2.8 months with docetaxel (HR 0.62; 95% CI, 0.47 to 0.81; p <0.001) or did 
not favor nivolumab in these populations. Regarding its safety profile, nivolumab is most 
commonly associated with immune-related adverse reactions. Most of these including severe 
reactions resolved following initiation of appropriate medical therapy, or withdrawal of 
nivolumab. In the pooled dataset of two studies in squamous NSCLC, the most frequent adverse 
reactions were fatigue (33%), decreased appetite (15%), and nausea (12%). The majority of 
adverse reactions were mild to moderate (Grades 1 or 2) (Opdivo® Prescribing Information). In
comparison, the efficacy of pembrolizumab was investigated in a sub-group of a cohort of 280 
patients enrolled in a multicenter, open-label multi-cohort, activity-estimating study which 
showed an overall response rate (ORR) of 41% (95% CI, 29 to 54) in both squamous and 
nonsquamous subjects. Serious adverse reactions occurred in 38% of patients receiving 
pembrolizumab and the most frequent reported in at least 2% of patients were pleural effusion, 
pneumonia, dyspnea, pulmonary embolism, and pneumonitis (Keytruda® Prescribing 
Information).
Similarly and as will be described below, the PD-L1 inhibitor durvalumab has demonstrated 
encouraging clinical activity both as a monotherapy and in combination with other agents 
including standard chemotherapies in metastatic melanoma, NSCLC and other advanced solid 
tumors, with acceptable and manageable reported toxicities.
1.2.
nab-Paclitaxel in NSCLC
nab-Paclitaxel is approved in the first-line setting in combination with carboplatin for patients 
with NSCLC in the US, EU, Japan, Argentina, Australia, New Zealand and other countries.  The 
approval was based on the evaluation of Phase I and II data (Belani, 2008; Rizvi, 2008; Socinski, 
2010), as well as the pivotal Phase 3 study (CA031), (Socinski, 2012). The pivotal Phase 3 study 
was a multicenter, randomized, open-label study conducted in 1052 chemo-naïve subjects with 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
21
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Stage IIIB/IV NSCLC to compare nab-paclitaxel in combination with carboplatin to paclitaxel 
injection in combination with carboplatin as first-line treatment in patients with advanced 
NSCLC. nab-Paclitaxel was administered as an IV infusion over 30 minutes at a dose of 
100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel injection was administered as 
an IV infusion over 3 hours at a dose of 200 mg/m2, following premedication. In both treatment 
arms carboplatin at a dose of area under the curve (AUC) = 6 mg*min/mL was administered IV
on Day 1 of each 21-day cycle after completion of nab-paclitaxel/paclitaxel infusion. Treatment 
was administered until disease progression, development of an unacceptable toxicity or patient 
withdrawal. The primary efficacy outcome measure was overall response rate (ORR) as
determined by a central independent review committee using RECIST guidelines (Version 1.0).
In the intent-to-treat (all-randomized) population, the median age was 60 years, 75% were men, 
81% were white, 49% had carcinoma/adenocarcinoma, 43% had squamous cell lung cancer, 76% 
were ECOG performance status (PS) 1, 15% were ≥70 years of age and 73% were current or 
former smokers. Patients received a median of 6 cycles of treatment in both study arms. Patients 
in the nab-paclitaxel/carboplatin arm had a statistically significantly higher overall response rate 
compared to patients in the paclitaxel injection/carboplatin arm [(33% versus 25%; response rate 
ratio, 1.313; 95% CI, 1.082 to 1.593; p = 0.005), see Table 2].
Non-inferiority analysis of overall survival (OS) demonstrated that nab-paclitaxel/carboplatin
(nab-p/C) treatment is not inferior to paclitaxel/carboplatin (P/C) treatment. Overall survival in 
the nab-paclitaxel arm was 12.1 months versus 11.2 months in the control arm (p = 0.271; HR = 
0.922). There was an approximately 10% increase in PFS in the nab-p/C versus P/C arm and PFS 
in the nab-p/C arm was noninferior to PFS in the P/C arm (HRnab-p/C/P/C 95% CI upper bound, 
1.086).
Table 2:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat
Population)
Variable
Category/Statistic
nab-Paclitaxel/
carboplatin
(N=521)
Paclitaxel/
carboplatin
(N=531)
Response Rate 
Ratio
(pA/pT)
p-value
Patients with Confirmed Complete or Partial Overall Response
n (%)
170 (33%)
132 (25%)
1.313
0.005*
Confidence Interval (CI) a
28.6, 36.7
21.2, 28.5
1.082, 1.593
Complete Response, n (%)
0
1 (< 1%)
Partial Response, n (%)
170 (33%)
131 (25%)
PA/PT: response rate of nab-paclitaxel/response rate of paclitaxel.
a 95% CI of response rate and 95.1% CI of response rate ratio.
* Indicates p-value < 0.049.
Note: p-value is based on a chi-square test.
Source: Data on File.
Adverse events (AEs) were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. The following common (≥ 10% incidence) AEs
&(/*(1(35235,(7$5<,1)250$7,21
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ource
ource:


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
were observed at a similar incidence in nab-paclitaxel/carboplatin and paclitaxel/carboplatin
arms: alopecia 56%, nausea 27%, fatigue 25%, decreased appetite 17%, asthenia 16%, 
constipation 16%, diarrhea 15%, vomiting 12%, dyspnea 12%, and rash 10% (incidence rates are 
for the nab-paclitaxel plus carboplatin treatment group). Toxicities, particularly neuropathy and 
Grade 3/4 neutropenia were less pronounced using nab-paclitaxel in the dose and schedule 
employed. Laboratory-detected abnormalities which occurred with a difference ≥5% for nab-
paclitaxel plus carboplatin versus paclitaxel injection plus carboplatin (Grades 1 to 4 [and Grade 
3/4]) were: anemia (98% vs 91% [28% vs 7%]), neutropenia (85% vs 83% [47% vs 58%]) and 
thrombocytopenia (68% vs 55% [18% vs 9%]).  
1.3.
Rationale for nab-Paclitaxel as Second/Third-line Treatment in
Subjects with Advanced NSCLC
Patients who fail first-line chemotherapy are eligible for second-line treatment with single agent 
docetaxel, pemetrexed or erlotinib. In patients with good performance (eg, ECOG PS 0 or 1) and 
general health status, further treatment with chemotherapy is an important consideration that has 
been shown to extend overall survival. Despite the availability of second-line therapy, the trend 
of increased use of pemetrexed, as well as erlotinib (in selected patients) in the first-line and 
maintenance settings, potentially limits the number of available second-line treatment options for 
many patients. Furthermore, the tolerability issues associated with the administration of 
docetaxel once every 3 weeks (q3w) has prompted active research in the past decade to evaluate 
whether weekly regimens of taxanes could be optimized to improve the toxicity profile. The 
availability of an effective second-line cytotoxic chemotherapy with an improved efficacy/safety
profile over current available options would be a valuable addition for both the patient and the 
treating physician. Paclitaxel has also demonstrated potential activity in second-line NSCLC in a 
few studies (Socinski, 1999; Juan, 2002; Socinski, 2002; Sculier, 2002; Buccheri, 2004; Ceresoli, 
2004; Yasuda, 2004). More recently, advances in immunotherapy have seen increased use of 
immune checkpoint inhibitors (eg, nivolumab, pembrolizumab) in the first and/or second-line 
setting for advanced NSCLC disease. 
nab-Paclitaxel exhibits 10-fold higher mean Cmax of free paclitaxel, delivers 33% higher drug 
concentration to tumors in preclinical xenograft models, and demonstrates enhanced transport 
across endothelial cell monolayers, when compared with paclitaxel (Desai, 2006; Gardner, 
2008). Distribution of nab-paclitaxel to peripheral tissues as demonstrated in a recent study was 
4-fold faster and 10-fold more extensive than of Cremophor EL-paclitaxel micelles, which 
results in a unique and distinct profile of paclitaxel in tissues (Li, 2015). The Cremophor EL-free 
medium enables nab-paclitaxel to be given over a shorter duration without the need for 
premedication to prevent solvent-related hypersensitivity reactions, thus also avoiding negative 
impact of steroids on paclitaxel induced apoptosis and decreased antitumoral activity of 
chemotherapeutic agents as reported in pre-clinical models glucocorticoids (Abraxane®
Prescribing Information; Zavodovskaya, 2015; Herr, 2003; Sui, 2006; Khan, 2013; Pang, 2006).
When administered with carboplatin in the first-line setting, weekly nab-paclitaxel has 
demonstrated a more favorable efficacy:safety profile compared to the every 3 weeks schedule.  
This weekly schedule of nab-paclitaxel allows the opportunity for closer (ie, shorter interval)
monitoring of side effects and optimizing dose-intensity through timely adjustments.  
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
23
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Finally, recently published data has demonstrated efficacy of nab-paclitaxel as monotherapy in 
the second line setting in advanced NSCLC with ORR ranging from 16.1% to 33% and a median 
PFS of up to 5 months (Chen, 2012; Saxena, 2012; Yuan, 2012).  
Rationale for dose and schedule
As previously noted, nab-paclitaxel 100 mg/m2 weekly (Days 1, 8 and 15) in combination with 
carboplatin (21 day cycle) is approved in the US, EU, Japan, Argentina, Australia, New Zealand 
and other countries for the treatment of locally advanced or metastatic NSCLC in the first-line 
setting.  However, there is limited data of monotherapy nab-paclitaxel in the second or third-line 
setting; hence, this study will assess the efficacy and tolerability of weekly nab-paclitaxel, when 
administered on Days 1 and 8 of each 21-day cycle.  The allowance of a one week rest period in 
this study (ie, no treatment on Day 15), takes into account research findings from other taxanes, 
whereby patients in the second-line setting are unlikely to tolerate the same dose-intensity 
compared to chemo-naïve patients (eg, sharper dose reduction in the second-line setting). 
Therefore, the proposed nab-paclitaxel schedule (2 weeks treatment, 1 week rest) could offer the 
option of maintaining consistent dose-intensity for NSCLC patients in this setting.
1.4.
Rationale for nab-Paclitaxel in Combination With Epigenetic 
Modifying Therapy of CC-486 as Second/Third-line Treatment in 
Subjects with Advanced NSCLC
CC-486 is an orally bioavailable formulation of the nucleoside analog 5-azacitidine (AZA).  
After its incorporation into a cell’s DNA during the S-phase of the cell cycle, CC-486 forms 
covalent adducts with DNA Methyltransferase 1 (DNMT1) and depletes this enzyme required for 
the maintenance of DNA methylation patterns, thereby altering the epigenetic status of the cell. 
Epigenetic changes are covalent modifications of chromatin (DNA and histone proteins) that 
mediate the stable transmission of a gene’s transcriptional status through cell division.  One of 
the first recognized epigenetic alterations in cancer was DNA methylation. The addition of a 
methyl group to cytosine in the dinucleotide CpG is catalyzed by DNA methyltransferases 
(DNMTs) and is associated with transcriptional repression of genes with high density of CpGs 
(CpG islands) in the vicinity of their promoters (Jones, 2007).  Genomic methylation patterns are 
precisely regulated during normal embryonic development and differentiation and have been 
found to be altered in specific ways in cancer. Specifically, cancer cell genomes are typified by 
reduced methylation globally with focal areas of aberrant hypermethylation in the CpG islands of 
genes encoding known tumor suppressors such as PTEN and BRCA1 as well as genes encoding 
proteins required for apoptosis, including caspase 8, DAPK and Apaf-1.  DNA methylation-
based silencing can thus contribute to the establishment and maintenance of the transformed state 
and limit the effectiveness of anti-cancer therapies.  The recognition of the role of aberrant 
methylation in carcinogenesis and its reversibility has led to the development of DNMT 
inhibitors for cancer. Subcutaneous (SC) AZA was the first DNMT inhibitor to be approved in 
myelodysplastic syndromes (MDS) in 2004 (Kaminskas, 2005).
The notion that sequential treatment with an epigenetic modifying agent followed by a cytotoxic
agent can result in improved response to the latter is supported by numerous preclinical 
experiments and now by early clinical results.  In breast cancer cell lines, restoring expression of 
the aberrantly methylated pro-apoptotic gene TMS1 with azacitidine can restore taxane 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
24
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
sensitivity (Gordian, 2009).  In a model of platinum resistant ovarian cancer, azacitidine reversed 
resistance to carboplatin (Li, 2009).  This effect required pretreatment of the cells with 
noncytotoxic levels of azacitidine for 24 hours before the addition of carboplatin and was not 
observed with concurrent exposure to both agents.  More recently, Juergens and colleagues 
observed an unusually high ORR of approximately 20% in multiple-relapsed NSCLC patients 
treated with a variety of regimens after being treated with a combination of SC AZA and another 
epigenetic agent, entinostat, a histone deacetylase inhibitor (Juergens, 2011).  In one case, a 
patient who had previously progressed on a regimen of paclitaxel, carboplatin and bevacizumab 
responded to the same triplet after treatment with SC AZA and entinostat, suggesting that the 
epigenetic modifying agents had reversed acquired resistance to the cytotoxic/anti-angiogenic 
regimen.  In a Phase 1/2 study of SC AZA with nab-paclitaxel in subjects with advanced 
metastatic solid tumors and breast cancer (Dumlao, 2011), escalating doses of SC AZA (75 to
100 mg/m2) were administered on Days 1 through 5, followed by nab-paclitaxel (100 mg/m2) 
intravenous (IV) on Days 8, 15, and 22 of a 28-day cycle.  Of 16 subjects treated at the time of 
publication, clinical activity has included 3 complete responses (CR, 1 Diffuse Large B-cell 
Lymphoma [DLBCL], 2 ovarian), 4 partial responses (PR) in ovarian and endometrial cancer 
and 4 stable diseases (SD, 2 lung, 1 pancreatic, and 1 sarcoma).  
CC-486 entered clinical testing in 2006 in subjects with MDS, chronic myelomonocytic 
leukemia [CMML], and acute myeloid leukemia [AML], with daily extended dosing schedules 
of 14 and 21 out of 28 days in a non-crossover fashion.  Daily doses of 300 mg CC-486 have 
proven to be tolerated on both the 14 and 21 out of 28-day schedules with myelosuppression, 
gastrointestinal symptoms, and fatigue being the most common toxicities (Garcia-Manero, 
2011).  Subjects treated with CC-486 for 14 or 21 days had DNA hypomethylation that persisted 
through the end of cycle.  This contrasts with the lack of persistent hypomethylation at the end of 
cycle when subjects were treated with SC AZA for 7 out of 28 days. 
 
 
 
  
 
 
 
 
 
 
 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
25
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
This Phase 2 study will test the hypothesis that epigenetic modifying therapy with CC-486 can 
improve the anti-tumor activity of nab-paclitaxel in second/third-line NSCLC patients (see 
Section 4.2 for study rationale). Although docetaxel has been assessed in other randomized 
studies as a chemotherapy backbone, the considerable neutropenia-related toxicity could 
potentially pose safety concerns if combined with CC-486, and the steroid premedication could 
confound the epigenetic impact of CC-486.  In addition, the q3w dosing schedule of docetaxel 
restricts dose adjustment options, thus potentially yielding lower chemotherapy dose-intensity.
Please refer to the Investigator’s Brochures (IBs) of CC-486 and nab-paclitaxel (ABI-007) for 
detailed information concerning the available pharmacology, toxicology, drug metabolism, 
clinical studies, and adverse event profile of the IPs.
 
 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
26
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
1.5.
Rationale for nab-Paclitaxel in Combination With Immunotherapy 
of Durvalumab as Second/Third-line Treatment in Subjects with 
Advanced NSCLC
Durvalumab 
Durvalumab is a human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa 
subclass that inhibits binding of PD-L1 to PD-1 and CD80 and is being developed by 
AstraZeneca/MedImmune for use in the treatment of cancer.  (MedImmune is a wholly owned 
subsidiary of AstraZeneca; AstraZeneca/MedImmune will be referred to as AstraZeneca 
throughout this document.)  As durvalumab is an engineered mAb, it does not induce antibody-
dependent cellular cytotoxicity or complement-dependent cytotoxicity.  The proposed 
mechanism of action for durvalumab is interference of the interaction of PD-L1 with PD-1 and 
CD80.
To date durvalumab has been given to more than 1900 patients as part of ongoing studies either 
as monotherapy or in combination with other anti-cancer agents.  Refer to the current 
durvalumab Investigator’s Brochure for a complete summary of non-clinical and clinical 
information including safety, efficacy and pharmacokinetics.  
A Phase 2 trial of durvalumab is currently ongoing to assess efficacy and safety of the immune 
checkpoint inhibitor (dose of 10 mg/kg once every two weeks [q2w]) in patients with locally 
advanced or metastatic NSCLC in the third-line setting (Rizvi, 2014) (ATLANTIC trial, 
NCT02087423). 
 
Preliminary data of an open-label Phase 1b study of durvalumab 20 mg/kg every 4 weeks plus 
tremelimumab 1 mg/kg in immunonaive patients with advanced or metastatic squamous or non-
squamous NSCLC showed a manageable tolerability profile, with antitumor activity irrespective 
of PD-L1 status (ORR 22%, 95% CI 9-44) (Antonia, 2016).  
 
 
 
 
 
 
 
 
 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
27
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
nab-Paclitaxel in combination with immune checkpoint inhibitors
Tumor lysis as a consequence of chemotherapy treatment leads to release of tumor antigens, 
which in turn are recognized by the immune system, thus priming the immune system for 
checkpoint inhibitor activity (Bracci, 2014; Chen, 2013; Mellman, 2011). Accumulating 
evidence suggests that immune activation plays an important role in chemotherapy efficacy
(Zitvogel, 2013). In addition to increasing tumor antigenicity, chemotherapy also reduces tumor 
burden and acts directly on immune cell populations, activating dendritic cells, depleting 
immunosuppressive regulatory T cells at low doses, depleting myeloid-derived suppressor cells, 
and increasing tumor-infiltrating lymphocytes (Tanaka, 2009; Banissi, 2009; Kodumudi, 2010; 
Dieci, 2014). Taxanes have been shown to facilitate dendritic cell maturation and cytokine 
secretion (Chen, 2013a). In patients with lung cancer, paclitaxel was associated with generation
of pro-inflammatory markers, including interleukin 2 and interferon gamma, and the expression 
of T cell activation markers (Zhang, 2008). Taxanes have been demonstrated to modulate the 
immune system by impairing regulatory T cells, which are drivers of peripheral tolerance, but 
not effector T cells, which are drivers of tumor-cell killing (Tanaka, 2009). Taxanes are also 
known to act on myeloid cells such as myeloid-derived suppressor cells and alternatively 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
28
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
differentiated (M2) macrophages to decrease their immunosuppressive functions (Kodumudi, 
2010).
The data above suggest a potential for synergistic activity of cytotoxic therapy, such as taxanes, 
with checkpoint inhibitors, including those that target PD-1 or PD-L1.  nab-Paclitaxel has 
demonstrated cytotoxic activity in non-small cell lung cancer (overall response rate = 33% vs 
25% with paclitaxel in a Phase III trial) (Socinski, 2012) and, as stated above, does not require 
steroid pretreatment, which may make it a logical choice for combination with immune 
checkpoint inhibitor.
Therefore, this Phase 2 study will further assess the potential synergistic activity of nab-
paclitaxel, a cytotoxic agent, in combination with the anti-PD-L1 checkpoint inhibitor 
durvalumab in second/third-line treatment for advanced NSCLC, from an efficacy and safety 
standpoint.  The current study will allow patients who progress on prior checkpoint inhibitor 
therapy (eg, as their first-line or second-line therapy) as it is hypothesized that the companion 
chemotherapy of nab-paclitaxel may re-sensitize the disease to allow patient to respond to 
checkpoint inhibitors.
!
nab-Paclitaxel in combination with anti-PD-L1
More recently, preliminary results of an ongoing Phase 1b trial in first line metastatic NSCLC of
another immune checkpoint anti-PD-L1 inhibitor, atezolizumab, showed high response rates in 
combination with the following platinum-based doublets: 60 % (95% CI: 15-95) in the 
carboplatin/paclitaxel cohort (Arm C; n = 5), 75% (95% CI: 43-95) in the 
carboplatin/pemetrexed arm (Arm D; n=14), and 62 % (95% CI: 32-86) with four patients 
experiencing complete response when atezolizumab was combined with carboplatin/nab-
paclitaxel regimen (Arm E; n=13) (Liu, 2015). The most frequent AEs included nausea (Arms C 
and D, 50%; Arm E, 73%), fatigue (Arm C, 38%; Arm D, 36%; Arm E, 73%) and constipation 
(Arm C, 25%; Arm D, 71%; Arm E, 27%). The most common MPDL3280A-related Grades 3 to 
4 AEs included anemia (Arms D and E, 7%), neutropenia (Arm C, 13%; Arm D, 7%) and 
thrombocytopenia (Arms D and E, 7%). No pneumonitis was seen. One MPDL3280A-related 
Grade 5 AE due to candidemia after prolonged neutropenia was seen in Arm D. Thirty patients
were efficacy evaluable (Arm C, 5; Arm D, 12; Arm E, 13). Overall, treatment with 
atezolizumab plus chemotherapy (including maintenance therapy) was well tolerated, without
apparent exacerbation of chemotherapy-associated adverse events.
 
 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
29
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Figure 1:
Anti-PD-L1 in Combination with Platinum-Based Doublets
Liu et al. ASCO- June 2015. Abstract 8030
!
nab-Paclitaxel in combination with anti-PD-1
An ongoing Celgene-sponsored Phase 1 trial (NCT02309177) in solid tumors is assessing the 
safety and efficacy of the anti-PD-1 agent nivolumab in combination with nab-paclitaxel and
carboplatin in a cohort of subjects with advanced NSCLC patients in the first-line setting (nab-
paclitaxel 100 mg/m2 on Days 1, 8 and 15 and carboplatin AUC 6 on Day 1 of each 21-day cycle 
(Cycles 1 to 4 only); nivolumab 5 mg/kg on Day 15 of each 21-day cycle starting in Cycle 1). 
Preliminary results show that amongst the 9 subjects having received study treatment including 
nivolumab, 6 had partial responses and 3 stable disease. No dose limiting toxicities were 
observed. Most common AEs were low grade vomiting, diarrhea, alopecia, peripheral 
neuropathy and neutropenia (data on file). These results are consistent with another Phase 1 trial 
comparing anti-PD-1 antibody nivolumab (10 mg/kg IV q3w) combined with three different 
platinum-doublet regimens in 52 patients with chemotherapy-naïve advanced NSCLC, with a
reported ORR of 33% with gemcitabine/cisplatin, 47% with pemetrexed/cisplatin, as well as with 
paclitaxel/carboplatin, while stable disease was reported in 58%, 47%, and 27% of subjects, 
respectively (Checkmate 012; NCT01454102); (Antonia, 2014). Grades 3 to 4 treatment-related 
adverse events were reported in 45% of patients (25% to 73% across arms), including 
pneumonitis (4 patients, 7%; managed by protocol algorithm), and fatigue and acute renal failure 
(3 patients, 5% each).
Rationale for fixed dose and schedule 
 
 
 
 
 
 
 
 
 
 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
30
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
was developed for tremelimumab using data from Phase 1 through Phase 3 (N=654; doses= 0.01 
to 15 mg/kg q4w or once every 90 days (Q90D); metastatic melanoma) (Wang, 2014). A 
population PK model indicated minor impact of body WT on the PK of tremelimumab 
(coefficient of ≤ 0.5). The WT-based (1 mg/kg q4w) and fixed dosing (75 mg/kg q4w; based on 
median body WT of ~75 kg) regimens were compared using predicted PK concentrations (5th, 
median and 95th percentiles) using a population PK model in a simulated population of 1000 
patients with body WT distribution of 40 to 120 kg. Similar to durvalumab, simulations indicated 
that both body WT-based and fixed dosing regimens of tremelimumab yield similar median 
steady state PK concentrations with slightly less between-subject variability with fixed dosing 
regimen.
Similar findings have been reported by others (Ng, 2006; Wang, 2009; Zhang, 2012; Narwal,
2013). Wang and colleagues investigated 12 monoclonal antibodies and found that fixed and 
body size-based dosing perform similarly, with fixed dosing being better for 7 of 12 antibodies 
(Wang, 2009). In addition, they investigated 18 therapeutic proteins and peptides and showed 
that fixed dosing performed better for 12 of 18 in terms of reducing the between-subject 
variability in PK/PD parameters (Zhang, 2012). 
A fixed dosing approach is preferred by the prescribing community due to ease of use and 
reduced dosing errors. Given the expectation of similar PK exposure and variability, it is 
considered feasible to switch to fixed dosing regimens.
Sequential administration of chemotherapy and checkpoint inhibitor will allow for limitation of 
potential interactions and better management of toxicities.
Please refer to the Investigator’s Brochures (IBs) of durvalumab and nab-paclitaxel (ABI-007) 
for detailed information concerning the available pharmacology, toxicology, drug metabolism, 
clinical studies, and adverse event profile of the investigational products (IPs).
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
31
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
2.
STUDY OBJECTIVES
2.1.
Primary Objective 
The primary objective of the study is:
!
To estimate the efficacy of nab-paclitaxel administered intravenously (IV) on Days 8 
and 15 with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 
14 every 21 days, or nab-paclitaxel administered intravenously (IV) on Days 1 and 8
with immunotherapy of durvalumab administered IV on Day 15 every 21 days, and 
nab-paclitaxel monotherapy administered IV on Days 1 and 8 every 21 days as 
second/third-line treatment for advanced NSCLC.
2.2.
Secondary Objective
The secondary objective of the study is:
!
To estimate the relative efficacy of each of the combination therapy arms to the 
monotherapy arm.
!
To evaluate the safety and tolerability of nab-paclitaxel administered IV on Days 8 
and 15 with epigenetic modifying therapy of CC-486 QD on Days 1 to 14 every 21 
days, or nab-paclitaxel administered intravenously (IV) on Days 1 and 8 with 
immunotherapy of durvalumab administered IV on Day 15 every 21 days, and nab-
paclitaxel monotherapy administered IV on Days 1 and 8 every 21 days as 
second/third-line treatment for advanced NSCLC.
2.3.
Exploratory Objectives
The exploratory objectives of the study are:
!
To assess healthcare resource utilization for the treatment arms.
!
To assess the quality of life (QoL) for the treatment arms.
!
To determine baseline tumor characteristics which predict response to nab-paclitaxel 
as a single agent and with epigenetic modifying therapy of CC-486 or immunotherapy 
of durvalumab. 
!
To evaluate genomic correlates of response to nab-paclitaxel as a single agent and 
with epigenetic modifying therapy of CC-486 or immunotherapy of durvalumab.
!
To evaluate anti-tumor activity of nab-paclitaxel/durvalumab combination therapy 
using investigator assessment according to immune related response criteria updated 
with RECIST 1.1 (irRECIST), and its association with PD-L1 expression.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
32
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
3.
STUDY ENDPOINTS
Study efficacy endpoints will be assessed by the Investigator using RECIST 1.1 guidelines.
3.1.
Primary Endpoint
The primary endpoint is:
!
Progression free survival.
3.2.
Secondary Endpoints
The secondary endpoints are: 
3.2.1.
Efficacy
!
Disease control rate.
!
Overall response rate.
!
Overall survival.
3.2.2.
Safety
!
The type, frequency, and severity of AEs and SAEs graded using National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, 
Version 4.0). 
!
Discontinuation rate.
!
The median dose intensity.
!
The incidence of dose reduction.
3.3.
Exploratory Endpoints
!
Healthcare resource utilization during the study via patient feedback.
!
Changes in the Lung Cancer Symptom Scale (LCSS), European Organisation for 
Research and Treatment of Cancer (EORTC) QLQ C30, and EuroQoL 5D-5L (EQ-
5D-5L).
!
The correlation between pretreatment tumor characteristics and response to the study 
treatment determined using next-generation sequencing methods, 
immunohistochemistry, or other analysis methods.
!
Analysis of PFS and DCR and their association with PD-L1 expression using 
Investigator’s assessments according to irRECIST. 
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In
In


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
33
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is a Phase 2, open-label, multicenter study to assess safety and efficacy of:
!
nab-paclitaxel in combination with epigenetic modifying therapy of CC-486,
!
nab-paclitaxel in combination with immunotherapy of durvalumab, 
!
and nab-paclitaxel monotherapy 
as second/third-line treatment in subjects with advanced NSCLC who have received no more 
than one prior chemotherapy regimen. Approximately 240 subjects with advanced NSCLC will 
be assigned 1:1:1 into one of the following treatment arms: nab-paclitaxel/CC-486, nab-
paclitaxel/durvalumab combination therapy or nab-paclitaxel monotherapy prior to receiving the 
first dose of investigational product (IP). Randomization (details in Section 10.1), when 
conducted, will be centralized and stratified by ECOG performance status (0 versus 1, see 
Appendix A), gender (males versus females), and smoker (yes versus no).
The study will consist of up to a 28-day Screening Period, a Treatment Period and a Follow-up 
Period.  
4.1.1.
Screening Period 
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of IP.
4.1.2.
Treatment Period 
The Treatment Period begins with the first dose of IP as described in Section 8.  Subjects will 
receive one of the following treatments based on the randomization/treatment assignment:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 
durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15 of each 21-
day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle.
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zoledronic acid, 
denosumab) is permitted as per the Investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, withdrawal of 
consent, or termination of the study by the Sponsor.
During the study, subjects will have computed tomography (CT) scans every 42 days (-3/+7 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the Sponsor. Tumor evaluations will be assessed by the 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
34
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
investigative sites and response will be determined according to RECIST 1.1 guidelines, and 
immune-related RECIST criteria (irRECIST) when applicable. All scheduled laboratory samples 
will be sent to a central laboratory for analysis. Local hematology and chemistry tests may be 
performed as required for subject management/treatment decisions. Local laboratory values that 
are considered abnormal and clinically significant will be recorded as an AE/SAE and also 
recorded on the laboratory eCRF (see Section 11.3).
4.1.2.1.
Treatment Beyond Progression for Subjects in the nab-Paclitaxel/Durvalumab 
Arm
Subjects in the nab-paclitaxel/durvalumab arm may be permitted to continue treatment beyond 
initial RECIST 1.1 defined progressive disease as long as they meet the following criteria:
!
Continue to meet all other study protocol eligibility criteria
!
Investigator assessed clinical benefit and absence of rapid disease progression or 
clinical deterioration
!
Stable performance status
!
Tolerance to IP
!
Treatment beyond progression will not delay an imminent intervention to prevent
serious complications of disease progression (eg, brain metastases)
Subjects will be re-consented with an informed consent document describing any reasonably 
foreseeable risks or discomforts and other alternative treatment options.
Response assessment should continue every 42 days (-3/+7 days) as per Table of Events
(Table 4). The assessment of clinical benefit should be balanced by clinical judgment as to 
whether the subject is clinically deteriorating and unlikely to receive any benefit from continued 
treatment with nab-paclitaxel/durvalumab. If the Investigator feels that the subject continues to 
achieve clinical benefit by continuing treatment and the subject consents, the subject may remain 
on the trial and will continue to receive monitoring according to the schedule in the Table of 
Events. The decision to continue treatment should be discussed with the Sponsor’s Medical 
Monitor and documented in the study source documents.
Study therapy should be discontinued if further progression is documented by irRECIST. 
4.1.3.
End-of-Treatment Visit
The End-of-Treatment Visit is defined as the visit when decision for treatment discontinuation is 
made. 
4.1.4.
Follow-up Period
All subjects who discontinue from treatment for reasons other than withdrawal of consent, lost to 
follow-up, death, or termination of the study by the Sponsor will enter the Follow-up Period. It 
will consist of a visit 28 days after last dose of IP or End-of-Treatment Visit, whichever is later,
followed by phone follow-up for survival approximately every 90 days (+/- 14 days) for at least
12 months after the last subject is randomized or 120 PFS events have been observed, whichever 
comes later, between the nab-paclitaxel/CC-486 combination and nab-paclitaxel monotherapy 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
35
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
arms. Subjects in the nab-paclitaxel/durvalumab arm will also attend a follow-up visit 90 days 
after the last dose of IP, and will be followed for survival in a similar manner for at least 12 
months after the last subject is assigned to this arm. Those subjects entering the Follow-up 
Period without documented progression will continue to have CT scans in accordance with local 
standard of care (or approximately every 90 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death, or termination of the study by the Sponsor. All 
post-treatment anticancer therapies will be recorded during the Follow-up Period.  
4.2.
Study Design Rationale
This is an open-label study designed to estimate the effects of adding CC-486 or durvalumab to 
nab-paclitaxel and nab-paclitaxel monotherapy in second/third-line NSCLC. A placebo-
controlled study would not be feasible for this population as blinding would be difficult and 
would need a double dummy design.  
A key objective in this study is to determine the chemo-priming effect of CC-486 and to estimate 
the effect of the combination of nab-paclitaxel with PD-L1 checkpoint inhibitor. Second/third-
line NSCLC enables a unique setting to evaluate epigenetics: 
a) It is currently unknown whether patients in second or later lines of treatment have 
optimal immune function/reserve which is critical for safety and activation of immune 
cells that target cancer cells,
b) Due to the overlapping (and dose-limiting) toxicities of doublet/triplet chemotherapy 
regimens in the first-line setting, it would be very challenging to combine epigenetic 
therapy at a dose level to elicit clinically meaningful benefit.
Although docetaxel has been assessed in other randomized studies as a chemotherapy backbone
as shown in Table 3, the considerable neutropenia-related toxicity could potentially pose safety 
concerns if combined with CC-486, and the steroid premedication could confound the epigenetic 
impact of CC-486.  In addition, the q3w dosing schedule of docetaxel restricts dose adjustment 
options, thus potentially yielding lower chemotherapy dose-intensity. As mentioned above, nab-
paclitaxel has shown benefit for both squamous and nonsquamous histologies. Furthermore, 
recent data with immune checkpoint inhibitors (eg, nivolumab) have shown greater efficacy in 
subjects with squamous histology versus nonsquamous histology with manageable toxicities. 
Hence it will be important in the current study to assess the efficacy and safety of nab-paclitaxel 
either as monotherapy or in combination treatment in subjects with squamous and nonsquamous 
NSCLC histologies.
For patients with NSCLC whose disease progressed after initial chemotherapy, the goal of 
therapy is to delay further progression for as long as possible; hence, the use of PFS as the 
primary endpoint for efficacy evaluation.  
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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36
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Table 3:
Data for Control Arms using Taxanes from Phase II and III Studies Blinded
Study compound
(year)
Doce
(Shepherd, 
2000)
Doce
(Hanna, 
2004)
nab-Pac
(Chen  
2012, 
Saxena, 
2012, 
Yuan 
2012)
Doce
(Reck, 
2014a)
LUME-1
Doce
(Garon, 
2014)
Doce
(Brahmer, 
2015)
Checkmate 
017 
Doce
(Borghaei, 
2015)
Checkmate 
057
Doce 
(Vansteenkiste, 
2015)
POPLAR
Phase
III
III
II
III
III
III
III
II
N
55 + 48
288
16 (x2) -  
33
272
625
137
290
143
Efficacy
ORR (%)
7.1
8.8
18 - 33
3.3
14
9
12
15
SD rate (or DCR)
(%)
42.7
46.4
31  -  42
37.9
53
34
33
n/a
PFS (TTP)
(median, in 
months)
na
2.9
2.1 – 5.0
2.7
3.0
2.8
4.2
3.0
OS (median, in 
months)
7.0
7.9
n/a
9.1
9.1
6.0
9.4
9.7
Toxicity
Neutropenia (%)
Neutrophils 
decreased (%)
67.3
40.2
n/a
12.1
29.9
39
33
31
n/a
Febrile 
neutropenia
1.8
12.7
n/a
4.7
10
11
10
n/a
Thrombocytopenia 
(%)
0
0.4
3
NR
1
n/a
n/a
n/a
Anemia (%)
5.5
4.3
3
3.5
6
22
20
n/a
Peripheral 
Neuropathy (%)
1.8
1.1
3
NR
2
12
n/a
n/a
Fatigue / Asthenia 
(%)
18.2
5.4
3
5.1
10*
46.5
46.6
n/a
DCR = disease control rate; Doce = docetaxel; nab-Pac = nab-paclitaxel; N = number of subjects randomized; n/a = not 
available; ORR = overall response rate; OS = overall survival; PFS = progression free survival; SD = standard deviation; TTP =
time to progression; *Grade ≥ 3.
Furthermore, maintaining quality of life during this period, especially in reducing/managing 
toxicity is also an important consideration.  Therefore, the proposed study is designed to 
optimize the evaluation of efficacy with a tolerable dose/schedule of chemotherapy, and its 
combination with an epigenetic modifying therapy or with an immune checkpoint inhibitor.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
37
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Figure 2:
Overall Study Design
IP = investigational product; IV = intravenous; OS = overall survival; PFS = progression-free survival; QD = once daily.
nab-paclitaxel 100 mg/m2 IV 
infusion over 30 minutes on 
Days 1 and 8 of each 21-day 
cycle until disease progression
(n = 80)
o
nab-paclitaxel 100 mg/m2 IV 
infusion over 30 minutes on Days 
1 and 8 of each 21-day cycle 
o
durvalumab 1125 mg IV over 
approximately 1 hour on Day 15 
of each 21-day cycle
until disease progression
(n = 80)
Follow-up Period: 28-day Follow-up Visit (after last dose of IP or End-of-Treatment Visit, whichever is later)
Monotherapy or CC-486 combination arms: followed for OS by phone approximately every 90 days for at least 12 months after last subject is randomized 
in either the monotherapy arm or the CC-486 combination arm or 120 PFS events have been observed, whichever is later
nab-paclitaxel/durvalumab arm: 90-Day Follow-up Visit and consequent follow-up for OS by phone approximately every 90 days for at least 12 months 
after last subject is allocated to this arm
o
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infusion over 30 minutes on Days 
8 and 15 of each 21-day cycle
o
CC-486 200 mg orally QD
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cycle
until disease progression
(n = 80)
Screening for Eligibility (up to 28 days)
(n=240)
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
38
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
4.3.
Study Duration 
Recruitment is expected to take approximately 28 months, and the final analysis of PFS between 
the nab-paclitaxel/CC-486 combination and nab-paclitaxel monotherapy arms will be performed 
when approximately 120 PFS events have occurred, estimated as approximately 25 months from 
first subject randomized. The final analysis for the nab-paclitaxel/durvalumab arm will be 
conducted when approximately 50 events have occurred in this arm. The total length of this 
Phase 2 study with follow-up is estimated to last approximately 40 months.
4.4.
End of Trial
The End of Trial is defined as either the:
!
date of the last visit of the last subject to complete the post-treatment follow-up, or 
!
date of receipt of the last data point from the last subject that is required for primary, 
secondary and/or exploratory analysis, as prespecified in the protocol, whichever is 
the later date.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
5.
TABLE OF EVENTS
Table 4:
Table of Events
Screening/ 
Baseline
Treatment Period
Every 21-day Cycle
Follow-Up Period
Assessment
Day -28 to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu
-ation Visit
28-day Follow-up 
Visit (after last 
dose of IP)
90-day Follow-up 
Visit for subjects in 
the nab-paclitaxel/ 
durvalumab arm
(after last dose of IP)
Survival Follow-upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
Informed Consent
X
-
-
-
-
-
-
-
-
Medical History (including Tobacco 
Exposure History), Prior Medication 
and Procedures
X
-
-
-
-
-
-
-
-
Serum β-hCG b
X
-
-
-
-
-
-
-
-
Urine Pregnancy Testb
-
X
-
-
-
X
X
(nab-paclitaxel/ 
durvalumab arm)
X
(nab-paclitaxel/ 
durvalumab arm)
-
Reminder to Avoid Pregnancyb
X
-
-
-
X
X
X
-
Complete Chest CT Scan and Any 
Other Studies Required for Tumor 
Imagingc
X
-
-
-
X
Xc
-
-
X
Weight and Heightd
X
X
X
X
-
-
-
-
-
ECOG Status
X
X
-
-
-
X
X
X
-
Concomitant Medication/Procedures
-
X
X
X
-
X
X
X
X
Peripheral Neuropathy Assessmente
X
X
-
-
-
X
X
-
-
Healthcare Resource Utilization 
Questionnaire
-
X
-
-
-
X
X
-
-
LCSS, EORTC QLQ C30 and EQ-
5D-5L
-
X
-
-
-
X
X
-
-
Hematologyf,g
X
X
X
X
-
X
X
Xk
-
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
40
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Table 4:
Table of Events (Continued)
Screening/ 
Baseline
Treatment Period
Every 21-day Cycle
Follow-Up Period
Assessment
Day -28 to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu
-ation Visit
28-day Follow-up 
Visit (after last 
dose of IP)
90-day Follow-up 
Visit for subjects in 
the nab-paclitaxel/ 
durvalumab arm 
(after last dose of IP)
Survival Follow-upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
Serum Chemistryf,h
X
X
-
-
-
X
X
Xk
-
Archived Tumor Tissue Sample for 
Biomarker (biopsy, surgical 
specimen, or other diagnostic tumor 
sample)
-
X
(C1D1 
only)
-
-
-
-
-
-
-
Plasma for Biomarker Analyses
-
X
(C1D1 only 
predose)
-
-
-
-
-
-
-
Blood for Pharmacogenomic 
Analyses
-
X
(C1D1 only 
predose)
-
-
-
-
-
-
-
Adverse Event Evaluation in the 
Monotherapy or nab-Paclitaxel/CC-
486 Combination Arm
After signing ICF and until 28 days after the last dose of IP
-
-
Adverse Event Evaluation in the nab-
Paclitaxel/Durvalumab combination
Arm
After signing ICF and until 90 days after the last dose of IP
X
-
nab-PaclitaxelMonotherapy Arm and   
nab-Paclitaxel/Durvalumab
Combination Arm
nab-Paclitaxel Administration/
Accountabilityi
-
X
X
-
-
-
-
-
nab-Paclitaxel/CC-486 Combination 
Arm
nab-Paclitaxel Administration/
Accountabilityi
-
-
X
X
-
-
-
-
-
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
41
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Table 4:
Table of Events (Continued)
Screening/ 
Baseline
Treatment Period
Every 21-day Cycle
Follow-Up Period
Assessment
Day -28 to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu
-ation Visit
28-day Follow-up 
Visit (after last 
dose of IP)
90-day Follow-up 
Visit for subjects in 
the nab-paclitaxel/ 
durvalumab arm 
(after last dose of IP)
Survival Follow-upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
nab-Paclitaxel/CC-486 Combination 
arm
CC-486 Administration/
Accountabilityi
-
X
-
-
-
-
-
nab-Paclitaxel/Durvalumab
Combination Arm
Durvalumab Administration/
Accountabilityi
-
-
-
X
-
-
-
-
-
Survival Phone Call
-
-
-
-
-
-
-
-
Xa
Physical Examinationj
X
X
-
-
-
X
-
-
-
Vital Signsj
X
X
X
X
-
X
-
-
-
Electrocardiogram (ECG)
X
Will be done as per standard of care during the Treatment Period and as clinically indicated; however, results will not be routinely 
collected in the eCRFs. If CT/bone scans show lesions pertinent for RECIST 1.1 or irRECIST criteria evaluation, data will be 
collected on the pertinent tumor evaluation eCRFs. If ECGs are abnormal and clinically significant, the data will be recorded on the 
AE/SAE eCRF.
Bone Scan (X-rays if needed)
If clinically 
indicated
CT Scan of the Head or Brain 
Magnetic Resonance Imaging (MRI)
If clinically 
indicated 
(mandatory if 
symptomatic)
AE = adverse event; β-HCG = beta human chorionic gonadotropin; C1D1 = Cycle 1 Day 1; CT = computed tomography; ECOG = Eastern Cooperative Oncology Group; eCRF =
electronic Case Report Form; EORTC QLQ C30 = European Organisation for Research and Treatment of Cancer QLQ C30; EQ-5D-5L = EuroQol 5D-5L; ICF = informed 
consent form; IP = investigational product; irRECIST = immune-related Response Evaluation Criteria in Solid Tumors; IV = intravenous; LCSS = Lung Cancer Symptom Scale;
QD = once daily; RECIST = Response Evaluation Criteria in Solid Tumors; SAE = serious adverse event.
a Every 90 (+/-14) days (from 28-day Follow-up Visit ) for at least 12 months after the last subject is randomized in either the monotherapy or the CC-486 combination arms or 
120 PFS events have been observed whichever comes later. Subjects in the nab-paclitaxel/durvalumab arm will be followed for survival in a similar manner for at least 12 
months after the last subject is assigned to this arm.
b All males and all women of child-bearing potential must be reminded to avoid pregnancy prior to administration of IP before beginning each new cycle, at the End-of-Treatment 
Visit and at the Follow-up Visits. A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a serum β-hCG pregnancy test 
must be performed to assess eligibility at Screening/Baseline. Note: the screening serum pregnancy test can be used as the Cycle 1 Day 1 test prior to study therapy if it is 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
42
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
performed within the 72-hour timeframe.  A urine pregnancy test must be performed prior to administration of IP before beginning each new cycle and at the End-of-Treatment 
Visit for all subjects, and at the Follow-up Visits for subjects in the nab-paclitaxel/durvalumab arm.
c All subjects must have a radiographically documented measurable tumor(s) by RECIST 1.1 criteria: Complete chest CT scan (including base of neck and adrenal gland) will be 
performed at Screening, every 42 days (-3/+7 days) (starting from Cycle 1 Day 1) until disease progression, withdrawal of consent, lost to follow-up, death, or termination of the 
study by the Sponsor. The results of a complete chest CT scan (including base of neck and adrenal gland) performed per standard of care may be accepted and not repeated 
during Screening provided it was performed within 28 days of the first dose of IP (Cycle 1 Day 1). The methods of assessment chosen at baseline to follow tumors are to remain 
consistent throughout study duration. Those subjects entering the Follow-up Period without documented progression will continue to have CT scans in accordance with local 
standard of care (or approximately every 90 days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, or termination of the study by the 
Sponsor.  If the CT scan was performed within 2 weeks of the End-of-Treatment Visit, this End-of-Treatment Visit CT scan will not need to be repeated. Subjects in the nab-
paclitaxel/durvalumab arm who continue beyond disease progression per RECIST 1.1 will continue to have CT scans every 42 days (-3/+7) until progression per immune-related 
RECIST criteria (irRECIST) version 1.1 (Nishino, 2013).
d Height will only be obtained at Screening Visit. Weight will be obtained at Screening and every visit during the Treatment Period before administration of IP.
e The occurrence of peripheral neuropathy will be reported by the Investigator per protocol as an AE or SAE.
f All scheduled laboratory samples will be sent to a central laboratory for analysis. Local hematology and chemistry tests may be performed as required for subject 
management/treatment decisions. Local laboratory values that are considered abnormal and clinically significant will be recorded as an AE/SAE and also recorded on the 
laboratory eCRF (see Section 11.3).
g Hematology panel: hemoglobin, hematocrit, red blood cell count and morphology, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin 
concentration, white blood cell count with absolute and differential and percent (neutrophils, lymphocytes, monocytes, eosinophils, basophils, bands), platelet count, 
reticulocytes, erythrocyte sedimentation rate, international normalized ratio, prothrombin time, partial thromboplastin time, and fibrinogen. Additional laboratory samples for 
safety may be collected as clinically indicated.
h Serum chemistry panel: sodium, potassium, bicarbonate, calcium, magnesium, phosphorus, blood urea nitrogen, serum creatinine and clearance, uric acid, glucose, lactic
dehydrogenase, total protein, albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, total, direct and indirect 
bilirubin, ferritin, amylase, lipase, thyroid stimulating hormone (TSH), T4, free T3, and free T4. Additional laboratory samples for safety may be collected as clinically indicated.
i nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 200 mg orally QD on Days 1 to 14 of each 21-day treatment cycle; nab-paclitaxel 
100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day treatment cycle; or nab-paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and
durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15.
j Physical examination and vital signs assessment should be performed prior to IP administration at these visits. Additional physical examination and vital signs assessments may 
be performed throughout the study as clinically indicated. Only abnormal and clinically significant physical examination data and/or vital signs will be recorded as an AE/SAE 
on the eCRF. Vital signs will be (at a minimum): blood pressure, heart rate, respiratory rate, body temperature.
k Hematology panel, serum chemistry will be performed at the 90-day Follow-up Visit for subjects in the nab-paclitaxel/durvalumab arm if applicable following AEs or abnormal 
assessments findings during the 28-day Follow-up Visit.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
43
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
6.
PROCEDURES
Subjects will be provided with a written Informed Consent Form (ICF), given the opportunity to 
ask any questions concerning the study and will sign an ICF prior to participating in any study 
procedures. After giving written informed consent, subjects will undergo a Screening Period to 
be assessed for eligibility. All subjects who sign an ICF must be entered into the Integrated 
Response Technology (IRT) immediately upon signature on the document. Subjects who do not 
meet the eligibility criteria will be considered screening failures and will not be eligible for the 
study. Subjects who fail initial screening may undergo re-screening up to 2 times at any time 
and an ICF will need to be resigned, as well as all screening procedures repeated (some 
procedures may not need to be done if previously done within 28 days prior to screening again).
Subjects that have met all eligibility criteria after the Screening Period will be eligible for
randomization /treatment assignment. 
6.1.
Medical History
A complete medical history including, but not limited to, evaluation for past (up to 5 years) or
present cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine,
lymphatic, hematological, immunologic, dermatological, psychiatric, genitourinary, obstetrical, 
surgical history or any other diseases or disorders will be performed at Screening. All NSCLC-
related medical history should be recorded regardless of time. Smoking status/tobacco exposure 
history will be captured on the eCRF.
6.2.
Prior and Concomitant Medications and Procedures
Prior medications are defined as any medications started before randomization/treatment
assignment. All NSCLC-related prior medications/procedures should be recorded regardless of 
time.
Concomitant medications are defined as any medication that was either initiated before 
randomization/treatment assignment and continued during the study treatment, or initiated 
on/after the date of randomization/treatment assignment and within 28 days after the last dose of 
IP for the monotherapy arm and the nab-paclitaxel/CC-486 combination arms, or 90 days after 
last dose of IP in the nab-paclitaxel/durvalumab combination arm. 
All subjects will have concomitant medications and procedures (including radiation therapy) 
recorded at each visit from the time of signature on the ICF until the 28-day Follow-up Visit for 
the monotherapy arm and the nab-paclitaxel/CC-486 combination arms or 90 days after last dose 
of IP in the nab-paclitaxel/durvalumab combination arm, for conditions that are clinically 
significant or ongoing. During the Follow-up Period only NSCLC-associated concomitant 
medications/procedures (including radiation therapy) will be recorded, ie, subsequent-line(s) of 
anti-cancer therapy. Additionally, for laboratory procedures performed per standard of care 
during follow-up, laboratory values that are considered abnormal and clinically significant will 
be recorded as an AE/SAE and also recorded on the laboratory eCRF.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
44
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
6.3.
Pregnancy Testing
All males and all women of child-bearing potential must be reminded to avoid pregnancy prior to 
administration of IP before beginning each new cycle, at the End-of-Treatment Visit and at the 
Follow-up Visits. A pregnancy test is required for women of child-bearing potential only. For 
women of child-bearing potential a serum β-hCG pregnancy test with sensitivity of at least 25
mIU/mL must be performed to assess eligibility at Screening/Baseline. Note: the screening 
serum pregnancy test can be used as the Cycle 1 Day 1 test prior to study therapy if it is 
performed within the 72-hour timeframe.  A urine pregnancy test must be performed prior to 
administration of IP before beginning each new cycle and at the End-of-Treatment Visit for all 
subjects, and at the Follow-up Visits for subjects in the nab-paclitaxel/durvalumab arm. The 
subject may not receive treatment until the Investigator has verified that the result of the 
pregnancy test is negative. See inclusion criteria for pregnancy testing requirements. Any 
pregnancies that occur in women who have received IP must be immediately reported to Celgene 
Drug Safety (See Section 11.4).
6.4.
Complete Chest Computed Tomography (CT) Scan
A complete chest CT scan (including base of neck and adrenal gland) and any other studies 
required for tumor imaging will be done at Screening, every 42 days (-3/+7 days) (starting from 
Day 1 Cycle 1), and End-of-Treatment, until documented progression of disease, withdrawal of 
consent, lost to follow-up, death, or termination of the study by the Sponsor. The results of a 
complete chest CT scan (including base of neck and adrenal gland) performed per standard of 
care may be accepted and not repeated during Screening provided it was performed within 28 
days of the first dose of IP (Cycle 1 Day 1). Those subjects entering the Follow-up Period 
without documented progression will continue to have CT scans in accordance with local 
standard of care (or approximately every 90 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death, or termination of the study by the Sponsor. If the 
CT scan was performed within 2 weeks of End-of-Treatment Visit, this End-of-Treatment CT 
scan will not need to be repeated. Additional CT scans may be done at any time during the study 
if clinically indicated. All CT scans and reports should be archived at the site according to site 
regulations and copies provided to the Sponsor if requested. All post-treatment anticancer 
therapies will be recorded during the Follow-up Period.  
6.5.
Weight and Height
Weight will be obtained at Screening and at every visit during the Treatment Period before 
administration of IP. Additional measurements of weight may be collected per local standards at 
any time during the study as needed. Height will only be collected at Screening. All weight and 
height data will be collected on eCRFs.
6.6.
ECOG Performance Score
Eastern Cooperative Oncology Group performance status score will be collected at Screening, 
Day 1 of every treatment cycle, at the End-of-Treatment Visit and at the Follow-up Visits. 
Additional ECOG assessments may be performed at any time during the study as clinically 
indicated.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
45
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
6.7.
Peripheral Neuropathy Assessment
Peripheral neuropathy (sensory or motor) assessment will be done at Screening, Day 1 of every 
treatment cycle, at the End-of-Treatment Visit and at the 28-day Follow-up Visit. Changes in 
neuropathy grade from baseline will be reported as an AE as per Section 11. Additional 
peripheral neuropathy assessments may be done at any time during the study as clinically 
indicated.
6.8.
Adverse Event Reporting
Adverse events will be recorded from time of signature on the ICF until 28 days after the last 
dose of IP for the monotherapy and the nab-paclitaxel/CC-486 combination arms and until 90 
days after the last dose of IP for the nab-paclitaxel/durvalumab combination arm during the 
Follow-up Visits, including any unscheduled visits. See Section 11 for details. 
6.9.
Quality of Life Questionnaires
The LCSS, EORTC QLQ C30 and EQ-5D-5L questionnaires will be used to measure quality of 
life (QoL) for subjects in the study. The LCSS is comprised of 9 questions to be completed by 
the subject using a visual analogue scale (VAS) to denote intensity of a symptom. The EQ-5D-
5L comprises 5 questions on mobility, self-care, usual activities, pain/discomfort, 
anxiety/depression and a VAS for overall QoL. These questionnaires will be completed by the 
subject prior to interaction with study personnel, at Day 1 of every Cycle, at the End-of-
Treatment Visit and at the 28-day Follow-up Visit.
6.10.
Healthcare Resource Utilization Questionnaire
A healthcare resource utilization questionnaire will be used to capture the additional use of 
healthcare resources, including hospitalizations, emergency room visits, doctor or nurse visits, 
procedures, and/or additional medication during the study period. The assessment will be 
completed on Day 1 of every treatment cycle, at the End-of-Treatment Visit and at the 28-day
Follow-up Visit. 
6.11.
Laboratory Assessments
Blood for hematology and chemistry evaluation will be collected as per Table 4, Table of Events. 
Blood for hematology will be collected at Screening, Days 1, 8, and 15 of every treatment cycle, 
at the End-of-Treatment Visit and at the 28-day Follow-up Visit. Blood for serum chemistry will 
be collected at Screening, Day 1 of every treatment cycle, at the End-of-Treatment Visit and at 
the 28-day Follow-up Visit. Hematology panel and serum chemistry will be performed at the 90-
day Follow-up Visit for subjects in the nab-paclitaxel/durvalumab arm if applicable following 
AEs or abnormal assessments findings during the 28-day Follow-up Visit. Hematology panel 
will consist of: hemoglobin, hematocrit, red blood cell count and morphology, mean corpuscular 
volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, white 
blood cell count with absolute and differential and percent (neutrophils, lymphocytes, 
monocytes, eosinophils, basophils, bands), platelet count, reticulocytes, erythrocyte 
sedimentation rate, international normalized ratio, prothrombin time, partial thromboplastin time
and fibrinogen. Serum chemistry panel includes: sodium, potassium, bicarbonate, calcium, 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
46
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
magnesium, phosphorus, blood urea nitrogen, serum creatinine and clearance, uric acid, glucose, 
lactic dehydrogenase, total protein, albumin, alkaline phosphatase, aspartate aminotransferase, 
alanine aminotransferase, gamma glutamyl transferase, total, direct and indirect bilirubin,
ferritin, amylase, lipase, thyroid stimulating hormone (TSH), T4, free T3, and free T4. 
Additional laboratory samples for safety may be collected as clinically indicated. 
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an AE/SAE and also recorded on the laboratory eCRF (see Section 11.3).
Abnormal and clinically significant laboratory assessments at Screening will be recorded as 
medical history, and after Screening, as AE or SAE (clinically significant laboratory 
abnormalities at Screening may result in a subject being ineligible for the study and should not 
be captured as an AE). 
Any abnormal values that persist should be followed at the discretion of the Investigator. The 
Investigator should file all copies of the reports, including faxes with the subject’s medical chart.
6.12.
Tumor Tissue Sample Collection and Peripheral Blood Collection
(Exploratory Assessments) 
Histologically or cytologically confirmed advanced NSCLC is a required inclusion criteria for 
entry into this study.  If a subject’s previously collected tumor tissue (also known as archival 
tumor) is available, these samples will be collected for biomarker testing as detailed below at 
Cycle 1 Day 1.  If such samples do not exist, have been depleted, or do not contain sufficient 
tumor material to be analyzed, this will not preclude participation in the study and a new biopsy 
or other procedure to collect tumor tissue will not be required. Table 5 delineates the specific 
requirements for commonly encountered archival tumor types.
Table 5:
Requirements for Collection Based on Archival Tumor Sample Type
Sample Type
Amount to Collect
Collection 
Requirement for 
Biomarkers
Comments/ Exceptions
Core biopsy or surgical 
specimen
10 slides ≥4 ∀M 
thickness. If a block is 
provided, a core of 
viable tumor will also 
be collected.
Mandatory if the sample 
exists. 
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is not sufficient, the 
available amount will be 
collected.
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(FNA)
10 slides ≥4 ∀M. If a 
block is provided, a 
core of viable tumor 
will also be collected. 
Mandatory if the sample 
exists, unless a core 
biopsy or surgical 
sample was provided. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Transbronchial 
endoscopy samples
10 slides ≥4 ∀M. If a 
block is provided, a 
core of viable tumor 
will also be collected.
Mandatory if the sample 
exists, unless a core 
biopsy or surgical 
sample was provided. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
47
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Table 5:
Requirements for Collection Based on Archival Tumor Sample Type 
(Continued)
Sample Type
Amount to Collect
Collection 
Requirement for 
Biomarkers
Comments/ Exceptions
Bronchial lavage, 
sputum, or other 
sample types
Slides or blocks 
representing >100,000 
tumor cells
Collection is strongly 
encouraged when these 
samples contain 
sufficient material.
Collection is strongly 
encouraged when these 
samples contain sufficient 
material.
In addition, test results for tumor mutational status of genes, including but not limited to EGFR,
ALK, KRAS and PD-L1 will be collected, if available from prior testing, and recorded on eCRF 
if these tests have been performed.
Plasma for cell-free nucleic acids analyses will be collected on Cycle 1 Day 1 prior to first dose 
of IP, as will a sample of whole blood or peripheral blood mononuclear cells for a germ-line 
reference comparison. Types of techniques planned to be used for tumor and plasma analyses 
include:
!
Gene expression by RNA sequencing
!
Immunohistochemistry 
!
DNA sequencing
!
DNA methylation profiling
Details regarding the collection, storage, and shipment of the samples are given in the Laboratory 
Manual.
6.13.
Electrocardiogram
Electrocardiograms (ECGs) will be done at Screening and as per standard of care during the 
Treatment Period, and as clinically indicated. Results will be collected in the eCRFs as AE or 
SAE only if results are abnormal, changed and clinically significant, unless the finding is already 
documented in medical history.
6.14.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI)
A CT scan of the head, or preferably brain MRI, will be done as per standard of care at 
Screening (mandatory if symptomatic), during the Treatment Period, and as clinically indicated.
If CT scans show lesions pertinent for RECIST 1.1 criteria evaluation, data will be collected on 
the pertinent tumor evaluation eCRFs.
6.15.
Bone Scans and X-rays
Bone scans and x-rays will be done as per standard of care at Screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs. If bone scans or X-
rays show lesions pertinent for RECIST 1.1 criteria evaluation, data will be collected on the 
pertinent tumor evaluation eCRFs.
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6.1


