A Phase II, Single Arm, Open-Label, Multicenter, Safety and Tolerability Trial With Nab-Paclitaxel (ABRAXANE®) Plus Carboplatin Followed by Nab-Paclitaxel Monotherapy as First-Line Treatment for Subjects With Locally Advanced or Metastatic Nonsmall Cell Lung Cancer (NSCLC) and an Eastern Cooperative Oncology Group Performance Status of 2 (ABOUND.PS2)
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Sponsor: Celgene

 
 
 
 
 
Protocol Title:   
A Phase II, Single Arm, Open-Label, Multi-Center, Safety 
and Tolerability Trial with nab-Paclitaxel (Abraxane®) Plus 
Carboplatin Followed by nab-Paclitaxel Monotherapy as 
First-Line Treatment For Subjects With Locally Advanced 
or Metastatic Non-Small Cell Lung Cancer (NSCLC) and 
an Eastern Cooperative Oncology Group Performance 
Status of 2 (Abound.PS 2). 
 
NCT Number:  NCT02289456 
Original Protocol Date:  12 January 2015 

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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-004 Final: 12 January 2015
TITLE PAGE
A PHASE II, SINGLE ARM, OPEN-LABEL, MULTI-
CENTER, SAFETY AND TOLERABILITY TRIAL WITH 
nab-PACLITAXEL (ABRAXANE®) PLUS CARBOPLATIN 
FOLLOWED BY nab-PACLITAXEL MONOTHERAPY 
AS FIRST-LINE TREATMENT FOR SUBJECTS WITH 
LOCALLY ADVANCED OR METASTATIC NON-
SMALL CELL LUNG CANCER (NSCLC) AND AN 
EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS OF 2 
(ABOUND.PS2)
INVESTIGATIONAL PRODUCT:
nab-Paclitaxel (Abraxane®)
PROTOCOL NUMBER:
ABI-007-NSCL-004
ORIGINAL DATE FINAL:
11 August 2014
AMENDMENT 1 DATE FINAL:
12 January 2015
EudraCT NUMBER:
Not applicable
IND NUMBER:
114882
SPONSOR NAME / ADDRESS:
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board.  The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations.  
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-004 Final: 12 January 2015
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information:
Name:
Title:
 
Address: 
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
Phone:
E-mail:
Contact Information:
Name:
Title:
Address: 
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
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-004
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-004 Final: 12 January 2015
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.  
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-004 Final: 12 January 2015
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-004 Final: 12 January 2015
PROTOCOL SUMMARY
Study Title
A Phase II, Single Arm, Open-Label, Multi-Center, Safety and Tolerability Trial with nab-
Paclitaxel (Abraxane®) Plus Carboplatin Followed by nab-Paclitaxel Monotherapy as First-Line 
Treatment For Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer 
(NSCLC) and an Eastern Cooperative Oncology Group Performance Status of 2 (Abound.PS 2).
Indication
First-line treatment of subjects with locally advanced or metastatic NSCLC and an Eastern 
Cooperative Oncology Group Performance Status 2 (ECOG PS 2). 
Objectives
Primary
!
To assess the safety and tolerability of the nab-paclitaxel and carboplatin combination 
dosing regimen for first-line treatment of locally advanced or metastatic NSCLC in 
subjects with an ECOG PS 2. 
Secondary 
!
To evaluate the efficacy (progresstion-free survival [PFS], disease control rate [DCR], 
overall survival [OS] and overall response rate [ORR]) of the nab-paclitaxel and 
carboplatin combination dosing regimen, followed by nab-paclitaxel monotherapy for 
first-line treatment of locally advanced or metastatic NSCLC in subjects with an ECOG
PS 2.
!
To assess the safety and tolerability of the nab-paclitaxel and carboplatin combination 
dosing regimen followed by nab-paclitaxel monotherapy for first-line treatment of locally 
advanced or metastatic NSCLC in subjects with an ECOG PS 2.
Exploratory 
!
To assess healthcare resource utilization
!
To assess co-morbidity status using the Charlson Co-Morbidity Index (CCI)
!
To assess quality of life
!
To explore the correlation between the physician- and patient-evaluated Eastern 
Cooperative Oncology Group Performance Status
!
To explore the correlation between the physician- and patient-evaluated Karnofsky 
Performance Status
!
To assess the safety and efficacy of continuous treatment with nab-paclitaxel as 
monotherapy after 4 cycles of nab-paclitaxel in combination with carboplatin
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-004 Final: 12 January 2015
Study Design
Approximately 50 subjects with stage IIIB or IV NSCLC and ECOG PS 2 will be enrolled in the 
study to receive nab-paclitaxel plus carboplatin for 4 cycles, followed by monotherapy with nab-
paclitaxel in the absence of disease progression.  
The study will consist of a 28-day screening period, induction with 4 cycles of nab-paclitaxel 
and carboplatin followed by nab-paclitaxel monotherapy, and follow-up. The screening period 
for eligibility determination begins upon subject written informed consent.  
Induction Part
Approximately 50 eligible subjects will be enrolled in the study.  In the induction part subjects 
will receive 4 cycles of nab-paclitaxel plus carboplatin, provided all eligibility criteria are met 
within a 28-day screening period prior to Cycle 1 Day 1.
Induction treatment will consist of: 
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion on Days 1 and 8 of each 21-day 
cycle  
!
Carboplatin area under the curve (AUC) = 5 mg*min/mL IV on Day 1 of each 21-day 
cycle after completion of nab-paclitaxel infusion.  
Monotherapy Part
Subjects may continue in the study and receive monotherapy with nab-paclitaxel in the 
absence of disease progression, after the completion of 4 cycles of the induction therapy.  
They will receive:
!
nab-Paclitaxel 100 mg/m2 IV infusion on Days 1 and 8 of each 21-day cycle.
Tumor evaluations will be assessed by the investigative sites and response will be determined 
according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, Version 1.1 
(Eisenhauer, 2009).
Follow-up Period
All subjects who discontinue treatment for any reason other than lost to follow-up or death, will 
enter the follow-up period.  All subjects will continue to have computed tomography (CT) scans 
in accordance with their institution’s standard of care and the findings will be reported on the 
appropriate electronic Case Report Form (eCRF) pages.  In addition, all post-treatment anti-
cancer therapy will be reported on the appropriate eCRF pages.  Minimally, all subjects will be 
followed for overall survival (OS) every 90 days by phone contact or chart review for 
documentation of last contact for up to 1 year after the last subject is enrolled.
Study Population
Adults ≥ 18 years old with locally advanced or metastatic NSCLC and PS 2 who have not 
received chemotherapy for their advanced disease and are not candidates for curative surgery or 
radiation therapy, will be eligible for this study. The study will enroll approximately 50 subjects.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-004 Final: 12 January 2015
Length of Study
Enrollment will last approximately 15 months.  The total length of this phase 2 study with 
induction, monotherapy and follow-up is estimated at approximately 27 months.
The End of Trial is defined as either the date of the last visit of the last subject, or the date of 
receipt of the last data point from the last subject that is required for primary, secondary and/or 
exploratory analysis, as pre-specified in the protocol and/or the Statistical Analysis Plan, 
whichever is the later date.
Study Treatments
nab-Paclitaxel
nab-Paclitaxel is designated as investigational product throughout the trial and will be packaged 
and supplied by Celgene Corporation.  The preparation for IV administration procedures for 
investigational product should be followed as per the approved local prescribing information.
Carboplatin
Carboplatin will be provided commercially, by prescription only.  The preparation for IV 
administration procedures for carboplatin should be followed as per the approved local 
prescribing information.
Overview of Statistical Methods
Approximately 50 subjects will be enrolled and treated in this study. Enrollment will be 
conducted and tracked centrally using an Interactive Response Technology (IRT) system.  The 
date of enrollment is defined as the date on which the subject is registered into the IRT system.
All evaluations of the safety and efficacy endpoints will be based on the point estimates and the 
associated two-sided 95% confidence intervals (CI). 
Overview of Safety Assessments
The treated population, which includes all subjects who received at least one dose of 
investigational product, will be the analysis population for all safety analyses. 
The primary endpoint for the study is the percentage of subjects who discontinue during the 
induction part due to treatment-emergent adverse events (TEAEs).  
Treatment-emergent adverse events are defined as any adverse event (AE) or serious adverse 
event (SAE) occurring or worsening on or after the first dose of the investigational product
through 28 days after the last dose of investigational product. In addition, any SAE with an onset 
date more than 28 days after the last dose of investigational product that is assessed by the 
Investigator as related to investigational product will be considered a TEAE. The TEAE rate will 
be summarized by descriptive statistics with the corresponding 95% confidence interval. 
In addition to the primary safety endpoint described above which focuses on the safety and 
tolerability of the induction regimen in subjects with performance status 2, the safety and 
tolerability of the treatment regimen for the entire study will be assessed by TEAE rate, Grade 3 
or higher TEAEs, SAEs, TEAEs leading to dose reduction, dose delay, and dose interruption,
TEAEs leading to treatment discontinuation, and TEAEs with an outcome of death for the entire 
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-004 Final: 12 January 2015
study will be summarized by the Medical Dictionary for Regulatory Activities (MedDRA)
system organ class and preferred terms. 
Overview of Efficacy Assessments
The treated population, which includes all subjects who received at least one dose of 
investigational product, will be used for all efficacy analyses.  
Progression-free survival, DCR, ORR, and OS over the entire study are the key efficacy 
endpoints of the study.
Progression-free survival is defined as the time from the date of first dose of investigational 
product 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 v1.1 guidelines. Baseline tumor measurements will be determined from 
the radiologic evaluation performed within 28 days before the start of investigational product. 
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time and PFS rates at regular intervals from the first day of investigational product treatment
(including two-sided 95% confidence interval [CI]).  
Disease control rate (percent of subjects who have continued stable disease, complete or partial 
response), and overall response rate (percent of subjects who have a radiologic complete or 
partial response), as evaluated by the Investigator based on the RECIST v1.1 guidelines, will be 
estimated along with the associated 2-sided 95% CIs.   
Overall survival will be summarized by descriptive statistics with the associated 95% CIs, as 
described for PFS.
The primary analysis of both the safety and efficacy endpoints will be performed at 
approximately 6 months after the last subject is enrolled.  Subjects will be followed for OS until 
1 year after the last subject is enrolled.  
Sample Size
The primary objective of the study is to assess the safety and tolerability of the nab-paclitaxel 
and carboplatin combination treatment regimen in the study population. All evaluations of the 
safety and efficacy endpoints will be based on the point estimates and the associated two-sided 
95% confidence intervals rather than formal inferential statistical tests.
The primary endpoint of the study is the percentage of subjects who discontinue during the 
induction part due to TEAEs. With a sample size of 50, the maximum width of the 95% 
confidence interval for any proportion is 28.9%. Of note, assuming the underlying percentage of 
subjects who will discontinue from study treatment due to TEAEs is 30%, a sample size of 50 
provides 80% power, with a one-sided significance level of 10%, to detect an increase of 15 
percentage points from 30%.
Scientific Steering Committee
An external Scientific Steering Committee (SSC) will be established, with the responsibilities for 
safeguarding the interests of study participants and monitoring the overall conduct of the study.
A charter will be established for regular safety data review. The SSC will have the ability to 
recommend termination of the study if a safety signal is discovered.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
9
ABI-007-NSCL-004 Final: 12 January 2015
Final recommendations of the SSC will reflect the judgment of the SSC members and will be 
considered advisory in nature to the Sponsor. The decision to implement the recommendations of 
the SSC will be made by the Sponsor.
&(/*(1(35235,(7$5<,1)250$7,21

('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
10
ABI-007-NSCL-004 Final: 12 January 2015
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................5
1.
INTRODUCTION..................................................................................................17
1.1.
Treatment of Advanced Stage Non-small Cell Lung Cancer ...................................17
1.2.
Treatment of Patients with Advanced Stage NSCLC and Poor Performance 
Status (PS)..............................................................................................................19
1.3.
Rationale For Schedule and Dosage Selection.........................................................20
2.
STUDY OBJECTIVES...........................................................................................22
2.1.
Primary Objective...................................................................................................22
2.2.
Secondary Objectives .............................................................................................22
2.3.
Exploratory Objectives ...........................................................................................22
3.
STUDY ENDPOINTS............................................................................................23
3.1.
Primary Endpoint....................................................................................................23
3.1.1.
Safety.....................................................................................................................23
3.2.
Secondary Endpoint(s)............................................................................................23
3.2.1.
Safety.....................................................................................................................23
3.2.2.
Efficacy..................................................................................................................23
3.3.
Exploratory Endpoint(s)..........................................................................................23
3.3.1.
Exploratory Endpoints............................................................................................23
4.
OVERALL STUDY DESIGN ................................................................................25
4.1.
Study Design ..........................................................................................................25
4.2.
Study Design Rationale ..........................................................................................25
4.3.
Study Duration .......................................................................................................28
4.3.1.
Duration of Treatment ............................................................................................28
4.4.
End of Trial ............................................................................................................28
5.
TABLE OF EVENTS.............................................................................................29
6.
PROCEDURES......................................................................................................34
6.1.
Medical History......................................................................................................34
6.2.
Prior Medications/Procedures .................................................................................34
6.3.
Pregnancy Testing ..................................................................................................34
6.4.
Complete Chest Computed Tomography (CT) Scan (including adrenal 
gland) With and Without Contrast ..........................................................................34
&(/*(1(35235,(7$5<,1)250$7,21
..... 19
1
.........
.......20
20
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SIGN ..
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Ratatioionale
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TABLE 
TABLE 
PRO
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M
6.2.
6.2

