Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Phase II, LOCALLY ADVANCED OR METASTATIC NON SMALL CELL LUNG CANCER (NSCLC) AND AN EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE STATUS OF 2 (ABOUND.PS2) LOCALLY ADVANCED OR METASTATIC NON SMALL CELL LUNG CANCER (NSCLC) SUBJECTS THAT AE NOT CANDIDATES FOR RADIATION OR CURATIVE SURGERY
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 40
Healthy volunteers: no

Brief summary:
4 cycles of induction treatment with nab-paclitaxel and carboplatin followed by nab-paclitaxel monotherapy for those subjects who are progression free at the end of 4 cycles.

Detailed description:

Arms:
arm 1: 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.

Interventions: intervention 1: nab-Paclitaxel intervention 2: Carboplatin
Intervention descriptions: intervention 1: None intervention 2: None

Protocol document:
Prot_002.pdf: 
 
 
 
 
 
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:  11 August 2014 


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nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-004 Final 11 August 2014
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
DATE FINAL:
11 August 2014
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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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-004 Final 11 August 2014
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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Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-004 Final 11 August 2014
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.  
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-004 Final 11 August 2014
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-004 Final 11 August 2014
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 ECOG 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 (PFS, DCR, OS and ORR) of the nab-paclitaxel and carboplatin 
combination dosing regimen, followed by nab-paclitaxel monotherapyfor 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 Statuses
!
To access the safety and efficacy of continuous treatment with nab-paclitaxel as 
monotherapy after 4 cycles of nab-paclitaxel in combination with carboplatin
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.
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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 11 August 2014
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 Part
All subjects who discontinue treatment for any reason other than lost to follow-up or death, will 
enter the Follow-up part.  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 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 50 subjects.
Length of Study
Enrollment will last approximately 18 months.  The total length of this Phase II study with 
Induction, Monotherapy and Follow-up is estimated at approximately 30 months.
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
study, or the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol and/or the 
Statistical Analysis Plan, whichever is the later date
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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 11 August 2014
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 
study will be summarized by 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 (PFS), Disease Control Rate (DCR), Overall Response Rate (ORR), 
and Overall Survival (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 
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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 11 August 2014
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.
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
9
ABI-007-NSCL-004 Final 11 August 2014
TABLE OF CONTENTS
Table of Contents
TITLE PAGE..............................................................................................................................1
1.
INTRODUCTION..................................................................................................16
1.1.
Treatment of Advanced Stage NSCLC....................................................................16
1.2.
Treatment of patients with advanced stage NSCLC and poor performance 
status (PS) ..............................................................................................................18
2.
STUDY OBJECTIVES...........................................................................................21
2.1.
Primary Objective...................................................................................................21
2.2.
Secondary Objectives .............................................................................................21
2.3.
Exploratory Objectives ...........................................................................................21
3.
STUDY ENDPOINTS............................................................................................22
3.1.
Primary Endpoint....................................................................................................22
3.1.1.
Safety.....................................................................................................................22
3.2.
Secondary Endpoint(s)............................................................................................22
3.2.1.
Safety.....................................................................................................................22
3.2.2.
Efficacy..................................................................................................................22
3.3.
Exploratory Endpoint(s)..........................................................................................22
3.3.1.
Exploratory Endpoints............................................................................................22
4.
OVERALL STUDY DESIGN ................................................................................24
4.1.
Study Design ..........................................................................................................24
4.2.
Study Design Rationale ..........................................................................................25
4.3.
Study Duration .......................................................................................................27
4.3.1.
Duration of Treatment ............................................................................................27
4.4.
End of Trial ............................................................................................................27
5.
TABLE OF EVENTS.............................................................................................28
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
6.5.
Height and Weight..................................................................................................35
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6.3


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6.6.
Body Surface Area (BSA) Calculation....................................................................35
6.7.
ECOG Performance Score ......................................................................................35
6.8.
Concomitant Medications/Procedures.....................................................................35
6.9.
Adverse Event Reporting........................................................................................35
6.10.
Lung Cancer Symptom Scale,  Subject-Reported ECOG PS, EQ-5D-5L, Co-
Morbidity, and Medical Outcomes Score Questionnaires ........................................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 .........................................................................................37
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...................................................................................................41
8.
DESCRIPTION OF INVESTIGATIONAL PRODUCT .........................................43
8.1.
Description of Investigational Product ....................................................................43
8.1.1
Nab-Paclitaxel ........................................................................................................43
8.1.2.
Carboplatin.............................................................................................................43
8.2.
Treatment Administration and Schedule .................................................................44
8.3.
Dose Delay and Dose Modifications .......................................................................44
8.4.
Method of Treatment Assignment...........................................................................45
8.5.
Packaging and Labeling..........................................................................................45
8.6.
Investigational Product Accountability and Disposal ..............................................46
8.7.
Investigational Product Compliance........................................................................46
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8.4.
.4


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8.8.
Overdose ................................................................................................................46
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................47
9.1.
Permitted Concomitant Medications and Procedures...............................................47
9.2.
Prohibited Concomitant Medications and Procedures..............................................47
9.3.
Required Concomitant Medications and Procedures................................................47
10.
STATISTICAL ANALYSES..................................................................................48
10.1.
Overview................................................................................................................48
10.2.
Study Population Definitions ..................................................................................48
10.2.1.
Treated Population..................................................................................................48
10.2.2.
Per-protocol (PP) Population ..................................................................................48
10.3.
Sample Size and Power Considerations...................................................................48
10.4.
Background and Demographic Characteristics........................................................49
10.5.
Subject Disposition.................................................................................................49
10.6.
Safety Analysis.......................................................................................................50
10.6.1.
Primary Safety Endpoint.........................................................................................50
10.6.2.
Adverse Events.......................................................................................................50
10.6.3.
Laboratory Assessments .........................................................................................50
10.6.4.
Investigational Product Exposure............................................................................51
10.7.
Efficacy Analysis....................................................................................................51
10.7.1.
Efficacy Endpoints .................................................................................................51
10.7.1.1.
Progression-free Survival........................................................................................51
10.7.1.2.
Disease Control Rate ..............................................................................................52
10.7.1.3.
Overall Survival .....................................................................................................52
10.7.1.4.
Overall Response Rate............................................................................................52
10.7.2.
Exploratory Endpoints............................................................................................52
10.7.2.1.
Health Care Utilization ...........................................................................................52
10.7.2.2.
Quality of Life and Lung Cancer Symptom Questionnaires.....................................52
10.7.2.3.
Physician and Subject Reported ECOG Performance Scores...................................52
10.7.2.4.
Treatment Response During the Monotherapy Part .................................................53
10.8.
Investigational Product Termination .......................................................................53
10.9.
Deaths ....................................................................................................................53
10.10.
Interim Analysis .....................................................................................................53
10.11.
Scientific Steering Committee ................................................................................53
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.......48
4
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0.7.2.4
10.8.
0.8.


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11.
ADVERSE EVENTS..............................................................................................54
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................54
11.2.
Evaluation of Adverse Events.................................................................................54
11.2.1.
Seriousness.............................................................................................................54
11.2.2.
Severity / Intensity..................................................................................................56
11.2.3.
Causality ................................................................................................................56
11.2.4.
Duration .................................................................................................................57
11.2.5.
Action Taken..........................................................................................................57
11.2.6.
Outcome.................................................................................................................57
11.3.
Abnormal Laboratory Values..................................................................................57
11.4.
Pregnancy...............................................................................................................57
11.4.1.
Females of Childbearing Potential: .........................................................................58
11.4.2.
Male Subjects.........................................................................................................58
11.5.
Reporting of Serious Adverse Events......................................................................58
11.5.1.
Safety Queries ........................................................................................................59
11.6.
Expedited Reporting of Adverse Events..................................................................59
12.
DISCONTINUATIONS .........................................................................................60
12.1.
Treatment Discontinuation......................................................................................60
12.2.
Study Discontinuation ............................................................................................60
13.
EMERGENCY PROCEDURES.............................................................................62
13.1.
Emergency Contact.................................................................................................62
13.2.
Emergency Identification of Investigational Product...............................................62
14.
REGULATORY CONSIDERATIONS...................................................................63
14.1.
Good Clinical Practice............................................................................................63
14.2.
Investigator Responsibilities...................................................................................63
14.3.
Subject Information and Informed Consent.............................................................63
14.4.
Confidentiality........................................................................................................64
14.5.
Protocol Amendments.............................................................................................64
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................64
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................65
14.8.
Closure of the Study ...............................................................................................65
15.
DATA HANDLING AND RECORDKEEPING.....................................................66
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.......57
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4.6.
4.6.
7


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nab-paclitaxel
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ABI-007-NSCL-004 Final 11 August 2014
15.1.
Data/Documents .....................................................................................................66
15.2.
Data Management...................................................................................................66
15.3.
Record Retention....................................................................................................66
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................68
16.1.
Study Monitoring and Source Data Verification......................................................68
16.2.
Audits and Inspections............................................................................................68
17.
PUBLICATIONS ...................................................................................................69
18.
REFERENCES.......................................................................................................70
19.
APPENDICES........................................................................................................72
Appendix A:  ECOG Performance Status Score ........................................................................72
Appendix B: Reversible Versus Non-Reversible .......................................................................72
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8
.......69
6
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7
..............
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('06'RF1XPEHU
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ABI-007-NSCL-004 Final 11 August 2014
LIST OF TABLES
Table 1:
Blinded Radiology Assessment of Overall Response Rate (Intent-to-treat 
Population).............................................................................................................18
Table 2:
Table of Events - Induction.....................................................................................28
Table 3:
Table of Events – Monotherapy..............................................................................31
Table 4:
Permanent Dose Reductions for Hematologic and Non-Hematologic 
Toxicities on the Study ...........................................................................................45
Table 5:
Precision of the Estimate for the Treatment Discontinuation Rate due to  
Treatment-Emergent Adverse Events Given a Sample Size of 50............................49
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.45
45
............
............49
4


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LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................26
&(/*(1(35235,(7$5<,1)250$7,21


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1.
INTRODUCTION 
1.1.
Treatment of Advanced Stage NSCLC
Lung cancer is the leading cause of cancer-related deaths among men and women worldwide, 
with 1.2 million new cases diagnosed each year. Non-small cell lung cancer (NSCLC) is the 
most common type of lung cancer, accounting for 80% of all new cases.  There are an estimated 
1.1 million lives lost per year (approximately 500,000 in the United States [US] and European 
Union [EU] alone) due to NSCLC. Smoking is the causative factor for up to 85% of cases 
(http://www.lungcancercoalition.org/en/pages/about/awareness).
The majority of patients are not diagnosed until the tumor has progressed beyond the primary 
site. Despite 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 (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 (e.g., 
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 H2 antagonists to reduce the incidence of hypersensitivity 
reactions and histamine release caused by a response to the formulation vehicle (Gelderblom, 
2001; Lorenz, 1997; 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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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 I and II data (Belani, 2008; Rizvi, 2008; 
Socinski, 2010), as well as the pivotal Phase III study (CA031). The pivotal Phase III 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 ECOG PS0 or PS1 
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 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 ORR as determined by a central 
independent review committee using RECIST guidelines (Version 1.0). In the intent-to-treat (all-
randomized) population, the median age was 60 years, 75% were men, 81% were white, 49% 
had carcinoma/adenocarcinoma, 43% had squamous cell lung cancer, 76% were ECOG 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; HR = 0.922, 95% 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; hazard ratio [HR], 0.902; 
95% CI, 0.767 to 1.060; P = .214) in the nab-PC arm versus the P/C arm.  
AEs were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 paclitaxel 
injection/carboplatin-treated patients. The following common (≥ 10% incidence) AEs were 
observed at a similar incidence in nab-paclitaxel/carboplatin and paclitaxel/carboplatin arms: 
alopecia 56%, nausea 27%, fatigue 25%, decreased appetite 17%, asthenia 16%, constipation 
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e. Paclita
e. Paclitaxe
200 m
200 mg/m
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ly higher
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95% CI, 0
95% CI, 
s


('06'RF1XPEHU
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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 G3-4 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 CR or 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 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 
&(/*(1(35235,(7$5<,1)250$7,21
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the
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24%: p
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he ABI
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007
nse Rate (In
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taxel
axel/l
rboplatin
boplatin
(N=531)
(N=531)
5<
Response
esponse
7$
13
13
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5,(
36.7
36.7
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5,
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35
0
23
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170
52
35
litaxel/
taxel/respon
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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 II 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 PS2 patients could 
benefit from platinum-doublet chemotherapy were supported prospectively in a Phase III 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), 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 III 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 
Patients With Advanced Non–Small-Cell Lung Cancer and Eastern Cooperative Oncology 
Group Performance Status of 2.
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('06'RF1XPEHU
nab-paclitaxel
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Celgene Corporation
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ABI-007-NSCL-004 Final 11 August 2014
In the Phase III 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 II trial of carboplatin AUC5 and nab-paclitaxel 100mg/m2 days 
1 and 8 every 21 days in locally advanced Stage III NSCLC patients with PS2 
 
