Conditions: Non-Small Cell Lung Cancer Carcinoma Squamous Cell Carcinoma Adenocarcinoma Carcinoma, Large Cell Lung Neoplasm
Keywords: NSCLC advanced non-small cell lung cancer squamous adenocarcinoma large cell carcinoma lung cancer elderly first line treatment abraxane carbo nab-paclitaxel
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 143
Healthy volunteers: no

Brief summary:
Study comparing two regimens of nab-paclitaxel and carboplatin combination in elderly subjects (≥ 70 years old) with advanced NSCLC

Detailed description:
This is a Phase IV, randomized, open-label, multicenter study of continuous weekly versus weekly times three with one-week break nab-paclitaxel in combination with carboplatin as first-line treatment in elderly subjects (≥ 70 years old) with advanced non small cell lung cancer who have not received prior chemotherapy for their advanced disease and are not candidates for curative surgery or radiation therapy. The primary study endpoint is the percentage of subjects with either peripheral neuropathy or myelosuppression adverse events. Patients will continue treatment until they develop progressive disease, unacceptable side-effects or wish to withdraw from the study, according to local standard of care. Patients will have radiographic evaluations every 6 weeks while on treatment.

Arms:
arm 1: nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, and 15 and Carboplatin AUC = 6 mg\*min/mL IV following nab-paclitaxel infusion on Day 1 of every 21-day treatment cycle arm 2: nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 21-day treatment followed by one-week break and Carboplatin AUC = 6 mg\*min/mL IV following nab-paclitaxel infusion on Day 1 of each 21-day treatment followed by one-week break

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

Protocol document:
SAP_002.pdf: 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
TITLE PAGE
SAFETY AND EFFICACY OF nab-PACLITAXEL 
(ABRAXANE®) IN COMBINATION WITH 
CARBOPLATIN AS FIRST LINE TREATMENT IN 
ELDERLY SUBJECTS WITH ADVANCED NON-SMALL 
CELL LUNG CANCER (NSCLC): A PHASE IV, 
RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY
(ABOUND.70+)
STUDY DRUG
nab-Paclitaxel (Abraxane®)
PROTOCOL NUMBER:
ABI-007-NSCL-005
ORIGINAL DATE FINAL:
06 Mar 2014
AMENDMENT 1 DATE FINAL:
09 Apr 2014
AMENDMENT 2 DATE FINAL:
05 Dec 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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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 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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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 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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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:
 
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
PROTOCOL SUMMARY
Study Title
Safety and efficacy of nab-paclitaxel (Abraxane) in combination with carboplatin as first line 
treatment in elderly subjects with advanced non-small cell lung cancer (NSCLC): A Phase IV, 
randomized, open-label, multicenter study (Abound.70+).
Indication
First-line treatment of advanced NSCLC in elderly subjects.
Objectives
Primary
!
To assess the safety and tolerability of continuous weekly versus weekly times three 
with one-week break nab-paclitaxel (Abraxane) in combination with carboplatin as 
first-line treatment for advanced NSCLC in elderly subjects (≥ 70 years old).
Secondary 
!
To evaluate the efficacy of nab-paclitaxel in combination with carboplatin in elderly 
subjects with advanced NSCLC.
Exploratory 
!
To assess healthcare resource utilization for the two nab-paclitaxel treatment arms.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ-5D) for the two nab-paclitaxel treatment arms.
!
 
 
!
 
Study Design
This is a Phase IV, randomized, open-label, multicenter study of continuous weekly versus 
weekly times three with one-week break nab-paclitaxel in combination with carboplatin as first-
line treatment in elderly subjects (≥ 70 years old) with advanced NSCLC who are not candidates 
for curative surgery or radiation therapy. Approximately 284 subjects with locally advanced or 
metastatic NSCLC will be randomized in this study to receive nab-paclitaxel in combination 
with carboplatin and will be randomized 1:1 into one of the two treatment arms prior to starting 
first dose of study drug. Randomization will be centralized and stratified by Eastern Cooperative 
Oncology Group (ECOG) performance status (0 versus 1, see Appendix A) and histology 
(squamous cell carcinoma versus non-squamous cell carcinoma).
The study will consist of a 28-day Screening Period, a Treatment Period, and a Follow-up 
Period.  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of study drug.
The Treatment Period begins with the first dose of study drug as described in Section 8.  Subjects 
will receive one of the following treatments based on the randomization assignment:
Arm A (21-day treatment cycle):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment cycle,
!
Carboplatin area under the curve (AUC) = 6 mg*min/mL IV on Day 1 of each 21-day 
treatment cycle after completion of nab-paclitaxel infusion.
Arm B (21-day treatment followed by one-week break cycle, 28-day duration):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment  followed by one-week break cycle (i.e. every 28 
days),
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment followed by 
one-week break cycle (i.e. every 28 days), after completion of nab-paclitaxel 
infusion. 
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of 
consent, in accordance with local standard of care.
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
(v1.1) (Eisenhauer, 2009).
Local laboratory test data for absolute neutrophil count (ANC), platelet count, hemoglobin and 
serum creatinine will be collected in the electronic case report forms (eCRFs). All other 
laboratory test data, except those mentioned above, will not be collected routinely in the eCRF. 
All abnormal and clinically significant laboratory test results will be reported as adverse events 
(AEs) or serious adverse events (SAEs), and the specific associated laboratory parameter(s) 
should be recorded on the laboratory assessments eCRF. Local safety laboratory data will also be 
the primary guide for eligibility and subject management. In addition, test results for tumor 
mutational status of genes including but not limited to EGFR, ALK, and KRAS will be collected 
and recorded on eCRF if these tests have been performed locally for routine diagnosis.  
All subjects who discontinue from treatment for any reason other than withdrawal of consent or
lost to follow-up will enter the Follow-up Period. It will consist of a visit 28 days after treatment 
discontinuation. Thereafter, subjects will be followed for survival approximately every 90 days 
(or when they are seen for routine care) by phone call or chart review for documentation of last 
contact for up to 6 months after the last subject is randomized or 192 progression-free survival 
(PFS) events have been observed, whichever comes later.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
Those subjects entering the Follow-up Period without documented progression will continue to 
have computed tomography (CT) scans in accordance with standard of care (at least every 90 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death or 
study closure. 
Study Population
Male and female subjects ≥ 70 years of age, with locally advanced or metastatic NSCLC 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.
Length of Study
The enrollment of 284 subjects on this study will take approximately 24 months. The total length 
of this Phase IV study with follow-up is estimated to be approximately 3 years.  
Study Treatments
Investigative sites will use standard of care (commercially available) product via prescription for 
nab-paclitaxel and carboplatin.
The preparation for IV administration procedures for nab-paclitaxel and carboplatin should be 
followed in accordance with the approved Prescribing Information for each drug.
Statistical Methods
Approximately 284 subjects will be randomized in a 1:1 ratio to one of two treatment arms 
(approximately 142 per arm).  Arm A will receive nab-paclitaxel 100 mg/m2 administered on 
Days 1, 8 and 15 in combination with carboplatin AUC = 6 mg*min/mL on Day 1 of each 21-
day treatment cycle, and Arm B will receive the same treatment in the same schedule as that of 
Arm A during the first 21 days, followed by a one-week break prior to the start of the next cycle
(28-day duration).  
Randomization will be stratified by ECOG performance status (0 versus 1) and histology 
(squamous cell carcinoma versus non-squamous cell carcinoma).
The primary objective of this study is to assess the safety and tolerability of the two treatment 
arms for first-line treatment of locally advanced or metastatic NSCLC in elderly subjects ( ≥ 70 
years old).  The primary study endpoint, correspondingly, is the percentage of subjects with 
either peripheral neuropathy of Grade ≥2 or myelosuppression AEs Grade ≥3 based on the local
laboratory values for ANC, platelet count, and hemoglobin, assessed using National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4.0). 
The peripheral neuropathy events will be identified from the clinical AE dataset using the 
Standardised MedDRA Queries (SMQs). For the purpose of this protocol, this endpoint will be 
referred to as the percentage of subjects with Grade ≥2 peripheral neuropathy or Grade ≥3 
myelosuppression laboratory adverse events.  
The study is designed to detect a difference of 16 percentage points between the 2 treatment arms
with respect to the primary safety endpoint with 80% power and a Type-I error rate of 5% (two-
sided), assuming 139 of the 142 randomized subjects per arm will receive at least one dose of 
study drug and the percentage of the treated subjects with the AEs specified above is 73% for 
Arm A.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
9
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
A non-binding interim analysis for futility with the primary safety endpoint will be conducted 
when approximately a total of 139 treated subjects have either completed 6 months of study 
treatment or discontinued from the study due to progression, adverse events, deaths, lost to 
follow up, or other reasons. The study may be stopped early for futility if the treatment 
difference is between ± 0.4%, given the interim analysis is performed at 50% information 
fraction. 
Overview of Safety Assessment
The treated population, which includes all randomized subjects who received at least one dose of 
study drug, will be the analysis population for all safety analyses.  
The primary study endpoint (a composite safety endpoint) will be the percentage of subjects with 
Grade ≥2 peripheral neuropathy or Grade ≥3 myelosuppression laboratory adverse events.  
The null (Ho) and alternative (Ha) hypotheses for this endpoint are as follows, where P is the rate 
of the AEs described for the primary safety endpoint: 
Ho:  P Arm B = P Arm A
Ha:  P Arm B ≠ P Arm A
The AE rate of the primary study endpoint will be summarized within each treatment arm by 
descriptive statistics.  The treatment difference in the AE rate will be analyzed using a Mantel-
Haenszel Chi-square test with ECOG performance status (0 versus 1) and histology (squamous 
cell carcinoma versus non-squamous cell carcinoma) as the stratification factors.  The ratio of the 
AE rates will be summarized along with the two-sided 95% confidence interval (CI). 
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AE or SAE that begins or worsens in grade on or after the start of the study drug
through 28 days after the last dose of the study drug. Additionally, any SAE that occurs beyond 
this period of observation and is assessed by the investigator as related to the study drug, will be 
reported and analyzed.  
Treatment-emergent adverse events will be summarized by treatment arm by system organ class
and preferred term. Grade 3 or higher TEAEs, SAEs, TEAEs leading to dose modification 
(reduction, delay not given, and interruption), TEAEs leading to treatment discontinuation, and 
TEAEs with an outcome of death will be summarized by treatment arm. Adverse events of 
special interest of the nab-paclitaxel and carboplatin combination identified in previous studies
in a similar population will be summarized in the same manner.
In order to investigate the maximal degree of myelosuppression, ANC, platelet count, and 
hemoglobin will be summarized by the most severe grade in each treatment cycle and by the 
most severe grade during the study using NCI CTCAE v4.0. 
Overview of Efficacy Assessment
All efficacy analyses will be based on the intent-to-treat (ITT) population, which includes all 
randomized subjects regardless of whether they receive any study drugs or have any efficacy 
assessments performed.  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
10
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
Progression-free Survival (PFS) based on investigator’s assessment of the subject’s radiologic 
response using RECIST v1.1 guidelines, Overall Response Rate (ORR), and Overall Survival 
(OS) are the key efficacy endpoints.  Since the primary research interest of this study is to 
evaluate the relative safety and toxicities of the two treatment arms, the sample size was
calculated based on the primary safety endpoint, the percentage of subjects with Grade ≥2
peripheral neuropathy or Grade ≥3 myelosuppression laboratory adverse events.  Consequently, 
a statistically non-significant treatment difference in PFS, ORR or OS could simply be a function 
of the sample size and/or the lack of statistical power. Therefore, the assessments of treatment 
differences in PFS and OS will be based on the hazard ratios and in ORR, the ratio of response 
rates, and the corresponding 95% confidence intervals. P-values for between-group comparisons 
will be provided to indicate the strength of association only.  No multiplicity adjustment with the 
Type-I error rate will be made. 
Progression-free survival is defined as the time from the randomization date to the start of 
disease progression or subject death from any cause, whichever occurs first. Subjects who do not 
have disease progression or have not died as of the data cutoff date for the statistical analysis will 
be censored at the time of the last radiologic assessment prior to the data cutoff date. Rules for 
censoring for missing visits and start of anticancer treatment are provided in Section 10. 
Progression-free survival will be summarized using the Kaplan-Meier method and by median 
PFS time (including two-sided 95% confidence interval [CI]) for each treatment arm along with 
the hazard ratio (including two-sided 95% CI) between treatment arms. The Kaplan-Meier curve 
for PFS will be presented graphically for each treatment arm. To illustrate the strength of 
association, the p-value for treatment difference in the curves will be reported from a stratified 
log-rank test with ECOG performance status (0 versus 1) and histology (squamous versus non-
squamous cell carcinoma) as the stratification factors.  
Of note, if recruitment is complete in 24 months, assuming that approximately 67% of the 284 
subjects randomized will experience a PFS event (approximately 192 PFS events total) within 28
months from first subject randomized, there is 73% power to detect a hazard ratio (HR) of 0.69 
for PFS improvement with Arm B over Arm A and an overall Type-I error rate of 5% (two-
sided).  Assuming an exponential distribution with a median time to PFS of 5.8 months for Arm 
A and proportional hazards, a hazard ratio of 0.69 constitutes a 2.6 months improvement for Arm 
B. 
Overall response rate (percent of subjects who had a radiologic complete or partial response 
according to the investigator’s assessment of response based on RECIST v1.1 guidelines) and 
OS also will be assessed by descriptive statistics with the associated 95% CIs.  P-values from a 
Chi-square test and a stratified log-rank test will be provided to indicate the strength of 
association for the treatment differences in ORR and OS, respectively.  
The analyses of the safety and efficacy endpoints for the clinical study report will be performed 
after ~192 PFS events have been observed.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
11
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
1.
INTRODUCTION..................................................................................................18
1.1.
Non-small Cell Lung Cancer ..................................................................................18
1.2.
nab-Paclitaxel in NSCLC .......................................................................................19
1.3.
Rationale for Further Study of nab-Paclitaxel as First-line Treatment in 
Elderly Subjects with Advanced NSCLC................................................................20
2.
STUDY OBJECTIVES...........................................................................................22
2.1.
Primary Objectives .................................................................................................22
2.2.
Secondary Objective...............................................................................................22
2.3.
Exploratory Objectives ...........................................................................................22
3.
STUDY ENDPOINTS............................................................................................23
3.1.
Primary Endpoint....................................................................................................23
3.2.
Secondary Endpoints ..............................................................................................23
3.2.1.
Safety.....................................................................................................................23
3.2.2.
Efficacy..................................................................................................................23
3.3.
Exploratory Endpoints............................................................................................23
4.
OVERALL STUDY DESIGN ................................................................................24
4.1.
Study Design ..........................................................................................................24
4.1.1.
Follow-up Period....................................................................................................25
4.2.
Study Design Rationale ..........................................................................................25
4.3.
Study Duration .......................................................................................................27
4.4.
End of Trial ............................................................................................................27
5.
TABLE OF EVENTS.............................................................................................28
6.
PROCEDURES......................................................................................................31
6.1.
Medical History......................................................................................................31
6.2.
Prior and Concomitant Medications/Procedures......................................................31
6.3.
Computed Tomography (CT) Scan of Complete Chest (including base of 
neck and adrenal glands).........................................................................................31
6.4.
Weight....................................................................................................................32
6.5.
Body Surface Area (BSA) Calculation and Height..................................................32
6.6.
ECOG Performance Score ......................................................................................32
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
12
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
6.7.
Peripheral Neuropathy Assessment.........................................................................32
6.8.
Adverse Event Reporting........................................................................................32
6.9.
Lung Cancer Symptom Scale Questionnaire and EQ-5D.........................................32
6.10.
Healthcare Resource Utilization Questionnaire .......................................................32
6.11.
Electrocardiogram ..................................................................................................33
6.12.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI) .......................33
6.13.
Bone Scans and X-rays...........................................................................................33
6.14.
Physical Examinations............................................................................................33
6.15.
Vital Signs..............................................................................................................33
6.16.
Laboratory Assessments .........................................................................................33
6.17.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) .....................................................................................34
6.18.
Survival..................................................................................................................34
7.
STUDY POPULATION.........................................................................................35
7.1.
Number of Subjects and Sites .................................................................................35
7.2.
Inclusion Criteria....................................................................................................35
7.3.
Exclusion Criteria...................................................................................................36
8.
DESCRIPTION OF STUDY TREATMENTS........................................................38
8.1.
Description of Study Drug(s)..................................................................................38
8.1.1.
nab-Paclitaxel.........................................................................................................38
8.1.2.
Carboplatin.............................................................................................................38
8.2.
Treatment Administration and Schedule .................................................................38
8.3.
Dose Modifications.................................................................................................39
8.4.
Method of Treatment Assignment...........................................................................41
8.5.
Packaging and Labeling..........................................................................................41
8.6.
Study Drug Accountability and Disposal ................................................................41
8.7.
Study Drug Compliance..........................................................................................41
8.8.
Overdose ................................................................................................................41
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................42
9.1.
Permitted Concomitant Medications and Procedures...............................................42
9.2.
Prohibited Concomitant Medications and Procedures..............................................42
9.3.
Required Concomitant Medications and Procedures................................................42
10.
STATISTICAL ANALYSES..................................................................................43
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
13
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
10.1.
Overview................................................................................................................43
10.2.
Study Population Definitions ..................................................................................43
10.2.1.
Intent-to-treat Population........................................................................................43
10.2.2.
Per-protocol (PP) Population ..................................................................................43
10.2.3.
Treated Population..................................................................................................43
10.3.
Sample Size and Power Considerations...................................................................43
10.4.
Background and Demographic Characteristics........................................................45
10.5.
Subject Disposition.................................................................................................45
10.6.
Safety Analysis.......................................................................................................45
10.6.1.
Primary Safety Endpoint.........................................................................................45
10.6.2.
Adverse Events.......................................................................................................46
10.6.3.
Laboratory Assessments .........................................................................................46
10.6.4.
Study Drug Exposure..............................................................................................47
10.7.
Efficacy Analysis....................................................................................................47
10.7.1.
Key Efficacy Endpoints..........................................................................................47
10.7.1.1.
Progression-free Survival........................................................................................47
10.7.1.2.
Overall Survival .....................................................................................................48
10.7.1.3.
Overall Response Rate............................................................................................48
10.7.2.
Exploratory Endpoints............................................................................................48
10.7.2.1.
Health Care Utilization and Quality of Life Questionnaire......................................48
10.8.
Study Therapy Termination ....................................................................................48
10.9.
Deaths ....................................................................................................................48
10.10.
Interim Analysis .....................................................................................................49
10.11.
Scientific Steering Committee ................................................................................49
11.
ADVERSE EVENTS..............................................................................................50
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................50
11.2.
Evaluation of Adverse Events.................................................................................50
11.2.1.
Seriousness.............................................................................................................50
11.2.2.
Severity / Intensity..................................................................................................52
11.2.3.
Causality ................................................................................................................52
11.2.4.
Duration .................................................................................................................53
11.2.5.
Action Taken..........................................................................................................53
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11.2.2.
1.2.2.
523