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
48
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
6.16.
Physical Examinations
Physical examinations will be done at Screening, on Day 1 of every treatment cycle, at the End-
of-Treatment Visit, and as clinically indicated. Results will be collected in the eCRFs as AE or 
SAE only if results are abnormal and clinically significant.
6.17.
Vital Signs
Vital signs (at a minimum blood pressure, heart rate, respiratory rate and body temperature) will 
be done at Screening, prior to IP administration on Days 1, 8, and 15 of every treatment cycle, at 
the End-of-Treatment Visit, and as clinically indicated. Results will be collected in the eCRFs as 
AE or SAE only if results are abnormal and clinically significant.
6.18.
Survival 
After the End-of-Treatment Visit, the subjects will have a 28-day Follow-up Visit followed by a 
phone call approximately every 90 days (+/- 14 days) for at least 12 months after the last subject 
is randomized in either the nab-paclitaxel/CC-486 combination therapy and nab-paclitaxel 
monotherapy arm or 120 PFS events have been observed between these two arms, whichever 
comes later. Subjects in the nab-paclitaxel/durvalumab arm will be followed for survival in a 
similar manner for at least 12 months after the last subject is assigned to this arm.
The subjects will also be asked questions about other medications they may be taking for their 
NSCLC. Those subjects entering the Follow-up Period without documented progression will 
continue to have CT scans in accordance with local standard of care (or approximately every 90 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the Sponsor.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
49
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Male and female subjects with advanced NSCLC who have received no more than one prior
chemotherapy regimen for their advanced disease will be eligible for this study (immunotherapy 
in prior line of treatment is allowed, including platinum doublet combination). Subjects will 
receive study therapy as second or third line of treatment for advanced disease. The study will 
randomize/assign a maximum of approximately 240 subjects if all 3 arms proceed to the end of 
the study. The study will be conducted at approximately 40 sites in the US, Canada, and Europe.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be randomized/assigned in the study:
1. Age ≥ 18 years at the time of signing the ICF.
2. Understand and voluntarily provide written informed consent prior to the conduct of any 
study related assessments/procedures.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Histologically or cytologically confirmed advanced NSCLC who will receive study 
therapy as second- or third-line of treatment for advanced disease.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease (defined by the presence of 
≥1 radiographically documented measurable lesion).
7. One prior platinum-containing chemotherapy for metastatic or recurrent NSCLC, unless 
patients are ineligible to receive it or if disease progressed within 6 months of a platinum-
containing neoadjuvant/adjuvant regimen. Patients may have received no more than one 
line of chemotherapy; immunotherapy in prior line of treatment (first or second line) is 
allowed.
8. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
9. Platelets ≥ 100,000 cells/mm3.
10. Hemoglobin (Hgb) ≥ 9 g/dL.
11. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and 
alanine transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper 
limit of normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
12. Total bilirubin ≤ 1.5 ULN (unless there is a known history of Gilberts Syndrome).
13. Serum creatinine ≤1.5 x ULN, or calculated creatinine clearance ≥60 mL/min (if renal 
impairment is suspected 24-hour urine collection for measurement is required).
14. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
15. Females of childbearing potential [defined as a sexually mature woman who (1) have not 
undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
50
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
(the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for 
at least 24 consecutive months (ie, has had menses at any time during the preceding 24 
consecutive months)] must:
a.
Have a negative pregnancy test (ß-hCG) as verified by the study doctor within 72 
hours prior to starting study therapy. She must agree to ongoing pregnancy testing 
during the course of the study, and after end of study therapy. This applies even if the 
subject practices true abstinence* from heterosexual contact.
b. Either commit to true abstinence* from heterosexual contact or agree to use, and be 
able to comply with, effective contraception without interruption, 28 days prior to 
starting IP, during the study therapy (including dose interruptions), and for 3 months 
after discontinuation of study therapy. 
Male subjects must:
a.
Practice true abstinence* or agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the study, 
during dose interruptions and for at least 6 months following IP discontinuation, even 
if he has undergone a successful vasectomy. 
b. Refrain from semen or sperm donation while taking durvalumab and for at least 3 
months after the last dose of durvalumab.
16. Females must abstain from breastfeeding during study participation and 3 months after IP 
discontinuation. 
7.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. Refractory to prior taxane therapy for advanced disease. Prior taxane used in the adjuvant 
setting does not exclude eligibility, provided there is no disease recurrence within 12 
months upon completion of chemotherapy in that setting.
2. Evidence of active brain metastases, including leptomeningeal involvement (prior 
evidence of brain metastasis are permitted only if asymptomatic and clinically stable for 
at least 8 weeks following completion of therapy). MRI of the brain (or CT scan 
w/contrast) is preferred. Antiepileptic treatment is permitted in the context of prophylaxis 
for seizures.
3. Only evidence of disease is non-measurable at study entry.
4. Patients with known activating mutations in EGFR (such as exon 19 deletions or L858R).
5. Patients with known activating mutations in EML4-ALK.
6. Preexisting peripheral neuropathy of Grade > 2 (per NCI CTCAE v4.0).
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic 
abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception].
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
51
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
7. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with 
the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion 
criteria.
8. Venous thromboembolism within 1 month prior to Cycle 1 Day 1.
9. Current congestive heart failure (New York Heart Association Class II-IV).
10. History of the following within 6 months prior to Cycle 1 Day 1: a myocardial infarction, 
severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart 
Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically 
significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG)
abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder.
11. Known hepatitis B or C virus (HBV/HCV) infection, known history of human 
immunodeficiency virus (HIV) infection, or receiving immunosuppressive or 
myelosuppressive medications that would in the opinion of the Investigator, increase the 
risk of serious neutropenic complications, history of active primary immunodeficiency, 
active tuberculosis (clinical evaluation that includes clinical history, physical examination 
and radiographic findings, and TB testing in line with local practice).
12. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, 
defined as ongoing signs/symptoms related to the infection without improvement despite 
appropriate antibiotics, antiviral therapy, and/or other treatment.
13. Subject has a history of interstitial lung disease, history of slowly progressive dyspnea
and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary 
hypersensitivity pneumonitis or multiple allergies. Any lung disease that may interfere 
with the detection or management of suspected drug-related pulmonary toxicity.
14. Subject has a clinically significant malabsorption syndrome, persistent diarrhea, or 
known sub-acute bowel obstruction > NCI CTCAE Grade 2, despite medical 
management.
15. Treatment with any chemotherapy, investigational product, biologic or hormonal therapy
for cancer treatment within 28 days prior to signing the ICF. Concurrent use of hormonal 
therapy for non-cancer-related conditions (eg, hormone replacement therapy) is 
acceptable.
16. History of or suspected allergy to any IP or their excipients.
17. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first 
dose of IP.  Note: Local surgery of isolated lesions for palliative intent is acceptable.
18. Currently enrolled in any other clinical protocol or investigational trial that involves
administration of experimental therapy and/or therapeutic devices.
19. Any other clinically significant medical condition, psychiatric illness, and/or organ 
dysfunction that will interfere with the administration of the therapy according to this 
protocol or which, in the views of Investigator, preclude combination chemotherapy.
20. Any other malignancy within 5 years prior to randomization/treatment assignment, or 
advanced malignant hepatic tumors, with the exception of adequately treated squamous 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
52
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
cell carcinoma of the skin, in-situ carcinoma of the cervix, uteri, non-melanomatous skin 
cancer, carcinoma in situ of the breast, or incidental histological finding of prostate 
cancer (TNM Classification of Malignant Tumours (TNM) stage of T1a or T1b). (All 
treatment of which should have been completed 6 months prior to signing ICF).
21. Radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting 
IP, and/or from whom ≥ 30% of the bone marrow was irradiated. Prior radiation therapy
to a target lesion is permitted only if there has been clear progression of the lesion since 
radiation was completed.
22. Any condition including the presence of laboratory abnormalities, which places the 
subject at unacceptable risk if he/she were to participate in the study.
23. Any medical condition that confounds the ability to interpret data from the study.
24. Female patients who are pregnant or breastfeeding or female patients of reproductive 
potential who are not willing to employ effective birth control from screening to 90 days 
after the last dose of durvalumab.  
25. Male patients of reproductive potential who are not willing to employ effective birth 
control from screening to 90 days after the last dose of durvalumab and from screening to 
6 months after the last dose of nab-paclitaxel.
26. History of allogenic organ transplantation.
27. Active or prior documented autoimmune or inflammatory disorders (including 
inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the 
exception of diverticulosis], celiac disease, irritable bowel disease, or other serious 
gastrointestinal chronic conditions associated with diarrhea, systemic lupus 
erythematosus, sarcoidosis syndrome, or Wegener’s syndrome [granulomatosis with 
polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]) within the 
past 3 years prior to the start of treatment.  The following are exceptions to this criterion:
-
Patients with vitiligo or alopecia
-
Patients with hypothyroidism (eg, following Hashimoto’s syndrome) stable on 
hormone replacement 
-
Any chronic skin condition that does not require systemic therapy
-
Patients without active disease in the last 5 years may be included but only after 
consultation with the study physician
28. Current or prior use of immunosuppressive medication within 14 days before the first 
dose of durvalumab.  The following are exceptions to this criterion:
-
Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular 
injection)
-
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of 
prednisone or its equivalent
-
Steroids as premedication for hypersensitivity reactions (eg, CT scan 
premedication)
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
53
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
29. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.  Note: 
Patients, if enrolled, should not receive live vaccine during the study and up to 30 days 
after the last dose of IP.
30. Prior enrollment and treatment in a previous durvalumab clinical study. 
31. Patients who have received prior anti-PD-1 or anti PD-L1:
# Must not have experienced a toxicity that led to permanent discontinuation of prior 
immunotherapy. 
# All AEs while receiving prior immunotherapy must have completely resolved or 
resolved to baseline prior to screening for this study.
# Must not have experienced a ≥ Grade 3 immune related AE or an immune related 
neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: 
Subjects with endocrine AE of ≤ Grade 2 are permitted to enroll if they are stably 
maintained on appropriate replacement therapy and are asymptomatic.
# Must not have required the use of additional immunosuppression other than
corticosteroids for the management of an AE, not have experienced recurrence of 
an AE if re-challenged, and not currently require maintenance doses of > 10 mg 
prednisone or equivalent per day.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
54
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Investigational Products
Subjects will receive open-label nab-paclitaxel / CC-486, nab-paclitaxel /durvalumab or nab-
paclitaxel monotherapy during the Treatment Period of the study. nab-paclitaxel, durvalumab
and CC-486 are designated as IP and will be packaged and supplied by the study Sponsor.
The reconstitution and IV administration of nab-paclitaxel should follow the local Prescribing 
Information for Abraxane®.
8.1.1.
nab-Paclitaxel
nab-Paclitaxel will be supplied by the Sponsor in single-use vials in single count cartons. Each 
single-use 50 mL vial will contain paclitaxel (100 mg) and human albumin as a stabilizer.
Please see local prescribing information for Abraxane® for detailed instructions on the 
reconstitution, storage conditions and IV administration of nab-paclitaxel. Reconstituted nab-
paclitaxel should be stored in an area accessible only to study personnel.
Temperature records for nab-paclitaxel must be made available to the Sponsor or other Sponsor-
nominated monitoring teams for verification of proper IP storage.
8.1.2.
CC-486 (Azacitidine for Oral Administration)
The Sponsor will supply azacitidine 100 mg tablets for oral administration. Each tablet is 
formulated using excipients that are generally regarded as safe and are used in marketed drug 
products.
All tablets will be packaged in blister cards. Only sufficient IP for one cycle of treatment will be 
provided to each subject at the start of each treatment cycle. All tablets should be swallowed 
whole, and should not be broken or chewed. CC-486 may be taken on an empty stomach or with 
food. Subjects should drink 8 ounces (240 mL) of room temperature water with each dose. It is 
strongly recommended that all subjects receive a dose of a prophylactic antiemetic, preferably a 
5-HT3 antagonist, approximately 30 minutes prior to each dose of CC-486.
The IP must be stored as directed on package label at controlled temperature and a temperature 
log must be maintained in the source documents. The storage area should be secure and have 
access limited to study personnel. 
8.1.3.
Durvalumab (MEDI4736)
Durvalumab will be supplied by the Sponsor in single use vials in single count cartons. Each 10R 
(10 mL) vial will be supplied as a liquid solution containing 500 mg (nominal) of IP at a 
concentration of 50 mg/mL. Durvalumab should be stored in accordance with the product label. 
The study site is to supply the following:
!
IV infusion bags of normal saline (0.9% [w/v] sodium chloride injection, 250 mL 
size). Saline bags must be latex-free and can be made of polypropylene, polyethylene, 
polyolefin copolymers, or polyvinyl chloride. Infusion lines should contain a 0.2-μm 
in-line filter.  
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
55
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
!
Since the compatibility of durvalumab with other IV medications and solutions, other 
than normal saline, is not known, the durvalumab solution should not be infused 
through an IV line in which other solutions or medications are being administered.
Durvalumab will be administered using an IV bag containing 0.9% (w/v) saline or 5% (w/v) 
dextrose, with a final durvalumab concentration ranging from 1 to 20 mg/mL, and delivered 
through an IV administration set with a 0.2- or 0.22-μm in-line filter.
The dose of durvalumab for administration must be prepared by the Investigator’s or site’s 
designated IP manager using aseptic technique. Total time from needle puncture of the 
MEDI4736 vial to the start of administration should not exceed:
!
24 hours at 2°C to 8°C (36°F to 46°F)
!
4 hours at room temperature
Standard infusion time is 1 hour. However, if there are interruptions during infusion, the total 
allowed time should not exceed 8 hours at room temperature. In the event that either preparation 
time or infusion time exceeds the time limits outlined above, a new dose must be prepared from 
new vials. Durvalumab does not contain preservatives, and any unused portion must be 
discarded.
For additional information on preparation and storage please refer to the pharmacy manual.
8.1.4.
Monitoring During/After Durvalumab Infusion 
First durvalumab infusion
On the first infusion day, subjects in the nab-paclitaxel/durvalumab combination arm will be 
monitored, and assessments collected/recorded in the eCRF prior to, during and after infusion of 
IP as presented in the bulleted list below.
Blood pressure (BP) and pulse will be collected from subjects before, during, and after each 
infusion at the following times (based on a 60-minute infusion):
!
Prior to the beginning of the infusion (measured once from approximately 30 minutes 
before up to 0 minutes [ie, the beginning of the infusion])
!
Approximately 30 minutes during the infusion (halfway through infusion) 
!
At the end of the infusion (approximately 60 minutes ±5 minutes)
!
If the infusion takes longer than 60 minutes, then BP and pulse measurements should 
follow the principles as described above or be taken more frequently if clinically 
indicated.  A 1-hour observation period is recommended after the first infusion of 
durvalumab.
Subsequent durvalumab infusions
BP, pulse and other vital signs should be measured, collected/recorded in eCRF prior to the start 
of the infusion. Subjects should be carefully monitored and BP and other vital signs should be 
measured during and post infusion as per institution standard and as clinically indicated. Any 
clinically significant changes in vital signs should be entered onto an unscheduled vital signs 
CRF page.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
56
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
For all infusions
In the event of a ≤ Grade 2 infusion-related reaction, the infusion rate of IP may be decreased by 
50% or interrupted until resolution of the event (up to 4 hours) and re-initiated at 50% of the 
initial rate until completion of the infusion. For subjects with a ≤ Grade 2 infusion-related 
reaction, subsequent infusions may be administered at 50% of the initial rate. 
Acetaminophen/paracetamol and/or an antihistamine (eg, diphenhydramine) or equivalent 
medications per institutional standard may be administered at the discretion of the investigator. If 
the infusion-related reaction is ≥ Grade 3 or higher in severity, IP will be discontinued. 
As with any antibody, allergic reactions to dose administration are possible. Appropriate drugs 
and medical equipment to treat acute anaphylactic reactions must be immediately available, and
study personnel must be trained to recognize and treat anaphylaxis. The study site must have 
immediate access to emergency resuscitation teams and equipment in addition to the ability to 
admit subjects to an intensive care unit if necessary.
8.2.
Treatment Administration and Schedule
Following administration of nab-paclitaxel, the intravenous line should be flushed with sodium
chloride 9 mg/mL (0.9%) solution for injection to ensure administration of the complete dose, 
according to local practice.
Once randomized (or assigned), subjects will be treated with nab-paclitaxel / CC-486, nab-
paclitaxel / durvalumab or nab-paclitaxel monotherapy until disease progression, development of 
an unacceptable toxicity, death, lost to follow-up, withdrawal of consent, or termination of the 
study by the Sponsor:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment cycle, or
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 
durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15 of each 21-
day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle
8.3.
Dose Omissions and Modifications
8.3.1.
Rules for Dose Omissions and Modified Schedules
nab-Paclitaxel Monotherapy Arm
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
!
Day 1 Dose Missed
If nab-paclitaxel cannot be administered on Day 1 within the 2 days allowable window,
 nab-paclitaxel may not be skipped but only delayed 
 Delay of Day 1 will automatically shift the following visit for this cycle 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
57
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
!
Day 8 Dose Missed
If the nab-paclitaxel dose for Day 8 is given >9 days from Day 1, the Day 8 dose, when 
administered, can be either considered as delayed or skipped, depending on the intention of the 
Investigator.
 nab-paclitaxel may be delayed up to Day 15: this dose will be considered as delayed 
Day 8; the next visit will be the planned Day 1 of the next cycle which will not be 
automatically pushed back
 nab-paclitaxel may be skipped: if the second nab-paclitaxel dose cannot be given in a 
cycle it may be skipped; the next dose would be administered as the Day 1 dose 
nab-Paclitaxel/CC-486 Combination Arm
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
If any doses of CC-486 are missed, skip that day and resume as appropriate, do not double up on
subsequent days.
!
Day 1 Dose Missed
If CC-486 cannot be administered on Day 1 within the 2 days allowable window,
 The nab-paclitaxel Day 8 dose would not necessarily be pushed back / delayed
 Doses of CC-486 would be skipped (exposure to CC-486 would be reduced on that 
cycle). 
For hematologic toxicity, dosing should be reassessed at the next visit on Day 8.
!
Day 8 Dose Missed
If nab-paclitaxel cannot be administered on Day 8 within the 2 days allowable window,
 nab-paclitaxel may be delayed (eg, for neuropathy): this dose will be considered as 
delayed Day 8; the next dose (Day 15) may also be delayed up to the original Day 1 of 
the next cycle (approximately 20 days from Day 1 of this cycle) to maintain the protocol 
specified visit gap
 nab-paclitaxel may be skipped (eg, hematotoxicity); the next dose would be administered 
as the Day 15 dose 
If the dose for Day 8 is given > 9 days from Day 1, the Day 8 dose, when administered, can be 
either considered as delayed or skipped, depending on the intention of the Investigator.
Upon resuming treatment after stopping both IPs on adjusted Day 8, consideration for nab-
paclitaxel resumption should take priority.
!
Day 15 Dose Missed
If nab-paclitaxel cannot be administered on Day 15 within the 2 days allowable window,
 nab-paclitaxel may be delayed: this dose will be considered as delayed Day 15 (up to 
Day 1 of the next cycle); CC-486 may be started on Day 1 as planned
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
58
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
 If the nab-paclitaxel dose cannot be administered within 14 days from the last dose, it 
will be considered as skipped
nab-Paclitaxel/Durvalumab Combination Arm
No dose reductions of durvalumab are allowed. In case of doubt, the Investigator should consult 
with the Study Physician.
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
!
Day 1 Dose Missed
If nab-paclitaxel cannot be administered on Day 1 within the 2 days allowable window,
 nab-paclitaxel may not be skipped but only delayed 
 Delay of Day 1 will automatically shift the following visit for this cycle 
!
Day 8 Dose Missed
If the nab-paclitaxel dose for Day 8 is given > 9 days from Day 1, the Day 8 nab-paclitaxel dose 
should be skipped
!
Day 15 Dose Missed
If durvalumab cannot be administered on Day 15 within the 2 days allowable window,
 Durvalumab may be delayed: this dose will be considered as delayed Day 15 
 If the durvalumab dose cannot be administered within 14 days from the last dose, it will 
be considered as skipped
8.3.2.
Rules for Dose Modifications
Subjects who experience any of the adverse drug reactions in Table 6 will be dose reduced as per 
Table 6 during treatment. 
nab-Paclitaxel Monotherapy Arm
!
Do not administer nab-paclitaxel on Day 1 of a cycle until ANC is at least 
1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment until 
counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and platelet 
count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil count of at least 
500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Day 8 of the cycle. 
Upon resumption of dosing, permanently reduce nab-paclitaxel doses as outlined in 
Table 6.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-paclitaxel 
at reduced doses (Table 6) when peripheral neuropathy improves to Grade 1 or 
completely resolves.
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to 
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Wit
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
59
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
the guidelines in Table 6. For any other Grade 3 or 4 nonhematologic toxicity or other 
Investigator defined unacceptable toxicity, interrupt treatment until the toxicity 
improves to ≤Grade 2, then restart treatment according to the guidelines in Table 6.
Re-escalation is not permitted at any time. 
nab-Paclitaxel/CC-486 Combination Arm
!
Do not administer nab-paclitaxel on Day 8 or CC-486 on Day 1 or 8 of a cycle until ANC 
is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe thrombocytopenia, withhold treatment until counts 
recover to a platelet count of at least 100,000 cells/mm3 on Days 1 and 8 for CC-486 and 
Day 8 for nab-paclitaxel or to a platelet count of at least 50,000 cells/mm3 on Day 15 of 
the cycle for nab-paclitaxel. Upon resumption of dosing, permanently reduce nab-
paclitaxel and/or CC-486 doses as outlined in Table 6.
!
In subjects who experience Grade ≥3 neutropenia, withhold treatment and start G-CSF 
treatment daily until the ANC ≥ 2000/mm3 (please refer to Section 9.3 for G-CSF 
administration). Upon resumption, permanently reduce nab-paclitaxel and/or CC-486 
dose as outlined in Table 6.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy (CC-486 does not need 
to be withheld). Resume nab-paclitaxel at reduced doses (Table 6) when peripheral 
neuropathy improves to Grade 1 or completely resolves. 
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to the 
guidelines in Table 6. For any other Grade 3 or 4 nonhematologic toxicity or other 
Investigator defined unacceptable toxicity, interrupt treatment until the toxicity improves 
to ≤Grade 2, then restart treatment according to the guidelines in Table 6.
Re-escalation is not permitted at any time. 
nab-Paclitaxel/Durvalumab Combination Arm
Guidelines for the management of toxicities for durvalumab and nab-paclitaxel are provided in 
Appendix C.
In addition:
!
Do not administer nab-paclitaxel on Day 1 of a cycle until ANC is at least 
1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment until 
counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and platelet 
count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil count of at least 
500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Day 8 of the cycle. 
Upon resumption of dosing, permanently reduce nab-paclitaxel doses as outlined in 
Table 6.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
60
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-paclitaxel 
at reduced doses (Table 6) when peripheral neuropathy improves to Grade 1 or 
completely resolves. 
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to the 
guidelines in Table 6. For any other Grade 3 or 4 nonhematologic toxicity or other 
Investigator defined unacceptable toxicity, interrupt treatment until the toxicity improves 
to ≤Grade 2, then restart treatment according to the guidelines in Table 6.
Following the first dose of IP, subsequent administration of durvalumab can be modified based 
on toxicities observed as described in the Dosing Modification and Toxicity Management 
Guidelines.  These guidelines have been prepared by the Sponsor to assist the Investigator in the 
exercise of his/her clinical judgment in treating these types of toxicities.  These guidelines apply 
to AEs considered causally related to the durvalumab containing regimen by the reporting 
Investigator.
Treatment modifications referring to ‘study regimen or treatment’ would apply to both nab-
paclitaxel and durvalumab unless AEs are not considered causally related to nab-paclitaxel by 
the reporting Investigator. In that case nab-paclitaxel or durvalumab treatment may be continued 
alone if deemed beneficial to the patient per Investigator’s assessment.
Re-escalation is not permitted at any time. 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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61
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Table 6:
Permanent Dose Reductions for Hematologic and Nonhematologic Toxicities and Dosing on the Study
Dose Modification During Treatment
Adverse Drug Reaction
Occurrence
Monotherapy Arm: nab-
paclitaxel Dose (mg/m2)
Combination Arm: nab-
paclitaxel Dose (mg/m2) / 
CC-486 Dose (mg)
Neutropenic Fever (ANC < 500/mm3 with fever >38°C)
OR
Delay of next cycle by > 7 days for ANC < 1500/mm3
OR
ANC < 500/mm3 for > 7 days
First
75
100/100
Second
50
75/100
Third
Discontinue Treatment*
50/100
Fourth
NA
Discontinue Treatment*
Platelet count < 50,000/mm3
First
75
100/100
Second
Discontinue Treatment*
75/100
Third
NA
Discontinue Treatment*
Peripheral Neuropathy Grade ≥3
First
75
75/200
Second
50
50/200
Third
Discontinue Treatment*
Grade 2 or 3 Cutaneous toxicity
Grade 3 Diarrhea
Grade 3 Mucositis
Any other Grade 3 or 4 nonhematologic toxicity or other 
Investigator defined unacceptable toxicity
First
75
100/100
Second
50
75/100
Third
Discontinue Treatment*
50/100
Fourth
NA
Discontinue Treatment*
Grade 4 Cutaneous toxicity, Diarrhea or Mucositis
First
Discontinue Treatment*
ANC = absolute neutrophil count; AUC = area under the curve; NA = not applicable.
* If an adverse event that requires dose reduction recurs after the dose has been reduced according to the table above, the subject should generally have treatment 
discontinued unless, at the discretion of the Investigator, there is evidence of continuing benefit to the subject that outweighs the risk of recurrent toxicity.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
8.4.
Method of Treatment Assignment
The Treatment Period of the study is open-label. Randomization/treatment assignment has been 
and will be carried out centrally using an IRT system.
8.5.
Packaging and Labeling
The label(s) for all IP will include Sponsor name, address and telephone number, the protocol 
number, IP name, dosage form and strength (where applicable), amount of IP per container, lot 
number, expiry date (where applicable), medication identification/kit number, dosing 
instructions, storage conditions, and required caution statements and/or regulatory statements as 
applicable. Additional information may be included on the label as applicable per local 
regulations.
8.6.
Investigational Product Accountability and Disposal
The Sponsor (or its designee) will review with the Investigator and relevant site personnel the 
process for IP return, disposal, and/or destruction including responsibilities for the site versus the 
responsibilities of the Sponsor (or designee).
The Sponsor will instruct the Investigator on the return, disposal and/or destruction of IP. Only 
completely unused IP vials should be retained by the site until a representative from the Sponsor
or other Sponsor-designated personnel have completed an inventory. Partially used and
completely used vials should be destroyed according to local guidelines, and disposition should 
be recorded on the Investigational Drug Accountability Record Form.
The Investigator(s) or designee(s) is responsible for accounting for all IP that is issued to and
returned by the subject during the course of the study according to applicable regulatory
requirements. Any unused CC-486 must be returned by a study subject and retained by the
investigative site for accountability to be conducted by a Sponsor representative (or its designee). 
If any IP is lost or damaged, its disposition should be documented. At the periodic monitoring
visits, a Sponsor representative (or its designee) will conduct IP accountability and address any
discrepancies. Upon satisfactory reconciliation of all IP, returned IP may be destroyed. At the
conclusion of the study, all remaining IP will be counted, reconciled with dispensing records, 
documented, and destroyed at the clinic site or allocated drug destruction location after
completion of drug accountability by a Sponsor representative (or its designee). The Sponsor
representative (or its designee) will ensure that a final report of drug accountability to the unit 
dose level (ie, tablet) is prepared and placed in both the Investigator study file and the central 
clinical study file.
Investigational product will not be loaned or dispensed by the Investigator to another 
Investigator or site. Under certain circumstances, and with Sponsor permission, cooperative 
groups may manage IP between locations within their network as clinical trial agreement and 
local guidelines permit.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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63
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
8.7.
Investigational Product Compliance
All IP will be administered only by study site personnel and accurate recording of all IP 
administration will be made in the appropriate section of the subject’s eCRF and source 
documents.
8.8.
Overdose
Overdose, as defined for this protocol, refers to nab-paclitaxel, CC-486, or durvalumab dosing.
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel, durvalumab or CC-486 to a given subject, regardless of any associated adverse events 
or sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate. For nab-paclitaxel, an infusion completed in less than 25 minutes may increase Cmax by 
approximately 20%, therefore a nab-paclitaxel infusion completed in less than 25 minutes will 
meet the infusion rate criterion for an overdose.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the AE case report form. See 
Section 11.1 for the reporting of adverse events associated with overdose.
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ed with o


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
64
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
Over the course of this study, additional medications may be required to manage aspects of the 
disease state of the subjects, including side effects from study treatments or disease recurrence. 
All supportive care (including but not limited to growth factors, antiemetics, analgesics, 
zoledronic acid, denosumab) is permitted as per the Investigator’s discretion and should be 
administered according to local institutional practice. All concomitant treatments, including 
blood and blood products, must be reported on the eCRF.
!
Antiemetics are not required during the study; however, it is strongly recommended 
that all subjects receive a dose of a prophylactic antiemetic, preferably a 5-HT3 
antagonist, approximately 30 minutes prior to each dose of CC-486.
!
Stable, therapeutic doses of anticoagulants are permitted; however, subjects on 
warfarin should have prothrombin time (PT) or international normalized ratio (INR)
and partial thromboplastin time (PTT) monitored as clinically indicated.
!
Subjects on erythropoietin or darbepoetin alfa for at least 4 weeks prior to starting the 
IP may continue their pretreatment doses throughout the study.
#
Note: If the subject is not on a stable dose of an erythropoiesis-stimulating agents 
(ESA) prior to study entry, the subject may not start an ESA during Cycle 1. 
However, medications such as ESAs, granulocyte colony-stimulating factors (G-
CSFs), etc., may be administered according to standard of care after Cycle 1.
!
Use of white blood cell growth factors (eg, filgrastim, G-CSF for the treatment of 
subjects with neutropenic fever is permitted at the Investigator’s discretion. Use of 
filgrastim rather than pegylated-filgrastim is indicated, because of the 14 day delay of 
the next cycle following treatment with peg-filgrastim.
!
Use of white blood cell growth factors (eg, filgrastim, G-CSF) for secondary
prophylaxis in subjects who experienced a neutropenic complication from a prior
cycle of chemotherapy (for which primary prophylaxis was not received) is permitted.
!
Flu vaccination with inactivated virus is permitted.
!
Routine infectious disease prophylaxis is not recommended, however, antibiotic,
antiviral, antipneumocystis, antifungal, or other prophylaxis may be implemented
during the study at the discretion of the Investigator.
!
Treatments with bisphosphonates (eg, pamidronate, zoledronate), or other agents (eg, 
denosumab) to prevent or delay progression of bone metastases are permitted.
Maintenance of a stable dosing regimen throughout the study is recommended.
!
Subjects may receive physiologic replacement doses of glucocorticoids as
maintenance therapy for adrenal insufficiency. Glucocorticoids may be administered
as an antiemetic with IV chemotherapy, if directed by local standard of care. Use of 
immunosuppressive medications for the management of durvalumab-related AEs, or 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
65
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
in subjects with contrast allergies is acceptable.  In addition, use of inhaled, topical, 
and intranasal corticosteroids is permitted.
!
Treatment with antidiarrheal medications is recommended at the first sign of diarrhea
as per the guidelines in Appendix B. Pre-medication with antidiarrheal medication for 
subsequent doses of CC-486 may be appropriate.
!
The potential drug-drug interactions precautions contained in the nab-paclitaxel 
prescribing information will be applied to this study, unless otherwise specified in the 
protocol. Specifically, the metabolism of paclitaxel is catalyzed by cytochrome P450 
isozymes CYP2C8 and CYP3A4. Caution is recommended when administering nab-
paclitaxel concomitantly with medicines known to inhibit (eg, ketoconazole and other 
imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, 
saquinavir, indinavir, and nelfinavir) or induce (eg, rifampicin, carbamazepine, 
phenytoin, efavirenz, nevirapine) either CYP2C8 or CYP3A4. For information 
regarding other drugs that may interact with either nab-paclitaxel or durvalumab and 
affect their metabolism, pharmacokinetics, or excretion, please see the respective IP 
product information (refer to Prescribing Information and/or IB).
!
Antiepileptic treatment is permitted, in the context of prophylaxis for seizures, for 
subjects with prior evidence of brain metastasis (asymptomatic and clinically stable 
for at least 8 weeks following completion of therapy for brain metastasis).
9.2.
Prohibited Concomitant Medications and Procedures
Other investigational therapies must not be used while the subject is enrolled in the study.
Anticancer therapy (chemotherapy, biologic or investigational therapy, and surgery) other than
the study treatments must not be given to subjects during the study. If such treatment is required,
the subject must be discontinued from the study. Focal palliative radiotherapy for treatment of
cancer-related symptoms is allowed during study treatment at the discretion of the Investigator.
The administration of either α-interferon and/or ribavirin, or drugs with known renal toxicity is
prohibited during study treatment. Monoclonal antibodies against CTLA-4, PD-1 or PD-L1 
should not be given concomitantly.
Immunosuppressive medications including, but not limited to, systemic corticosteroids at doses 
exceeding 10 mg/day of prednisone or equivalent, methotrexate, azathioprine, and tumor 
necrosis factor-α blockers should not be given during the study unless required for management 
of immune-related toxicities (Appendix C).
Live attenuated vaccines should not be given through 30 days after the last dose of IP.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) EGFR TKIs should 
not be given concomitantly with durvalumab, and should be used with caution in the 90 days 
post last dose of durvalumab. Increased incidences of pneumonitis (with third generation EGFR 
TKIs) and increased incidence of transaminase increases (with first generation EGFR TKIs) has 
been reported when durvalumab has been given concomitantly.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
66
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
9.3.
Required Concomitant Medications and Procedures for Subjects 
Receiving CC-486
Data regarding G-CSF administration should be recorded on the eCRF provided for G-CSF 
administration.
9.3.1.
Description of G-CSF
This medication stimulates the blood system (bone marrow) to make white blood cells, helping
fight infections. This medication is given to those whose ability to make white blood cells has
been reduced. Filgrastim (also known as G-CSF, or granulocyte colony stimulating factor) is a
man-made version of a certain natural substance found in the body. It is produced using a certain
bacteria. It will be obtained commercially and relabeled as clinical supplies. It should be stored,
and administered according to the manufacturer’s recommendation.
9.3.2.
Administration of G-CSF
For subjects who experience Grade ≥3 neutropenia, G-CSF 5 ∀g/kg daily will be administered
subcutaneously. During any cycle when Grade ≥3 neutropenia occurs, CC-486 and other 
cytotoxic agents will be held, and G-CSF will begin immediately (a minimum of 24 hours after 
the last dose of CC-486 and chemotherapy). In subsequent cycles, G-CSF will begin on Day 16. 
G-CSF will continue daily until the ANC ≥2000/mm3. In subjects receiving G-CSF, the next 
cycle should begin no sooner than 48 hours after discontinuation of G-CSF. 
For complete details on drug administration, storage, clinical pharmacology, and the human PK 
of G-CSF (filgrastim), please see the G-CSF (filgrastim) package insert.
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rastim) pac
rastim) pa