.  During this Phase II 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 PS2 patients, i.e. 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
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Confidential and Proprietary
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ABI-007-NSCL-004 Final 11 August 2014
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 PS2.
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 PS2.
!
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 access 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
22
ABI-007-NSCL-004 Final 11 August 2014
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 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 EQ5D-5L and LCSS 
!
Summary of the Medical Outcome Scale and Charlson Co-Morbidity Index (CCI) at 
baseline
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
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ABI-007-NSCL-004 Final 11 August 2014
!
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 11 August 2014
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 Part
All subjects who discontinue treatment for any reason other than lost to follow-up or death, will 
enter the Follow-up part.  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 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
25
ABI-007-NSCL-004 Final 11 August 2014
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 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,  
2011).  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 (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 PS2 patients.  There is limited data of carboplatin plus 
nab-paclitaxel in the locally advanced or metastatic NSCLC setting for patient with PS2 status.  
Nevertheless, the encouraging results from a Phase II study in Stage III NSCLC patients 
provides important insight that PS2 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 PS2 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 III 
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
26
ABI-007-NSCL-004 Final 11 August 2014
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 study drug).   
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
27
ABI-007-NSCL-004 Final 11 August 2014
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 18 months.  The total length of this Phase II study with 
Induction, Monotherapy, and Follow-up is estimated at approximately 30 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 to complete the 
study, or the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol and/or the 
Statistical Analysis Plan (SAP), whichever is the later date.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-004
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5.
TABLE OF EVENTS
Table 2:
Table of Events - Induction
CYCLES 1 To 4
(21-days)
Assessment
Screening
Baseline -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/ 
Survival o
Unscheduled
Visits
Informed Consent
X
-
-
-
-
-
-
-
Medical History 
X
-
-
-
-
-
-
-
Prior Medication and Proceduresb
X
-
-
-
-
-
-
-
Serum β-hCGc
X
-
-
-
-
-
-
-
Complete Chest CT Scan (including adrenal 
glands) with or without contrast and any 
other studies required for tumor imagingd
X
-
-
X
X
-
X
Xa
Height and Weighte
X
X
X
-
-
-
-
Xa
Body Surface Area (BSA) Calculationf
X
X
X
-
-
-
-
Xa
Physician-Reported ECOG PS
X
X
-
-
X
-
-
Xa
Concomitant Medication/Proceduresg
-
X
X
X
X
X
-
Xa
Histology and mutation Statush
X
-
-
-
-
-
-
-
Hematology, Serum Chemistry, albumin i
X
X
X
-
X
X
-
Xa
Adverse Event Evaluation
X
X
X
X
X
X
-
Xa
nab-paclitaxel Administration
-
X
X
-
-
-
-
-
Carboplatin Administration
-
X
-
-
-
-
-
-
Electrocardiogram (ECG)
X
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-
-
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
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ABI-007-NSCL-004 Final 11 August 2014
Table 2:
Table of Events - Induction (Continued)
CYCLE 1 to 4
(21-days)
Assessment
Screening/
Baseline 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
Discon
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Follow-
up visit
Follow-up/ 
Survival o
Unscheduled
Visits
Baseline TNM Stage
X
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-
-
-
-
-
-
Charlson Co-morbidity 
Questionnaire and Medical 
Outcomes Scale
X
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-
-
-
-
-
-
CT Scan of Head or Brain 
Magnetic Resonance Imaging 
(MRI), bone scan (X-rays if 
needed) j
X
-
-
X
X
-
X
Xa
Physical Examinationk
X
-
-
-
X
-
-
Xa
Vital Signsk
X
-
-
-
X
-
-
Xa
Smoking Historyl
X
-
-
-
-
-
-
-
Spirometry and Pulse Oximetrym
X
X
-
-
X
X
-
Xa
Calculated Creatinine Clearance 
(24 hour urine collection)n
X
X
-
-
-
X
-
Xa
Healthcare Resource Utilization 
Questionnaire
-
X
-
-
X
X
-
Xa
Subject-Reported ECOG PS
X
X
-
-
X
-
-
Xa
LCSS and EQ5D-5L
X
X
-
-
X
-
-
Xa
Subjects Weight 6 Months Prior 
to Baseline (signing the ICF)
X
-
-
-
-
-
-
-
Reversibility of PS 2 Statusp
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-
-
-
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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 11 August 2014
beta hCG: beta human chorionic gonadotropin, CT: Computed Tomography, ECOG: Eastern Cooperative Oncology Group, EQ5D-5L: EuroQol-5D, ICF: Informed 
Consent Form, LCSS: Lung Cancer Symptom Score, PS: Performance status, Tumor, node and metastasis (TNM) stage
a Unscheduled visits can be conducted at any time throughout the trial if clinically indicated and the proper eCRF pages are required to be completed
b 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
c A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a Serum β-hCG pregnancy test must be performed to assess 
eligibility at screening only .
d 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 contrast, unless contraindicated, to be performed at screening, within 28 days of signing the ICF. Scans will be performed after every 2 cycles of treatment
and at treatment 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.  
e 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.    
f BSA will be calculated at baseline and recalculated before each drug administration 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.
g 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 study treatment.   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 Part, post study anti-cancer therapy and procedures will be collected and reported on the appropriate eCRF.
h Histology should be obtained from the local pathology and reported on the appropriate eCRF page.  Mutation status will be collected from the local pathology report and 
reported on the appropriate eCRF page
i 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.
j 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.  
k 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.
l Smoking history will be collected and reported on the appropriate eCRF page and will include details such as the number of years and exposure to second hand smoke, etc.
m 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.
n Creatinine clearance (CrCl) will be calculated using Cockcroft-Gault equation (if renal impairment is suspected 24 hour urine collection for measurement is required – but only 
at baseline), these data will be collected on the eCRFs.
o All subjects who discontinue from treatment for reasons other than withdrawal of consent, lost to follow-up or death, will enter the Follow-up part.  It will consist of one visit 28 
days after the last dose of study drug(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.
p 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
31
ABI-007-NSCL-004 Final 11 August 2014
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 k
Unscheduled 
Visits
Complete Chest CT Scan 
(including adrenal glands) with
or without contrast and any other 
studies required for tumor 
imaging b
-
-
X
X
-
-
Xa
CT Scan of Head or Brain 
Magnetic Resonance Imaging 
(MRI) and Bone Scan (X-rays if 
needed)c
-
-
X
X
-
X
Xa
Weightd
X
X
-
-
X
-
Xa
Body Surface Area (BSA) 
Calculatione
X
X
-
-
-
-
Xa
Concomitant 
Medication/Proceduresf
X
X
X
X
X
X
Xa
Hematology, Serum Chemistry, 
albuming
X
X
-
X
X
X
Xa
Adverse Event Evaluation
X
X
X
X
X
-
Xa
nab-paclitaxel Administration
X
X
-
-
-
-
Survival Phone Call 
-
-
-
-
-
X
-
Healthcare Resource Utilization 
Questionnaire
X
-
-
X
X
-
Xa
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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 11 August 2014
Table 3:
Table of Events – Monotherapy (Continued)
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 k
Unscheduled 
Visits
Physical Examinationh
-
-
-
X
-
-
Xa
Vital Signsh
X
-
-
X
-
-
Xa
Subject and Physician-Reported ECOG
PS
X
-
-
X
-
-
Xa
LCSS and EQ5D-5L 
Questionnaires
X
-
-
X
-
-
Xa
Spirometry and Pulse Oximetryi
X
-
-
X
X
-
Xa
Calculated Creatinine Clearancej
X
-
-
-
X
-
Xa
ALT: alanine transaminase, AST: aspartate transaminase, CT: Computed Tomography, ECOG: Eastern Cooperative Oncology Group, EQ5D-5L: EuroQol-5D, ICF: 
Informed Consent Form, LCSS: Lung Cancer Symptom Score, PS: Performance status,
aUnscheduled visits can be conducted at any time throughout the trial if clinically indicated and the proper eCRF pages are required to be completed
b 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.
c 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.  
d Weight will be measured before drug administration and recorded on the appropriate eCRF page.  
e BSA will be calculated at baseline and recalculated before each drug administration and recorded in the subject’s medical records.  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 study treatment.   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 Part, 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.  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 
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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 11 August 2014
(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 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
i 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.
j Creatinine clearance (CrCl) will be calculated using Cockcroft-Gault equation,  these data will be collected on the eCRFs.
k All subjects who discontinue from treatment for reasons other than withdrawal of consent, lost to follow-up or death, will enter the Follow-up part.  It will consist of one visit 28 
days after the last dose of study drug(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: 11 August 2014
6.
PROCEDURES
Subjects will be provided with a written informed consent form (ICF), given the opportunity to 
ask any questions concerning the study, and will sign an ICF prior to participating in any study 
procedures. After giving written informed consent, subjects will undergo a screening period to 
be assessed for eligibility. 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 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: 11 August 2014
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 will be calculated at baseline and will be recalculated before each administration of nab-
paclitaxel.  These data will be recorded in the subject’s medical record only.  
6.7.
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. The data generated will be analyzed per 
the description in the SAP.
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 
study treatment.   Reporting of concomitant medications and procedures associated with non-
SAEs will include all cancer related procedures, 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 Part, 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 11 for details. 
6.10.
Lung Cancer Symptom Scale, Subject-Reported ECOG PS, EQ-5D-
5L, Co-Morbidity, and Medical Outcomes Score Questionnaires
The Medical Outcomes Score and Co-Morbidity questionnaires will be used to measure quality 
of life and co-existing medical conditions (other than NSCLC), for subjects in the trial.  These 
data will be collected at baseline only and will be summarized per the description in the SAP.  
The subject-reported ECOG PS , 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 screening, Day 1 of every cycle, and at treatment 
discontinuation.  Additional subject reported outcomes  may be assessed and reported at any time 
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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: 11 August 2014
during the study if deemed clinically necessary. The data generated from these questionnaires 
will be analyzed per the description in the SAP.
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.
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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: 11 August 2014
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 
count, platelet count, serum creatinine, calculated creatinine clearance, 24 hour urine collection 
(where applicable) hemoglobin, AST/serum glutamic oxaloacetic 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 part.  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 visit, investigational product
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
38
ABI-007-NSCL-004 Final: 11 August 2014
discontinuation, 28 days post last dose of investigational product and as clinically indicated.  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.
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. 
&(/*(1(35235,(7$5<,1)250$7,21
centage
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-004 Final: 11 August 2014
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: 11 August 2014
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 study drug 
discontinuation, even if he has undergone a successful vasectomy. 
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. 
[Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are 
not acceptable methods of contraception].
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
41
ABI-007-NSCL-004 Final: 11 August 2014
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 21days 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. Venous thromboembolism within 1 month prior to signing ICF.
6. Current congestive heart failure (New York Heart Association Class II-IV).
7. 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.
8. 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.
9. 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.
10. History of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or  
pulmonary hypersensitivity pneumonitis.
11. Treatment with any investigational product within 28 days prior to signing the ICF.
12. History of or suspected allergy to nab-paclitaxel, carboplatin and human albumin or any 
other platinum-based therapy.
13. Currently enrolled in any other clinical protocol or investigational trial that involves 
administration of experimental therapy and/or therapeutic devices.
14. 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.
15. 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 
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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: 11 August 2014
histological finding of prostate cancer (TNM stage of T1a or T1b). All treatment should 
have been completed 6 months prior to signing ICF.
16. Any condition including the presence of laboratory abnormalities, which places the 
subject at unacceptable risk if he/she were to participate in the study.
17. Any medical condition that confounds the ability to interpret data from the study.  This 
includes subjects with known psychiatric disorders.
18. Pregnant or breast-feeding females.
19. 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
43
ABI-007-NSCL-004 Final: 11 August 2014
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
44
ABI-007-NSCL-004 Final: 11 August 2014
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
45
ABI-007-NSCL-004 Final: 11 August 2014
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
46
ABI-007-NSCL-004 Final: 11 August 2014
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
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
47
ABI-007-NSCL-004 Final: 11 August 2014
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
nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-004 Final: 11 August 2014
10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the study are described 
below. Additional analyses of these endpoints as well as exploratory endpoints or subgroup 
analyses will be described in detail in the SAP. The SAP supersedes the analyses described in the 
protocol should there be differences between the two.
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. 
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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: 11 August 2014
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 
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 (e.g., subject-reported ECOG PS and Charlson Co-morbidity
Index score) 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 
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and Follow-up Periods. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
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 TEAEs, 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, 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. 
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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.
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. 
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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.  
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 Scores
ECOG performance 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 performance scores will be explored by cross-tabulation of the two endpoints.  Other 
methods for exploration will be described in the SAP.  
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10.7.2.4.
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 part 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 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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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 (i.e., 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 sequela of 
an accidental or intentional overdose of an investigational product should be reported as an AE 
on the AE CRF. If the sequela of an overdose is an SAE, then the sequela must be reported on 
an SAE report form and on the AE CRF. The overdose resulting in the SAE should be identified 
as the cause of the event on the SAE report form and CRF but should not be reported as an SAE 
itself.
In the event of 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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!
Is life-threatening (i.e., 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 (e.g., 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 (i.e., 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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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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‘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 (e.g., 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 (e.g., record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
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Celgene Corporation
Confidential and Proprietary
58
ABI-007-NSCL-004 Final: 11 August 2014
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 (e.g., 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 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
59
ABI-007-NSCL-004 Final: 11 August 2014
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available.  Any follow-up data 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 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 (e.g., 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 (i.e., 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.
via a 
5) business
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
60
ABI-007-NSCL-004 Final: 11 August 2014
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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review a
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
61
ABI-007-NSCL-004 Final: 11 August 2014
!
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.