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11.2.6.
Outcome.................................................................................................................53
11.3.
Abnormal Laboratory Values..................................................................................53
11.4.
Pregnancy...............................................................................................................53
11.4.1.
Female Subjects......................................................................................................54
11.4.2.
Male Subjects.........................................................................................................54
11.5.
Reporting of Serious Adverse Events......................................................................54
11.5.1.
Safety Queries ........................................................................................................55
11.6.
Expedited Reporting of Adverse Events..................................................................55
12.
DISCONTINUATIONS .........................................................................................56
12.1.
Study Treatment Discontinuation............................................................................56
12.2.
Study Discontinuation ............................................................................................56
12.3.
Subject Replacement ..............................................................................................57
13.
EMERGENCY PROCEDURES.............................................................................58
13.1.
Emergency Contact.................................................................................................58
14.
REGULATORY CONSIDERATIONS...................................................................59
14.1.
Good Clinical Practice............................................................................................59
14.2.
Investigator Responsibilities ...................................................................................59
14.3.
Subject Information and Informed Consent.............................................................59
14.4.
Confidentiality........................................................................................................60
14.5.
Protocol Amendments.............................................................................................60
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................60
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................61
14.8.
Closure of the Study ...............................................................................................61
15.
DATA HANDLING AND RECORDKEEPING.....................................................62
15.1.
Data/Documents .....................................................................................................62
15.2.
Data Management...................................................................................................62
15.3.
Record Retention....................................................................................................62
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................64
16.1.
Study Monitoring and Source Data Verification......................................................64
16.2.
Audits and Inspections............................................................................................64
17.
PUBLICATIONS ...................................................................................................65
18.
REFERENCES.......................................................................................................66
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19.
APPENDICES........................................................................................................68
Appendix A:
ECOG Performance Status Score.......................................................................68
&(/*(1(35235,(7$5<,1)250$7,21


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ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
LIST OF TABLES
Table 1:
Blinded Radiology Assessment of Overall Response Rate (ITT Population) ...........20
Table 3:
Table of Events.......................................................................................................28
Table 4:
Permanent Dose Reductions for Hematologic and Neurologic Toxicities and 
Dosing on the Study ...............................................................................................40
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.40
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Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................26
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ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer
Lung cancer is the leading cause of cancer-related deaths among men and women worldwide, 
with 1.2 million new cases diagnosed each year. Non-small cell lung cancer (NSCLC) is the 
most common type of lung cancer, accounting for 80% of all new cases. There are an estimated 
1.1 million lives lost per year (approximately 500,000 in the United States [US] and European 
Union [EU] alone) due to NSCLC. Smoking is the causative factor for up to 85% of cases 
(http://www.lungcancercoalition.org/en/pages/about/awareness).
The majority of patients are not diagnosed until the tumor has progressed beyond the primary 
site. Despite step-wise advances in patient selection, targeted agents and optimizing
chemotherapy regimens, patients with advanced NSCLC continue to have an unmet medical 
need (Schiller, 2013).
Platinum-containing chemotherapy regimens remain the standard first-line treatment in the 
majority of patients, in the US and Japan. In the EU, a third-generation chemotherapeutic agent 
(docetaxel, gemcitabine, paclitaxel, or vinorelbine), most commonly gemcitabine or vinorelbine, 
plus a platinum drug is used for advanced NSCLC (NICE, 2011). For first-line therapy in 
patients with Stage IV NSCLC and good performance status, the American Society of Clinical 
Oncology (ASCO) clinical practice guideline recommends treatment with a platinum-based 
two-drug combination of cytotoxic drugs (Azzoli, 2009). A trend that is becoming more 
prevalent is personalized NSCLC treatment based on tumor histology (squamous versus
non-squamous), on molecular characteristics of the tumor, and on the patient’s clinical status 
using agents targeting specific receptors and kinases and pathways (ie, epidermal growth factor 
receptor [EGFR], echinoderm microtubule-associated protein-like 4 [EML4] and anaplastic 
lymphoma kinase [ALK] fusion protein).
In advanced NSCLC, the prevalently used combination of solvent-based 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, and requires the use of specialized infusion sets and in-line 
filters that do not contain di[2-ethylhexyl] phthalate (DEHP).
Compared with solvent-based paclitaxel, nab-paclitaxel exhibits 10-fold higher mean Cmax of 
free paclitaxel, delivers 33% higher drug concentration to tumors in preclinical xenograft 
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-005
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ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
models, and demonstrates enhanced transport across endothelial cell monolayers (Desai, 2006; 
Gardner, 2008). The Cremophor EL-free medium enables nab-paclitaxelto be given in a shorter
duration without the need for premedication to prevent solvent-related hypersensitivity reactions.
In addition, standard tubing and intravenous (IV) bags may be used for the IV administration of 
nab-paclitaxel. 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. 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.
1.2.
nab-Paclitaxel in NSCLC
The Food and Drug Administration (FDA) approval of nab-paclitaxel 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. 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%), see Table 1].
Non-inferiority analysis of overall survival (OS) demonstrated that nab-paclitaxel/carboplatin
(nab-p/C) treatment is not inferior to solvent-based paclitaxel/carboplatin (sb-P/C) treatment. 
Overall survival in the nab-paclitaxel arm was 12.1 months versus 11.2 months in the control 
arm (p = 0.271; HR = 0.922).  Toxicities, particularly neuropathy and neutropenia were less 
pronounced using nab-paclitaxel in the dose and schedule employed.
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Table 1:
Blinded Radiology Assessment of Overall Response Rate (ITT Population)
Variable
Category/Statistic
nab-Paclitaxel/
Carboplatin
(N=521)
sb-Paclitaxel/
Carboplatin
(N=531)
Response Rate 
Ratio
(pA/pT)a
p-value
Patients with Confirmed Complete or Partial Overall Response
n (%)
170 (33%)
132 (25%)
1.313
0.005*
Confidence Interval (CI) b
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%)
a PA/PT equals response rate of nab-paclitaxel/response rate of sb paclitaxel.
b 95% CI of response rate and 95.1% CI of response rate ratio.
* Indicates p-value < 0.049.Note: P-value is based on a chi-square test.
Source: Data on File.
Adverse events were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. The following common (≥ 10% incidence) 
adverse events were observed at a similar incidence in nab-paclitaxel and paclitaxel 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).
1.3.
Rationale for Further Study of nab-Paclitaxel as First-line Treatment 
in Elderly Subjects with Advanced NSCLC
The tolerability of doublet chemotherapy in elderly patients with advanced NSCLC is an
important therapeutic consideration, whereby the landmark IFCT 0501 reported that first-line sb-
paclitaxel given weekly three weeks out of four coupled with carboplatin every 4 weeks (i.e.
21days of treatment followed by one-week break) improved efficacy over single-agent 
chemotherapy (either gemcitabine or vinorelbine) in patients 70 years or older with advanced 
NSCLC. The results demonstrated that doublet chemotherapy was feasible in this elderly
population with an acceptable toxicity profile, when sb-paclitaxel/carboplatin was given as 21
days of treatment followed by one-week rest. The combination also resulted in a significant 
improvement in OS (median, 10.3 versus 6.2 months; HR = 0.639, 95% CI:0.52-0.79, p <
0.0001), with 1-year survival rates of 45.1% versus 26.9% for doublet therapy and monotherapy.  
This prospective trial set a standard, against which doublet-regimens must be measured in the 
elderly population with advanced NSCLC.
In the CA031 study of nab-paclitaxel (Abraxane) in combination with carboplatin, patients were 
stratified by age (< 70 years old versus ≥ 70 years old). Fifteen percent of ITT patients were 
elderly (≥70 years: nab-paclitaxel, n = 74: sb-paclitaxel, n = 82). Baseline characteristics were 
generally well balanced between treatment arms in elderly population, and subgroup analyses 
were performed to assess the influence of age on the primary efficacy endpoint of overall 
response rate as well as PFS and OS (Socinski, 2013). 
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Of note, the post-hoc analysis of the CA031 trial showed marked improvement in survival in the 
nab-paclitaxel/carboplatin arm. Amongst 156 elderly (≥70 years of age) subjects randomized on 
the study, OS was 19.9 months versus 10.4 months (HR: 0.583, p = 0.009) in favor of the nab-
p/C arm compared to sb-p/C. The proportion of patients who had complete or partial response 
were consistently higher in all age stratum groups for the nab-paclitaxel/carboplatin regimen 
relative to the sb-paclitaxel/carboplatin regimen (in patients ≥ 70 years of age 34% versus 24% 
respectively, ratio of rates 1.385, p = 0.196, 
).
 