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6.5.
Height and Weight..................................................................................................35
6.6.
Body Surface Area (BSA) Calculation....................................................................35
6.7.
Physician-Reported ECOG Performance Score.......................................................35
6.8.
Concomitant Medications/Procedures.....................................................................35
6.9.
Adverse Event Reporting........................................................................................35
6.10.
Lung Cancer Symptom Scale, Subject- and Physician-Reported KPS, 
Subject-Reported ECOG PS, EQ-5D-5L, and Charlson Co-Morbidity Index ..........35
6.11.
Healthcare Resource Utilization Questionnaire .......................................................36
6.12.
Electrocardiogram ..................................................................................................36
6.13.
CT Scan of Head or Brain Magnetic Resonance Imaging (MRI).............................36
6.14.
Bone Scans and X-rays...........................................................................................36
6.15.
Physical Examinations............................................................................................36
6.16.
Vital Signs..............................................................................................................36
6.17.
Laboratory Assessments .........................................................................................36
6.18.
Follow-Up / Survival..............................................................................................37
6.19.
Histology and Mutation Status:...............................................................................37
6.20.
Spirometry and Pulse Oximetry..............................................................................37
6.21.
Baseline Tumor, Node and Metastasis (TNM) Stage...............................................38
6.22.
Assessment of Nutritional Status ............................................................................38
6.23.
Reversibility of PS 2 Status ....................................................................................38
7.
STUDY POPULATION.........................................................................................39
7.1.
Number of Subjects and Sites .................................................................................39
7.2.
Inclusion Criteria....................................................................................................39
7.3.
Exclusion Criteria...................................................................................................40
8.
DESCRIPTION OF INVESTIGATIONAL PRODUCT .........................................42
8.1.
Description of Investigational Product ....................................................................42
8.1.1.
nab-Paclitaxel.........................................................................................................42
8.1.2.
Carboplatin.............................................................................................................42
8.2.
Treatment Administration and Schedule .................................................................43
8.3.
Dose Delay and Dose Modifications .......................................................................43
8.4.
Method of Treatment Assignment...........................................................................44
8.5.
Packaging and Labeling..........................................................................................44
8.6.
Investigational Product Accountability and Disposal ..............................................45
&(/*(1(35235,(7$5<,1)250$7,21
..35
35
........
.......36
36
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sis (TNM) 
sis (TNM
s ...........
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N............
.........
s and Sites
and Sites
ria..........
.....
Cri
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ter
i
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2.
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8.3.
.3

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8.7.
Investigational Product Compliance........................................................................45
8.8.
Overdose ................................................................................................................45
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................46
9.1.
Permitted Concomitant Medications and Procedures...............................................46
9.2.
Prohibited Concomitant Medications and Procedures..............................................46
9.3.
Required Concomitant Medications and Procedures................................................46
10.
STATISTICAL ANALYSES..................................................................................47
10.1.
Overview................................................................................................................47
10.2.
Study Population Definitions ..................................................................................47
10.2.1.
Treated Population..................................................................................................47
10.2.2.
Per-protocol (PP) Population ..................................................................................47
10.3.
Sample Size and Power Considerations...................................................................47
10.4.
Background and Demographic Characteristics........................................................48
10.5.
Subject Disposition.................................................................................................48
10.6.
Safety Analysis.......................................................................................................49
10.6.1.
Primary Safety Endpoint.........................................................................................49
10.6.2.
Adverse Events.......................................................................................................49
10.6.3.
Laboratory Assessments .........................................................................................49
10.6.4.
Investigational Product Exposure............................................................................50
10.7.
Efficacy Analysis....................................................................................................50
10.7.1.
Efficacy Endpoints .................................................................................................50
10.7.1.1.
Progression-free Survival........................................................................................50
10.7.1.2.
Disease Control Rate ..............................................................................................51
10.7.1.3.
Overall Survival .....................................................................................................51
10.7.1.4.
Overall Response Rate............................................................................................51
10.7.2.
Exploratory Endpoints............................................................................................51
10.7.2.1.
Health Care Utilization ...........................................................................................51
10.7.2.2.
Quality of Life and Lung Cancer Symptom Questionnaires.....................................51
10.7.2.3.
Physician- and Subject-Reported ECOG Performance Status..................................51
10.7.2.4.
Physician- and Subject-Reported Karnofsky Performance Status............................51
10.7.2.5.
Treatment Response During the Monotherapy Part .................................................52
10.8.
Investigational Product Termination .......................................................................52
10.9.
Deaths ....................................................................................................................52
&(/*(1(35235,(7$5<,1)250$7,21
6
.......47
4
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4
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ure
ure.........
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urvival..
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urvival
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all Respons
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0.7.2.3
10.7.2.4
0.7.2.

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10.10.
Interim Analysis .....................................................................................................52
10.11.
Scientific Steering Committee ................................................................................52
11.
ADVERSE EVENTS..............................................................................................53
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................53
11.2.
Evaluation of Adverse Events.................................................................................53
11.2.1.
Seriousness.............................................................................................................53
11.2.2.
Severity / Intensity..................................................................................................55
11.2.3.
Causality ................................................................................................................55
11.2.4.
Duration .................................................................................................................56
11.2.5.
Action Taken..........................................................................................................56
11.2.6.
Outcome.................................................................................................................56
11.3.
Abnormal Laboratory Values..................................................................................56
11.4.
Pregnancy...............................................................................................................56
11.4.1.
Females of Childbearing Potential: .........................................................................57
11.4.2.
Male Subjects.........................................................................................................57
11.5.
Reporting of Serious Adverse Events......................................................................57
11.5.1.
Safety Queries ........................................................................................................58
11.6.
Expedited Reporting of Adverse Events..................................................................58
12.
DISCONTINUATIONS .........................................................................................59
12.1.
Treatment Discontinuation......................................................................................59
12.2.
Study Discontinuation ............................................................................................59
13.
EMERGENCY PROCEDURES.............................................................................61
13.1.
Emergency Contact.................................................................................................61
13.2.
Emergency Identification of Investigational Product...............................................61
14.
REGULATORY CONSIDERATIONS...................................................................62
14.1.
Good Clinical Practice............................................................................................62
14.2.
Investigator Responsibilities ...................................................................................62
14.3.
Subject Information and Informed Consent.............................................................62
14.4.
Confidentiality........................................................................................................63
14.5.
Protocol Amendments.............................................................................................63
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................63
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................64
&(/*(1(35235,(7$5<,1)250$7,21
3
.......55
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vents......
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ROCEDUR
ROCEDU
ontact
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4.4.
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14.5.
4.5.

('06'RF1XPEHU
nab-Paclitaxel
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14.8.
Closure of the Study ...............................................................................................64
15.
DATA HANDLING AND RECORDKEEPING.....................................................65
15.1.
Data/Documents .....................................................................................................65
15.2.
Data Management...................................................................................................65
15.3.
Record Retention....................................................................................................65
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................67
16.1.
Study Monitoring and Source Data Verification......................................................67
16.2.
Audits and Inspections............................................................................................67
17.
PUBLICATIONS ...................................................................................................68
18.
REFERENCES.......................................................................................................69
19.
APPENDICES........................................................................................................71
Appendix A:  ECOG Performance Status Score ........................................................................71
Appendix B: Reversible Versus Non-Reversible .......................................................................71
&(/*(1(35235,(7$5<,1)250$7,21
7
.......67
6
..........
.... 67
6
..............
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.............
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.... ..........
......

('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-004 Final: 12 January 2015
LIST OF TABLES
Table 1:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat 
Population).............................................................................................................19
Table 2:
Table of Events - Induction.....................................................................................29
Table 3:
Table of Events – Monotherapy..............................................................................32
Table 4:
Permanent Dose Reductions for Hematologic and Non-Hematologic 
Toxicities on the Study ...........................................................................................44
Table 5:
Precision of the Estimate for the Treatment Discontinuation Rate due to 
Treatment-Emergent Adverse Events Given a Sample Size of 50............................48
&(/*(1(35235,(7$5<,1)250$7,21
.44
44
............
............48
4

('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
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ABI-007-NSCL-004 Final: 12 January 2015
LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................27
&(/*(1(35235,(7$5<,1)250$7,21

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ABI-007-NSCL-004 Final: 12 January 2015
1.
INTRODUCTION
1.1.
Treatment of Advanced Stage 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 
(Global Lung Cancer Coalition, 2015).
The majority of patients are not diagnosed until the tumor has progressed beyond the primary 
site. Despite several advances in patient selection, development of targeted agents and
optimization of chemotherapy regimens, the majority of patients with advanced NSCLC continue 
to have an unmet medical need (Schiller, 2013).
Platinum-containing chemotherapy doublet regimens remain the standard first-line treatment in 
the majority of patients, in the US and Japan. Similarly, 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 (National Institute 
for Health & Clinical Excellence [NICE], 2011).  In recent years, NSCLC treatment decisions 
are being determined based on tumor histology (squamous versus non-squamous), or based on 
molecular characteristics of the tumor for the use of agents targeting specific receptor kinases 
involved in oncogenic signaling pathways (eg, epidermal growth factor receptor [EGFR], 
echinoderm microtubule-associated protein-like 4 [EML4] and anaplastic lymphoma kinase 
[ALK] fusion protein).
In advanced NSCLC, the combination of paclitaxel/carboplatin results in modest response rate, 
survival, and toxicity. Paclitaxel is currently available in the proprietary product Taxol®
(paclitaxel) Injection, manufactured by Bristol-Myers Squibb (New York, NY) and by several 
other generic drug manufacturers. Taxol consists of paclitaxel dissolved in a proprietary solvent, 
Cremophor® EL (BASF, Ludwigshafen, Germany), and ethanol. While this solvent system 
addresses the poor water solubility of paclitaxel, the Taxol formulation has a number of other 
limitations. For example, Taxol administration requires routine premedication with 
corticosteroids, diphenhydramine, and histamine H2 receptor antagonists to reduce the incidence 
of hypersensitivity reactions and histamine release caused by a response to the formulation 
vehicle (Gelderblom, 2001; Lorenz, 1977; Weiss, 1990). Furthermore, the solvent alters drug 
pharmacokinetics (PK), leading to highly increased systemic drug exposure, decreased drug 
clearance, nonlinear PK, and lack of dose-dependent antitumor activity (Sparreboom, 1999; ten 
Tije, 2003; van Tellingen, 1999). Also, Taxol must be administered over a period of either 3 
hours or 24 hours.
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he primary
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ed NSCLC 
ed NSCLC
ard 
rd first
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orelbine
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years,
ears, NSC
NS
us s versus
versus
agents targe
agents targe
derm
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gro
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e 4 [EML4]
4 [EML4
f paclitaxel
f paclitax
urrently ava
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ed by
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rs. Taxol c
Taxol c
dwigshafen
dwigshafen
solubilit
solubility o
le, Taxo
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nab-Paclitaxel approval in first-line locally advanced or metastatic NSCLC:
nab-Paclitaxel for Injectable Suspension is approved for the treatment of metastatic breast cancer 
(globally) and for the treatment of adenocarcinoma of the pancreas (US). For NSCLC, nab-
paclitaxel is approved in the US in combination with carboplatin for first-line treatment of 
patients with locally advanced or metastatic NSCLC who are not candidates for curative surgery 
or radiation therapy. Compared with paclitaxel, 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 (Desai, 2006; 
Gardner, 2008).  The Cremophor EL-free medium enables nab-paclitaxelto be given over a 
shorter duration without the need for steroid premedication to prevent solvent-related 
hypersensitivity reactions.  The recommended dose of nab-paclitaxel for the NSCLC indication 
is 100 mg/m2 administered as an intravenous infusion over 30 minutes on Days 1, 8, and 15 of 
each 21-day cycle.
The Food and Drug Administration (FDA) approval of nab-paclitaxel in combination with 
carboplatin was based on the evaluation of phase 1 and 2 data (Belani, 2008; Rizvi, 2008; 
Socinski, 2010), as well as the pivotal phase 3 study (CA031). The pivotal phase 3 study was a 
multicenter, randomized, open-label study conducted in 1052 chemo-naive subjects with Stage 
IIIB/IV non-small cell lung cancer to compare nab-paclitaxel in combination with carboplatin to 
paclitaxel injection in combination with carboplatin as first-line treatment in patients with 
advanced non-small cell lung cancer. This study enrolled patients that were Eastern Cooperative 
Oncology Group (ECOG) performance status (PS) 0 or PS 1 only.  nab-Paclitaxel was 
administered as an intravenous 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 intravenous 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 
intravenously 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 Response Evaluation 
Criteria in Solid Tumors (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 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%).
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.  Median overall 
survival in the nab-paclitaxel arm was 12.1 months versus 11.2 months in the control arm (p = 
0.271; hazard ratio [HR] = 0.922, 95% confidence interval [CI], 0.797 to 1.066; p = .271). There 
was an approximately 10% improvement in progression-free survival (median, 6.3 v 5.8 months; 
HR, 0.902; 95% CI, 0.767 to 1.060; p = .214) in the nab-paclitaxel arm versus the P/C arm.  
Adverse events (AEs) were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. The following common (≥ 10% incidence) AEs
&(/*(1(35235,(7$5<,1)250$7,21
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utes
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median 
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ly
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0.271; ha
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as an

