A Phase 2, Open-Label, Multi-Center 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+
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Sponsor: Celgene

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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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nab-paclitaxel
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 
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 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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nab-paclitaxel
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
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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 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
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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
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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.
4.1.3
1.4.
1 4

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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

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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
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6

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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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1

('06'RF1XPEHU
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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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/Durvalum
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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 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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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
&(/*(1(35235,(7$5<,1)250$7,21

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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
nab-Paclitaxel/
carboplatin
(N=521)
Paclitaxel/
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Response Rate 
Ratio
(pA/pT)
p-value
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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%)
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.
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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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('06'RF1XPEHU
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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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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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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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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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
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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
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infusion over 30 minutes on Days 
8 and 15 of each 21-day cycle
o
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cycle
until disease progression
(n = 80)
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(n=240)
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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
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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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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
Confidential and Proprietary
70
ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 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.
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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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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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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and dea
are lost to 
are lost to
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censored
utoff date w
toff da
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ar ma
manner
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marized by t
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ribed in a S
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10.6.3.4.
0.6.3.4.
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('06'RF1XPEHU
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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
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nab-
set date mo
set date mo
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IP
P will be su
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29 d
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CTCAE, V
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TEAEs, se
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0.7.3.
0.7.3.
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('06'RF1XPEHU
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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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('06'RF1XPEHU
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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
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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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('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
!
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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Celgene Corporation
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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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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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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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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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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.
d d 
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Celgene Corporation
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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
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ABI-007-NSCL-006 Amendment 3.0 Final: 14 Apr 2016
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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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cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000;18(10), 2095-
103.
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.
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(8):981
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xel as secon
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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, 
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. 
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.
Sui M, Chen F, Chen Z, Fan W. Glucocorticoids interfere with therapeutic efficacy of paclitaxel 
against human breast and ovarian xenograft tumors. Int J Cancer. 2006;119(3), 712-7.
Tanaka H, Matshushima H, Mizumoto N, Takashima A. Classification of chemotherapeutic 
agents based on their differential in vitro effects on dendritic cells. Cancer Res. 
2009;69(17):6978-86.
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Journal of Cancer 2015 Sep 1 (Vol. 51, pp. S716-S717). 
Wang DD, Zhang S, Zhao H, Men AY, Parivar K. Fixed dosing versus body size-based dosing 
of monoclonal antibodies in adult clinical trials. J Clin Pharmacol. 2009 Sep 1;49(9):1012-24. 
Wang E, Kang D, Bae KS, Marshall MA, Pavlov D, Parivar K. Population pharmacokinetic and 
pharmacodynamic analysis of tremelimumab in patients with metastatic melanoma. J Clin
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 
treatments. Oncology 2004;66:347–52.
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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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
Confidential and Proprietary
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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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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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iscontinuatio
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nab-paclitaxel
Protocol ABI-007-NSCL-006
Celgene Corporation
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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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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
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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
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 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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 antifungals 
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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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ALP = alkalin
ALP = alkalin
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PCP = pneum
PCP = pne
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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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CTC = Comm
CTC = Co

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