 
 
Although it was a statistically significant treatment effect in favor of nab-paclitaxel in the elderly 
subgroup from CA031 trial, 46% of patients in the nab-paclitaxel/carboplatin arm experienced 
dose reductions or dose delays. Approximately 92% of dose modifications and reductions were 
due to AEs. The most common clinical AEs in this subgroup were hematologic Grade ≥ 3 
neutropenia (45%), anemia (22%) and thrombocytopenia (19%). Approximately 18% of the 
elderly population in the CA031 trial had Grade ≥ 2 peripheral neuropathy. Despite that,
approximately 10% more elderly patients in the nab-paclitaxel arm were able to receive second-
line therapy compared to sb-paclitaxel (61% versus 50%, respectively), possibly because they 
may have been in better shape due to a better tolerated first-line regimen with nab-paclitaxel or 
better disease and symptom control as demonstrated as improvement in ORR.
The results from the elderly subset in CA031 trial showed the combination of nab-paclitaxel and 
carboplatin to be particularly promising. We hypothesize that the tolerability can be improved 
further by introducing a one week break at the end of each treatment cycle (similar to the 
schedule advocated by Quoix, 2011) among elderly patients.  Reducing the rate of the most 
common AEs (Grade ≥ 3 myelosuppression toxicities and Grade ≥ 2 peripheral neuropathy) by 
16% will be clinically meaningful as it can potentially improve tolerability, quality of life and 
allow patients to receive treatment for a longer period of time, without necessarily compromising 
efficacy.  
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2.
STUDY OBJECTIVES
2.1.
Primary Objectives 
!
To assess the safety and tolerability of continuous weekly versus weekly times three 
with one-week break nab-paclitaxel (Abraxane) in combination with carboplatin as 
first-line treatment for advanced NSCLC in elderly subjects (≥ 70 years old).
2.2.
Secondary Objective
!
To evaluate the efficacy of nab-paclitaxel in combination with carboplatin in elderly 
subjects with advanced NSCLC.
2.3.
Exploratory Objectives
!
To assess healthcare resource utilization for the two nab-paclitaxel treatment arms.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ-5D) for the two nab-paclitaxel treatment arms.
!
 
 
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3.
STUDY ENDPOINTS
3.1.
Primary Endpoint
!
The primary study endpoint is the percentage of subjects with either peripheral 
neuropathy of Grade ≥2 or myelosuppression AEs of Grade ≥3 based on the local
laboratory values for ANC, platelet count, and hemoglobin. All AEs will be graded 
using NCI CTCAE v4.0. 
3.2.
Secondary Endpoints
The secondary endpoints are: 
3.2.1.
Safety
!
The type, frequency, and severity of AEs and SAEs. 
!
Discontinuation rate.
!
Dose intensity administered.
!
The incidence of dose reduction and dose delay.
3.2.2.
Efficacy
!
Progression-free Survival (PFS).
!
Overall response rate (ORR) using RECIST v1.1 guidelines.
!
Overall Survival (OS).
3.3.
Exploratory Endpoints
!
Healthcare resource utilization during the study using a questionnaire.
!
Changes in the LCSS and EQ-5D.
!
 
 
!
 
!
Additional exploratory endpoints may be defined in the statistical analysis plan 
(SAP), if applicable.
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4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is a Phase IV, randomized, open-label, multicenter study of continuous weekly versus
weekly times three with one-week break nab-paclitaxel in combination with carboplatin as first-
line treatment in elderly subjects (≥ 70 years old) with advanced NSCLC who are not candidates 
for curative surgery or radiation therapy.
Subjects will be randomized 1:1 to receive one of the following treatments:
Arm A (21-day treatment cycle):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment cycle after 
completion of nab-paclitaxel infusion 
Arm B (21-day treatment followed by one-week break cycle, 28-day duration):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment  followed by one-week break cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment followed by 
one-week break cycle, after completion of nab-paclitaxel infusion 
The study will consist of a 28-day Screening Period, a Treatment Period, and a Follow-up
Period.
The Screening Period will start from signing the Informed Consent Form (ICF) until first dose of 
study drug. 
The Treatment Period will start from first dose of study drug until End-of-Treatment Visit 
(which is defined as visit with last dose of study drug).
Follow-up Period will start after End-of-Treatment visit.
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of 
consent, in accordance with local standard of care.
Tumor evaluations will be assessed locally and response (Complete Response [CR] or Partial 
Response [PR]) will be determined according to RECIST guidelines, Version 1.1. In both 
treatment arms, tumor assessments will be conducted at screening and every 42 days (-3/+7
days) (starting from Day 1 Cycle 1) until disease progression, withdrawal of consent, lost to 
follow-up, death, or if clinically indicated while on treatment.
Local laboratory test data for ANC, platelet count, hemoglobin and serum creatinine will be 
collected in the eCRFs. All other routine laboratory test data except those mentioned above will 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
25
ABI-007-NSCL-005 Amendment -2.0 Final: 05 Dec 2014
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 AE, or SAE, 
and the specific associated laboratory parameter(s) should be recorded in the laboratory 
assessments eCRF. Local safety laboratory data will also be the primary guide for eligibility and 
subject management. In addition, test results for tumor mutational status of genes including but 
not limited to EGFR, ALK, and KRAS will be collected and recorded on eCRF if these tests 
have been performed locally for routine diagnosis.  
4.1.1.
Follow-up Period
All subjects who discontinue from treatment for reasons other than withdrawal of consent or lost 
to follow-up will enter the Follow-up Period. It will consist of a visit 28 days after treatment 
discontinuation following by follow-up for survival approximately every 90 days (+/- 14 days or 
when they are seen for routine care) by phone call or chart review for documentation of last 
contact for up to 6 months after the last subject is randomized or 192 PFS events have been 
observed, whichever comes later.
Those subjects entering the Follow-up Period without documented progression will continue to 
have CT scans in accordance with standard of care (at least every 90 days) until documented 
progression of disease, withdrawal of consent, lost to follow-up, death, or study closure.
4.2.
Study Design Rationale
The nab-paclitaxel schedule used in Arm A is in accordance with pivotal trial CA031,
ie,100 mg/m2 administered once per week on Days 1, 8 and 15 combined with carboplatin 
AUC = 6 mg*min/mL administered on Day 1 every 21 days, as approved by the FDA.  The nab-
paclitaxel/carboplatin schedule used in Arm B is the same schedule as the current approved nab-
paclitaxel label with introduction of a one-week break following 21 days of treatment. This 
study will determine whether the one-week break can further improve tolerability without 
compromising efficacy (similar to the schedule advocated by Quoix, 2011) among elderly 
patients.  Reducing the rate of the most common AEs (Grade ≥ 3 myelosuppression toxicities 
and Grade ≥ 2 peripheral neuropathy) by 16% will be clinically meaningful as it can potentially 
improve tolerability, quality of life and allow subjects to receive treatment for a longer period of 
time.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
26
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
Figure 1:
Overall Study Design
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
27
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
4.3.
Study Duration
Recruitment is expected to take approximately 24 months, and the analysis of PFS will be 
performed when approximately 192 PFS events have occurred, estimated as approximately 28
months from first subject randomized. The total length of this Phase IV study with follow-up is 
estimated to last approximately 3 years.
4.4.
End of Trial
The End of Trial is defined as either the:
!
date of the last visit of the last subject to complete the study, or 
!
the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol
and/or the SAP, whichever is the later date.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
28
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
5.
TABLE OF EVENTS
Table 3:
Table of Events
Screening
/ Baseline
Treatment Perioda
Every cycle starting with Cycle 1
Follow-Up Period
Assessment
Day -28 
to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days) 
(counting from 
Day 1 Cycle 1)
End-of-
Treatment
Visit (last dose 
of study drug)
28-day Follow-up 
Visit (after last 
dose of study 
drug)
Survival Follow-Upb
Every 90 days (+/-
14 days) (after 28-
day follow-up visit)
Informed Consent
X
-
-
-
-
-
-
-
Medical History, Prior Medication and Procedures
X
-
-
-
-
-
-
-
CT Scan of Complete Chest (including base of neck 
and adrenal glands) and any other studies required 
for Tumor Imagingc
X
-
-
-
X c
X c
-
X c
Weight and Heightd
X
X
X
X
-
-
-
-
Body Surface Area (BSA) Calculationd
X
-
-
-
-
-
-
-
ECOG status
X
X
-
-
-
X
X
-
Concomitant Medication/Procedures
-
X
X
X
-
X
X
X
Peripheral Neuropathy Assessmente
X
X
X
X
-
X
X
-
Healthcare Resource Utilization Questionnaire
-
X
-
-
-
X
X
-
Hematologyf (ANC, platelet count, Hgb)
X
X
X
X
-
X
X
-
Serum Chemistryf (serum creatinine)
X
X
-
-
-
X
X
-
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
29
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
Table 3:
Table of Events (Continued)
Screening
/ Baseline
Treatment Perioda
Every cycle starting with Cycle 1
Follow-Up Period
Assessment
Day -28 
to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days) 
(starting Day 1 
Cycle 1)
End-of-
Treatment
(last dose of 
study drug)
28-day Follow-up 
Visit (after last 
dose of study 
drug)
Survival Follow-Upb
Every 90 days (+/-
14 days) (after 28-
day follow-up visit)
Blood for Pharmacogenomic Analyses
-
X
(C1D1 only)
-
-
-
-
-
-
Adverse Event Evaluation
After signing ICF and until 28 days after the last dose of study drug
nab-paclitaxel Administration/accountabilityg
-
X
X
X
-
-
-
-
Carboplatin Administration/accountabilityg
-
X
-
-
-
-
-
-
LCSS and EQ-5D
-
X
-
-
-
X
X
-
Survival phone call (or chart review for 
documentation of last contact or when they are seen 
for routine care
-
-
-
-
-
-
-
Xb
Electrocardiogram (ECG)
Will be done as per standard of care at screening, during the Treatment Period and as clinically indicated; however, results 
will not be routinely collected in the eCRFs. Results will be collected in the eCRFs as AE or SAE only if results are abnormal 
and clinically significant.
CT Scan of the Head or Brain Magnetic Resonance 
Imaging (MRI)
Bone Scan (X-rays if needed)
Physical Examination
Vital Signs
AE = Adverse Event; ANC = absolute neutrophil count; C1D1 = Cycle 1, Day 1; CT = Computed Tomography; ECOG = Eastern Cooperative Oncology Group; eCRF =
electronicCase Report Form; EQ-5D = EuroQol 5D; ICF = informed consent form; LCSS = Lung Cancer Symptom Scale; SAE = Serious Adverse Event; RECIST=Response 
Evaluation Criteria in Solid Tumors; PFS=Progression Free Survival.
a Treatment Period:  Arm A: nab-paclitaxel Days 1, 8, and 15 and carboplatin Day 1. Arm B: nab-paclitaxel Days 1, 8, and 15 and carboplatin Day 1 followed by one-week break.
b Every 90 (+/-14) days (from 28-day Follow-up Visit) or when they are seen for routine care for up to 6 months after the last subject is randomized or 192 PFS events have been 
observed, whichever comes later.
c All subjects must have a radiographically documented measurable tumor(s) by RECIST Version 1.1 criteria: CT scan of complete chest (including base of neck and adrenal 
glands) are performed at screening, every 42 days (-3/+7 days) thereafter (counting from Day 1 Cycle 1) until disease progression, withdrawal of consent, lost to follow-up, 
death and if clinically indicated while on treatment. The methods of assessment chosen at baseline to follow tumors are to remain consistent throughout study duration. Those 
subjects entering the Follow-up Period without documented progression will continue to have CT scans in accordance with standard of care (at least every 90 days) until 
documented progression of disease, withdrawal of consent, lost to follow-up, death or study closure.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
30
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
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 recalculated. Height 
will only be obtained at Screening Visit. Weight will be obtained at screening and every visit during the Treatment Period before administration of study drug, but will only be 
collected on the eCRF for the Screening Visit.
e The occurrence of peripheral neuropathy will be reported by the investigator per protocol as an AE or SAE.
f Laboratory assessments will be done prior to each nab-paclitaxel treatment as per standard of care during the study and as clinically indicated. ANC, platelet count, hemoglobin
(Hgb) level and serum creatinine results will be collected in the eCRFs (all other routine laboratory test data except those mentioned above will not be collected in the eCRF
unless it is clinically significant, which will then be reported as AEs or SAEs, and the specific associated laboratory parameter(s) should be recorded on the laboratory 
assessments eCRF).
g nab-Paclitaxel administration followed by carboplatin administration.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
31
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
6.
PROCEDURES
Subjects will be provided with a written ICF, given the opportunity to ask any questions 
concerning the study and will sign an ICF prior to participating in any study procedures. Serum 
Chemistry assessments or CT scans performed in accordance with the local standard of care 
within 28 days before the first dose of study drug, even if they took place prior to signing of the 
ICF, can be used for the screening assessment. After giving written informed consent, subjects 
will undergo a Screening Period to be assessed for eligibility. All subjects who sign an ICF must 
be entered into the Interactive Randomization Technology (IRT) system immediately upon 
signature on the document. Subjects who do not meet the eligibility criteria will be considered 
screening failures and will not be eligible for the study. Subjects who screen fail may re-screen 
up to 2 times at any time and an ICF will need to be re-signed, as well as all screening 
procedures repeated (some procedures may not need to be done if previously done within 28 
days prior to screening again). Subjects that have met all eligibility criteria after the Screening 
Period will be eligible to be randomized. 
6.1.
Medical History
Only clinically significant or ongoing medical conditions will be recorded at screening on the 
eCRF. 
6.2.
Prior and Concomitant Medications/Procedures
Prior medications are defined as all medications that were started before the date of the first dose 
of study drug. Only prior medications/procedures (of clinically significant or ongoing medical 
conditions) within 28 days of the time of signature on the ICF should be recorded. All NSCLC-
related prior medications/procedures (including radiation therapy) should be recorded regardless 
of time. 
Concomitant medications are considered 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. All 
subjects will have concomitant medications and procedures (including radiation therapy) 
recorded from the time of signature on the ICF until the 28-day Follow-up Visit, for conditions 
that are clinically significant or ongoing. During the Follow-up Period only NSCLC-associated 
concomitant medications/procedures (including radiation therapy) will be recorded, ie, 
subsequent-line(s) of anti-cancer therapy.
6.3.
Computed Tomography (CT) Scan of Complete Chest (including 
base of neck and adrenal glands)
A CT scan of complete chest (including base of neck and adrenal glands) and any other studies 
required for tumor imaging will be done at screening, every 42 days (-3/+7 days) (starting from 
Day 1 Cycle 1) until treatment discontinuation or withdrawal of consent. Those subjects entering 
the Follow-up Period without documented progression will continue to have CT scans in 
accordance with standard of care (at least every 90 days) until documented progression of 
disease, withdrawal of consent, lost to follow-up, death or study closure. Additional CT scans
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
32
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
may be done at any time during the study if clinically indicated. All CT scans and reports should 
be archived at the site according to site regulations and copies provided to Sponsor if requested.
6.4.
Weight
Weight will be obtained at screening and at every visit during the Treatment Period before 
administration of study drug, but will only be collected on the eCRF for the Screening Visit.
Additional weights may be collected per local standards at any time during the study as needed.
6.5.
Body Surface Area (BSA) Calculation and Height
Height will be collected at screening only, and BSA will be calculated at screening of the study.
BSA will be recalculated if body weight changes by more than 10% during the study.
6.6.
ECOG Performance Score
Eastern Cooperative Oncology Group performance score will be collected at screening, Day 1 of 
every treatment cycle, at the End-of-Treatment visit and at the 28-day Follow-up Visit. 
Additional ECOG assessments may be performed at any time during the study as clinically 
indicated.
6.7.
Peripheral Neuropathy Assessment
Peripheral neuropathy (sensory or motor) assessment will be done at screening, Day 1, 8, 15 of 
every treatment cycle, at the End-of-Treatment visit and at the 28-day Follow-up Visit. Changes 
in neuropathy grade from baseline will be reported as an AE as per Section 11. Additional 
peripheral neuropathy assessments may be done at any time during the study as clinically 
indicated.
6.8.
Adverse Event Reporting
Adverse events will be recorded from time of signature on the ICF until 28 days after the last 
dose of study drug, including any unscheduled visits. See Section 11 for details. 
6.9.
Lung Cancer Symptom Scale Questionnaire and EQ-5D
The LCSS and EQ-5D questionnaires will be used to measure quality of life (QoL) for subjects 
in the study. The LCSS is comprised of 9 questions to be completed by the subject using a visual 
analogue scale (VAS) to denote intensity of a symptom. The EQ-5D comprises 5 questions on 
mobility, self-care, usual activities, pain/discomfort, anxiety/depression and a VAS for overall 
QoL. These questionnaires will be completed at Day 1 of every Treatment Period, at the End-of-
Treatment Visit and at the 28-day Follow-up Visit.
6.10.
Healthcare Resource Utilization Questionnaire
A healthcare resource utilization questionnaire will be used to capture the additional use of 
healthcare resources, including hospitalizations, emergency room visits, doctor or nurse visits, 
procedures, and/or additional medication during the study period. The assessment will be 
completed at Day 1 of every treatment cycle, at the End-of-Treatment visit and at 28-day Follow-
up Visit. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
33
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
6.11.
Electrocardiogram
Electrocardiograms (ECGs) will be done per standard of care at screening, during the Treatment 
Period and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if 
results are abnormal, changed, and clinically significant.
6.12.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI)
A CT scan of the head, or preferably brain MRI, will be done as per standard of care at 
screening, during the Treatment Period, and as clinically indicated. Results will be collected in 
the eCRFs as an AE or SAE only if the results are abnormal and clinically significant.
6.13.
Bone Scans and X-rays
Bone scans and x-rays will be done as per standard of care at screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if 
results are abnormal and clinically significant.
6.14.
Physical Examinations
Physical examinations will be done as per standard of care at screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if 
results are abnormal and clinically significant.
6.15.
Vital Signs
Vital signs will be done as per standard of care at screening, during the Treatment Period, and as 
clinically indicated. Results will be collected in the eCRFs as AE or SAE only if results are 
abnormal and clinically significant.
6.16.
Laboratory Assessments
Laboratory assessments will be done as indicated in Table 3 by local laboratories as per standard 
of care during the study and as clinically indicated. Local laboratory test data for ANC, platelet 
count and hemoglobin must be collected at screening, each visit before administration of study 
drug, at the End-of-Treatment visit and at the 28-day Follow-up Visit in the eCRF. Serum 
creatinine must be collected at screening, Day 1 of each cycle, at the End-of-Treatment visit and 
at the 28-day Follow-up Visit in the eCRF. Normal ranges for these selected parameters will be 
collected on the eCRF. All other laboratory test data, except those mentioned above, will not be 
collected routinely in the eCRF. Local safety laboratory data will also be the primary guide for 
eligibility and subject management. It is the responsibility of the investigator to assess the 
clinical significance of all abnormal values as defined by the reference ranges from the local 
laboratory. All clinically significant laboratory abnormalities (Section 11.3) are to be recorded as 
AEs on the AE eCRF, and the specific laboratory parameter(s) as well as the corresponding 
normal ranges should be recorded on the laboratory assessments eCRF. Clinically significant 
laboratory abnormalities at screening may result in subject ineligibility for the study and should 
not be captured as AE. Any abnormal values that persist should be followed at the discretion of 
the investigator. The investigator should file all copies of the reports, including faxes with the 
subject’s medical chart.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
34
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
6.17.
Tumor Tissue Sample Collection and Peripheral Blood Collection
(Exploratory Assessments) 
Provision of tumor tissue is mandatory for study enrollment, except when no tumor tissue is 
extant and this requirement would necessitate a new procedure such as a biopsy to collect it.  
 