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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 vs paclitaxel injection plus carboplatin grade 3-4 were: anemia 28% 
vs 7%, neutropenia 47% vs 58% and thrombocytopenia 18% vs 9%.  
Per protocol, patients were stratified by NSCLC histology (squamous cell carcinoma vs 
adenocarcinoma vs other histology). Subgroup analyses were performed to assess the influence 
of squamous vs non-squamous histology on the primary efficacy endpoint of overall response 
rate (the percentage of patients who achieved an objective confirmed complete response (CR) or 
partial response (PR) based on the blinded radiological review using RECIST response 
guidelines, Version 1.0). The proportion of patients with squamous cell carcinoma who 
responded was significantly higher for the ABI-007/carboplatin regimen relative to the 
Taxol/carboplatin regimen (41% vs 24%: pA/pT: 1.680; p < 0.001). The proportion of patients 
with non-squamous cell carcinoma with a confirmed complete or partial overall response was 
comparable between the ABI-007 and Taxol/carboplatin arms (26% vs 25%: pA/pT: 1.034; p = 
0.808).
Table 1:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat 
Population)
Variable
Category/Statistic
nab-Paclitaxel/
carboplatin
(N=521)
Paclitaxel/
carboplatin
(N=531)
Response Rate 
Ratio
(pA/pT)
p-value
Patients with Confirmed Complete or Partial Overall Response
n (%)
170 (33%)
132 (25%)
1.313
0.005*
Confidence Interval (CI) a
28.6, 36.7
21.2, 28.5
1.082, 1.593
Complete Response, n (%)
0
1 (< 1%)
Partial Response, n (%)
170 (33%)
131 (25%)
PA/PT: response rate of nab-paclitaxel/response rate of paclitaxel.
a 95% CI of response rate and 95.1% CI of response rate ratio.
* Indicates p-value < 0.049.
Note: p-value is based on a chi-square test.
Source: Data on File.
1.2.
Treatment of Patients with Advanced Stage NSCLC and Poor 
Performance Status (PS)
The functional status of patients with NSCLC is commonly assessed by two widely used 
measures of PS; the ECOG Scale (Oken, 1982) and the Karnofsky Performance Scale 
(Karnofsky, 1948).  These scales equate variables such as the ability to carry out normal daily 
activities, the proportion of waking hours a patient is ambulatory, and symptom burden, to a 
&(/*(1(35235,(7$5<,1)250$7,21
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CR)
sponse
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lative to th
ive to th
proportion
proportio
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ial overal
6% vs 25%
% vs 25%
l Response
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Paclita
carb
carb
7$
5,(
Overall Res
Overall Res
5,
5,
5,
70 (33%)
70 (33%
35
28.6, 36
28.6, 3
23
52
35
3
)
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
20
ABI-007-NSCL-004 Final: 12 January 2015
numerical value of PS.  Despite the general subjectivity of PS assessment, and the multiple 
contributing factors, PS is an important prognostic factor for survival in patients with NSCLC 
upon which treatment decisions are commonly made (Kelly, 2004).  Patients with a borderline or 
poor performance status (ie, ECOG PS ≥2) comprise about 30 to 40 percent of patients with 
NSCLC (Lilenbaum, 2008).
The majority of research in advanced non-small cell lung cancer (NSCLC) has generally focused 
on patients with good performance status (ECOG PS 0-1). However, a significant proportion of 
patients with advanced NSCLC have ECOG PS 2, either due to bulky disease or related to 
medical co-morbidities.  Treatment of ECOG PS 2 patients varies, due to concerns regarding 
treatment-related toxicities, rapid deterioration of performance status and poor overall survival 
relative to patients with ECOG PS 0-1, and thus there is a high unmet need which warrants 
further clinical research in this patient population. Patients with ECOG PS 2 have a worse 
prognosis than those with PS 0-1 with median overall survival (OS) of 36 and 26 weeks 
respectively versus 10 weeks for PS 2 patients (Hoang, 2005).
The potential toxicity of cytotoxic chemotherapy can pose special concerns in poor performance 
status patients with advanced NSCLC, and thus earlier treatment guidelines lacked consensus on 
specific treatment recommendations, particularly with respect to single-agent versus combination 
chemotherapy. A randomized phase 2 trial of paclitaxel plus carboplatin or gemcitabine plus 
cisplatin in ECOG PS 2, NSCLC enrolled 103 patients, all histologies (ECOG 1599).  The one 
year OS rates were 4.2 months for gemcitabine plus cisplatin versus 6.2 months in paclitaxel and 
carboplatin.  The median number of cycles administered per arm was 3 cycles.  The results 
suggest that platinum-based combination chemotherapy for PS 2 patients with NSCLC is feasible 
with acceptable toxicity, but survival remains inferior to that of PS 0-1 patients (Langer, 2007). 
Furthermore, the combined data from the STELLAR 3 and 4 studies provided important 
retrospective analyses of the potential efficacy and tolerability of paclitaxel-carboplatin relative 
to single-agent chemotherapy (Lilenbaum, 2009).  The hypothesis that PS 2 patients could 
benefit from platinum-doublet chemotherapy were supported prospectively in a phase 3 study of 
pemetrexed-carboplatin vs pemetrexed (Zukin 2013); in this trial, combination chemotherapy 
resulted in superior outcomes of ORR (23.8 % vs 10.3%, p = 0.032), progression-free survival 
(PFS) (5.8 months vs 2.8 months, HR 0.46, p < 0.001) and OS (9.3 months vs 5.3 months, HR 
0.62, p = 0.001). 
1.3.
Rationale For Schedule and Dosage Selection
Patients with NSCLC and an ECOG PS 2 are at risk of more toxicities, lower response rates and 
shorter survival times than healthier patients, when treated with standard chemotherapy.  This is 
due in large part to disease burden and co-morbidities.  Therefore dosage and schedule selection 
is critical in order to balance toxicities while optimizing treatment benefit. Recent phase 3 trials 
demonstrated that platinum-doublet chemotherapy can provide substantial clinical benefits, 
including improved overall survival, for older patients and those with ECOG PS 2 (Lilenbaum, 
2008).
The dose of carboplatin AUC 5 (though less than the standard dose of AUC 6 used in the PS 0-1 
setting) is chosen for this PS 2 protocol, based upon the efficacy and tolerability results from the 
Randomized Phase III Trial of Single-Agent Pemetrexed Versus Carboplatin and Pemetrexed in 
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
21
ABI-007-NSCL-004 Final: 12 January 2015
Patients With Advanced Non–Small-Cell Lung Cancer and Eastern Cooperative Oncology 
Group Performance Status of 2.
In the phase 3 trial, standard dose of pemetrexed (500mg/m2) was administered in both arms, 
however, carboplatin AUC 5 was administered in the combination arm.  The reduced carboplatin 
dose of AUC 5 alleviated the toxicity burden of the combination chemotherapy, whereby the 
Grade 3 and 4 AE profile was only marginally worse in the carboplatin-pemetrexed arm.  
However, only 53.9% of patients completed 4 cycles of treatment, compared to 70.9% of patients 
in the carboplatin- pemetrexed arm.  The principal reasons for discontinuation in the pemetrexed 
and combination arms included early death (14.7% versus 9.7%), early progression (15.7% 
versus 7.8%), clinical deterioration (12.7% versus 6.8%), toxicity (0% versus 1.9%) and others 
(4% versus 2%), respectively.  As expected therapy delays (20.6% versus 44.7%) and dose 
reductions (2.9% versus 3.9%) were more common in the combination arm (Zukin 2013).  
The dose for nab-paclitaxel in this protocol will be in accordance with the current approved label 
in NSCLC, however, the schedule for nab-paclitaxel will be modified to include only Days 1 and 
8 every 21 days.  The day 15 dose will be omitted to minimize toxicities.  This dose/schedule had 
been investigated in a phase 2 trial of carboplatin AUC5 and nab-paclitaxel 100mg/m2 days 1 
and 8 every 21 days in locally advanced Stage III NSCLC patients with PS 2 
 
.  During this phase 2 study, the preliminary toxicity profile of 
continuous weekly dosing of nab-paclitaxel resulted in Grade 3/4 neutropenia that necessitated 
day 15 dose omission, leading to a protocol amendment.  Nevertheless, this modified schedule 
was shown to be feasible with manageable side-effects and encouraging efficacy (ORR 67%, 
median PFS 11 months and median OS 17 months).  Therefore, this proposed protocol aims to 
build on the data from prior studies in PS 2 patients, ie, slightly lower dose-intensity of 
combination chemotherapy provides a tolerable toxicity profile while maintaining reasonable 
efficacy outcomes.  After 4 cycles of nab-paclitaxel and carboplatin, patients will have the option 
of continuing on nab-paclitaxel monotherapy, which will have the potential of being better 
tolerated than the chemotherapy doublet. This will also allow us to evaluate efficacy and safety 
for use of nab-paclitaxel as a continuous maintenance treatment.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
22
ABI-007-NSCL-004 Final: 12 January 2015
2.
STUDY OBJECTIVES
2.1.
Primary Objective
!
To assess the safety and tolerability of the nab-paclitaxel and carboplatin combination 
dosing regimen for first-line treatment of locally advanced or metastatic NSCLC in 
subjects with an ECOG PS 2.
2.2.
Secondary Objectives
!
To evaluate the efficacy (PFS, DCR, OS and ORR) of the nab-paclitaxel and 
carboplatin combination dosing regimen, followed by nab-paclitaxel monotherapy for 
first-line treatment of locally advanced or metastatic NSCLC in subjects with an
ECOG PS 2.
!
To assess the safety and tolerability of the nab-paclitaxel and carboplatin combination 
dosing regimen, followed by nab-paclitaxel monotherapy for first-line treatment of 
locally advanced or metastatic NSCLC in subjects with an ECOG PS 2.
2.3.
Exploratory Objectives
The exploratory objectives of the study are:
!
To assess healthcare resource utilization
!
To assess co-morbidity status using the Charlson Co-Morbidity Index (CCI)
!
To assess quality of life 
!
To explore the correlation between the physician- and patient-evaluated ECOG PS
!
To explore the correlation between the physician- and patient-evaluated Karnofsky 
performance status (KPS) at baseline
!
To assess the safety and efficacy of continuous treatment with nab-paclitaxel as 
monotherapy after 4 cycles of nab-paclitaxel in combination with carboplatin
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
23
ABI-007-NSCL-004 Final: 12 January 2015
3.
STUDY ENDPOINTS
3.1.
Primary Endpoint
3.1.1.
Safety
!
Percentage of subjects who discontinue study treatment during the induction part due 
to treatment emergent AEs (TEAEs).
3.2.
Secondary Endpoint(s)
The secondary endpoints listed below will be evaluated across the induction and monotherapy 
parts.  
3.2.1.
Safety
!
The type, frequency, and severity of AEs and serious adverse events (SAEs) graded 
using National Cancer Institute (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE, Version 4.0)
!
Discontinuation rate
!
The dose intensity
!
The incidence of dose reduction
3.2.2.
Efficacy
!
Progression free survival
!
Disease control rate
!
Overall survival
!
Overall response rate
3.3.
Exploratory Endpoint(s)
The exploratory endpoints listed below will be evaluated across the induction and monotherapy 
parts, unless indicated otherwise.
3.3.1.
Exploratory Endpoints
!
Healthcare resource utilization throughout the study using a questionnaire 
!
Changes in Physician-Reported ECOG PS
!
Changes in the EuroQol-5D (EQ5D-5L) and Lung Cancer Symptom Score (LCSS)
!
Summary of the Charlson Co-Morbidity Index (CCI) at baseline
!
Correlation between Subject-Reported ECOG PS and Physician-Reported ECOG PS 
during the treatment period
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
24
ABI-007-NSCL-004 Final: 12 January 2015
!
Correlation between Subject-Reported KPS and Physician-Reported KPS at baseline
&(/*(1(35235,(7$5<,1)250$7,21