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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67
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the study are described 
below.  Additional analyses of these endpoints as well as exploratory endpoints or subgroup 
analyses will be described in detail in the statistical analysis plan (SAP).  The SAP supersedes 
the analyses described in the protocol should there be differences between the two.
Evaluations of the study endpoints will be based primarily on the point estimates and the 
associated 95% confidence intervals of the within- and between-treatment differences. 
10.1.
Overview
Approximately 240 subjects will be assigned 1:1:1 to one of the three treatment arms 
(approximately 80 subjects per group). The combination arms will receive nab-paclitaxel with 
epigenetic modifying therapy of CC-486 or nab-paclitaxel with immunotherapy of durvalumab,
and the monotherapy arm will receive nab-paclitaxel alone.  All regimens will be administered 
in 21-day cycles. All subjects will receive the assigned study treatment until disease progression, 
unacceptable toxicity, death, lost to follow-up, withdrawal of consent, or termination of the 
study by the Sponsor, in accordance with local standard of care. Treatment beyond progression 
defined by RECIST 1.1 will be permitted per irRECIST criteria for those subjects in the nab-
paclitaxel/durvalumab arm (see Section 4.1.2.1).
Prior to Protocol Amendment 4.0, all subjects were randomized 1:1 to the nab-paclitaxel/CC-
486 combination therapy and nab-paclitaxel monotherapy arms using a permuted-block 
randomization method with the following baseline stratification factors: 
!
ECOG performance status (0 versus 1)
!
Gender (males versus females)
!
Smoker (yes versus no)
Randomization was carried out centrally using an IRT system. As Protocol Amendment 4.0 
implementation was in effect after enrollment completed in the nab-paclitaxel/CC-486 
combination therapy and nab-paclitaxel monotherapy arms (with each arm reaching a total of 
approximately 80 subjects), all subjects enrolled while Protocol Amendment 4.0 is in effect and 
at the time of Protocol Amendment 5.0 implementation will be assigned to the nab-
paclitaxel/durvalumab combination therapy arm until approximately 80 subjects have been 
enrolled in that arm. Hence, treatment assignment of subjects to the nab-paclitaxel/CC-486 
combination therapy and nab-paclitaxel monotherapy arms was in effect conducted completely 
in a randomized fashion and randomization between the nab-paclitaxel/durvalumab combination 
and nab-paclitaxel monotherapy arms will not apply.
A data monitoring committee (DMC) will be used to review the safety and efficacy data during 
the study.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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68
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
10.2.
Study Population Definitions
10.2.1.
Intent-to-treat Population
The primary efficacy analysis will be performed on the intent-to-treat (ITT) population, which 
includes all randomized (assigned) subjects regardless of whether the subject receives any IP or 
has any efficacy assessments performed. 
10.2.2.
Per-protocol (PP) Population
The PP population is defined as all eligible subjects randomized/assigned who receive at least 
one dose of the IP, have been treated in the arm they were assigned and meet the major eligibility
criteria of the protocol.  Additional analyses utilizing the PP population will be described in the 
SAP.
10.2.3.
Treated Population
The treated population will consist of all randomized/assigned subjects who receive at least one 
dose of IP. The safety analyses will be based on the treatment as received if different from the 
assigned treatment by randomization/treatment assignment.
10.3.
Sample Size and Power Considerations
The primary objective of this study is to estimate the efficacy of the nab-paclitaxel/CC-486 
combination therapy, that of the nab-paclitaxel/durvalumab combination therapy, and that of the 
nab-paclitaxel monotherapy.
A secondary efficacy objective is to estimate the relative efficacy of each of the combination 
regimens to the nab-paclitaxel monotherapy regimen. 
The effect of the treatment regimens with respect to the efficacy endpoints will be based on the 
point estimates and the associated 95% confidence intervals. The sample size was chosen to 
support the estimation of the within- treatment effects with reasonable precision. In the 
durvalumab arm, a sample size of 80 subjects will further allow the estimation of the treatment 
effect with reasonable precision when stratification by prior checkpoint inhibitor exposure 
(checkpoint naïve and prior exposure to checkpoint inhibitors) is performed. 
No inferential statistical tests will be performed and no multiplicity adjustments are planned for 
the statistical analyses.
Table 7 below summarizes the two-sided 95% confidence intervals for a range of hypothetical 
observed disease control rates given a sample size of 80 subjects in a treatment arm. If the 
observed disease control rate is 0.30, then the actual width of the 2-sided 95% confidence 
interval is 0.21 (95% CI is [0.20, 0.41]).
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0.21 (


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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69
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Table 7:
Disease Control Rate –Two-Sided 95% Confidence Interval of Hypothetical 
Disease Control Rate with a Sample Size of 80 Subjects in a Treatment Arm
Hypothetical Observed 
Disease Control Rate
Actual Width of 95% 
Confidence Interval
95% Confidence Intervala
0.20
0.186
(0.119, 0.304)
0.25
0.199
(0.16, 0.359)
0.30
0.21
(0.203, 0.413)
0.35
0.218
(0.247, 0.465
0.40
0.224
(0.292, 0.516)
0.45
0.227
(0.338, 0.565)
0.50
0.228
(0.386, 0.614)
a Based on the Clopper-Pearson exact method.
The between-treatment effect with respect to PFS can be estimated based on the point estimate of 
the hazard ratio and the associated 95% confidence interval. Table 8 below summarizes the 
precision that can be achieved given different scenarios of hypothetical observed hazard ratios 
between the treatment arms for PFS events, assuming a total of 120 events are observed. 
Table 8:
Progression-Free Survival – Two-Sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms
Hypothetical Number of 
Events Observed
Hypothetical Observed 
Hazard Ratio of PFS Events
95% Confidence Interval of 
Hazard Ratioa
120
0.60
(0.42, 0.86)
0.65
(0.45, 0.93)
0.70
(0.49, 1.00)
a Assuming a standard error of 0.18 [estimated based on (4/120)1/2] for the log hazard ratio.
Assuming the median times of PFS are 4.17 and 2.5 months, respectively, for the nab-
paclitaxel/CC-486 combination therapy and nab-paclitaxel monotherapy arms, and an 
approximate 23 months accrual period for a total of 160 subjects, it is estimated that a total of 
120 PFS events will have been observed approximately 2 months after the last subject is 
randomized to these 2 arms, assuming an exponential distribution for PFS. The final analysis of 
the nab-paclitaxel/CC-486 combination and nab-paclitaxel monotherapy arms will be performed 
when a total of approximately 120 PFS events have been observed between these two arms.
While there is published data demonstrating efficacy of nab-paclitaxel as monotherapy in a 
second line setting in advanced NSCLC with ORR ranging from 16.1 to 33% and a median PFS 
of up to 5 months, it is difficult to place an assumed treatment effect on nab-paclitaxel as a 
monotherapy (Chen, 2012; Saxena, 2012; Yuan, 2012).  The assumption of 2.5 months PFS in 
the monotherapy arm is in line with this data and other efficacy data previously observed 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
70
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
following monotherapy treatment of advanced disease with other agents (Shepherd, 2000; 
Hanna, 2004; Reck, 2014; Garon, 2014).
[Of note, with 120 PFS events, this study has an 80% power (1-sided, Type-1 error of 2.5%) to 
detect a HR of 0.60 for PFS between two treatment arms.]
Assuming the median time of PFS is 4.25 months for the nab-paclitaxel/durvalumab 
combination therapy, and an approximate 13 months accrual period for a total of approximately
80 subjects, it is estimated that a total of approximate 50 PFS events will have been observed at 
approximately 3 months after the last subject is assigned to this arm, assuming an exponential
distribution for PFS. The final analysis for PFS for the nab-paclitaxel/durvalumab arm will be 
performed when approximately 50 PFS events have been observed in this arm.
One nonbinding interim analysis for PFS with an early stopping rule for futility between the nab-
paclitaxel/CC-486 combination and nab-paclitaxel monotherapy arms will be conducted when 
approximately 60 events have been observed. The nab-paclitaxel/CC-486 combination arm may 
be stopped early for futility if the observed HR is > 1.10, and/or if recommended by the DMC 
based on the safety profile of this combination regimen. A HR> 1.10 when half of the target 
events of 120 have occurred signals a low probability for observing a meaningful difference in 
favor of the nab-paclitaxel/CC-486 combination therapy should the study continue to the end. 
With the assumptions stated above, it will take approximately 15 months from the first subject 
randomized to observe approximately 60 PFS events for the interim analysis.
An additional interim analysis for futility with the PFS endpoint between the nab-
paclitaxel/durvalumab combination therapy and nab-paclitaxel monotherapy arms will be 
conducted when approximately 30 PFS events have been observed in the nab-paclitaxel/
durvalumab combination arm. It is projected that 60 or more PFS events will have been observed 
in the nab-paclitaxel monotherapy arm at that point. The nab-paclitaxel/durvalumab combination 
arm may be stopped early for futility if the observed HR is ≥ 1.10, and/or if recommended by the 
DMC based on the safety profile of this combination regimen. With the assumptions stated 
above, it will take approximately 13 months from the first subject randomized to the nab-
paclitaxel/durvalumab arm to observe the events needed for this interim analysis. As the 
enrollment in the nab-paclitaxel/durvalumab combination arm started after the enrollment in the 
nab-paclitaxel/CC-486 and nab-paclitaxel monotherapy arms ended, randomization between the 
nab-paclitaxel monotherapy and nab-paclitaxel/durvalumab arms does not apply.  Nevertheless, 
the futility boundary for the interim analysis between the two arms will still be utilized as a 
guidance to the DMC for their recommendations.
At the interim analysis data review on 
, based on the recommendation of the DMC, 
treatment with CC-486 was discontinued in the nab-paclitaxel/CC-486 combination arm; 
subjects in this arm may be allowed to continue on nab-paclitaxel single agent, at the 
Investigator’s discretion.  
Similarly, following the outcome of the interim analysis between nab-paclitaxel/durvalumab 
combination and nab-paclitaxel monotherapy arms, and taking into account the DMC 
recommendations, subjects may be allowed to remain on either nab-paclitaxel or durvalumab as 
a single agent or both agents, at the Investigator’s discretion.
Disease control rate, OS, and ORR within and the difference between the nab-paclitaxel/CC-486 
combination and nab-paclitaxel monotherapy treatment arms will be estimated at the time of the 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
71
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
final analysis of the PFS endpoint when approximately 120 PFS events have been observed
between these two arms. The same endpoints will be estimated within the nab-
paclitaxel/durvalumab arm and between this and the nab-paclitaxel monotherapy arms when 
approximately 50 PFS events have been observed in the nab-paclitaxel/durvalumab arm. 
All subjects in the nab-paclitaxel/CC-486 combination and nab-paclitaxel monotherapy arms 
will continue to be followed for OS for at least 12 months after the last subject is randomized to
either of these two arms or 120 PFS events have been observed between these two arms, 
whichever comes later. All subjects in the nab-paclitaxel/durvalumab arm will be followed for 
OS for at least 12 months after the last subject is assigned to this arm.
The study milestones for the scenario that all 3 arms proceed to the end of the study are
summarized in the table below:
Study Milestone
Time from First Subject 
Randomized (Day 1)
First subject randomized to either the nab-paclitaxel/CC-486 and nab-
paclitaxel monotherapy arms (1:1 randomization ratio)
Day 1
Interim analysis for nab-paclitaxel/CC-486 vs. nab-paclitaxel 
monotherapy (~60 PFS events total)
~ 15 months
Addition of the nab-paclitaxel/durvalumab arm to the study; 
randomization in a 1:1:1 ratio to the nab-paclitaxel/CC-486, nab-
paclitaxel/durvalumab, and nab-paclitaxel arms begins.
~ 15 months
Last subject randomized to the nab-paclitaxel/CC-486 and nab-
paclitaxel arms
~ 23 months
Assignment of all incoming subjects to the durvalumab arm begins.
~ 24 months
Final analysis for nab-paclitaxel/CC-486 vs. nab-paclitaxel (~120 PFS 
events total)
~25 months
Last subject assigned to the nab-paclitaxel/durvalumab arm
~ 28 months
Interim analysis for nab-paclitaxel/durvalumab vs. nab-paclitaxel (~30 
PFS events from nab-paclitaxel/durvalumab, ≥60 from nab-paclitaxel 
monotherapy)
~28 months
Final analysis for nab-paclitaxel/durvalumab vs. nab-paclitaxel (~50
PFS events have been observed in the nab-paclitaxel/durvalumab arm)
~ 31 months
End of OS Follow-up for subjects in nab-paclitaxel/CC-486 and nab-
paclitaxel arms
~ 35 months
End of OS Follow-up for durvalumab subjects
~40 months
10.4.
Background and Demographic Characteristics
The baseline characteristics of all randomized/assigned subjects will be summarized. Subject’s 
age, height, weight, and baseline characteristics will be summarized using descriptive statistics, 
while gender, race and other categorical variables will be provided using frequency tabulations. 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
72
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Selected medical history data will be summarized using frequency tabulations by system organ 
class and preferred term.
10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both Treatment 
and Follow-up Periods. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
10.6.
Efficacy Analysis
10.6.1.
Primary Efficacy Endpoints 
The primary efficacy endpoint is progression-free survival, which is defined as the time from the 
date of randomization/treatment assignment to the date of disease progression or death (any 
cause) on or prior to the data cutoff date for analyses, whichever occurs first, based on the 
Investigator’s assessment of the data from CT scans using RECIST 1.1 guidelines. Baseline 
tumor measurements will be determined from the radiologic evaluation performed within 28 
days before the start of study therapy. 
Subjects who do not have disease progression and are alive as of the data cutoff date for the 
statistical analysis will be censored at the date of the last radiologic assessment prior to the data 
cutoff date.  Similarly, subjects who discontinue from the study prior to disease progression or 
death will be censored at the date of the last radiologic assessment prior to the data cutoff date.  
In the event that a new anticancer treatment occurs prior to documented progression, the subject 
will be censored at the date of the last radiologic assessment where the subject was documented 
to be progression-free prior to the new anticancer treatment. Subjects with a single missing 
radiologic assessment prior to a visit with documented disease progression (or death) will be 
analyzed as a PFS event at the date of the radiologic assessment that shows progression or death 
(whichever is earlier). Subjects with two or more missing radiologic assessments prior to a visit 
with documented disease progression (or death) will be censored at the date of the last radiologic 
assessment where the subject was documented to be progression-free prior to the first of the two 
missing visits.  Subjects who are alive and drop out early without any post baseline radiologic 
tumor assessment will be censored on the date of randomization/treatment assignment. 
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% CI) for each treatment arm. The Kaplan-Meier curve for PFS will 
be presented graphically for each treatment arm. The relative treatment effect between the 
combination and monotherapy arms on PFS will be estimated by the hazard ratio (HR) and the 
associated two-sided 95% CIs using the stratified Cox proportional hazard model with ECOG 
performance status (0 versus 1), gender (males versus females), and smoker (yes versus no) as 
the stratification factors, given the number of events in each cell is adequate. No statistical 
inferential tests will be performed.
To assess the impact on PFS of radiologic assessments not occurring at the regularly scheduled 
assessment times, the frequency of these unscheduled/off-scheduled assessments will be 
presented for each treatment arm. In addition, confirmatory and sensitivity analyses may be 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
73
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
performed to further assess the impact of missed radiologic assessments. An additional analysis 
of PFS, where death or new treatment will be considered as an event, will be conducted to 
address the impact of next line therapy. 
To explore the effect of treatment post initial progression, PFS defined by irRECIST criteria may
be estimated for the subjects in the nab-paclitaxel/durvalumab arm.  
10.6.2.
Secondary Efficacy Endpoints
10.6.2.1.
Disease Control Rate
Disease control rate is defined as the percent of subjects who have a radiologic complete 
response, partial response, or stable disease according to RECIST 1.1 guidelines, as determined 
by the Investigator.
Disease control rate for each treatment arm will be summarized by the observed DCR rate and 
the associated two-sided 95% CI. The relative treatment effect will be summarized by the 
absolute difference and ratio of the response rates and the associated two-sided 95% CI.
10.6.2.2.
Overall Survival
Overall survival is defined as the time between randomization/treatment assignment and death. 
All deaths, regardless of the cause of death, will be included. All subjects who are lost to follow-
up prior to the end of the study or who are withdrawn from the study will be censored at the time 
of last contact. Subjects who are still receiving treatment as of the data cutoff date will be 
censored at the cutoff date. Overall survival will be analyzed in a similar manner as that for PFS.
10.6.2.3.
Overall Response Rate 
Overall response rate is defined as the percent of subjects who have a radiologic complete or 
partial response according to RECIST 1.1 guidelines determined by the Investigator.  
Overall response rate will be assessed using the same statistical methods as those for the DCR 
endpoint.
10.6.3.
Exploratory Endpoints
10.6.3.1.
HealthCare Utilization 
Healthcare utilization will be summarized by treatment. Additional analyses will be described in 
detail in the SAP.
10.6.3.2.
Quality of Life Questionnaires
The score or VAS value and the corresponding change from baseline at each timepoint will be 
summarized by treatment for the EQ-5D-5L, EORTC QLQ C30 and LCSS questionnaires. 
Additional analyses will be described in detail in the SAP. 
10.6.3.3.
Biomarker, Tumor Characteristics, and Genomic Analyses 
Statistical analysis of the biomarkers, tumor characteristics, and genomic correlates will be 
described in a SAP separate from that described above.
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Additioion


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
74
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
10.6.3.4.
Anti-tumor Activity and PD-L1 Expression (nab-Paclitaxel/Durvalumab Arm)
An exploratory analysis of PFS and DCR using investigator’s assessments based according to 
irRECIST criteria, and their association with PD-L1 expression will be performed for subjects in 
the nab-paclitaxel/durvalumab arm.  
10.7.
Safety Analysis
The treated population, which includes all subjects who receive at least one dose of IP, will be 
the analysis population for all safety analyses.
The safety/tolerability of the treatment arms will be monitored through continuous reporting and 
evaluated by adverse events and serious adverse events, and incidence of subjects experiencing 
dose modifications, dose interruptions, and/or premature discontinuation of IP.
10.7.1.
Adverse Events
TEAEs will be defined as any AE or SAE occurring or worsening on or after the day of the first 
dose of the IP through 28 days after the last dose of IP for the monotherapy arm and the nab-
paclitaxel/CC-486 combination arms, or 90 days after last dose of IP in the nab-
paclitaxel/durvalumab combination arm.  In addition, any serious AE with an onset date more 
than 28 days after the last dose of IP that is assessed by the Investigator as related to IP will be 
considered a TEAE. TEAEs occurring up to 28 days after the last dose of IP will be summarized. 
In addition, for the nab-paclitaxel/durvalumab arm, AEs with an onset from 29 days up to 90 
days after the last dose of IP will be summarized separately.
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA). The severity of AEs will be graded based on NCI CTCAE, Version 4.0; 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Treatment-emergent adverse events, Grade 3 or higher TEAEs, serious AEs, TEAEs leading to 
dose reduction, and dose interruption, TEAEs leading to treatment discontinuation, and TEAEs 
with an outcome of death will be summarized per treatment arms by MedDRA system organ 
class and preferred terms. 
Adverse events of special interest relevant to the nab-paclitaxel/CC-486 combination, nab-
paclitaxel/durvalumab combination, and nab-paclitaxel monotherapy regimens observed in 
previous studies in a similar population may be identified and summarized by worst NCI 
CTCAE grade, and MedDRA preferred terms.
By-subject listings will be provided for all relevant safety data. Graphical displays and figures 
will be provided where useful to assist in the interpretation of results.
10.7.2.
Laboratory Assessments
Treatment group differences in each laboratory parameter with respect to the NCI CTCAE 
grades will be summarized by the frequency distribution of subjects with the AE grades.  
All laboratory parameters will be summarized by descriptive statistics within each treatment arm, 
as appropriate. 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
75
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
10.7.3.
IP Exposure
The extent of exposure to the IPs will be assessed based on the descriptive statistics on the 
number of cycles and IP doses administered, cumulative dose, average dose intensity, and 
percentage of protocol dose administered.  The incidences of CC-486, nab-paclitaxel, and 
durvalumab dose reductions (although not expected for durvalumab) and dose interruptions will 
be summarized by treatment arm.  
10.8.
Study Therapy Termination
Reasons for stopping study therapy will be presented in listings and summarized by frequency of 
occurrence and corresponding percentage of occurrence.
10.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the IP
through 28 days post last dose of the IP will be summarized by frequency of occurrence and 
corresponding percentage by cause of death per period (during treatment or follow-up). In 
addition, deaths that occur from 29 to 90 days post last dose will be summarized in a similar 
manner for the nab-paclitaxel/durvalumab combination therapy arm.
10.10.
Interim Analysis
One nonbinding interim analysis for PFS with an early stopping rule for futility will be 
conducted when approximately 60 events have been observed between the nab-paclitaxel/CC-
486 combination and nab-paclitaxel monotherapy arms. The nab-paclitaxel/CC-486 combination 
arm may be stopped early for futility if the observed HR is ≥1.10 given the assumed number of 
PFS events above, and/or if recommended by the DMC based on the safety profile of this 
combination regimen.   
An additional interim analysis for futility with the PFS endpoint between the nab-
paclitaxel/durvalumab combination therapy and nab-paclitaxel monotherapy arms will be 
conducted when approximately 30 PFS have been observed in the nab-paclitaxel/durvalumab 
combination arm. This is similar to approximately half of the number of events that are planned 
for the interim analysis between the nab-paclitaxel/CC-486 combination and nab-paclitaxel 
monotherapy arms mentioned above. At this time point, it is projected that approximately ≥ 60 
PFS events will have been observed in the nab-paclitaxel monotherapy arm. The nab-
paclitaxel/durvalumab combination therapy arm may be stopped early for futility if the observed 
HR is ≥ 1.10, and/or if recommended by the DMC based on the safety profile of this 
combination regimen. Should this occur, enrollment in the study may discontinue. The futility 
boundary for the interim analysis between the two arms is provided as a guidance to the DMC 
for their recommendations.
At the interim analysis data review on 
, based on the recommendation of the DMC, 
treatment with CC-486 was discontinued in the nab-paclitaxel/CC-486 combination arm; 
subjects in this arm may be allowed to continue on nab-paclitaxel single agent, at the 
Investigator’s discretion.  
Similarly, following the outcome of the interim analysis between nab-paclitaxel/durvalumab 
combination and nab-paclitaxel monotherapy arms, and taking into account the DMC 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
76
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
recommendations, subjects may be allowed to remain on either nab-paclitaxel or durvalumab as 
a single agent or both agents, at the Investigator’s discretion.
10.11.
Data Monitoring Committee
An independent DMC will be established with the responsibilities for safeguarding the interests 
of study subjects and monitoring the overall conduct of the study. Final recommendations of the 
DMC will reflect the judgment of the DMC members and will be considered advisory in nature 
to the Sponsor. The decision to implement the recommendations of the DMC will be made by
the Sponsor, following consultation with the coordinating Investigator and Steering Committee.
Operational details for the DMC will be detailed in the DMC charter. 
10.12.
Scientific Steering Committee
The conduct of this study will be overseen by a Steering Committee. The Steering Committee 
will serve in an advisory capacity to the Sponsor.
&(/*(1(35235,(7$5<,1)250$7,21
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
77
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the eCRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of NSCLC will not require reporting as 
an adverse event. However, signs and symptoms (events) related to disease progression may be 
reported as adverse events. If reported, events of disease progression for NSCLC (including 
deaths due to disease progression for indications that are considered to be fatal) will be assessed 
as expected adverse events and will not be reported as expedited safety reports to regulatory 
authorities.
Abuse, withdrawal, sensitivity or toxicity to an investigational product should be reported as an 
AE. Overdose, accidental or intentional, whether or not it is associated with an AE should be 
reported as an AE. (See Section 8.8 for the definition of overdose.) Any sequela of an accidental 
or intentional overdose of an investigational product should be reported as an AE on the AE 
CRF. If the sequela of an overdose is an SAE, then the sequela must be reported on an SAE 
report form and on the AE CRF. The overdose resulting in the SAE should be identified as the 
cause of the event on the SAE report form and CRF but should not be reported as an SAE itself.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for nab-paclitaxel,
CC-486 or durvalumab overdose. Actual treatment should depend on the severity of the clinical 
situation and the judgment and experience of the treating physician.
All subjects will be monitored for AEs during the study. Assessments may include monitoring of 
any or all of the following parameters: the subject’s clinical symptoms, laboratory, pathological, 
radiological or surgical findings, physical examination findings, or findings from other 
appropriate tests and procedures.
All AEs will be recorded by the Investigator from the time the subject signs informed consent to
28 days after the last dose of IP for the monotherapy and CC-486 combination arms or to 90 days 
for the durvalumab combination arm, and those SAEs made known to the Investigator at any 
time thereafter that are suspected of being related to IP. AEs and serious adverse events (SAEs) 
will be recorded on the AE page of the eCRF and in the subject’s source documents. All SAEs 
must be reported to Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the 
event by facsimile, or other appropriate method, using the SAE Report Form, or approved 
equivalent form.
11.2.
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to: 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
78
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
!
Results in death;
!
Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the eCRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of or an elective procedure for a pre-existing condition 
unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
79
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to IP, action taken regarding IP, and outcome.
11.2.2.
Severity / Intensity
For both AEs and SAEs, the Investigator must assess the severity/intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current active minor version of NCI CTCAE, Version 4.0
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Adverse events that are not defined in the NCI CTCAE should be evaluated for severity/intensity 
according to the following scale:
!
Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required
!
Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required
!
Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible
!
Grade 4 = Life threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable
!
Grade 5 = Death – the event results in death
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.
Seriousness, not severity, serves as a guide for defining regulatory obligations.
11.2.3.
Causality 
The Investigator must determine the relationship between the administration of IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
Means a causal relationship of the adverse event to IP
administration is unlikely or remote, or other medications, 
therapeutic interventions, or underlying conditions provide a 
sufficient explanation for the observed event.
Suspected:
Means there is a reasonable possibility that the administration 
of IP caused the adverse event.  ‘Reasonable possibility’ means 
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Not su


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
80
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
there is evidence to suggest a causal relationship between the IP
and the adverse event.
Causality should be assessed and provided for every AE/SAE based on currently available 
information.  Causality is to be reassessed and provided as additional information becomes 
available.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP
that has not been manufactured or provided by the Sponsor, please provide the name of the 
manufacturer when reporting the event.
11.2.4.
Duration
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event.
11.2.5.
Action Taken
The Investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(eg, discontinuation or reduction of IP, as appropriate) and report if concomitant and/or 
additional treatments were given for the event. 
11.2.6.
Outcome
The Investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered or death (due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or
!
is judged to be of significant clinical importance by the Investigator.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF. If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE.
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
81
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
11.4.1.
Females of Childbearing Potential
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on IP, or within 3 months of the 
subject’s last dose of IP, are considered immediately reportable events. IP is to be discontinued 
immediately. The pregnancy, suspected pregnancy, or positive pregnancy test must be reported 
to Celgene Drug Safety immediately by facsimile, or other appropriate method, using the 
Pregnancy Initial Report Form, or approved equivalent form. The female subject should be 
referred to an obstetrician-gynecologist or another appropriate healthcare professional for further 
evaluation.
The Investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the Investigator
should report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate 
method, within 24 hours of the Investigator’s knowledge of the event using the SAE Report 
Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the Investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the Investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving IP or within 
6 months of the last dose of IP, the male subject taking IP should notify the Investigator, and the 
pregnant female partner should be advised to call her healthcare provider immediately. If the 
male subject is receiving IP, the IP may need to be discontinued in the male subject, but may be 
resumed later at the discretion of the Investigator and medical monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The Investigator is required to ensure that the data on these forms are accurate and consistent.
This requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent to at least 28 days after the last dose of IP for 
the monotherapy and CC-486 combination arms or 90 days after the last dose of IP for the 
durvalumab combination arm) and those made known to the Investigator at any time thereafter 
that are suspected of being related to IP. SAEs occurring prior to treatment (after signing the 
ICF) will be captured.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
82
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
The SAE report should provide a detailed description of the SAE and include a concise summary
of hospital records and other relevant documents. If a subject died and an autopsy has been 
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available. Any follow-up data will be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety.
Where required by local legislation, the Investigator is responsible for informing the Independent 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The Investigator must keep copies of all SAE 
information on file including correspondence with the Sponsor and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than five (5) business 
days. Urgent queries (eg, missing causality assessment) may be handled by phone.
11.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to nab-paclitaxel, CC-486 or durvalumab based on the
Investigator Brochures of the respective IPs.
In the US, all suspected unexpected serious adverse reactions (SUSARs) will be reported in an 
expedited manner in accordance with 21 CFR 312.32.
For countries within the European Economic Area (EEA), the Sponsor or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 
presentation of adverse reaction reports arising from clinical trials on investigational products for 
human use (ENTR/CT3) and also in accordance with country-specific requirements.
The Sponsor or its authorized representative shall notify the Investigator of the following
information: 
!
Any AE suspected of being related to the use of IP in this study or in other studies
that is both serious and unexpected (ie, SUSAR);
!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with the Sponsor and the IRB/EC. (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form/Completion Guidelines or to the Pregnancy Report Form/Completion Guidelines.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
83
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
11.7.
Definition of Adverse Events of Special Interest
An adverse event of special interest (AESI) is one of scientific and medical interest specific to 
the understanding of the IP and may require close monitoring and rapid communication by the 
Investigator to the Sponsor. An AESI may be serious or nonserious. The rapid reporting of 
AESIs allows ongoing surveillance of these events in order to characterize and understand them 
in association with the use of this IP. Further information on risks (eg, presenting symptoms) can
be found in the current version of the Investigator Brochure, including guidelines for their 
evaluation and treatment.


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
84
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the IP:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent
!
Death
!
Lost to follow-up
!
Protocol violation
The reason for discontinuation should be recorded in the eCRF and in the source documents.
The decision to discontinue a subject remains the responsibility of the treating physician, which
will not be delayed or refused by the Sponsor. However, prior to discontinuing a subject, the
Investigator may contact the Medical Monitor and forward appropriate supporting documents for 
review and discussion.
All subjects discontinued from IP for any reason will have a treatment discontinuation visit at the 
time of discontinuation and should undergo treatment discontinuation procedures.
All subjects discontinued from IP will be followed for a period of 28 days after last dose of IP
for the monotherapy and CC-486 combination arms or 90 days after the last dose of IP for the 
durvalumab combination arm for the collection of AEs.
Additionally subjects who withdraw from or discontinue treatment should be followed for 
progressive disease (if applicable), survival and any new anticancer therapy given.
12.2.
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
study:
!
Withdrawal of consent
!
Death
!
Lost to follow-up
The following events may be considered sufficient reasons for discontinuing a subject from the 
study:
!
Adverse events(s)
!
Protocol violation
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. The Investigator must notify the Medical Monitor immediately when a subject has 
been discontinued/withdrawn due to an AE (any unacceptable toxicity). All subjects who are 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
85
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
withdrawn from the study should complete all protocol-required evaluations scheduled for early 
termination at the time of withdrawal.
Since follow-up of subjects who discontinue prematurely is of particular importance, every 
attempt should be made to collect all survival information and NSCLC treatment/therapy, unless 
the subject has specifically withdrawn consent from further follow-up. The Investigator must 
make every effort to obtain minimal information regarding the subject’s survival status before 
determining that the subject is lost to follow-up.
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.
&(/*(1(35235,(7$5<,1)250$7,21


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
86
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page). This global 
Emergency Call Center is available 24 hours a day and 7 days a week. The representatives are 
responsible for obtaining your call-back information and contacting the on call Sponsor/Contract 
Research Organization (CRO) Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
13.2.
Emergency Identification of Investigational Products
This is an open-label study; therefore, IP will be identified on the package labeling. 
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the pack


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
87
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that the Sponsor, its authorized 
representative, and Investigator abide by Good Clinical Practice (GCP), as described in 
International Conference on Harmonization (ICH) Guideline E6 and in accordance with the 
general ethical principles outlined in the Declaration of Helsinki. The study will receive approval 
from an IRB/EC prior to commencement. The Investigator will conduct all aspects of this study 
in accordance with applicable national, state, and local laws of the pertinent regulatory 
authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. The Sponsor staff or its authorized representative will evaluate and approve 
all Investigators who in turn will select their staff.
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions. 
The Investigator should maintain a list of sub-Investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The Investigator is responsible for keeping a record of all subjects who sign an ICF and are 
screened for entry into the study. Subjects who fail screening must have the reason(s) recorded in 
the subject’s source documents.
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The Investigator must ensure timely and accurate completion of eCRFs and queries.
The information contained in the protocol and amendments (with the exception of the 
information provided by the Sponsor on public registry websites) is considered the Sponsor’s 
confidential information. Only information that is previously disclosed by the Sponsor on a 
public registry website may be freely disclosed by the Investigator or its institution, or as 
outlined in the Clinical Trial Agreement. The Sponsor’s protocol, amendment and IB 
information is not to be made publicly available (for example on the Investigator’s or their 
institution’s website) without express written approval from the Sponsor. Information proposed 
for posting on the Investigator’s or their institution’s website must be submitted to the Sponsor
for review and approval, providing at least 5 business days for review. 
At the time results of this study are made available to the public the Sponsor will provide 
Investigators with a summary of the results that is written for the lay person. The Investigator is 
responsible for sharing these results with the subject and/or their caregiver as agreed by the 
subject.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
88
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
14.3.
Subject Information and Informed Consent
The Investigator must obtain informed consent of the subject and/or the subject’s legal 
representative prior to any study-related procedures.
Documentation that informed consent occurred prior to the subject’s entry into the study and of 
the informed consent process should be recorded in the subject’s source documents including the 
date. The original ICF signed and dated by the subject and by the person consenting the subject
prior to the subject’s entry into the study, must be maintained in the Investigator’s study files and 
a copy given to the subject. In addition, if a protocol is amended and it impacts the content of the 
informed consent, the ICF must be revised. Subjects participating in the study when the amended 
protocol is implemented must be re-consented with the revised version of the ICF. The revised 
ICF signed and dated by the subject and by the person consenting the subject must be maintained 
in the Investigator’s study files and a copy given to the subject. Subjects in the nab-
paclitaxel/durvalumab arm who continue treatment beyond disease progression per RECIST 1.1 
will be requested to sign a consent form at time of progression and prior to treatment 
continuation.
14.4.
Confidentiality
The Sponsor affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). The Sponsor
requires the Investigator to permit the Sponsor's representatives and, when necessary, 
representatives from regulatory authorities, to review and/or copy any medical records relevant 
to the study in accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the Investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Sponsor’s Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the Investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
89
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
IP can only be supplied to an Investigator by the Sponsor or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
the Sponsor or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB/EC should mention the protocol title, number, amendment number 
(if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by the Sponsor and 
the IRB/EC prior to use.
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
The Sponsor reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the Investigator or the Sponsor has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
90
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and distribution of the IP are complete, accurate, filed and retained. Examples of source 
documents include: hospital records; clinic and office charts; laboratory notes; memoranda; 
subject’s diaries or evaluation checklists; dispensing records; recorded data from automated 
instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy and the laboratories, as well 
as copies of CRFs or CD-ROM.
15.2.
Data Management
Data will be collected via eCRF and entered into the clinical database per the Sponsor’s Standard 
Operating Procedures (SOPs). This data will be electronically verified through use of 
programmed edit checks specified by the clinical team. Discrepancies in the data will be brought 
to the attention of the clinical team, and investigational site personnel, if necessary. Resolutions 
to these issues will be reflected in the database. An audit trail within the system will track all 
changes made to the data.
15.3.
Record Retention
Essential documents must be retained by the Investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IP. The Investigator must retain these 
documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the Investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the Investigator, Sponsor, and their authorized 
representative(s);
!
List of sub-Investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of CRFs (if paper) and of documentation of corrections for all subjects;
!
IP accountability records;
!
Record of any body fluids or tissue samples retained;
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
91
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
!
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The Investigator must notify the Sponsor if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.
The Investigator must obtain approval in writing from the Sponsor prior to destruction of any 
records. If the Investigator is unable to meet this obligation, the Investigator must ask the 
Sponsor for permission to make alternative arrangements. Details of these arrangements should 
be documented. 
All study documents should be made available if required by relevant health authorities. The 
Investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
92
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
16.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by the Sponsor or its authorized 
representative for compliance with applicable government regulations with respect to current 
GCP and standard operating procedures.
16.1.
Study Monitoring and Source Data Verification
The Sponsor ensures that appropriate monitoring procedures are performed before, during and 
after the study. All aspects of the study are reviewed with the Investigator and the staff at a study 
initiation visit and/or at an Investigator meeting. Prior to enrolling subjects into the study, a 
Sponsor representative or designee will review the protocol, eCRFs, procedures for obtaining 
informed consent, record keeping, and reporting of AEs/SAEs with the Investigator. Monitoring 
will include on-site visits with the Investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, IP 
storage area, eCRFs, subject’s source documents, and all other study documentation will be
inspected/reviewed by the Sponsor representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the eCRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff. Any necessary 
corrections will be made directly to the eCRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within the Sponsor. Representatives of this unit will conduct audits of clinical 
research activities in accordance with the Sponsor’s SOPs to evaluate compliance with Good 
Clinical Practice guidelines and regulations.
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, eCRFs and applicable supporting records of subject participation for audits 
and inspections by IRB/IECs, regulatory authorities (eg, FDA, European Medicines Agency 
[EMA], Health Canada) and company authorized representatives. The Investigator should make 
every effort to be available for the audits and/or inspections. If the Investigator is contacted by 
any regulatory authority regarding an inspection, he/she should contact the Sponsor immediately.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
93
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
17.
PUBLICATIONS
As described in Section 14.2, all protocol- and amendment-related information, with the 
exception of the information provided by the Sponsor on public registry websites, is considered 
Sponsor’s confidential information and is not to be used in any publications. The Sponsor
protocol-related information proposed for use in a publication must be submitted to the Sponsor
for review and approval, and should not be utilized in a publication without express written 
approval from the Sponsor, or as described in the Clinical Trial Agreement. 
The Sponsor will ensure sponsored studies are considered for publication in the scientific 
literature in a peer-reviewed journal, irrespective of the results. At a minimum, this applies to 
results from all Phase 3 clinical studies, and any other study results of significant medical 
importance. This also includes results relating to investigational medicines whose development 
programs have been discontinued. 
Study results may also be presented at one or more medical congresses, and may be used for 
scientific exchange and teaching purposes. Additionally, this study and its results may be 
submitted for inclusion in all appropriate health authority study registries, as well as publication 
on health authority study registry websites, as required by local health authority regulations. 
Eligibility for external authorship, as well as selection of first authorship, will be based on  
several considerations, including, but not limited to, contribution to protocol development, study 
recruitment, data quality, participation in data analysis, participation in study steering committee 
(when applicable) and contribution to abstract, presentation and/or publication development.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
94
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
18.
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Celgene Corporation
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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2013 Nov 1
2013 Nov 
tititutute for H
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1;23(6):12
;23(6):12
shin
shin


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
97
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
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(8):981
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cini


EDMS Doc. Number: 
nab-paclitaxel
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Confidential and Proprietary
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EDMS Doc. Number: 
nab-paclitaxel
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19.
APPENDICES
Appendix A: ECOG Performance Status Score
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5
Dead
Oken, 1982.
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EDMS Doc. Number: 
nab-paclitaxel
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ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Appendix B: Recommendations for Management of Treatment-Induced 
Diarrhea
The following published guidelines (Benson, 2004) were modified in order to be consistent with 
the clinical study protocol.
&(/*(1(35235,(7$5<,1)250$7,21