 
 
 
 
 
 
 
 
 
 
In addition, test results for tumor mutational status of genes including but not limited to EGFR, 
ALK, and KRAS will be collected and recorded on eCRF if these tests have been performed
locally for routine diagnosis.
 
 
 
 
 
 
6.18.
Survival 
After the End-of-Treatment Visit, the subjects will have a 28-day Follow-up Visit followed by a 
call or chart review for documentation of last contact approximately every 90 days (or when they 
are seen for routine care) for up to 6 months after the last subject is randomized or 192 PFS 
events have been observed, whichever comes later. The subjects will also be asked questions 
about other medications they may be taking for their NSCLC or their medical records will be 
reviewed to determine a last contact date for routine purposes. Those subjects entering the 
Follow-up Period without documented progression will continue to have CT scans in accordance 
with standard of care (at least every 90 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death or study closure.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
35
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Elderly (≥70 years of age) male and female subjects with locally advanced or metastatic NSCLC 
with no prior chemotherapy for metastatic disease will be eligible for this study. The study will 
enroll approximately 284 subjects. The study will be conducted at approximately 65 sites in the 
United States.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be randomized in the study:
1. Age ≥ 70 years at the time of signing the ICF.
2. Understand and voluntarily provide written informed consent prior to the conduct of any 
study related assessments/procedures.  
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Histologically or cytologically confirmed locally advanced or metastatic NSCLC who are 
not candidates for curative surgery or radiation therapy.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease per RECIST v1.1.
7. No prior chemotherapy for the treatment of metastatic disease. Adjuvant chemotherapy is 
permitted providing that cytotoxic chemotherapy was completed 12 months prior to 
signing the ICF and without disease recurrence. Patients with previously known EGFR 
mutation or ALK gene translocation must have failed or had intolerance to one treatment 
with EGFR tyrosine kinase inhibitor or ALK inhibitor therapy, respectively.
8. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
9. Platelets ≥ 100,000 cells/mm3.
10. Hemoglobin (Hgb) ≥ 9 g/dL.
11. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]), alanine
transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper limit of 
normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
12. Total bilirubin ≤ 1.5 mg/dL (unless there is a known history of Gilberts Syndrome).
13. Creatinine clearance (CrCl) > 40 mL/min calculated using Cockcroft-Gault equation (if 
renal impairment is suspected 24 hour urine collection for measurement is required).
14. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
15. Females who (1) have undergone hysterectomy (the surgical removal of the uterus) or 
bilateral oophorectomy (the surgical removal of both ovaries) or (2) have been naturally 
postmenopausal for at least 24 consecutive months (ie, has not had menses at any time 
during the preceding 24 consecutive months).
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
36
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
Male subjects must:
a.
Practice true abstinence or agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the 
study, during dose interruptions, and for 6 months following study drug 
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
≥4 weeks 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. Preexisting 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 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 a study drug: 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.
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 allergy or hypersensitivity to nab-paclitaxel or carboplatin.
14. Currently enrolled in any other clinical protocol or investigational trial that involves
administration of experimental therapy and/or therapeutic devices.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
37
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
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 randomization. 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 of 
which 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.
19. Females who (1) have not undergone hysterectomy (the surgical removal of the uterus) or 
bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been 
naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any 
time during the preceding 24 consecutive months).
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
38
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Study Drug(s)
Treatment
Subjects will receive open-label nab-paclitaxel and carboplatin during the Treatment Period of 
the study. Investigative sites will use standard of care (commercially available) product via 
prescription for nab-paclitaxel and carboplatin.
The preparation for IV administration procedures should be followed as per approved 
Prescribing Information.
8.1.1.
nab-Paclitaxel
Each single-use 50 mL vial contains paclitaxel (100 mg) and approximately 900 mg human 
albumin as a stabilizer.
Unreconstituted nab-paclitaxel should be stored in accordance with the product label. 
Reconstituted nab-paclitaxel should be used immediately. Both forms should be stored in an area 
free of environmental extremes and should be accessible only to study personnel. Reconstitution 
and administration should follow local prescribing information and local practice. Temperature 
records for nab-paclitaxel must be made available to Celgene or other Sponsor- nominated 
monitoring teams for verification of proper study drug storage.
8.1.2.
Carboplatin
Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic
agent. The chemical name for carboplatin is platinum diammine [1,1-
cyclobutane-dicarboxylato (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 package insert. 
8.2.
Treatment Administration and Schedule
Approximately 284 subjects will be treated with nab-paclitaxel plus carboplatin until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of 
consent.
Treatment will commence on Day 1, in accordance with standard of care of first-line treatment of 
NSCLC: 
Arm A:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day treatment cycle,
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment cycle, after 
completion of nab-paclitaxel infusion
OR
Arm B:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day treatment with one-week break cycle (i.e. every 28 days),
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment with one-
week break cycle (i.e. every 28 days), after completion of nab-paclitaxel infusion.
8.3.
Dose Modifications
Subjects who experience any of the adverse drug reactions in Table 4 will be dose reduced as per 
Table 4 during treatment. 
!
Do not administer nab-paclitaxel on Day 1 of a cycle until ANC is at least 
1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment 
until counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and 
platelet count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil 
count of at least 500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on 
Days 8 or 15 of the cycle. Upon resumption of dosing, permanently reduce nab-
paclitaxel and carboplatin doses as outlined in Table 4.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-
paclitaxel and carboplatin at reduced doses (Table 4) when peripheral neuropathy 
improves to Grade 1 or completely resolves.
Re-escalation is not permitted at any time. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
40
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
Table 4:
Permanent Dose Reductions for Hematologic and Neurologic Toxicities and Dosing on the Study
Dose Modification During Treatment for A and B arms
Adverse Drug Reaction
Occurrence
nab-Paclitaxel Dose 
(mg/m2)
Carboplatin Dose 
(AUC 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
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Platelet count < 50,000/mm3
First
75
4.5
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Discontinue Treatment*
Sensory Neuropathy Grade 3 or 4
First
75
4.5
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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
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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 twice, the subject should generally have treatment discontinued unless, at 
the discretion of the investigator, there is evidence of continuing benefit to the subject that outweighs the risk of recurrent toxicity. Re-Escalation is not 
permitted at anytime.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
41
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
8.4.
Method of Treatment Assignment
The Treatment Period of the study is open-label. Enrollment/randomization will occur via IRT 
system for all periods of the study. 
8.5.
Packaging and Labeling
Investigative sites will use standard of care (commercially available) product via prescription for 
nab-paclitaxel and carboplatin.
8.6.
Study Drug Accountability and Disposal
Investigative sites will use standard of care (commercially available) product via prescription for 
nab-paclitaxel and carboplatin. Accurate recordings of all study drug administration should be 
made.
Procedures for proper handling and disposal of anticancer drug must comply with the relevant 
health, safety, and environment regulations.
8.7.
Study Drug Compliance
Study drug will be administered only by study site personnel and accurate recording of all study 
drug 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 or carboplatin dosing only.
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel or carboplatin given to a subject, regardless of any associated adverse events or 
sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. See 
Section 11.1 for the reporting of adverse events associated with overdose.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
42
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
Over the course of this study, additional medications may be required to manage aspects of the 
disease state of the subjects, including side effects from study treatments or disease recurrence. 
All supportive care (including but not limited to antiemetic medications, white blood cell (WBC)
growth factors, erythrocyte stimulating agents, zolendronic acid, and denosumab) is permitted
and may be administered at the discretion of the investigator, according to local guidelines. 
9.2.
Prohibited Concomitant Medications and Procedures
Other antineoplastic agents or Investigational Product 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-005
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 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 284 subjects will be randomized in a 1:1 ratio to two treatment arms (142 
subjects per group).  Arm A will receive nab-paclitaxel 100 mg/m2 administered on Days 1, 8 
and 15 followed by carboplatin AUC = 6 mg*min/mL on Day 1 of each 21-day treatment cycle. 
Arm B will receive the same treatment in the same schedule as that of Arm A during the first 21 
days of treatment, but followed by a one-week break prior to the start of next cycle (28-day 
duration). All subjects will receive the assigned study treatment until disease progression, 
unacceptable toxicity, death, lost to follow-up, or withdrawal of consent, in accordance of local 
standard of care.  A permuted-block randomization method will be employed, and the 
randomization will be carried out centrally using an IRT system. The randomization will be 
stratified based on the following 2 baseline or prognostic factors:
!
ECOG performance status (0 versus 1)
!
Histology (squamous cell carcinoma versus non-squamous cell carcinoma)
10.2.
Study Population Definitions
10.2.1.
Intent-to-treat Population
The primary efficacy analysis will be performed on the ITT population, which includes all 
randomized subjects regardless of whether the subject receives any study drug or has any 
efficacy assessments performed. 
10.2.2.
Per-protocol (PP) Population
The PP population is defined as all eligible subjects randomized who receive at least one dose of 
the study drug and have been treated in the arm they were assigned to. Additional analyses 
utilizing the PP population will be described in the SAP.
10.2.3.
Treated Population
The treated population will consist of all randomized subjects who receive at least one dose of 
study drug. The treatment groups for the safety analyses will be based on the treatment as 
received if different from the assigned treatment by randomization.
10.3.
Sample Size and Power Considerations
The primary objective of this study is to assess the safety and tolerability of nab-paclitaxel in 
combination with carboplatin administered in 21-day treatment cycles continuously or with a 
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('06'RF1XPEHU
nab-paclitaxel
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Celgene Corporation
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ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
one-week break in between cycles for the treatment of locally advanced or metastatic NSCLC in 
elderly subjects (≥ 70 years old). 
The primary study endpoint (also the primary safety endpoint) is the percentage of subjects with 
either peripheral neuropathy of Grade ≥2 or myelosuppression AEs of Grade ≥3 based on the 
local laboratory values for ANC, platelet count, and hemoglobin.  For the purpose of this 
protocol, this endpoint will be referred to as the percentage of subjects with Grade ≥2 peripheral 
neuropathy or Grade ≥3 myelosuppression laboratory adverse events.  
In Protocol CA031, the Phase 3 NSCLC study of the nab-paclitaxel development program, 
approximately 2% of the elderly subjects randomized discontinued from the study prior to 
receiving any study drug.  In addition, approximately 73% of the treated elderly subjects had 
AEs that fell in the category of AEs described above for the primary safety endpoint of the 
current study.  