('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
25
ABI-007-NSCL-004 Final: 12 January 2015
4.
OVERALL STUDY DESIGN
4.1.
Study Design
Approximately 50 subjects with stage IIIB or IV NSCLC and ECOG PS 2 will be enrolled in the 
study to receive nab-paclitaxel plus carboplatin for 4 cycles, followed by monotherapy with nab-
paclitaxel in the absence of disease progression.  
The study will consist of a 28-day screening period, induction with 4 cycles of nab-paclitaxel 
and carboplatin followed by nab-paclitaxel monotherapy, and follow-up.
The screening period for eligibility determination begins upon subject written informed consent.  
Induction Part
Approximately 50 eligible subjects will be enrolled in the study.  In the induction part subjects 
will receive 4 cycles of nab-paclitaxel plus carboplatin, provided all eligibility criteria are met 
within a 28-day screening period prior to Cycle 1 Day 1.
Induction treatment will consist of: 
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion on Days 1 and 8 of each 21-day 
cycle  
!
Carboplatin AUC = 5 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion.  
Monotherapy Part
Subjects may continue in the study and receive monotherapy with nab-paclitaxel in the 
absence of disease progression, after the completion of 4 cycles of the induction therapy.  
They will receive:
!
nab-Paclitaxel 100 mg/m2 IV infusion on Days 1 and 8 of each 21-day cycle.
Tumor evaluations will be assessed by the investigative sites and response will be determined 
according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, Version 1.1 
(Eisenhauer, 2009).
Follow-up Period
All subjects who discontinue treatment for any reason other than lost to follow-up or death, will 
enter the follow-up period.  All subjects will continue to have computed tomography (CT) scans 
in accordance with their institution’s standard of care and the findings will be reported on the 
appropriate electronic Case Report Form (eCRF) pages.  In addition, all post-treatment anti-
cancer therapy will be reported on the appropriate eCRF pages.  Minimally, all subjects will be 
followed for overall survival (OS) every 90 days by phone contact or chart review for 
documentation of last contact for up to 1 year after the last subject is enrolled.
4.2.
Study Design Rationale
nab-Paclitaxel demonstrated clinically meaningful benefit when studied in a phase 3 comparative 
study evaluating the use of carboplatin with either nab-paclitaxel (100 mg/m2 weekly) or 
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
26
ABI-007-NSCL-004 Final: 12 January 2015
paclitaxel (200 mg/m2 every 3 weeks) in the first-line treatment of advanced stage NSCLC 
patients with PS of 0-1.  A higher response rate was demonstrated for the nab-paclitaxel -
carboplatin arm (33%) compared to the paclitaxel-carboplatin arm (25%), p = 0.005 (Socinski, 
2012).  There was an approximate 8% difference in PFS and OS between the study arms (non-
statistically significant) favoring nab-paclitaxel.  In subgroup analyses, NSCLC subjects with 
squamous histology and elderly subjects (≥75 years of age) were observed to have experienced 
particularly robust clinical benefit.  The most common treatment-related Grade 3 or 4 
hematologic adverse events included neutropenia, leucopenia, anemia, and thrombocytopenia.  
The most common treatment-related Grade 3 or 4 non-hematologic adverse events were fatigue, 
sensory neuropathy, anorexia, nausea, myalgia and arthralgia.  nab-Paclitaxel plus carboplatin 
was associated with significantly lower rates of Grade 3 and 4 sensory neuropathy, arthralgia, 
myalgia and neutropenia, but higher rates of anemia and thrombocytopenia.
The treatment landscape for PS 2 patients can include single-agents or platinum-based doublets 
as reasonable options (National Comprehensive Cancer Network [NCCN] 2014).  So far there is 
no compelling data from clinical trials which shows superiority of one doublet regimen over 
another and there is no consensus on specific treatment recommendations for PS 2 patients.  
There is limited data of carboplatin plus nab-paclitaxel in the locally advanced or metastatic 
NSCLC setting for patient with PS 2 status.  Nevertheless, the encouraging results from a phase 
2 study in Stage III NSCLC patients provides important insight that PS 2 patients can benefit 
from the combination of carboplatin and nab-paclitaxel, albeit with slight modification to the 
regimen.  Therefore, to further characterize the tolerability and efficacy of this modified regimen 
in PS 2 NSCLC patients in the locally advanced/metastatic setting, this open-label, single-arm 
study is proposed. 
The role of continued maintenance chemotherapy has been demonstrated in several phase 3
trials, eg, pemetrexed, gemcitabine, docetaxel and bevacizumab; albeit with varied toxicity and 
efficacy outcomes.  However, the impact of continued maintenance therapy in prolonging tumor 
response or stable disease for PS 2 NSCLC patients remains to be elucidated.  Consequently, this 
study provides a unique opportunity to evaluate the impact of continuing nab-paclitaxel as 
maintenance chemotherapy after 4 cycles of induction, at the discretion of the treating 
Investigator’s benefit:risk assessment.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
27
ABI-007-NSCL-004 Final: 12 January 2015
Figure 1:
Overall Study Design
Screening for Eligibility / Enrollment (up to 28 days)
4 Cycles of Induction (N = 50)
nab-paclitaxel 100 mg/m2 IV infusion on Days 1 and 8 of each 21-day cycle
carboplatin AUC = 5 mg*min/mL IV on Day 1 of each 21-day cycle after completion of nab-paclitaxel
Absence of Clinical or Radiological Disease Progression
nab-Paclitaxel Monotherapy
nab-paclitaxel 100 mg/m2 IV infusion on Days 1 and 8 of each 21-day cycle
Treatment Until Progression or Unacceptable Toxicity
Follow-Up / Survival
A 28-day Follow-up Visit (after the last dose of investigational product(s)).
All subjects that come off treatment will be followed for post-study anti-cancer therapy, procedures and disease assessment via radiologic 
scanning in accordance with the institution’s standard of care, and every 90 days for survival until 1 year after the last subject is enrolled.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
28
ABI-007-NSCL-004 Final: 12 January 2015
4.3.
Study Duration 
4.3.1.
Duration of Treatment
All subjects will be treated until disease progression, unacceptable toxicity, death, lost to follow-
up or physician and/or patient decision to discontinue treatment.
Enrollment will last approximately 15 months.  The total length of this phase 2 study with 
induction, monotherapy, and follow-up is estimated at approximately 27 months, including a 1 
year follow-up from the last patient enrolled in the study.
4.4.
End of Trial
The end of trial is defined as either the date of the last visit of the last subject, or the date of 
receipt of the last data point from the last subject that is required for primary, secondary and/or 
exploratory analysis, as pre-specified in the protocol and/or the Statistical Analysis Plan (SAP), 
whichever is the later date.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
29
ABI-007-NSCL-004 Final: 12 January 2015
5.
TABLE OF EVENTS
Table 2:
Table of Events - Induction
Screening/
Baseline
CYCLES 1 To 4
(21-days)
Assessment
Day -28 to
Day 1
Day 1
(±2 days)
Day 8
(±2 days)
Post Every 2 
Cycles of 
Treatment
(-3/+7 days)
Treatment
Discontinuation
28-day 
Follow up 
visit
Follow-up/ 
Survivall
Informed Consent
X
-
-
-
-
-
-
Medical History, Prior Medication and Proceduresa
X
-
-
-
-
-
-
Serum β-hCGb
X
-
-
-
-
-
-
Complete Chest CT Scan (including adrenal glands) with 
and without contrast and any other studies required for 
tumor imagingc
X
-
-
X
X
-
X
Height and Weightd
X
X
X
-
-
-
-
Body Surface Area (BSA) Calculatione
X
X
X
-
-
-
-
Physician-Reported ECOG PS
X
X
-
-
X
-
-
Concomitant Medication/Proceduresf
-
X
X
-
X
X
X
Histology and Mutation Status
X
-
-
-
-
-
-
Hematology and Serum Chemistryg
X
X
X
-
X
X
-
Adverse Event Evaluation
X
X
X
-
X
X
-
nab-paclitaxel Administration
-
X
X
-
-
-
-
Carboplatin Administration
-
X
-
-
-
-
-
Electrocardiogram (ECG)
X
-
-
-
-
-
-
Baseline TNM Stage
X
-
-
-
-
-
-
Charlson Co-morbidity Index
X
-
-
-
-
-
-
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
30
ABI-007-NSCL-004 Final: 12 January 2015
Table 2:
Table of Events - Induction (Continued)
Screening/
Baseline
CYCLE 1 to 4
(21-days)
Assessment
Day -28 to
Day 1
Day 1
(±2 days)
Day 8
(±2 days)
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Cycles of 
Treatment
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Treatment
Discontinuation
28-day 
Follow-up 
visit
Follow-up/ 
Survivall
CT Scan of Head or Brain Magnetic Resonance Imaging 
(MRI), bone scan (X-rays if needed)h
X
-
-
-
-
-
-
Physical Examinationi
X
-
-
-
X
-
-
Vital Signsi
X
-
-
-
X
-
-
Smoking History
X
-
-
-
-
-
-
Spirometry and Pulse Oximetryj
X
X
-
-
X
X
-
Calculated Creatinine Clearance (24-hour urine collection)k
X
X
-
-
-
X
-
Healthcare Resource Utilization Questionnaire
-
X
-
-
X
X
-
Subject-Reported ECOG PS
-
X
-
-
X
-
-
Subject- and Physician-Reported KPS
-
X
-
-
-
-
-
LCSS and EQ5D-5L
-
X
-
-
X
-
-
Subjects Weight 6 Months Prior to signing the ICF for 
nutritional status assessment 
X
-
-
-
-
-
-
Reversibility of PS 2 Statusm
X
-
-
-
-
-
-
Survival Phone Call (or chart review for documentation of 
last contact)
-
-
-
-
-
-
X
ALT: alanine transaminase, ANC: absolute neutrophil count, AST: aspartate transaminase, beta hCG: beta human chorionic gonadotropin, CT: Computed Tomography, ECOG: 
Eastern Cooperative Oncology Group, eCRF: electronic case report form, EQ5D-5L: EuroQol-5D, ICF: Informed Consent Form, KPS: Karnofsky Performance Status: LCSS: 
Lung Cancer Symptom Score, NSCLC: non-small cell lung cancer, PS: Performance status, RECIST: Response Evaluation Criteria in Solid Tumors, TNM: tumor, node and 
metastasis, WBC = white blood cell
a Significant prior medications and procedures; provided and or performed within 28 days of signing the ICF will be recorded. All NSCLC-related prior 
medications/procedures/prior radiation therapy will be recorded regardless of time.
b Apregnancy 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 within 72 hours of the first administration of investigational product.
c All subjects must have measurable disease via objective scanning as defined by the RECIST v1.1 criteria. Required is a complete chest CT scan (including base of neck and 
adrenal glands) with and without contrast, unless contraindicated, to be performed at screening. Scans will be performed after every 2 cycles of treatment and at treatment 
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
31
ABI-007-NSCL-004 Final: 12 January 2015
discontinuation. The method of assessment utilized at baseline will remain consistent throughout study duration. A complete chest CT scan will be performed at each protocol 
required time point regardless of the location of the baseline disease.  Scans will be archived as per institution standards.  
d Height is only measured at baseline and will be recorded on the appropriate eCRF page. Weight will be measured at baseline and every visit, before drug administration and 
recorded on the appropriate eCRF page.    
e BSA will be calculated at screening and recalculated if body weight changes by more than 10% since baseline, or since the previous visit when BSA was last recalculated and 
recorded in the subject’s medical record only. BSA and body mass index will be a derived value, using the height, and weights reported.
f All concomitant medications and procedures associated with serious adverse events (SAEs) will be recorded on the eCRF from the time of signing the ICF through 28-days post 
last dose of investigational product(s).  Reporting of concomitant medications and procedures associated with non-SAEs will include all cancer-related procedures, analgesics, 
steroids, transfusions, growth factors, bisphosphonates, denosumab, and antibiotics.  All treatments and procedures provided as part of best supportive care (BSC) will require 
reporting on the eCRFs.  During the follow-up period, post-study anti-cancer therapy and procedures will be collected and reported on the appropriate eCRF.
g Local laboratory assessments will be done prior to each nab-paclitaxel treatment during the study and as clinically indicated. Note: the Cycle 1 Day 1 hematology and serum 
chemistry will not require repeating if the screening hematology and serum chemistry were performed within 2 days of the Cycle 1Day 1 visit. ANC, WBC, platelet count, 
AST/serum glutamic oxaloacetic transaminase, ALT/serum glutamic pyruvic transaminase, albumin, serum creatinine, total bilirubin, and hemoglobin (Hgb) results will be 
collected routinely on the appropriate eCRF pages. All other routine laboratory test data will not be collected in the eCRF unless it is clinically significant, which will then be 
reported as an AE, and the specific associated laboratory parameter(s) will be recorded on the laboratory assessments eCRF.
h CT Scan of Head or Brain Magnetic Resonance Imaging (MRI) and Bone Scan (X-rays if needed) will be performed ONLY if deemed appropriate by the treating physician.  
i Physical exam and vital signs data will not be captured in the eCRFs unless deemed clinically significant by the treating physician, in which case the event will be captured as an 
adverse event. At screening, findings deemed clinically significant will be captured as medical history.
j Spirometry will be measured using an FDA approved, portable spirometer. The following values will be measured and reported on the appropriate eCRF page: forced expiratory 
volume in 1 second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF). In addition pulse oximetry will be used to measure the saturation of peripheral oxygen 
(sPO2). These data will be reported on the appropriate eCRF page.
k Creatinine clearance (CrCl) will be calculated (if renal impairment is suspected 24-hour urine collection for measurement is required – but only at baseline), and these data will 
be collected on the eCRFs.
l All subjects who discontinue from treatment for reasons other than withdrawal of consent, lost to follow-up or death, will enter follow-up. It will consist of one visit 28 days after 
the last dose of investigational product(s). Thereafter subjects will return to the clinic for objective scanning per the institution’s policy and collection of post study anti-cancer 
therapy.  In addition, at minimum, subjects will be contacted by phone for survival status, approximately every 90 days (+/- 14 days). Survival status can also be gleaned from 
clinic visits / records. All data will be reported on the appropriate eCRF for up to 1 year after the last subject is enrolled.
m The treating oncologist will use his/her best clinical judgment to predict if treatment with the protocol regimen could improve poor PS of the patient, see Appendix B for more 
details.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
32
ABI-007-NSCL-004 Final: 12 January 2015
Table 3:
Table of Events – Monotherapy
EVERY CYCLE
(21-days)
Assessment
Day 1
(±2 days)
Day 8
(±2 days)
Post Every 2 
Cycles of 
Treatment
(-3/+7 days)
Treatment 
Discontinuation
28-day 
Follow-up 
Visit
Follow-up/Survivali
Complete Chest CT Scan (including adrenal 
glands) with or without contrast and any other 
studies required for tumor imaginga
-
-
X
X
-
X
CT Scan of Head or Brain Magnetic 
Resonance Imaging (MRI) and Bone Scan (X-
rays if needed)b
-
-
X
X
-
X
Weightc
X
X
-
-
X
-
Body Surface Area (BSA) Calculationd
X
X
-
-
-
-
Concomitant Medication/Procedurese
X
X
-
X
X
X
Hematology and Serum Chemistryf
X
X
-
X
X
-
Adverse Event Evaluation
X
X
-
X
X
-
nab-paclitaxel Administration
X
X
-
-
-
Survival Phone Call (or chart review for 
documentation of last contact)
-
-
-
-
-
X
Healthcare Resource Utilization Questionnaire
X
-
-
X
X
-
Physical Examinationg
-
-
-
X
-
-
Vital Signsg
X
-
-
X
-
-
Subject and Physician-Reported ECOG PS
X
-
-
X
-
-
LCSS and EQ5D-5L Questionnaires
X
-
-
X
-
-
Spirometry and Pulse Oximetryh
X
-
-
X
X
-
Calculated Creatinine Clearance
X
-
-
-
X
-
ALT: alanine transaminase, ANC: absolute neutrophil count, AST: aspartate transaminase, CT: computed tomography, ECOG: Eastern Cooperative Oncology Group, eCRF: 
electronic case report form, EQ5D-5L: EuroQol-5D, ICF: Informed Consent Form, LCSS: Lung Cancer Symptom Score, PS: performance status, WBC: white blood cell
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
33
ABI-007-NSCL-004 Final: 12 January 2015