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ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Appendix C: Treatment Modification and Toxicity Management for nab-
Paclitaxel /Durvalumab arm
(based on updated guidelines for Durvalumab/MEDI4736 - 09 Aug 2016 version)
General guidelines regarding treatment modification for MEDI4736 and/or nab-paclitaxel are 
provided below for immune-related AEs (Table C1), infusion-related reactions (Table C2), and 
non-immune-mediated reactions (Table C3). 
These guidelines apply to AEs considered causally related to the durvalumab containing regimen 
by the reporting Investigator. Treatment modifications referring to “study regimen” would apply 
to both nab-paclitaxel and durvalumab unless AEs are not considered causally related to nab-
paclitaxel by the reporting Investigator. In that case nab-paclitaxel treatment may be continued 
alone if deemed beneficial to the subject per Investigator’s assessment. 
&(/*(1(35235,(7$5<,1)250$7,21
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EDMS Doc. Number: 
nab-paclitaxel
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ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Table C1:
Treatment Modification and Toxicity Management Guidelines for Immune-related Adverse Events
Event
Dose Modifications
Toxicity Management
Immune-related 
AEs (overall 
management for 
toxicities not 
noted below)
Drug administration modifications of IP/study 
regimen will be made to manage potential 
immune-related AEs based on severity of 
treatment-emergent toxicities graded per NCI 
CTCAE v4.03.
In addition to the criteria for permanent 
discontinuation of IP/regimen based on CTC 
Grade/severity (table below), permanently 
discontinue IP/study regimen for the following 
conditions:
• Inability to reduce corticosteroid to a dose of 
≤10 mg of prednisone per day (or equivalent) 
within 12 weeks after last dose of IP/regimen
• Recurrence of a previously experienced Grade 3 
treatment-related AE following resumption of 
dosing
It is recommended that management of irAEs follow the guidelines 
presented in this table
- Subjects should be thoroughly evaluated to rule out any alternative 
etiology (e.g. disease progression, concomitant medications, 
infections, etc.)
- In the absence of a clear alternative etiology, all events should be 
considered potentially immune related
- Symptomatic and topical therapy should be considered for low-
grade (Grade 1 or 2, unless otherwise specified) events
- For persistent (greater than 3 to 5 days) low-grade (Grade 2) or 
severe (Grade ≥3) events promptly start prednisone 1-2mg/kg/day PO 
or IV equivalent
- If symptoms recur or worsen during corticosteroid tapering 28 days 
of taper), increase the corticosteroid dose (prednisone dose [e.g. up to 
2-4mg/kg/day PO or IV equivalent]) until stabilization or 
improvement of symptoms, then resume corticosteroid tapering at a 
slower rate (> 28 days of taper)
- More potent immunosuppressives such as TNF inhibitors (eg, 
infliximab) – (also refer to the individual sections of the immune 
related adverse event for specific type of immunosuppressive) should 
be considered for events not responding to systemic steroids 
- Discontinuation of IP is not mandated for Grade 3 / 4 inflammatory 
reactions attributed to local tumor response (e.g. inflammatory 
reaction at sites of metastatic disease, lymph nodes etc.). 
Continuation of IP in this situation should be based upon a 
benefit/risk analysis for that subject
Grade 1
No dose modification
Grade 2
Hold IP/study regimen dose 
until Grade 2 resolution to ≤ 
Grade 1
• If toxicity worsens then treat 
as Grade 3 or Grade 4
• IP/study treatment can be 
resumed once event stabilizes 
to Grade ≤1 after completion 
of steroid taper
Subjects with endocrinopathies 
who may require prolonged or 
continued steroid replacement 
can be retreated with IP/study 
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EDMS Doc. Number: 
nab-paclitaxel
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ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Event
Dose Modifications
Toxicity Management
regimen on the following 
conditions: 
1) the event stabilizes and is
controlled, 
2) the subject is clinically 
stable as per Investigator or 
treating physician’s clinical 
judgment, and 
3) doses of prednisone are at 
less than or equal to 10mg/day 
or equivalent.
Grade 3
Depending on the individual 
toxicity, may permanently 
discontinue IP/study regimen. 
Please refer to guidelines 
below
Grade 4
Permanently discontinue 
IP/study regimen
Note: For Grade 3 and above asymptomatic 
amylase or lipase levels hold IP/regimen and if 
complete work up shows no evidence of 
pancreatitis, may continue or resume IP/regimen
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
Pneumonitis/ILD
Grade of 
Pneumonitis 
(CTCAE version 
4.03)
General guidance
- Monitor subjects for signs and symptoms of pneumonitis or ILD 
(new onset or worsening shortness of breath or cough). Subjects 
should be evaluated with imaging and pulmonary function tests 
including other diagnostic procedures as described below
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EDMS Doc. Number: 
nab-paclitaxel
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ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
- Initial work-up may include clinical evaluation, monitoring of 
oxygenation via pulse oximetry (resting and exertion), laboratory 
work-up and high-resolution CT scan.
Grade 1 
(asymptomatic,
clinical or
diagnostic
observations only,
intervention not 
indicated)
No dose modification 
required. However, consider 
holding IP/study regimen 
dosing as clinically 
appropriate and during 
diagnostic work-up for other 
etiologies
For Grade 1 (radiographic changes only)
- Monitor and closely follow up in 2-4 days for clinical symptoms, 
pulse oximetry (resting and exertion) and laboratory work-up and 
then as clinically indicated
- Consider pulmonary and infectious disease consult
Grade 2
(symptomatic,
medical
intervention
indicated, limiting
instrumental 
ADL)
• Hold IP/study regimen 
dose until Grade 2 
resolution to ≤ Grade 1
• If toxicity worsens then 
treat as Grade 3 or Grade 4
• If toxicity improves to ≤ 
Grade 1 then the decision to 
reinitiate IP/regimen will be 
based upon treating 
physician’s clinical 
judgment and after 
completion of steroid taper.
For Grade 2 (mild to moderate new symptoms)
- Monitor symptoms daily and consider hospitalization
- Promptly start systemic steroids (eg, prednisone 1-2 mg/kg/day PO 
or IV equivalent)
- Reimaging as clinically indicated
- If no improvement within 3-5 days, additional workup should be 
considered and prompt treatment with IV methylprednisolone 2-4 
mg/kg/day started
- If still no improvement within 3-5 days despite IV
methylprednisone at 2-4 mg/kg/day, promptly start
immunosuppressive therapy such as TNF inhibitors (eg, infliximab at 
5 mg/kg every 2 weeks). Caution: Important to rule out sepsis and 
refer to infliximab label for general guidance before using infliximab
- Once improving, gradually taper steroids over ≥28 days and 
consider prophylactic antibiotics, antifungal or anti PCP treatment 
(refer to current NCCN guidelines for treatment of cancer-related 
infections (Category 2B recommendation)2
2 ASCO Educational Book 2015 “Managing Immune Checkpoint Blocking Antibody Side Effects” by Michael Postow MD.
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EDMS Doc. Number: 
nab-paclitaxel
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ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
- Consider pulmonary and infectious disease consult
- Consider as necessary discussing with study physician
Grade 3 or 4
(Grade 3: severe
symptoms; 
limiting self-care 
ADL; oxygen 
indicated;
Grade 4: life
threatening
respiratory
compromise, 
urgent
intervention
indicated [e.g. 
tracheostomy or 
intubation])
Permanently discontinue 
IP/study regimen
For Grade 3 or 4 (severe or new symptoms, new/worsening hypoxia, 
life threatening
- Promptly initiate empiric IV methylprednisolone 1 to 4 mg/kg/day 
or equivalent
- Obtain pulmonary and infectious disease consult
- Hospitalize the subject
- Supportive Care (oxygen, etc.)
- If no improvement within 3-5 days, additional workup should be 
considered and prompt treatment with additional immunosuppressive 
therapy such as TNF inhibitors (eg, infliximab at 5mg/kg every 2 
weeks dose) started. Caution: rule out sepsis and refer to infliximab
label for general guidance before using infliximab
- Once improving, gradually taper steroids over ≥28 days and 
consider prophylactic antibiotics, antifungals and in particular, anti 
PCP treatment (please refer to current NCCN guidelines for treatment 
of cancer-related infections (Category 2B recommendation) 2
Diarrhea/
enterocolitis
Grade of Diarrhea 
(CTCAE version 
4.03)
General Guidance
- Monitor for symptoms that may be related to diarrhea/ enterocolitis 
(abdominal pain, cramping, or changes in bowel habits such as 
increased frequency over baseline or blood in stool) or related to 
bowel perforation (such as sepsis, peritoneal signs and ileus)
- Subjects should be thoroughly evaluated to rule out any alternative 
etiology (eg, disease progression, other medications, infections 
including testing for clostridium difficile toxin, etc.)
- Steroids should be considered in the absence of clear alternative 
etiology, even for low grade events, in order to prevent potential 
progression to higher grade event
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EDMS Doc. Number:
nab-paclitaxel
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106
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
- Use analgesics carefully; they can mask symptoms of perforation 
and peritonitis
Grade 1 diarrhea
(stool frequency 
of <4 over 
baseline per day)
No dose modification
For Grade 1 diarrhea:
- Close monitoring for worsening symptoms
- Consider symptomatic treatment including hydration, electrolyte 
replacement, dietary changes (eg, American Dietetic Association 
colitis diet), and loperamide. Use of probiotics as per treating 
physician’s clinical judgment.
Grade 2 diarrhea
(stool frequency 
of 4-6 over 
baseline per day)
• Hold IP/study regimen 
until resolution to ≤ Grade 1
• If toxicity worsens then 
treat as Grade 3 or Grade 4
• If toxicity improves to ≤ 
Grade 1 then IP/study 
regimen can be resumed 
after completion of steroid 
taper
For Grade 2 diarrhea:
- Consider symptomatic treatment including hydration, electrolyte 
replacement, dietary changes (e.g., American Dietetic Association 
colitis diet), and loperamide and/or budesonide
- Promptly start prednisone 1 to 2 mg/kg/day PO or IV equivalent
- If event is not responsive within 3-5 days or worsens despite 
prednisone at 1-2 mg/kg/day PO or IV equivalent, GI consult should 
be obtained for consideration of further workup such as imaging 
and/or colonoscopy to confirm colitis and rule out perforation, and 
prompt treatment with IV methylprednisolone 2 to 4mg/kg/day 
started.
- If still no improvement within 3-5 days despite 2 to 4 mg/kg IV 
methylprednisolone, promptly start immunosuppressives such as 
(infliximab at 5mg/kg once every 2 weeks). Caution: important to 
rule out bowel perforation and refer to infliximab label for general
guidance before using infliximab
- Consult study physician if no resolution to ≤ Grade 1 in 3-4 days
- Once improving, gradually taper steroids over ≥28 days and 
consider prophylactic antibiotics, antifungals and anti PCP treatment 
(please refer to current NCCN guidelines for treatment of cancer-
related infections
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
107
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
[Category 2B recommendation])2
Grade 3 or 4
Diarrhea
(Grade 3: stool
frequency of ≥7
over baseline per
day;
Grade 4: life
threatening
consequences)
Permanently discontinue 
IP/study regimen
For Grade 3 or 4 diarrhea:
- Promptly initiate empiric IV methylprednisolone 2 to 4 mg/kg/day 
or equivalent
- Monitor stool frequency and volume and maintain hydration
- Urgent GI consult and imaging and/or colonoscopy as appropriate
- If still no improvement within 3-5 days of IV methylprednisolone 2 
to 4mg/kg/day or equivalent, promptly start further 
immunosuppressives (eg, infliximab at 5mg/kg once every 2 weeks).
- Caution: ensure GI consult to rule out bowel perforation and refer to 
infliximab label for general guidance before using infliximab.
- Once improving, gradually taper steroids over ≥28 days and 
consider prophylactic antibiotics, antifungals and anti PCP treatment 
(please refer to current NCCN guidelines for treatment of cancer-
related infections
[Category 2B recommendation])2
Hepatitis (elevated 
LFTs)
Infliximab
should not be
used for
management of
immune related
hepatitis
Grade of liver
function test
elevation (CTCAE
version 4.03)
Any grade
Grade 1 (AST or 
ALT > to 3 times 
ULN and/or TB > 
to 1.5 times ULN)
No dose modification
If it worsens, treat as Grade 
2 event
- Monitor and evaluate liver function test: AST, ALT, ALP and total 
bilirubin
- Evaluate for alternative etiologies (eg, viral hepatitis, disease 
progression, concomitant medications)
For Grade 1 AST or ALT and/or TB elevation
- Continue LFT monitoring per protocol
Grade 2 (AST or 
ALT > 3 to 5 
times ULN and/or 
Hold IP/study regimen dose 
until Grade 2 resolution to ≤ 
Grade 1
For Grade 2 AST or ALT and or TB elevation:
- Regular and frequent checking of LFTs (e.g. every 1-2 days) until 
elevations of these are improving or resolved.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
108
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
TB >1.5-3.0 times 
ULN)
• If toxicity worsens then 
treat as Grade 3 or Grade 4
• If toxicity improves to ≤ 
Grade 1 then resume 
IP/study regimen after
completion of steroid taper
- If no resolution to ≤ Grade 1 in 1-2 days, discuss with study 
physician.
- If event is persistent (> 3-5 days) or worsens, promptly start 
prednisone 1-2mg/kg/day PO or IV equivalent.
- If still no improvement within 3-5 days despite 1- 2mg/kg/day of 
prednisone PO or IV equivalent, consider additional workup and 
prompt treatment with IV methylprednisolone 2-4mg/kg/day.
- If still no improvement within 3-5 days despite 2-4mg/kg/day of IV 
methylprednisolone, promptly start immunosuppressives 
(mycophenolate mofetil). Discuss with study physician if 
mycophenolate mofetil is not available. Infliximab should NOT be 
used.
- Once improving, gradually taper steroids over ≥28 days and 
consider prophylactic antibiotics, antifungals and anti PCP treatment 
(please refer to current NCCN guidelines for treatment of cancer-
related infections [Category 2B recommendation])2
Grade 3
(AST or ALT >5-
20 times ULN 
and/or TB > 3.0-
10 times ULN
For elevations in 
transaminases ≤ 8 × ULN, 
or elevations in bilirubin ≤ 5 
× ULN:
• Hold IP/study regimen 
dose until resolution to ≤ 
Grade 1 or baseline
• Resume IP/study regimen 
if elevations downgrade ≤ 
Grade 1 or baseline within 
14 days, and after 
completion of steroid taper
• Permanently discontinue 
IP/study regimen if the 
For Grade 3 or 4 AST or ALT and/or TB elevation:
- Promptly initiate empiric IV methylprednisolone at 1 to 4mg/kg/day 
or equivalent
- If still no improvement within 3-5 days despite 1 to 4 mg/kg/day 
methylprednisolone IV or equivalent, promptly start treatment with 
immunosuppressive therapy (mycophenolate mofetil). Discuss with 
study physician if mycophenolate is not available. Infliximab should 
NOT be used.
- Hepatology consult, abdominal workup, and imaging as
appropriate.
- Once improving, gradually taper steroids over ≥28 days and 
consider prophylactic antibiotics, antifungals and anti PCP treatment 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
109
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
elevations do not downgrade
to ≤Grade 1 or baseline 
within 14 days
• For elevations in 
transaminases > 8 × ULN or 
elevations in bilirubin > 5 × 
ULN, discontinue IP/study 
regimen
• Permanently discontinue 
IP/study regimen for any 
case meeting Hy’s law 
criteria (AST and/or ALT > 
3x ULN + bilirubin > 2x
ULN without initial findings 
of cholestasis (ie, elevated 
alkaline P04) and in the 
absence of any alternative 
cause3
(please refer to current NCCN guidelines for treatment of cancer-
related infections
[Category 2B recommendation])2
Grade 4
(AST or ALT > 20 
times ULN and/or 
TB > 10 times 
ULN)
Permanently discontinue 
IP/study regimen
Nephritis or renal
dysfunction
(elevated serum
creatinine)
Grade of elevated
serum creatinine
(CTCAE version
4.03)
Any grade
General guidance
- Consult with nephrologist
- Monitor for signs and symptoms that may be related to changes in 
renal function (e.g. routine urinalysis, elevated serum BUN and 
creatinine, decreased creatinine clearance, electrolyte imbalance, 
decrease in urine output, proteinuria, etc.)
3 FDA Liver Guidance Document 2009 Guidance for Industry: Drug Induced Liver Injury – Premarketing Clinical Evaluation.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
110
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
- Subjects should be thoroughly evaluated to rule out any alternative 
etiology (e.g. disease progression, infections, etc.)
- Steroids should be considered in the absence of clear alternative 
etiology even for low grade events (Grade 2), in order to prevent 
potential progression to a higher grade event
Grade 1 [serum
creatinine > 1-
1.5X baseline; > 
ULN to 1.5X  
ULN]
No dose modification
For Grade 1 elevated creatinine:
- Monitor serum creatinine weekly and any accompanying symptom
!
If creatinine returns to baseline, resume its regular 
monitoring per study protocol.
!
If it worsens, depending on the severity, treat as Grade 2 or 
Grade 3 or 4
- Consider symptomatic treatment including hydration, electrolyte 
replacement, diuretics, etc.
Grade 2 [serum
creatinine>1.5-
3.0X baseline; 
>1.5X- 3.0XULN]
Hold IP/study regimen until 
resolution to ≤ Grade 1 or 
baseline
• If toxicity worsens then 
treat as Grade 3 or Grade 4
• If toxicity improves to ≤ 
Grade 1 or baseline then 
resume IP/study regimen 
after completion of steroid 
taper
For Grade 2 elevated creatinine:
- Consider symptomatic treatment including hydration,
electrolyte replacement, diuretics, etc.
- Carefully monitor serum creatinine every 2-3 days and as clinically 
warranted
- Consult nephrologist and consider renal biopsy if clinically 
indicated
- If event is persistent (> 3-5 days) or worsens, promptly start 
prednisone 1 to 2 mg/kg/day PO or IV equivalent
- If event is not responsive within 3-5 days or worsens despite 
prednisone at 1-2 mg/kg/day PO or IV equivalent, additional workup 
should be considered and prompt treatment with IV 
methylprednisolone at 2-4mg/kg/day started.
- Once improving gradually taper steroids over ≥28 days and 
consider prophylactic antibiotics, antifungals and anti PCP treatment 
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in the absen
in the absen
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events (Grad
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creatinine:
reatinine we
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Grade 3
Grade 3
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5,


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
111
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
(please refer to current NCCN guidelines for treatment of cancer-
related infections [Category 2B recommendation])2.
- When event returns to baseline, resume IP/study regimen and 
routine serum creatinine monitoring per study protocol.
Grade 3 or 4
(Grade 3: serum
creatinine > 3.0 X
baseline; >3.0-6.0
X ULN
Grade 4: Serum 
Creatinine > 6.0 X 
ULN)
Permanently discontinue 
IP/study regimen
- Carefully monitor serum creatinine on daily basis
- Consult Nephrologist and consider renal biopsy if clinically 
indicated
- Promptly start prednisone 1 to 2 mg/kg/day PO or IV equivalent
- If event is not responsive within 3-5 days or worsens despite 
prednisone at 1-2 mg/kg/day PO or IV equivalent, additional workup 
should be considered and prompt treatment with IV 
methylprednisolone 2-4mg/kg/day started.
- Once improving, gradually taper steroids over ≥28 days and 
consider prophylactic antibiotics, antifungals and anti PCP treatment 
(please refer to current NCCN guidelines for treatment of cancer-
related infections [Category 2B recommendation]2
Rash (excluding
bullous skin
formations)
Grade of Skin 
Rash (Please refer 
to NCICTCAE 
version 4.03 for 
definition of 
severity/grade 
depending on type 
of skin rash)
General guidance
• Monitor for signs and symptoms of dermatitis (rash and pruritus)
• **IF THERE IS ANY BULLOUS FORMATION, THE STUDY 
PHYSICIAN SHOULD BE CONTACTED AND IP
DISCONTINUED**
Grade 1
No dose modification
For Grade 1:
- Consider symptomatic treatment including oral antipruritics (e.g.
diphenhydramine or hydroxyzine) and topical therapy (e.g. urea 
cream)
pri
prietet
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2
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ommendatio
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e, resum IP
IP
nitoring per
nitoring per
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rt prednison
rt prednison
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s not respo
one at 1-
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2 m
d be consid
d be consi
ethylprednis
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- Once
Once imp
im
conside
consid
(plea
(plea
rer
)2
5,
35
1
No d
No d
1
(/ (1


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
112
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
Grade 2
For persistent (> 1- 2 weeks) 
Grade 2 events, hold 
scheduled IP/study regimen 
until resolution to ≤ Grade 1 
or baseline
• If toxicity worsens then 
treat as Grade 3
• If toxicity improves to 
Grade ≤ 1 or baseline, then 
resume
IP/study regimen after 
completion of steroid taper
For Grade 2:
- Obtain dermatology consult
- Consider symptomatic treatment including oral antipruritics (e.g.
diphenhydramine or hydroxyzine) and topical therapy (e.g. urea 
cream)
- Consider moderate-strength topical steroid
- If no improvement of rash/skin lesions occurs within 3-5 days or is 
worsening despite symptomatic treatment and/or use of moderate 
strength topical steroid, discuss with study physician and promptly 
start systemic steroids prednisone 1-2 mg/kg/day PO or IV equivalent
- Consider skin biopsy if persistent for >1-2 weeks or recurs
Grade 3
• Hold IP/study regimen 
until resolution to ≤ Grade 1 
or baseline
• If temporarily holding the 
study drug/study regimen 
does not provide 
improvement of the Grade 3 
skin rash to ≤ Grade 1 or 
baseline within 30 days, 
then permanently 
discontinue IP/study 
regimen
For Grade 3 or 4:
- Consult dermatology
- Promptly initiate empiric IV methylprednisolone 1 to 4 mg/kg/day 
or equivalent
- Consider hospitalization
- Monitor extent of rash [Rule of Nines]
- Consider skin biopsy (preferably more than 1) as clinically feasible.
- Once improving, gradually taper steroids over ≥28 days and 
consider prophylactic antibiotics, antifungals and anti PCP treatment 
(please refer to current NCCN guidelines for treatment of cancer-
related infections [Category 2B recommendation])2
- Discuss with study physician
Grade 4
Permanently discontinue 
IP/study regimen
Endocrinopathy
(eg,
hyperthyroidism,
Any grade
(Depending on the 
type of 
General guidance
- Consult Endocrinologist
- Monitor subjects for signs and symptoms of endocrinopathies. Non-
specific symptoms include headache, fatigue, behavior changes, 
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*(
(/ (


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
113
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
hypothyroidism,
hypopituitarism,
adrenal
insufficiency, etc.)
endocrinopathy, 
refer to NCI 
CTCAE version 
4.03 for defining 
the CTC 
grade/severity)
changed mental status, vertigo, abdominal pain, unusual bowel 
habits, hypotension and weakness.
- Subjects should be thoroughly evaluated to rule out any alternative 
etiology (e.g. disease progression including brain metastases,
infections, etc.)
- Monitor and evaluate thyroid function tests: TSH, free T3 and free 
T4 and other relevant endocrine labs depending on suspected 
endocrinopathy.
- If a subject experiences an AE that is thought to be possibly of 
autoimmune nature (e.g. thyroiditis, pancreatitis, hypophysitis, 
diabetes insipidus), the investigator should send a blood sample for 
appropriate autoimmune antibody testing
Grade 1
(depending on the
type of
endocrinopathy,
refer to NCI
CTCAE version
4.03 for defining
the CTC Grade 1)
No dose modification
For Grade 1: (including those with asymptomatic TSH elevation)
- Monitor subject with appropriate endocrine function tests
- If TSH < 0.5X LLN, or TSH >2X ULN or consistently out of range 
in 2 subsequent measurements, include FT4 at subsequent cycles as 
clinically indicated and consider endocrinology consult.
Grade 2
(depending on the
type of
endocrinopathy,
refer to NCI
CTCAE version
4.03 for defining
the CTC 
Grade/severity 2)
For Grade 2 endocrinopathy 
other than hypothyroidism, 
hold IP/study regimen dose 
until subject is clinically 
stable
• If toxicity worsens then 
treat as Grade 3 or Grade 4
• IP/study regimen can be 
resumed once event 
For Grade 2 (including those with symptomatic endocrinopathy):
- Isolated hypothyroidism may be treated with replacement therapy 
without treatment interruption and without corticosteroids
- Initiate hormone replacement as needed for management
- Evaluate endocrine function, and as clinically indicated, consider 
pituitary scan
- For subjects with abnormal endocrine work up, except for those 
with isolated hypothyroidism, consider short-term, corticosteroids 
(eg, 1-2 mg/kg/day methylprednisolone or IV equivalent) and prompt
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until subje
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52
(1


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
114
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
stabilizes and after 
completion of steroid taper
Subjects with 
endocrinopathies who may 
require prolonged or 
continued steroid 
replacement can be retreated 
with IP/study regimen on 
the following conditions: 
1) the event stabilizes and is
controlled,
2) the subject is clinically 
stable as per Investigator or 
treating physician’s clinical
judgement, and 
3) doses of prednisone are at
less than or equal to 
10mg/day or equivalent.
initiation of treatment with relevant hormone replacement (eg,
levothyroxine, hydrocortisone, or sex hormones). 
- Once improving, gradually taper steroids over ≥28 days and 
consider prophylactic antibiotics, antifungals and anti PCP treatment 
(please refer to current NCCN guidelines for treatment of cancer-
related infections
[Category 2B recommendation])2
- For subjects with normal endocrine work up (lab or MRI scans), 
repeat labs/MRI as clinically indicated.
Grade 3 or 4
(depending on the
type of
endocrinopathy,
refer to NCI
CTCAE version
4.03 for defining
the CTC Grade/
severity 3 or 4)
• For Grade 3 or 4 
endocrinopathy other than 
hypothyroidism, hold 
IP/study regimen dose until 
endocrinopathy symptom(s) 
are controlled
• IP/study regimen can be 
resumed once event 
stabilizes and after 
completion of steroid taper
For Grade 3 or 4:
- Consult endocrinologist
- Isolated hypothyroidism may be treated with replacement therapy 
without treatment interruption and without corticosteroids
- Promptly initiate empiric IV methylprednisolone 1 to 2 mg/kg/day 
or equivalent
- Administer hormone replacement therapy as necessary
- For adrenal crisis, severe dehydration, hypotension, or shock: 
immediately initiate intravenous corticosteroids with 
mineralocorticoid activity
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23
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
115
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
- Once improving, gradually taper immunosuppressive steroids over 
≥28 days and consider prophylactic antibiotics, antifungals and anti 
PCP treatment (please refer to current NCCN guidelines for treatment 
of cancer related infections [Category 2B recommendation])2
- Discuss with study physician
Immune mediated
neurotoxicity (to
include but not
limited to limbic
encephalitis.
autonomic
neuropathy,
excluding
myasthenia gravis
and Guillain-
Barre)
Grade of 
Neurotoxicity
Depending on the 
type of 
neurotoxicity refer 
to NCI CTCAE 
version 4.03 for 
defining the CTC 
grade/severity
General guidance
- Subjects should be evaluated to rule out any alternative etiology 
(eg, disease progression, infections, metabolic syndromes and 
medications, etc.)
- Monitor subject for general symptoms (headache, nausea, vertigo, 
behavior change, or weakness)
- Consider appropriate diagnostic testing (e.g. electromyogram and 
nerve conduction investigations)
- Symptomatic treatment with neurological consult as appropriate
Grade 1
No dose modifications
See “Any Grade” recommendations above.
Grade 2
• For acute motor 
neuropathies or
neurotoxicity, hold IP/study
regimen dose until 
resolution to ≤ Grade 1
• For sensory neuropathy/ 
neuropathic pain, consider 
holding IP/study regimen 
dose until resolution to ≤ 
Grade 1
- If toxicity worsens then 
treat as Grade 3 or Grade 4
• IP/study regimen can be 
resumed once event 
For Grade 2:
- Discuss with the study physician
- Obtain Neurology Consult
- Sensory neuropathy/ neuropathic pain may be managed by 
appropriate medications (e.g. gabapentin, duloxetine, etc.)
- Promptly start systemic steroids prednisone 1-2mg/kg/day PO or IV 
equivalent
- If no improvement within 3-5 days despite 1-2mg/kg/day
prednisone PO or IV equivalent consider additional workup and 
promptly treat with additional immunosuppressive therapy (e.g.
IVIG)
pri
prietet
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urrent NCCN
urrent NCC
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ician
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
116
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
improves to Grade ≤1 and 
after completion of steroid 
taper
Grade 3
• Hold IP/study regimen 
dose until resolution to ≤ 
Grade 1
• Permanently discontinue 
IP/study regimen if Grade 3 
irAE does not resolve to ≤ 
Grade 1 within 30 days.
For Grade 3 or 4:
- Discuss with study physician
- Obtain Neurology Consult
- Consider hospitalization
- Promptly initiate empiric IV methylprednisolone 1 to 2 mg/kg/day 
or equivalent
- If no improvement within 3-5 days despite IV corticosteroids, 
consider additional workup and promptly treat with additional 
immunosuppressants (e.g. IVIG)
- Once stable, gradually taper steroids over ≥28 days
Grade 4
Permanently discontinue 
IP/study regimen
Immune mediated
peripheral
neuromotor
syndromes, such
as Guillain-Barre
and myasthenia
gravis
General guidance
- The prompt diagnosis of immune-mediated peripheral neuromotor 
syndromes is important, since certain subjects may unpredictably 
experience acute decompensations which can result in substantial 
morbidity or in the worst case, death. Special care should be taken for 
certain sentinel symptoms which may predict a more severe outcome, 
such as prominent dysphagia, rapidly progressive weakness, and 
signs of respiratory insufficiency or autonomic instability
- Subjects should be evaluated to rule out any alternative etiology 
(e.g. disease progression, infections, metabolic syndromes and 
medications, etc.). It should be noted that the diagnosis of immune-
mediated peripheral neuromotor syndromes can be particularly 
challenging in subjects with underlying cancer, due to the multiple 
potential confounding effects of cancer (and its treatments) 
throughout the neuraxis. Given the importance of prompt and 
accurate diagnosis, it is essential to have a low threshold to obtain a 
neurological consult
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
117
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
- Neurophysiologic diagnostic testing (e.g. electromyogram and 
nerve conduction investigations, and “repetitive stimulation” if 
myasthenia is suspected) are routinely indicated upon suspicion of 
such conditions and may be best facilitated by means of a neurology 
consultation
Important to consider that the use of steroids as the primary treatment 
of Guillain-Barre is not typically considered effective. Subjects 
requiring treatment should be started with IVIG and followed by 
plasmapheresis if not responsive to IVIG
Grade 1
No dose modification
For Grade 1:
- Discuss with the study physician
- Care should be taken to monitor subjects for sentinel symptoms of a 
potential decompensation as described above
- Obtain a neurology consult unless the symptoms are very minor and 
stable
Grade 2
• Hold IP/study regimen 
dose until resolution to ≤ 
Grade 1
• Permanently discontinue 
IP/study regimen if it does 
not resolve to ≤ Grade 1 
within 30 days or if there 
are signs of respiratory 
insufficiency or autonomic 
instability
For Grade 2:
- Discuss with the study physician
- Care should be taken to monitor subjects for sentinel symptoms of a 
potential decompensation as described above
- Obtain a Neurology Consult
- Sensory neuropathy/ neuropathic pain may be managed by 
appropriate medications (eg, gabapentin, duloxetine, etc.)
MYASTHENIA GRAVIS
o Steroids may be successfully used to treat Myasthenia Gravis. 
Important to consider that steroid therapy (especially with high 
doses) may result in transient worsening of myasthenia and should 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
118
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
typically be administered in a monitored setting under supervision of 
a consulting neurologist.
o Subjects unable to tolerate steroids may be candidates for treatment 
with plasmapheresis or IVIG. Such decisions are best made in 
consultation with a neurologist, taking into account the unique needs 
of each subject.
o If Myasthenia Gravis-like neurotoxicity present, consider starting 
AChE inhibitor therapy in addition to steroids. Such therapy, if 
successful, can also serve to reinforce the diagnosis.
GUILLAIN-BARRE:
o Important to consider here that the use of steroids as the primary 
treatment of Guillain-Barre is not typically considered effective.
Subjects requiring treatment should be started with IVIG and 
followed by plasmapheresis if not responsive to IVIG.
Grade 3
• Hold IP/study regimen 
dose until resolution to ≤ 
Grade 1
• Permanently discontinue 
IP/study regimen if Grade 3 
irAE does not resolve to ≤ 
Grade 1 within 30 days or if 
there are signs of respiratory 
insufficiency or autonomic 
instability
For severe or life threatening (Grade 3 or 4) events:
- Discuss with study physician
- Recommend hospitalization
- Monitor symptoms and obtain neurological consult
MYASTHENIA GRAVIS
o Steroids may be successfully used to treat Myasthenia Gravis. It 
should typically be administered in a monitored setting under 
supervision of a consulting neurologist.
o Subjects unable to tolerate steroids may be candidates for treatment 
with plasmapheresis or IVIG.
Grade 4
Permanently discontinue 
IP/study regimen
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
119
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Grade of the 
Event (NCI 
CTCAE version 
4.03)
Dose Modifications
Toxicity Management
o If Myasthenia Gravis-like neurotoxicity present, consider starting 
AChE inhibitor therapy in addition to steroids. Such therapy, if 
successful, can also serve to reinforce the diagnosis.
GUILLAIN-BARRE:
◦Important to consider here that the use of steroids as the primary 
treatment of Guillain-Barre is not typically considered effective. 
Subjects requiring treatment should be started with IVIG and
followed by plasmapheresis if not responsive to IVIG
AChE = acetylcholine esterase; ADL = activities of daily living; AE = adverse event; ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = 
aspartate aminotransferase; BUN = blood urea nitrogen; CT = computed tomography; CTC = Common Terminology Criteria; FT4 = free thyroxine; GI = 
gastrointestinal; ILD = interstitial lung disease; irAE = immune-related adverse event; IV = intravenous; IVIG = intravenous immunoglobulin; LFT = liver 
function test; LLN = lower limit of normal; MRI = magnetic resonance imaging; NCCN = National Comprehensive Cancer Network; NCI CTCAE = National 
Cancer Institute Common Terminology Criteria for Adverse Events; PCP = pneumocystis pneumonia; PO = oral; TB = total bilirubin; TNF = tumor necrosis 
factor; TSH = thyroid-stimulating hormone; ULN = upper limit of normal.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
120
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Table C2:
Treatment Modification and Toxicity Management Guidelines for Infusion-related Adverse Events
Severity Grade of the 
Event (NCI CTCAE 
version 4.03)
Dose Modifications
Toxicity Management
Any grade
General guidance
- Management per institutional standard at the discretion of 
investigator
- Monitor subjects for signs and symptoms of infusion-related 
reactions (e.g. fever and/or shaking chills, flushing and/or itching, 
alterations in heart rate and blood pressure, dyspnea or chest 
discomfort, skin rashes etc.) and anaphylaxis (eg, generalized 
urticaria, angioedema, wheezing, hypotension, tachycardia, etc.)
Grade 1
The infusion rate of IP/study regimen may 
be decreased by 50% or temporarily 
interrupted until resolution of the event
For Grade 1 or Grade 2:
- Acetaminophen and/or antihistamines may be administered per 
institutional standard at the discretion of the investigator
- Consider premedication per institutional standard prior to 
subsequent doses
- Steroids should not be used for routine premedication of ≤Grade 2 
infusion reactions
Grade 2 
The infusion rate of IP/study regimen may 
be decreased 50% or temporarily interrupted 
until resolution of the event
Subsequent infusions may be given at 50% 
of the initial infusion rate
Grade 3 or 4
Permanently discontinue IP/study regimen
For Grade 3 or 4:
Manage severe infusion-related reactions per institutional standards
(e.g. IM epinephrine, followed by IV diphenhydramine and 
ranitidine, and IV glucocorticoid) 
IM = intramuscular; IV = intravenous.
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5


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
121
ABI-007-NSCL-006 Amendment 5.0 Final: 09 Dec 2016
Table C3:
Treatment Modification and Toxicity Management Guidelines for Non-immune-mediated Reactions
Severity Grade of the 
Event (NCI CTCAE 
version 4.03)
Dose Modifications
Toxicity Management
Any grade
Note: dose modifications are not required for adverse events not 
deemed to be related to study treatment (i.e. events due to 
underlying disease) or for laboratory abnormalities not deemed 
to be clinically significant.
Treat accordingly as per institutional standard
Grade 1
No dose adjustment 
Treat accordingly as per institutional standard
Grade 2 
Hold IP/study regimen until resolution to ≤ Grade 1 or baseline
Treat accordingly as per institutional standard
Grade 3
Hold IP/study regimen until resolution to ≤ Grade 1 or baseline
For AEs that downgrade to ≤ Grade 2 within 7 days or resolve to 
≤ Grade 1 or baseline within 14 days, resume IP/study regimen 
administration. Otherwise, discontinue IP/study regimen
Treat accordingly as per institutional standard
Grade 4
Discontinue IP/study regimen (Note for Grade 4 labs, decision to 
discontinue would be based on accompanying clinical 
signs/symptoms and as per Investigator’s clinical judgment and
in consultation with the sponsor)
Treat accordingly as per institutional standard
AE = adverse event; CTC = Common Terminology Criteria.
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EDMS Doc. Number: 
Celgene Signing Page
This is a representation of an electronic record that was signed electronically in Livelink.
This page is the manifestation of the electronic signature(s) used in compliance with
the organizations electronic signature policies and procedures.
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nab-Paclitaxel (Abraxane®))/CC-486
Statistical Analysis Plan. Protocol [ABI-007-NSCL-006]
Celgene Corporation
Confidential and Proprietary
1
STATISTICAL ANALYSIS PLAN
A PHASE 2, RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY TO ASSESS 
SAFETY AND EFFICACY OF NAB®-PACLITAXEL (ABI-007) WITH EPIGENETIC
MODIFYING THERAPY OF CC-486, AND NAB®-PACLITAXEL MONOTHERAPY AS 
SECOND-LINE TREATMENT IN SUBJECTS WITH ADVANCED NONSQUAMOUS NON-
SMALL CELL LUNG CANCER (NSCLC): ABOUND.2L
STUDY DRUG:
nab-PACLITAXEL  (ABRAXANE®), CC-486
PROTOCOL NUMBER:
ABI-007-NSCL-006
DATE FINAL:
25Aug2016
Prepared by:
On behalf of 
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
CONFIDENTIAL
The information contained in this document is regarded as confidential 
and, except to the extent necessary to obtain informed consent, may not be 
disclosed to another party unless such disclosure is required by law or 
regulations.  Persons to whom the information is disclosed must be 
informed that the information is confidential and may not be further 
disclosed by them.
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35
(/
(/


nab-Paclitaxel (Abraxane®))/CC-486
Statistical Analysis Plan. Protocol [ABI-007-NSCL-006]
Celgene Corporation
Confidential and Proprietary
2
TABLE OF CONTENTS
SIGNATURE PAGE...................................................................................................................6
1.
LIST OF ABBREVIATIONS...................................................................................8
2.
INTRODUCTION..................................................................................................10
3.
STUDY OBJECTIVES...........................................................................................11
3.1.
Primary Objective...................................................................................................11
3.2.
Secondary Objectives .............................................................................................11
3.3.
Exploratory Objectives ...........................................................................................11
4.
INVESTIGATIONAL PLAN .................................................................................12
4.1.
Overall Study Design and Plan ...............................................................................12
4.2.
Study Endpoints .....................................................................................................13
4.2.1.
Primary Efficacy Endpoint......................................................................................13
4.2.2.
Secondary Efficacy Endpoints ................................................................................13
4.2.3.
Safety Endpoints.....................................................................................................13
4.2.4.
Exploratory Endpoints............................................................................................14
4.3.
Stratification, Randomization, and Blinding............................................................14
4.4.
Sample Size Determination.....................................................................................14
5.
GENERAL STATISTICAL CONSIDERATIONS .................................................16
5.1.
Reporting Conventions ...........................................................................................16
5.2.
Analysis Populations ..............................................................................................16
5.2.1.
Intent-to-treat Population........................................................................................16
5.2.2.
Per-protocol (PP) Population ..................................................................................17
5.2.3.
Treated Population..................................................................................................17
6.
SUBJECT DISPOSITION......................................................................................18
7.
PROTOCOL DEVIATIONS/VIOLATIONS ..........................................................20
8.
DEMOGRAPHICS AND BASELINE CHARACTERISTICS................................21
8.1.
Demographics.........................................................................................................21
8.2.
Baseline Characteristics..........................................................................................21
8.3.
Medical History and Cancer Diagnosis ...................................................................21
8.3.1.
Medical History......................................................................................................21
8.3.2.
Lung Cancer History...............................................................................................22
8.4.
Prior Therapy..........................................................................................................22
&(/*(1(35235,(7$5<,1)250$7,21
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11
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11
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............11
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3 1


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8.4.1.
Prior Systemic Anti-Cancer Therapy.......................................................................22
8.4.2.
Prior Radiation Therapy..........................................................................................22
8.4.3.
Prior Non-small Cell Lung Cancer Surgeries ..........................................................23
8.5.
Prior and Concomitant Medications........................................................................23
8.5.1.
Prior Medications ...................................................................................................23
8.5.2.
Concomitant Medications .......................................................................................23
8.5.3.
Concomitant Radiation Therapy and Surgeries/Procedures .....................................23
9.
STUDY TREATMENTS AND EXTENT OF EXPOSURE....................................24
9.1.
Treatment and Cycle Start and End Dates ...............................................................24
9.2.
Dosing Period for Each Study Drug........................................................................24
9.3.
Treatment Duration.................................................................................................26
9.4.
Cumulative Dose ....................................................................................................26
9.5.
Dose Intensity.........................................................................................................27
9.6.
Percentage of Protocol Dose ...................................................................................27
9.7.
Exposure, Dose Reduction/Delay, and Doses not Administered..............................27
10.
EFFICACY ANALYSIS ........................................................................................29
10.1.
Multiplicity.............................................................................................................29
10.2.
Analysis of Primary Efficacy Endpoint...................................................................29
10.3.
Analyses of Secondary Efficacy Endpoints.............................................................32
10.3.1.
Disease Control Rate ..............................................................................................32
10.3.2.
Overall Survival .....................................................................................................32
10.3.3.
Tumor Response and Overall Response Rate ..........................................................33
10.3.4.
Time to Response (TTR) ........................................................................................33
10.3.5.
Duration of Response .............................................................................................33
10.4.
Subgroup Analyses.................................................................................................34
10.5.
Analyses of Exploratory Endpoints.........................................................................34
10.5.1.
Healthcare Resource Utilization..............................................................................34
11.
SAFETY ANALYSIS ............................................................................................35
11.1.
Adverse Events.......................................................................................................35
11.3.
Peripheral Neuropathy............................................................................................38
11.4.
Clinical Laboratory Evaluations..............................................................................39
11.4.1.
Hematology............................................................................................................39
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11.4.2.
Clinical Chemistry..................................................................................................39
12.
QUALITY OF LIFE ANALYSIS...........................................................................40
12.1.
LCSS......................................................................................................................40
12.2.
EQ-5D-5L ..............................................................................................................41
12.3.
EORTC QLQ C30 ..................................................................................................42
13.
FOLLOW UP TREATMENTS...............................................................................43
14.
INTERIM ANALYSIS...........................................................................................44
14.1.
General Information................................................................................................44
14.2.
Statistical Approaches for Control of Alpha............................................................44
15.
CHANGES TO THE STATISTICAL ANALYSES SECTION OF THE 
PROTOCOL...........................................................................................................45
16.
REFERENCES.......................................................................................................46
17.
APPENDICES........................................................................................................47
17.1.
Study schematic......................................................................................................47
17.2.
Handling of Dates...................................................................................................47
17.2.1.
Calculation Using Dates .........................................................................................48
17.3.
Date Imputation Guideline......................................................................................49
17.3.1.
Impute Missing Dates for Adverse Events/ Prior or Concomitant 
Medications............................................................................................................49
17.3.2.
Adverse Events.......................................................................................................50
17.3.3.
Prior/Concomitant Medications/Procedures ............................................................50
17.3.4.
Medical History......................................................................................................50
17.4.
Tumor Response Windows .....................................................................................51
17.6.
MedDRA Versions and Dates.................................................................................52
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LIST OF TABLES
Table 1: Abbreviations and Specialist Terms …….……………………………………...……..8
Table 2: PFS – Two-Sided 95% CIs of Hypothetical Observed HRs………………………...15
Table 3: Derivation of Dosing Period End Date for Each study Drug ………………………..26
Table 4: Censoring Rules for PFS ……………………………..………………………………30
Table 5: Relative Day Ranges for CT Scans……………………………..…………………….52
Table 7: MedDRA Versions and Dates ……………………………………………………......53
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nab-Paclitaxel (Abraxane®))/CC-486
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1.
LIST OF ABBREVIATIONS
Table 1:
Abbreviations and Specialist Terms
ADT
Analysis date
AE
Adverse event
ALT
Alanine aminotransferase (SGPT)
ANC
Absolute neutrophil count
ANCOVA
Analysis of covariance
AST
Aspartate aminotransferase (SGOT)
ATC
Anatomical Therapeutic Chemical
BMI
Body mass index
CI
Confidence interval
CMH
Cochran-Mantel-Haenszel
CR
Complete response
CRF
Case Report Form
CT
Computerized tomography
CTCAE
Common Terminology Criteria for Adverse Events
DCR
Disease control rate
DMC
Data Monitoring Committee
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic case report form
EORTC
European Organisation for Research and Treatment of Cancer
EQ-5D-5L
EuroQol 5-dimensional quality of life instrument
HR
Hazard ratio
IP
Investigational product
IRT
Interactive Response Technology
ITT
Intent-to-treat
IV
Intravenous
riteria for A
riteria for A
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ITT
TT


nab-Paclitaxel (Abraxane®))/CC-486
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LCSS
Lung cancer symptom scale
MedDRA
Medical dictionary for regulatory activities
NCI
National Cancer Institute
NSCLC
Non-small-cell lung cancer
ORR
Overall response rate
OS
Overall survival
PD
Progressive disease
PFS
Progression-free survival
PR
Partial response
PP
Per-Protocol
PT
Preferred term
QoL
Quality of Life
RECIST
Response evaluation criteria in solid tumors
SAE
Serious adverse event
SAP
Statistical analysis plan
SD
Stable disease
SE
Standard error 
SOC
System organ class
STDEV
Standard deviation
SGOT
Serum glutamic oxaloacetic transaminase (AST)
SGPT
Serum glutamic pyruvic transaminase (ALT)
TEAE
Treatment emergent adverse event
TEAEoSI
TEAEs of special interest
UE
Un-evaluable
US
United States
VAS
Visual analog scale
WBC
White blood cell
WHO 
World Health Organization 
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2.
INTRODUCTION
This statistical analysis plan (SAP) describes the analyses and data presentations for Celgene’s 
protocol ABI-007-NSCL-006 “A PHASE 2, RANDOMIZED, OPEN-LABEL, MULTICENTER 
STUDY TO ASSESS SAFETY AND EFFICACY OF NAB®-PACLITAXEL (ABI-007) WITH 
EPIGENETIC MODIFYING THERAPY OF CC-486, AND NAB®-PACLITAXEL
MONOTHERAPY AS SECOND-LINE TREATMENT IN SUBJECTS WITH ADVANCED
NONSQUAMOUS NON-SMALL CELL LUNG CANCER (NSCLC): ABOUND.2L” which 
was amended on 18 JULY 2014.
These analyses include all the dry runs described in the Scope of Work, the non-binding interim 
analysis described in the protocol, and the final analysis for the clinical study report. Throughout 
this SAP, the monotherapy arm will be referred to as the nab-paclitaxel arm, while the 
combination treatment arm will be referred to as the nab-paclitaxel with CC-486 treatment arm. 
The purpose of the SAP is to ensure the credibility of the study findings by pre-specifying the 
statistical approaches to the analysis of study data prior to database lock and any data analysis for 
the interim analysis. This SAP is developed after the finalization of the protocol and will be 
finalized and signed prior to the clinical database lock for the interim analysis. All statistical 
analyses detailed in this SAP will be conducted using SAS® Version 9.2 or higher. The clinical 
cutoff date will be determined based on the occurrence of approximately 60 progression-free 
survival (PFS) events for the non-binding interim analysis (for futility, analyzing PFS) and 
approximately 120 PFS events for the final analysis. All subjects who discontinue from treatment 
will continue to be followed for overall survival (OS) up to 12 months after the last subject is 
randomized or 120 PFS events have been observed, whichever comes later.
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3.
STUDY OBJECTIVES
3.1.
Primary Objective
The primary objective of the study is:
!
To assess the efficacy of nab-paclitaxel administered intravenously (IV) on Days 8 
and 15 with CC-486 once daily (QD) on Days 1 to 14 every 21 days, and nab-
paclitaxel administered IV on Days 1 and 8 every 21 days as second-line treatment
for advanced nonsquamous NSCLC, and the relative efficacy of these two treatment 
regimens.
3.2.
Secondary Objectives
The secondary objective of the study is:
!
To evaluate the safety and tolerability of nab-paclitaxel administered IV on Days 8 
and 15 with CC-486 once daily (QD) on Days 1 to 14 every 21 days, and nab-
paclitaxel administered IV on Days 1 and 8 every 21 days as second-line treatment
for advanced nonsquamous NSCLC.
3.3.
Exploratory Objectives
The exploratory objectives of the study are:
!
To assess healthcare resource utilization for the two treatment arms.
!
To assess the quality of life (QoL) for the two treatment arms.
!
To determine baseline tumor characteristics which predict response to nab-paclitaxel
as a single agent and in combination with epigenetic modifying therapy of CC-486. 
!
To evaluate genomic correlates of response to nab-paclitaxel as a single agent and in 
combination with epigenetic modifying therapy of CC-486.
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4.
INVESTIGATIONAL PLAN
4.1.
Overall Study Design and Plan
This is a Phase 2, randomized, open-label, multicenter study to assess efficacy and safety of nab-
paclitaxel in combination with epigenetic modifying therapy of CC-486, and nab-paclitaxel
monotherapy as second-line treatment in subjects with advanced nonsquamous NSCLC who 
have received one platinum-containing chemotherapy regimen. 
Approximately 160 subjects with advanced nonsquamous NSCLC will be randomized 1:1 into 
one of the two treatment arms: nab-paclitaxel/CC-486 combination therapy or nab-paclitaxel
monotherapy prior to receiving first dose of investigational product (IP). Randomization will be 
centralized and stratified by Eastern Cooperative Oncology Group (ECOG) performance status 
(0 versus 1), gender (males versus females), and current smoker (yes versus no). 
The study will consist of up to a 28-day Screening Period, a Treatment Period and a Follow-up 
Period. The Treatment Period begins with the first dose of IP (CC-486 for the nab-paclitaxel
with CC-486 arm or nab-paclitaxel for the nab-paclitaxel arm). Subjects will receive one of the 
following treatments based on the randomization assignment:
!
nab-paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days  1 to 14 of each 21-day treatment cycle, or  
!
nab-paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle
No additional anticancer agents are allowed during study treatment. All supportive care is 
permitted as per the investigator’s discretion and should be administered according to local 
institutional practice. Subjects will continue treatment until disease progression, development of 
an unacceptable toxicity, death, lost to follow-up, withdrawal of consent, or termination of the 
study by the sponsor. Tumor evaluations will be assessed by the investigative sites and response 
will be determined according to Response Evaluation Criteria in Solid Tumors (RECIST) 
guidelines, Version 1.1. All subjects who discontinue from treatment for any reason other than 
withdrawal of consent, lost to follow-up, death, or termination of the study by the sponsor will 
enter the Follow-up Period. It will consist of a visit 28 days after treatment discontinuation. 
Thereafter, subjects will be followed for survival by phone call contact approximately every 90 
days (+/- 14 days) for 12 months after the last subject is randomized or 120 PFS events have 
been observed, whichever comes later. During the study, subjects will have computed 
tomography (CT) scans every 42 days (-3/+7 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death, or termination of the study by the sponsor. Those 
subjects entering the Follow-up Period without documented progression will continue to have 
CT scans in accordance with local standard of care (or approximately every 90 days)  until 
documented progression of disease, withdrawal of consent, lost to follow-up, death, or 
termination of the study by the sponsor. All post-treatment anticancer therapies will be recorded 
during the Follow-up Period. The study schematic is presented in Section 17.1 .
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4.2.
Study Endpoints
4.2.1.
Primary Efficacy Endpoint
The primary endpoint is PFS in months, which is defined as the time from the date of 
randomization to the date of disease progression or death (from any cause) on or prior to the data 
cutoff date for analyses, whichever occurs first, based on the investigator’s assessment of the 
data from CT scans using RECIST 1.1 guidelines. 
4.2.2.
Secondary Efficacy Endpoints
Secondary efficacy endpoints specified in the protocol include the following:
!
Disease control rate (DCR)
Disease control rate is defined as the percent of subjects who have a radiologic 
complete response, partial response, or stable disease according to RECIST 1.1 
guidelines, as determined by the investigator.
!
Overall survival (OS) 
Overall survival is defined as the time between randomization and death. All deaths, 
regardless of the cause of death, will be included. 
!
Overall response rate (ORR) 
Overall response rate is defined as the percent of subjects who have a radiologic 
complete or partial response according to RECIST 1.1 guidelines determined by the 
investigator.  
Other secondary efficacy endpoints:
!
Time to Response (TTR)
Time to response is defined as the time from the date of randomization to the first 
occurrence of response (complete response or partial response).
!
Duration of Response (DOR) 
For subjects who have a complete response (CR) or partial response (PR), duration of 
response is defined as the time interval from the first occurrence of CR or PR 
according to RECIST 1.1 criteria to the first documented progressive disease date.
4.2.3.
Safety Endpoints
!
The type, frequency, and severity of adverse events (AEs) and serious adverse events 
(SAEs) graded using National Cancer Institute (NCI) Common Terminology Criteria 
for Adverse Events (CTCAE, Version 4.0)
!
Discontinuation rate
!
The median dose intensity 
!
The incidences of dose reductions
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Celgene Corporation
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4.2.4.
Exploratory Endpoints
!
Healthcare resource utilization during the study using a questionnaire.
!
Changes in the Lung Cancer Symptom Scale (LCSS), European Organisation for 
Research and Treatment of Cancer (EORTC) QLQ C30, and EuroQoL 5D-5L (EQ-
5D-5L).
The following exploratory endpoints will be described in a separate SAP:
!
The correlation between pretreatment tumor characteristics and response to the study 
treatment determined using next-generation sequencing methods, 
immunohistochemistry, or other analysis methods.
4.3.
Stratification, Randomization, and Blinding
Once the subject has met all eligibility criteria during the Screening Period, they will be 
randomized to one of two treatment arms to enter the Treatment Period. Randomization will be 
centralized using an Interactive Response Technology (IRT) system and stratified by Eastern 
Cooperative Oncology Group (ECOG) performance status (0 versus 1), gender (males versus 
females), and current smoker (yes versus no). Approximately 160 subjects will be randomized to 
one of two treatment arms in a 1:1 ratio. A permuted-block randomization method will be 
employed. The Treatment Period which is open label, begins with the first dose of IP (CC-486 
for the nab-paclitaxel with CC-486 arm or nab-paclitaxel for the nab-paclitaxel arm). Subjects 
will receive one of the following treatments based on the randomization assignment:
!
nab-paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment cycle, or  
!
nab-paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment cycle
The study is open label due to the differences in scheduling the treatments.
4.4.
Sample Size Determination
Assuming the median times of PFS are 4.17 and 2.5 months, respectively, for the nab-paclitaxel
with CC-486 arm and the nab-paclitaxel monotherapy arm, and an approximate 24 months 
accrual period for a total of 160 subjects, it is estimated that a total of 120 PFS events will have 
been observed approximately 2 months after the last subject is randomized, assuming an 
exponential distribution for PFS. With 120 PFS events, this study has an 80% power (1-sided, 
Type-1 error of 2.5%) to detect a hazard ratio (HR) of 0.60 for PFS improvement with the nab-
paclitaxel with CC-486 arm over the nab-paclitaxel monotherapy arm. 
One nonbinding interim analysis for PFS with an early stopping rule for futility will be 
conducted when approximately 60 events are observed. The nab-paclitaxel with CC-486 arm of
the study may be stopped early for futility if the observed HR is > 1.10 given an approximate 60 
PFS events have occurred at the time of the interim analysis. A HR> 1.10 when half of the target 
events of 120 have occurred signals a low probability for observing a meaningful difference in 
favor of the nab-paclitaxel with CC-486 therapy should the study continue to the end. With the 
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assumptions stated above, it will take approximately 16 months from the first subject randomized 
to observe approximately 60 PFS events for the interim analysis.
If futility is declared, enrollment in the monotherapy nab-paclitaxel arm will continue up to a 
total of 80 subjects.
Table 2 below summarizes the precision that can be achieved given different scenarios of 
hypothetical observed hazard ratios between the two treatment arms for PFS events, assuming a 
total of 120 events are observed. 
Table 2:
Progression-Free Survival – Two-Sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms
Hypothetical Number of Events 
Observed
Hypothetical Observed Hazard 
Ratio of PFS Events
95% Confidence Interval of 
Hazard Ratioa
120
0.60
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0.65
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,1