The study is designed to detect a difference of 16 percentage points between the 2 treatment arms 
with respect to the primary safety endpoint with 80% power and a Type-I error of 5% (two-
sided), assuming the percentage of subjects with the AEs specified above is 73% for Arm A.  
Therefore, the current study is planned to randomize approximately 284 subjects to the 2 
treatment arms in a 1:1 ratio, with the expectation that approximately 278 subjects (139 per 
group) will receive at least one dose of study drug (as observed in CA031) and be included in the 
treated population for the analysis of the primary safety endpoint.
A non-binding interim analysis for futility with the primary safety endpoint will be conducted 
when approximately a total of 139 treated subjects have either completed 6 months of study 
treatment or discontinued from the study due to progression, adverse events, deaths, lost to 
follow up, or other reasons. The stopping rule and the final marginal significance level are 
determined based on the Gamma family spending function with parameter = -7 (Hwang, 1990) to
control the Type-II error rate at 20%. The study may be stopped early for futility if the treatment 
difference is between ± 0.4% (Z-score ± 0.054) given the interim analysis is performed at 50% 
information fraction.  
Progression free survival, OS, and ORR are the key efficacy endpoints of the study.  Since the 
primary research interest of this study is to evaluate the relative safety and toxicities of the 2 
treatment arms, the sample size was calculated based on the primary safety endpoint, the 
percentage of subjects with Grade ≥2 peripheral neuropathy or Grade ≥3 myelosuppression 
laboratory AEs, hence, the study is underpowered for the key efficacy endpoint, PFS, OS and 
ORR.  Consequently, a non-significant treatment difference in PFS, OS or ORR could simply be 
a function of the sample size and/or the lack of statistical power. Therefore, the assessments of 
all efficacy endpoints will be based on the point estimates and the associated 95% confidence 
intervals for the within-group parameters of interest and the between-group differences.  P-
values for between-group comparisons will be provided to indicate the strength of association 
only.  No multiplicity adjustment with the Type-I error rate will be made. 
Of note, based on the data from CA031 it is expected that approximately 67% of the 284
randomized subjects will have a PFS event during the study (i.e. approximately 192 PFS events 
total).  With 192 PFS events, there is 73% power to detect a hazard ratio (HR) of 0.69 for PFS 
improvement with Arm B over Arm A and an overall Type-I error of 5% (two-sided).  Assuming 
s had 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
45
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
an exponential distribution with a median time to PFS of 5.8 months for Arm A and proportional 
hazards, a hazard ratio of 0.69 constitutes a 2.6 months improvement for Arm B.  
As an illustration for timeline projection, assuming an exponential distribution for PFS, a 24-
month recruitment period for 284 subjects, and a median PFS of approximately 5.8 months for 
Arm A, it will take approximately 28 months from the first subject randomized to observe 192 
PFS events.
The analysis of both the safety and efficacy endpoints for the clinical study report will be 
performed when approximately 192 PFS events have been observed.  No adjustment for the 
multiple treatment comparisons among the primary and secondary study endpoints will be made.  
Subjects will be followed for OS for at least 6 months after the last subject is randomized or 192 
PFS events have been observed, whichever comes later.
10.4.
Background and Demographic Characteristics
The baseline characteristics of all randomized subjects will be summarized. Subject’s age, 
height, weight, and baseline characteristics will be summarized using descriptive statistics, while 
gender, race and other categorical variables will be provided using frequency tabulations. 
Selected medical history data will be summarized using frequency tabulations by system organ 
class and preferred term.
10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both Treatment
and Follow-up Periods. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
10.6.
Safety Analysis
The treated population, which includes all randomized subjects who received at least one dose of 
study drug, will be the analysis population for all safety analyses.
The safety/tolerability of the two treatment arms will be monitored through continuous reporting 
and evaluated by the primary safety endpoint, adverse events and serious adverse events, 
abnormalities in ANC, platelet count and hemoglobin, and incidence of subjects experiencing 
dose modifications, dose interruptions, and/or premature discontinuation of study drug.
10.6.1.
Primary Safety Endpoint
The primary endpoint for this study is a composite safety endpoint, namely, the percentage of 
subjects who develop either peripheral neuropathy of Grade ≥2 or myelosuppression AEs of 
Grade ≥3 based on the local laboratory values for ANC, platelet count and hemoglobin.  The 
peripheral neuropathy events will be identified from the clinical AE dataset using the 
Standardised MedDRA Queries (SMQs). 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
The null (Ho) and alternative (Ha) hypotheses for this endpoint are as follows, where P is the rate 
of the AEs described for the primary safety endpoint: 
Ho:  P Arm B = P Arm A
Ha:  P Arm B ≠ P Arm A
The rate of the AEs described for the primary endpoint will be summarized within each 
treatment schedule by descriptive statistics. The treatment difference in the AE rate will be 
analyzed using a Mantel-Haenszel Chi-square test with ECOG performance status (0 versus 1)
and histology (squamous cell carcinoma versus non-squamous cell carcinoma) as the
stratification factors.  The ratio of the AE rates will be summarized along with the two-sided 
95% confidence interval (CI). 
10.6.2.
Adverse Events
Adverse events will be analyzed in terms of TEAEs, defined as any AE or SAE occurring or 
worsening on or after the first dose of the study drug through 28 days after the last dose of study 
drug.  In addition, any serious AE with an onset date more than 28 days after the last dose of 
study drug that is assessed by the investigator as related to study drug 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
Treatment-emergent adverse events, Grade 3 or higher TEAEs, serious AEs, TEAEs leading to
dose reduction, dose delay, and dose interruption, TEAEs leading to treatment discontinuation, 
and TEAEs with an outcome of death will be summarized per treatment arms by MedDRA 
system organ class and preferred terms.
Adverse events of special interest of the nab-paclitaxel plus carboplatin combination identified in 
previous studies in a similar population will be summarized in the same manner.
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, 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 for each treatment arm.  
All other laboratory parameters reported on the eCRFs will be summarized by descriptive 
statistics by visit and treatment if the number of subjects with data is adequate. In addition, NCI 
CTCAE v 4.0 grades for the reported parameters will be summarized, if applicable.  
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
47
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
10.6.4.
Study Drug Exposure
The extent of exposure to the study drugs will be assessed based on the descriptive statistics on 
the number of cycles and study drug 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 by treatment 
arm. 
10.7.
Efficacy Analysis
10.7.1.
Key Efficacy Endpoints 
10.7.1.1.
Progression-free Survival
Progression-free survival is defined as the time from the date of randomization to the date of 
disease progression or death (any cause) on or prior to the data cutoff date for analyses, 
whichever 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 study therapy.
Subjects who do not have disease progression, or 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 randomization.
The null (Ho) and alternative (Ha) hypotheses for testing the PFS endpoint are: 
Ho: HR Arm B / Arm A = 1
Ha: HR Arm B / Arm A ≠ 1
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% CI) for each treatment schedule along with the hazard ratio 
estimated using Cox proportional hazards model (including two-sided 95% CI). The Kaplan-
Meier curve for PFS will be presented graphically for each treatment schedule.  P-value from a
stratified log-rank test will be reported as an indication for the strength of association for the 
difference between the two curves, where the strata include ECOG performance status (0 versus 
1) and histology (squamous versus non-squamous cell carcinoma), if the number of events in 
each cell is adequate.  
o the date o
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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 for each treatment schedule. In addition, confirmatory and sensitivity analyses will be 
performed to further assess the impact of missed radiologic assessments. An additional analysis 
of PFS, where death or new treatment will be considered as an event, will be conducted to 
address the impact of second-line therapy. 
10.7.1.2.
Overall Survival
Overall survival is defined as the time between randomization and death. All deaths, regardless 
of the cause of death, will be included. All subjects who are lost to follow-up prior to the end of
the study or who are withdrawn from the study will be censored at the time of last contact. 
Subjects who are still receiving treatment as of the data cutoff date will be censored at the cutoff 
date. Overall survival will be analyzed similarly as PFS.
10.7.1.3.
Overall Response Rate 
Overall response rate is defined as the percent of subjects who had a radiologic complete or 
partial response according to RECIST Version 1.1 guidelines determined by the investigator and 
confirmed by repeat radiologic assessment performed no less than 28 days after the criteria for 
response were first met.
Overall response rate for each treatment arm will be presented with the two-sided 95% CI.  
Relative treatment effect will be summarized by the difference in response rate and the 
associated two-sided 95% CI.  P-value from a Chi-square test will be reported to indicate the 
strength of association of the relative treatment effect.  
10.7.2.
Exploratory Endpoints
10.7.2.1.
Health Care Utilization and Quality of Life Questionnaire
The analysis of health care utilization and quality of life questionnaire data will be described in 
detail in the SAP.
 
10.8.
Study Therapy Termination
Reasons for stopping study therapy will be presented in listings and summarized by frequency of 
occurrence and corresponding percentage of occurrence.
10.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the study 
drug through 28 days post last dose of the study drug) 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).
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
10.10.
Interim Analysis
A non-binding interim analysis for futility with the primary safety endpoint will be conducted 
when approximately a total of 139 treated subjects have either completed 6 months of study 
treatment or discontinued from the study due to progression, adverse events, deaths, lost to 
follow up, or other reasons. The stopping rule and the final marginal significance level are 
determined based on the Gamma family spending function with parameter = -7 (Hwang, 1990) to 
control the Type-II error rate at 20%. The study may be stopped early for futility if the treatment 
difference is between ± 0.4% (Z-score ± 0.054) given the interim analysis is performed at 50% 
information fraction.
10.11.
Scientific Steering Committee
The conduct of this study will be overseen by a Steering Committee. The Steering Committee 
will serve in an advisory capacity to the Sponsor. 
&(/*(1(35235,(7$5<,1)250$7,21
g Co
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('06'RF1XPEHU
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Confidential and Proprietary
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ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the eCRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of NSCLC will not require reporting as 
an adverse event.
An overdose, accidental or intentional, whether or not it is associated with an AE, or abuse, 
withdrawal, sensitivity or toxicity to a study drug should be reported as an AE. If an overdose is 
associated with an AE, the overdose and adverse event should be reported as separate terms. See 
Section 8.8 for the definition of overdose.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for nab-paclitaxel, or 
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 
appropriate tests and procedures.
All AEs will be recorded by the investigator from the time the subject signs informed consent to
28 days after the last dose of study drug, and those SAEs made known to the investigator at any 
time thereafter that are suspected of being related to study drug. AEs and serious adverse events 
(SAEs) will be recorded on the AE page of the eCRF and in the subject’s source documents. All 
SAEs must be reported to Celgene Drug Safety within 24 hours of the investigator’s knowledge 
of the event by facsimile, or other appropriate method, using the SAE Report Form, or approved 
equivalent form.
11.2.
Evaluation of Adverse Events
A qualified investigator will evaluate all adverse events as to: 
11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
!
Results in death;
ome
ome
ymptoms of
ymptoms o
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equire repo
with an AE
with an AE
d as an AE
as an AE
e reported a
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pecific ant
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e subject’s c
subject’s c
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invest
investigato
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study drug
drug
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AE
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acsimile, or
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m.
Evalua
Evalu
ualified 
ualified 
&
inv
inv
11.2.1.
1.2.1.
ser