a Scans will be performed after the completion of every 2 cycles and at treatment discontinuation (-3/+7 days).  The method of assessment utilized at baseline will remain 
consistent throughout study duration.  A complete chest CT scan with contrast, unless contraindicated, will be performed at each protocol required time point regardless of the 
location of the baseline disease. Scans will be archived as per institution standards.
b CT Scan of Head or Brain Magnetic Resonance Imaging (MRI) and Bone Scan (X-rays if needed) will be performed ONLY if deemed appropriate by the treating physician.  
c Weight will be measured before drug administration and recorded on the appropriate eCRF page.  
d BSA will be calculated at screening and recalculated if body weight changes by more than 10% since baseline, or since the previous visit when BSA was last recalculated and 
recorded in the subject’s medical records. Body mass index will be a derived value, using the height, and weights reported.
e All concomitant medications and procedures associated with serious adverse events (SAEs) will be recorded on the eCRF from the time of signing the ICF through 28 days post 
last dose of investigational product(s). Reporting of concomitant medications and procedures associated with non-SAEs will include all cancer related procedures, analgesics, 
steroids, transfusions, growth factors, bisphosphonates, denosumab and antibiotics. All treatments and procedures provided as part of best supportive care (BSC) will require 
reporting on the eCRFs. During the Follow-up period, post study anti-cancer therapy and procedures will be collected and reported on the appropriate eCRF.
f Local laboratory assessments will be done prior to each nab-paclitaxel treatment during the study and as clinically indicated. ANC, WBC, platelet count, AST/serum glutamic 
oxaloacetic transaminase, ALT/serum glutamic pyruvic transaminase, albumin, serum creatinine, total bilirubin, prothrombin time, partial thromoplastin time and hemoglobin 
(Hgb) results will be collected routinely on the appropriate eCRF pages. All other routine laboratory test data will not be collected in the eCRF unless it is clinically significant, 
which will then be reported as an AE, and the specific associated laboratory parameter(s) will be recorded on the laboratory assessments eCRF.
g Physical exam and vital signs data will not be captured in the eCRFs unless deemed clinically significant by the treating physician, in which case the event will be captured as an 
adverse event
h Spirometry will be measured using an FDA approved, portable spirometer. The following values will be measured and reported on the appropriate eCRF page: forced expiratory 
volume in 1 second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF).  In addition pulse oximetry will be used to measure the saturation of peripheral 
oxygen (sPO2). These data will be reported on the appropriate eCRF page. In addition the use of bronchodilators pre and post spirometry assessment will be collected on the 
appropriate eCRF page.
i All subjects who discontinue from treatment for reasons other than withdrawal of consent, lost to follow-up or death, will enter the Follow-up period. It will consist of one visit 
28 days after the last dose of investigational product(s).  Thereafter subjects will return to the clinic for objective scanning per the institution’s policy and collection of post study 
anti-cancer therapy.  In addition, at minimum, subjects will be contacted by phone for survival status, approximately every 90 days (+/- 14 days). Survival status can also be 
gleaned from clinic visits / records. All data will be reported on the appropriate eCRF for up to 1 year after the last subject is enrolled.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
34
ABI-007-NSCL-004 Final: 12 January 2015
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. Subjects who do not meet the inclusion/exclusion criteria will be 
considered screening failures and will not be eligible for the study. Subjects that have satisfied 
all eligibility criteria after the screening period will be eligible for enrollment. Subjects who 
screen fail may re-screen 2 additional times, the ICF process will need to be performed each 
time, as well as all screening procedures will be repeated, unless they are still within 28 days of 
Cycle 1 Day 1.  Assessments performed as standard of care and prior to signing the ICF for this 
trial, may be used to assess eligibility if performed within 28 days of Cycle 1 Day 1. 
6.1.
Medical History
A complete medical history including, but not limited to, evaluation for past or present 
significant cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine, 
lymphatic, hematological, immunologic, dermatological, psychiatric, genitourinary, obstetrical, 
surgical history or any other diseases or disorders will be recorded at screening.  The medical 
history will include a full review of the subject’s smoking history, past and present including
exposure to second hand smoke.  These data will be collected on the appropriate eCRF page and 
will include significant past medical history up to 5 years prior to signing the ICF.
6.2.
Prior Medications/Procedures
Only significant prior medications and procedures provided and or performed within 28 days of 
signing the ICF.  All NSCLC-related prior medications, procedures, including radiation therapy, 
will be recorded regardless of time.
6.3.
Pregnancy Testing
Serum pregnancy test with sensitivity of at least 25 mIU/mL is to be obtained in females of 
childbearing potential (FCBP) at screening.  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 
investigational product must be immediately reported to Celgene Drug Safety, see Section 11.4.
6.4.
Complete Chest Computed Tomography (CT) Scan (including 
adrenal gland) With and Without Contrast
A CT scan of complete chest (including the base of neck and adrenal glands) with and without 
contrast, unless medically contraindicated, and any other studies required for complete tumor 
imaging, will be done at screening, after every 2 cycles of investigational product treatment (-
3/+7 days) until treatment discontinuation, lost to follow-up, withdrawal of consent or death.   
The same modality used at screening should be used throughout the trial.  All CT scans and 
reports should be archived at the site according to the institution’s policy.  Copies will be 
provided to the sponsor if requested.  Screening scans must be within 28 days of Cycle 1 Day 1.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
35
ABI-007-NSCL-004 Final: 12 January 2015
6.5.
Height and Weight
Weight will be measured at screening and every treatment visit, prior to drug administration and 
recorded on the appropriate eCRF page.  Additional weights may be measured at any time as 
clinically indicated.  Height is only measured at baseline and will be recorded on the appropriate 
eCRF page.  
6.6.
Body Surface Area (BSA) Calculation
BSA may be recalculated if body weight changes by more than 10% since baseline or since the 
previous visit when BSA was last recalculated. These data will be recorded in the subject’s 
medical record only.  
6.7.
Physician-Reported ECOG Performance Score
ECOG PS will be assessed and reported on the appropriate eCRF at screening, Day 1 of each 
cycle and at treatment discontinuation.  Additional ECOG PS may be assessed and reported at 
any time during the study if deemed clinically necessary.
6.8.
Concomitant Medications/Procedures
All concomitant medications and procedures associated with serious adverse events (SAEs) will 
be recorded on the eCRF from the time of signing the ICF through 28-days post last dose of 
investigational product(s).  Reporting of concomitant medications and procedures associated 
with non-SAEs will include all cancer-related procedures, analgesics, steroids, transfusions, 
growth factors, bisphosphonates, denosumab and antibiotics.  All treatments and procedures 
provided as part of best supportive care (BSC) will require reporting on the eCRFs.  During the 
follow-up period, post-study anti-cancer therapy and procedures will be collected and reported on 
the appropriate eCRF.
6.9.
Adverse Event Reporting
All subjects will have AEs recorded from the time of signing the ICF through 28 days post last
dose of investigational product.  See Section 11 for details. 
6.10.
Lung Cancer Symptom Scale, Subject- and Physician-Reported KPS, 
Subject-Reported ECOG PS, EQ-5D-5L, and Charlson Co-
Morbidity Index
The Charlson Co-Morbidity Index will be used to measure co-existing medical conditions (other 
than NSCLC) at screening, for subjects in the trial. The subject-reported and physician-reported 
ECOG PS and KPS will be used to measure the performance status of subjects. LCSS and EQ-
5D-5L questionnaires will be used to measure quality of life (QoL) for subjects in the trial. The 
LCSS is a 9 question survey the subject completes using a visual analogue scale (VAS) to denote 
intensity of a symptom. The EQ-5D comprises 5 questions on mobility, self-care, usual 
activities, pain/discomfort, anxiety/depression and a VAS for overall QoL. The subject-reported 
ECOG PS , LCSS and EQ-5D-5L questionnaires will be completed at Day 1 of every cycle, and 
at treatment discontinuation. The subject and physician-reported KPS will be completed on Day 
1 of Cycle 1 only. 
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
36
ABI-007-NSCL-004 Final: 12 January 2015
6.11.
Healthcare Resource Utilization Questionnaire
A healthcare resource utilization eCRF 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 at Day 1 
of every cycle, 28-day follow-up visit and treatment discontinuation.
6.12.
Electrocardiogram 
An electrocardiogram (ECG) will be done at screening and as clinically indicated. However 
results will not be routinely collected in the eCRFs. If the results are abnormal and clinically 
significant at screening, the result will be recorded as medical history, and if results are abnormal 
and clinically significant after screening, they will be recorded as AE or SAE.
6.13.
CT Scan of Head or Brain Magnetic Resonance Imaging (MRI)
CT scan of head or brain MRI will be done as clinically indicated. However the results will not 
be collected in the eCRFs unless deemed medically significant by the treating physician. In 
addition if scans show new disease involvement by NSCLC or progression of NSCLC disease, 
this information will be collected on the appropriate eCRF. 
6.14.
Bone Scans and X-rays
Bone scans and x-rays will be done as per standard of care during the study and as clinically 
indicated. However, the results will not be collected in the eCRFs unless deemed medically 
significant by the treating physician. In addition if scans show new disease involvement by 
NSCLC or progression of NSCLC, this information will be collected on the appropriate eCRF 
pages. 
6.15.
Physical Examinations
Physical examinations will be performed per institutional policy, at screening and treatment 
discontinuation, in addition to any other time as clinically indicated. However results will not be 
routinely collected on the eCRFs. If the findings are abnormal and clinically significant at 
screening, they will be recorded as medical history, and if findings are abnormal and clinically 
significant after screening, they will be recorded as an AE.  
6.16.
Vital Signs
Vital signs will be measured at screening, treatment discontinuation and any other time as 
clinically indicated / standard of care for the institution. However results will not be routinely 
collected on the eCRFs. If the findings are abnormal and clinically significant at screening, they 
will be recorded as medical history, and if findings are abnormal and clinically significant any 
time after screening, they will be recorded as an AE.
6.17.
Laboratory Assessments
Local laboratory assessments will be performed at screening, prior to administration of 
investigational product treatment, treatment discontinuation, 28 days post last dose of 
investigational product and as clinically indicated. Absolute neutrophil count, white blood cell 
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
37
ABI-007-NSCL-004 Final: 12 January 2015
count, platelet count, serum creatinine, calculated creatinine clearance, 24 hour urine collection 
(where applicable) hemoglobin, aspartate transaminase (AST)/serum glutamic oxaloacetic 
transaminase, alanine transaminase (ALT)/serum glutamic pyruvic transaminase, albumin, total 
bilirubin will be recorded during the time points outlined above and captured on the appropriate 
eCRF page, along with the local lab normal ranges. All other laboratory values, except those 
mentioned above, will not be routinely reported on the eCRF.
If any laboratory value is found to be abnormal during screening, the value(s) will be recorded 
on the medical history eCRF with the associated NCI CTCAE grade. If any laboratory value is 
found to be abnormal and clinically significant post-screening, the value(s) will be recorded on 
the laboratory assessment eCRF along with the local lab normal range and the appropriate 
diagnosis will be recorded on the AE eCRF page. It is the responsibility of the Investigator to 
assess the clinical significance of all abnormal laboratory values as defined by the reference 
ranges of the individual local laboratory. Any abnormal values that persist should be followed at 
the discretion of the Investigator. The Investigator should file all laboratory reports, including 
faxes, in the subject’s medical chart.
6.18.
Follow-Up / Survival
All subjects who discontinue from treatment for reasons other than withdrawal of consent, lost to 
follow-up or death, will enter the follow-up period. It will consist of one visit 28 days after the 
last dose of investigational product. Thereafter subjects will return to the clinic for objective 
scanning per the institution’s policy and collection of post study anti-cancer therapy and 
procedures. In addition, at minimum, subjects will be contacted by phone approximately every 
90 days (+/- 14 days) up to 1 year after the last subject is enrolled. Survival status can also be 
gleaned from clinic visits / records. All data will be reported on the appropriate eCRF page. 
6.19.
Histology and Mutation Status:  
Histology will be obtained from the local pathology report and recorded on the appropriate eCRF 
page. Mutation status will be obtained from the local pathology report if available, these data 
will be collected on the appropriate eCRF page. Re-biopsies for the purpose of the study are not 
required.
6.20.
Spirometry and Pulse Oximetry
Spirometry, per the American Thoracic Society (ATS) guidelines, will be measured using an 
FDA approved portable spirometer. The following values will be measured and reported on the 
appropriate eCRF page: forced expiratory volume in 1 second (FEV1), forced vital capacity 
(FVC) and peak expiratory flow (PEF). In addition pulse oximetry will be used to measure the 
saturation of peripheral oxygen (sPO2) and these data will be reported on the appropriate eCRF 
page.  Spirometry and pulse oximetry measurements will be performed at screening, prior to 
administration of investigational product on Day 1 of every cycle, investigational product
discontinuation, 28 days post last dose of investigational product. In addition, those subjects 
prescribed bronchodilators will require spirometry assessments both pre and post bronchodilator 
usage. These data will be collected on the appropriate eCRF page.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
38
ABI-007-NSCL-004 Final: 12 January 2015
6.21.
Baseline Tumor, Node and Metastasis (TNM) Stage
The baseline TNM staging will be assessed and reported by the Investigator and collected on the 
appropriate eCRF page.
6.22.
Assessment of Nutritional Status
Nutritional status will be assessed using laboratory values, body mass index and the percentage 
of unintentional weight loss. Laboratory values will be analyzed and reported on the appropriate 
eCRFs according to Table 2 and Table 3. Body mass index will be derived using the height and 
weight reported on the eCRFs and the percentage of unintentional weight loss will be derived 
using the baseline body weight and the subject’s weight approximately 6 months prior to 
baseline. These data will be analyzed per the description in the SAP.
6.23.
Reversibility of PS 2 Status
This assessment will be made at baseline only and reported on the appropriate eCRF page. 
nd 
nd 
ved 
ved 
o
riate eCRF 
iate eCRF 