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5.
GENERAL STATISTICAL CONSIDERATIONS
5.1.
Reporting Conventions
The following reporting conventions apply generally to tables, listings, and figures:
!
Data from all study centers will be pooled for analysis.
!
All stratified efficacy analyses will use the stratification factors for randomizations, 
including ECOG performance status (0 versus 1), gender (males versus females), and 
current smoker (yes versus no).
!
Confidence intervals (CIs) will be presented as 2-sided 95% CIs unless specified 
differently for a given analysis.
!
Summary statistics will consist of the number and percentage of subjects (or cycles, if 
appropriate) in each category for discrete variables, and the sample size, mean, 
standard deviation (SD), median, first and third quartile (Q1, Q3), minimum, and 
maximum for continuous variables.
!
All mean, median, and percentile/quartiles values will be formatted to one more 
decimal place than the measured value. Standard deviation values will be formatted to 
two more decimal places than the measured value. Minimum and maximum will be 
formatted to the same decimal place as the measured value.
!
All percentages will be rounded to one decimal place. The number and percentage of 
responses will be presented in the form XX (XX.X), where the percentage is in the 
parentheses.
!
All listings will be sorted for presentation in order of treatment arm, study site, 
subject, and date of procedure or event. Data for all subjects will be included in 
subject data listings, according to the analysis population specified.
!
All analysis and summary tables will have the analysis population sample size (i.e., 
number of subjects).
!
Baseline value will be defined as the last non-missing value obtained before or on the 
day the first dose of study drug is administered. For subjects who were not treated, 
the baseline will be the last non-missing value obtained on or prior to the 
randomization date.
!
All laboratory data will be reported using international system of units (SI).
5.2.
Analysis Populations
5.2.1.
Intent-to-treat Population
The primary efficacy analysis will be performed on the intent-to-treat (ITT) population, which 
includes all randomized subjects regardless of whether the subject receives any IP or has any 
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2.1.
2 1


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efficacy assessments performed. Efficacy analyses will be based on this population and 
randomized treatment groups.
5.2.2.
Per-protocol (PP) Population
The PP population is defined as all eligible subjects randomized who receive at least one dose of 
the IP and have been treated on the arm they were assigned to, and meet the major 
inclusion/exclusion criteria of the protocol.
The PP population will be used for the analyses of the primary efficacy endpoint PFS and key 
secondary efficacy endpoint DCR, as part of sensitivity/robustness analysis of efficacy findings.
5.2.3.
Treated Population
The treated population will consist of all randomized subjects who receive at least one dose of 
IP. The safety analyses will be based on this population and the treatment as received if different 
from the assigned treatment by randomization.
&(/*(1(35235,(7$5<,1)250$7,21
dings.
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one dose 
ceived if d
ceived if 


nab-Paclitaxel (Abraxane®))/CC-486
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6.
SUBJECT DISPOSITION
The total number of subjects screened will be presented. The subjects with screen failure and 
reasons for screen failure will be summarized by frequency and percentage of total number of 
subjects screened. A summary of analysis populations will also be presented.
The number and percentage of subjects who are randomized and treated, discontinued treatment, 
and discontinued the study will be presented for the ITT population by treatment arm and for all 
subjects combined. Reasons for treatment discontinuation will be summarized for all subjects 
who discontinue study treatment with the following categories:
!
Death
!
Adverse event
!
Pregnancy
!
Progressive disease
!
Symptomatic deterioration
!
Withdrawal by subject
!
Lost to follow-up
!
Study terminated by sponsor
!
Protocol violation
!
Other
Reasons for study discontinuation will be summarized for all subjects who discontinue study 
with the following categories:
!
Screen failure
!
Death
!
Adverse event
!
Pregnancy
!
Withdrawal by subject
!
Lost to follow up
!
Protocol violation
!
Study terminated by Sponsor
!
Other
Finally, the number and percentage of subjects who enter into the follow up period of the study 
will be presented. The above disposition tables, along with all subjects enrolled and subjects 
randomized will also be presented for each site.
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ll
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summarize
summariz
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drawal by s
drawal by s
ost to follo
ost to follo
Protoco
Protoco
!
Stu
Stu
!
nally
nally


nab-Paclitaxel (Abraxane®))/CC-486
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Celgene Corporation
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19
Listings will be provided for analysis population, for subjects randomized but not treated, for 
discontinued subjects with reasons for study or treatment discontinuation, and for screen failure 
subjects who did not meet eligibility criteria.
&(/*(1(35235,(7$5<,1)250$7,21


nab-Paclitaxel (Abraxane®))/CC-486
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7.
PROTOCOL DEVIATIONS/VIOLATIONS
The protocol deviations/violations were identified and assessed by clinical research physician or 
designee following company standard operational procedure. Protocol deviations and violations 
will be reviewed before database lock to determine the per protocol population. 
It should be noted that not all deviations or violations will constitute the exclusion of subject 
from the per-protocol population. Events that could trigger exclusion from the per protocol 
population include but are not limited to non-adherence to inclusion/exclusion criteria, failure to 
take study drug as assigned, randomization errors, prohibited concomitant medications and 
procedures.
The protocol deviations/violations will be summarized separately by treatment arm for the ITT 
population. A by-subject listing of subjects with protocol violations in the ITT population will be 
provided.
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col
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f
th
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popul
populatatioi n


nab-Paclitaxel (Abraxane®))/CC-486
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8.
DEMOGRAPHICS AND BASELINE CHARACTERISTICS
The demographics and baseline characteristics will be summarized for the ITT population. 
Individual subject listings will be provided to support the summary tables.
8.1.
Demographics
Age (years), height (cm), weight (kg), body mass index (BMI), body surface area (BSA) at 
baseline will be summarized descriptively. Age category (<65 versus ≥65 years, <70 versus ≥70 
years, and < 75 versus ≥ 75 years), sex, race, and ethnicity will be summarized by frequency 
counts.
Age will be calculated as follows: age = Integer ∀[(Date of informed consent – Date of Birth + 
1) / 365.25]. 
BMI will be calculated as follows: BMI = weight in kg / (height in m)2.
BSA will be calculated as follows: BSA m2 = 0.007184 × (weight in kg)0.425 × (height in cm)0.725
(Du Bois, 1917).
Provided the numbers of subjects are sufficient, demographics will also be summarized within 
the following subgroups:
1. Age (< 65 years and ≥ 65 years, < 70 years and ≥ 70 years, < 75 years and ≥ 75 years); 
2. ECOG status (0 vs. 1) at baseline;
3. Sex (male and female); 
4. Current smoker (yes vs. no).
8.2.
Baseline Characteristics
The following baseline characteristics will be presented descriptively:
!
ECOG performance status at baseline (0 or 1);
!
Smoking history (current vs. past vs. never);
8.3.
Medical History and Cancer Diagnosis
8.3.1.
Medical History
A summary of medical and surgical history will be presented by system organ class (SOC) and 
preferred term (PT), coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA) Version 17.0 or above. A similar summary will be generated for the currently active 
abnormalities only, by SOC and PT.
8.3.1.1.
Smoking/Tobacco Exposure History 
A detailed summary of smoking and other tobacco exposure will be reported as follows:
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s ≥70
≥70
ency 
ency 
Date of Bir
Date of Bir
kg)
kg)0.425
0.425 × (h
× (h
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will als
≥ 7
≥ 70 years
years
tics
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rist
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will
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status at 
y (current v
(current 
y
ical Histo
ical Histo
Medical H
Medical H
mmary
mmary of
of m
f
ferred 
erred term
term
(MedDRA)
MedDRA)
abnorm
bnorm


nab-Paclitaxel (Abraxane®))/CC-486
Statistical Analysis Plan. Protocol [ABI-007-NSCL-006]
Celgene Corporation
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22
!
Smoking status (current vs. past vs. never);
!
For past and current smokers: duration, and number of packs/pipes/cigars. For current 
smokers, the date of informed consent will be used for duration. Frequency of use
will also be summarized;
!
Exposure to second hand smoke;
!
Frequency of tobacco chewing;
!
Frequency of tobacco sniffing.
8.3.2.
Lung Cancer History
The following items will be summarized for cancer diagnosis:
!
Disease stage at enrollment;
!
The time from specimen collection date to randomization date in months, defined as 
(randomization date – specimen collection date + 1)/ 30.4375;
!
Method of specimen collection (biopsy, surgical specimen, fine needle cytology 
(FNC), other);
!
Confirmation of nonsquamous cell histology (Adenocarcinoma, Large cell carcinoma, 
Adenosquamous carcinoma, Carcinoid tumor, other);
!
Mutational gene status (KRAS, EGFR, ALK, other or unknown).
!
Time from latest systemic anti-cancer therapy to the randomization date in months
!
Time from latest radiation therapy to the randomization date in months
!
Time from latest prior cancer surgery to the randomization date in months
!
Time from latest cancer therapy (last to occur of systemic anti-cancer therapy, 
radiation, or cancer surgery) to the randomization date in months
Subject listings will be provided for all of the above, as well as date of specimen collection.
8.4.
Prior Therapy
8.4.1.
Prior Systemic Anti-Cancer Therapy
Prior systemic therapies (e.g. chemotherapy) will be coded to therapeutic drug classes and 
generic drug names using the Anatomical Therapeutic Chemical (ATC) drug classification by the 
World Health Organization (WHO) Drug Dictionary Enhanced version WHO-DDE Q3 2014 or 
later. Prior systemic anti-cancer therapy will be summarized by treatment group and ATC levels. 
The start/end date and/or the duration, the number of cycles (if known), intent, and the best 
response will all be presented in a listing.
8.4.2.
Prior Radiation Therapy
The number and percentage of subjects who had any prior radiation therapy will be presented. 
For subjects with prior radiation therapy, the number and percentage of subjects with each site of 
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tart/e
response
espons


nab-Paclitaxel (Abraxane®))/CC-486
Statistical Analysis Plan. Protocol [ABI-007-NSCL-006]
Celgene Corporation
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23
radiation therapy will be presented. Dose and fraction (where known) will be summarized. Intent 
(adjuvant, curative, palliative, unknown) and setting (stand-alone, concurrent with other anti-
cancer therapy, sequential to other anti-cancer therapy) will also be summarized.
8.4.3.
Prior Non-small Cell Lung Cancer Surgeries
Prior non-small cell lung cancer surgeries will be coded by MedDRA system organ class and 
preferred term. A summary showing the number and percentage of subjects who had prior non-
small cell lung cancer surgery will be presented by system organ class and preferred term. 
Prior surgeries will be listed.
8.5.
Prior and Concomitant Medications
Medications reported on the Prior and Concomitant medications case report form (CRF) pages 
will be coded to therapeutic drug classes and generic drug names using the WHO drug dictionary 
version WHO-DDE Q3 2014 or later. Medications initiated prior to randomization and continued 
afterwards will be counted as both prior and concomitant medications.
Prior and concomitant medications will be listed.
8.5.1.
Prior Medications
Prior medications are defined as medications that were started before randomization. A summary 
showing the number and percentage of subjects who took prior medications will be presented by 
WHO therapeutic drug class and generic drug name for the ITT population.
8.5.2.
Concomitant Medications
Concomitant medications are defined as medications that were either initiated before 
randomization and continued afterwards, or initiated on/after the date of randomization and 
within 28 days after the last dose date.
A summary showing the number and percentage of subjects who took concomitant medications 
will be presented by WHO therapeutic drug class and generic drug name for the ITT population. 
The summary of concomitant immunostimulants (growth factors) initiation by cycle may also be 
presented.
8.5.3.
Concomitant Radiation Therapy and Surgeries/Procedures
The number of subjects having concomitant radiation, surgeries, or procedures performed will be 
summarized.
Concomitant radiation, surgeries, and procedures will be listed.
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mitant radia


nab-Paclitaxel (Abraxane®))/CC-486
Statistical Analysis Plan. Protocol [ABI-007-NSCL-006]
Celgene Corporation
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24
9.
STUDY TREATMENTS AND EXTENT OF EXPOSURE
Study treatment and extent of exposure summaries will be provided based on the treated 
population. Descriptive statistics will be provided for treatment duration, number of cycles, 
cumulative dose, dose intensity, and percentage of protocol dose by treatment arm. The summary 
of full doses, dose level by week and number of doses by cycle will also be presented.
9.1.
Treatment and Cycle Start and End Dates
Treatment will commence on Day 1, and planned cycle lengths are 21 days. Day 1 of Treatment 
is defined as the first day of any study drug.
Start date of a cycle is defined as the Day 1 of study drug for that cycle as recorded on the eCRF. 
The end date of a cycle is defined as the day before Day 1 of the following cycle. Cycle end date 
of the last cycle is the treatment end date.
9.2.
Dosing Period for Each Study Drug
Dosing period for each study drug will be defined and used as the denominator for the 
calculation of dose intensity for each drug. Dosing period will also be used in the definition of 
treatment duration for subjects who are still on treatment at the time of study closure or clinical 
cutoff.
For each study drug, dosing period = dosing period end date – Day 1 of Treatment +1, where 
Day 1 of treatment is defined as the first day of any study drug.
For this study, the dosing period for a study drug is the time period starting at the first dose of the 
any study drug and ending a protocol- and subject-specific number of days after the last dose, 
depending on the subject dosing schedule for the study drug. Ending the dosing period on the 
date of last dose would lead to an overestimation of the dose intensity. To avoid such 
overestimation, additional days of dosing period beyond the date of the last dose allow for the 
calculated dose intensity to reflect the degree to which the subject’s dosing schedule aligned with 
the protocol-specified dose intensity. A subject’s dosing period never extends beyond the date of
death, but it can extend beyond the treatment discontinuation date in some circumstances.
For nab-paclitaxel, since the two protocol-specified doses are administered at uneven intervals, 
the end date of the dosing period depends on whether the last dose administered day is a Day 1 
or a Day 8 dose for monotherapy, or Day 8 or Day 15 for combination therapy. If the subject is 
administered only one dose during the last cycle, then the subject will be given half of the 
protocol-specified nab-paclitaxel doses for the last cycle, he/she will be allotted half of the 
cycle’s length (the closest integer 11 days is given) in their nab-paclitaxel dosing period for the 
last cycle. If the subject is given both of the 2 protocol-specified doses for the last cycle, then the 
end date of the dosing period will be the last planned day of the cycle.
For CC-486, since the protocol-specified 14 doses are credited over 21 days of cycle length, 
proportionally, 1.5 days ( i.e., 21 days divided by 14 doses) of dosing period will be credited for 
each dose. Hence, the dosing period end date will depend on the number of doses of CC-486 
recorded on eCRF during the last cycle. That is, the dosing period for the last cycle will be 
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date of 
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For CC
CC
po


nab-Paclitaxel (Abraxane®))/CC-486
Statistical Analysis Plan. Protocol [ABI-007-NSCL-006]
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derived as the number of dose recorded for the last cycle multiply by 1.5 days and rounded to
integer.
More specifically, dosing period end date will be derived as follows:
1. If the subject is still on treatment at the time of study closure or clinical cutoff, the following 
rules will be used to derive the dosing period end date for each drug:
For nab-paclitaxel monotherapy treatment arm:
!
If the last dose given for the last cycle is Day 1, the dosing period end date for nab-
paclitaxel will be derived as Day 1 date of the last cycle + 10 days (i.e., rounded integer 
of protocol specified cycle length/number of doses planned for each cycle); 
!
If the last dose given for the last cycle is Day 8, the dosing period end date for nab-
paclitaxel will be derived as min [(Day 8 date + 13), Day 21 date].
For nab-paclitaxel with CC-486 combination therapy arm: 
!
Dosing period end date for CC-486 will be derived as the date of last cycle Day of {the 
number of doses recorded in the last cycle ×1.5 days and rounded to integer}. The 
number of doses recorded in the last cycle will be calculated as the end date of the last 
dosing record - the start date of the first dosing record in the last cycle + 1, no matter 
whether the actual dose is taken or not.
!
Dosing period end date for nab-paclitaxel will be derived as follows:
o
If the last dose given for the last cycle is Day 8, then the dosing period end date 
for nab-paclitaxel will be derived as max[(Day 1 date +10), Day 8 date];
o
If the last dose given for the last cycle is Day 15, then the dosing period end date 
for nab-paclitaxel will be derived as min[(Day 15 date + 6), Day 21 date].
2. If the subject discontinued the treatment, the dosing period end date for each study drug will 
be derived as min{death date, max[treatment discontinuation date, dosing period end date for 
that specific drug as derived above]}.
The above derivation rules of dosing period end date can be illustrated in the following Table 3.
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nteger 
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a
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es of dosin
dos
f


nab-Paclitaxel (Abraxane®))/CC-486
Statistical Analysis Plan. Protocol [ABI-007-NSCL-006]
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26
Table 3  Derivation of Dosing Period End Date for Each study Drug
For Subjects Who Are Still on Treatment at the Time of Study Closure or Clinical Cutoff
Treatment 
Arm
Study 
Drug
Last Dose Date          
is Day 1
Last Dose Date is 
Day 8
Last Dose Date    
is Day 15
nab-paclitaxel
Monotherapy
nab-
paclitaxel
Day 1 date + 10 days 
min [(Day 8 date + 
13), Day 21 date]
-
nab-paclitaxel  
+  CC-486 
Combination 
Therapy
CC-486
Date of last cycle Day of {the number of 
doses recorded in the last cycle ×1.5 days and 
rounded to integer}.
   -
nab-
paclitaxel
-
max [(Day 1 date 
+10), Day 8 date]
min [(Day 15 date 
+ 6),   Day 21
date]
For Subjects Who Discontinued Treatment
For each drug: min{death date, max[treatment discontinuation date, dosing period end date for 
that specific drug as derived above]}
9.3.
Treatment Duration
For a given study drug, treatment duration (in weeks) is defined as: 
Treatment Duration = [(Treatment end date) – (Day 1 of Treatment) + 1]/7. 
For subjects who discontinued treatment, the treatment end date will be derived as the 
discontinuation date from treatment disposition form on eCRF. For the subjects who are still on 
treatment at the time of study closure or clinical cutoff, the treatment end date will be derived as 
the maximum of the dosing period end date for CC-486 and the dosing period end date for nab-
paclitaxel.
Cycle duration is defined as the time period from Day 1 of each cycle to one day prior to Day 1 
of subsequent cycle; for the last treatment cycle, the end date is the treatment end date as defined 
above.
Descriptive statistics will be provided for treatment duration and total number of cycles for both 
the nab-paclitaxel with CC-486 and the nab-paclitaxel arms. Descriptive statistics will also be 
provided for number of doses received for both nab-paclitaxel (the nab-paclitaxel with CC-486 
and the nab-paclitaxel arms) and CC-486 separately.
9.4.
Cumulative Dose
Cumulative dose will be computed separately for nab-paclitaxel and CC-486. Cumulative dose 
for nab-paclitaxel is defined as the sum of the values entered on the dose assigned field on the 
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minin [(Da
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25
1)
atment
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(inin weeks)
weeks)
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treatm
reat ent
en
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dispo
dy
dy clcl
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osure o
osure
ing 
in period 
perio
defined as t
defined as 
cy
cycle; for th
cle; for
ive statisti
ive statist
ab
ab-paclitax
paclita
ovi
ovided 
ded 
&
fofor
and the
nd the na
na


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Statistical Analysis Plan. Protocol [ABI-007-NSCL-006]
Celgene Corporation
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27
exposure eCRF, taken across the treatment period in mg/m2. Only the assigned doses when the 
doses were actually administered (i.e., when the actual doses administered not equal to 0) will be 
included in the calculation of the cumulative dose. 
Cumulative dose for CC-486 is defined as the sum of all actual doses, defined as the values 
entered on the actual dose administered field on the dosing eCRF, taken across the treatment 
period in mg. Descriptive statistics will be presented for cumulative dose for the subjects treated.
9.5.
Dose Intensity
Dose intensity during the treatment is defined as the cumulative dose divided by the dosing 
period in weeks. Dose intensity will be calculated separately for nab-paclitaxel and CC-486.  
Dose intensities will be calculated as follows:
!
Dose intensity for nab-paclitaxel (mg/m2/wk) = [cumulative dose for nab-paclitaxel in 
mg/m2]/[dosing period for nab-paclitaxel in weeks].
!
Dose intensity for CC-486 (mg/ wk) = [cumulative dose for CC-486 in mg]/[ dosing 
period for CC-486 in weeks].
Dose intensity for the treatment period will be presented for each study drug by treatment arm
for the treated population.
9.6.
Percentage of Protocol Dose
Percentage of protocol dose (also called relative dose intensity) is the dose intensity divided by 
the protocol weekly dose, expressed as a percentage.
!
Percentage of protocol dose = (dose intensity / protocol weekly dose) * 100%
The protocol weekly doses for the nab-paclitaxel with CC-486 arm are as follows:
!
nab-paclitaxel: 200/3 mg/m2/wk (100 mg/m2 each for days 8 and 15 for each 21 day 
cycle)
!
CC-486: 2800/3 mg /wk (200 mg each day on days 1 to 14 of each 21 day cycle)
The protocol weekly doses for the nab-paclitaxel arm are as follows:
!
nab-paclitaxel: 200/3 mg/m2/wk (100 mg/m2 each for days 1 and 8, for each 21 day 
cycle)
Percentage of protocol dose nab-paclitaxel and CC-486 will be categorized into <70%, ≥70% to 
< 80%, and ≥80 to <90% and ≥90%, and frequency counts will be provided for the treated 
population.
9.7.
Exposure, Dose Reduction/Delay, and Doses not Administered
Dose reduction is defined as when the dose assigned after Cycle 1 Day 1 is at a lower dose level 
than the assigned dose at the previous dosing visit.
Dose delay is defined as when the scheduled dose is administered greater than or equal to 3 days 
after the scheduled dosing date. Dose delay is only defined for the doses that were administered. 
If a dose is not administered, dose delay will not be defined for that particular dosing record. 
&(/*(1(35235,(7$5<,1)250$7,21
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Celgene Corporation
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To determine whether the current administered dose is a dose delay or not, if the previous dose is 
not administered (skipped dose) with missing dose date but non-missing visit date, the non-
missing visit date will be used as the reference date to determine if the current dose is delayed. If, 
however, there is no visit date either for the skipped dose, then the previous last dose record that 
had at least either a visit date or dose date will be searched and its dose date (or visit date if dose 
date is missing) will be used as the start reference date to calculate the missing dose date and 
thereafter to determine if a dose is delayed. Since the protocol allows a ±2-day window for each 
dosing schedule, we will add in 2 extra days when we calculate the missing dosing date for the 
skipped dose visit when define dose delay. For example, if a dose is not administered and with 
both visit date and dose date missing, we will assume the scheduled date for this skipped dose as 
the previous dose date (or visit date if the dose date is missing) + 9 days. Same logic will be used
for each skipped dose visit when multiple doses were not administered consecutively and with 
both dose date and visit date missing. That is, 9-day interval between dosing visits were assumed 
and used to calculate the missing dose date for each skipped dose visit when we define dose 
delays. Dose not administered (missed dose) is defined as a case when the dose for a visit is 
recorded on eCRF as not administered.
Treatment exposure and dose reductions and delays will be summarized as follows (separately 
for each IP):
!
Number of cycles and doses administered;
!
Number and percentage of subjects with at least 1 dose reduction, number of dose 
reductions, and reasons (adverse event, or other) for reduction, by cycle and overall;
!
Number and percentage of subjects with at least one dose delay, number of dose 
delays, by cycle and overall.
!
Number and percentage of subjects with at least one dose not administered, number 
of dose not administered, and reasons (adverse events or other) for dose not 
administered, by cycle and overall. If the reason for dose not administered is not 
given, it will be categorized as “Data Not Available” in summary tables.
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th
dose as
dose as
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d overall I
orized as “D
rized as “


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10.
EFFICACY ANALYSIS
All efficacy evaluations will be conducted using the ITT population and subjects will be 
analyzed according to the treatment arm to which they were randomized. Supportive analysis of 
the primary and key secondary efficacy endpoints using the PP population will be conducted for 
the final analysis.
The percent change from nadir in sum of lengths of longest diameters of target lesions is required 
to assess target lesions for tumor progression. This is calculated as follows:
Percent change from nadir at a given visit= (total length – nadir in total length) / (nadir in total 
length) x 100%, where nadir is calculated using all measurements prior to the visit in question, 
including baseline.
Data review of tumor response (CR, PR, SD, and PD) will be performed based on programmed 
data listings according to the RECIST 1.1 criteria:
!
Per subject visit:
o
Date of assessment
o
Total length of target lesions
o
Percent change from nadir of sum of longest diameters of target lesions (derived 
as above to review assessment of progressive disease)
o
Percent change from baseline of sum of longest diameters of target lesions to 
review assessment of response
o
Assessment of target lesions
o
Assessment of non-target lesions
o
Appearance of new lesions
o
Presence of symptomatic deterioration
o
Overall tumor response 
!
Per lesion at each subject visit:
o
Location
o
Method of assessment
o
Tumor length (target lesions only)
!
Overall per subject
o
The best overall response 
10.1.
Multiplicity
Not applicable for this study, as no formal statistical inferential testing will be conducted.
10.2.
Analysis of Primary Efficacy Endpoint
The primary efficacy endpoint is PFS, which is defined as the time in months from the date of 
randomization to the date of disease progression according to RECIST 1.1 criteria (documented 
by CT-scan result, not including symptomatic deterioration) or death (any cause) on or prior to 
the clinical cutoff date, whichever occurs earlier. 
Subjects who do not have disease progression and have not died, regardless of whether they were 
discontinued from treatment or not, will be censored at the date of last tumor assessment, on or 
&(/*(1(35235,(7$5<,1)250$7,21
ed 
ed 
n total
total
quest
questioion,n,
d on progra
on progr
ameters of 
ameters 
e disease)
disease)
ongest diam
ngest di
deterioration
deterioratio
sit:t:
ssment
ssment
th (target l
h (target l
ect
ect
est overall 
st overal
ltiplicity
ltiplicity
able for th
ble for thisis
An
Ana
he
he primary
primar
rando
an
miz
miz
CT
CT


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prior to the clinical cutoff date that the subject was progression-free. If a subject begins a 
subsequent anti-cancer chemotherapy prior to documented disease progression (or death), the 
subject will be censored at the date of last assessment when the subject was documented as 
progression-free prior to the intervention. In the event that curative radiotherapy or surgery at 
lesion sites occurs, the subject will be censored at the date of last assessment when the subject 
was documented as progression-free prior to the intervention. Subjects with a single missing 
radiologic assessment immediately prior to a visit with documented disease progression (or 
death) will be analyzed as a PFS event at the time of the radiologic assessment that shows 
progression or death (whichever is earlier). Subjects with two or more consecutive missing 
radiologic assessments immediately prior to an assessment with documented progression (or 
death) will be censored at the date of last assessment when the subject was documented as 
progression-free prior to the first of the two or more missing assessments. Subjects who are 
discontinued due to symptomatic deterioration without documented progression will be censored 
at the last assessment where the subject was documented as progression-free before treatment 
discontinuation. This is further illustrated in Table 4.
Table 4:
Censoring Rules for PFS
Situation On or Before Clinical 
Cutoff Date 
Analysis Date 
Censored or 
Event
Disease progression, and time interval 
between progression date and 
previous tumor assessment date with 
progression-free response is less than 
or equal to 91 days
Date of disease progression 
recorded at the first tumor 
assessment with overall response 
of PD
Event
Disease progression, and time interval 
between the progression date and the 
previous tumor assessment date with 
progression-free response is greater 
than 91 days.
Latest of:
!
the last 
progression-free 
assessment date
!
randomization 
date
Censored
Death without any post-baseline 
radiological assessment, and time 
interval between death date and 
randomization date is less than or 
equal to 91 days
Death date
Event
Death before documented progression, 
and time interval between death date 
and previous tumor assessment date 
with progression-free response is less 
than or equal to 91 days
Death date
Event
efore docum
ore docum
me interva
me interva
d d previ
previous 
ous 
wi
with
th
i
progr
progr
h
*(1(3523
235,(7$5<,1)250$7,21
s s 
sing
ng
ion
on (or 
(or 
mented
nted as 
a
ects
ects who 
who a
will
ill be
be cens
cen
bef
before
ore
f
tr
1
ogressi
ogres on
first tum
st tumor
o
with overall
with overal
<
est of:
est of:
!
th
th
(
23
baseline
baseline
ent, and tim
nt, and tim
eath date a
th date a
date
date is 
is less 
less
days
ys
35
th
than or 
an or 
*(
&


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Death without any post-baseline 
radiological assessment, and time 
interval between death date and 
randomization date is greater than 91
days
Randomization date
Censored
Death before documented progression, 
and time interval between death date 
and previous tumor assessment date 
with progression-free response is 
greater than 91 days
The last progression-free 
assessment date
Censored
No death or disease progression, and 
no subsequent anti-cancer therapy 
(i.e., systemic anti-cancer therapy, 
anti-cancer surgery, curative 
radiotherapy).
Latest of 
!
the last progression-free 
assessment date
!
randomization date
Censored
Subsequent anti-cancer treatment (i.e., 
systemic anti-cancer therapy, anti-
cancer surgery, curative radiotherapy) 
started prior to progression
Latest of 
!
the last progression-free 
assessment date prior to 
start of anti-cancer 
treatment
!
randomization date
Censored
Treatment discontinuation due to 
symptomatic deterioration prior to 
disease progression or death
Latest of 
!
the last progression-free 
assessment date before 
treatment discontinuation
!
randomization date
Censored
Note: Progression-free response refers to a response that was neither progressive disease 
(PD) nor un-evaluable (UE). 
The survival distribution of PFS will be estimated using the Kaplan-Meier method, the median 
PFS including two-sided 95% CI for each treatment arm will be provided. Stratification factors 
include ECOG performance status (0 versus 1), gender (males versus females), and current 
smoker (yes versus no). The associated HR and two-sided 95% CI will be estimated by using 
stratified Cox proportional hazard model. Kaplan-Meier curves will be provided by treatment 
arm. 
The number and percent of subjects surviving without progression will be provided for every 2 
months relative to randomization. The denominator for percentages at each time point will be the 
number of subjects at risk at each time point.
The following analyses will be conducted as supporting or sensitivity analyses using the same 
methods (i.e. HR and two-sided 95% CI from the Cox model with stratification factors):
!
PFS where subsequent anti-cancer therapy is considered an event.
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$7
ensored
nsored
0$
1)
$
ssion
ssion-free
date prior t
date prior
nti-i-cancer 
cancer
entnt
ndo
domizat
mizatio
1)
1)
1)
1)
of 
of 
!
th
the la
e la
as
as
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23
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se refers t
E). 
). 
52
3
n of 
n of PFS
PFS
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ded 95% 
erformance
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rsus no) T
ox proport
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number an
number an
mo
montnths
hs relat
rela
number o
number o
e f


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!
An additional analysis of PFS will be performed using the European Medicines 
Agency methodology for analysis of a PFS endpoint. Similar to the approach 
described above, PFS will be defined as the time from the randomization date to the 
start of disease progression or subject death (any cause) on or prior to the clinical 
cutoff date, whichever occurs first. Subjects who do not have disease progression or 
have not died will be censored at the last known time that the subject is progression 
free (i.e. the last tumor assessment). However, occasional missing observations or 
initiation of subsequent anticancer therapy will not result in censoring for this 
analysis.
!
In addition, to assess the effect of unscheduled radiologic assessments, the frequency 
and percentage of unscheduled or off-schedule radiologic assessments will be 
presented by treatment group. Sensitivity analyses may be performed where subjects 
with events and censorings that occur at a time other than the regularly scheduled 
visit assessment, will have PFS time based on the date of the next regularly scheduled 
assessment rather than the actual off-schedule date.
!
Sensitivity analyses to address the impact of measurability of endpoints and 
adherence to protocol will be done by performing the PFS analyses mentioned above 
on the per protocol population.
10.3.
Analyses of Secondary Efficacy Endpoints
All secondary efficacy endpoints will be analyzed using the ITT population. For the tumor
response evaluations, the lesion data and response assessments that occur on or after the date of a 
subsequent anti-cancer therapy, subsequent curative-intent radiation therapy, or subsequent 
curative-intent surgery will be excluded.
10.3.1.
Disease Control Rate
Disease Control rate is defined as the percent of subjects who have stable disease (SD) or 
complete response (CR) or partial response (PR) according to RECIST 1.1 guidelines, as 
evaluated by the Investigator. Disease control rate along with associated Clopper-Pearson 95%
CI will be presented. The relative treatment effect will be summarized by the ratio of the disease 
control rate and the associated two-sided 95% CI.
10.3.2.
Overall Survival
Overall survival (OS) is defined as the time (in months) between randomization and death and 
will be calculated as follows:
OS = (Date of Death – Date of Randomization + 1) / 30.4375
Subjects who die before or on the date of data cut-off will be considered to have had an OS 
event. All deaths, regardless of the cause of death, will be included. All subjects who do not have 
a death record prior to or on the cutoff date will be censored at the ‘last date known alive’.
Last date known alive is defined as the last valid date of subject assessment prior to or on the 
data cutoff date in the clinical database. For subjects who have withdrawn consent during the 
study, the last date known alive will be the date of consent withdrawal from the study. For all 
other subjects, the last date known alive will be derived by searching through all valid 
equency
uency
be
be
here
here subjec
subjec
rlyly schedule
schedule
y
regularly s
regularly s
of f endpo
endpoinin
FS analyse
FS analys
oints
oints
ng the ITT 
ng the ITT 
assessment
assessmen
tive-
ve-int
in ent 
ent 
percent of
percent
response (
response (
Disease con
isease con
atative treatm
ive tre
ated two
ed tw -
Survival
urvival
(OS)
(OS) is de
is de
ated as fo
ated as fol
ate of Deat
of Dea
ects
ects who 
who d
vent. All de
vent. All de
a death re
death re
st d


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assessment dates in all study datasets to identify the last valid subject assessment date available 
for each subject. If the last valid subject assessment date available is on or prior to the data cutoff 
date, it is used as the last date known alive. If the last valid subject assessment date available is 
after the data cutoff date, the data cut-off date is used as the last date known alive. 
Overall survival will be analyzed in a similar manner as that for PFS.
To assess the impact of starting subsequent anticancer therapy on subject survival, a sensitivity 
analysis will be conducted. Subjects who start a subsequent anti-cancer therapy or surgery will 
be censored at the initiation date of the subsequent anti-cancer therapy or surgery; a method 
similar to the primary analysis will be applied to estimate the medians of OS and compare the 
survival distributions between two treatment arms. 
10.3.3.
Tumor Response and Overall Response Rate
The number and percentage of those with a best overall tumor response of SD, PR, or CR will be 
presented, as well as the number and percentage with each of progressive disease (PD), SD, PR, 
CR, and un-evaluable (UE). This analysis will be presented for each protocol-specified CT as 
defined in Section 17.4 . If there is more than one CT scan within a relative day range, the best 
response will be counted. 
Overall response rate (ORR) –a secondary efficacy endpoint- is the percentage of subjects who 
achieved best response of PR or CR compared with baseline among all tumor assessments, 
where baseline is the last CT scan obtained prior to or on Day 1 of Treatment. In this study, per 
RECIST1.1, since ORR is not a primary endpoint, confirmation of response is not required. The 
ORR along with 95% Clopper-Pearson CI will be presented. The relative treatment effect will be 
summarized by the ratio of the response rates and the associated two-sided 95% CI. 
10.3.4.
Time to Response (TTR)
Time to response is defined as the time from the date of randomization to the first occurrence of 
response (CR or PR). Only subjects with a CR or PR as a best overall response will be included 
in this analysis. TTR will be analyzed using descriptive statistics.
10.3.5.
Duration of Response 
For subjects who have a CR or PR, duration of response is defined as the time interval from the 
first occurrence of Complete or Partial Response (CR or PR) according to RECIST 1.1 criteria to 
the first documented progressive disease date.
Subjects who are non-responders (i.e., do not achieve at least a PR) will be excluded from this 
analysis. Subjects who do not have PD after the response will be censored on the date of last 
tumor assessment. If a subject died without PD, then the subject will be censored on the date of 
death.
Duration of response will be analyzed using the Kaplan-Meier method. The median time of 
response (including 2-sided 95% CI) will be summarized for each treatment arm; the associated 
hazard ratio with two-sided 95% confidence interval will be estimated using the Cox 
proportional hazard model (Cox, 1972).
&(/*(1(35235,(7$5<,1)250$7,21
the
, PR, or CR
PR, or C
disease (PD
disease (PD
protocol
rotoco -sp
rel
relatative
ive da
da
is th
the per
p
eline
eline am
a o
n n Day
Day 1
y
of
nfirmat
nfirmatioi n
presented.
presented.
d d the assoc
the ass
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from the 
wi
with
i
a CR
a CR
h
lyzed using
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sponse 
pons
a a CR 
CR or P
r P
om
omplete or
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m
nted progre
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are
are non
non-r
Subject
ubjects s w
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ent
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Durati
Duration 
on o
espons
espon
ar


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10.4.
Subgroup Analyses
Progression-free survival, OS, and DCR will all be analyzed within the following subgroups 
(with subgroup data based on the clinical database rather than IRT). Subgroup factors will not be 
used as regression adjustment covariates for relevant analyses, but otherwise these analyses will 
parallel the analyses for the endpoint performed on the whole population. The following 
subgroup factors will be used:
1. Age ( < 65 years and ≥ 65 years, < 70 years and ≥ 70 years, < 75 years and ≥ 75 years); 
2. ECOG status (0 vs. 1) at baseline;
3. Sex (male and female); 
4. Current smoker (yes vs. no).
For the time-to-event endpoints PFS and OS, forest plots will be provided displaying the HR and 
corresponding 95% CIs for each subgroup.
For DCR, forest plots will be provided displaying the rate ratios and corresponding 95% 
Clopper-Pearson CIs for each subgroup.
10.5.
Analyses of Exploratory Endpoints
10.5.1.
Healthcare Resource Utilization  
Summary statistics for number/location of care (number of office visits, hospital outpatient visits, 
hospital inpatient visits, emergency room visits, home healthcare visits, hospice, unknown, and 
other utilizations) and provider (general physician, specialist, nurse practitioner/physician 
assistant, paramedical care, unknown, and other) will be presented by treatment arm at each time 
point the utilization questionnaire is given (i.e. Day 1 of every cycle, End-of -Treatment Visit, 
and 28-day follow up visit).
aying
aying th
the H
responding
spond
er of office
er of offic
om
ome healt
health
ysici
ysician,
an
sp
her) will be
her) will be
n (i(i.e.
.e. Day
Day


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11.
SAFETY ANALYSIS
The purpose of this section is to describe the safety analyses for the study. All summaries of 
safety data will be conducted using the treated population.
11.1.
Adverse Events
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AE or SAE occurring or worsening on or after the day of the first dose of the IP 
through 28 days after the last dose of IP. In addition, any serious AE with an onset date more 
than 28 days after the last dose of IP that is assessed by the investigator as related to IP will be 
considered a TEAE. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA, Version 17.0 or above). The severity of AEs will be graded based on NCI CTCAE, 
Version 4.0.
The following rules will be implemented for cycle calculations for TEAEs:
!
TEAEs which occur on Day 1 Cycle 1 belong to Cycle 1.
!
After Cycle 1, TEAEs will be categorized by the “throw-back rule”, that is, AEs that 
occur on Day 1 of a cycle will be allocated to the previous cycle.
!
All TEAEs which occur after Day 1 of the last cycle will be included only in the last 
cycle.
Adverse events of special interest of the nab-paclitaxel with CC-486 and the nab-paclitaxel
regimens will be summarized by worst NCI CTCAE grade, AEs of special interest categories
and MedDRA preferred terms.
For the summary of treatment-related AEs, a treatment-related TEAE is defined as an adverse 
event which was considered to be related, reported as “suspected” in eCRF, to either drug. 
Additionally, for treatment-related AEs, reported as “suspected” in eCRF to each individual 
drug, nab-paclitaxel or CC-486 will be summarized for each study drug. If a subject experiences 
multiple occurrences of the same AE with different relationship to study medication categories, 
the subject will be counted once, as a relationship category of treatment-related. AE relationship 
to a study drug should always be collected on eCRF. In the rare cases relationships are missing, 
the relationships to a study drug will be taken as “related” in all relevant statistical analyses. 
The incidence of TEAEs/treatment related TEAEs will be summarized by MedDRA system 
organ class (SOC) and/or preferred term (PT). If a subject experiences multiple AEs under the 
same preferred term (system organ class), then the subject will be counted only once for that 
preferred term (system organ class).
The intensity of AEs will be graded 1 to 5 according to the National Cancer Institute Common 
Terminology Criteria for Adverse Events (CTCAE) Version 4.0. For all other AEs not described 
in the CTCAE criteria, the intensity will be assessed by the investigator as mild (grade 1), 
moderate (grade 2), severe (grade 3), life-threatening (grade 4) or death (grade 5). If a subject 
experiences the same AE more than once with different toxicity grade, then the event with the 
&(/*(1(35235,(7$5<,1)250$7,21
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will be
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y
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ed on 
o
NC
NC
EAEs
AEs:
e 1.1.
“th
throw
r
h
-ba
b
he previ
he previou
ou
e last 
la
cycl
cycle
b-paclitaxe
paclitaxe
CI 
CI CTCAE
CTCAE
ed 
ed AEs, 
AEs, a
be
be rel
re ated
ate
lated 
ated AEs,
AEs
486 will
486 will b
l
he
h same
am A
unted once
unted on
ulu d d always
alway
to a study
to a study
ce
ce of
of T
f
EA
EA
ss (SOC) 
(SOC)
preferred 
preferred t
ferred term
erred term
The
Th intnten
en
ermin
ermin


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highest grade will be tabulated in “by grade” tables. In addition, AEs with a missing intensity 
will be presented in the summary table as an intensity category of “Missing.”
Tables summarizing the number of subjects experiencing TEAEs and subject incidence for
TEAEs will be generated for each of the following:
!
Overall summary of TEAEs;
!
TEAEs presented by MedDRA system organ class and preferred term;
!
All TEAEs by worst CTCAE grade as well as grade category;
!
Treatment-related TEAEs;
!
Treatment-related TEAEs by grade category;
!
Serious TEAE;
!
Treatment-related serious TEAEs;
!
TEAEs with action as study drug withdrawn;
!
Treatment-related TEAEs with action as study drug withdrawn; 
!
TEAEs with action as study drug dose reduced or interrupted;
!
Treatment-related TEAEs with action as study drug dose reduced or interrupted;
!
TEAEs with fatal outcome ;
!
Treatment-related TEAEs with fatal outcome ;
!
All deaths within 28 days of last dose with cause of death and deaths during follow 
up period with cause of death (ITT population for both);
!
Most frequent TEAEs ( ≥ 5% in either treatment arm);
!
TEAEs for the following baseline subgroups (provided the number of subjects are 
sufficient):
o
Age (<65, 65 - ≤74 and ≥75 years); 
o
ECOG status (0 vs. 1) at baseline;
o
Sex (male and female); 
o
Current smoker (yes vs. no).
In addition TEAEs will be summarized by cycle. 
Listings for treatment-emergent and non-treatment-emergent AEs will be provided. 
 