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Celgene Corporation
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!
Is life-threatening (ie, in the opinion of the investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the eCRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of or an elective procedure for a pre-existing condition 
unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
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Celgene Corporation
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For each SAE, the investigator will provide information on severity, start and stop dates, 
relationship to study drug, action taken regarding study drug, 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 National Cancer Institute (NCI) Common Terminology Criteria 
for Adverse Events (CTCAE, Version 4.0)
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Adverse events that are not defined in the NCI CTCAE should be evaluated for severity/intensity 
according to the following scale:
!
Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required
!
Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required
!
Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible
!
Grade 4 = Life threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable
!
Grade 5 = Death – the event results in death
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.
Seriousness, not severity, serves as a guide for defining regulatory obligations.
11.2.3.
Causality 
The investigator must determine the relationship between the administration of study drug 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 study drug
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 study drug caused the adverse event.  ‘Reasonable 
possibility’ means there is evidence to suggest a causal 
relationship between the study drug and the adverse event.
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Celgene Corporation
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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 study 
drug 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 study drug as a result of an AE or SAE, as 
applicable (eg, discontinuation or reduction of study drug, as appropriate) and report if 
concomitant and/or additional treatments were given for the event. 
11.2.6.
Outcome
The investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered or death (due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of study drug dose, or any other 
therapeutic intervention; or
!
is judged to be of significant clinical importance.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF. If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE.
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
54
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
11.4.1.
Female Subjects
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 study drug, or within 28 days
of the subject’s last dose of study drug, are considered immediately reportable events. Study drug
is to be discontinued immediately. The pregnancy, suspected pregnancy, or positive pregnancy 
test must be reported to Celgene Drug Safety immediately by facsimile, or other appropriate 
method, using the Pregnancy Initial Report Form, or approved equivalent form. The female 
subject should be referred to an obstetrician-gynecologist or another appropriate healthcare 
professional for further evaluation.
The investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the investigator
should report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate 
method, within 24 hours of the investigator’s knowledge of the event using the SAE Report 
Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the investigator suspects is 
related to the in utero exposure to the study drug should also be reported to Celgene Drug Safety 
by facsimile, or other appropriate method, within 24 hours of the investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving study drug
or within 6 months of the last dose of study drug, the male subject taking study drug should 
notify the investigator, and the pregnant female partner should be advised to call her healthcare 
provider immediately. If the male subject is receiving study drug, the study drug may need to be 
discontinued in the male subject, but may be resumed later at the discretion of the investigator
and Medical Monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The investigator is required to ensure that the data on these forms is accurate and consistent. This 
requirement applies to all SAEs (regardless of relationship to study drug) that occur during the 
study (from the time the subject signs informed consent to at least 28 days after the last dose of
study drug) and those made known to the investigator at anytime thereafter that are suspected of 
being related to study drug. SAEs occurring prior to treatment (after signing the ICF) will be 
captured.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
55
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
The SAE report should provide a detailed description of the SAE and include a concise summary
of hospital records and other relevant documents. If a subject died and an autopsy has been 
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available. Any follow-up data will be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety.
Where required by local legislation, the investigator is responsible for informing the Independent 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The investigator must keep copies of all SAE 
information on file including correspondence with Celgene and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than five (5) business 
days. Urgent queries (eg, missing causality assessment) may be handled by phone.
11.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to nab-paclitaxel 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 study drug 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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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
56
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the study 
drug:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent
!
Death
!
Lost to follow-up
!
Protocol violation
The decision to discontinue a subject remains the responsibility of the treating physician, which 
will not be delayed or refused by the sponsor. However, prior to discontinuing a subject, the 
investigator may contact the Medical Monitor and forward appropriate supporting documents for 
review and discussion.
All subjects discontinued from study drug for any reason will have a treatment discontinuation 
visit at the time of discontinuation and should undergo treatment discontinuation procedures.
All subjects discontinued from nab-paclitaxel will be followed for a period of 28 days after last 
dose of study drug for the collection of AEs.
Additionally subjects who withdraw from or discontinue treatment should be followed for 
progressive disease (if applicable), survival and any new anticancer therapy given.
The reason for treatment discontinuation should be recorded in the eCRF and in the source 
documents.
12.2.
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
study:
!
Withdrawal of consent
!
Death
!
Lost to follow-up
The following events may be considered sufficient reasons for discontinuing a subject from the 
study:
!
Adverse events(s)
!
Protocol violation
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
57
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. The investigator must notify the Medical Monitor immediately when a subject has 
been discontinued/withdrawn due to an AE (any unacceptable toxicity). All subjects who are 
withdrawn from the study should complete all protocol-required evaluations scheduled for early 
termination at the time of withdrawal.
Since follow-up of subjects who discontinue prematurely is of particular importance, every 
attempt should be made to collect all survival information and NSCLC treatment/therapy, unless 
the subject has specifically withdrawn consent from further follow-up. The investigator must 
make every effort to obtain minimal information regarding the subject’s survival status before 
determining that the subject is lost to follow-up.
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
58
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the investigator should contact the responsible Clinical Research
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page).This global Emergency 
Call Center is available 24 hours a day and 7 days a week. The representatives are responsible 
for obtaining your call-back information and contacting the on call Celgene/Contract Research 
Organization (CRO) Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
59
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative,
and investigator abide by Good Clinical Practice (GCP), as described in International Conference 
on Harmonization (ICH) Guideline E6 and in accordance with the general ethical principles 
outlined in the Declaration of Helsinki. The study will receive approval from an IRB/EC prior to 
commencement. The investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. Celgene staff or an authorized representative will evaluate and approve all 
investigators who in turn will select their staff.
The investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions. 
The investigator should maintain a list of sub-investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The investigator is responsible for keeping a record of all subjects who sign an ICF and are 
screened for entry into the study. Subjects who fail screening must have the reason(s) recorded in 
the subject’s source documents.
The investigator, or a designated member of the investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The investigator must ensure timely and accurate completion of eCRFs and queries.
14.3.
Subject Information and Informed Consent
The investigator must obtain informed consent of the subject and/or the subject’s legal
representative prior to any study-related procedures.
Documentation that informed consent occurred prior to the subject’s entry into the study and of 
the informed consent process should be recorded in the subject’s source documents including the 
date. The original ICF signed and dated by the subject and by the person consenting the subject 
prior to the subject’s entry into the study, must be maintained in the investigator’s study files and 
a copy given to the subject. In addition, if a protocol is amended and it impacts the content of the 
informed consent, the ICF must be revised. Subjects participating in the study when the amended 
protocol is implemented must be re-consented with the revised version of the ICF. The revised 
ICF signed and dated by the subject and by the person consenting the subject must be maintained 
in the investigator’s study files and a copy given to the subject.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
60
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
This documentation must also include a list of the members of the IRB/EC and their occupation 
and qualifications. If the IRB/EC will not disclose the names, occupations and qualifications of 
the committee members, it should be asked to issue a statement confirming that the composition 
of the committee is in accordance with GCP. For example, the IRB General Assurance Number 
may be accepted as a substitute for this list. Formal approval by the IRB/EC should mention the 
protocol title, number, amendment number (if applicable), study site (or region or area of 
jurisdiction, as applicable), and any other documents reviewed. It must mention the date on 
which the decision was made and must be officially signed by a committee member. Before the 
first subject is enrolled in the study, all ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
The investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a coordinating investigator and the IRB/EC. This statement also applies to any 
communication between the investigator (or coordinating investigator, if applicable) and 
regulatory authorities.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
61
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
62
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The investigator must ensure that the records and documents pertaining to the conduct of the 
study and distribution of the study drug 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 eCRFs or CD-ROM.
15.2.
Data Management
Data will be 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 study drug. The investigator must retain 
these documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the investigator, Celgene, and their authorized 
representative(s);
!
List of sub-investigators and other appropriately qualified persons to whom the 
investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of eCRFs (if paper) and of documentation of corrections for all subjects;
!
Study drug accountability records;
!
Record of any body fluids or tissue samples retained;
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
63
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
!
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.
The investigator must obtain approval in writing from Celgene prior to destruction of any
records. If the investigator is unable to meet this obligation, the investigator must ask Celgene 
for permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
64
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 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, eCRFs, procedures for obtaining informed 
consent, record keeping, and reporting of AEs/SAEs with the investigator. Monitoring will 
include on-site visits with the investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, 
eCRFs, subject’s source documents, and all other study documentation will be
inspected/reviewed by the Celgene representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the eCRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the investigator and/or his/her staff. Any necessary 
corrections will be made directly to the eCRFs or via queries by the investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene. Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The investigator is required to permit direct access to the facilities where the study took place, 
source documents, eCRFs and applicable supporting records of subject participation for audits 
and inspections by IRB/IECs, regulatory authorities (eg, FDA, European Medicines Agency 
[EMA], Health Canada) and company authorized representatives. The investigator should make 
every effort to be available for the audits and/or inspections. If the investigator is contacted by 
any regulatory authority regarding an inspection, he/she should contact Celgene immediately.
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or autho
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y


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
65
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
17.
PUBLICATIONS
The results of this study may be published in a medical publication, journal, or may be used for 
teaching purposes. Additionally, this study and its results may be submitted for inclusion in all 
appropriate health authority study registries, as well as publication on health authority study 
registry websites, as required by local health authority regulations. Selection of first authorship 
will be based on several considerations, including, but not limited to study participation, 
contribution to the protocol development, and analysis and input into the manuscript, related 
abstracts, and presentations in a study.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
66
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
18.
REFERENCES
Azzoli CG, Baker Jr. S, Temin S, Pao W, Aliff T, Brahmer J, et al. American Society of Clinical 
Oncology clinical practice guideline update on chemotherapy for Stage IV non-small-cell lung 
cancer. J Clin Oncol. 2009;27:6251-66.
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;26:468-73.
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, Dancey J, et al. New 
response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J 
Cancer. 2009 Jan;45(2):228-47. 
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.
Hwang IK, Shih WJ, De Cani JS. Group sequential designs using a family of type I error
probability spending functions. Stat Med. 1990;9:1439-45.
Lorenz W, Reimann HJ, Schmal A, Dormann P, Schwarz B, Neugebauer E, et al. Histamine 
release in dogs by Cremophor El and its derivatives: oxethylated oleic acid is the most effective 
constituent. Agents Actions 1977;7:63-7.
National Institute for Health & Clinical Excellence (NICE): The Diagnosis and Treatment of 
Lung Cancer: Methods, Evidence & Guidance, 2011.
Oken, MM, Creech, RH, Tormey, DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and 
Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol. 
1982;5(6):649-55.
Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, et al. Intergroupe Francophone 
de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared 
with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 
randomised, phase 3 trial. Lancet. 2011;378(9796):1079-88. 
Rizvi NA, Riely GJ, Azzoli CG, Miller VA, Ng KK, Fiore J, et al. Phase I/II trial of weekly 
intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with Stage IV 
non-small-cell lung cancer. J Clin Oncol. 2008;26(4):639-43.
Schiller JH, Gandara DR, Goss GD, Vokes EE.  Non-small-cell lung cancer: then and now. 
J Clin Oncol. 2013;31(8):981-3.
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eated 
ated
intratum
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or
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es
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R, Dancey J
Danc
ine (versio
ne (versio
g JB, Desai 
JB, Des
el and nab-
and nab
Crem
Cremopho
op
on. Eur J 
Eur J C
uential desi
uential desi
1990;9:143
1990;9:143
ormann P, 
ormann P, 
nd its deriv
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7;7:63
7;7:63-7.
-7.
& Clinical
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Evidence &
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55.
alcman G, 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
67
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
Socinski MA, Langer CJ, Okamoto I, Hon JK, Hirsh V, Dakhil SR, et al. Safety and efficacy of 
weekly nab®-paclitaxel in combination with carboplatin as first-line therapy in elderly patients 
with advanced non-small-cell lung cancer. Ann Oncol. 2013;24(2):314-21. 
Socinski MA, Manikhas GM, Stroyakovsky DL, Makhson AN, Cheporov SV, Orlov SV, et al. A 
dose finding study of weekly and every-3-week nab-paclitaxel followed by carboplatin as 
first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol. 
2010;5(6):852-61.
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. 
Review.
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.
&(/*(1(35235,(7$5<,1)250$7,21
latatioion
):665
):665-85.
85
Sparreboom
parreboom
lasma phar
asma pha
18-24.
-24.
Trump DL
Trump DL
(7):1263
(7):1263-8.
-8


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
68
ABI-007-NSCL-005 Amendment 2.0 Final: 05 Dec 2014
19.
APPENDICES
Appendix A: ECOG Performance Status Score
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up 
and about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of waking 
hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5
Dead
Oken, 1982.
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This is a representation of an electronic record that was signed electronically in Livelink.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-005 Final: 06 Mar 2014
TITLE PAGE
SAFETY AND EFFICACY OF nab-PACLITAXEL 
(ABRAXANE®) IN COMBINATION WITH 
CARBOPLATIN AS FIRST LINE TREATMENT IN 
ELDERLY SUBJECTS WITH ADVANCED NON-SMALL 
CELL LUNG CANCER (NSCLC): A PHASE IV, 
RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY
(ABOUND.70+)
STUDY DRUG
nab-Paclitaxel (Abraxane®)
PROTOCOL NUMBER:
ABI-007-NSCL-005
DATE FINAL:
06 Mar 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.
&(/*(1(35
ovided to you
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TUDY
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Abraxa
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11488
48
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rsons to whom
rsons to whom
52
35
/*
/*


nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-005 Final: 06 Mar 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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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-005 Final: 06 Mar 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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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-005 Final: 06 Mar 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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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-005 Final: 06 Mar 2014
COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:
 
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-005 Final: 06 Mar 2014
PROTOCOL SUMMARY
Study Title
Safety and efficacy of nab-paclitaxel (Abraxane) in combination with carboplatin as first line 
treatment in elderly subjects with advanced non-small cell lung cancer (NSCLC): A Phase IV, 
randomized, open-label, multicenter study (Abound.70+).
Indication
First-line treatment of advanced NSCLC in elderly subjects.
Objectives
Primary
!
To assess the safety and tolerability of continuous weekly versus weekly times three 
with one-week break nab-paclitaxel (Abraxane) in combination with carboplatin as 
first-line treatment for advanced NSCLC in elderly subjects (≥ 70 years old).
Secondary 
!
To evaluate the efficacy of nab-paclitaxel in combination with carboplatin in elderly 
subjects with advanced NSCLC.
Exploratory 
!
To assess healthcare resource utilization for the two nab-paclitaxel treatment arms.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ-5D) for the two nab-paclitaxel treatment arms.
!
 
 
!
 