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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-004 Final: 12 January 2015
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Adults ≥ 18 years old with locally advanced or metastatic NSCLC and PS 2 who have not 
received chemotherapy for their advanced disease and are not candidates for curative surgery or 
radiation therapy, will be eligible for this study. The induction part of the study will enroll 
approximately 50 subjects. Subjects, after 4 cycles of nab-paclitaxel and carboplatin may begin 
monotherapy with nab-paclitaxel in the absence of clinical or radiological disease progression. 
The study will be conducted at approximately 8 to 10 sites in the United States.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled:
General and Demographics
1. Age ≥ 18 years of age at the time of signing the ICF.
2. Understand and voluntarily provide written consent to the ICF prior to conducting any 
study related assessments/procedures. 
3. Able to adhere to the study visit schedule and other protocol requirements.
Disease Specific
4. Histologically or cytologically confirmed Stage IIIB or IV NSCLC.
5. Radiographically documented measurable disease at study entry per RECIST v1.1.
6. No prior anti-cancer therapy for the treatment of metastatic disease at the time of signing 
the ICF. Adjuvant treatment is permitted providing cytotoxic chemotherapy was 
completed 12 months prior to signing the ICF and without disease recurrence.
7. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
8. Platelets ≥ 100,000 cells/mm3. 
9. Hemoglobin (Hgb) ≥ 9 g/dL.
10. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]), alanine
transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper limit of 
normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
11. Total bilirubin ≤ 1.5 × ULN except in cases of Gilbert’s disease and liver metastases. 
12. Serum creatinine ≤1.5 x ULN, or calculated creatinine clearance ≥40 mL/min (if renal 
impairment is suspected 24-hour urine collection for measurement is required). 
13. Eastern Cooperative Oncology Group Performance Status 2.
14. 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-004
Celgene Corporation
Confidential and Proprietary
40
ABI-007-NSCL-004 Final: 12 January 2015
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.
b. You must commit to complete abstinence from heterosexual contact, or agree to use 
medical doctor-approved contraception throughout the study without interruption; 
while receiving study medication or for a longer period if required by local 
regulations. 
Male subjects must:
c.
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 investigational product
discontinuation, even if he has undergone a successful vasectomy. 
7.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. Evidence of active brain metastases, including leptomeningeal involvement (prior 
evidence of brain metastasis are permitted only if treated and stable and off therapy for at 
least 21 days prior to signing ICF). MRI of the brain (or CT scan w/contrast) is preferred 
for diagnosis.
2. History of leptomeningeal disease.
3. Only evidence of disease is non-measurable.
4. Pre-existing peripheral neuropathy of Grade 2, 3, or 4 (per CTCAE v4.0).
5. Subject has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 
weeks prior to starting investigational product (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.
6. Venous thromboembolism within 1 month prior to signing ICF.
7. Current congestive heart failure (New York Heart Association Class II-IV).
8. History of the following within 6 months prior to first administration of investigational 
product: 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 ECG abnormality, cerebrovascular accident, transient ischemic attack, or 
seizure disorder.
9. Subject has a known infection with hepatitis B or C, or history of human 
immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or 
myelosuppressive medications that would in the opinion of the Investigator, increase the 
risk of serious neutropenic complications.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
41
ABI-007-NSCL-004 Final: 12 January 2015
10. Subject has an 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.
11. History of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or 
pulmonary hypersensitivity pneumonitis.
12. Treatment with any investigational product within 28 days prior to signing the ICF.
13. History of or suspected allergy to nab-paclitaxel, carboplatin and human albumin or any 
other platinum-based therapy.
14. Currently enrolled in any other clinical protocol or investigational trial that involves 
administration of experimental therapy and/or therapeutic devices.
15. 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.
16. Subject has any other malignancy within 5 years prior to signing the ICF. Exceptions 
include the following: 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 stage of T1a or T1b). All treatment should 
have been completed 6 months prior to signing ICF.
17. Any condition including the presence of laboratory abnormalities, which places the 
subject at unacceptable risk if he/she were to participate in the study.
18. Any medical condition that confounds the ability to interpret data from the study.  This 
includes subjects with known psychiatric disorders.
19. Pregnant or breast-feeding females.
20. Subjects with an ECOG PS other than 2.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
42
ABI-007-NSCL-004 Final: 12 January 2015
8.
DESCRIPTION OF INVESTIGATIONAL PRODUCT
8.1.
Description of Investigational Product
Induction 
Subjects will receive open-label nab-paclitaxel and carboplatin during the induction part of the 
study.
nab-Paclitaxel is designated as investigational product and will be supplied by Celgene. 
Carboplatin will be supplied commercially, by prescription only.
The preparation for IV administration procedures should be followed as per the locally approved 
prescribing information. 
Monotherapy  
Subjects will receive open-label nab-paclitaxel. 
nab-Paclitaxel is designated as investigational product and will be supplied by Celgene. 
The preparation for IV administration procedures should be followed as per the locally approved 
prescribing information. 
8.1.1.
nab-Paclitaxel
nab-Paclitaxel is designated as investigational product and will be supplied by the Sponsor, 
Celgene Corporation.  nab-Paclitaxel is supplied in single-use vials in single count cartons.   
Each single-use 50 mL vial will contain paclitaxel (100 mg) and approximately 900 mg 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.
Temperature records for nab-paclitaxel must be made available to Celgene or other Sponsor-
nominated monitoring teams for verification of proper investigational product storage.
8.1.2.
Carboplatin
Carboplatin will be provided commercially, by prescription only. 
Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic 
agent. The chemical name for carboplatin is platinum diammine [1,1-cyclobutanedicarboxylato 
(2-)0,0’]-,(SP-4-2). Carboplatin is a crystalline powder with the molecular formula of 
C6Hl2N204Pt and a molecular weight of 371.25. It is soluble in water at a rate of approximately 
14 mg/mL, and the pH of a 1% solution is 5 to 7. It is virtually insoluble in ethanol, acetone, and 
dimethylacetamide. 
For additional information about carboplatin storage, preparation, and administration please refer 
to the locally approved prescribing information. 
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
43
ABI-007-NSCL-004 Final: 12 January 2015
8.2.
Treatment Administration and Schedule
Induction
Approximately 50 subjects will be treated with nab-paclitaxel plus carboplatin for 4 cycles.
Induction treatment will consist of: 
!
nab-Paclitaxel 100 mg/m2 IV infusion on Days 1 and 8 of each 21-day cycle.
!
Carboplatin AUC = 5 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion.
Monotherapy
Subjects may begin monotherapy with nab-paclitaxel in the absence of clinical or radiological 
disease progression:
!
nab-Paclitaxel 100 mg/m2 IV infusion on Days 1 and 8 of each 21-day cycle.
8.3.
Dose Delay and Dose Modifications
A dose delay will be considered if for
Day 1: Treatment to be administered is delayed, the 21-day cycle will not be considered 
to start until the day the investigational product is actually administered to the patient
Day 8: Treatment is ≥3 days late
!
In subjects who experience any of the adverse drug reactions in Table 4 nab-
paclitaxel on Day 1 of a cycle will not be administered 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 treatment will be 
withheld 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, doses of nab-paclitaxel 
and carboplatin will be permanently reduced as outlined in Table 4. Withhold nab-
paclitaxel for Grade 3 or 4 peripheral neuropathy. Reduced doses of nab-paclitaxel 
and carboplatin will be resumed (Table 4) when peripheral neuropathy improves to 
Grade 1 or completely resolves. 
For Grade 2 or 3 cutaneous toxicity, Grade 3 mucositis, or Grade 3 diarrhea, 
treatment will be interrupted until the toxicity improves to ≤Grade 1, then restarted
according to the guidelines in Table 4. For any other Grade 3 or 4 non-hematologic 
toxicity, treatment will be interrupted until the toxicity improves to ≤Grade 2, then 
restarted according to the guidelines in Table 4.
Re-escalation is not permitted at any time. 
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
44
ABI-007-NSCL-004 Final: 12 January 2015
Table 4:
Permanent Dose Reductions for Hematologic and Non-Hematologic 
Toxicities on the Study
Adverse Drug Reaction
Occurrence
nab-Paclitaxel 
Dose (mg/m2)
Carboplatin 
Dose (AUC=5 
mg*min/mL)
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
4.5
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50
3.0
Third
Discontinue Treatment*
Platelet count < 50,000/mm3
First
75
4.5
Second
Discontinue Treatment*
Peripheral Neuropathy Grade 3 or 4
First
75
4.5
Second
50
3.0
Third
Discontinue Treatment*
Grade 2 or 3 cutaneous toxicity
Grade 3 diarrhea
Grade 3 mucositis
Any other Grade 3 or 4 nonhematologic toxicity 
First
75
4.5
Second
50
3.0
Third
Discontinue Treatment*
Grade 4 cutaneous toxicity, diarrhea or mucositis
First
Discontinue Treatment*
ANC = absolute neutrophil count; AUC = area under the curve.
* If an adverse event that requires dose reduction recurs after the dose has been reduced according to the table 
above, the subject should 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. 
8.4.
Method of Treatment Assignment
This is a single arm, open-label trial. 
8.5.
Packaging and Labeling
The label(s) for investigational product will include sponsor name, address and telephone 
number, the protocol number, investigational product name, dosage form and strength (where 
applicable), amount of investigational product 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.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
45
ABI-007-NSCL-004 Final: 12 January 2015
8.6.
Investigational Product Accountability and Disposal
Celgene (or designee) will review with the Investigator and relevant site personnel the process 
for investigational product return, disposal, and/or destruction including responsibilities for the 
site vs. Celgene (or designee).
Celgene will instruct the Investigator on the return, disposal and/or destruction of investigational 
product and/or medical device materials if applicable. Only completely unused investigational 
product vials should be retained by the site until a representative from Celgene or other Celgene-
designated personnel have completed an inventory. Partially used and completely used vials 
should be destroyed according to local guidelines, and disposition should be recorded on the 
Investigational Product Accountability Record Form.
The Investigator, or designee, shall record the dispensing of investigational product to subjects in 
an investigational product accountability record. The investigational product record will be made 
available to Celgene, or other authorized Celgene-designated monitoring personnel for the 
purpose of accounting for the investigational product supply. Inspections of the investigational 
product supply for inventory purposes and assurance of proper storage will be conducted as 
necessary. Any significant discrepancy will be recorded and reported to Celgene or their 
designee and a plan for resolution will be documented.
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 investigational product between locations within their network as clinical 
trial agreement and local guidelines permit.
8.7.
Investigational Product Compliance
All investigational product will be administered only by study site personnel and accurate 
recording of all investigational product administration will be made in the appropriate section of 
the subject’s eCRF and source documents
8.8.
Overdose
Overdose, as defined for this protocol, refers to nab-paclitaxel and carboplatin dosing only.  
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel or carboplatin to a given subject, regardless of any associated adverse events or 
sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency. 
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. See 
Section 11 for the reporting of adverse events associated with overdose. 
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
46
ABI-007-NSCL-004 Final: 12 January 2015
9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
All supportive care is permitted in accordance with local standard of care.  Subjects may receive 
BSC as needed per Investigator discretion and should be recorded on the appropriate eCRF 
pages.
BSC is defined as the best palliative care per Investigator (including but not limited to: 
antibiotics, analgesics, anti-emetics, thoracentesis, pleurodesis, blood transfusions, nutritional 
support, and/or focal external-beam radiation for control of pain, cough, dyspnea, or 
hemoptysis), excluding anti-neoplastic agents.
9.2.
Prohibited Concomitant Medications and Procedures
Other anti-neoplastic agents or investigational products other than what is specified in the 
protocol are prohibited.
9.3.
Required Concomitant Medications and Procedures
Not Applicable.
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
47
ABI-007-NSCL-004 Final: 12 January 2015
10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the study are described 
below. Additional analyses of these endpoints as well as exploratory endpoints or subgroup 
analyses will be described in detail in the SAP. The SAP supersedes the analyses described in the 
protocol should there be differences between the two.
10.1.
Overview
Approximately 50 subjects will be enrolled and treated in this study. All subjects enrolled will 
have an ECOG performance status 2.  All subjects will receive nab-paclitaxel 100 mg/m2 on 
Days 1 and 8, and carboplatin AUC = 5 mg*min/mL on Day 1 of each 21-day cycle for the first
4 cycles. Subjects will have CT scans after every 2 cycles of investigational product treatment 
(-3/+7 days). At the end of 4 cycles subjects may begin monotherapy with nab-paclitaxel 100 
mg/m2 on Days 1 and 8 of each 21-day cycle in the absence of clinical or radiological disease 
progression, until documented radiologic progression or unacceptable toxicity.
Enrollment will be conducted and tracked centrally using an Interactive Response Technology 
(IRT) system to ensure that approximately 50% of the study population will be subjects with 
adenocarcinoma and 50% with squamous cell NSCLC.  
The date of enrollment is defined as the date on which the subject is registered into the IRT 
system.
10.2.
Study Population Definitions
10.2.1.
Treated Population
The treated population will consist of all subjects who received at least one dose of 
investigational product.
10.2.2.
Per-protocol (PP) Population
The PP population is defined as all eligible subjects enrolled who receive at least one dose of the 
investigational product and have a baseline and at least one post-baseline efficacy measurement 
for the endpoint of interest.  Additional analyses utilizing the PP population will be described in 
the SAP.
10.3.
Sample Size and Power Considerations