('06'RF1XPEHU
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
62
ABI-007-NSCL-004 Final: 11 August 2014
13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research 
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page).This global Emergency 
Call Center is available 24 hours a day and 7 days a week. The representatives are responsible 
for obtaining your call-back information and contacting the on call Celgene/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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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
63
ABI-007-NSCL-004 Final: 11 August 2014
14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, 
and Investigator abide by Good Clinical Practice (GCP), as described in International 
Conference on Harmonization (ICH) Guideline E6 and in accordance with the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
IRB/EC prior to commencement. The Investigator will conduct all aspects of this study in 
accordance with applicable national, state, and local laws of the pertinent regulatory authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations.  Celgene staff or an authorized representative will evaluate and approve all 
Investigators who in turn will select their staff.
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, 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 (e.g., 
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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('06'RF1XPEHU
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
64
ABI-007-NSCL-004 Final: 11 August 2014
14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the Investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed 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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('06'RF1XPEHU
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
65
ABI-007-NSCL-004 Final: 11 August 2014
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.  
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (e.g., IRB/EC, regulatory authorities, etc...).
In addition, the Investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
66
ABI-007-NSCL-004 Final: 11 August 2014
15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and 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 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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('06'RF1XPEHU
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
67
ABI-007-NSCL-004 Final: 11 August 2014
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
!
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The Investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.  
The Investigator must obtain approval in writing from Celgene prior to destruction of any 
records. If the Investigator is unable to meet this obligation, the Investigator must ask Celgene 
for permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.
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destruction
destruction


('06'RF1XPEHU
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
68
ABI-007-NSCL-004 Final: 11 August 2014
16.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative 
for compliance with applicable government regulations with respect to current GCP and standard 
operating procedures.
16.1.
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study.  All aspects of the study are reviewed with the Investigator and the staff at a study 
initiation visit and/or at an investigator meeting.  Prior to enrolling subjects into the study, a 
Celgene representative 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 (e.g., 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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nab-paclitaxel
Protocol ABI-007-NSCL-004
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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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nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-004 Final: 11 August 2014
18.
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intratum
ntratumor
or
n-bound 
bound 
es
es.
R, Dancey J
Danc
ine (versio
ne (versio
g JB, Desai 
JB, Des
el and nab
and nab-
Crem
Cremopho
op
on. Eur J C
Eur J 
to predict s
to predict s
with third
with third-ge
ge
Clin Oncol
Clin Onco
Burchenal, 
Burchenal, 
ng and iden
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Semin Onco
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phase II tria
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
71
ABI-007-NSCL-004 Final: 11 August 2014
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Verweij J, S
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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: 11 August 2014
19.
APPENDICES
Appendix A:  ECOG Performance Status Score
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more 
than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5
Dead
Oken, 1982.
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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Prot_001.pdf: 
 
 
 
 
 
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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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
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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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CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
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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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Protocol ABI-007-NSCL-004
Celgene Corporation
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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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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
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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
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Celgene Corporation
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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
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Celgene Corporation
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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
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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
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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
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8.3.
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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
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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
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4.5.


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ABI-007-NSCL-004 Final: 12 January 2015
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
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7
.......67
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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
15
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
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Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-004 Final: 12 January 2015
LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................27
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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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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
18
ABI-007-NSCL-004 Final: 12 January 2015
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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as an


('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
19
ABI-007-NSCL-004 Final: 12 January 2015
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
uence
uence
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CR)
sponse
sponse
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% vs 25%
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carb
carb
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5,(
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Overall Res
5,
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5,
70 (33%)
70 (33%
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28.6, 3
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52
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f


('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 
&(/*(1(35235,(7$5<,1)250$7,21
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2008
200 ).).


('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.
&(/*(1(35235,(7$5<,1)250$7,21
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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
&(/*(1(35235,(7$5<,1)250$7,21
nd d 
noth
otherapy
rapy
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with
th
i
an
a
h
carboplat
arbopl in
or first
r first-line
lin
an ECOG
an ECOG P
he Charlson
e Charlson
etween the p
tween th
n between 
n between
KPS) at bas
KPS) at bas
ty y and effi
and e
fter 4 cy
r 4 c
f
cl


('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
&(/*(1(35235,(7$5<,1)250$7,21
notherapy
notherapy
e events (
e events S
ogy
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y
ter
ter
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ate
ate
ry Endp
ry Endpo
dpoint
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s liste
cated other
cated other
Explorator
Explorato
!
Heal
Health
th
l
!
Ch
Ch
!


('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 
&(/*(1(35235,(7$5<,1)250$7,21
l
ed consent
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&
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llowed for
wed fo
docum
documen


('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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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), 
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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)
Post Every 2 
Cycles of 
Treatment
(-3/+7 days)
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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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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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 
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('06'RF1XPEHU
nab-Paclitaxel
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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Celgene Corporation
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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
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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
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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
Second
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
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Grade 2 or 3 cutaneous toxicity
Grade 3 diarrhea
Grade 3 mucositis
Any other Grade 3 or 4 nonhematologic toxicity 
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Grade 4 cutaneous toxicity, diarrhea or mucositis
First
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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
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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
nab-Paclitaxel
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
nab-Paclitaxel
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
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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
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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
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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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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
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
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11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE.  A diagnosis or syndrome 
should be recorded on the AE page of the 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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!
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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Celgene Corporation
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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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Celgene Corporation
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56
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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Celgene Corporation
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57
ABI-007-NSCL-004 Final: 12 January 2015
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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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
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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nab-Paclitaxel
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.
&(/*(1(35235,(7$5<,1)250$7,21


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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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Protocol ABI-007-NSCL-004
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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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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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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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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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
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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('06'RF1XPEHU
nab-Paclitaxel
Protocol ABI-007-NSCL-004
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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.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-Paclitaxel
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Celgene Corporation
Confidential and Proprietary
69
ABI-007-NSCL-004 Final: 12 January 2015
18.
REFERENCES
Belani CP, Ramalingam S, Perry MC, LaRocca RV, Rinaldi D, Gable PS, et al. Randomized, 
phase III study of weekly paclitaxel in combination with carboplatin versus standard 
every-3-weeks administration of carboplatin and paclitaxel for patients with previously untreated 
advanced non-small-cell lung cancer. J Clin Oncol. 2008;26(3):468-73.
Desai N, Trieu V, Yao Z, Louie L, Ci S, Yang A, et al. Increased antitumor activity, intratumor 
paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound 
paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res. 
2006;12(4):1317-24.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response 
evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 
2009;45(2):228-47
Gardner ER, Dahut WL, Scripture CD, Jones J, Aragon-Ching JB, Desai N, et al. Randomized 
crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Clin Cancer 
Res. 2008;14(13):4200-5. 
Gelderblom H, Verweij J, Nooter K, Sparreboom A. Cremophor EL: the drawbacks and 
advantages of vehicle selection for drug formulation. Eur J Cancer. 2001;37(13):1590-8.
Hoang T, Xu R, Schiller JH, Bonomi P, Johnson DH. Clinical model to predict survival in 
chemonaive patients with advanced non–small-cell lung cancer treated with third-generation 
chemotherapy regimens based on eastern cooperative oncology group data. J Clin Oncol.
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Karnofsky DA, Abelmann WH, Craver LF, Burchenal JH. The use of nitrogen mustards in the 
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Kelly, K. Challenges in defining and identifying patients with non-small cell lung cancer and 
poor performance status. Semin Oncol. 2004;31:3-7.
Langer C, Li S, Schiller J, Tester W, Rapoport BL, Johnson DH; Eastern Cooperative Oncology 
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ECOG performance status patients: ECOG 1599. J Clin Oncol. 2007;25(4):418-23. 
Lilenbaum RC, Cashy J, Hensing TA, Young S, Cella D. Prevalence of poor performance status 
in lung cancer patients: implications for research. J Thorac Oncol. 2008;3(2):125–9.
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versus combination chemotherapy in patients with advanced non-small cell lung cancer and a 
performance status of 2: prognostic factors and treatment selection based on two large 
randomized clinical trials. J Thorac Oncol. 2009;4(7):869-74.
Lorenz W, Reimann HJ, Schmal A, et al. Histamine release in dogs by Cremophor El and its 
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Lung Cancer Awareness. Global Lung Cancer Coalition Website. Available from: 
http://www.lungcancercoalition.org/en/pages/about/awareness. Accessed Jan , 2015.
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ew response
w respon
ur J Cancer
ur J Canc
i N,
N, et al
et a . R
paclitaxel.
paclitaxel.
or EL: the 
or EL: t
Cancer
Cancer. 20
. 20
Clinical mo
Clinical mo
ung cancer
ung canc
tive onco
tive oncolol
, Burchena
Burchena
er 194
194;1: 6
1: 
d ident
identifyin
ify
Onco
Oncol.l. 200
200
ester W,
ester W, R
e II t
e II tririala of
l
atus patien
atus patien
ashy
shy J, Hen
J, Hen
y
pa
patitients: im
ents: im
RC, Villaf
RC, Villaf
ombinat
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rm
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nc stat
ndo
domized 
mized c
Lorenz W
Lorenz W
riva
riva


('06'RF1XPEHU
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Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-004 Final: 12 January 2015
National Institute for Health & Clinical Excellence: The Diagnosis and Treatment of Lung 
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response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol, 1982;5(6):649-
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Rizvi NA, Riely GJ, Azzoli CG, Miller VA, Ng KK, Fiore J, et al. Phase I/II trial of weekly 
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non-small-cell lung cancer. J Clin Oncol. 2008;26(4):639-43.
Schiller JH, Gandara DR, Goss GD, Vokes EE. Non-small-cell lung cancer: then and now. J Clin 
Oncol. 2013;31(8):981-3.
Socinski MA, Manikhas GM, Stroyakovsky DL, Makhson AN, Cheporov SV, Orlov SV, et al. A 
dose finding study of weekly and every 3 week nab-paclitaxel followed by carboplatin as 
first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol. 
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Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, et al.
Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus 
carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final 
results of a phase III trial.  J Clin Oncol.2012;30(17):2055-62.
Sparreboom A, van Zuylen L, Brouwer E, Loos WJ, de Bruijn P, Gelderblom H, et al. 
Cremophor EL-mediated alteration of paclitaxel distribution in human blood: clinical 
pharmacokinetic implications. Cancer Res. 1999;59(7):1454-7.
ten Tije AJ, Verweij J, Loos WJ, Sparreboom A. Pharmacological effects of formulation 
vehicles: implications for cancer chemotherapy. Clin Pharmacokinet. 2003;42(7):665-85. 
van Tellingen O, Beijnen JH, Verweij J, Scherrenburg EJ, Nooijen WJ, Sparreboom A. Rapid 
esterase-sensitive breakdown of polysorbate 80 and its impact on the plasma pharmacokinetics of 
docetaxel and metabolites in mice. Clin Cancer Res. 1999;5(10):2918-24.
Weiss RB, Donehower RC, Wiernik PH, Ohnuma T, Gralla RJ, Trump DL, et al.
Hypersensitivity reactions from taxol. J Clin Oncol. 1990;8(7):1263-8.
Zukin, M, Barrios C, Pereira, JR, Ribeiro Rde A, Beato CA, do Nascimento YN, et al.
Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in 
patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group 
performance status of 2. 2013; J Clin Oncol. 31(23):2841-3.
age IV
ge IV
nd now. J
nd now. J
SV, Orlov S
SV, Orlov 
by carbopl
carb
y
. J T
J Thorac 
horac 
ynnychenko
nnychen
sus 
us sol
olvent
ve
d non
on-smal
m
2055
205 -62.
-62
WJ, de Brui
WJ, de Bru
el distribut
el distribut
1999;59(7)
1999;59(7)
eboom A. P
boom A. 
motherapy
motherap
erweij J, Sc
erweij J, Sc
of polysor
polysor
in mice. Cl
n mice. C
r RC, Wier
RC, Wier
actioions
ns fro
fro
os
os C, Pere
C, Pe
phase III
hase III
with advanc
dvanc
mance
an
statatutu
a


('06'RF1XPEHU
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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Celgene Signing Page
This is a representation of an electronic record that was signed electronically in Livelink.
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SAP_000.pdf: 
 
 
 
 
 
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 
Statistical Analysis Plan Date:  11 April 2017 


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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
1
STATISTICAL ANALYSIS PLAN
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)
STUDY DRUG:
nab-Paclitaxel (Abraxane®)
PROTOCOL NUMBER:
ABI-007-NSCL-004
DATE FINAL:
11 APR 2017
Prepared by:
On behalf of Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
CONFIDENTIAL
The information contained in this document is regarded as confidential 
and, except to the extent necessary to obtain informed consent, may not be 
disclosed to another party unless such disclosure is required by law or 
regulations.  Persons to whom the information is disclosed must be 
informed that the information is confidential and may not be further 
disclosed by them.
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
3
TABLE OF CONTENTS
STATISTICAL ANALYSIS PLAN ............................................................................................1
SIGNATURE PAGE...................................................................................................................2
TABLE OF CONTENTS............................................................................................................3
LIST OF TABLES......................................................................................................................6
LIST OF FIGURES ....................................................................................................................7
1.
LIST OF ABBREVIATIONS...................................................................................8
TABLE 1: ABBREVIATIONS AND SPECIALIST TERMS......................................................8
2.
INTRODUCTION..................................................................................................11
3.
STUDY OBJECTIVES...........................................................................................12
3.1.
Primary Objective...................................................................................................12
3.2.
Secondary Objectives .............................................................................................12
3.3.
Exploratory Objectives ...........................................................................................12
4.
INVESTIGATIONAL PLAN .................................................................................13
4.1.
Overall Study Design and Plan ...............................................................................13
FIGURE 1: STUDY SCHEMATIC FOR ABI-007-NSCL-004 .................................................15
4.2.
Study Endpoints .....................................................................................................16
4.2.1.
Primary Endpoint....................................................................................................16
4.2.2.
Secondary Endpoints ..............................................................................................16
4.2.3.
Exploratory Endpoints............................................................................................16
4.3.
Stratification, Randomization and Blinding.............................................................17
4.4.
Sample Size Determination.....................................................................................17
5.
GENERAL STATISTICAL CONSIDERATIONS .................................................18
5.1.
Reporting Conventions ...........................................................................................18
5.2.
Analysis Populations ..............................................................................................19
5.2.1.
Treated Population..................................................................................................19
5.2.2.
Per-Protocol Population..........................................................................................19
6.
SUBJECT DISPOSITION......................................................................................20
7.
PROTOCOL DEVIATIONS/VIOLATIONS ..........................................................22
8.
DEMOGRAPHICS AND BASELINE CHARACTERISTICS................................23
8.1.
Demographics.........................................................................................................23
8.2.
Baseline Characteristics..........................................................................................23
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7.