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hdrawn;
rawn;
terrupted;
errup
drug dose re
ug dose 
utcome ;
utcome ;
ose with ca
ose with ca
TT populat
TT populat
% in eit
% in ei her 
he
ng baseline 
baseline 
5, 65 
, 65 - ≤74 
≤7
OG status (0
G status (
Sex (m
Sex (male a
ale a
o
Current
Curr
TEAEs wi
TEAEs wi
gs s fof r treatm
treatm
&(/
&


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&(/*(1(35235,(7$5<,1)250$7,21
52
352
( 3
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11.3.
Peripheral Neuropathy
Peripheral neuropathy events will be reported as AEs and will be included in analyses described 
in Section 11.1 . In addition, time from first dose to the first onset of peripheral neuropathy based 
on Standardized MedDRA Queries and time to improvement in peripheral neuropathy will be 
evaluated as follows:
&(/
1.3.
1.3.
P
Peri
Periphe
phe
i
S
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!
Time to first onset of grade 3 or higher peripheral neuropathy: The summary of time 
to first onset will be presented descriptively for those subjects who experienced 
peripheral neuropathy of grade 3 or higher. 
!
Time to improvement of grade 3 or higher peripheral neuropathy by at least 1 grade:
The summary of time to improvement will include only subjects who experienced 
peripheral neuropathy of grade 3 or higher. Subjects who do not experience 
improvement by at least 1 grade will be censored at the last time the subject is 
evaluated for adverse events. Kaplan Meier methods will be used to attain the median 
and 95% CI.
!
Time to improvement of grade 3 or higher peripheral neuropathy to grade 1 or better: 
The summary of time to improvement will include only subjects who experienced 
peripheral neuropathy of grade 3 or higher. Subjects who do not experience an 
improvement to grade 1 or better will be censored at the last time the subject is 
evaluated for adverse events. Kaplan Meier methods will be used to attain the median 
and 95% CI.
11.4.
Clinical Laboratory Evaluations
Clinical laboratory values from the central laboratory will be graded according to NCI CTCAE
version 4.0 for applicable tests. Normal ranges will be used to determine the categories of High, 
Low, and Normal for lab tests that have no severity grade, if available. 
Listings will be provided for the central laboratory data.
11.4.1.
Hematology
The worst NCI CTCAE grade for absolute neutrophil counts (ANC), white blood cell (WBC)
counts, platelet counts, and hemoglobin at each treatment cycle and overall will be cross-
tabulated with the grade at baseline (shift table).
A summary of hematology lab results and changes from baseline by visit and/or overall may be 
needed. Additionally, the nadir of each myelosuppression parameter may be needed for each 
treatment cycle and overall. Therefore, these variables will be derived in the analysis datasets.
11.4.2.
Clinical Chemistry
The worst NCI CTCAE grade for alkaline phosphatase, ALT (SGPT), AST (SGOT), total 
bilirubin, creatinine, creatinine clearance,  glucose, and fibrinogen at each treatment cycle and 
overall will be cross-tabulated with the grade at baseline (shift table).
A summary of chemistry lab results and changes from baseline by visit and/or overall may be 
needed. Additionally, the most severe value of each chemistry parameter may be needed for each 
treatment cycle and overall. Therefore, these variables will be derived in the analysis datasets.
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12.
QUALITY OF LIFE ANALYSIS
The Lung Cancer Symptom Scale (LCSS), EORTC QLQ C30 and EQ-5D-5L questionnaires will 
be used to measure quality of life (QoL) for subjects in the trial. The LCSS is a 9 question 
assessment the subject completes using a visual analogue scale (VAS) to denote intensity of a 
symptom. The EQ-5D-5L comprises 5 questions on mobility, self-care, usual activities, 
pain/discomfort, anxiety/depression and a VAS for overall QoL. In addition, there is an overall 
index score that is derived from the 5 questions. The EORTC QLQ-C30 includes five functional 
scales, three symptom scales, a global health status/QoL scale, and six single items. These 
questionnaires will be completed at Day 1 of every cycle, and at the End-of-Treatment Visit and 
at the 28-day Follow-up Visit and analyzed by treatment arm. Baseline scores are defined as 
scores captured on Day 1 (first dose date). In the case of multiple assessments on Day 1, the later 
assessment will be used. Missing baseline scores will not be imputed.
12.1.
LCSS
The LCSS is designed to measure quality of life specifically affected by lung cancer and its 
symptoms. It evaluates burden due to six major symptoms:
!
Appetite
!
Fatigue
!
Coughing
!
Shortness of breath
!
Blood in sputum
!
Pain
In addition, it measures how bad a subject’s symptoms are, how much it has affected normal 
activities, and quality of life.
The LCSS consists of two scales: one to be filled out by the subject and one by the health care 
provider. For this study, only the portion filled out by the subject will be used. The subject will 
respond to each of the 9 items using marks on a 100 mm visual analog scale (VAS). For analysis 
and presentation purposes, the scores will be presented such that 0 mm corresponds to the worst 
possible health state and 100 mm corresponds to the best possible health state.
The average of the VAS score of all 9 items as well as the change from baseline in this average 
will be calculated for each subject and will be referred to as the LCSS score. The symptom 
burden score is the average of the 6 major symptom scores. The average of the coughing, 
shortness of breath, and blood in sputum items will be referred to as the Respiratory Symptom 
Scale. The average of the appetite and fatigue items (the first 2 items) will be referred to as the 
overall constitutional score. The sum of the symptoms item (item 7), the normal activities item 
(item 8), and the global quality of life item (item 9) will be referred to as the 3-item scale. 
Summary statistics of the LCSS score and symptom burden score, and the change from baseline, 
will be summarized for the ITT population at every time point at which the instrument is given, 
and at End of Treatment. Descriptive statistics will be presented for each individual item at each 
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time point. In addition, the change from baseline to the best LCSS score during treatment will be 
presented. For each individual LCSS item, the best score on treatment is the highest score at
cycle 2 day 1 through the treatment discontinuation visit. For the summary scores, the best score 
on treatment is the highest value of the summary score at cycle 2 day 1 through the treatment 
discontinuation visit.  Finally, the change from baseline to the LCSS score during treatment, 
defined as the difference between the last reported LCSS score, either the end of treatment visit 
or the last reported LCSS score before clinical cutoff for subjects who have not had an end of 
treatment visit, will be presented.
12.2.
EQ-5D-5L
The EQ-5D-5L has been designed as an international, standardized, generic instrument for 
describing and valuing health-related quality of life. It contains only the domains common to 
generic health status measures, contains the minimum number of questions for each domain, was 
designed for ease of self-administration, and produces a single index for analysis. 
The EQ-5D-5L consists of EQ-5D-5L descriptive system and the EQ Visual Analogue scale (EQ 
VAS). The descriptive system comprises 5 dimensions:
!
Mobility
!
Self-care
!
Usual Activities
!
Pain/Discomfort
!
Anxiety/Depression
Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, 
and extreme problems. Responses from the 5 dimensions are coded so that a ‘1’ indicates no 
problem on that dimension, and ‘5’ indicates the most serious problem. The responses for the 
five dimensions can be combined in a five-digit number describing the respondent’s health state 
For instance, a state of 11111 indicates no problem with any of the 5 dimensions, but a state of 
55555 indicates the most difficulty on all 5. Missing and un-interpretable values (e.g. two 
responses are given for a single dimension) which are not recoverable through queries will be 
coded as ‘9’. 
The EQ VAS records the respondent’s self-rated health on a 20 cm vertical, visual analogue 
scale with endpoints labeled ‘the best health you can imagine’ and ‘the worst health you can 
imagine’. The EQ VAS scale is numbered from 0 to 100 with 0 corresponding to the worst 
imaginable health state and 100 corresponding to the best imaginable health state.  A utility score 
will be calculated using the US Crosswalk Index Value Set obtained from the EuroQol website. 
The range of possible values for the utility score based on the US Crosswalk Index Value Set is -
0.109 to 1.000.
The utility score and change from baseline in the utility score will be summarized for every time 
point at which the instrument is given for the ITT population. In addition, the change from 
baseline to the utility score during treatment, defined as the difference between the last reported 
utility score, either the end of treatment visit or the last reported overall score before clinical 
cutoff for subjects who have not had an end of treatment visit will be presented.
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Summary statistics of the EQ VAS (with the exception of the missing values) score, change from 
baseline, and percent change from baseline will also be presented for every time point at which 
the instrument is given. In addition, the change from baseline to the last reported overall score, 
end of treatment visit or the last reported overall score before clinical cutoff for subjects who 
have not had an end of treatment visit will be presented.
Shifts from baseline to each time point at which the instrument is given will be presented for 
each dimension for the ITT population. 
12.3.
EORTC QLQ C30
The EORTC QLQ-C30 (version 3.0) is composed of both multi-item scales and single-item
measures. These include five functional scales (physical, role, emotional, cognitive, social), three 
symptom scales (fatigue, nausea/vomiting, pain), a global health status / QoL scale, and six 
single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). Each 
of the multi-item scales includes a different set of items - no item occurs in more than one scale. 
All of the scales and single-item measures range in score from 0 to 100. A high scale score 
represents a higher response level. Thus a high score for a functional scale represents a high / 
healthy level of functioning, a high score for the global health status / QoL represents a high 
QoL, but a high score for a symptom scale / item represents a high level of symptomatology / 
problems. Scale scores are calculated by averaging items within scales and transforming average 
scores linearly. Scoring schemas for each scale are provided on the EORTC website. 
Summary statistics for the scale scores and the change from baseline will be presented for global 
health dimension and each functional and symptom scale or single item at each time point. In 
addition, the change from baseline to the scale score during treatment, defined as the difference 
between the last reported scale score, either the end of treatment visit or the last reported scale
score before clinical cutoff for subjects who have not had an end of treatment visit will be 
presented.
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13.
FOLLOW UP TREATMENTS
First subsequent systemic anti-cancer regimens will be summarized by treatment arm. 
To assess how quickly the third line therapy will be initiated for the subjects who discontinued 
the study treatment for reasons other than lost to follow-up or death and enter follow-up, time to 
third line therapy (systemic anti-cancer therapies during follow-up period), defined as the time 
interval from the last dose date of study drug to the start date of the first subsequent anti-cancer 
regimen. The start date of the first subsequent anti-cancer regimen is the earliest start date of any 
anti-cancer therapy taken in the follow-up/survival period. Subjects who don’t have a subsequent 
therapy and have not died as of the cutoff date for the statistical analysis will be censored at the 
last follow-up date. Subjects who die before initiating a subsequent therapy will be censored at 
the date of death.
Time to third line therapy will be analyzed using the Kaplan-Meier method. The median time 
(including 2-sided 95% CI) will be summarized for each treatment arm; the associated hazard 
ratio with two-sided 95% confidence interval will be estimated using the Cox proportional 
hazard model (Cox, 1972).
In addition, first subsequent anti-cancer treatment regimens will be summarized by the number 
and percentage of subjects receiving each regimen category and regimen; the number of cycles 
overall, and the number of cycles for each regimen category and regimen administered. The best 
response overall and for each regimen category and regimen administered will be summarized. 
Treatment duration, defined as (date of last dose of any treatment in a regimen -  date of first 
dose of any treatment in the same regimen) + 1 will be summarized as well. Additional 
subsequent anti-cancer treatment regimens will be listed
Anti-cancer surgeries during follow-up period will be summarized by treatment group and by 
system organ class and preferred term. Follow-up surgeries will be listed.
Radiation therapy during follow-up period will be summarized by treatment arm and by category 
(prior, concomitant, follow-up); type (External beam, radio-immuno therapy, brachytherapy, 
other); location (if external beam); dose; fraction; intent (adjuvant, curative, palliative, 
unknown); and setting (stand alone radiation therapy, concurrent with other anti-cancer therapy, 
sequential to other anti-cancer therapy). Follow-up radiation therapy will be listed.
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14.
INTERIM ANALYSIS
14.1.
General Information
An independent Data Monitoring Committee (DMC) will be convened with experts not 
otherwise involved in the study as investigators. During the course of the study, the DMC will 
review the progression-free survival efficacy data once and overall survival data separately in 
accordance with the guidelines for the pre-planned interim analysis. The committee will also 
review safety data periodically. Operational details for the DMC and the algorithm and its 
validation by an expert panel will be detailed in the DMC charter.
The DMC is advisory in nature, and the decision to implement DMC recommendations will be 
made by the sponsor. Specifically, the futility analysis for PFS is non-binding.
14.2.
Statistical Approaches for Control of Alpha
There will be one nonbinding interim analysis for PFS with an early stopping rule for futility that 
will be conducted when approximately 60 events are observed. The nab-paclitaxel with CC-486 
arm of the study may be stopped early for futility if the observed HR is > 1.10 given an 
approximate 60 PFS events have occurred at the time of the interim analysis (Hwang, 1990). A 
HR> 1.10 when half of the target events of 120 have occurred signals a low probability for 
observing a meaningful difference in favor of the nab-paclitaxel with CC-486 therapy should the 
study continue to the end. With the assumptions stated above, it will take approximately 16 
months from the first subject randomized to observe approximately 60 PFS events for the interim 
analysis.
If futility is declared, enrollment in the nab-paclitaxel monotherapy arm will continue up to a 
total of 80 subjects. 
This study is for estimation only, so no control of alpha is planned.
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15.
CHANGES TO THE STATISTICAL ANALYSES SECTION OF 
THE PROTOCOL
The PFS censoring rules given in protocol section 10.6.1 are elaborated with clarification of 
derivation rules in section 10.2 of this document.
The protocol states that PFS is the primary efficacy endpoint, DCR, OS, and ORR are the
secondary efficacy endpoints of the study. The following secondary efficacy endpoints will be 
added to the efficacy analysis section of the SAP: 
!
Time to response 
!
Duration of response
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16.
REFERENCES
Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European 
Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for 
use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365-376.
Cox, DR. Regression Models and Life-Tables. Journal of the Royal Statistical Society. Series B. 
1972; 34 (2): 187-220.
Du Bois, D, & Du Bois, E. A formula to estimate the approximate surface area if height and 
weight be known. Archives of Internal Medicine 1917, 17(6), 863-71.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, et al. New 
response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J 
Cancer 2009 Jan;45(2):228-47.
Hwang IK, Shih WJ and DeCani JS. Group sequential designs using a family of type I error 
probability spending functions. Statistics in Medicine 1990, 9, 1439-1445.
Fayers PM, Aaronson NK, Bjordal K, Groenvold M, Curran D, Bottomley A, on behalf of the 
EORTC Quality of Life Group. The EORTC QLQ-C30 Scoring Manual (3rd Edition). Published 
by: European Organisation for Research and Treatment of Cancer, Brussels 2001.
Mantel N. and Fleiss J.L., 1980. Minimum Expected Cell Size Requirements for the Mantel-
Haenszel One-Degree-of-Freedom Chi-Square Test and a Related Rapid Procedure. American 
Journal of Epidemiology, Volume 112, pp. 129-134.
Mantel N. and Haenszel W., 1959. Statistical aspects of the analysis of data from retrospective 
studies of disease. Journal of the National Cancer Institute Volume 22 (4), pp. 719–748.
&(/*(1(35235,(7$5<,1)250$7,21
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t and 
cey J, et al. 
ey J, et a
rsio
rsion 1.1). E
n 1.1)
g a fami
a family
439-1445.
-1445.
n D, Bottom
D, Bottom
Scoring Ma
coring M
nt of Cance
nt of Cance
cted Cell S
cted Cell S
e Test and 
e Test and 
. 129
129-134.
134.
atist
atisticicala asp
l
National Ca
National Ca


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17.
APPENDICES
17.1.
Study schematic
17.2.
Handling of Dates
Dates will be stored as numeric variables in the SAS analysis files and reported in 
DDMMMYYYY format (ie, the Date9. datetime format in SAS).  Dates in the clinical database 
are classified into the categories of procedure dates, log dates, milestone dates, outcome dates, 
and special dates.
!
Procedure Dates are the dates on which given protocol-specified procedure are 
performed.  They include the dates of laboratory testing, physical examinations,
tumor scans, etc.  They should be present whenever data for a protocol-specified 
procedure are present and should only be missing when a procedure are marked as 
NOT DONE in the database.  Procedure dates will not be imputed.
Screening for Eligibility  (up to 28 days)
(n=160)
Follow-up Period
28-day Follow-up visit (after last dose of IP)
Followed for OS by phone approximately every 90 days for up o 12 months after last subject is randomized or 120 PFS 
events have been observed, whichever is later
nab-paclitaxel 100 mg/m2  IV infusion over 30 minutes 
on Days 1 and 8 of each 21-day cycle until disease 
progression
(n = 80)
•nab-paclitaxel 100 mg/m2  IV infusion over 30 minutes on 
Days 8 and 15 of each 21-day cycle until disease progression
•CC-486 200 mg orally QD Days 1 to 14 of each 21-day cycle 
until disease progression
(n = 80)
1:1
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!
Log Dates are dates recorded in eCRF data logs.  Specifically, they are the start and 
end dates for adverse events and concomitant medications/procedures.  They should 
not be missing unless an event or medication is marked as ongoing in the database.  
Otherwise, incomplete log dates will be imputed according to the rules in Appendix 
17.3.1 (eg, for duration or cycle assignment, etc). However, in listings, log dates will 
be shown as recorded without imputation.
!
Milestone Dates are dates of protocol milestones such as randomization, study drug 
start date, study drug termination date, study closure date, etc.  They should not be 
missing if the milestone occurs for a subject.  They will not be imputed.
!
Outcome Dates are dates corresponding to study endpoints such as survival, 
progression, etc.  In most cases they are derived either from a milestone (eg, the 
survival date is derived from the death date), or a procedure date (eg, the progression 
date is derived from the date of the tumor scan that was used to determine 
progression).  They may be subject to endpoint-specific censoring rules if the 
outcome did not occur, but are not otherwise subject to imputation.
!
Special Dates cannot be classified in any of the above categories and they include the 
date of birth.  They may be subject to variable-specific censoring and imputation 
rules. 
!
Last Contact Dates for the survival analysis are the maximum date collected in the 
database, if the imputed date used for response date or AE date, the last contact dates 
should be the latest date of those imputed date and maximum date in the database.
Dates recorded in comment fields will not be imputed or reported in any specific format. 
17.2.1.
Calculation Using Dates
Calculations using dates (eg, subject’s age or relative day after the first dose of study drug) will 
adhere to the following conventions: 
!
Study days after the start day of study drug will be calculated as the difference 
between the date of interest and the first date of dosing of study drug plus 1 day. The 
generalized calculation algorithm for relative day is the following: 
#
If TARGET DATE >= DSTART then STUDY DAY = (TARGET DATE –
DSTART) + 1; 
#
Else use STUDY DAY = TARGET DATE – DSTART.
Note that Study Day 1 is the first day of treatment of study drug. Negative study days 
are reflective of observations obtained during the baseline/screening period.  Note: 
Partial dates for the first study drug are not imputed in general. All effort should be 
made to avoid incomplete study drug start dates. 
!
Partial birth date: impute missing day as 15th of the month; impute missing month as 
July; set missing age for missing year
!
Intervals that are presented in weeks will be transformed from days to weeks by using 
(without truncation) the following conversion formula:
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WEEKS = DAYS /7
!
Intervals that are presented in months will be transformed from days to months by 
using (without truncation) the following conversion formula:
MONTHS = DAYS /30.4375
17.3.
Date Imputation Guideline
17.3.1.
Impute Missing Dates for Adverse Events/ Prior or Concomitant Medications 
Incomplete Start Date
!
If the stop date is not missing, and the imputed start date is after the stop date, the 
start date will be imputed by the stop date. 
Missing day and month
!
If the year is the same as the year of the first dosing date, then the day and month of 
the first dosing date will be assigned to the missing fields.
!
If the year is prior to the year of first dosing date, then December 31 will be assigned 
to the missing fields.
!
If the year is after the year of first dosing, then January 1 will be assigned to the 
missing fields.
Missing day only 
!
If the month and year are the same as the year and month of first dosing date, then the 
first dosing date will be assigned to the missing day.
!
If either the year of the partial date is before the year of the first dosing date or the 
years of the partial date and the first dosing date are the same but the month of partial 
date is before the month of the first dosing date, then the last day of the month will be
assigned to the missing day.
!
If either the year of the partial date is after the year of the first dosing date or the 
years of the partial date and the first dose date are the same but the month of partial 
date is after the month of the first dosing date, then the first day of the month will be 
assigned to the missing day.
Missing day, month, and year
!
No imputation is needed, the corresponding AE will be included as TEAE if end date 
of AE is after the first dose date or the end date is also missing. 
Incomplete Stop Date
!
If the imputed stop date is before the start date, then the imputed stop date will be 
equal to the start date.
Missing day and month
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No imput
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plete St
m
!


nab-Paclitaxel (Abraxane®))/CC-486
Statistical Analysis Plan. Protocol [ABI-007-NSCL-006]
Celgene Corporation
Confidential and Proprietary
50
!
If the year of the incomplete stop date is the same as the year of the last dosing date, 
then the day and month of the last dosing date will be assigned to the missing fields. 
!
If the year of study drug start and stop are different, and the year of the incomplete 
stop date is the same as the year of the first dosing date, then December 31 will be 
assigned to the missing fields.
!
If the year of the incomplete stop date is prior to the year of the last dosing date but 
is the same as the year of the first dosing date, then the first dosing date will be 
assigned to the missing date. 
!
If the year of the incomplete stop date is after the year of the last dosing date, then 
January 1 will be assigned to the missing fields.
Missing day only 
!
If the month and year of the incomplete stop date are the same as the month and year 
of the last dosing date, then the day of the last dosing date will be assigned to the 
missing day. 
!
If either the year of the partial date is not equal to the year of the last dosing date or 
the years of the partial date and the last dosing date are the same but the month of 
partial date is not equal to the month of the last dosing date, then the last day of the 
month will be assigned to the missing day. 
17.3.2.
Adverse Events
Partially missing AE start dates will be imputed in the derived dataset for AEs, but partially 
missing AE end dates will not be imputed in the same dataset. If the AE end date is complete 
with no missing year, month, or day, and the partially missing start date imputed by the rules 
below is after the AE end date, then the start date will be imputed by the AE end date.
17.3.3.
Prior/Concomitant Medications/Procedures
Partially missing start/stop dates for prior/concomitant medications and partially missing start 
dates for prior/concomitant procedures will be imputed in the derived
dataset for 
prior/concomitant medications/procedures. For prior/concomitant medications, if the stop date is 
complete with no missing year, month, or day, and the partially missing start date imputed by the 
rule below is after the stop date, then the start date will be imputed by the stop date.
Partially missing prior/concomitant medication/procedure start dates will be imputed by the 
earliest possible date given the non-missing field(s) of the date.
Partially missing prior/concomitant medication stop dates will be imputed by the latest possible 
date given the non-missing field(s) of the date.
17.3.4.
Medical History
Partially missing medical history start dates will be imputed in the derived dataset for medical 
history. The 16th of the month will be used to impute a partially missing start date that has only 
the day missing, and July 1st will be used to impute a partially missing start date that has both the 
month and day missing.
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17.3.4.
7.3.4.
rti


nab-Paclitaxel (Abraxane®))/CC-486
Statistical Analysis Plan. Protocol [ABI-007-NSCL-006]
Celgene Corporation
Confidential and Proprietary
51
17.4.
Tumor Response Windows
Table 5.
Relative Day Ranges for CT-Scans
Study Week
Relative Days in 
Study
6
2 - 63
12
64 - 105
18
106 - 147
24
148 - 189
30
190 - 231
36
232 - 273
42
274 - 315
48
316 - 357
54
358 - 399
60
400 - 441
66
442 - 483
72
484 - 525
78
526 - 567
84
568 - 609
90
610 - 651
96
652 - 693
102
694 - 735
108
736 - 777
114
778 - 819
120
820 - 861
126
862 - 903
132
904 – 945
138
946 - 987
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nab-Paclitaxel (Abraxane®))/CC-486
Statistical Analysis Plan. Protocol [ABI-007-NSCL-006]
Celgene Corporation
Confidential and Proprietary
52
17.6.
MedDRA Versions and Dates
Table 7 gives the MedDRA versions used in this study and the dates of implementation
Table 7
MedDRA Versions and Dates
For reports dated:
MedDRA Version
May 2016 - present
19.0
May 2015 – May 2016
18.0
June 2014 – May 2015
17.0
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-006 Final: 29 May 2014
TITLE PAGE
A PHASE 2, RANDOMIZED, OPEN-LABEL, 
MULTICENTER STUDY TO ASSESS SAFETY AND 
EFFICACY OF NAB®-PACLITAXEL (ABI-007) WITH 
EPIGENETIC MODIFYING THERAPY OF
CC-486, AND NAB®-PACLITAXEL MONOTHERAPY AS 
SECOND-LINE TREATMENT IN SUBJECTS WITH 
ADVANCED NONSQUAMOUS NON-SMALL CELL 
LUNG CANCER (NSCLC): ABOUND.2L
INVESTIGATIONAL PRODUCTS:
nab-Paclitaxel (ABI-007)
CC-486 
PROTOCOL NUMBER:
ABI-007-NSCL-006
DATE FINAL:
29 May 2014
EudraCT NUMBER
2014-001105-41
IND NUMBER
114882
SPONSOR NAME / ADDRESS:
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
United States
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board. The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations.
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them.
protocol is pro
rotocol is pr
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-006 Final: 29 May 2014
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information:
Name:
Title:
Address: 
86 Morris Avenue
Summit, NJ 07901
United States
Phone:
E-mail:
Contact Information:
Name:
Title:
Address: 
86 Morris Avenue
Summit, NJ 07901
United States
Phone:
E-mail:
Note: The back-up 24 hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls.
Back-up 24 Hour Global Emergency Contact Call Center: 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-006 Final: 29 May 2014
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}.
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
 
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-006 Final: 29 May 2014
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-006 Final: 29 May 2014
COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:_______________________________________
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-006 Final: 29 May 2014
PROTOCOL SUMMARY
Study Title
A Phase 2, randomized, open-label, multicenter study to assess safety and efficacy of nab-
paclitaxel (ABI-007) with epigenetic modifying therapy of CC-486, and nab-paclitaxel 
monotherapy as second-line treatment in subjects with advanced nonsquamous non-small cell
lung cancer (NSCLC): ABOUND.2L
Indication
Second-line treatment of advanced nonsquamous NSCLC.
Objectives
Primary
!
To assess the efficacy of nab-paclitaxel1 administered intravenously (IV) on Days 8 
and 15 with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 
14 every 21 days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 
every 21 days as second-line treatment for advanced nonsquamous NSCLC, and the 
relative efficacy of these two treatment regimens.
Secondary 
!
To evaluate the safety and tolerability of nab-paclitaxel administered IV on Days 8 
and 15 in combination with epigenetic modifying therapy of CC-486 once daily (QD) 
on Days 1 to 14 every 21 days, and nab-paclitaxel monotherapy administered IV on 
Days 1 and 8 every 21 days as second-line treatment for advanced nonsquamous 
NSCLC.
Exploratory 
!
To assess healthcare resource utilization for the two treatment arms.
!
To assess the quality of life (QoL) for the two treatment arms.
!
To determine baseline tumor characteristics which predict response to nab-paclitaxel 
as a single agent and in combination with epigenetic modifying therapy of CC-486. 
!
To evaluate genomic correlates of response to nab-paclitaxel as a single agent and in 
combination with epigenetic modifying therapy of CC-486.
Study Design
This is a Phase 2, randomized, open-label, multicenter study to assess efficacy and safety of  
nab-paclitaxel in combination with epigenetic modifying therapy of CC-486, and nab-paclitaxel 
monotherapy as second-line treatment in subjects with advanced nonsquamous NSCLC who 
have received one platinum-containing chemotherapy regimen. Approximately 160 subjects with 
advanced nonsquamous NSCLC will be randomized 1:1 into one of the two treatment arms: nab-
paclitaxel / CC-486 combination therapy or nab-paclitaxel monotherapy prior to receiving first 
1 nab® is a registered trademark of Celgene Corporation
&(/*(1(35235,(7$5<,1)250$7,21
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istered IV
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nonsquam
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ab-paclitax
aclitax
mo
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difying 
ab-paclitax
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-006 Final: 29 May 2014
dose of investigational product (IP). Randomization will be centralized and stratified by Eastern 
Cooperative Oncology Group (ECOG) performance status (0 versus 1, see Appendix A), gender
(males versus females), and smoker (yes versus no).
The study will consist of up to a 28-day Screening Period, a Treatment Period and a Follow-up 
Period.  
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of IP.
The Treatment Period begins with the first dose of IP as described in Section 8.  Subjects will 
receive one of the following treatments based on the randomization assignment:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days  1 to 14 of each 21-day treatment cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment  cycle
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, withdrawal of 
consent, or termination of the study by the sponsor.
Tumor evaluations will be assessed by the investigative sites and response will be determined 
according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, Version 1.1
(Eisenhauer, 2009).
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an adverse event (AE)/serious adverse event (SAE) and also recorded on the 
laboratory electronic Case Report Form (eCRF) (see Section 11.3).  
All subjects who discontinue from treatment for any reason other than withdrawal of consent, 
lost to follow-up, death, or termination of the study by the sponsor will enter the Follow-up
Period. It will consist of a visit 28 days after treatment discontinuation. Thereafter, subjects will 
be followed for survival by phone call contact approximately every 90 days (+/- 14 days) for 12
months after the last subject is randomized or 120 progression-free survival (PFS) events have 
been observed, whichever comes later.
During the study, subjects will have computed tomography (CT) scans every 42 days (-3/+7 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the sponsor. Those subjects entering the Follow-up Period without 
documented progression will continue to have CT scans in accordance with local standard of 
care (or approximately every 90 days) until documented progression of disease, withdrawal of
consent, lost to follow-up, death, or termination of the study by the sponsor. All posttreatment 
anticancer therapies will be recorded during the Follow-up Period.  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-006 Final: 29 May 2014
Study Population
Male and female subjects with advanced nonsquamous NSCLC who have received one 
platinum-containing chemotherapy regimen for their advanced disease will be eligible for this 
study.
Length of Study
The enrollment of 160 subjects on this study will take approximately 24 months. The total length 
of this Phase 2 study with follow-up is estimated to be approximately 3 years.
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
study, or the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol and/or the 
Statistical Analysis Plan, whichever is the later date.
Study Treatments
Subjects will receive nab-paclitaxel in combination with CC-486 or nab-paclitaxel monotherapy 
during the study. The CC-486 and nab-paclitaxel for both arms are designated as IP and will be 
packaged and supplied by Celgene Corporation.
Overview of Statistical Methods
The primary objective of this study is to evaluate the efficacy of the CC-486 and nab-paclitaxel 
combination therapy and that of the nab-paclitaxel monotherapy, and the relative efficacy of 
these two treatment regimens.  
Approximately 160 subjects will be randomized to the two treatment arms in a 1:1 ratio.  A 
permuted-block randomization method will be employed, and the randomization will be carried 
out centrally using an Interactive Response Technology (IRT) system. The randomization will be 
stratified based on the following baseline factors: ECOG performance status (0 versus 1), gender 
(males versus females), and smoker (yes versus no).
Evaluations of the study endpoints will be based primarily on the point estimates and the 
associated 95%  confidence intervals of the within- and between-treatment differences. However, 
nominal p-values from statistical tests may be provided in the clinical study report to indicate the 
strength of the treatment differences evaluated. 
An independent Data Monitoring Committee (DMC) will be established to review the interim 
safety and efficacy data.  
Efficacy Analyses
The intent-to-treat population, which includes all randomized subjects regardless of whether the 
subject receives any IP or has any efficacy assessments performed, will be used for all efficacy 
analyses. The primary efficacy endpoint is PFS, which is defined as the time from the date of 
randomization to the date of disease progression or death (from any cause) on or prior to the data 
cutoff date for analyses, whichever occurs first, based on the investigator’s assessment of the 
data from CT scans using RECIST 1.1 guidelines. Baseline tumor measurements will be 
determined from the radiologic evaluation performed within 28 days before the start of study 
therapy. 
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Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% confidence interval [CI]) for each treatment arm.  The relative 
treatment effect between the combination and monotherapy arms with respect to PFS will be 
estimated by the hazard ratio (HR) and the associated two-sided 95% CIs using the stratified Cox 
proportional hazard model with ECOG performance status (0 versus 1), gender (males versus 
females), and smoker (yes versus no) as the stratification factors. No statistical inferential tests 
will be performed. 
The secondary endpoints include disease control rate (DCR), overall response rate (ORR), and 
overall survival (OS). Disease control rate and ORR will be summarized within each treatment 
arm by the observed rates and the associated 95% CIs. The relative treatment effect will be 
summarized by the absolute difference and the  ratio of the observed rates. Overall survival will 
be analyzed using similar statistical method as that for the PFS endpoint.
Safety Analyses
The treated population, which includes all randomized subjects who receive at least one dose of 
IP, will be the analysis population for all safety analyses. 
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AE or SAE occurring or worsening on or after the day of the first dose of the IP
through 28 days after the last dose of IP.  In addition, any SAE with an onset date more than 28 
days after the last dose of IP that is assessed by the investigator as related to IP will be 
considered a TEAE.
Treatment-emergent adverse events, Grade 3 or higher TEAEs, SAEs, TEAEs leading to dose 
reduction, dose delay, and dose interruption, TEAEs leading to treatment discontinuation, and 
TEAEs with an outcome of death will be summarized by treatment arms using MedDRA system 
organ class and preferred terms.
Sample Size
This study is designed to estimate the treatment effect within each of the combination and 
monotherapy arms and the relative effect between the two arms with respect to the primary and 
secondary efficacy endpoints. The sample size was chosen to support the estimation of the 
within- and between-treatment effects with reasonable precision. Table 1 below summarizes the 
precisions that can be achieved given different scenarios of hypothetical observed hazard ratios 
between the two treatment arms for PFS events, assuming a total of 120 events are observed, and 
the time to PFS has an exponential distribution. 
Table 1:
Progression-Free Survival – Two-side 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms
Hypothetical Number of 
Events Observed
Hypothetical Observed Hazard 
Ratio of PFS Events
95% Confidence Interval of 
Hazard Ratioa
120
0.60
(0.42, 0.86)
0.65
(0.45, 0.93)
0.70
(0.49, 1.00)
a Assuming a standard error of 0.18 for the log hazard ratio.
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vival will
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marized by
marized by
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Events
Events
/*
&(


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Assuming the median times of PFS are 4.17 and 2.5 months, respectively, for the nab-
paclitaxel/CC-486 combination therapy
and nab-paclitaxel
monotherapy arms, and an 
approximate 24 months accrual period for a total of 160 subjects, it is estimated that a total of 
120 PFS events will be observed approximately 2 months after the last subject is randomized, 
assuming an exponential distribution for PFS. 
One nonbinding interim analysis for PFS with early stopping rule for futility will be conducted 
when approximately 60 events are observed. 
Data Monitoring Committee
An independent Data Monitoring Committee (DMC) will be established with the responsibilities 
for safeguarding the interests of study participants and monitoring the overall conduct of the 
study. Final recommendations of the DMC will reflect the judgment of the DMC members and 
will be considered advisory in nature to the sponsor. The decision to implement the 
recommendations of the DMC will be made by the sponsor, following consultation with the trial 
Coordinating Investigator and Steering Committee. A DMC charter will be established.
&(/*(1(35235,(7$5<,1)250$7,21
ibilit
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TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
1.
INTRODUCTION..................................................................................................18
1.1.
Non-small Cell Lung Cancer ..................................................................................18
1.2.
nab-Paclitaxel in NSCLC .......................................................................................19
1.3.
Rationale for nab-Paclitaxel as Second-line Treatment in Subjects with 
Advanced Nonsquamous NSCLC ...........................................................................20
1.4.
Rationale for nab-Paclitaxel in Combination With Epigenetic Modifying 
Therapy of CC-486 as Second-line Treatment in Subjects with Advanced 
Nonsquamous NSCLC............................................................................................21
2.
STUDY OBJECTIVES...........................................................................................24
2.1.
Primary Objective...................................................................................................24
2.2.
Secondary Objective...............................................................................................24
2.3.
Exploratory Objectives ...........................................................................................24
3.
STUDY ENDPOINTS............................................................................................25
3.1.
Primary Endpoint....................................................................................................25
3.2.
Secondary Endpoints ..............................................................................................25
3.2.1.
Efficacy..................................................................................................................25
3.2.2.
Safety.....................................................................................................................25
3.3.
Exploratory Endpoints............................................................................................25
4.
OVERALL STUDY DESIGN ................................................................................26
4.1.
Study Design ..........................................................................................................26
4.1.1.
Screening Period.....................................................................................................26
4.1.2.
Treatment Period ....................................................................................................26
4.1.3.
Follow-up Period....................................................................................................27
4.2.
Study Design Rationale ..........................................................................................27
4.3.
Study Duration .......................................................................................................29
4.4.
End of Trial ............................................................................................................29
5.
TABLE OF EVENTS.............................................................................................30
6.
PROCEDURES......................................................................................................33
6.1.
Medical History......................................................................................................33
6.2.
Prior and Concomitant Medications and Procedures ...............................................33
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20
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.............
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DESIGN
DESIGN
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w-up Peri
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5.


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6.3.
Pregnancy Testing ..................................................................................................33
6.4.
Complete Chest Computed Tomography (CT) Scan................................................34
6.5.
Weight and Height..................................................................................................34
6.6.
ECOG Performance Score ......................................................................................34
6.7.
Peripheral Neuropathy Assessment.........................................................................34
6.8.
Adverse Event Reporting........................................................................................34
6.9.
Quality of Life Questionnaires................................................................................35
6.10.
Healthcare Resource Utilization Questionnaire .......................................................35
6.11.
Laboratory Assessments .........................................................................................35
6.12.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) .....................................................................................35
6.13.
Electrocardiogram ..................................................................................................36
6.14.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI) .......................37
6.15.
Bone Scans and X-rays...........................................................................................37
6.16.
Physical Examinations............................................................................................37
6.17.
Vital Signs..............................................................................................................37
6.18.
Survival..................................................................................................................37
7.
STUDY POPULATION.........................................................................................38
7.1.
Number of Subjects and Sites .................................................................................38
7.2.
Inclusion Criteria....................................................................................................38
7.3.
Exclusion Criteria...................................................................................................39
8.
DESCRIPTION OF STUDY TREATMENTS........................................................41
8.1.
Description of Investigational Products...................................................................41
8.1.1.
nab-Paclitaxel.........................................................................................................41
8.1.2.
CC-486 (Azacitidine for Oral Administration) ........................................................41
8.2.
Treatment Administration and Schedule .................................................................41
8.3.
Dose Omissions and Modifications.........................................................................42
8.3.1.
Rules for Dose Omissions and Modified Schedules ................................................42
8.3.2.
Rules for Dose Modifications .................................................................................42
8.4.
Method of Treatment Assignment...........................................................................45
8.5.
Packaging and Labeling..........................................................................................45
8.6.
Investigational Product Accountability and Disposal ..............................................45
8.7.
Investigational Product Compliance........................................................................46
&(/*(1(35235,(7$5<,1)250$7,21
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.......35
3
..........
.... 35
3
..............
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.............
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ging (MRI)
ng (MRI)
.............
..
..............
........
................
...............
..............
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..............
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..............
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F STUDY
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8.4.
.4


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8.8.
Overdose ................................................................................................................46
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................47
9.1.
Permitted Concomitant Medications and Procedures...............................................47
9.2.
Prohibited Concomitant Medications and Procedures..............................................48
9.3.
Required Concomitant Medications and Procedures for Patients Receiving 
CC-486...................................................................................................................48
9.3.1.
Description of G-CSF.............................................................................................48
9.3.2.
Administration of G-CSF........................................................................................48
10.
STATISTICAL ANALYSES..................................................................................49
10.1.
Overview................................................................................................................49
10.2.
Study Population Definitions ..................................................................................49
10.2.1.
Intent-to-treat Population........................................................................................49
10.2.2.
Per-protocol (PP) Population ..................................................................................49
10.2.3.
Treated Population..................................................................................................50
10.3.
Sample Size and Power Considerations...................................................................50
10.4.
Background and Demographic Characteristics........................................................51
10.5.
Subject Disposition.................................................................................................52
10.6.
Efficacy Analysis....................................................................................................52
10.6.1.
Primary Efficacy Endpoints....................................................................................52
10.6.2.
Secondary Efficacy Endpoints ................................................................................53
10.6.2.1.
Disease Control Rate ..............................................................................................53
10.6.2.2.
Overall Survival .....................................................................................................53
10.6.2.3.
Overall Response Rate............................................................................................53
10.6.3.
Exploratory Endpoints............................................................................................53
10.6.3.1.
HealthCare Utilization............................................................................................53
10.6.3.2.
Quality of Life Questionnaires................................................................................53
10.6.3.3.
Biomarker, Tumor Characteristics, and Genomic Analyses.....................................53
10.7.
Safety Analysis.......................................................................................................53
10.7.1.
Adverse Events.......................................................................................................54
10.7.2.
Laboratory Assessments .........................................................................................54
10.7.3.
Study Drug Exposure..............................................................................................54
10.8.
Study Therapy Termination ....................................................................................54
10.9.
Deaths ....................................................................................................................54
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........
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7


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10.10.
Interim Analysis .....................................................................................................55
10.11.
Data Monitoring Committee ...................................................................................55
10.12.
Scientific Steering Committee ................................................................................55
11.
ADVERSE EVENTS..............................................................................................56
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................56
11.2.
Evaluation of Adverse Events.................................................................................56
11.2.1.
Seriousness.............................................................................................................56
11.2.2.
Severity / Intensity..................................................................................................58
11.2.3.
Causality ................................................................................................................58
11.2.4.
Duration .................................................................................................................59
11.2.5.
Action Taken..........................................................................................................59
11.2.6.
Outcome.................................................................................................................59
11.3.
Abnormal Laboratory Values..................................................................................59
11.4.
Pregnancy...............................................................................................................59
11.4.1.
Females of Childbearing Potential ..........................................................................60
11.4.2.
Male Subjects.........................................................................................................60
11.5.
Reporting of Serious Adverse Events......................................................................60
11.5.1.
Safety Queries ........................................................................................................61
11.6.
Expedited Reporting of Adverse Events..................................................................61
12.
DISCONTINUATIONS .........................................................................................62
12.1.
Study Treatment Discontinuation............................................................................62
12.2.
Study Discontinuation ............................................................................................62
12.3.
Subject Replacement ..............................................................................................63
13.
EMERGENCY PROCEDURES.............................................................................64
13.1.
Emergency Contact.................................................................................................64
13.2.
Emergency Identification of Investigational Products .............................................64
14.
REGULATORY CONSIDERATIONS...................................................................65
14.1.
Good Clinical Practice............................................................................................65
14.2.
Investigator Responsibilities ...................................................................................65
14.3.
Subject Information and Informed Consent.............................................................65
14.4.
Confidentiality........................................................................................................66
14.5.
Protocol Amendments.............................................................................................66
6
.......56
5
..........
.... 58
5
..............
...........
..............
............
.............
.............
..............
............
.............
.............
.............
.....
.............
...........
.............
.............
.............
............
..............
..........
se Events
se Events
.............
....
ontinuation
tinuation
tioion ......
.
acement
cement ..
NCY PRO
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4.2
4.2.
14.3.
4.3.