Study Design
This is a Phase IV, randomized, open-label, multicenter study of continuous weekly versus 
weekly times three with one-week break nab-paclitaxel in combination with carboplatin as first-
line treatment in elderly subjects (≥ 70 years old) with advanced NSCLC who are not candidates 
for curative surgery or radiation therapy. Approximately 284 subjects with locally advanced or 
metastatic NSCLC will be randomized in this study to receive nab-paclitaxel in combination 
with carboplatin and will be randomized 1:1 into one of the two treatment arms prior to starting 
first dose of study drug. Randomization will be centralized and stratified by Eastern Cooperative 
Oncology Group (ECOG) performance status (0 versus 1) and histology (squamous cell 
carcinoma versus non-squamous cell carcinoma).
The study will consist of a 28-day Screening Period, a Treatment Period and a Follow-up Period.  
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352


nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-005 Final: 06 Mar 2014
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of study drug.
The Treatment Period begins with the first dose of study drug as described in Section 8.  Subjects 
will receive one of the following treatments based on the randomization assignment:
Arm A (21-day treatment cycle):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment cycle,
!
Carboplatin area under the curve (AUC) = 6 mg*min/mL IV on Day 1 of each 21-day 
treatment cycle after completion of nab-paclitaxel infusion.
Arm B (21-day treatment followed by one-week break cycle, 28-day duration):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment  followed by one-week break cycle (ie, every 28 
days),
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment followed by 
one-week break cycle (ie, every 28 days), after completion of nab-paclitaxel infusion. 
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of 
consent, in accordance with local standard of care.
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
(v1.1).
Local laboratory test data for absolute neutrophil count (ANC), platelet count, hemoglobin and 
serum creatinine will be collected in the electronic case report forms (eCRFs). All other 
laboratory test data, except those mentioned above, will not be collected routinely in the eCRF. 
All abnormal and clinically significant laboratory test results will be reported as adverse events 
(AEs) or serious adverse events (SAEs), and the specific associated laboratory parameter(s) 
should be recorded on the laboratory assessments eCRF. Local safety laboratory data will also be 
the primary guide for eligibility and subject management. In addition, test results for tumor 
mutational status of genes including but not limited to EGFR, ALK, and KRAS will be collected 
and recorded on eCRF if these tests have been performed locally for routine diagnosis.  
All subjects who discontinue from treatment for any reason other than withdrawal of consent or 
lost to follow-up will enter the Follow-up Period. It will consist of a visit 28 days after treatment 
discontinuation. Thereafter, subjects will be followed for survival approximately every 90 days 
(or when they are seen for routine care) by phone call or chart review for documentation of last 
contact for up to 6 months after the last subject is randomized or 192 progression-free survival 
(PFS) events have been observed, whichever comes later.
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nab-paclitaxel
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Celgene Corporation
Confidential and Proprietary
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Those subjects entering the Follow-up Period without documented progression will continue to 
have computed tomography (CT) scans in accordance with standard of care (at least every 90 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death or 
study closure. 
Study Population
Male and female subjects ≥ 70 years of age, with locally advanced or metastatic NSCLC 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.
Length of Study
The enrollment of 284 subjects on this study will take approximately 24 months. The total length 
of this Phase IV study with follow-up is estimated to be approximately 3 years.  
Study Treatments
nab-Paclitaxel and carboplatin are designated as non-investigational products and investigative 
sites will use standard of care (commercially available) product via routine prescription.
The preparation for IV administration procedures for nab-paclitaxel and carboplatin should be 
followed in accordance with the approved Prescribing Information for each drug.
Statistical Methods
Approximately 284 subjects will be randomized in a 1:1 ratio to one of two treatment arms 
(approximately 142 per arm).  Arm A will receive nab-paclitaxel 100 mg/m2 administered on 
Days 1, 8 and 15 in combination with carboplatin AUC = 6 mg*min/mL on Day 1 of each 21-
day treatment cycle, and Arm B will receive the same treatment in the same schedule as that of 
Arm A during the first 21 days, followed by a one-week break prior to the start of the next cycle
(28-day duration).  
Randomization will be stratified by ECOG performance status (0 versus 1) and histology 
(squamous cell carcinoma versus non-squamous cell carcinoma).
The primary objective of this study is to assess the safety and tolerability of the two treatment 
arms for first-line treatment of locally advanced or metastatic NSCLC in elderly subjects ( ≥ 70 
years old).  The primary study endpoint, correspondingly, is the percentage of subjects with 
either peripheral neuropathy of Grade ≥2 or myelosuppression AEs Grade ≥3 based on the local
laboratory values for ANC, platelet count, and hemoglobin, assessed using National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4.0). 
The peripheral neuropathy events will be identified from the clinical AE dataset using the 
Standardised MedDRA Queries (SMQs). For the purpose of this protocol, this endpoint will be 
referred to as the percentage of subjects with Grade ≥2 peripheral neuropathy or Grade ≥3 
myelosuppression laboratory adverse events.  
The study is designed to detect a difference of 16 percentage points between the 2 treatment arms
with respect to the primary safety endpoint with 80% power and a Type-I error rate of 5% (two-
sided), assuming 139 of the 142 randomized subjects per arm will receive at least one dose of 
study drug and the percentage of the treated subjects with the AEs specified above is 73% for 
Arm A.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
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A non-binding interim analysis for futility with the primary safety endpoint will be conducted 
when approximately a total of 139 treated subjects have either completed 6 months of study 
treatment or discontinued from the study due to progression, adverse events, deaths, lost to 
follow up, or other reasons. The study may be stopped early for futility if the treatment 
difference is between ± 0.4%, given the interim analysis is performed at 50% information 
fraction. 
Overview of Safety Assessment
The treated population, which includes all randomized subjects who received at least one dose of 
study drug, will be the analysis population for all safety analyses.  
The primary study endpoint (a composite safety endpoint) will be the percentage of subjects with 
Grade ≥2 peripheral neuropathy or Grade ≥3 myelosuppression laboratory adverse events.  
The null (Ho) and alternative (Ha) hypotheses for this endpoint are as follows, where P is the rate 
of the AEs described for the primary safety endpoint: 
Ho:  P Arm B = P Arm A
Ha:  P Arm B ≠ P Arm A
The AE rate of the primary study endpoint will be summarized within each treatment arm by 
descriptive statistics.  The treatment difference in the AE rate will be analyzed using a Mantel-
Haenszel Chi-square test with ECOG performance status (0 versus 1) and histology (squamous 
cell carcinoma versus non-squamous cell carcinoma) as the stratification factors.  The ratio of the 
AE rates will be summarized along with the two-sided 95% confidence interval (CI). 
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AE or SAE that begins or worsens in grade on or after the start of the study drug
through 28 days after the last dose of the study drug. Additionally, any SAE that occurs beyond 
this period of observation and is assessed by the investigator as related to the study drug, will be 
reported and analyzed.  
Treatment-emergent adverse events will be summarized by treatment arm by system organ class
and preferred term. Grade 3 or higher TEAEs, SAEs, TEAEs leading to dose modification 
(reduction, delay not given, and interruption), TEAEs leading to treatment discontinuation, and 
TEAEs with an outcome of death will be summarized by treatment arm. Adverse events of 
special interest of the nab-paclitaxel and carboplatin combination identified in previous studies
in a similar population will be summarized in the same manner.
In order to investigate the maximal degree of myelosuppression, ANC, platelet count, and 
hemoglobin will be summarized by the most severe grade in each treatment cycle and by the 
most severe grade during the study using NCI CTCAE v4.0. 
Overview of Efficacy Assessment
All efficacy analyses will be based on the intent-to-treat (ITT) population, which includes all
randomized subjects regardless of whether they receive any study drugs or have any efficacy 
assessments performed.  
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Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Final: 06 Mar 2014
Progression-free Survival (PFS) based on investigator’s assessment of the subject’s radiologic 
response using RECIST v1.1 guidelines, Overall Response Rate (ORR), and Overall Survival 
(OS) are the key efficacy endpoints.  Since the primary research interest of this study is to 
evaluate the relative safety and toxicities of the two treatment arms, the sample size was
calculated based on the primary safety endpoint, the percentage of subjects with Grade ≥2
peripheral neuropathy or Grade ≥3 myelosuppression laboratory adverse events.  Consequently, 
a statistically non-significant treatment difference in PFS, ORR or OS could simply be a function 
of the sample size and/or the lack of statistical power. Therefore, the assessments of treatment 
differences in PFS and OS will be based on the hazard ratios and in ORR, the ratio of response 
rates, and the corresponding 95% confidence intervals. P-values for between-group comparisons 
will be provided to indicate the strength of association only.  No multiplicity adjustment with the 
Type-I error rate will be made. 
Progression-free survival is defined as the time from the randomization date to the start of 
disease progression or subject death from any cause, whichever occurs first. Subjects who do not 
have disease progression or have not died as of the data cutoff date for the statistical analysis will 
be censored at the time of the last radiologic assessment prior to the data cutoff date. Rules for 
censoring for missing visits and start of anticancer treatment are provided in Section 10. 
Progression-free survival will be summarized using the Kaplan-Meier method and by median 
PFS time (including two-sided 95% confidence interval [CI]) for each treatment arm along with 
the hazard ratio (including two-sided 95% CI) between treatment arms. The Kaplan-Meier curve 
for PFS will be presented graphically for each treatment arm. To illustrate the strength of 
association, the p-value for treatment difference in the curves will be reported from a stratified 
log-rank test with ECOG performance status (0 versus 1) and histology (squamous versus non-
squamous cell carcinoma) as the stratification factors.  
Of note, if recruitment is complete in 24 months, assuming that approximately 67% of the 284 
subjects randomized will experience a PFS event (approximately 192 PFS events total) within 28
months from first subject randomized, there is 73% power to detect a hazard ratio (HR) of 0.69 
for PFS improvement with Arm B over Arm A and an overall Type-I error rate of 5% (two-
sided).  Assuming an exponential distribution with a median time to PFS of 5.8 months for Arm 
A and proportional hazards, a hazard ratio of 0.69 constitutes a 2.6 months improvement for Arm 
B. 
Overall response rate (percent of subjects who had a radiologic complete or partial response 
according to the investigator’s assessment of response based on RECIST v1.1 guidelines) and 
OS also will be assessed by descriptive statistics with the associated 95% CIs.  P-values from a 
Chi-square test and a stratified log-rank test will be provided to indicate the strength of 
association for the treatment differences in ORR and OS, respectively.  
The analyses of the safety and efficacy endpoints for the clinical study report will be performed 
after ~192 PFS events have been observed.  
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Final: 06 Mar 2014
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
1.
INTRODUCTION..................................................................................................18
1.1.
Non-small Cell Lung Cancer ..................................................................................18
1.2.
nab-Paclitaxel in NSCLC .......................................................................................19
1.3.
Rationale for Further Study of nab-Paclitaxel as First-line Treatment in 
Elderly Subjects with Advanced NSCLC................................................................20
2.
STUDY OBJECTIVES...........................................................................................22
2.1.
Primary Objectives .................................................................................................22
2.2.
Secondary Objective...............................................................................................22
2.3.
Exploratory Objectives ...........................................................................................22
3.
STUDY ENDPOINTS............................................................................................23
3.1.
Primary Endpoint....................................................................................................23
3.2.
Secondary Endpoints ..............................................................................................23
3.2.1.
Safety.....................................................................................................................23
3.2.2.
Efficacy..................................................................................................................23
3.3.
Exploratory Endpoints............................................................................................23
4.
OVERALL STUDY DESIGN ................................................................................24
4.1.
Study Design ..........................................................................................................24
4.1.1.
Follow-up Period....................................................................................................25
4.2.
Study Design Rationale ..........................................................................................25
4.3.
Study Duration .......................................................................................................27
4.4.
End of Trial ............................................................................................................27
5.
TABLE OF EVENTS.............................................................................................28
6.
PROCEDURES......................................................................................................31
6.1.
Medical History......................................................................................................31
6.2.
Prior and Concomitant Medications/Procedures......................................................31
6.3.
Computed Tomography (CT) Scan of Complete Chest (including base of 
neck and adrenal glands).........................................................................................31
6.4.
Weight....................................................................................................................32
6.5.
Body Surface Area (BSA) Calculation and Height..................................................32
6.6.
ECOG Performance Score ......................................................................................32
9
.........
.......20
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.....
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.....
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..
E OF EVE
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Medical 
Medical 
Pririor
3.3.
C
4


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6.7.
Peripheral Neuropathy Assessment.........................................................................32
6.8.
Adverse Event Reporting........................................................................................32
6.9.
Lung Cancer Symptom Scale Questionnaire and EQ-5D.........................................32
6.10.
Healthcare Resource Utilization Questionnaire .......................................................32
6.11.
Electrocardiogram ..................................................................................................33
6.12.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI) .......................33
6.13.
Bone Scans and X-rays...........................................................................................33
6.14.
Physical Examinations............................................................................................33
6.15.
Vital Signs..............................................................................................................33
6.16.
Laboratory Assessments .........................................................................................33
6.17.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) .....................................................................................34
6.18.
Survival..................................................................................................................34
7.
STUDY POPULATION.........................................................................................35
7.1.
Number of Subjects and Sites .................................................................................35
7.2.
Inclusion Criteria....................................................................................................35
7.3.
Exclusion Criteria...................................................................................................36
8.
DESCRIPTION OF STUDY TREATMENTS........................................................38
8.1.
Description of Study Drug(s)..................................................................................38
8.1.1.
nab-Paclitaxel.........................................................................................................38
8.1.2.
Carboplatin.............................................................................................................38
8.2.
Treatment Administration and Schedule .................................................................38
8.3.
Dose Modifications.................................................................................................39
8.4.
Method of Treatment Assignment...........................................................................41
8.5.
Packaging and Labeling..........................................................................................41
8.6.
Study Drug Accountability and Disposal ................................................................41
8.7.
Study Drug Compliance..........................................................................................41
8.8.
Overdose ................................................................................................................41
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................42
9.1.
Permitted Concomitant Medications and Procedures...............................................42
9.2.
Prohibited Concomitant Medications and Procedures..............................................42
9.3.
Required Concomitant Medications and Procedures................................................42
10.
STATISTICAL ANALYSES..................................................................................43
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9.1.
9.1