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
4
8.3.
Medical History and Cancer Diagnosis ...................................................................23
8.3.1.
Medical History......................................................................................................23
8.3.2.
Lung Cancer History...............................................................................................24
8.4.
Prior and Concomitant Therapy ..............................................................................24
8.4.1.
Prior Systemic Anti-cancer Therapies.....................................................................24
8.4.2.
Prior Radiation Therapy..........................................................................................25
8.4.3.
Prior Cancer Surgeries............................................................................................25
8.4.4.
Concomitant Procedures/Surgeries .........................................................................25
8.5.
Prior and Concomitant Medications........................................................................25
8.5.1.
Prior Medications ...................................................................................................25
8.5.2.
Concomitant Medications .......................................................................................25
9.
STUDY TREATMENTS AND EXTENT OF EXPOSURE....................................26
9.1.
Treatment and Cycle Start and End Dates ...............................................................26
9.2.
Dosing Period for Each Study Drug........................................................................26
TABLE 2: CALCULATION OF DOSING PERIOD FOR EACH STUDY DRUG 
BASED ON CYCLE DAY NUMBER OF LAST DOSE OF THE STUDY 
DRUG ....................................................................................................................28
9.3.
Treatment Duration.................................................................................................29
9.4.
Cumulative Dose ....................................................................................................29
9.5.
Dose Intensity.........................................................................................................29
9.6.
Percentage of Protocol Dose ...................................................................................30
9.7.
Exposure, Dose Reduction/Delay and Doses Not Administered..............................30
10.
SAFETY ANALYSIS ............................................................................................32
10.1.
Primary Endpoint....................................................................................................32
10.2.
Treatment-emergent Adverse Events ......................................................................32
10.3.
Adverse Events of Special Interest..........................................................................34
10.4.
Peripheral Neuropathy............................................................................................34
10.5.
Clinical Laboratory Evaluations..............................................................................34
11.
EFFICACY ANALYSIS ........................................................................................35
11.1.1.
Progression-free Survival........................................................................................35
11.1.2.
Disease Control Rate ..............................................................................................36
11.1.3.
Overall Survival .....................................................................................................36
11.1.4.
Tumor Response and Overall Response Rate ..........................................................36
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1 2


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
5
11.1.5.
Time to Response ...................................................................................................36
11.1.6.
Duration of Response .............................................................................................37
11.1.7.
Subgroup Analyses.................................................................................................37
12.
EXPLORATORY ANALYSIS...............................................................................38
12.1.1.
Healthcare Care Utilization.....................................................................................38
12.1.2.
Quality of Life........................................................................................................38
12.1.3.
Charlson Comorbidity Index Score.........................................................................40
12.1.4.
Physician- and Subject-Reported ECOG Performance Status..................................40
12.1.5.
Physician- and Subject-Reported Karnofsky Performance Status............................41
12.1.6.
Spirometry and Pulse Oximetry..............................................................................41
12.1.7.
Tumor Response During the Monotherapy Part ......................................................42
13.
FOLLOW UP TREATMENTS...............................................................................43
14.
INTERIM ANALYSIS...........................................................................................44
15.
CHANGES TO THE STATISTICAL ANALYSES SECTION OF THE 
PROTOCOL...........................................................................................................45
16.
REFERENCES.......................................................................................................46
17.
APPENDICES........................................................................................................47
17.1.
Handling of Dates...................................................................................................47
17.2.
Date Imputation Guideline......................................................................................48
17.2.1.
Impute Missing Dates for Adverse Events/ Prior or Concomitant 
Medications............................................................................................................48
17.3.
Relative Day Ranges for CT-Scans.........................................................................49
TABLE 3: RELATIVE DAY RANGES FOR CT SCANS ........................................................49
17.4.
Adverse Events of Special Interest..........................................................................49
TABLE 4: TREATMENT-EMERGENT ADVERSE EVENTS OF SPECIAL 
INTEREST FILE AND DATES.............................................................................50
17.5.
MedDRA Versions and Dates.................................................................................50
TABLE 5: MEDDRA VERSIONS AND DATES.....................................................................50
17.6.
PFS Censoring Rules..............................................................................................50
TABLE 6: PFS CENSORING RULES......................................................................................50
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TABLE 6: 
TABLE 6: 


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
6
LIST OF TABLES
Table 1: Abbreviations and Specialist Terms...............................................................................8
Table 2:
Calculation of Dosing Period for Each Study Drug Based on Cycle Day 
Number of Last Dose of the Study Drug .................................................................28
Table 3: Relative Day Ranges for CT Scans..............................................................................49
Table 4: Treatment-emergent Adverse Events of Special Interest File and Dates.......................50
Table 5: MedDRA Versions and Dates......................................................................................50
Table 6: PFS Censoring Rules...................................................................................................50
49
49
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
7
LIST OF FIGURES
Figure 1: Study Schematic for ABI-007-NSCL-004 ..................................................................15
&(/*(1(35235,(7$5<,1)250$7,21


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
8
1.
LIST OF ABBREVIATIONS
Table 1: Abbreviations and Specialist Terms
ADT
Analysis date
AE
Adverse event
ALK
Anaplastic lymphoma kinase
ALT
Alanine aminotransferase (SGPT)
ANC
Absolute neutrophil count
AST
Aspartate aminotransferase (SGOT)
AUC
Area under the curve
BMI
Body mass index
BSA
Body surface area
CCI
Charlson Co-Morbidity Index
CI
Confidence interval
CR
Complete response
CT
Computerized tomography
CTCAE
Common Terminology Criteria for Adverse Events
DCR
Disease control rate
DMC
Data Monitoring Committee
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EGFR
Epidermal growth factor receptor 
EOS
End of study
EQ-5D-5L
EuroQoL Group 5-Dimension 5-Level
FEV1
Forced expiratory volume in 1 second 
FNC
Fine needle cytology
FVC
Forced vital capacity
Hgb
Hemoglobin
HR
Hazard ratio
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
9
ICF
Informed consent form
IRT
Interactive Response Technology
IV
Intravenous
IVRS
Interactive voice response system
KPS
Karnofsky performance status
KRAS
Kirsten rat sarcoma viral oncogene homolog
LCSS
Lung Cancer Symptom Scale
MedDRA
Medical Dictionary for Regulatory Activities
MRI
Magnetic resonance imaging
NA
Not applicable
NE
Not evaluable
NCI
National Cancer Institute
NSCLC
Non-small cell lung cancer
ORR
Overall response rate
OS
Overall survival
PD
Progressive disease
PEF
Peak expiratory flow
PFS
Progression-free survival
PP
Per protocol
PR
Partial response
PS
Performance status
PT
Preferred term
RECIST
Response evaluation criteria in solid tumors
SAE
Serious adverse event
SAP
Statistical analysis plan
SD
Stable disease
SGOT
Serum glutamic oxaloacetic transaminase
SGPT
Serum glutamic pyruvic transaminase
SI
International System of Units (Le Système International d’unités)
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
10
SMQ
Standardized MedDRA query
SOC
System organ class
TEAE
Treatment-emergent adverse event
TTR
Time-to-response
UE
Unevaluable
US
United States
VAS
Visual analog scale
WBC
White blood cell 
WHO
World Health Organization
WHO-DDE
World Health Organization Drug Dictionary Enhanced
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
11
2.
INTRODUCTION
This statistical analysis plan (SAP) describes the analyses and data presentations for Celgene’s 
protocol ABI-007-NSCL-004 “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)” which was issued 
on 11Aug 2014 and amended on 12 Jan 2015. It contains definitions of analysis populations, 
derived variables and statistical methods for the analysis of efficacy and safety.
These analyses include one interim review and one final analysis. Throughout this SAP, the 
study treatment will be referred to as induction therapy, consisting of nab-paclitaxel plus 
carboplatin (21-day cycle for 4 cycles), and monotherapy, nab-paclitaxel only (continuous 21-
day cycles until disease progression or unacceptable toxicity). The purpose of the SAP is to 
ensure the credibility of the study findings by pre-specifying the statistical approaches to the 
analysis of study data prior to database lock and any data analysis for the first interim/final 
analysis. This SAP will be finalized and signed prior to the clinical database lock. All statistical 
analyses detailed in this SAP will be conducted using SAS® Version 9.2 or higher. 
An interim review of the percentage of subjects discontinued due to treatment-emergent adverse 
events (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.
In August 2016, Celgene management informed sites and regulatory authorities of its decision to 
end enrollment prior to enrolling the planned number of subjects, due to slower than expected 
enrollment. The clinical cutoff date for the final safety and efficacy analysis will be 24 February 
2017.
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
12
3.
STUDY OBJECTIVES
3.1.
Primary Objective
The primary objective is as follows:
!
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 Eastern Cooperative Oncology Group Performance Status 2 (ECOG PS 
2).
3.2.
Secondary Objectives
The secondary objectives are as follows:
!
To evaluate the efficacy (progression-free survival [PFS], disease control rate [DCR], 
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.
3.3.
Exploratory Objectives
The exploratory objectives are as follows:
!
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 subject-evaluated ECOG PS
!
To explore the correlation between the physician- and subject-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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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
13
4.
INVESTIGATIONAL PLAN
4.1.
Overall Study Design and Plan
Forty subjects (originally planned to be 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
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.
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 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.
The Screening Period will start from signing the Informed Consent Form (ICF) until Day 1 of 
Treatment. The Treatment Period will start on the date of the first dose of study drug and will 
end on the treatment end date. The Follow-up Period will start the day after the treatment end 
date.
No additional anti-cancer agents are allowed during study treatment. All supportive care 
(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, 
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
14
cough, dyspnea, or hemoptysis, excluding anti-neoplastic agents) is permitted as per the 
investigator’s discretion and will be recorded on the appropriate eCRF pages. 
Local laboratory test data for absolute neutrophil count (ANC), white blood cell (WBC) count, 
platelet count, hemoglobin (Hgb), serum creatinine, calculated creatinine clearance, 24 hour 
urine collection (where applicable), aspartate transaminase (AST/serum glutamic oxaloacetic 
transaminase [SGOT]), alanine transaminase (ALT/serum glutamic pyruvic transaminase 
[SGPT]), albumin, total bilirubin will be collected in the eCRFs. All other routine laboratory test 
data except those mentioned above will not be collected in the eCRF unless they are determined 
to be clinically significant laboratory abnormalities. A clinically significant laboratory 
abnormality will be reported as an adverse event (AE), or serious adverse event (SAE) and the 
specific associated laboratory parameter should be recorded in the laboratory assessments eCRF. 
Local safety laboratory data will also be the primary guide for eligibility and subject 
management. 
Tumor evaluations will be assessed locally and response (Complete Response (CR) or Partial 
Response (PR) will be determined according to Response Evaluation Criteria in Solid Tumor 
(RECIST) guidelines, Version 1.1 (Eisenhauer, et al., 2009). Tumor assessments will be 
conducted at Screening and after every 2 cycles (-3/+7 days) until treatment discontinuation, 
withdrawal of consent, lost to follow-up, or death. During follow-up, 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 eCRF pages.
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 a study visit 28 days after 
the last dose of investigational product. Thereafter subjects 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 for up to 1 year after the last 
subject is enrolled. All data will be reported on the appropriate eCRF page.
The study schematic is given in Figure 1.
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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Figure 1: Study Schematic for ABI-007-NSCL-004
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 infusion
Absence of Clinical or Radiological Disease Progression
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 for up to 1 year after the last subject is enrolled.
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
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Celgene Corporation
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4.2.
Study Endpoints
4.2.1.
Primary Endpoint
The primary study endpoint is the percentage of subjects who discontinue study treatment during 
the induction part due to TEAEs. 
4.2.2.
Secondary Endpoints
4.2.2.1.
Safety
!
The type, frequency, and severity of AEs and SAEs graded using National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0)
!
Discontinuation rate
!
The dose intensity 
!
The incidence of dose reduction 
4.2.2.2.
Efficacy
Efficacy endpoints include the following:
!
Progression free survival 
!
Disease control rate 
!
Overall survival 
!
Overall response rate 
Other secondary efficacy endpoints include:
!
Time to response
!
Duration of response
4.2.3.
Exploratory Endpoints
The exploratory endpoints listed below will be evaluated across induction and monotherapy 
parts, unless indicated otherwise.
!
Healthcare resource utilization throughout the study using a questionnaire
!
Changes from baseline in physician-reported ECOG PS 
!
Changes from baseline in the EuroQol-5D (EQ-5D-5L) and Lung Cancer Symptom Score 
(LCSS)
!
Summary of the CCI at baseline 
!
Correlation between subject-reported ECOG PS and physician-reported ECOG PS during 
the treatment period
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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!
Correlation between subject-reported KPS and physician-reported KPS at baseline
!
Changes from baseline in spirometry and pulse oximetry parameters
!
Treatment response during the monotherapy part compared with response at the start of 
monotherapy.
4.3.
Stratification, Randomization and Blinding
This is a single arm, open-label study. No randomization or blinding is done. 
4.4.
Sample Size Determination
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 PS 2. All evaluations of the safety and efficacy 
endpoints will be based on the point estimates and the associated 2-sided 95% confidence 
intervals (CI) 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 
width of the 95% CI 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 Section 10.3 of the protocol demonstrates the precision of the estimate that can be 
attained given a sample size of 50 for a range of hypothetical rates 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% CI is 26.7%, 
and the estimated 95% CI is (17.9% - 44.6%).
The data cutoff for the analysis of both the safety and efficacy endpoints for the clinical study 
report will be 24 February 2017. 
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7. .