The primary objective of this study is to assess the safety and tolerability of nab-paclitaxel in 
combination with carboplatin for 4 cycles for the first-line treatment of locally advanced or 
metastatic NSCLC in subjects with an ECOG performance status 2. All evaluations of the safety 
and efficacy endpoints will be based on the point estimates and the associated two-sided 95% 
confidence intervals rather than formal inferential statistical tests. 
The primary study endpoint (also the primary safety endpoint) is the percentage of subjects who 
discontinue during the induction part due to TEAEs. With a sample size of 50, the maximum 
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
48
ABI-007-NSCL-004 Final: 12 January 2015
width of the 95% confidence interval for any proportion is 28.9%. Of note, assuming the 
underlying percentage of subjects who will discontinue from study treatment due to TEAEs is 
30%, a sample size of 50 provides 80% power, with a one-sided significance level of 10%, to 
detect an increase of 15 percentage points from 30%.
Table 5 below demonstrates the precision of the estimate that can be attained given a sample size 
of 50 for a range of hypothetical rate of study treatment discontinuation due to TEAEs during the 
induction part of the study. For example, for a hypothetical discontinuation rate of 30%, the 
width of the associated two-sided 95% confidence interval is 26.7%, and the estimated 95% 
confidence interval is (17.9% - 44.6%).
Table 5:
Precision of the Estimate for the Treatment Discontinuation Rate due to
Treatment-Emergent Adverse Events Given a Sample Size of 50
Hypothetical Discontinuation 
Rate due to Treatment-
Emergent Adverse Events
Actual Widtha of 95% 
Confidence Interval
Two-sided 95%
Confidence Intervala
30.0%
26.7%
(17.9% - 44.6%)
35.0%
27.7%
(22.1% - 49.8%)
40.0%
28.4%
(26.4% - 54.8%)
45.0%
28.8%
(30.9% - 59.7%)
50.0%
28.9%
(35.5% - 64.5%)
a Estimated using the Clopper-Pearson exact method.
The analysis of both the safety and efficacy endpoints for the clinical study report will be 
performed at approximately 6 months after the last subject is enrolled. Subjects will be followed 
for OS until 12 months after the last subject is enrolled.  
10.4.
Background and Demographic Characteristics
The baseline characteristics of all enrolled subjects will be summarized. Subject’s age, height, 
weight, and baseline characteristics will be summarized using descriptive statistics, while gender, 
race and other categorical variables will be provided using frequency tabulations. Selected 
medical history data will be summarized using frequency tabulations by system organ class and 
preferred term.
10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both treatment 
and follow-up periods. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
49
ABI-007-NSCL-004 Final: 12 January 2015
10.6.
Safety Analysis
The treated population, which includes all enrolled subjects who received at least one dose of
investigational product, will be the analysis population for all safety analyses.  
The safety and tolerability of the treatment regimen will be monitored through continuous 
reporting and evaluated by the primary safety endpoint, TEAEs, and serious adverse events 
(SAEs), and incidence of subjects experiencing dose modifications, dose delay, dose 
interruptions during infusion, and/or premature discontinuation of investigational product. 
10.6.1.
Primary Safety Endpoint
The primary endpoint for this study (also the primary safety endpoint) is the percentage of 
subjects who discontinue study treatment during the induction part due to TEAEs.  
Treatment-emergent AEs are defined as any AE or SAE occurring or worsening on or after the 
day of the first dose of the investigational product through 28 days after the last dose of 
investigational product.  In addition, any serious AE with an onset date more than 28 days after 
the last dose of investigational product that is assessed by the Investigator as related to 
investigational product will be considered a TEAE. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA). The severity of AEs will be graded based on NCI Common Terminology Criteria 
for Adverse Events (CTCAE, Version 4.0);
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40
10.6.2.
Adverse Events
In addition to the analysis described above for the primary safety endpoint which focuses on the 
safety and tolerability of the induction regimen, the safety and tolerability of the treatment 
regimen for the entire study will be assessed by TEAE rate, Grade 3 or higher TEAEs, serious 
AEs, TEAEs leading to dose reduction, dose delay, and dose interruption, TEAEs leading to 
treatment discontinuation, and TEAEs with an outcome of death for the entire study will be 
summarized by MedDRA system organ class and preferred terms. 
Adverse events of special interest of the nab-paclitaxel plus carboplatin combination identified in 
previous studies in a similar population may be identified and summarized by worst NCI 
CTCAE grade, System Organ Class (SOC) and MedDRA preferred terms.
By-subject listings will be provided for all relevant safety data. Graphical displays and figures 
will be provided where useful to assist in the interpretation of results.
10.6.3.
Laboratory Assessments
Hematology Parameters: In order to investigate the maximal degree of myelosuppression, the 
NCI CTCAE v 4.0 grades for ANC, platelet count, white blood cell (WBC) count, and 
hemoglobin concentration will be summarized by the most severe grade in each treatment cycle 
and by the most severe grade anytime during the study. 
Hepatic and renal function will be summarized using the most severe NCI CTCAE grade for 
ALT (SGPT), AST (SGOT), total bilirubin, and creatinine clearance by cycle and at any time 
during the treatment.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
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Other laboratory parameters reported by the Investigators will also be graded by NCI CTCAE 
V4.0 criteria, as appropriate.  All laboratory parameters will be summarized by descriptive
statistics by visit. 
10.6.4.
Investigational Product Exposure
The extent of exposure to the investigational products will be assessed based on the descriptive 
statistics on the number of cycles and investigational products doses administered, cumulative 
dose, average dose intensity, and percentage of protocol dose administered.  The incidences of
nab-paclitaxel and/or carboplatin dose reductions, dose interruptions, and dose delays will be 
summarized.  
10.7.
Efficacy Analysis
The treated population will be the primary analysis population for all efficacy endpoints.
10.7.1.
Efficacy Endpoints 
10.7.1.1.
Progression-free Survival
Progression-free survival is defined as the time from the date of the first dose of investigational
product to the date of disease progression or death (any cause) on or prior to the data cutoff date 
for analyses, whichever occurred 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 investigational product. 
Subjects who do not have disease progression and are alive as of the data cutoff date for the 
statistical analysis will be censored at the date of the last radiologic assessment prior to the data 
cutoff date. Similarly, subjects who discontinue from the study prior to disease progression or 
death will be censored at the date of the last radiologic assessment prior to the data cutoff date.  
In the event that a new anticancer treatment occurs prior to documented progression, the subject 
will be censored at the date of the last radiologic assessment where the subject was documented 
to be progression-free prior to the new anticancer treatment. Subjects with a single missing 
radiologic assessment prior to a visit with documented disease progression (or death) will be 
analyzed as a PFS event at the date of the radiologic assessment that shows progression or death 
(whichever is earlier). Subjects with two or more missing radiologic assessments prior to a visit 
with documented disease progression (or death) will be censored at the date of the last radiologic 
assessment where the subject was documented to be progression-free prior to the first of the two 
missing visits.  Subjects who drop out early or die without any post-baseline radiologic tumor 
assessment will be censored on the date of enrollment.   
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time and PFS rates at 2-month intervals from the day of the first dose of IP (including two-sided 
95% CI). The Kaplan-Meier curve for PFS will be presented graphically. 
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.  
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('06'RF1XPEHU
nab-Paclitaxel
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Celgene Corporation
Confidential and Proprietary
51
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10.7.1.2.
Disease Control Rate
Disease control rate is defined as the percent of subjects who have stable disease, complete 
response or partial response during the course of the study, according to RECIST 1.1 guidelines, 
as evaluated by the Investigator.  
Disease control rate will be summarized by the observed DCR rate and the associated two-sided 
95% CI.
10.7.1.3.
Overall Survival
Overall survival is defined as the time between the date of the first dose of investigational 
product 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 alive as of the data cutoff date will be 
censored at the cutoff date. Overall survival will be summarized similarly as PFS.
10.7.1.4.
Overall Response Rate 
Overall response rate is defined as the percent of subjects who have a radiologic complete or 
partial response during the course of the study evaluated by the Investigator, according to 
RECIST v1.1 guidelines.  
Overall response rate will be presented with the two-sided 95% CI.    
10.7.2.
Exploratory Endpoints
10.7.2.1.
Health Care Utilization 
Healthcare utilization will be summarized with all subjects treated.  Additional analyses will be 
described in detail in the SAP.
10.7.2.2.
Quality of Life and Lung Cancer Symptom Questionnaires 
The score and the corresponding change from baseline at each time point will be summarized for 
the LCSS and EQ5D-5L. Additional analyses will be described in detail in the SAP.
10.7.2.3.
Physician- and Subject-Reported ECOG Performance Status
ECOG PS scores as reported by the physician and the subject will be summarized by the actual 
score and change from baseline score over time.  The correlation between the two sets of ECOG 
PS scores will be explored by cross-tabulation of the two endpoints.  Other methods for 
exploration will be described in the SAP.  
10.7.2.4.
Physician- and Subject-Reported Karnofsky Performance Status
KPS as reported by the physician and the subject at baseline will be summarized.  The 
correlation between the two sets of KPS scores will be explored by cross-tabulation of the two 
endpoints.  
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('06'RF1XPEHU
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Celgene Corporation
Confidential and Proprietary
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10.7.2.5.
Treatment Response During the Monotherapy Part
The number and percentage of subjects who attain a greater degree of treatment response (from 
stable disease [SD] to CR or PR and from PR to CR) during the monotherapy part compared 
with the response at the start of the monotherapy with nab-paclitaxel will be summarized. 
10.8.
Investigational Product Termination
Reasons for stopping investigational product 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 
investigational product through 28 days post last dose of the investigational product) and deaths 
that occur during the follow-up period will be summarized by frequency of occurrence and 
corresponding percentage by cause of death per period (during treatment or follow-up). 
10.10.
Interim Analysis
In addition to the continuous monitoring and reporting of the TEAEs and safety-related data, an 
interim review of the percentage of subjects discontinued due to TEAEs will be conducted when 
20 subjects have either completed 4 cycles of induction therapy, or have discontinued due to 
reasons other than lost to follow-up prior to completing 4 cycles of induction therapy to 
safeguard the safety of the subjects enrolled in the study.  Data will be reviewed by the Scientific 
Steering Committee.   
10.11.
Scientific Steering Committee
A Scientific Steering Committee will be established, with the responsibilities for safeguarding 
the interests of study participants and monitoring the overall conduct of the study. A charter will 
be established for regular safety data review.  The Scientific Steering Committee (SSC) will have 
the ability to recommend termination of the study if a safety signal is discovered.  Final 
recommendations of the SSC will reflect the judgment of the SSC members and will be 
considered advisory in nature to the Sponsor. The decision to implement the recommendations of 
the SSC will be made by the Sponsor.
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
53
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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 CRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
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 on the overdose CRF. (See Section 8.8 for the definition of overdose.) Any sequelae 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 sequelae 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 an overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary.  There is no known specific antidote for nab-paclitaxel or 
carboplatin 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 tests and/or procedures.
All AEs will be recorded by the Investigator from the time the subject signs informed consent 
until 28 days after the last dose of investigational product and those SAEs made known to the 
Investigator at any time thereafter that are suspected of being related to investigational product.  
AEs and serious adverse events (SAEs) will be recorded on the AE page of the CRF and in the 
subject’s source documents.  All SAEs must be reported to Celgene Drug Safety within 24 hours 
of the Investigator’s knowledge of the event by facsimile, or other appropriate method, using the 
SAE Report Form, or approved equivalent form.  
11.2.
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to: 
11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
!
Results in death;
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('06'RF1XPEHU
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Celgene Corporation
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!
Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.  
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration.  However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication.  However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling).  However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the CRF.  Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of or an elective procedure for a pre-existing condition 
unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the CRF and the SAE Report Form 
must be completed.
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
55
ABI-007-NSCL-004 Final: 12 January 2015
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to investigational product, action taken regarding investigational product, 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 the Common Terminology Criteria for Adverse Events 
(CTCAE, Version 4.0); 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40
AEs that are not defined in the 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 investigational 
product 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 
investigational product administration is unlikely or remote, or 
other medications, therapeutic interventions, or underlying 
conditions provide a sufficient explanation for the observed 
event.
Suspected:
Means there is a reasonable possibility that the administration 
of investigational product caused the adverse event.  
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-004
Celgene Corporation