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14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................66
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................67
14.8.
Closure of the Study ...............................................................................................67
15.
DATA HANDLING AND RECORDKEEPING.....................................................68
15.1.
Data/Documents .....................................................................................................68
15.2.
Data Management...................................................................................................68
15.3.
Record Retention....................................................................................................68
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................70
16.1.
Study Monitoring and Source Data Verification......................................................70
16.2.
Audits and Inspections............................................................................................70
17.
PUBLICATIONS ...................................................................................................71
18.
REFERENCES.......................................................................................................72
Appendix A:
ECOG Performance Status Score.......................................................................75
Appendix B: Recommendations for Management of Treatment-Induced Diarrhea.....................76
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..68
68
........
.......68
68
..............
............ 7
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ent-Induced
Induce


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LIST OF TABLES
Table 1:
Progression-Free Survival – Two-side 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms ................................9
Table 2:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat 
Population).............................................................................................................20
Table 3:
Table of Events.......................................................................................................30
Table 4:
Requirements for Collection Based on Archival Tumor Sample Type.....................36
Table 5:
Permanent Dose Reductions for Hematologic and Nonhematologic 
Toxicities and Dosing on the Study.........................................................................44
Table 6:
Disease Control Rate –Two-Sided 95% Confidence Interval of Hypothetical 
Disease Control Rate with a Sample Size of 80 Subjects in a Treatment Arm .........50
Table 7:
Progression-Free Survival – Two-Sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms..............................51
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LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................28


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1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer
Lung cancer is the leading cause of cancer-related deaths among men and women worldwide, 
with 1.2 million new cases diagnosed each year. Non-small cell lung cancer (NSCLC) is the 
most common type of lung cancer, accounting for 80% of all new cases. There are an estimated 
1.1 million lives lost per year (approximately 500,000 in the United States [US] and European 
Union [EU] alone) due to NSCLC. Smoking is the causative factor for up to 85% of cases 
(http://www.lungcancercoalition.org/en/pages/about/awareness).
The majority of patients are not diagnosed until the tumor has progressed beyond the primary 
site. Despite step-wise advances in patient selection, targeted agents, and optimizing
chemotherapy regimens, patients with advanced NSCLC continue to have an unmet medical 
need (Schiller, 2013).
Platinum-containing chemotherapy regimens remain the standard first-line treatment in the 
majority of patients in the US and Japan. In the EU, a third-generation chemotherapeutic agent 
(docetaxel, gemcitabine, paclitaxel, or vinorelbine), most commonly gemcitabine or vinorelbine, 
plus a platinum drug is used for advanced NSCLC (NICE, 2011). For first-line therapy in 
patients with Stage IV NSCLC and good performance status, the American Society of Clinical 
Oncology (ASCO) clinical practice guideline recommends treatment with a platinum-based 
two-drug combination of cytotoxic drugs (Azzoli, 2009). For patients without disease 
progression, the option of maintenance monotherapy with pemetrexed or erlotinib could also be 
considered (Gerber, 2013; Schiller, 2013). A trend that is becoming more prevalent is 
personalized NSCLC treatment based on tumor histology (squamous versus nonsquamous), on 
molecular characteristics of the tumor, and on the patient’s clinical status using agents targeting 
specific receptors, kinases and pathways (ie, epidermal growth factor receptor [EGFR], 
echinoderm microtubule-associated protein-like 4 [EML4] and anaplastic lymphoma kinase 
[ALK] fusion protein).
Single agent chemotherapy (pemetrexed, EGFR-inhibitors and taxanes) are standards of care for 
second-line treatment of patients with locally advanced or metastatic NSCLC after failure of 
prior platinum-based chemotherapy. Docetaxel has been widely evaluated in this setting, and is 
currently approved by the US Food and Drug Administration (FDA) and the European 
Medicines Agency (EMA) as a single agent for the treatment of patients with locally advanced or 
metastatic NSCLC after failure of prior chemotherapy  (the US label specifies prior platinum-
based chemotherapy). For patients with a good performance status at the time of disease 
progression following first-line chemotherapy, docetaxel, despite a low response rate, was
associated with a 10% to 20% prolongation of 1-year survival and an improved quality of life 
when compared with ifosfamide, vinorelbine, or best supportive care (BSC) alone (Hanna, 
2004). Erlotinib is indicated in the US and EU for the treatment of patients with locally advanced 
or metastatic NSCLC after failure of at least one prior chemotherapy regimen, although no 
survival benefit has been demonstrated in patients with EGFR-IHC negative tumors. 
Pemetrexed is indicated in the US and EU as a single agent for the treatment of patients with 
locally advanced or metastatic nonsquamous NSCLC after prior chemotherapy. However, the 
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approval and subsequent increased use of pemetrexed and erlotinib in the first-line setting poses 
an unmet need in the second-line setting, whereby new therapeutic options are needed.
1.2.
nab-Paclitaxel in NSCLC
nab-Paclitaxel is approved in the first-line setting in combination with carboplatin for patients 
with NSCLC in the US, Japan, Argentina, Australia, and New Zealand.  The approval  was based 
on the evaluation of Phase I and II data (Belani, 2008; Rizvi, 2008; Socinski, 2010), as well as 
the pivotal Phase 3 study (CA031), (Socinski, 2012). The pivotal Phase 3 study was a 
multicenter, randomized, open-label study conducted in 1052 chemo-naïve subjects with Stage 
IIIB/IV NSCLC to compare nab-paclitaxel in combination with carboplatin to paclitaxel 
injection in combination with carboplatin as first-line treatment in patients with advanced 
NSCLC. nab-Paclitaxel was administered as an IV infusion over 30 minutes at a dose of 
100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel injection was administered as 
an IV infusion over 3 hours at a dose of 200 mg/m2, following premedication. In both treatment 
arms carboplatin at a dose of area under the curve (AUC) = 6 mg*min/mL was administered IV
on Day 1 of each 21-day cycle after completion of nab-paclitaxel/paclitaxel infusion. Treatment 
was administered until disease progression, development of an unacceptable toxicity or patient 
withdrawal. The primary efficacy outcome measure was overall response rate (ORR) as
determined by a central independent review committee using RECIST guidelines (Version 1.0).
In the intent-to-treat (all-randomized) population, the median age was 60 years, 75% were men, 
81% were white, 49% had carcinoma/adenocarcinoma, 43% had squamous cell lung cancer, 76% 
were ECOG performance status (PS) 1, 15% were ≥70 years of age and 73% were current or 
former smokers. Patients received a median of 6 cycles of treatment in both study arms. Patients 
in the nab-paclitaxel/carboplatin arm had a statistically significantly higher overall response rate 
compared to patients in the paclitaxel injection/carboplatin arm [(33% versus 25%; response rate 
ratio, 1.313; 95% CI, 1.082 to 1.593; p=0.005), see Table 2].
Non-inferiority analysis of overall survival (OS) demonstrated that nab-paclitaxel/carboplatin
(nab-p/C) treatment is not inferior to paclitaxel/carboplatin (P/C) treatment. Overall survival in 
the nab-paclitaxel arm was 12.1 months versus 11.2 months in the control arm (p = 0.271; HR = 
0.922). There was an approximately 10% increase in PFS in the nab-p/C versus P/C arm and PFS 
in the nab-p/C arm was noninferior to PFS in the P/C arm (HRnab-p/C/P/C 95% CI upper bound, 
1.086).
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-006
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Table 2:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat
Population)
Variable
Category/Statistic
nab-Paclitaxel/
carboplatin
(N=521)
Paclitaxel/
carboplatin
(N=531)
Response Rate 
Ratio
(pA/pT)
p-value
Patients with Confirmed Complete or Partial Overall Response
n (%)
170 (33%)
132 (25%)
1.313
0.005*
Confidence Interval (CI) a
28.6, 36.7
21.2, 28.5
1.082, 1.593
Complete Response, n (%)
0
1 (< 1%)
Partial Response, n (%)
170 (33%)
131 (25%)
PA/PT: response rate of nab-paclitaxel/response rate of paclitaxel.
a 95% CI of response rate and 95.1% CI of response rate ratio.
* Indicates p-value < 0.049.
Note: p-value is based on a chi-square test.
Source: Data on File.
Adverse events (AEs) were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. The following common (≥ 10% incidence) AEs
were observed at a similar incidence in nab-paclitaxel/carboplatin and paclitaxel/carboplatin
arms: alopecia 56%, nausea 27%, fatigue 25%, decreased appetite 17%, asthenia 16%, 
constipation 16%, diarrhea 15%, vomiting 12%, dyspnea 12%, and rash 10% (incidence rates are 
for the nab-paclitaxel plus carboplatin treatment group). Toxicities, particularly neuropathy and 
Grade 3/4 neutropenia were less pronounced using nab-paclitaxel in the dose and schedule 
employed. Laboratory-detected abnormalities which occurred with a difference ≥5% for nab-
paclitaxel plus carboplatin versus paclitaxel injection plus carboplatin (Grades 1 to 4 [and Grade 
3/4]) were: anemia (98% vs 91% [28% vs 7%]), neutropenia (85% vs 83% [47% vs 58%]) and 
thrombocytopenia (68% vs 55% [18% vs 9%]).  
1.3.
Rationale for nab-Paclitaxel as Second-line Treatment in Subjects 
with Advanced Nonsquamous NSCLC
Patients who fail first-line chemotherapy are eligible for second-line treatment with single agent 
docetaxel, pemetrexed or erlotinib. In patients with good performance (eg, ECOG PS 0 or 1) and 
general health status, further treatment with chemotherapy is an important consideration that has 
been shown to extend overall survival. Despite the availability of second-line therapy, the trend 
of increased use of pemetrexed, as well as erlotinib (in selected patients) in the first-line and 
maintenance settings, potentially limits the number of available second-line treatment options for 
many patients. Furthermore, the tolerability issues associated with the administration  of 
docetaxel once every 3 weeks (q3w) has prompted active research in the past decade to evaluate 
whether weekly regimens of taxanes could be optimized to improve the toxicity profile. The 
availability of an effective second-line cytotoxic chemotherapy with an improved efficacy/safety
profile over current available options would be a valuable addition for both the patient and the 
treating physician. Paclitaxel has also demonstrated potential activity in second-line NSCLC in a 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
21
ABI-007-NSCL-006 Final: 29 May 2014
few studies (Socinski, 1999; Juan, 2002; Socinski, 2002; Sculier, 2002; Buccheri, 2004; Ceresoli, 
2004; Yasuda, 2004).
nab-Paclitaxel exhibits 10-fold higher mean Cmax of free paclitaxel, delivers 33% higher drug 
concentration to tumors in preclinical xenograft models, and demonstrates enhanced transport 
across endothelial cell monolayers, when compared with paclitaxel (Desai, 2006; Gardner, 
2008). The Cremophor EL-free medium enables nab-paclitaxel to be given over a shorter 
duration without the need for premedication to prevent solvent-related hypersensitivity reactions.
When administered with carboplatin in the first-line setting, weekly nab-paclitaxel has 
demonstrated a more favorable efficacy:safety profile compared to the every 3 weeks schedule.  
This weekly schedule schedule of nab-paclitaxel allows the opportunity for closer (ie, shorter 
interval) monitoring of side effects and optimizing dose-intensity through timely adjustments.  
As previously noted, nab-paclitaxel 100 mg/m2 weekly (Days 1, 8 and 15) in combination with 
carboplatin (21 day cycle) is approved in the US, Japan, Argentina, Australia, and New Zealand 
for the treatment of locally advanced or metastatic NSCLC in the first-line setting.  However, 
there is limited data of monotherapy nab-paclitaxel in the second-line setting; hence, this study 
will  assess the efficacy and tolerability of weekly nab-paclitaxel, when administered on Days 1 
and 8 of each 21-day cycle.  The allowance of a one week rest period in this study (ie, no 
treatment on Day 15), takes into account research findings from other taxanes, whereby patients 
in the second-line setting are unlikely to tolerate the same dose-intensity compared to chemo-
naïve patients (eg, sharper dose reduction in the second-line setting). Therefore, the proposed 
nab-paclitaxel schedule (2 weeks treatment, 1 week rest) could offer the option of maintaining 
consistent dose-intensity for NSCLC patients in this setting.
1.4.
Rationale for nab-Paclitaxel in Combination With Epigenetic 
Modifying Therapy of CC-486 as Second-line Treatment in Subjects 
with Advanced Nonsquamous NSCLC
CC-486 is an orally bioavailable formulation of the nucleoside analog 5-azacitidine (AZA).  
After its incorporation into a cell’s DNA during the S-phase of the cell cycle, CC-486 forms 
covalent adducts with DNA Methyltransferase 1 (DNMT1) and depletes this enzyme required for 
the maintenance of DNA methylation patterns, thereby altering the epigenetic status of the cell. 
Epigenetic changes are covalent modifications of chromatin (DNA and histone proteins) that 
mediate the stable transmission of a gene’s transcriptional status through cell division.  One of 
the first recognized epigenetic alterations in cancer was DNA methylation.  The addition of a 
methyl group to cytosine in the dinucleotide CpG is catalyzed by DNA methyltransferases 
(DNMTs) and is associated with transcriptional repression of genes with high density of CpGs 
(CpG islands) in the vicinity of their promoters (Jones, 2007).  Genomic methylation patterns are 
precisely regulated during normal embryonic development and differentiation and have been 
found to be altered in specific ways in cancer. Specifically, cancer cell genomes are typified by 
reduced methylation globally with focal areas of aberrant hypermethylation in the CpG islands of 
genes encoding known tumor suppressors such as PTEN and BRCA1 as well as genes encoding 
proteins required for apoptosis, including caspase 8, DAPK and Apaf-1.  DNA methylation-
based silencing can thus contribute to the establishment and maintenance of the transformed state 
and limit the effectiveness of anti-cancer therapies.  The recognition of the role of aberrant 
methylation in carcinogenesis and its reversibility has led to the development of DNMT 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
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Confidential and Proprietary
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ABI-007-NSCL-006 Final: 29 May 2014
inhibitors for cancer. Subcutaneous (SC) AZA was the first DNMT inhibitor to be approved in 
myelodysplastic syndromes (MDS) in 2004 (Kaminskas, 2005).
The notion that sequential treatment with an epigenetic modifying agent followed by a cytotoxic
agent can result in improved response to the latter is supported by numerous preclinical 
experiments and now by early clinical results.  In breast cancer cell lines, restoring expression of 
the aberrantly methylated pro-apoptotic gene TMS1 with azacitidine can restore taxane 
sensitivity (Gordian, 2009).  In a model of platinum resistant ovarian cancer, azacitidine reversed 
resistance to carboplatin (Li, 2009).  This effect required pretreatment of the cells with 
noncytotoxic levels of azacitidine for 24 hours before the addition of carboplatin and was not 
observed with concurrent exposure to both agents.  More recently, Juergens and colleagues 
observed an unusually high ORR of approximately 20% in multiple-relapsed NSCLC patients 
treated with a variety of regimens after being treated with a combination of SC AZA and another 
epigenetic agent, entinostat, a histone deacetylase inhibitor (Juergens, 2011).  In one case, a 
patient who had previously progressed on a regimen of paclitaxel, carboplatin and bevacizumab 
responded to the same triplet after treatment with SC AZA and entinostat, suggesting that the 
epigenetic modifying agents had reversed acquired resistance to the cytotoxic/anti-angiogenic 
regimen.  In a Phase 1/2 study of SC AZA with nab-paclitaxel in subjects with advanced 
metastatic solid tumors and breast cancer (Dumlao, 2011), escalating doses of SC AZA (75 to
100 mg/m2) were administered on Days 1 through 5, followed by nab-paclitaxel (100 mg/m2) 
intravenous (IV) on Days 8, 15, and 22 of a 28-day cycle.  Of 16 subjects treated at the time of 
publication, clinical activity has included 3 complete responses (CR, 1 Diffuse Large B-cell 
Lymphoma [DLBCL], 2 ovarian), 4 partial responses (PR) in ovarian and endometrial cancer 
and 4 stable diseases (SD, 2 lung, 1 pancreatic, and 1 sarcoma).  
CC-486 entered clinical testing in 2006 in subjects with MDS, chronic myelomonocytic 
leukemia [CMML], and acute myeloid leukemia [AML], with daily extended dosing schedules 
of 14 and 21 out of 28 days in a non-crossover fashion.  Daily doses of 300 mg CC-486 have 
proven to be tolerated on both the 14 and 21 out of 28-day schedules with myelosuppression, 
gastrointestinal symptoms, and fatigue being the most common toxicities (Garcia-Manero, 
2011).  Subjects treated with CC-486 for 14 or 21 days had DNA hypomethylation that persisted 
through the end of cycle.  This contrasts with the lack of persistent hypomethylation at the end of 
cycle when subjects were treated with SC AZA for 7 out of 28 days. 
 
 
 
 
  
 
 
 
 
 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Final: 29 May 2014
  
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
This Phase 2 study will test the hypothesis that epigenetic modifying therapy with CC-486 can 
improve the anti-tumor activity of nab-paclitaxel in second-line NSCLC patients (see Section 4.2
for study rationale). Although docetaxel has been assessed in other randomized studies as a 
chemotherapy backbone, the considerable neutropenia-related toxicity could potentially pose 
safety concerns if combined with CC-486, and the steroid premedication could confound the 
epigenetic impact of CC-486.  In addition, the q3w dosing schedule of docetaxel restricts dose 
adjustment options, thus potentially yielding lower chemotherapy dose-intensity.
Please refer to the Investigator’s Brochures (IBs) of CC-486 and nab-paclitaxel (ABI-007) for 
detailed information concerning the available pharmacology, toxicology, drug metabolism, 
clinical studies, and adverse event profile of the IPs.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-006 Final: 29 May 2014
2.
STUDY OBJECTIVES
2.1.
Primary Objective 
The primary objective of the study is:
!
To assess the efficacy of nab-paclitaxel administered intravenously (IV) on Days 8 
and 15 with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 
14 every 21 days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 
every 21 days as second-line treatment for advanced nonsquamous NSCLC, and the 
relative efficacy of these two treatment regimens.
2.2.
Secondary Objective
The secondary objective of the study is:
!
To evaluate the safety and tolerability of nab-paclitaxel administered IV on Days 8 
and 15 with epigenetic modifying therapy of CC-486 QD on Days 1 to 14 every 21 
days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 every 21 
days as second-line treatment for advanced nonsquamous NSCLC.
2.3.
Exploratory Objectives
The exploratory objectives of the study are:
!
To assess healthcare resource utilization for the two treatment arms.
!
To assess the QoL for the two treatment arms.
!
To determine baseline tumor characteristics which predict response to nab-paclitaxel 
as a single agent and with epigenetic modifying therapy of CC-486. 
!
To evaluate genomic correlates of response to nab-paclitaxel as a single agent and 
with epigenetic modifying therapy of CC-486.
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('06'RF1XPEHU
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3.
STUDY ENDPOINTS
Study efficacy endpoints will be assessed by the investigator using RECIST 1.1 guidelines.
3.1.
Primary Endpoint
The primary endpoint is:
!
Progression free survival.
3.2.
Secondary Endpoints
The secondary endpoints are: 
3.2.1.
Efficacy
!
Disease control rate.
!
Overall response rate.
!
Overall survival.
3.2.2.
Safety
!
The type, frequency, and severity of AEs and SAEs graded using National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, 
Version 4.0). 
!
Discontinuation rate.
!
The median dose intensity.
!
The incidence of dose reduction.
3.3.
Exploratory Endpoints
!
Healthcare resource utilization during the study using a questionnaire.
!
Changes in the Lung Cancer Symptom Scale (LCSS), European Organisation for 
Research and Treatment of Cancer (EORTC) QLQ C30, and EuroQoL 5D-5L (EQ-
5D-5L).
!
The correlation between pretreatment tumor characteristics and response to the study 
treatment determined using next-generation sequencing methods, 
immunohistochemistry, or other analysis methods.
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('06'RF1XPEHU
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4.
OVERALL STUDY DESIGN 
4.1.
Study Design
This is a Phase 2, randomized, open-label, multicenter study to assess safety and efficacy of  
nab-paclitaxel in combination with epigenetic modifying therapy of CC-486, and nab-paclitaxel 
monotherapy as second-line treatment in subjects with advanced nonsquamous NSCLC who 
have received one platinum-containing chemotherapy regimen. Approximately 160 subjects with 
advanced nonsquamous NSCLC will be randomized 1:1 into one of the two treatment arms: nab-
paclitaxel / CC-486 or nab-paclitaxel monotherapy prior to receiving first dose of investigational 
product (IP). Randomization will be centralized and stratified by ECOG performance status (0 
versus 1), gender (males versus females), and smoker (yes versus no).
The study will consist of up to a 28-day Screening Period, a Treatment Period and a Follow-up 
Period.  
4.1.1.
Screening Period 
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of IP.
4.1.2.
Treatment Period 
The Treatment Period begins with the first dose of IP as described in Section 8. Subjects will 
receive one of the following treatments based on the randomization assignment:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment  cycle, or  
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment  cycle.
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, withdrawal of 
consent, or termination of the study by the sponsor.
During the study, subjects will have computed tomography (CT) scans every 42 days (-3/+7 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, 
or termination of the study by the sponsor. Tumor evaluations will be assessed by the 
investigative sites and response will be determined according to RECIST 1.1 guidelines.
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an AE/SAE and also recorded on the laboratory eCRF (see Section 11.3).   
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-006
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4.1.3.
Follow-up Period
All subjects who discontinue from treatment for reasons other than withdrawal of consent, lost to 
follow-up, death, or termination of the study by the sponsor will enter the Follow-up Period. It 
will consist of a visit 28 days after treatment discontinuation followed by phone follow-up for 
survival approximately every 90 days (+/- 14 days) for up to 12 months after the last subject is 
randomized or 120 PFS events have been observed whichever comes later.
Those subjects entering the Follow-up Period without documented progression will continue to 
have CT scans in accordance with local standard of care (or approximately every 90 days) until 
documented progression of disease, withdrawal of consent, lost to follow-up, death, or 
termination of the study by the sponsor. All posttreatment anticancer therapies will be recorded 
during the Follow-up Period.  
4.2.
Study Design Rationale
This is an open-label, randomized study designed to evaluate the effects of adding CC-486 to 
nab-paclitaxel and nab-paclitaxel monotherapy in second-line NSCLC. A placebo-controlled 
study would not be feasible for this population as blinding would be difficult and would need a 
double dummy design.  A key objective in this study is to determine the chemo-priming effect of
CC-486. The inclusion of only patients with nonsquamous NSCLC histology allows for a more 
homogenous population, hence, reducing the impact of potential confounding factors. Second-
line NSCLC enables a unique setting to evaluate epigenetics: 
a) compared to more heavily treated patients, patients eligible for second-line treatment
have better immune function/reserve which is critical for safety and activation of immune 
cells that target cancer cells,
b) due to the overlapping (and dose-limiting) toxicities of doublet/triplet chemotherapy 
regimens in the first-line setting, it would be very challenging to combine epigenetic 
therapy at a dose level to elicit clinically meaningful benefit.  
Although docetaxel has been assessed in other randomized studies as a chemotherapy backbone, 
the considerable neutropenia-related toxicity could potentially pose safety concerns if combined 
with CC-486, and the steroid premedication could confound the epigenetic impact of CC-486.  In 
addition, the q3w dosing schedule of docetaxel restricts dose adjustment options, thus potentially 
yielding lower chemotherapy dose-intensity.
For patients with NSCLC whose disease progressed after initial platinum-based chemotherapy, 
the goal of therapy is to delay further progression for as long as possible; hence, the use of PFS 
as the primary endpoint for efficacy evaluation.  Furthermore, maintaining quality of life during 
this period, especially in reducing/managing toxicity is also an important consideration.  
Therefore, the proposed study is designed to optimize the evaluation of efficacy with a tolerable 
dose/schedule of chemotherapy, and its combination with an epigenetic modifying therapy.  
  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
28
ABI-007-NSCL-006 Final: 29 May 2014
Figure 1:
Overall Study Design
IP = investigational product; PFS = progression-free survival; QD = once daily; OS = overall survival
Screening for Eligibility  (up to 28 days)
(n=160)
Follow-up Period
28-day Follow-up visit (after last dose of IP)
Followed for OS by phone approximately every 90 days for up o 12 months after last subject is randomized or 120 
PFS events have been observed, whichever is later
nab-paclitaxel 100 mg/m2  IV infusion over 30 
minutes on Days 1 and 8 of each 21-day cycle 
until disease progression
(n = 80)
-
nab-paclitaxel 100 mg/m2  IV infusion over 30 
minutes on Days 8 and 15 of each 21-day cycle 
until disease progression
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CC-486 200 mg orally QD Days 1 to 14 of each 
21-day cycle until disease progression
(n = 80)
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
29
ABI-007-NSCL-006 Final: 29 May 2014
4.3.
Study Duration 
Recruitment is expected to take approximately 24 months, and the analysis of PFS will be 
performed when approximately 120 PFS events have occurred, estimated as approximately 26
months from first subject randomized. The total length of this Phase 2 study with follow-up is 
estimated to last approximately 3 years.
4.4.
End of Trial
The End of Trial is defined as either the:
!
date of the last visit of the last subject to complete the study, or 
!
the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol
and/or the Statistical Analysis Plan (SAP), whichever is the later date.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
30
ABI-007-NSCL-006 Final: 29 May 2014
5.
TABLE OF EVENTS
Table 3:
Table of Events
Screening
/ Baseline
Treatment Period
Every 21-day Cycle
Follow-up Period
Assessment
Day -28 
to
Day -1
Day 1
( ±2 
days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu
ation Visit 
28-day Follow-up 
Visit (after last 
dose of IP)
Survival Follow-upa
Every 90 days (+/- 14 
days) (after 28-day 
follow-up visit)
Informed Consent
X
-
-
-
-
-
-
-
Medical History (including Tobacco Exposure History), 
Prior Medication and Procedures
X
-
-
-
-
-
-
-
Serum β-hCG b
X
-
-
-
-
-
-
-
Urine Pregnancy Test b
-
X
-
-
-
X
-
-
Complete Chest CT Scan and Any Other Studies 
Required for Tumor Imagingc
X
-
-
-
X
X
-
X
Weight and Heightd
X
X
X
X
-
-
-
-
ECOG Status
X
X
-
-
-
X
X
-
Concomitant Medication/Procedures
-
X
X
X
-
X
X
X
Peripheral Neuropathy Assessmente
X
X
-
-
-
X
X
-
Healthcare Resource Utilization Questionnaire
-
X
-
-
-
X
X
-
Hematologyf
X
X
X
X
-
X
X
-
Serum Chemistryf
X
X
-
-
-
X
X
-
Archived Tumor Tissue Sample for Biomarker (biopsy, 
surgical specimen, or other diagnostic tumor sample)
-
X
(C1D1 
only)
-
-
-
-
-
-
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
31
ABI-007-NSCL-006 Final: 29 May 2014
Table 3:
Table of Events (Continued)
Screening/ 
Baseline
Treatment Period
Every 21-day Cycle
Follow-Up Period
Assessment
Day -28 to
Day -1
Day 1
( ±2 
days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days)
(starting Day 1
Cycle 1)
End-of-
Treatment/
Discontinu-
ation Visit 
28-day Follow-up 
Visit (after last 
dose of IP)
Survival Follow-Upa
Every 90 days (+/- 14 
days) (after 28-day
follow-up visit)
Plasma for Biomarker Analyses
-
X
(C1D1 
only
predose)
-
-
-
-
-
-
Blood for Pharmacogenomic Analyses
-
X
(C1D1 
only 
predose)
-
-
-
-
-
-
Adverse Event Evaluation
After signing ICF and until 28 days after the last dose of IP
-
nab-PaclitaxelMonotherapy 
Administration/Accountabilityg
-
X
X
-
-
-
-
nab-Paclitaxel Combination 
Administration/Accountabilityg
-
-
X
X
-
-
-
-
CC-486 Administration/Accountabilityg
-
X
-
-
-
-
LCSS, EORTC QLQ C30 and EQ-5D-5L
-
X
-
-
-
X
X
-
Survival Phone Call
-
-
-
-
-
-
-
Xa
Electrocardiogram (ECG)
X
Will be done as per standard of care during the Treatment Period and as clinically indicated; however, results 
will not be routinely collected in the eCRFs. If CT/bone scans show lesions pertinent for RECIST 1.1 criteria 
evaluation, data will be collected on the pertinent tumor evaluation eCRFs. If ECGs, physical examinations, 
and/or vital signs are abnormal and clinically significant, the data will be recorded on the AE/SAE eCRF.
Vital Signs
X
Physical Examination
X
Bone Scan (X-rays if needed)
If clinically 
indicated
CT Scan of the Head or Brain Magnetic Resonance 
Imaging (MRI)
If clinically 
indicated
(mandatory if 
symptomatic)
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
32
ABI-007-NSCL-006 Final: 29 May 2014
AE = Adverse Event; β-HCG = beta human chorionic gonadotropin; C1D1 = Cycle 1 Day 1; CT = Computed Tomography; ECOG = Eastern Cooperative Oncology Group; eCRF
= electronic Case Report Form; EORTC QLQ C30 = European Organisation for Research and Treatment of Cancer QLQ C30; EQ-5D-5L = EuroQol 5D-5L; ICF = informed 
consent form; IP = investigational product; LCSS = Lung Cancer Symptom Scale; QD = once daily; RECIST = Response Evaluation Criteria in Solid Tumors; SAE = Serious 
Adverse Event.
a Every 90 (+/-14) days (from 28-day Follow-up Visit ) for up 12 months after the last subject is randomized or 120 PFS events have been observed whichever comes later.
b A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a Serum β-hCG pregnancy test must be performed to assess 
eligibility at Screening/Baseline. Note: the screening serum pregnancy test can be used as the Cycle 1 Day 1 test prior to study therapy if it is performed within the 72-hour 
timeframe.  A urine pregnancy test must be performed prior to administration of IP before beginning each new cycle and at the End-of-Treatment Visit.
c All subjects must have a radiographically documented measurable tumor(s) by RECIST 1.1 criteria: Complete chest CT scan (including base of neck and adrenal gland) will be 
performed at Screening, every 42 days (-3/+7 days) (starting from Day 1 Cycle 1) until disease progression, withdrawal of consent, lost to follow-up, death, or termination of the 
study by the sponsor. The results of a complete chest CT scan (including base of neck and adrenal gland) performed per Standard of Care may be accepted and not repeated 
during Screening provided it was performed within 28 days of the first dose of study drug (Cycle 1 Day 1). The methods of assessment chosen at baseline to follow tumors are to 
remain consistent throughout study duration. Those subjects entering the Follow-up Period without documented progression will continue to have CT scans in accordance with 
local standard of care (or approximately every 90 days) until documented progression of disease, withdrawal of consent, lost to follow-up, death, or termination of the study by 
the sponsor.
d Height will only be obtained at screening visit. Weight will be obtained at Screening and every visit during the Treatment Period before administration of IP.
e The occurrence of peripheral neuropathy will be reported by the investigator per protocol as an AE or SAE.
f All scheduled laboratory samples will be sent to a central laboratory for analysis. Local hematology and chemistry tests may be performed as required for subject 
management/treatment decisions. Local laboratory values that are considered abnormal and clinically significant will be recorded as an AE/SAE and also recorded on the 
laboratory eCRF (see Section 11.3).
g nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 200 mg orally QD on Days 1 to14 of each 21-day treatment cycle or nab-paclitaxel 
100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day treatment cycle.
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Oncology Gro
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5D-5L;
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ICF = 
d Tumors;
Tumo
SA
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ved whicheve
ved whichev
st must be per
st must be p
it is performe
it is performe
Treatment V
Treatment V
uding base of n
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ntnt, lost to foll
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
33
ABI-007-NSCL-006 Final: 29 May 2014
6.
PROCEDURES
Subjects will be provided with a written Informed Consent Form (ICF), given the opportunity to 
ask any questions concerning the study and will sign an ICF prior to participating in any study 
procedures. After giving written informed consent, subjects will undergo a Screening Period to 
be assessed for eligibility. All subjects who sign an ICF must be entered into the Integrated 
Response Technology (IRT) immediately upon signature on the document. Subjects who do not 
meet the eligibility criteria will be considered screening failures and will not be eligible for the 
study. Subjects who fail initial screening may undergo re-screening up to 2 times at any time 
and an ICF will need to be resigned, as well as all screening procedures repeated (some 
procedures may not need to be done if previously done within 28 days prior to screening again).
Subjects that have met all eligibility criteria after the Screening Period will be eligible for
randomization. 
6.1.
Medical History
A complete medical history including, but not limited to, evaluation for past (up to 5 years) or
present cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine,
lymphatic, hematological, immunologic, dermatological, psychiatric, genitourinary, obstetrical, 
surgical history or any other diseases or disorders will be performed at Screening. All NSCLC-
related medical history should be recorded regardless of time. Smoking status/tobacco exposure 
history will be captured on the eCRF.
6.2.
Prior and Concomitant Medications and Procedures
Prior medications are defined as any medications started before the first dose of IP and stopped 
either prior to the date of the first dose of IP or continued after study treatment. All prior 
medications/procedures of clinically significant or ongoing medical conditions taken up to 28 
days of time of signature on the ICF should be recorded. All NSCLC-related prior 
medications/procedures should be recorded regardless of time.
Concomitant medication is defined as the medication that was either initiated before the first 
dose of IP and continued during the study treatment, or initiated on/after the date of the first dose 
of IP but on or before 28 days after the last dose of IP. All subjects will have concomitant 
medications and procedures (including radiation therapy) recorded at each visit from the time of 
signature on the ICF until the 28-day Follow-up Visit, for conditions that are clinically 
significant or ongoing. During the Follow-up Period only NSCLC-associated concomitant 
medications/procedures (including radiation therapy) will be recorded, ie, subsequent-line(s) of 
anti-cancer therapy.
6.3.
Pregnancy Testing
A pregnancy test is required for women of child-bearing potential only. For women of child-
bearing potential a serum β-hCG pregnancy test with sensitivity of at least 25 mIU/mL must be 
performed to assess eligibility at Screening/Baseline. Note: the screening serum pregnancy test 
can be used as the Cycle 1 Day 1 test prior to study therapy if it is performed within the 72-hour 
timeframe.  A urine pregnancy test must be performed prior to administration of IP before 
&(/*(1(35235,(7$5<,1)250$7,21
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tions
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rte
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IP or conti
or cont
gnificant o
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should be
should b
be recorded
e recorded
efined as th
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during the 
during t
28 days afte
28 days aft
ocedures 
edures (in
(in
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ICF unt
until th
il th
ongoing. D
ngoing. D
s/procedur
/procedur
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arini


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
34
ABI-007-NSCL-006 Final: 29 May 2014
beginning each new cycle and at the End-of-Treatment Visit. The subject may not receive 
treatment until the investigator has verified that the result of the pregnancy test is negative. See 
inclusion criteria for pregnancy testing requirements. Any pregnancies that occur in women who 
have received IP must be immediately reported to Celgene Drug Safety (See Section 11.4).
6.4.
Complete Chest Computed Tomography (CT) Scan
A complete chest CT scan (including base of neck and adrenal gland) and any other studies 
required for tumor imaging will be done at Screening, every 42 days (-3/+7 days) (starting from 
Day 1 Cycle 1), and End-of-Treatment, until documented progression of disease, withdrawal of 
consent, lost to follow-up, death, or termination of the study by the sponsor. The results of a 
complete chest CT scan (including base of neck and adrenal gland) performed per Standard of 
Care may be accepted and not repeated during Screening provided it was performed within 28 
days of the first dose of study drug (Cycle 1 Day 1). Those subjects entering the Follow-up 
Period without documented progression will continue to have CT scans in accordance with local 
standard of care (or approximately every 90 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death, or termination of the study by the sponsor. 
Additional CT scans may be done at any time during the study if clinically indicated. All CT
scans and reports should be archived at the site according to site regulations and copies provided 
to sponsor if requested. All posttreatment anticancer therapies will be recorded during the 
Follow-up Period.  
6.5.
Weight and Height
Weight will be obtained at Screening and at every visit during the Treatment Period before 
administration of IP. Additional measurements of weight may be collected per local standards at 
any time during the study as needed. Height will only be collected at Screening. All weight and 
height data will be collected on eCRFs.
6.6.
ECOG Performance Score
Eastern Cooperative Oncology Group performance status score will be collected at Screening, 
Day 1 of every treatment cycle, at the End-of-Treatment Visit and at the 28-day Follow-up Visit. 
Additional ECOG assessments may be performed at any time during the study as clinically 
indicated.
6.7.
Peripheral Neuropathy Assessment
Peripheral neuropathy (sensory or motor) assessment will be done at Screening, Day 1 of every 
treatment cycle, at the End-of-Treatment Visit and at the 28-day Follow-up Visit. Changes in 
neuropathy grade from baseline will be reported as an AE as per Section 11. Additional 
peripheral neuropathy assessments may be done at any time during the study as clinically 
indicated.
6.8.
Adverse Event Reporting
Adverse events will be recorded from time of signature on the ICF until 28 days after the last 
dose of IP, including any unscheduled visits. See Section 11 for details. 
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8


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
35
ABI-007-NSCL-006 Final: 29 May 2014
6.9.
Quality of Life Questionnaires
The LCSS, EORTC QLQ C30 and EQ-5D-5L questionnaires will be used to measure quality of 
life (QoL) for subjects in the study. The LCSS is comprised of 9 questions to be completed by 
the subject using a visual analogue scale (VAS) to denote intensity of a symptom. The EQ-5D-
5L comprises 5 questions on mobility, self-care, usual activities, pain/discomfort, 
anxiety/depression and a VAS for overall QoL. These questionnaires will be completed by the 
subject prior to interaction with study personnel, at Day 1 of every Cycle, at the End-of-
Treatment Visit and at the 28-day Follow-up Visit.
6.10.
Healthcare Resource Utilization Questionnaire
A healthcare resource utilization questionnaire will be used to capture the additional use of 
healthcare resources, including hospitalizations, emergency room visits, doctor or nurse visits, 
procedures, and/or additional medication during the study period. The assessment will be 
completed on Day 1 of every treatment cycle, at the End-of-Treatment Visit and at the 28-day
Follow-up Visit. 
6.11.
Laboratory Assessments
Blood for hematology and chemistry evaluation will be collected as per Table 3, Table of Events. 
Blood for hematology will be collected at Screening, Days 1, 8, and 15 of every treatment cycle, 
at the End-of-Treatment Visit and at the 28-day Follow-up Visit. Blood for serum chemistry will 
be collected at Screening, Day 1 of every treatment cycle, at the End-of-Treatment Visit and at 
the 28-day Follow-up Visit. Additional laboratory samples for safety may be collected as 
clinically indicated. 
All scheduled laboratory samples will be sent to a central laboratory for analysis. Local 
hematology and chemistry tests may be performed as required for subject management/treatment 
decisions. Local laboratory values that are considered abnormal and clinically significant will be 
recorded as an AE/SAE and also recorded on the laboratory eCRF (see Section 11.3).   
Abnormal and clinically significant laboratory assessments at Screening will be recorded as 
medical history, and after Screening, as AE or SAE (clinically significant laboratory 
abnormalities at Screening may result in a subject being ineligible for the study and should not 
be captured as an AE). 
Any abnormal values that persist should be followed at the discretion of the investigator. The 
investigator should file all copies of the reports, including faxes with the subject’s medical chart.
6.12.
Tumor Tissue Sample Collection and Peripheral Blood Collection
(Exploratory Assessments) 
Histologically or cytologically confirmed advanced nonsquamous NSCLC is a required inclusion 
criteria for entry into this study.  If a subject’s previously collected tumor tissue (also known as 
archival tumor) is available, these samples will be collected for biomarker testing as detailed 
below at Cycle 1 Day 1.  If such samples do not exist, have been depleted, or do not contain 
sufficient tumor material to be analyzed, this will not preclude participation in the study and a 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
36
ABI-007-NSCL-006 Final: 29 May 2014
new biopsy or other procedure to collect tumor tissue will not be required.  Table 4 delineates the 
specific requirements for commonly encountered  archival tumor types.
Table 4:
Requirements for Collection Based on Archival Tumor Sample Type
Sample Type
Amount to Collect
Collection 
Requirement for 
Biomarkers
Comments/ Exceptions
Core biopsy or surgical 
specimen
10 slides ≥4 ∀M 
thickness. If a block is 
provided, a core of 
viable tumor will also 
be collected.
Mandatory if the sample 
exists. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Fine needle aspirates 
(FNA)
10 slides ≥4 ∀M. If a 
block is provided, a 
core of viable tumor 
will also be collected. 
Mandatory if the sample 
exists, unless a core 
biopsy or surgical 
sample was provided. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Transbronchial 
endoscopy samples
10 slides ≥4 ∀M. If a 
block is provided, a 
core of viable tumor 
will also be collected.
Mandatory if the sample 
exists, unless a core 
biopsy or surgical 
sample was provided. 
If the quantity of material 
is not sufficient, the 
available amount will be 
collected.
Bronchial lavage, 
sputum, or other
sample types
Slides or blocks 
representing >100,000 
tumor cells
Collection is strongly 
encouraged when these 
samples contain 
sufficient material.
Collection is strongly 
encouraged when these 
samples contain sufficient 
material.
In addition, test results for tumor mutational status of genes, including but not limited to EGFR,
ALK, and KRAS will be collected and recorded on eCRF if these tests have been performed.
Plasma for cell-free nucleic acids analyses will be collected on Cycle 1 Day 1 prior to first dose 
of IP, as will a sample of whole blood or peripheral blood mononuclear cells for a germ-line 
reference comparison. Types of techniques planned to be used for tumor and plasma analyses 
include:
!
Gene expression by RNA sequencing
!
Immunohistochemistry 
!
DNA sequencing
!
DNA methylation profiling
Details regarding the collection, storage, and shipment of the samples are given in the Laboratory 
Manual.
6.13.
Electrocardiogram
Electrocardiograms (ECGs) will be done at Screening and as per standard of care during the 
Treatment Period, and as clinically indicated. Results will be collected in the eCRFs as AE or 
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ails regardi
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13.
13


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
37
ABI-007-NSCL-006 Final: 29 May 2014
SAE only if results are abnormal, changed and clinically significant, unless the finding is already 
documented in medical history.
6.14.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI)
A CT scan of the head, or preferably brain MRI, will be done as per standard of care at 
Screening, during the Treatment Period, and as clinically indicated. If CT scans show lesions 
pertinent for RECIST 1.1 criteria evaluation, data will be collected on the pertinent tumor 
evaluation eCRFs.
6.15.
Bone Scans and X-rays
Bone scans and x-rays will be done as per standard of care at Screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs. If bone scans or X-
rays show lesions pertinent for RECIST 1.1 criteria evaluation, data will be collected on the 
pertinent tumor evaluation eCRFs.
6.16.
Physical Examinations
Physical examinations will be done at Screening and as per standard of care during the 
Treatment Period, and as clinically indicated. Results will be collected in the eCRFs as AE or 
SAE only if results are abnormal and clinically significant.
6.17.
Vital Signs
Vital signs will be done at Screening and as per standard of care during the Treatment Period, 
and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if results 
are abnormal and clinically significant.
6.18.
Survival 
After the End-of-Treatment Visit, the subjects will have a 28-day Follow-up Visit followed by a 
phone call approximately every 90 days (+/- 14 days) for at least 12 months after the last subject 
is randomized or 120 PFS events have been observed whichever comes later. The subjects will 
also be asked questions about other medications they may be taking for their NSCLC. Those 
subjects entering the Follow-up Period without documented progression will continue to have 
CT scans in accordance with local standard of care (or approximately every 90 days) until 
documented progression of disease, withdrawal of consent, lost to follow-up, death, or 
termination of the study by the sponsor.
&(/*(1(35235,(7$5<,1)250$7,21
reatment
reatment
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
38
ABI-007-NSCL-006 Final: 29 May 2014
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Male and female subjects with advanced nonsquamous NSCLC who have received one 
platinum-containing chemotherapy regimen for their advanced disease will be eligible for this 
study. The study will randomize approximately 160 subjects. The study will be conducted at 
approximately 30 to 60 sites in the United States, Canada, and Europe.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be randomized in the study:
1. Age ≥ 18 years at the time of signing the ICF.
2. Understand and voluntarily provide written informed consent prior to the conduct of any 
study related assessments/procedures.  
3. Able to adhere to the study visit schedule and other protocol requirements
4. Histologically or cytologically confirmed advanced nonsquamous NSCLC.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease (defined by the presence of 
≥1 radiographically documented measurable lesion).
7. One prior platinum-containing chemotherapy for the treatment of advanced disease.
8. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
9. Platelets ≥ 100,000 cells/mm3.
10. Hemoglobin (Hgb) ≥ 9 g/dL.
11. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and 
alanine transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper 
limit of normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
12. Total bilirubin ≤ 1.5 ULN  (unless there is a known history of Gilberts Syndrome).
13. Serum creatinine ≤1.5 x ULN, or calculated creatinine clearance ≥60 mL/min (if renal 
impairment is suspected 24-hour urine collection for measurement is required).
14. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
15. Females of childbearing potential [defined as a sexually mature woman who (1) have not 
undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy 
(the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for 
at least 24 consecutive months (ie, has had menses at any time during the preceding 24 
consecutive months)] must:
a.
Have a negative pregnancy test (ß-hCG) as verified by the study doctor within 72 
hours prior to starting study therapy. She must agree to ongoing pregnancy testing 
o th
the cond
cond
requiremen
equiremen
squamous 
squam
N
ncer therap
cer therap
se (defined
se (define
lesio
lesion).
rapy
rapy f
y or the
or the
f
500
00 cells/m
cells/m
(AST/serum
AST/serum
(ALT/seru
(ALT/seru
nge (ULN) 
e (ULN) 
≤1.5 
1.5 ULN
U
atinine
tinine ≤1
ment is susp
ment is su
stern Coope
ern Coop
Females o
Females o
underg
underg
(the
(the
a