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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5.
GENERAL STATISTICAL CONSIDERATIONS
5.1.
Reporting Conventions
The following reporting conventions apply generally to tables, listings, and figures:
!
Data from all study centers will be combined for analysis;
!
P-values will be rounded to 4 decimal places. P-values that round to 0.0000 will be 
presented as ‘<0.0001’ and p-values that round to 1.0000 will be presented as ‘>0.9999’; 
!
Confidence intervals will be presented as 2-sided 95% CIs unless specified differently for 
a given analysis;
!
Summary statistics will consist of the number and percentage of subjects (or cycles, if 
appropriate) in each category for discrete variables, and the sample size, mean, standard 
deviation, median, the 25th (Q1) and 75th (Q3) percentiles, minimum, and maximum for 
continuous variables;
!
All mean, median, and percentile values will be formatted to one more decimal place than
the measured value. Standard deviation values will be formatted to two more decimal 
places than the measured value. Minimum and maximum will be formatted to the same 
decimal place as the measured value;
!
All percentages will be rounded to one decimal place. Tables that show only number and 
percentage of responses will be presented in the form XX (XX.X), where the percentage 
is in the parentheses. Tables that show number and percentage of responses in addition to 
summary statistics will be presented in the form XX (XX.X%), where the percentage is in 
the parentheses;
!
All listings will be sorted for presentation in order of study site, subject, and date of 
procedure or event. Data for all treated subjects will be included in subject data listings;
!
All analysis and summary tables will have the analysis population sample size (i.e., 
number of subjects);
!
Baseline value will be defined as the last non-missing value obtained before or on the day 
the first dose of study drug is administered; if multiple values are present for the same 
date, the average of these values will be used as the baseline. For subjects who were not 
treated, the baseline will be the last non-missing assessment value taken on or before the 
IRT enrollment visit date; 
!
Partial dates will be imputed based on the rules specified in Appendix 16.2; 
!
All laboratory data will be reported using standard international (SI) units; 
!
Summaries of the most severe toxicity grade in clinical laboratory in each treatment cycle 
and most severe grade post-baseline overall and shifts from baseline to most severe 
toxicity grade post-baseline by-visit and overall will include all scheduled and 
unscheduled assessments;
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!


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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!
For safety analyses, data obtained through the last dose date + 28 days will be used.
5.2.
Analysis Populations
5.2.1.
Treated Population
The treated population will consist of all subjects who received at least one dose of 
investigational product. Unless otherwise specified, the treated population will be the analysis 
population for all safety analyses. Only subjects with clear documentation that no study drug was 
administered will be excluded from the treated population.  
5.2.2.
Per-Protocol Population
The per-protocol (PP) population is defined as all eligible subjects enrolled who receive at least 
one dose of the investigational product; have a baseline and at least one evaluable post baseline 
radiological assessment; and do not have any relevant protocol violations or deviations. The PP 
population will be used in a replication of the efficacy analyses.
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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6.
SUBJECT DISPOSITION
The number of subjects screened but not treated, the number and percentage of subjects included 
in the treated population will be summarized. The percentages will be based on the number of 
subjects screened. A summary of analysis populations will be presented for treated population 
and per-protocol population.
Subject study disposition will be presented separately for subjects who signed informed consent 
but were not treated, and for all treated subjects. Additionally, treatment disposition will be 
summarized overall and by study part (i.e. induction part and monotherapy part) for all treated 
subjects.
The primary reasons for study discontinuation will be summarized with the following categories:
!
Screen failure
!
Death
!
Adverse event
!
Withdrawal by subject
!
Lost to follow up
!
Protocol violation
!
Study terminated by sponsor
!
Other
The primary reasons for treatment discontinuation in the treated population will be summarized 
by study part (induction, monotherapy and overall) with the following categories:
!
Death
!
Adverse event
!
Progressive disease
!
Symptomatic deterioration
!
Withdrawal by subject
!
Lost to follow-up
!
Study terminated by sponsor
!
Protocol violation
!
Other
Deaths reported during treatment (defined as deaths from the first administration of the study 
drug through 28 days post last dose of study drug); deaths that occur during the Follow-up 
Period; and all deaths will be summarized by frequency of occurrence and corresponding 
percentage by cause of death. Cause of death will be categorized by the categories on the death 
eCRF and by coded cause of death.
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Othe
Oth
Deaths r
Deaths


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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A summary of subjects treated by site will be provided. Listings will be provided for 
discontinued subjects with reason for treatment discontinuation and reason for study 
discontinuation, and for screen failure subjects who did not meet eligibility criteria.
&(/*(1(35235,(7$5<,1)250$7,21


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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7.
PROTOCOL DEVIATIONS/VIOLATIONS
The protocol deviations/violations will be identified and assessed by the clinical monitor of the 
sponsor or designee following company standard operational procedure.
Protocol deviations/violations will be summarized using frequency tabulations. Additionally, a
by-subject listing of subjects with protocol violations or deviations in the treated population will 
be provided. 
Protocol deviations and violations will be reviewed before database lock. Not all deviations or 
violations will constitute the exclusion of subject from the per-protocol population; events that 
could trigger exclusion from the per protocol population include major inclusion/exclusion 
criteria violations, failure to take IP as assigned, and prohibited concomitant medications and 
procedures.
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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8.
DEMOGRAPHICS AND BASELINE CHARACTERISTICS
The demographics and baseline characteristics will be summarized for all treated subjects. 
Individual subject listings will be provided to support the summary tables. Provided the numbers 
of subjects are sufficient, the demographics and baseline characteristics will also be summarized 
within the following subgroups:
!
Age (< 65 years, 65 – 74 years, and ≥ 75 years)
!
Sex (Male, Female)
!
Histology (Squamous, non-Squamous)
8.1.
Demographics
Age (years), height (cm), weight (kg), body mass index (BMI; kg/m2), body surface area (BSA) 
(m²) at baseline will be summarized descriptively. Sex, Age category, race, and ethnicity will be 
summarized by frequency counts.
Age will be calculated as follows: Age = Integer part of [(Date of informed consent– Date of 
Birth + 1) / 365.25]. 
BMI will be calculated as follows: BMI = weight in kg / (height in m)2.
For the purposes of data listings and tables, BSA will be calculated as follows: 
BSA = 0.007184 × (weight in kg)0.425 × (height in cm)0.725.
8.2.
Baseline Characteristics
Baseline characteristics indicated below will be summarized descriptively:
!
Subject- and physician-reported ECOG performance status at baseline and physician-
reported ECOG performance status at screening visit
!
Charlson Co-morbidity Index score at baseline
!
Subject- and physician-reported KPS at baseline
!
Histology (squamous cell carcinoma vs. non-squamous cell carcinoma) at baseline
!
Baseline tumor, node and metastasis (TNM) stage
!
Weight change, expressed as percent change from weight approximately 6 months prior 
to date of informed consent
!
Reversibility of PS 2 status
8.3.
Medical History and Cancer Diagnosis
8.3.1.
Medical History
A summary of medical and surgical history will be presented by system and organ class (SOC) 
and preferred term (PT), coded according to the Medical Dictionary for Regulatory Activities 
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8.3.
8.3


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(MedDRA). A similar summary will be generated for the currently active abnormalities only, by 
SOC and PT.
8.3.2.
Lung Cancer History
The following items will be summarized for cancer diagnosis:
!
Stage at enrollment
!
The time from specimen collection date to first dose date in months, defined as (first dose 
date – specimen collection date)/ 30.4375
!
Method of specimen collection (biopsy, surgical specimen, FNC, other)
!
Histology (squamous, adenocarcinoma, large cell, other)
!
Squamous cell histology type (papillary, clear cell, basaloid, and other)
!
Adenocarcinoma cell type (acinar, papillary, broncholoalveolar carcinoma, solid 
adenocarcinoma with mucin, adenocarcinoma with mixed subtypes, and other)
!
Mutational gene status for patients with adenocarcinoma cell histology confirmed 
(KRAS, EGFR, FGFR 1/2/3/4, ALK, other)
!
Number of prior systemic anti-cancer therapies for non-small cell lung cancer
!
Time from latest systemic anti-cancer therapy to first dose date in months
!
Number of prior radiation therapies
!
Time from latest radiation therapy to first dose date in months
!
Number of prior cancer surgeries for non-small cell lung cancer
!
Time from latest prior cancer surgery to first dose date in months
!
Time from latest cancer therapy (last to occur of systemic anti-cancer therapy, radiation, 
or cancer surgery) to first dose date in months.
Subject listings will be provided for all of the above, as well as date of specimen collection.
8.4.
Prior and Concomitant Therapy
Prior therapies are defined as the therapies that were started before the start of the study 
treatment. 
8.4.1.
Prior Systemic Anti-cancer Therapies
Prior systemic therapies (e.g. chemotherapy) will be coded to therapeutic drug class and generic 
drug names using the World Health Organization (WHO) Drug Dictionary Enhanced version 
WHO-DDE 01 Mar 2015 or later. The number and percentage of subjects who had prior 
systemic anti-cancer therapies will be presented by drug class and generic drug name and 
overall.
Prior systemic anti-cancer therapies will be listed.
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nab-Paclitaxel (Abraxane®)
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8.4.2.
Prior Radiation Therapy
The number and percentage of subjects who had any prior radiation therapy will be presented. 
For subjects with prior radiation therapy, the number and percentage of subjects with each
treatment site of radiation therapy will be summarized with frequency counts and percentages.
The dose, duration of radiation therapy in days, and the number of fractions (where known), will 
be summarized descriptively. Intent (adjuvant, curative, palliative, unknown), and setting (stand-
alone, concurrent with other anti-cancer therapy, sequential to other anti-cancer therapy) will be 
summarized. Prior radiation therapies will be listed.
8.4.3.
Prior Cancer Surgeries
Prior non-small cell lung cancer surgeries will be coded by MedDRA system organ class and 
preferred term. A summary showing the number and percentage of subjects who had prior anti-
cancer surgery will be presented by system organ class and preferred term, and overall. 
Additionally, the time from the last prior cancer surgery to the first dose of study drug will be 
summarized. 
Prior surgeries will be listed.
8.4.4.
Concomitant Procedures/Surgeries
Concomitant procedures/surgeries are considered any procedures/surgeries that occurred on or 
after the date of the first dose of study drug. The number of subjects having concomitant 
surgeries or procedures performed will be summarized.
Concomitant surgeries and procedures will be listed.
8.5.
Prior and Concomitant Medications
Medications reported on the Prior and Concomitant medications eCRF pages will be coded to 
therapeutic drug classes and generic drug names using the WHO drug dictionary version WHO-
DDE 01 Mar 2015. Medications initiated prior to the start of study treatment and continued after 
the start of study treatment will be counted as both prior and concomitant medications.
Prior and concomitant medications will be listed.
8.5.1.
Prior Medications
Prior medications are defined as all medications that were started before the date of first dose of 
study drug. A summary showing the number and percentage of subjects who took prior 
medications will be presented by WHO drug dictionary therapeutic drug class and generic drug 
name. This summary will be presented for the treated population.
8.5.2.
Concomitant Medications
Concomitant medications are any medications that were taken on or after the date of the first 
dose of study drug and on or before 28 days after the last dose of study drug. Summaries 
showing the number and percentage of subjects who took concomitant medications will be 
presented by WHO therapeutic drug class and generic drug name for the treated population. 
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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9.
STUDY TREATMENTS AND EXTENT OF EXPOSURE
All study treatment and extent of exposure summaries will be provided based on the treated 
population. Descriptive statistics will be provided for treatment duration, number of cycles, 
cumulative dose, dose intensity, and percentage of protocol dose by study part (induction, 
monotherapy, and entire study), as applicable. The study treatments and extent of exposure 
summaries for nab-paclitaxel and carboplatin are presented separately for the induction part.
9.1.
Treatment and Cycle Start and End Dates
Day 1 of treatment for a subject is the same as Day 1 of treatment for the induction part and is 
defined as the first day of any study drug administered to the subject in the induction part (i.e., 
Cycle 1 Day 1). The first day of a cycle in the induction part is the first date of carboplatin 
administration for that cycle. Day 1 of monotherapy treatment for a subject is the first day of 
study drug administered to the subject in cycle 5. The first day of a cycle in the monotherapy part 
is the first administration of nab-paclitaxel for that cycle. The last day of a cycle (other than the 
last cycle) is defined as the day before the first day of the next cycle.
The treatment end date and the end date of the last cycle will be defined as follows:
!
For subjects who discontinued treatment, the treatment end date is the discontinuation 
date from the treatment disposition form on eCRF. 
!
For subjects who are still on treatment at the time of study closure or clinical cutoff, the 
treatment end date is defined as the date corresponding to the integer part of the day 
number of the maximum of the nab-paclitaxel dosing period and the carboplatin dosing 
period. Dosing periods are defined in Section 9.2.
The induction part end date is defined as:
!
For subjects who do not participate in the monotherapy part and discontinue prior to the 
clinical cutoff date, the induction part end date is equal to the treatment end date as
defined above. 
!
For subjects who are still on treatment in the induction part at the time of study closure or 
clinical cutoff, the induction part end date is equal to the treatment end date as defined 
above.
!
For subjects who participate in the monotherapy part, the induction part end date is the 
day before the first dose in cycle 5.
The treatment end date in the monotherapy part is defined only for subjects who start 
monotherapy and is equal to the treatment end date.
9.2.
Dosing Period for Each Study Drug
Dosing periods will be defined for each study drug and will be used as the denominators for the 
calculation of dose intensity for each drug. Dosing period will also be used in the definition of 
treatment end date for subjects who are still on treatment at the time of study closure or clinical 
cutoff. 
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9.2.
9.2