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ABI-007-NSCL-004 Final: 12 January 2015
‘Reasonable possibility’ means there is evidence to suggest a 
causal relationship between the investigational product 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 
investigational product that has not been manufactured or provided by Celgene, please provide 
the name of the manufacturer when reporting the event.
11.2.4.
Duration
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event.
11.2.5.
Action Taken
The Investigator will report the action taken with investigational product as a result of an AE or 
SAE, as applicable (eg, discontinuation, interruption, or reduction of investigational product, as 
appropriate) and report if concomitant and/or additional treatments were given for the event.
11.2.6.
Outcome
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 investigational product dose, or any 
other therapeutic intervention; or
!
is judged to be of significant clinical importance.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.  
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the CRF.  If the abnormality was not a 
part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE. If 
possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
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11.4.1.
Females of Childbearing Potential:
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on investigational product, or 
within 28 days after the subject’s last dose of investigational product, are considered immediately 
reportable events.  Investigational product 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 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 investigational product 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 receiving study medication or within 6 months after the last 
becomes pregnant, the male subject taking investigational product should notify the Investigator.
The pregnant female partner should be advised to call their healthcare provider immediately.   
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 CRF.  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 is accurate and consistent.  
This requirement applies to all SAEs (regardless of relationship to investigational product) that 
occur during the study (from the time the subject signs informed consent until 28 days after the 
last dose of investigational product) or any SAE made known to the Investigator at anytime 
thereafter that are suspected of being related to investigational product.  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 
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Celgene Corporation
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58
ABI-007-NSCL-004 Final: 12 January 2015
Safety as soon as these become available.  Any follow-up data should 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 Institutional 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The Investigator must keep copies of all SAE 
information on file including correspondence with Celgene and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail.  The response time is expected to be no more than five (5) business 
days.  Urgent queries (eg, missing causality assessment) may be handled by phone.
11.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to Celgene investigational product based on the Investigator 
Brochure.
In the United States, all suspected unexpected serious adverse reactions (SUSARs) will be 
reported in an expedited manner in accordance with 21 CFR 312.32.
Celgene or its authorized representative shall notify the Investigator of the following information 
!
Any AE suspected of being related to the use of investigational product in this study 
or in other studies that is both serious and unexpected (ie, SUSAR);
!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC.  (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form Completion Guidelines or to the Pregnancy Report Form Completion Guidelines.
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
59
ABI-007-NSCL-004 Final: 12 January 2015
12.
DISCONTINUATIONS
12.1.
Treatment Discontinuation
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.
The following events are considered sufficient reasons for discontinuing a subject from the 
investigational product and/or from the study:
!
Adverse event
!
Disease progression
!
Withdrawal by subject or treating physician
!
Death
!
Lost to follow-up
!
Protocol violation
The reason for treatment discontinuation should be recorded in the CRF and in the source 
documents.
All subjects discontinued from nab-paclitaxel for any reason will have a treatment
discontinuation visit at the time of nab-paclitaxel discontinuation and should undergo early 
termination procedures.
All subjects discontinued from nab-paclitaxel will return to the clinic 28 days after the last dose 
of investigational product for the collection of AEs. 
The Investigator must notify the Medical Monitor immediately when a subject has been 
discontinued/withdrawn due to an AE (any unacceptable toxicity). All subjects who are 
withdrawn from the study should complete all protocol-required evaluations scheduled for early 
termination at the time of withdrawal.
The reason for treatment discontinuation should be recorded in the eCRF and in the source 
documents.
12.2.
Study Discontinuation
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.
The following are considered sufficient reasons for discontinuing a subject from the study:
!
Withdrawal of consent (decision from the subject not to provide follow-up 
information)
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
60
ABI-007-NSCL-004 Final: 12 January 2015
!
Death
!
Lost to follow-up
The following may be considered a sufficient reason for discontinuing a subject from the study:
!
Protocol violation
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents.
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Celgene Corporation
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61
ABI-007-NSCL-004 Final: 12 January 2015
13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research 
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page).This global Emergency 
Call Center is available 24 hours a day and 7 days a week. The representatives are responsible 
for obtaining your call-back information and contacting the on call Celgene/Contract Research 
Organization (CRO) Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
13.2.
Emergency Identification of Investigational Product
This is an open-label study; therefore, IP will be identified on the package labeling.
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Celgene Corporation
Confidential and Proprietary
62
ABI-007-NSCL-004 Final: 12 January 2015
14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, 
and Investigator abide by Good Clinical Practice (GCP), as described in International 
Conference on Harmonisation (ICH) Guideline E6 and in accordance with the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
IRB/EC prior to commencement. The Investigator will conduct all aspects of this study in 
accordance with applicable national, state, and local laws of the pertinent regulatory authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations.  Celgene staff or an authorized representative will evaluate and approve all 
Investigators who in turn will select their staff.
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, investigational products, 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 informed consent 
document 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 CRFs and queries.
14.3.
Subject Information and Informed Consent
The Investigator must obtain informed consent of a subject and/or a subject’s legal representative 
prior to any study-related procedures.
Documentation that informed consent occurred prior to the study subject’s entry into the study 
and of the informed consent process should be recorded in the study subject’s source documents 
including the date.  The original informed consent document signed and dated by the study 
subject and by the person consenting the study subject prior to the study subject’s entry into the 
study, must be maintained in the Investigator’s study files and a copy given to the study subject.  
In addition, if a protocol is amended and it impacts on the content of the informed consent, the 
informed consent document must be revised.  Study subjects participating in the study when the 
amended protocol is implemented must be re-consented with the revised version of the informed 
consent document.  The revised informed consent document signed and dated by the study 
subject and by the person consenting the study subject must be maintained in the Investigator’s 
study files and a copy given to the study subject.  
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Celgene Corporation
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63
ABI-007-NSCL-004 Final: 12 January 2015
14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the Investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed informed consent document, it is the responsibility of the Investigator to obtain 
such permission in writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor.  Amendments will be submitted to the IRB/EC for written approval.  
Written approval must be obtained before implementation of the amended version occurs.  The 
written signed approval from the IRB/EC should specifically reference the Investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, informed consent document, 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.
Investigational product can only be supplied to an Investigator by Celgene or its authorized 
representative after documentation on all ethical and legal requirements for starting the study has 
been received by Celgene or its authorized representative. This documentation must also include 
a list of the members of the IRB/EC and their occupation and qualifications. If the IRB/EC will 
not disclose the names, occupations and qualifications of the committee members, it should be 
asked to issue a statement confirming that the composition of the committee is in accordance 
with GCP. For example, the IRB General Assurance Number may be accepted as a substitute for 
this list. Formal approval by the IRB/EC should mention the protocol title, number, amendment 
number (if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the informed consent document 
should also be revised.
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Celgene Corporation
Confidential and Proprietary
64
ABI-007-NSCL-004 Final: 12 January 2015
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.  
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc...).
In addition, the Investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
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Celgene Corporation
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65
ABI-007-NSCL-004 Final: 12 January 2015
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 the distribution of the investigational product 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 CRF and entered into the clinical database per Celgene standard 
operating procedures (SOPs). This data will be electronically verified through use of 
programmed edit checks specified by the clinical team.  Discrepancies in the data will be brought 
to the attention of the clinical team, and investigational site personnel, if necessary.  Resolutions 
to these issues will be reflected in the database.  An audit trail within the system will track all 
changes made to the data.
15.3.
Record Retention
Essential documents must be retained by the Investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product. 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 informed consent documents for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the Investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the Investigator, Celgene, and their authorized 
representative(s);
!
List of Sub-Investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of CRFs (if paper) and of documentation of corrections for all subjects;
!
Investigational product accountability records;
!
Record of any body fluids or tissue samples retained;
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Celgene Corporation
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66
ABI-007-NSCL-004 Final: 12 January 2015
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
!
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The Investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.  
The Investigator must obtain approval in writing from Celgene prior to destruction of any 
records. If the Investigator is unable to meet this obligation, the Investigator must ask Celgene 
for permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.
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Celgene Corporation
Confidential and Proprietary
67
ABI-007-NSCL-004 Final: 12 January 2015
16.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative 
for compliance with applicable government regulations with respect to current GCP and standard 
operating procedures.
16.1.
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study.  All aspects of the study are reviewed with the Investigator and the staff at a study 
initiation visit and/or at an investigator meeting.  Prior to enrolling subjects into the study, a 
Celgene representative will review the protocol, CRFs, 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, 
investigational product storage area, CRFs, subject’s source documents, and all other study 
documentation will be inspected/reviewed by the Celgene representative in accordance with the 
Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the CRFs 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 CRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified.  Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene.  Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, CRFs and applicable supporting records of study subject participation for 
audits and inspections by IRB/IECs, regulatory authorities (eg, FDA, EMA, Health Canada) and 
company authorized representatives.  The Investigator should make every effort to be available 
for the audits and/or inspections.  If the Investigator is contacted by any regulatory authority 
regarding an inspection, he/she should contact Celgene immediately.
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Celgene Corporation
Confidential and Proprietary
68
ABI-007-NSCL-004 Final: 12 January 2015
17.
PUBLICATIONS
The results of this study may be published in a medical publication, journal, or may be used for 
teaching purposes.  Additionally, this study and its results may be submitted for inclusion in all 
appropriate health authority study registries, as well as publication on health authority study 
registry websites, as required by local health authority regulations.  Selection of first authorship 
will be based on several considerations, including, but not limited to study participation, 
contribution to the protocol development, and analysis and input into the manuscript, related 
abstracts, and presentations in a study.
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18.
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SV, Orlov S
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nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
71
ABI-007-NSCL-004 Final: 12 January 2015
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.
Appendix B: Reversible Versus Non-Reversible
If you treated this subject with doublet chemotherapy, based on your best clinical judgment do 
you think that you will see an improvement in their poor performance status? 
This explores the concept of a patient whose poor performance status may be caused 
predominantly by tumor burden and may derive benefit from chemotherapy doublets to a greater 
degree (reversible) than a patient whose poor performance status may be caused predominantly 
by co-morbidities and who may not derive much benefit from chemotherapy doublets 
(irreversible). 
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