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-006 Final: 29 May 2014
during the course of the study, and after end of study therapy. This applies even if the 
subject practices true abstinence* from heterosexual contact.
b. Either commit to true abstinence* from heterosexual contact (which must be reviewed 
on a monthly basis) or agree to use, and be able to comply with, effective 
contraception without interruption, 28 days prior to starting IP, during the study 
therapy (including dose interruptions), and for 3 months after discontinuation of study 
therapy. 
Male subjects must:
a.
Practice true abstinence* or agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the study, 
during dose interruptions and for at least 6 months following IP discontinuation, even 
if he has undergone a successful vasectomy. 
16. Females must abstain from breastfeeding during study participation and 3 months after IP 
discontinuation. 
7.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. Squamous cell NSCLC.
2. Prior taxane therapy.    
3. Evidence of active brain metastases, including leptomeningeal involvement (prior 
evidence of brain metastasis are permitted only if asymptomatic and clinically stable for 
at least 8 weeks following completion of therapy). MRI of the brain (or CT scan 
w/contrast) is preferred.   
4. Only evidence of disease is non-measurable.
5. Known EGFR mutation.
6. Known EML4-ALK mutation.
7. Preexisting peripheral neuropathy of Grade > 2 (per NCI CTCAE v4.0).
8. Venous thromboembolism within 1 month prior to Cycle 1 Day 1.
9. Current congestive heart failure (New York Heart Association Class II-IV).
10. History of the following within 6 months prior to Cycle 1 Day 1: a myocardial infarction, 
severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart
Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically 
significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG)
abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder.
11. Known hepatitis B or C virus (HBV/HCV) infection, known history of human 
immunodeficiency virus (HIV) infection, or receiving immunosuppressive or 
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic 
abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception].
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the study,
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
40
ABI-007-NSCL-006 Final: 29 May 2014
myelosuppressive medications that would in the opinion of the investigator, increase the 
risk of serious neutropenic complications.
12. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, 
defined as ongoing signs/symptoms related to the infection without improvement despite 
appropriate antibiotics, antiviral therapy, and/or other treatment.
13. History of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or 
pulmonary hypersensitivity pneumonitis.
14. Subject has a clinically significant malabsorption syndrome, persistent diarrhea, or 
known sub-acute bowel obstruction > NCI CTCAE Grade 2, despite medical 
management.
15. Treatment with any investigational product within 28 days prior to signing the ICF.
16. History of or suspected allergy to nab-paclitaxel, azacitidine, human albumin or 
mannitol.
17. Currently enrolled in any other clinical protocol or investigational trial that involves
administration of experimental therapy and/or therapeutic devices.
18. Any other clinically significant medical condition, psychiatric illness, and/or organ 
dysfunction that will interfere with the administration of the therapy according to this 
protocol or which, in the views of investigator, preclude combination chemotherapy.
19. Any other malignancy within 5 years prior to randomization, or advanced malignant 
hepatic tumors, with the exception of adequately treated squamous cell carcinoma of the 
skin, in-situ carcinoma of the cervix, uteri, non-melanomatous skin cancer, carcinoma in 
situ of the breast, or incidental histological finding of prostate cancer (TNM 
Classification of Malignant Tumours (TNM) stage of T1a or T1b). (All treatment of 
which should have been completed 6 months prior to signing ICF).
20. Any condition including the presence of laboratory abnormalities, which places the 
subject at unacceptable risk if he/she were to participate in the study.
21. Any medical condition that confounds the ability to interpret data from the study.
22. Pregnant or breastfeeding females.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
41
ABI-007-NSCL-006 Final: 29 May 2014
8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Investigational Products
Subjects will receive open-label nab-paclitaxel / CC-486 or nab-paclitaxel monotherapy during 
the Treatment Period of the study. The nab-paclitaxel and CC-486 are designated as IP and will 
be packaged and supplied by Celgene Corporation.
The reconstitution and IV administration of nab-paclitaxel should follow the local Prescribing 
Information for Abraxane.
8.1.1.
nab-Paclitaxel
nab-Paclitaxel will be supplied by the sponsor, Celgene Corporation, in single-use vials in single 
count cartons. Each single-use 50 mL vial will contain paclitaxel (100 mg) and human albumin 
as a stabilizer.
Please see local prescribing information for Abraxane for detailed instructions on the 
reconstitution, storage conditions and IV administration of nab-paclitaxel. Reconstituted nab-
paclitaxel should be stored in an area accessible only to study personnel.
Temperature records for nab-paclitaxel must be made available to Celgene or other sponsor-
nominated monitoring teams for verification of proper IP storage.
8.1.2.
CC-486 (Azacitidine for Oral Administration)
Celgene Corporation will supply azacitidine 100 mg tablets for oral administration. Each tablet is 
formulated using excipients that are generally regarded as safe and are used in marketed drug 
products.
All tablets will be packaged in blister cards. Only sufficient IP for one cycle of treatment will be 
provided to each subject at the start of each treatment cycle. All tablets should be swallowed 
whole, and should not be broken or chewed. CC-486 may be taken on an empty stomach or with 
food. Subjects should drink 8 ounces (240 mL) of room temperature water with each dose. It is 
strongly recommended that all subjects receive a dose of a prophylactic antiemetic, preferably a 
5-HT3 antagonist, approximately 30 minutes prior to each dose of CC-486.
The IP must be stored as directed on package label at controlled temperature and a temperature 
log must be maintained in the source documents The storage area should be secure and have 
access limited to study personnel. 
8.2.
Treatment Administration and Schedule
Approximately 160 subjects will be treated with nab-paclitaxel / CC-486 or nab-paclitaxel
monotherapy until disease progression, development of an unacceptable toxicity, death, lost to 
follow-up, withdrawal of consent, or termination of the study by the sponsor:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 8 and 15 and CC-486 
200 mg orally QD on Days 1 to 14 of each 21-day treatment  cycle  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
42
ABI-007-NSCL-006 Final: 29 May 2014
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day treatment  cycle
8.3.
Dose Omissions and Modifications
8.3.1.
Rules for Dose Omissions and Modified Schedules
nab-Paclitaxel Monotherapy Arm
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
!
Day 1 Dose Missed
If the dose held or missed was to be given on Day 1 of the next cycle, that next cycle will 
not be considered to start until the day the first dose is actually administered to the 
subject (ie, D1-D8-Rest, X-D1-D8-Rest, etc).
!
Day 8 Dose Missed
That dose will be skipped.  Next dose (if laboratory results permit) will be Day 1 of the 
next scheduled cycle (ie, D1-X-Rest, D1-D8-Rest, etc).
nab-Paclitaxel/CC-486 Combination Arm
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered plus or minus 2 days from the scheduled date.
If any doses of CC-486 are missed, skip that day and resume as appropriate, do not double up on
subsequent days.
For nab-paclitaxel: 
!
Day 8 Dose Missed
That dose will be skipped. Next dose (if laboratory results permit) will be at Day 15 (ie, 
Rest-X-D15, Rest-D8-D15, etc).
!
Day 15 Dose Missed
That dose will be skipped.  Next dose (if laboratory results permit) will be Day 8 of the 
next scheduled cycle (ie, Rest-D8-X, Rest-D8-D15, etc).
8.3.2.
Rules for Dose Modifications
Subjects who experience any of the adverse drug reactions in Table 5 will be dose reduced as per 
Table 5 during treatment. 
nab-Paclitaxel Monotherapy Arm
!
Do not administer nab-paclitaxel on Day 1 of a cycle until ANC is at least 
1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment until 
counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and platelet 
count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil count of at least 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
43
ABI-007-NSCL-006 Final: 29 May 2014
500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Day 8 of the cycle. 
Upon resumption of dosing, permanently reduce nab-paclitaxel doses as outlined in 
Table 5.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-paclitaxel 
at reduced doses (Table 5) when peripheral neuropathy improves to Grade 1 or 
completely resolves.
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to 
the guidelines in Table 5. For any other Grade 3 or 4 nonhematologic toxicity or other 
investigator defined unacceptable toxicity, interrupt treatment until the toxicity 
improves to ≤Grade 2, then restart treatment according to the guidelines in Table 5.
Re-escalation is not permitted at any time. 
nab-Paclitaxel/CC-486 Combination Arm
!
Do not administer nab-paclitaxel on Day 8 or CC-486 on Day 1 or 8 of a cycle until ANC 
is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment until 
counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and platelet 
count of at least 100,000 cells/mm3 on Day 1 and 8 for CC-486 and Day 8 for nab-
paclitaxel or to an absolute neutrophil count of at least 500 cells/mm3 and platelet count 
of at least 50,000 cells/mm3 on Day 15 of the cycle for nab-paclitaxel. Upon resumption 
of dosing, permanently reduce nab-paclitaxel and/or CC-486 doses as outlined in Table 5.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy (CC-486 does not need 
to be withheld). Resume nab-paclitaxel at reduced doses (Table 5) when peripheral 
neuropathy improves to Grade 1 or completely resolves. 
!
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, interrupt 
treatment until the toxicity improves to ≤Grade 1, then restart treatment according to 
the guidelines in Table 5. For any other Grade 3 or 4 nonhematologic toxicity or 
other investigator defined unacceptable toxicity, interrupt treatment until the toxicity 
improves to ≤Grade 2, then restart treatment according to the guidelines in Table 5.
Re-escalation is not permitted at any time. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
44
ABI-007-NSCL-006 Final: 29 May 2014
Table 5:
Permanent Dose Reductions for Hematologic and Nonhematologic Toxicities and Dosing on the Study
Dose Modification During Treatment
Adverse Drug Reaction
Occurrence
Monotherapy Arm: nab-
paclitaxel Dose (mg/m2)
Combination Arm: nab-
paclitaxel Dose (mg/m2) / 
CC-486 Dose (mg)
Neutropenic Fever (ANC < 500/mm3 with fever >38°C)
OR
Delay of next cycle by > 7 days for ANC < 1500/mm3
OR
ANC < 500/mm3 for > 7 days
First
75
100/100
Second
50
75/100
Third
Discontinue Treatment*
50/100
Fourth
NA
Discontinue Treatment*
Platelet count < 50,000/mm3
First
75
100/100
Second
Discontinue Treatment*
75/100
Third
NA
Discontinue Treatment*
Peripheral Neuropathy Grade ≥3
First
75
75/200
Second
50
50/200
Third
Discontinue Treatment*
Grade 2 or 3 Cutaneous toxicity
Grade 3 Diarrhea
Grade 3 Mucositis
Any other Grade 3 or 4 nonhematologic toxicity or other 
investigator defined unacceptable toxicity
First
75
100/100
Second
50
75/100
Third
Discontinue Treatment*
50/100
Fourth
NA
Discontinue Treatment*
Grade 4 Cutaneous toxicity, Diarrhea or Mucositis
First
Discontinue Treatment*
ANC = absolute neutrophil count; AUC = area under the curve; NA = not applicable.
* If an adverse event that requires dose reduction recurs after the dose has been reduced according to the table  above , the subject should generally have 
treatment discontinued unless, at the discretion of the investigator, there is evidence of continuing benefit to the subject that outweighs the risk of recurrent 
toxicity.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
45
ABI-007-NSCL-006 Final: 29 May 2014
8.4.
Method of Treatment Assignment
The Treatment Period of the study is open-label. Enrollment/randomization will occur 1:1 via 
IRT. 
8.5.
Packaging and Labeling
The label(s) for all IP will include sponsor name, address and telephone number, the protocol 
number, IP name, dosage form and strength (where applicable), amount of IP per container, lot 
number, expiry date (where applicable), medication identification/kit number, dosing 
instructions, storage conditions, and required caution statements and/or regulatory statements as 
applicable. Additional information may be included on the label as applicable per local 
regulations.
8.6.
Investigational Product Accountability and Disposal
Celgene (or designee) will review with the investigator and relevant site personnel the process 
for IP return, disposal, and/or destruction including responsibilities for the site versus the 
responsibilities of Celgene (or designee).
Celgene will instruct the investigator on the return, disposal and/or destruction of IP. Only 
completely unused IP vials should be retained by the site until a representative from Celgene or 
other Celgene-designated personnel have completed an inventory. Partially used and completely 
used vials should be destroyed according to local guidelines, and disposition should be recorded 
on the Investigational Drug Accountability Record Form.
The investigator(s) or designee(s) is responsible for accounting for all IP that is issued to and
returned by the subject during the course of the study according to applicable regulatory
requirements. Any unused CC-486 must be returned by a study subject and retained by the
investigative site for accountability to be conducted by a Celgene representative (or designee). If
any IP is lost or damaged, its disposition should be documented. At the periodic monitoring
visits, a Celgene representative (or designee) will conduct IP accountability and address any
discrepancies. Upon unsatisfactory reconciliation of all IP, returned IP may be destroyed. At the
conclusion of the study, all remaining IP will be counted, reconciled with dispensing records, 
documented, and destroyed at the clinic site or allocated drug destruction location after
completion of drug accountability by a Celgene representative (or designee). The Celgene
representative (or designee) will ensure that a final report of drug accountability to the unit dose
level (ie, tablet) is prepared and placed in both the investigator study file and the central clinical
study file.
Investigational product will not be loaned or dispensed by the investigator to another investigator 
or site. Under certain circumstances, and with sponsor permission, cooperative groups may 
manage IP between locations within their network as clinical trial agreement and local guidelines 
permit.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
46
ABI-007-NSCL-006 Final: 29 May 2014
8.7.
Investigational Product Compliance
All IP will be administered only by study site personnel and accurate recording of all IP 
administration will be made in the appropriate section of the subject’s eCRF and source 
documents.
8.8.
Overdose
Overdose, as defined for this protocol, refers to nab-paclitaxel and CC-486 dosing.
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel or CC-486 to a given subject, regardless of any associated adverse events or sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. See 
Section 11.1 for the reporting of adverse events associated with overdose.
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('06'RF1XPEHU
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9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
Over the course of this study, additional medications may be required to manage aspects of the 
disease state of the subjects, including side effects from study treatments or disease recurrence. 
All supportive care (including but not limited to growth factors, antiemetics, analgesics, 
zolendronic acid, denosumab) is permitted as per the investigator’s discretion and should be 
administered according to local institutional practice. All concomitant treatments, including 
blood and blood products, must be reported on the eCRF.
!
Antiemetics are not required during the study; however, it is strongly recommended 
that all subjects receive a dose of a prophylactic antiemetic, preferably a 5-HT3 
antagonist, approximately 30 minutes prior to each dose of CC-486.
!
Stable, therapeutic doses of anticoagulants are permitted; however, subjects on 
warfarin should have prothrombin time (PT) or international normalized ratio (INR)
and partial thromboplastin time (PTT) monitored as clinically indicated.
!
Subjects on erythropoietin or darbepoetin alfa for at least 4 weeks prior to starting the 
IP may continue their pretreatment doses throughout the study.
#
Note: If the subject is not on a stable dose of an erythropoiesis-stimulating agents 
(ESA) prior to study entry, the subject may not start an ESA during Cycle 1. 
However, medications such as ESAs, granulocyte colony-stimulating factors (G-
CSFs), etc., may be administered according to standard of care after Cycle 1.
!
Use of white blood cell growth factors (eg, filgrastim, G-CSF for the treatment of 
subjects with neutropenic fever is permitted at the investigator’s discretion. Use of 
filgrastim rather than pegylated-filgrastim is indicated, because of the 14 day delay 
of the next cycle following treatment with peg-filgrastim.
!
Use of white blood cell growth factors (eg, filgrastim, G-CSF) for secondary
prophylaxis in subjects who experienced a neutropenic complication from a prior
cycle of chemotherapy (for which primary prophylaxis was not received) is permitted.
!
Flu vaccination is permitted.
!
Suppressive antiviral therapy (eg, entecavir, tenofovir, or lamivudine) is
recommended for subjects with chronic HBV infection (eg, those who are HBsAg
positive).
!
Routine infectious disease prophylaxis is not recommended, however, antibiotic,
antiviral, antipneumocystis, antifungal, or other prophylaxis may be implemented
during the study at the discretion of the investigator.
!
Treatments with bisphosphonates (eg, pamidronate, zolendronate), or other agents
(eg, denosumab) to prevent or delay progression of bone metastases are permitted.
Maintenance of a stable dosing regimen throughout the study is recommended.
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!
Subjects may receive physiologic replacement doses of glucocorticoids as
maintenance therapy for adrenal insufficiency. Glucocorticoids may be administered
as an antiemetic with IV chemotherapy, if directed by local standard of care.
!
Treatment with antidiarrheal medications is recommended at the first sign of diarrhea
as per the guidelines in Appendix B. Pre-medication with antidiarrheal medication for 
subsequent doses of CC-486 may be appropriate.
9.2.
Prohibited Concomitant Medications and Procedures
Other investigational therapies must not be used while the subject is enrolled in the study.
Anticancer therapy (chemotherapy, biologic or investigational therapy, and surgery) other than
the study treatments must not be given to subjects during the study. If such treatment is required,
the subject must be discontinued from the study. Focal palliative radiotherapy for treatment of
cancer-related symptoms is allowed during study treatment at the discretion of the investigator.
The administration of either α-interferon and/or ribavirin, or drugs with known renal toxicity is
prohibited during study treatment.
9.3.
Required Concomitant Medications and Procedures for Patients 
Receiving CC-486
If a subject experiences ≥Grade 3 neutropenia, that subject will be treated with G-CSF 5 ∀g/kg 
daily until the ANC ≥2000/mm3. In subsequent cycles, that subject should receive G-CSF 
5∀g/kg daily beginning on Day 16 and continuing until the ANC ≥2000/mm3. In subjects
receiving G-CSF, the next cycle should begin no sooner than 48 hours after discontinuation of G-
CSF. Data regarding G-CSF administration should be recorded on the eCRF provided for G-CSF 
administration.
9.3.1.
Description of G-CSF
This medication stimulates the blood system (bone marrow) to make white blood cells, helping
fight infections. This medication is given to those whose ability to make white blood cells has
been reduced. Filgrastim (also known as G-CSF, or granulocyte colony stimulating factor) is a
man-made version of a certain natural substance found in the body. It is produced using a certain
bacteria. It will be obtained commercially and relabeled as clinical supplies. It should be stored,
and administered according to the manufacturer’s recommendation.
9.3.2.
Administration of G-CSF
For subjects who experience Grade ≥3 neutropenia, G-CSF 5 ∀g/kg daily will be administered
subcutaneously. During any cycle when Grade ≥3 neutropenia occurs, CC-486 and other 
cytotoxic agents will be held, and G-CSF will begin immediately (a minimum of 24 hours after 
the last dose of CC-486 and chemotherapy). In subsequent cycles, G-CSF will begin on Day 16. 
G-CSF will continue daily until the ANC ≥2000/mm3. For complete details on drug
administration, storage, clinical pharmacology, and the human PK of G-CSF (filgrastim), please
see the G-CSF(filgrastim) package insert.
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er than
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10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the study are described 
below.  Additional analyses of these endpoints as well as exploratory endpoints or subgroup 
analyses will be described in detail in the SAP.  The SAP supersedes the analyses described in 
the protocol should there be differences between the two.
Evaluations of the study endpoints will be based primarily on the point estimates and the 
associated 95% confidence intervals of the within- and between-treatment differences. However, 
statistical tests may be conducted and the nominal p-values may be provided in the clinical study 
report to indicate the strength of the treatment differences evaluated.
10.1.
Overview
Approximately 160 subjects will be randomized in a 1:1 ratio to two treatment arms (80 subjects 
per group). Arm A will receive nab-paclitaxel with epigenetic modifying therapy of CC-486 and 
Arm B will receive nab-paclitaxel as a monotherapy.  Both regimens will be administered in 21-
day cycles. All subjects will receive the assigned study treatment until disease progression, 
unacceptable toxicity, death, lost to follow-up, withdrawal of consent, or termination of the 
study by the sponsor, in accordance with local standard of care.  A permuted-block 
randomization method will be employed, and the randomization will be carried out centrally 
using an IRT system. The randomization will be stratified based on the following baseline
factors: 
!
ECOG performance status (0 versus 1)
!
Gender (males versus females)
!
Smoker (yes versus no)
A DMC will be used to review the safety and efficacy data during the study.   
10.2.
Study Population Definitions
10.2.1.
Intent-to-treat Population
The primary efficacy analysis will be performed on the intent-to-treat (ITT) population, which 
includes all randomized subjects regardless of whether the subject receives any IP or has any 
efficacy assessments performed. 
10.2.2.
Per-protocol (PP) Population
The PP population is defined as all eligible subjects randomized who receive at least one dose of 
the IP and have been treated in the arm they were assigned.  Additional analyses utilizing the PP 
population will be described in the SAP.
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ever,
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the IP
IP and 
and 
opu
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lat


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10.2.3.
Treated Population
The treated population will consist of all randomized subjects who receive at least one dose of 
IP. The safety analyses will be based on the treatment as received if different from the assigned 
treatment by randomization.
10.3.
Sample Size and Power Considerations
The primary objective of this study is to evaluate the efficacy of the CC-486/nab-paclitaxel 
combination therapy and that of the nab-paclitaxel monotherapy, and the relative efficacy of 
these two treatment regimens. 
The effect of the two treatment regimens with respect to the efficacy endpoints will be based on 
the point estimates and the associated 95% confidence intervals. The sample size was chosen to 
support the estimation of the within- and between-treatment effects with reasonable precision. 
Table 6 below summarizes the two-sided 95% confidence intervals for a range of hypothetical
observed disease control rates given a sample size of 80 subjects in a treatment arm. If the 
observed disease control rate is 0.30, then the actual width of the 2-sided 95% confidence 
interval is 0.21 (95% CI is [0.20, 0.41]).
Table 6:
Disease Control Rate –Two-Sided 95% Confidence Interval of Hypothetical 
Disease Control Rate with a Sample Size of 80 Subjects in a Treatment Arm
Hypothetical Observed Disease 
Control Rate
Half Width of 95% Confidence 
Interval
95% Confidence Intervala
0.20
0.186
(0.119, 0.304)
0.25
0.199
(0.16, 0.359)
0.30
0.21
(0.203, 0.413)
0.35
0.218
(0.247, 0.465
0.40
0.224
(0.292, 0.516)
0.45
0.227
(0.338, 0.565)
0.50
0.228
(0.386, 0.614)
a Based on the Clopper-Pearson exact method.
Table 7 below summarizes the precision that can be achieved given different scenarios of 
hypothetical observed hazard ratios between the two treatment arms for PFS events, assuming a 
total of 120 events are observed. 
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based on
based on
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ange
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86
(7$
0.199
0.199
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0.21
5,
0
35
23
52
35
35
35
( 35
earson exact 
earson exa
summarize
summari
observed 
observed h
20 events a
events a


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Table 7:
Progression-Free Survival – Two-Sided 95% Confidence Interval of 
Hypothetical Observed Hazard Ratio between Treatment Arms
Hypothetical Number of Events 
Observed
Hypothetical Observed Hazard 
Ratio of PFS Events
95% Confidence Interval of 
Hazard Ratioa
120
0.60
(0.42, 0.86)
0.65
(0.45, 0.93)
0.70
(0.49, 1.00)
a Assuming a standard error of 0.18 for the log hazard ratio.
Assuming the median times of PFS are 4.17 and 2.5 months, respectively, for the nab-
paclitaxel/CC-486
combination therapy
and nab-paclitaxel monotherapy arms, and an 
approximate 24 months accrual period for a total of 160 subjects, it is estimated that a total of 
120 PFS events will have been observed approximately 2 months after the last subject is 
randomized, assuming an exponential distribution for PFS. 
Of note, with 120 PFS events, this study has an 80% power (1-sided, Type-1 error of 2.5%)  to 
detect a HR of 0.60 for PFS improvement with the nab-paclitaxel/CC-486 arm over the nab-
paclitaxel monotherapy arm.    
One nonbinding interim analysis for PFS with an early stopping rule for futility will be 
conducted when approximately 60 events are observed. The nab-paclitaxel/CC-486 combination 
arm of the study may be stopped early for futility if the observed HR is > 1.10 given an 
approximate 60 PFS events have occurred at the time of the interim analysis. A HR> 1.10 when 
half of the target events of 120 have occurred signals a low probability for observing a 
meaningful difference in favor of the nab-paclitaxel/CC-486 combination therapy should the 
study continue to the end. With the assumptions stated above, it will take approximately 16 
months from the first subject randomized to observe approximately 60 PFS events for the interim 
analysis.    
If futility is declared, enrollment in the monotherapy nab-paclitaxel arm will continue up to a 
total of 80 subjects. 
Disease control rate, OS, and ORR will be evaluated within each treatment arm and between the 
treatment arms at the time of the final analysis of the PFS endpoint when approximately 120 PFS 
events have been observed.  
All subjects will continue to be followed for OS up to 12 months after the last subject is 
randomized or 120 PFS events have been observed, whichever comes later.
10.4.
Background and Demographic Characteristics
The baseline characteristics of all randomized subjects will be summarized. Subject’s age, 
height, weight, and baseline characteristics will be summarized using descriptive statistics, while 
gender, race and other categorical variables will be provided using frequency tabulations. 
Selected medical history data will be summarized using frequency tabulations by system organ 
class and preferred term.
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ime of the
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signals a lo
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observed
will cont
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or 120 P
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10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both Treatment 
and Follow-up Periods. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
10.6.
Efficacy Analysis
10.6.1.
Primary Efficacy Endpoints 
The primary efficacy endpoint is progression-free survival, which is defined as the time from the 
date of randomization to the date of disease progression or death (any cause) on or prior to the 
data cutoff date for analyses, whichever occurs first, based on the investigator’s assessment of 
the data from CT scans using RECIST 1.1 guidelines. Baseline tumor measurements will be 
determined from the radiologic evaluation performed within 28 days before the start of study 
therapy. 
Subjects who do not have disease progression and are alive as of the data cutoff date for the 
statistical analysis will be censored at the date of the last radiologic assessment prior to the data 
cutoff date.  Similarly, subjects who discontinue from the study prior to disease progression or 
death will be censored at the date of the last radiologic assessment prior to the data cutoff date.  
In the event that a new anticancer treatment occurs prior to documented progression, the subject 
will be censored at the date of the last radiologic assessment where the subject was documented 
to be progression-free prior to the new anticancer treatment. Subjects with a single missing 
radiologic assessment prior to a visit with documented disease progression (or death) will be 
analyzed as a PFS event at the date of the radiologic assessment that shows progression or death 
(whichever is earlier). Subjects with two or more missing radiologic assessments prior to a visit 
with documented disease progression (or death) will be censored at the date of the last radiologic 
assessment where the subject was documented to be progression-free prior to the first of the two 
missing visits.  Subjects who drop out early or die without any postbaseline radiologic tumor 
assessment will be censored on the date of randomization. 
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% CI) for each treatment arm. The Kaplan-Meier curve for PFS will 
be presented graphically for each treatment arm. The relative treatment effect between the 
combination and monotherapy arms on PFS will be estimated by the hazard ratio (HR) and the 
associated two-sided 95% CIs using the stratified Cox proportional hazard model with ECOG 
performance status (0 versus 1), gender (males versus females), and smoker (yes versus no) as 
the stratification factors, given the number of events in each cell is adequate.  No statistical 
inferential tests will be performed.
To assess the impact on PFS of radiologic assessments not occurring at the regularly scheduled 
assessment times, the frequency of these unscheduled/off-scheduled assessments will be 
presented for each treatment arm. In addition, confirmatory and sensitivity analyses will be 
performed to further assess the impact of missed radiologic assessments. An additional analysis 
of PFS, where death or new treatment will be considered as an event, will be conducted to 
address the impact of next line therapy. 
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10.6.2.
Secondary Efficacy Endpoints
10.6.2.1.
Disease Control Rate
Disease control rate is defined as the percent of subjects who have a radiologic complete 
response, partial response, or stable disease according to RECIST 1.1 guidelines, as determined 
by the investigator.
Disease control rate for each treatment arm will be summarized by the observed DCR rate and 
the associated two-sided 95% CI. The relative treatment effect will be summarized by the 
absolute difference and ratio of the response rates and the associated two-sided 95% CI.    
10.6.2.2.
Overall Survival
Overall survival is defined as the time between randomization and death. All deaths, regardless 
of the cause of death, will be included. All subjects who are lost to follow-up prior to the end of
the study or who are withdrawn from the study will be censored at the time of last contact. 
Subjects who are still receiving treatment as of the data cutoff date will be censored at the cutoff 
date. Overall survival will be analyzed in a similar manner as that for PFS.
10.6.2.3.
Overall Response Rate 
Overall response rate is defined as the percent of subjects who have a radiologic complete or 
partial response according to RECIST 1.1 guidelines determined by the investigator.  
Overall response rate will be assessed using the same statistical methods as those for the DCR 
endpoint.    
10.6.3.
Exploratory Endpoints
10.6.3.1.
HealthCare Utilization 
Healthcare utilization will be summarized by treatment. Additional analyses will be described in 
detail in the SAP.
10.6.3.2.
Quality of Life Questionnaires
The score or VAS value and the corresponding change from baseline at each timepoint will be 
summarized by treatment for the EQ-5D-5L, EORTC QLQ C30 and LCSS questionnaires. 
Additional analyses will be described in detail in the SAP. 
10.6.3.3.
Biomarker, Tumor Characteristics, and Genomic Analyses 
Statistical analysis of the biomarkers, tumor characteristics, and genomic correlates will be 
described in a SAP separate from that described above.
10.7.
Safety Analysis
The treated population, which includes all randomized subjects who receive at least one dose of 
IP, will be the analysis population for all safety analyses.
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hs, regardle
s, regardl
pririor to the 
or to th
of last cont
of last con
e censored
e censo
PFS.
FS.
ho ha
ho have
v a ra
a r
rmined by
rmined by
statist
statistical
ical
marized by t
rized by 
Questionn
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e and the c
e and the c
ment f
ent for th
or t
f
ses will be
ses will be
Biomarker
Biomarker
cal analysis
cal analysis
ribed in a S
ribed in a 
&
10.7.
10
e tr


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The safety/tolerability of the two treatment arms will be monitored through continuous reporting 
and evaluated by adverse events and serious adverse events, and incidence of subjects 
experiencing dose modifications, dose interruptions, and/or premature discontinuation of IP.
10.7.1.
Adverse Events
Adverse events will be analyzed in terms of TEAEs, defined as any AE or SAE occurring or 
worsening on or after the day of the first dose of the IP through 28 days after the last dose of IP.  
In addition, any serious AE with an onset date more than 28 days after the last dose of IP that is 
assessed by the investigator as related to IP will be considered a TEAE. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA). The severity of AEs will be graded based on NCI CTCAE, Version 4.0; 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Treatment-emergent adverse events, Grade 3 or higher TEAEs, serious AEs, TEAEs leading to 
dose reduction, dose delay, and dose interruption, TEAEs leading to treatment discontinuation, 
and TEAEs with an outcome of death will be summarized per treatment arms by MedDRA 
system organ class and preferred terms. 
Adverse events of special interest of the nab-paclitaxel/CC-486 combination and nab-paclitaxel 
monotherapy regimens identified in previous studies in a similar population may be identified 
and summarized by worst NCI CTCAE grade, System Organ Class (SOC) and MedDRA
preferred terms.
By-subject listings will be provided for all relevant safety data. Graphical displays and figures 
will be provided where useful to assist in the interpretation of results.
10.7.2.
Laboratory Assessments
Treatment group differences in each laboratory parameter with respect to the NCI CTCAE 
grades will be summarized by the frequency distribution of subjects with the AE grades.  
All laboratory parameters will be summarized by descriptive statistics within each treatment arm, 
as appropriate. 
10.7.3.
Study Drug Exposure
The extent of exposure to the IPs will be assessed based on the descriptive statistics on the 
number of cycles and IP doses administered, cumulative dose, average dose intensity, and 
percentage of protocol dose administered.  The incidences of CC-486 and nab-paclitaxel dose 
reductions, dose interruptions, and dose delays will be summarized by treatment arm.  
10.8.
Study Therapy Termination
Reasons for stopping study therapy will be presented in listings and summarized by frequency of 
occurrence and corresponding percentage of occurrence.
10.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the IP
through 28 days post last dose of the IP) and deaths that occur during the Follow-up Period will 
&(/*(1(35235,(7$5<,1)250$7,21
ties
es 
40.
TEAEs lead
EAEs lea
ent discont
ent discont
arms by M
rms by
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mbinatioio
ar populati
ar popu
an Class (
n Class (S
afet
afety y data. 
dat
rpretation o
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oratory 
oratory pa
p
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e summariz
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Exposure
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urere to the
to the IP
I
and 
and IP
IP dos
dos
protocol do
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dose interr
dose interr
Stud
tud
Reasons for 
easons for 
occurrenc
occurrenc


('06'RF1XPEHU
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ABI-007-NSCL-006 Final: 29 May 2014
be summarized by frequency of occurrence and corresponding percentage by cause of death per 
period (during treatment or follow-up). 
10.10.
Interim Analysis
One nonbinding interim analysis for PFS with an early stopping rule for futility will be 
conducted when approximately 60 events are observed. The nab-paclitaxel/CC-486 combination 
arm of the study may be stopped early for futility if the observed HR is ≥1.10 given an 
approximate 60 PFS events have occurred at the time of the interim analysis. Should this occur, 
enrollment in the monotherapy nab-paclitaxel arm will continue up to a total of 80 subjects.  
10.11.
Data Monitoring Committee
An independent DMC will be established with the responsibilities for safeguarding the interests 
of study participants and monitoring the overall conduct of the study. Final recommendations of 
the DMC will reflect the judgment of the DMC members and will be considered advisory in 
nature to the sponsor. The decision to implement the recommendations of the DMC will be made 
by the sponsor, following consultation with the coordinating investigator and Steering 
Committee.
Operational details for the DMC will be detailed in the DMC charter. 
10.12.
Scientific Steering Committee
The conduct of this study will be overseen by a Steering Committee. The Steering Committee 
will serve in an advisory capacity to the sponsor.
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11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the eCRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of NSCLC will not require reporting as 
an adverse event.
An overdose, accidental or intentional, whether or not it is associated with an AE, or abuse, 
withdrawal, sensitivity or toxicity to an investigational product should be reported as an AE.  If 
an overdose is associated with an AE, the overdose and adverse event should be reported as 
separate terms.  See Section 8.8 for the definition of overdose.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for nab-paclitaxel or   
CC-486 overdose. Actual treatment should depend on the severity of the clinical situation and 
the judgment and experience of the treating physician.
All subjects will be monitored for AEs during the study. Assessments may include monitoring of 
any or all of the following parameters: the subject’s clinical symptoms, laboratory, pathological, 
radiological or surgical findings, physical examination findings, or findings from other 
appropriate tests and procedures.
All AEs will be recorded by the investigator from the time the subject signs informed consent to
28 days after the last dose of IP, and those SAEs made known to the investigator at any time 
thereafter that are suspected of being related to IP. AEs and serious adverse events (SAEs) will 
be recorded on the AE page of the eCRF and in the subject’s source documents. All SAEs must 
be reported to Celgene Drug Safety within 24 hours of the investigator’s knowledge of the event 
by facsimile, or other appropriate method, using the SAE Report Form, or approved equivalent 
form.
11.2.
Evaluation of Adverse Events
A qualified investigator will evaluate all adverse events as to: 
11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
!
Results in death;
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!
Is life-threatening (ie, in the opinion of the investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the eCRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of or an elective procedure for a pre-existing condition 
unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
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For each SAE, the investigator will provide information on severity, start and stop dates, 
relationship to IP, action taken regarding IP, and outcome.
11.2.2.
Severity / Intensity
For both AEs and SAEs, the investigator must assess the severity/intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current active minor version of NCI CTCAE, Version 4.0
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Adverse events that are not defined in the NCI CTCAE should be evaluated for severity/intensity 
according to the following scale:
!
Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required
!
Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required
!
Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible
!
Grade 4 = Life threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable
!
Grade 5 = Death – the event results in death
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.
Seriousness, not severity, serves as a guide for defining regulatory obligations.
11.2.3.
Causality 
The investigator must determine the relationship between the administration of IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
Means a causal relationship of the adverse event to IP
administration is unlikely or remote, or other medications, 
therapeutic interventions, or underlying conditions provide a 
sufficient explanation for the observed event.
Suspected:
Means there is a reasonable possibility that the administration 
of IP caused the adverse event.  ‘Reasonable possibility’ means 
there is evidence to suggest a causal relationship between the IP
and the adverse event.
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ABI-007-NSCL-006 Final: 29 May 2014
Causality should be assessed and provided for every AE/SAE based on currently available 
information.  Causality is to be reassessed and provided as additional information becomes 
available.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP
that has not been manufactured or provided by Celgene, please provide the name of the 
manufacturer when reporting the event.
11.2.4.
Duration
For both AEs and SAEs, the investigator will provide a record of the start and stop dates of the 
event.
11.2.5.
Action Taken
The investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(eg, discontinuation or reduction of IP, as appropriate) and report if concomitant and/or 
additional treatments were given for the event. 
11.2.6.
Outcome
The investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered or death (due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or
!
is judged to be of significant clinical importance.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF. If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE.
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
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11.4.1.
Females of Childbearing Potential
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on IP, or within 3 months of the 
subject’s last dose of IP, are considered immediately reportable events. IP is to be discontinued 
immediately. The pregnancy, suspected pregnancy, or positive pregnancy test must be reported 
to Celgene Drug Safety immediately by facsimile, or other appropriate method, using the 
Pregnancy Initial Report Form, or approved equivalent form. The female subject should be 
referred to an obstetrician-gynecologist or another appropriate healthcare professional for further 
evaluation.
The investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the investigator
should report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate 
method, within 24 hours of the investigator’s knowledge of the event using the SAE Report 
Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving IP or within 
6 months of the last dose of IP, the male subject taking IP should notify the investigator, and the 
pregnant female partner should be advised to call her healthcare provider immediately. If the 
male subject is receiving IP, the IP may need to be discontinued in the male subject, but may be 
resumed later at the discretion of the investigator and medical monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The investigator is required to ensure that the data on these forms are accurate and consistent.
This requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent to at least 28 days after the last dose of IP) and 
those made known to the investigator at anytime thereafter that are suspected of being related to 
IP. SAEs occurring prior to treatment (after signing the ICF) will be captured.
The SAE report should provide a detailed description of the SAE and include a concise summary
of hospital records and other relevant documents. If a subject died and an autopsy has been 
er 
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61
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performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available. Any follow-up data will be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety.
Where required by local legislation, the investigator is responsible for informing the Independent 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The investigator must keep copies of all SAE 
information on file including correspondence with Celgene and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than five (5) business 
days. Urgent queries (eg, missing causality assessment) may be handled by phone.
11.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to nab-paclitaxel and CC-486 based on the Investigator
Brochures.
In the United States, all suspected unexpected serious adverse reactions (SUSARs) will be 
reported in an expedited manner in accordance with 21 CFR 312.32.
For countries within the European Economic Area (EEA), Celgene or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 
presentation of adverse reaction reports arising from clinical trials on investigational products for 
human use (ENTR/CT3) and also in accordance with country-specific requirements.
Celgene or its authorized representative shall notify the investigator of the following 
information: 
!
Any AE suspected of being related to the use of IP in this study or in other studies
that is both serious and unexpected (ie, SUSAR);
!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
The investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC. (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form/Completion Guidelines or to the Pregnancy Report Form/Completion Guidelines.
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12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the IP:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent
!
Death
!
Lost to follow-up
!
Protocol violation
The reason for discontinuation should be recorded in the eCRF and in the source documents.
The decision to discontinue a subject remains the responsibility of the treating physician, which
will not be delayed or refused by the sponsor. However, prior to discontinuing a subject, the
investigator may contact the Medical Monitor and forward appropriate supporting documents for 
review and discussion.
All subjects discontinued from IP for any reason will have a treatment discontinuation visit at the 
time of discontinuation and should undergo treatment discontinuation procedures.
All subjects discontinued from IP will be followed for a period of 28 days after last dose of IP
for the collection of AEs.
Additionally subjects who withdraw from or discontinue treatment should be followed for 
progressive disease (if applicable), survival and any new anticancer therapy given.
12.2.
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
study:
!
Withdrawal of consent
!
Death
!
Lost to follow-up
The following events may be considered sufficient reasons for discontinuing a subject from the 
study:
!
Adverse events(s)
!
Protocol violation
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. The investigator must notify the Medical Monitor immediately when a subject has 
been discontinued/withdrawn due to an AE (any unacceptable toxicity). All subjects who are 
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withdrawn from the study should complete all protocol-required evaluations scheduled for early 
termination at the time of withdrawal.
Since follow-up of subjects who discontinue prematurely is of particular importance, every 
attempt should be made to collect all survival information and NSCLC treatment/therapy, unless 
the subject has specifically withdrawn consent from further follow-up. The investigator must 
make every effort to obtain minimal information regarding the subject’s survival status before 
determining that the subject is lost to follow-up.
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.
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13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the investigator should contact the responsible Clinical Research
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page). This global 
Emergency Call Center is available 24 hours a day and 7 days a week. The representatives are 
responsible for obtaining your call-back information and contacting the on call Celgene/Contract 
Research Organization (CRO) Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
13.2.
Emergency Identification of Investigational Products
This is an open-label study; therefore, IP will be indentified on the package labeling. 
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14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative,
and investigator abide by Good Clinical Practice (GCP), as described in International Conference 
on Harmonization (ICH) Guideline E6 and in accordance with the general ethical principles 
outlined in the Declaration of Helsinki. The study will receive approval from an IRB/EC prior to 
commencement. The investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. Celgene staff or an authorized representative will evaluate and approve all 
investigators who in turn will select their staff.
The investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions. 
The investigator should maintain a list of sub-investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The investigator is responsible for keeping a record of all subjects who sign an ICF and are 
screened for entry into the study. Subjects who fail screening must have the reason(s) recorded in 
the subject’s source documents.
The investigator, or a designated member of the investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The investigator must ensure timely and accurate completion of eCRFs and queries.
14.3.
Subject Information and Informed Consent
The investigator must obtain informed consent of the subject and/or the subject’s legal 
representative prior to any study-related procedures.
Documentation that informed consent occurred prior to the subject’s entry into the study and of 
the informed consent process should be recorded in the subject’s source documents including the 
date. The original ICF signed and dated by the subject and by the person consenting the subject
prior to the subject’s entry into the study, must be maintained in the investigator’s study files and 
a copy given to the subject. In addition, if a protocol is amended and it impacts the content of the 
informed consent, the ICF must be revised. Subjects participating in the study when the amended 
protocol is implemented must be re-consented with the revised version of the ICF. The revised 
ICF signed and dated by the subject and by the person consenting the subject must be maintained 
in the investigator’s study files and a copy given to the subject.
e
rior to
or to
th
ical Practic
ical Practic
evaluate an
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study
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re
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al charts
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btain infof
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protocol il
CF si
CF si


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
66
ABI-007-NSCL-006 Final: 29 May 2014
14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
IP can only be supplied to an Investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
Celgene or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB/EC should mention the protocol title, number, amendment number 
(if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
&(/*(1(35235,(7$5<,1)250$7,21
arch
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
67
ABI-007-NSCL-006 Final: 29 May 2014
The investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating investigator and the IRB/EC. This statement also applies to any 
communication between the investigator (or coordinating investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
&(/*(1(35235,(7$5<,1)250$7,21
e;e;
ed risk to su
ed risk to su
reasonable
asonable
e appropria
e appropr
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ta collect
a collectioi
;
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o the study


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
68
ABI-007-NSCL-006 Final: 29 May 2014
15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The investigator must ensure that the records and documents pertaining to the conduct of the 
study and distribution of the IP are complete, accurate, filed and retained. Examples of source 
documents include: hospital records; clinic and office charts; laboratory notes; memoranda; 
subject’s diaries or evaluation checklists; dispensing records; recorded data from automated 
instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy and the laboratories, as well 
as copies of CRFs or CD-ROM.
15.2.
Data Management
Data will be collected via eCRF and entered into the clinical database per Celgene Standard 
Operating Procedures (SOPs). This data will be electronically verified through use of 
programmed edit checks specified by the clinical team. Discrepancies in the data will be brought 
to the attention of the clinical team, and investigational site personnel, if necessary. Resolutions 
to these issues will be reflected in the database. An audit trail within the system will track all 
changes made to the data.
15.3.
Record Retention
Essential documents must be retained by the investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IP. The investigator must retain these 
documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the investigator, Celgene, and their authorized 
representative(s);
!
List of sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of CRFs (if paper) and of documentation of corrections for all subjects;
!
IP accountability records;
!
Record of any body fluids or tissue samples retained;
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Celgene Sta
Celgene Sta
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
69
ABI-007-NSCL-006 Final: 29 May 2014
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
!
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.
The investigator must obtain approval in writing from Celgene prior to destruction of any 
records. If the investigator is unable to meet this obligation, the investigator must ask Celgene 
for permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.
&(/*(1(35235,(7$5<,1)250$7,21
e
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destruction


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
70
ABI-007-NSCL-006 Final: 29 May 2014
16.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative
for compliance with applicable government regulations with respect to current GCP and standard 
operating procedures.
16.1.
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study. All aspects of the study are reviewed with the investigator and the staff at a study 
initiation visit and/or at an investigator meeting. Prior to enrolling subjects into the study, a 
Celgene representative or designee will review the protocol, eCRFs, procedures for obtaining 
informed consent, record keeping, and reporting of AEs/SAEs with the investigator. Monitoring 
will include on-site visits with the investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, IP 
storage area, eCRFs, subject’s source documents, and all other study documentation will be
inspected/reviewed by the Celgene representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of
the entries made onto the eCRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the investigator and/or his/her staff. Any necessary 
corrections will be made directly to the eCRFs or via queries by the investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene. Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The investigator is required to permit direct access to the facilities where the study took place, 
source documents, eCRFs and applicable supporting records of subject participation for audits 
and inspections by IRB/IECs, regulatory authorities (eg, FDA, European Medicines Agency 
[EMA], Health Canada) and company authorized representatives. The investigator should make 
every effort to be available for the audits and/or inspections. If the investigator is contacted by 
any regulatory authority regarding an inspection, he/she should contact Celgene immediately.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
71
ABI-007-NSCL-006 Final: 29 May 2014
17.
PUBLICATIONS
The results of this study may be published in a medical publication, journal, or may be used for 
teaching purposes. Additionally, this study and its results may be submitted for inclusion in all 
appropriate health authority study registries, as well as publication on health authority study 
registry websites, as required by local health authority regulations. Selection of first authorship 
will be based on several considerations, including, but not limited to study participation, 
contribution to the protocol development, and analysis and input into the manuscript, related 
abstracts, and presentations in a study.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
72
ABI-007-NSCL-006 Final: 29 May 2014
18.
REFERENCES
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Oncology clinical practice guideline update on chemotherapy for Stage IV non–small-cell lung 
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Belani CP, Ramalingam S, Perry MC, LaRocca RV, Rinaldi D, Gable PS, et al. Randomized, 
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advanced non-small-cell lung cancer. J Clin Onc 2008;26:468-73.
Benson AB 3rd, Ajani JA, Catalano RB, Engelking C, Kornblau SM, Martenson JA Jr, et al.
Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol
2004 Jul 15;22(14):2918-2926.
Buccheri G, Ferrigno D. Second-line weekly paclitaxel in patients with inoperable non-small cell 
lung cancer who fail combination chemotherapy with cisplatin. Lung Cancer 2004;45:227–36.
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Garcia-Manero G, Gore SD, Cogle C, Ward R, Shi T, Macbeth KJ, et al. Phase I study of oral 
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Gardner ER, Dahut WL, Scripture CD, Jones J, Aragon-Ching JB, Desai N, et al. Randomized 
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Gerber DE, Schiller JH. Maintenance chemotherapy for advanced non-small-cell lung cancer: 
new life for an old idea. J Clin Oncol 2013 Mar 10;31(8):1009-20.
Gordian E, Ramachandran K, Singal R. Methylation mediated silencing of TMSl in breast cancer 
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&(/*(1(35235,(7$5<,1)250$7,21
eated 
ated
Jr, et al.
Jr, et al.
Clin Onco
Clin Onc
perable non
perable no
ancer 2004;
cer 20
zzarini C,
arini C, e
nced non
ed non-sm
reased ant
ased ant
of cremop
of cremop
ed paclitaxe
ed paclita
HT. A phase
HT. A phase
bound pacl
bound pac
Clin Onco
lin Oncol
gaerts J, Sch
gaerts J, Sc
n so
solid tum
lid tum
-47. 
47. 
re SD, Cog
e SD, Cog
odysplast
odysplasticic
Onco
Oncol 201
20
, Dahut WL
, Dahut WL
r pharmaco
harmaco
14(13):4200
4(13):4200
rber DE
ber DE, S
new life fo
new life fo
ordi
ordi


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
73
ABI-007-NSCL-006 Final: 29 May 2014
Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, et al. Randomized 
Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non–Small-Cell Lung Cancer 
Previously Treated With Chemotherapy. J Clin Oncol 2004;22:1589-97.
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paclitaxel as second-line treatment for advanced non-small cell lung cancer: a phase II study. Jpn 
J Clin Oncol 2002;32:449–54.
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epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer. 
Cancer Discov 2011 Dec;1(7):598-607.
Kaminskas E, Farrell AT, Wang YC, Sridhara R, Pazdur R. FDA Drug Approval Summary: 
Azacitidine (5-azacytidine, Vidaza™) for Injectable Suspension. The Oncologist 2005 
Mar;10(3):176-82.
Li Y, Hu W, Shen DY, Kavanagh JJ, Fu S. Azacitidine enhances sensitivity of platinum-resistant 
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Rizvi NA, Riely GJ, Azzoli CG, Miller VA, Ng KK, Fiore J, et al. Phase I/II trial of weekly 
intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with Stage IV 
non-small-cell lung cancer. J Clin Oncol 2008;26(4):639-43.
Schiller JH, Gandara DR, Goss GD, Vokes EE.  Non-small-cell lung cancer: then and now. 
J Clin Oncol 2013;31(8):981-3.
Sculier JP, Berghmans T, Lafitte JJ, Richez M, Recloux P, Van Cutsem O, et al. A phase II study 
testing paclitaxel as second-line single agent treatment for patients with advanced non-small cell 
lung cancer failing after a first-line chemotherapy. Lung Cancer 2002;37:73–7.
Socinski MA, Manikhas GM, Stroyakovsky DL, Makhson AN, Cheporov SV, Orlov SV, et al. A 
dose finding study of weekly and every-3-week nab-paclitaxel followed by carboplatin as 
first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol 
2010;5(6):852-61.
Socinski MA, Schell MJ, Bakri K, Peterman A, Lee JH, Unger P, et al. Second-line, low-dose, 
weekly paclitaxel in patients with stage IIIB/IV nonsmall cell lung carcinoma who fail first-line 
chemotherapy with carboplatin plus paclitaxel. Cancer 2002;95:1265–73. 
Socinski MA, Steagall A, Gillenwater H. Second-line chemotherapy with 96-hour infusional 
paclitaxel in refractory non-small cell lung cancer: report of a phase II trial. Cancer Invest 
1999;17:181–8. 
&(/*(1(35235,(7$5<,1)250$7,21
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ummary:
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Ng KK, Fio
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axel as init
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, Vokes EE
Vokes E
afitte JJ, Ri
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nikhas GM
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udy
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of
y
week
w
f
rapy in pat
rapy in pat
):852
52-61.
-61.
nski MA, S
nski MA, 
eekly paclit
eekly paclit
chemother
hemother
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
74
ABI-007-NSCL-006 Final: 29 May 2014
Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, et al. 
Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus 
carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final 
results of a phase III trial. J Clin Oncol 2012 Jun 10;30(17):2055-62.
Yasuda K, Igishi T, Kawasaki Y, Kato K, Matsumoto S, Katayama S, et al. Phase II study of 
weekly paclitaxel in patients with non-small cell lung cancer who have failed previous 
treatments. Oncology 2004;66:347–52.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
75
ABI-007-NSCL-006 Final: 29 May 2014
Appendix A: ECOG Performance Status Score
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5
Dead
Oken, 1982.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
76
ABI-007-NSCL-006 Final: 29 May 2014
Appendix B: Recommendations for Management of Treatment-Induced 
Diarrhea
The following published guidelines (Benson, 2004) were modified in order to be consistent with 
the clinical study protocol.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
Celgene Signing Page
This is a representation of an electronic record that was signed electronically in Livelink.
This page is the manifestation of the electronic signature(s) used in compliance with
the organizations electronic signature policies and procedures.
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