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Conceptually, the dosing period for an IP is the time period starting at the first dose of the IP and 
ending a protocol- and subject-specific number of days after the last dose, depending on the 
dosing schedule for the IP. Ending the dosing period on the date of last dose would lead to an 
overestimation of the dose intensity. To avoid such overestimation, additional days of dosing 
period beyond the date of the last dose allow for the calculated dose intensity to reflect the 
degree to which the subject’s dosing schedule aligned with the protocol-specified dose intensity.
A subject’s dosing period never extends beyond the date of death, but it can extend beyond the 
treatment discontinuation date in some circumstances.
For nab-paclitaxel, since the two protocol-specified doses are administered at uneven intervals, 
the end of the dosing period depends on whether the last dose administered was a Day 1 or a Day 
8 dose. If the last dose of nab-paclitaxel was a Day 1 dose, then the subject had half of the 
protocol-specified nab-paclitaxel doses for the last cycle, so they are allotted half of the cycle’s 
length (10.5 days) in their nab-paclitaxel dosing period. If the subject had all of the doses for the 
last cycle, as is always the case for carboplatin, and for the nab-paclitaxel when the last dose was 
a Day 8 dose, then the end of the dosing period is the last planned day of the cycle. If they have 
discontinued treatment, then the nab-paclitaxel dosing period can be extended to the treatment 
discontinuation date if that date is beyond the last cycle’s halfway point. If death occurs after the 
treatment discontinuation date but before the cycle’s halfway point, then the date of death is the 
end of the dosing period. The specific calculations of the dosing period for each IP are given in
Table 2.
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Table 2:
Calculation of Dosing Period for Each Study Drug Based on Cycle Day Number of Last Dose of the Study Drug
Overall Dosing Period
Investigational Product
Last Dose of IP is Day 1
Last Dose of IP is Day 8
nab-Paclitaxel
Min{study day of death, Max[study day treatment 
discontinuation, study day of last dose of nab-
paclitaxel + 9.5]}
Min{study day of death, Max[study day of 
treatment discontinuation, study day of last dose* 
of nab-paclitaxel + 13]}
Carboplatin
Min{study day of death, Max[study day of 
treatment discontinuation, study day of last dose* 
of carboplatin + 20]}
NA
Induction Dosing Period
nab-Paclitaxel
For subjects who do not participate in the monotherapy part and discontinue prior to the clinical cutoff 
date, equal to overall dosing period.
For subjects who are still on treatment in the induction part at the time of clinical cutoff, equal to overall 
dosing period.
For subjects who participate in the monotherapy part, study day number of the treatment end date for 
the induction part as defined in Section 9.1.
Carboplatin
Equal to overall dosing period
Monotherapy Dosing Period
nab-Paclitaxel
For subjects who participate in the monotherapy part, overall nab-paclitaxel dosing period – study day 
of induction part end date as defined in Section 9.1.
* date of last dose is the date of the latest dated record on the exposure eCRF (i.e., the last record for which there is a non-missing 
visit date or dose date, or both)
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9.3.
Treatment Duration
Treatment duration (months) is defined as (treatment end date – Day 1 of treatment + 1)/30.4375, 
where treatment end date is defined as in Section 9.1.
In addition, the following are the treatment duration definitions for the two parts of the study:
!
Induction treatment duration (months): 
(induction part end date – Day 1 of treatment + 1)/30.4375
!
Monotherapy Treatment Duration (months, defined for monotherapy subjects only): 
(treatment end date – Day 1 of monotherapy treatment + 1)/30.4375
Descriptive statistics will be provided for treatment duration, total number of cycles 
administered, and total number of doses of each study drug (where applicable) administered for 
the entire study and for the Induction and Monotherapy parts separately. 
9.4.
Cumulative Dose 
Cumulative dose for the entire study is defined as the sum of all assigned doses for all visits at 
which the actual dose administered > 0 mg. Cumulative dose will be computed separately for 
nab-paclitaxel and carboplatin. 
Induction part cumulative dose is defined as the sum of all assigned doses for all visits during the 
induction part at which the actual dose administered > 0mg. The induction doses will be 
identified by cycle numbers on the corresponding eCRF dose forms. Cumulative dose will be 
computed separately for nab-paclitaxel and carboplatin. 
Monotherapy part cumulative dose is defined as the sum of all assigned doses for all visits during 
the monotherapy part at which the actual dose administered > 0mg. Cumulative dose will be 
computed for nab-paclitaxel only in the monotherapy part. 
Descriptive statistics for cumulative dose will be presented for each study drug by study part as 
applicable (induction, monotherapy, and entire study) for the treated population.
9.5.
Dose Intensity
Dose intensity during the treatment is defined as the cumulative dose divided by the dosing 
period in weeks. Dose intensity will be calculated separately for nab-paclitaxel and carboplatin.  
Dose intensities will be calculated as follows:
!
Dose intensity for carboplatin (mg*min/mL/wk) = [cumulative dose for carboplatin in 
mg*min/mL] / [carboplatin dosing period in weeks];
!
Dose intensity for nab-paclitaxel (mg/m2/wk) = [cumulative dose for nab-paclitaxel in 
mg/m2] / [nab-paclitaxel dosing period in weeks].
!
Induction part dose intensity for nab-paclitaxel (mg/m2/wk) = [induction part cumulative 
dose for nab-paclitaxel in mg/m2] / [nab-paclitaxel induction part dosing period in 
weeks].
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Do
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!
Monotherapy part dose intensity for nab-paclitaxel (mg/m2/wk) = [monotherapy part 
cumulative dose for nab-paclitaxel in mg/m2] / [nab-paclitaxel monotherapy part dosing 
period in weeks].
Descriptive statistics for dose intensity will be presented for each study drug by study part as 
applicable (induction, monotherapy, and entire study) for the treated population.
9.6.
Percentage of Protocol Dose
Percentage of protocol dose is the dose intensity divided by the protocol weekly dose, expressed 
as a percentage.
Percentage of protocol dose = (dose intensity / protocol weekly dose) * 100%
The protocol weekly doses are as follows:
!
nab-Paclitaxel: 100 mg/m2 × 2 doses/cycle ÷ 3 weeks/cycle = 66.67 mg/m2/week
!
Carboplatin: 5 mg*min/mL × 1 dose/cycle ÷ 3 weeks/cycle = 1.67 mg*min/mL/week
The percentage of protocol dose for carboplatin and nab-paclitaxel will be summarized using 
descriptive statistics. Percentage of protocol dose will also be categorized and frequency counts 
will be provided. For nab-paclitaxel, the summary will be presented for the induction and 
monotherapy parts as well as for the entire study using the treated population.
9.7.
Exposure, Dose Reduction/Delay and Doses Not Administered
A dose reduction occurs when the dose assigned at a visit is lower than the dose assigned at the
previous visit. At Cycle 1 Day 1, any dose lower than 100 mg/m2 for nab-paclitaxel and 5 
mg*min/mL AUC for carboplatin is a dose reduction.
Any dose that is administered ≥ 3 days after scheduled date will be considered a dose delay.
Scheduled Day 1 of a cycle (other than Cycle 1 Day 1) is defined as
!
the date of Day 1 dose from previous cycle + 21
Scheduled Day 8 of a cycle = date of Day 1 dose + 7
Dose not administered is defined as any visit at which the question “Was dose administered?” on 
the exposure form is answered “No”. The incidences of nab-paclitaxel and carboplatin missed 
doses will be tabulated by frequency.
Treatment exposure, dose reductions, dose delays and missed doses will be summarized for the 
entire study and for the induction and monotherapy parts as applicable, as follows:
!
Number of doses administered by cycle;
!
Number and percentage of doses administered at each dose level by cycle;
!
Number and percentage of subjects with at least 1 dose reduction, number of dose 
reductions, and reasons (per protocol, adverse event, or other) for reduction, by study 
part, cycle and overall;
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!
Number and percentage of subjects with at least one dose delay, number of dose delays, 
by study part, cycle and overall;
!
Number and percentage of subjects with at least one dose not administered; number of 
doses not administered, by study part, cycle and overall; reason for dose not 
administered.
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10.
SAFETY ANALYSIS
The purpose of this section is to define the safety analyses for the study. All summaries of safety 
data will be conducted using the treated population. Safety analyses will be presented for the 
entire study; summaries of adverse events will also be presented by study part in which they 
started or worsened as applicable.
10.1.
Primary 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. A subject 
meets the primary endpoint if:
!
Adverse Event is the reason for treatment discontinuation as recorded in the eCRF; 
and
!
The subject had no doses administered beyond cycle 4.
The number and percentage of subjects who discontinue study treatment during the induction 
part due to TEAEs will be presented in a summary table along with a two-sided 95% CI.
10.2.
Treatment-emergent Adverse Events
TEAEs 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.
For subjects who enter monotherapy part, TEAEs with onset on or before Cycle 5 Day 1 will be 
considered TEAEs during the induction part. For subjects who discontinue before entering the 
monotherapy part, all TEAEs will be considered TEAEs during the induction part. For subjects 
who enter the monotherapy part, TEAEs with onset after Cycle 5 Day 1 will be considered 
TEAEs during the monotherapy part.
Adverse events will be coded according to the MedDRA, Version 19.0 or higher. Appendix 17.5
gives the dates of application of new versions of MedDRA. The severity of AEs will be graded 
based on NCI CTCAE, Version 4.0;
The incidence of TEAEs will be summarized by MedDRA system organ class (SOC) and 
preferred term (PT). For all other AEs not described in the CTCAE criteria, the severity will be 
assessed by the investigator as mild (grade 1), moderate (grade 2), severe (grade 3), life-
threatening (grade 4) or death (grade 5). 
The following rules will be implemented for cycle calculations:
!
TEAEs which start on Cycle 1 Day 1 belong to only Cycle 1.
!
After Cycle 1, TEAEs will be categorized by the “throw-back rule”, that is, AEs that start 
on Day 1 of a cycle will be allocated to only the previous cycle.
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!
All TEAEs which start after Day 1 of last cycle will be included only in the last cycle.
A treatment-related TEAE is defined as an adverse event which was suspected to be related to 
either study drug. Where feasible, summaries of treatment-related TEAEs will be presented by 
the individual study drug to which the AE was related. If a subject experiences multiple 
occurrences of the same AE with different relationship to study drug, the subject will be counted 
once, as treatment-related. AEs with a missing relationship will be presented in the summary 
table as treatment-related.
If a subject experiences the same AE more than once with different toxicity grade, then the event 
with the highest grade will be tabulated in “by grade” tables. If a subject experiences multiple 
AEs under the same PT (and/or SOC), then the subject will be counted only once for that PT
(and/or SOC). 
Tables summarizing the incidence of TEAEs will be generated for each of the following:
!
Overall summary of TEAEs;
!
TEAEs presented by MedDRA system organ class, preferred term, and maximum 
CTCAE grade
!
Treatment-related TEAEs by CTCAE grade category (grade 1-2 vs. grade 3-4 vs. grade 
5; overall and by cycle);
!
Serious TEAEs by maximum CTCAE grade ;
!
Treatment-related serious TEAE by maximum CTCAE grade;
!
TEAEs with action of study drug withdrawn;
!
Treatment-related TEAEs with action of study drug withdrawn;
!
TEAEs with action of study drug dose reduced or interrupted;
!
Treatment-related TEAEs with action of study drug dose reduced or interrupted;
!
TEAEs with fatal outcome;
!
Treatment-related TEAEs with fatal outcome;
!
All deaths;
!
Most frequent TEAEs ( ≥ 5% of subjects; by PT only, without SOC)
!
TEAEs for the following baseline subgroups (provided the number of subjects are 
sufficient): 
o
Age (<65 years, 65 – 74 years,  ≥75 years); 
o
Sex (male versus female); 
The following individual listings will be provided: 
!
Listing of TEAEs by subject;
!
Listing of non-TEAEs by subject;
!
Listing of TEAEs of special interest by subject.
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10.3.
Adverse Events of Special Interest
Specific adverse events of special interest are listed in Appendix 17.4. 
The following summaries will be provided for TEAEs included in the selected AEs of special 
interest: 
!
All TEAEs by maximum CTCAE grade; 
!
TEAEs with action of action of study drug withdrawn;
!
TEAEs with action of study drug dose reduced or interrupted;  
!
TEAEs by age group for risks specific to patients older than 75 (<65 years, 65 – 74 years, 
≥75 years).
10.4.
Peripheral Neuropathy
Peripheral neuropathy events will be reported as AEs and will be included in analyses described 
in Section 10.2. 
10.5.
Clinical Laboratory Evaluations
All clinical laboratory data (e.g., hematology and clinical chemistry) will be listed.
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11.
EFFICACY ANALYSIS
The primary objective of this study is safety. The treated population will be the primary analysis 
population for all efficacy endpoints. Supportive analysis of the efficacy endpoints PFS, OS, and 
ORR using the PP population will be conducted to assess the effect of major protocol deviations 
on efficacy.
The percent change from nadir during the Treatment Period in sum of lengths of longest 
diameters of target lesions is required to assess target lesions for tumor progression. This is 
calculated as follows:
Percent change from nadir at a given visit= (total length – nadir in total length) / (nadir in total 
length) x 100%, where nadir is calculated using all measurements prior to the visit in question, 
including baseline.
11.1.1.
Progression-free Survival
Progression-free survival (PFS) is defined as the time in months from Day 1 of Treatment to the 
date of disease progression based on investigator assessment according to RECIST 1.1 criteria 
(documented by radiological assessment) or death (any cause) on or prior to the clinical cutoff 
date, whichever occurs earlier. 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 time 
of the radiologic assessment that shows progression or the death date (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 time of the last radiologic assessment 
where the subject was documented to be progression-free prior to the first of the two missing 
visits. Missing radiologic assessments will be identified by comparing the dates of non-missing 
and evaluable overall response records to the 42-day protocol-specified assessment schedule and 
the 3-day window (see appendix section 17.6). Subjects who do not have disease progression and 
have not died, regardless of whether they discontinued treatment, will be censored at the date of 
last tumor assessment, on or prior to the clinical cutoff date, when the subject was progression-
free. This is further illustrated in Table 6.
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.
An additional analysis of PFS will be performed using the European Medicines Agency 
methodology for analysis of a PFS endpoint. Similar to the approach described above, PFS will 
be defined as the time from day 1 of treatment to the date of disease progression or subject death 
(any cause), whichever occurs first. Subjects who do not have disease progression or have not 
died will be censored at the last known time that the subject is progression free (i.e. the last 
tumor assessment). However, occasional missing observations or initiation of subsequent
anticancer therapy will not result in censoring for this analysis.
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11.1.2.
Disease Control Rate
Disease control rate is defined as the percent of subjects who have SD, CR or PR during the 
course of the study, according to RECIST 1.1 guidelines, as evaluated by the Investigator. 
Disease control rate will be summarized by number and percent of all treated subjects and 
presented with the associated Clopper-Pearson 95% confidence interval.
11.1.3.
Overall Survival
Overall survival is defined as the time in months between the day 1 of treatment and death from 
any cause. Thus, it is calculated as follows:
OS = (date of death or censoring – Day 1 of treatment + 1) /30.4375
Subjects who are still alive or lost to follow-up as of the clinical cutoff date will have their 
overall survival censored at the date of last contact. For subjects not lost to follow-up, the last 
contact date is the study disposition date. For subjects who are lost to follow-up the date of last 
contact is the last known alive date.
Overall survival will be summarized similarly to PFS described in Section 11.1.1. In addition, to 
assess the impact of starting subsequent anticancer therapy on subject survival, a sensitivity 
analysis will be conducted. Subjects who start a subsequent anti-cancer therapy will be censored 
at the initiation date of the subsequent chemotherapy; a method similar to the primary analysis 
will be applied to estimate the median OS and the survival distribution.
11.1.4.
Tumor Response and Overall Response Rate
Tumor response will be summarized by timing of lesion assessment and overall. Tumor 
assessments that occur after the initiation of subsequent anti-cancer therapy are excluded from 
the analysis. The number and percentage of subjects with a visit response or best overall 
response of PD, SD, PR, CR, and unevaluable (UE) will be presented. This analysis will be 
presented for each protocol-specified CT scan. If there is more than one CT scan within a 
relative day range, the best response will be counted. Relative study day windows are presented 
in Appendix 17.3.
The overall response rate (ORR) is the percent of subjects who achieve a best overall response of 
PR or CR compared with baseline, where baseline is the last CT-scan obtained prior to or on Day 
1 of study treatment and the best response is the best tumor response occurring between Day 1 of 
treatment and the start of subsequent anti-cancer therapy, death, or study discontinuation.  . The 
ORR along with 95% Clopper-Pearson confidence interval will be presented.
11.1.5.
Time to Response 
Time to response (TTR) is defined as the time from Day 1 of Study Treatment to the first 
occurrence of response (CR or PR). Only subjects with a CR or PR as a best overall response 
will be included in this analysis. TTR will be analyzed using descriptive statistics.
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11.1.6.
Duration of Response 
For subjects who had a CR or PR, the duration of overall response is measured from the time 
measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that 
recurrent or progressive disease is radiologically documented (taking as reference for progressive 
disease the smallest measurements recorded on study).
Subjects who are non-responders (i.e., do not achieve at least a PR) will be excluded from this 
analysis. Subjects who do not have PD after the response will be censored on the date of last 
tumor assessment. If a subject died before PD, then the subject will be censored on the date of 
death.
Duration of response will be analyzed using the Kaplan-Meier method. The median time of 
response (including 2-sided 95% CI) will be summarized. 
11.1.7.
Subgroup Analyses
If subject numbers in the subgroups are sufficient, PFS, OS, and ORR will be analyzed within 
the following subgroups (with subgroup data based on the clinical database rather than IRT). 
These analyses will parallel the analyses for the endpoint performed on the whole population:  
!
Age (< 65 years and ≥ 65 years, < 70 years and ≥ 70 years, < 75 years and ≥ 75 years);
!
Sex (Male, Female);
!
Histology (Squamous, Non-squamous)
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12.
EXPLORATORY ANALYSIS
12.1.1.
Healthcare Care Utilization
Frequency tabulations for location of care (number of office visits, hospital outpatient visits, 
hospital inpatient visits, emergency room visits, home healthcare visits, hospice, unknown, and 
other utilizations) and provider (general physician, specialist, nurse practitioner/physician 
assistant, paramedical care, unknown, and other) will be presented.
12.1.2.
Quality of Life
The Lung Cancer Symptom Scale (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 assessment the subject 
completes using a visual analogue scale (VAS) to denote intensity of a symptom. The EQ-5D-5L 
comprises 5 questions on mobility, self-care, usual activities, pain/discomfort, anxiety/depression 
and a VAS for overall QoL. In addition, there is an overall utility score that is derived from the 5 
questions. These questionnaires will be completed at Day 1 of every cycle, and at End of 
Treatment. Baseline scores are defined as scores captured on Day 1 of treatment (first dose date). 
In the case of multiple assessments on Day 1 of treatment, the later assessment will be used. 
Missing baseline scores will not be imputed.
12.1.2.1.
Lung Cancer Symptom Scale
The Lung Cancer Symptom Scale (LCSS) is designed to measure quality of life specifically 
affected by lung cancer and its symptoms. It evaluates burden due to six major symptoms:
!
Appetite
!
Fatigue
!
Coughing
!
Shortness of breath
!
Blood in sputum
!
Pain
In addition, it measures how bad a subject’s symptoms are, how much it has affected normal 
activities, and quality of life. 
The LCSS consists of two scales: one to be filled out by the subject and one by the health care 
provider. For this study, only the portion filled out by the subject will be used. The subject will 
respond to each of the 9 items using marks on a 100 mm visual analog scale (VAS). For analysis 
and presentation purposes, the scores will be presented such that 0 mm corresponds to the worst 
possible health state and 100 mm corresponds to the best possible health state. This reversal of 
scores will be accomplished by subtracting the raw score from 100 mm. The reversed scores will 
be used for all subsequent calculations, e.g., the summary scores.
The average of the VAS score of all 9 items will be calculated for each subject and will be 
referred to as the LCSS total score. The symptom burden index is the average of the 6 symptom-
specific items (the first 6 items). The average of the coughing, shortness of breath and blood in 
sputum items will be referred to as the Respiratory Symptom Scale. The average of the appetite 
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nab-Paclitaxel (Abraxane®)
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and fatigue items (the first 2 items) will be referred to as the overall constitutional score. The 
sum of the symptoms item (item 7), the normal activities item (item 8), and the global quality of 
life item (item 9) will be referred to as the 3-item scale.
Summary statistics of the individual LCSS items and summary scale scores, and the change from 
baseline will be summarized for the Treated population at every time point at which the 
instrument is given. In addition, the change from baseline to the best LCSS score during 
treatment will be presented. For each individual LCSS item, the best score on treatment is the 
highest reversed score at cycle 2 day 1 through the treatment discontinuation visit. For the 
summary scores, the best score on treatment is the highest value of the summary score at cycle 2 
day 1 through the treatment discontinuation visit. Finally, the change from baseline to the last 
LCSS score, defined as the difference between the last reported LCSS score at the treatment
discontinuation visit or the last reported LCSS score before clinical cutoff for subjects who have 
not had a treatment discontinuation visit will be presented. 
12.1.2.2.
EuroQoL Group 5-Dimension 5-Level
The EQ-5D-5L has been designed as an international, standardized, generic instrument for 
describing and valuing health-related quality of life. It contains only the domains common to 
generic health status measures, contains the minimum number of questions for each domain, was 
designed for ease of self-administration, and produces a single index for analysis. 
Five dimensions are covered by the EQ-5D-5L:
!
Mobility
!
Self-care
!
Usual Activities
!
Pain/Discomfort
!
Anxiety/Depression
The 5 dimensions are scored on a 5-point Likert scale. In addition, there is a question covering 
perceived change in health status over the previous 12 months measured on a 20 cm vertical 
visual analog scale “thermometer” to summarize one’s overall health status at administration on 
a 100 point scale.
Responses from the 5 dimensions are coded so that a ‘1’ indicates no problem on that dimension, 
and ‘5’ indicates the most serious problem. A profile is comprised of 5 digits consisting of 1s, 2s, 
3s, 4s, and 5s. For instance, a profile of 11111 indicates no problem with any of the 5 
dimensions, while a profile of 55555 indicates the most difficulty on all 5. Health state scores are 
based on the VAS with zero corresponding to the worst imaginable health state and 100 
corresponding to the best imaginable health state.  Missing or uninterpretable values (e.g. lines 
that cross the VAS twice) that are not recoverable by queries will be coded as ‘999.’
A utility score will be calculated using the US Crosswalk Index Value set obtained from the 
EuroQol website. The range of possible values for the utility score based on the US Crosswalk 
Index Value Set is -0.109 to 1.000. 
Shifts from baseline to each time point at which the instrument is given, as well as from baseline 
to the best post-baseline value and the last on-treatment value, will be presented for each 
dimension for the Treated population. 
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nab-Paclitaxel (Abraxane®)
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The utility score change from baseline in the utility score will be summarized for every time 
point at which the instrument is given for the Treated Population. In addition, the change from 
baseline to the best utility score reported during treatment, including the end of treatment visit,
will be presented. Finally, the change from baseline to the last on-treatment utility score, defined 
as the utility score at the end of treatment visit or the last reported overall score before clinical 
cutoff for subjects who have not had an end of treatment visit will be presented.
Summaries of the VAS results and the change from baseline will be presented for every time 
point at which the instrument is given. In addition, the change from baseline In addition, the 
change from baseline to the best VAS reported during treatment, including the end of treatment 
visit, will be presented. Finally, the change from baseline to the last on-treatment VAS, defined 
as the utility score at the end of treatment visit or the last reported overall score before clinical 
cutoff for subjects who have not had an end of treatment visit will be presented.
12.1.3.
Charlson Comorbidity Index Score
The Charlson comorbidity index (Charlson et al., 1987) predicts the ten-year mortality for a 
patient who may have a range of comorbid conditions, such as heart disease, AIDS, or cancer . 
Each condition is assigned a score of 1, 2, 3, or 6, depending on the risk of dying associated with 
each one. Scores are summed to provide a total score to predict mortality. 
Clinical conditions and associated scores are as follows:
!
1 each: Myocardial infarction, heart failure, peripheral vascular disease, Alzheimer’s, 
dementia from any etiology or serious cognitive impairment, cerebrovascular accident or 
transient ischemic heart disease, asthma, chronic lung disease, chronic bronchitis, 
emphysema, rheumatic or connective tissue disease, gastric or peptic ulcers, mild chronic 
liver disease, diabetes without end-organ damage.
!
2 each: Hemiplegia, moderate or severe renal disease, diabetes with end organ damage, 
any hematologic cancer (i.e., lymphoma, leukemia or myeloma).
!
3 each: Moderate or severe liver disease.
!
6 each: Metastatic solid tumor (all patients will have a weight of 6 assigned for their 
advanced NSCLC), AIDS (patients with a known HIV infection will be excluded from 
this study).
A summary of Charlson comorbidity index values will be presented in the demographic baseline 
characteristics table.
12.1.4.
Physician- and Subject-Reported ECOG Performance Status
The Eastern Cooperative Oncology Group (ECOG) score (Oken, 1982) runs from 0 to 5, with 0 
denoting perfect health and 5 death. These scales and criteria are used by doctors and researchers 
to assess how a patient's disease is progressing, assess how the disease affects the daily living 
abilities of the patient, and determine appropriate treatment and prognosis. The ECOG 
performance scores are as follows:
!
0: Fully active, able to carry on all pre-disease performance without restriction.
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nab-Paclitaxel (Abraxane®)
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!
1: Restricted in physically strenuous activity but ambulatory and able to carry out work of 
a light or sedentary nature, e.g., light house work, office work.
!
2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up 
and about more than 50% of waking hours.
!
3: Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours.
!
4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
!
5: Dead.
Physician-reported ECOG PS will be assessed and reported on the appropriate eCRF at 
screening, Day 1 of each cycle and at treatment discontinuation. Subject-reported ECOG PS will 
be completed at Day 1 of each cycle, and at treatment discontinuation. The agreement between 
the two sets of ECOG PS scores will be explored by cross-tabulation of the two endpoints.
Percent agreement will be provided as a measure of agreement between subject and physician. A 
shift table representing the shift from the baseline to the worst post-baseline ECOG PS scores
will be provided for subject-reported and physician-reported ECOG PS scores. Finally, the 
number and percent of subjects who improved and worsened in ECOG PS compared to baseline 
by visit and over the course of the study will be summarized.
12.1.5.
Physician- and Subject-Reported Karnofsky Performance Status
The Karnofsky Performance Status (KPS) Index allows patients to be classified as to their 
functional impairment. It is a standard way of measuring the ability of cancer patients to perform 
ordinary tasks. KPS scores range from 0 to 100. A higher score means the patient is more able to 
carry out daily activities. KPS scores may be used to determine a patient's prognosis and to 
measure changes in a patient’s ability to function.
The physician- and subject-reported KPS will be completed on Day 1 of Cycle 1 only.
KPS as reported by the physician and the subject at baseline will be summarized with descriptive 
statistics. In addition, KPS scores will be categorized into the following:  ≤40, 50, 60 ~70, 80
~90 and 100, and frequency counts by these categories will be provided. The boundaries of these 
categories may be adjusted if necessary depending on the distribution of the data. The correlation 
between the two sets (physician vs. self-reported) of KPS scores will be explored by cross-
tabulation with the above categories. Cohen’s kappa coefficient will be provided as a measure of 
inter-rater agreement of agreement between subject and physician.
12.1.6.
Spirometry and Pulse Oximetry
Summary statistics of actual values, as well as change and percent change from baseline in lung 
function as measured by the spirometry items below will be summarized for the treated 
population by visit.
!
Forced expiratory volume in 1 second (FEV1)
!
Forced vital capacity (FVC)
!
Peak expiratory flow (PEF)
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nab-Paclitaxel (Abraxane®)
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Summary statistics of actual values, change from baseline, and percent change from baseline in
oxygen saturation of blood as measured by pulse oximetry will be summarized for the treated 
population by visit. For subjects who use bronchodilators, both pre- and post-bronchodilator 
values will be presented in listings; post-bronchodilator values will be included in the statistical 
summaries.
12.1.7.
Tumor Response During the Monotherapy Part
A separate summary for tumor response during the monotherapy part will be presented: the 
number and percentage of subjects who attain a greater degree of treatment response (SD to PR 
or CR, PR to CR) during the monotherapy part compared with the response at the start of 
monotherapy will be summarized.
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13.
FOLLOW UP TREATMENTS
First subsequent systemic anti-cancer regimens will be summarized. 
To assess how quickly the second line therapy will be initiated for the subjects who discontinued 
the study treatment for reasons other than lost to follow-up or death and enter follow-up, the time 
to first subsequent systemic anti-cancer therapy during follow up period will be analyzed. Time 
to first subsequent systemic anti-cancer therapy is defined as the time interval from the date of 
treatment discontinuation to the date that subsequent therapy is initiated. The start date of the 
first subsequent anti-cancer regimen is the earliest start date of any anti-cancer therapy taken in 
the follow-up/survival period. Subjects who don’t have a subsequent therapy and have not died 
as of the cutoff date for the statistical analysis will be censored at the last follow up date. 
Subjects who died before initiating a subsequent therapy will be censored at the date of death.
The time to second line therapy will be analyzed using the Kaplan-Meier method. The median 
time (including 2-sided 95% CI) will be summarized.
In addition, first subsequent anti-cancer treatment regimens will be summarized by the number 
and percentage of subjects receiving each regimen category and regimen; the number of cycles 
overall, and the number of cycles for each regimen category and regimen administered. The best 
response overall and for each regimen category and regimen administered will be summarized. 
Treatment duration, defined as (date of last dose of any treatment in a regimen - date of first dose 
of any treatment in the same regimen) + 1 will be summarized as well. Additional subsequent 
anti-cancer treatment regimens will be listed
Anti-cancer surgeries during follow-up will be summarized by system organ class and preferred 
term Follow-up surgeries will be listed.
Radiation therapy during follow-up will be summarized by category (prior, concomitant, follow 
up); type (External beam, radio-immuno therapy, brachytherapy, other); location (if external 
beam); dose; fraction; intent (adjuvant, curative, palliative, unknown); and setting (stand-alone
radiation therapy, concurrent with other anti-cancer therapy, sequential to other anti-cancer 
therapy). Follow-up radiation therapy will be listed.
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14.
INTERIM ANALYSIS
An interim review of the primary safety endpoint will be conducted when approximately a total 
of 20 treated subjects have either completed 4 cycles of study treatment or 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.
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15.
CHANGES TO THE STATISTICAL ANALYSES SECTION OF 
THE PROTOCOL
The protocol stated that approximately 50 subjects would be enrolled. After the interim review, it 
was decided by the Steering Committee as well as Celgene Leadership to close enrollment early. 
A total of 40 subjects were treated in this study.
Differing from the definition in Protocol Section 10.2.2, the per-protocol (PP) population in this 
SAP is defined as all eligible subjects enrolled who receive at least one dose of the 
investigational product; have a baseline and at least one evaluable post baseline radiological 
assessment; and do not have any relevant protocol violations or deviations.
In Protocol Section 10.4, it was stated that “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.” In this SAP, the demographics and baseline 
characteristics will be summarized for all treated subjects. Individual subject listings will be 
provided to support the summary tables.
The protocol stated that PFS, DCR, ORR, and OS over the entire study are the key efficacy 
endpoints of the study. The following secondary efficacy endpoints will be added to the efficacy 
analysis section of the SAP to further characterize the ORR endpoint: time to response and
duration of response. Additionally, PFS, OS, and ORR will be analyzed on the whole population 
and on subgroups (i.e. age, sex, race and histology type). The PFS censoring rules given in 
protocol section 10.7.1.1 are elaborated with clarification of derivation rules in section 11.1.1 of 
this document.
Finally, while the collection of spirometry and pulse oximetry data were specified in the 
protocol, this SAP adds changes from baseline in spirometry and pulse oximetry parameters as 
exploratory endpoints.
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nab-Paclitaxel (Abraxane®)
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16.
REFERENCES
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic 
comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987; 40(5):373-
83. PubMed PMID: 3558716.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, et al. New 
response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur 
JCancer. 2009 Jan; 45(2):228-47.
Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, 
P.P.: Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin 
Oncol, 1982 5:649-655.
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17.
APPENDICES 
17.1.
Handling of Dates 
Dates will be stored as numeric variables in the SAS analysis files and reported in 
DDMMMYYYY format (ie, the Date9. datetime format in SAS).  Dates in the clinical database 
are classified into the categories of procedure dates, log dates, milestone dates, outcome dates, 
and special dates.
!
Procedure Dates are the dates on which given protocol-specified procedure are 
performed.  They include the dates of laboratory testing, physical examinations, tumor 
scans, etc.  They should be present whenever data for a protocol-specified procedure are 
present and should only be missing when a procedure are marked as NOT DONE in the 
database.  Procedure dates will not be imputed.
!
Log Dates are dates recorded in eCRF data logs.  Specifically, they are the start and end 
dates for adverse events and concomitant medications/procedures.  They should not be 
missing unless an event or medication is marked as ongoing in the database.  Otherwise, 
incomplete log dates will be imputed according to the rules in Appendix 16.2 (e.g., for 
duration or cycle assignment, etc). However, in listings, log dates will be shown as 
recorded without imputation.
!
Milestone Dates are dates of protocol milestones such as study drug start date, study 
drug termination date, study closure date, etc.  They should not be missing if the 
milestone occurs for a subject.  They will not be imputed.
!
Outcome Dates are dates corresponding to study endpoints such as survival, progression, 
etc.  In most cases they are derived either from a milestone (e.g., the survival date is 
derived from the death date), or a procedure date (e.g., the progression date is derived 
from the date of the tumor scan that was used to determine progression).  They may be 
subject to endpoint-specific censoring rules if the outcome did not occur, but are not 
otherwise subject to imputation.
!
Special Dates cannot be classified in any of the above categories and they include the 
date of birth.  They may be subject to variable-specific censoring and imputation rules. 
!
Last Contact Dates for the survival analysis are the maximum date collected in the 
database, if the imputed date used for response date or AE date, the last contact dates 
should be the latest date of those imputed date and maximum date in the database.
Dates recorded in comment fields will not be imputed or reported in any specific format. 
Calculation Using Dates
Calculations using dates (e.g., subject’s age or relative day after the first dose of study drug) will 
adhere to the following conventions: 
!
Study days after the start day of study drug will be calculated as the difference between 
the date of interest and the first date of dosing of study drug plus 1 day. The generalized 
calculation algorithm for relative day is the following: 
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∀
If TARGET DATE >= DSTART then STUDY DAY = (TARGET DATE –
DSTART) + 1; 
∀
Else use STUDY DAY = TARGET DATE – DSTART.
Note that Study Day 1 is the first day of treatment of study drug. Negative study days are 
reflective of observations obtained during the baseline/screening period.  Note: Partial dates for 
the first study drug are not imputed in general. All effort should be made to avoid incomplete 
study drug start dates. 
!
Age (expressed in days) is calculated: AGE = INFORMED CONSENT DATE – DATE 
of BIRTH + 1.  In practice, age will be transformed to years by dividing the difference by 
365.25 days, then truncating.
∀
Partial birth date: impute missing day as 15th of the month; impute missing month 
as July; set missing age for missing year
!
Intervals that are presented in weeks will be transformed from days to weeks by using 
(without truncation) the following conversion formula:
WEEKS = DAYS /7
!
Intervals that are presented in months will be transformed from days to months by using 
(without truncation) the following conversion formula:
MONTHS = DAYS /30.4375
17.2.
Date Imputation Guideline
17.2.1.
Impute Missing Dates for Adverse Events/ Prior or Concomitant Medications
Incomplete Start Date:
!
If the stop date is not missing, and the imputed start date is after the stop date, the start 
date will be imputed by the stop date.
Missing day and month
!
If the year is the same as the year of the first dosing date, then the day and month of the 
first dosing date will be assigned to the missing fields.
!
If the year is prior to the year of first dosing date, then December 31 will be assigned to 
the missing fields.
!
If the year is after the year of first dosing, then January 1 will be assigned to the missing 
fields.
Missing day only 
!
If the month and year are the same as the year and month of first dosing date, then the 
first doing date will be assigned to the missing day.
!
If either the year of the partial date is before the year of the first dosing date or the years 
of the partial date and the first dosing date are the same but the month of partial date is 
TE
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nab-Paclitaxel (Abraxane®)
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Confidential and Proprietary
49
before the month of the first dosing date, then the last day of the month will be assigned 
to the missing day.
!
If either the year of the partial date is after the year of the first dosing date or the years of 
the partial date and the first dose date are the same but the month of partial date is after
the month of the first dosing date, then the first day of the month will be assigned to the 
missing day.
Missing day, month, and year
!
No imputation is needed, the corresponding AE will be included as TEAE if end date 
of AE is after the first dose date or the end date is also missing. 
Incomplete End Date:
Missing day and month
!
December 31 will be assigned to the missing fields. 
Missing day only 
!
The last day of the month will be assigned to the missing day. 
17.3.
Relative Day Ranges for CT-Scans
Table 3: Relative Day Ranges for CT Scans
Study Week
Relative Days in 
Study
Study Week
Relative Days in 
Study
6
2 - 63
78
526 - 567
12
64 - 105
84
568 - 609
18
106 - 147
90
610 - 651
24
148 - 189
96
652 - 693
30
190 - 231
102
694 - 735
36
232 - 273
108
736 - 777
42
274 - 315
114
778 - 819
48
316 - 357
120
820 - 861
54
358 - 399
126
862 - 903
60
400 - 441
132
904 – 945
66
442 - 483
138
946 - 987
72
484 - 525
17.4.
Adverse Events of Special Interest
Table 4 provides the spreadsheets of adverse events of special interest that were used for data 
summaries up to the dates provided.
&(/*(1(35235,(7$5<,1)250$7,21
date
dat
ay
ay. 
Stu
Study W
y
7$
,(
5,
5,
5,
5,
5,
47
35
- 189
189
23
90 - 231
90 - 231
52
232 - 27
232 - 27
52
274 -
274 -
35
31
3
( 3
(
1(
1(
1(
1(
1(
(1
72
*(
/*
4.4.
Ad
Ad
Table
Ta
4 p
umma
umma


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
50
Table 4: Treatment-emergent Adverse Events of Special Interest File and Dates
For reports through: 
File
MedDRA version
04May2015 – 01May2016
ABRAXANE 
ABI-007-NSCL-004_V1
18.0
02May2016 - present
ABRAXANE 
ABI-007-NSCL-004_V
19.0
17.5.
MedDRA Versions and Dates
Table 5 gives the MedDRA versions used in this study and the dates of implementation.
Table 5: MedDRA Versions and Dates
For reports dated: 
MedDRA version
04May2015 – 01May2016
18.0
02May2016 – present 
19.0
17.6.
PFS Censoring Rules
Table 6 gives the specific rules for determining PFS analysis dates and identifying events and 
censored observations. The 91 day criterion assumes that tumor assessments should be 
performed every 42 days plus up to 3 days. Therefore, after 45 days have passed, one tumor 
assessment has been missed. After 90 days have passed (starting from 91 days) two tumor 
assessments have been missed.
Table 6: PFS Censoring Rules
Situation
Analysis Date 
Censored or 
Event
Disease progression, and time interval 
between progression date and 
previous tumor assessment date with 
progression-free response is less than 
or equal to 91 days
Date of disease progression 
recorded on overall response form 
where overall response is PD
Event
Disease progression at first post-
baseline tumor assessment and the 
time interval between progression date 
and first dose date is less than or equal 
to 91 days
Date of disease progression 
recorded on overall response form 
where overall response is PD
Event
&(/*(1
progressi
progression
on
en progress
n progress
vious tumo
vious tumo
progression
progression
or equal 
or equal 
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7
50$7
mplementat
mpleme
5
$5
$5
$5
(7$5
mining PF
mining P
iteri
teri
i
on assu
on a
o 3 days. T
o 3 days. T
fter 90 days
ter 90 days
d.d.
g Rules
g Rules
ituation
uation
(
(1
(1
&
Di
Dise
s
b
&(
&


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-004
Celgene Corporation
Confidential and Proprietary
51
Disease progression, and time interval 
between the progression date and the 
previous tumor assessment date with 
progression-free response is greater 
than 91 days.
The last progression-free assessment 
date
Censored
Disease progression at first post-
baseline tumor assessment and time 
interval between the progression date 
and first dose date is greater than 91
days.
First dose date
Censored
Death without any post-baseline 
radiological assessment, and time 
interval between death date and first 
dose date is less than or equal to 91
days
Death date
Event
Death before documented progression, 
and time interval between death date 
and previous tumor assessment date 
with progression-free response is less 
than or equal to 91 days
Death date
Event
Death without any post-baseline 
radiological assessment, and time 
interval between death date and first 
dose date is greater than 91 days
First dose date
Censored
Death before documented progression, 
and time interval between death date 
and previous tumor assessment date 
with progression-free response is 
greater than 91 days
The last progression-free 
assessment date
Censored
No death or disease progression and 
no new anti-cancer therapy (i.e., 
systemic anti-cancer therapy, anti-
cancer surgery, curative radiotherapy).
Latest of 
!
the last progression-free 
assessment date
!
first dose date
Censored
Subsequent anti-cancer treatment (i.e., 
systemic anti-cancer therapy, anti-
cancer surgery, curative radiotherapy) 
started prior to progression
Latest of 
!
the last progression-free 
assessment date prior to start 
of anti-cancer treatment
!
first dose date
Censored
Note: Progression-free response refers to a response that was neither progressive disease 
(PD) nor un-evaluable (UE). 
&(/*(
quent anti
uent anti-
*(1(35235,(7$5<,1)250$7,21
$7
Event
Event
0$
)2
1)
se date
e date
$5
on, 
on, 
date
date
nt date
t dat
nse is
nse is
The
he la
ass
5
23
progressi
progressio
er therapy
er therapy (
y
cancer thera
ancer thera
ery
ery, curativ
, curativ
3
temic anti
emic anti-
cancer surg
ancer surg
started pr
started pr
*(
&
N
&