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10.1.
Overview................................................................................................................43
10.2.
Study Population Definitions ..................................................................................43
10.2.1.
Intent-to-treat Population........................................................................................43
10.2.2.
Per-protocol (PP) Population ..................................................................................43
10.2.3.
Treated Population..................................................................................................43
10.3.
Sample Size and Power Considerations...................................................................43
10.4.
Background and Demographic Characteristics........................................................45
10.5.
Subject Disposition.................................................................................................45
10.6.
Safety Analysis.......................................................................................................45
10.6.1.
Primary Safety Endpoint.........................................................................................45
10.6.2.
Adverse Events.......................................................................................................46
10.6.3.
Laboratory Assessments .........................................................................................46
10.6.4.
Study Drug Exposure..............................................................................................47
10.7.
Efficacy Analysis....................................................................................................47
10.7.1.
Key Efficacy Endpoints..........................................................................................47
10.7.1.1.
Progression-free Survival........................................................................................47
10.7.1.2.
Overall Survival .....................................................................................................48
10.7.1.3.
Overall Response Rate............................................................................................48
10.7.2.
Exploratory Endpoints............................................................................................48
10.7.2.1.
Health Care Utilization and Quality of Life Questionnaire......................................48
10.8.
Study Therapy Termination ....................................................................................48
10.9.
Deaths ....................................................................................................................48
10.10.
Interim Analysis .....................................................................................................49
10.11.
Scientific Steering Committee ................................................................................49
11.
ADVERSE EVENTS..............................................................................................50
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................50
11.2.
Evaluation of Adverse Events.................................................................................50
11.2.1.
Seriousness.............................................................................................................50
11.2.2.
Severity / Intensity..................................................................................................52
11.2.3.
Causality ................................................................................................................52
11.2.4.
Duration .................................................................................................................53
11.2.5.
Action Taken..........................................................................................................53
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11.2.2.
1.2.2.
523


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11.2.6.
Outcome.................................................................................................................53
11.3.
Abnormal Laboratory Values..................................................................................53
11.4.
Pregnancy...............................................................................................................53
11.4.1.
Female Subjects......................................................................................................54
11.4.2.
Male Subjects.........................................................................................................54
11.5.
Reporting of Serious Adverse Events......................................................................54
11.5.1.
Safety Queries ........................................................................................................55
11.6.
Expedited Reporting of Adverse Events..................................................................55
12.
DISCONTINUATIONS .........................................................................................56
12.1.
Study Treatment Discontinuation............................................................................56
12.2.
Study Discontinuation ............................................................................................56
12.3.
Subject Replacement ..............................................................................................57
13.
EMERGENCY PROCEDURES.............................................................................58
13.1.
Emergency Contact.................................................................................................58
14.
REGULATORY CONSIDERATIONS...................................................................59
14.1.
Good Clinical Practice............................................................................................59
14.2.
Investigator Responsibilities ...................................................................................59
14.3.
Subject Information and Informed Consent.............................................................59
14.4.
Confidentiality........................................................................................................60
14.5.
Protocol Amendments.............................................................................................60
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................60
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................61
14.8.
Closure of the Study ...............................................................................................61
15.
DATA HANDLING AND RECORDKEEPING.....................................................62
15.1.
Data/Documents .....................................................................................................62
15.2.
Data Management...................................................................................................62
15.3.
Record Retention....................................................................................................62
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................64
16.1.
Study Monitoring and Source Data Verification......................................................64
16.2.
Audits and Inspections............................................................................................64
17.
PUBLICATIONS ...................................................................................................65
18.
REFERENCES.......................................................................................................66
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6
2


nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Final: 06 Mar 2014
19.
APPENDICES........................................................................................................68
Appendix A:
Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 ..............68
Appendix B:
ECOG Performance Status Score.......................................................................72
&(/*(1(35235,(7$5<,1)250$7,21


nab-paclitaxel
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Celgene Corporation
Confidential and Proprietary
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LIST OF TABLES
Table 1:
Blinded Radiology Assessment of Overall Response Rate (ITT Population) ...........20
Table 3:
Table of Events.......................................................................................................28
Table 4:
Permanent Dose Reductions for Hematologic and Neurologic Toxicities and 
Dosing on the Study ...............................................................................................40
Table 5:
Evaluation of Target Lesions ..................................................................................70
Table 6:
Evaluation of Non-Target Lesions ..........................................................................70
.40
40
........
.......70
70
.............
.......
7


nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
17
ABI-007-NSCL-005 Final: 06 Mar 2014
LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................26
&(/*(1(35235,(7$5<,1)250$7,21


nab-paclitaxel
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Celgene Corporation
Confidential and Proprietary
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1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer
Lung cancer is the leading cause of cancer-related deaths among men and women worldwide, 
with 1.2 million new cases diagnosed each year. Non-small cell lung cancer (NSCLC) is the 
most common type of lung cancer, accounting for 80% of all new cases. There are an estimated 
1.1 million lives lost per year (approximately 500,000 in the United States [US] and European 
Union [EU] alone) due to NSCLC. Smoking is the causative factor for up to 85% of cases 
(http://www.lungcancercoalition.org/en/pages/about/awareness).
The majority of patients are not diagnosed until the tumor has progressed beyond the primary 
site. Despite step-wise advances in patient selection, targeted agents and optimizing
chemotherapy regimens, patients with advanced NSCLC continue to have an unmet medical 
need (Schiller, 2013).
Platinum-containing chemotherapy regimens remain the standard first-line treatment in the 
majority of patients, in the US and Japan. In the EU, a third-generation chemotherapeutic agent 
(docetaxel, gemcitabine, paclitaxel, or vinorelbine), most commonly gemcitabine or vinorelbine, 
plus a platinum drug is used for advanced NSCLC (NICE, 2011). For first-line therapy in 
patients with Stage IV NSCLC and good performance status, the American Society of Clinical 
Oncology (ASCO) clinical practice guideline recommends treatment with a platinum-based 
two-drug combination of cytotoxic drugs (Azzoli, 2009). A trend that is becoming more 
prevalent is personalized NSCLC treatment based on tumor histology (squamous versus
non-squamous), on molecular characteristics of the tumor, and on the patient’s clinical status 
using agents targeting specific receptors and kinases and pathways (ie, epidermal growth factor 
receptor [EGFR], echinoderm microtubule-associated protein-like 4 [EML4] and anaplastic 
lymphoma kinase [ALK] fusion protein).
In advanced NSCLC, the prevalently used combination of solvent-based 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, and requires the use of specialized infusion sets and in-line 
filters that do not contain di[2-ethylhexyl] phthalate (DEHP).
Compared with solvent-based paclitaxel, nab-paclitaxel exhibits 10-fold higher mean Cmax of 
free paclitaxel, delivers 33% higher drug concentration to tumors in preclinical xenograft 
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nab-paclitaxel
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ABI-007-NSCL-005 Final: 06 Mar 2014
models, and demonstrates enhanced transport across endothelial cell monolayers (Desai, 2006; 
Gardner, 2008). The Cremophor EL-free medium enables nab-paclitaxelto be given in a shorter
duration without the need for premedication to prevent solvent-related hypersensitivity reactions.
In addition, standard tubing and intravenous (IV) bags may be used for the IV administration of 
nab-paclitaxel. 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. 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.
1.2.
nab-Paclitaxel in NSCLC
The Food and Drug Administration (FDA) approval of nab-paclitaxel 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. 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%), see Table 1].
Non-inferiority analysis of overall survival (OS) demonstrated that nab-paclitaxel/carboplatin
(nab-p/C) treatment is not inferior to solvent-based paclitaxel/carboplatin (sb-P/C) treatment. 
Overall survival in the nab-paclitaxel arm was 12.1 months versus 11.2 months in the control 
arm (p = 0.271; HR = 0.922).  Toxicities, particularly neuropathy and neutropenia were less 
pronounced using nab-paclitaxel in the dose and schedule employed.
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Table 1:
Blinded Radiology Assessment of Overall Response Rate (ITT Population)
Variable
Category/Statistic
nab-Paclitaxel/
Carboplatin
(N=521)
sb-Paclitaxel/
Carboplatin
(N=531)
Response Rate 
Ratio
(pA/pT)a
p-value
Patients with Confirmed Complete or Partial Overall Response
n (%)
170 (33%)
132 (25%)
1.313
0.005*
Confidence Interval (CI) b
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%)
a PA/PT equals response rate of nab-paclitaxel/response rate of sb paclitaxel.
b 95% CI of response rate and 95.1% CI of response rate ratio.
* Indicates p-value < 0.049.Note: P-value is based on a chi-square test.
Source: Data on File.
Adverse events were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. The following common (≥ 10% incidence) 
adverse events were observed at a similar incidence in nab-paclitaxel and paclitaxel 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).
1.3.
Rationale for Further Study of nab-Paclitaxel as First-line Treatment 
in Elderly Subjects with Advanced NSCLC
The tolerability of doublet chemotherapy in elderly patients with advanced NSCLC is an
important therapeutic consideration, whereby the landmark IFCT 0501 reported that first-line sb-
paclitaxel given weekly three weeks out of four coupled with carboplatin every 4 weeks (ie, 
21days of treatment followed by one-week break) improved efficacy over single-agent 
chemotherapy (either gemcitabine or vinorelbine) in patients 70 years or older with advanced 
NSCLC. The results demonstrated that doublet chemotherapy was feasible in this elderly
population with an acceptable toxicity profile, when sb-paclitaxel/carboplatin was given as 21
days of treatment followed by one-week rest. The combination also resulted in a significant 
improvement in OS (median, 10.3 versus 6.2 months; HR = 0.639, 95% CI:0.52-0.79, p <
0.0001), with 1-year survival rates of 45.1% versus 26.9% for doublet therapy and monotherapy.  
This prospective trial set a standard, against which doublet-regimens must be measured in the 
elderly population with advanced NSCLC.
In the CA031 study of nab-paclitaxel (Abraxane) in combination with carboplatin, patients were 
stratified by age (< 70 years old versus ≥ 70 years old). Fifteen percent of ITT patients were 
elderly (≥70 years: nab-paclitaxel, n = 74: sb-paclitaxel, n = 82). Baseline characteristics were 
generally well balanced between treatment arms in elderly population, and subgroup analyses 
were performed to assess the influence of age on the primary efficacy endpoint of overall 
response rate as well as PFS and OS (Socinski, 2013). 
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Of note, the post-hoc analysis of the CA031 trial showed marked improvement in survival in the 
nab-paclitaxel/carboplatin arm. Amongst 156 elderly (≥70 years of age) subjects randomized on 
the study, OS was 19.9 months versus 10.4 months (HR: 0.583, p = 0.009) in favor of the nab-
p/C arm compared to sb-p/C. The proportion of patients who had complete or partial response 
were consistently higher in all age stratum groups for the nab-paclitaxel/carboplatin regimen 
relative to the sb-paclitaxel/carboplatin regimen (in patients ≥ 70 years of age 34% versus 24% 
respectively, ratio of rates 1.385, p = 0.196, 
).
 
 
 
Although it was a statistically significant treatment effect in favor of nab-paclitaxel in the elderly 
subgroup from CA031 trial, 46% of patients in the nab-paclitaxel/carboplatin arm experienced 
dose reductions or dose delays. Approximately 92% of dose modifications and reductions were 
due to AEs. The most common clinical AEs in this subgroup were hematologic Grade ≥ 3 
neutropenia (45%), anemia (22%) and thrombocytopenia (19%). Approximately 18% of the 
elderly population in the CA031 trial had Grade ≥ 2 peripheral neuropathy. Despite that,
approximately 10% more elderly patients in the nab-paclitaxel arm were able to receive second-
line therapy compared to sb-paclitaxel (61% versus 50%, respectively), possibly because they 
may have been in better shape due to a better tolerated first-line regimen with nab-paclitaxel or 
better disease and symptom control as demonstrated as improvement in ORR.
The results from the elderly subset in CA031 trial showed the combination of nab-paclitaxel and 
carboplatin to be particularly promising. We hypothesize that the tolerability can be improved 
further by introducing a one week break at the end of each treatment cycle (similar to the 
schedule advocated by Quoix, 2011) among elderly patients.  Reducing the rate of the most 
common AEs (Grade ≥ 3 myelosuppression toxicities and Grade ≥ 2 peripheral neuropathy) by 
16% will be clinically meaningful as it can potentially improve tolerability, quality of life and 
allow patients to receive treatment for a longer period of time, without necessarily compromising 
efficacy.  
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2.
STUDY OBJECTIVES
2.1.
Primary Objectives 
!
To assess the safety and tolerability of continuous weekly versus weekly times three 
with one-week break nab-paclitaxel (Abraxane) in combination with carboplatin as 
first-line treatment for advanced NSCLC in elderly subjects (≥ 70 years old).
2.2.
Secondary Objective
!
To evaluate the efficacy of nab-paclitaxel in combination with carboplatin in elderly 
subjects with advanced NSCLC.
2.3.
Exploratory Objectives
!
To assess healthcare resource utilization for the two nab-paclitaxel treatment arms.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ-5D) for the two nab-paclitaxel treatment arms.
!
 
 
!
 
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3.
STUDY ENDPOINTS
3.1.
Primary Endpoint
!
The primary study endpoint is the percentage of subjects with either peripheral 
neuropathy of Grade ≥2 or myelosuppression AEs of Grade ≥3 based on the local
laboratory values for ANC, platelet count, and hemoglobin. All AEs will be graded 
using NCI CTCAE v4.0. 
3.2.
Secondary Endpoints
The secondary endpoints are: 
3.2.1.
Safety
!
The type, frequency, and severity of AEs and SAEs. 
!
Discontinuation rate.
!
Dose intensity administered.
!
The incidence of dose reduction and dose delay.
3.2.2.
Efficacy
!
Progression-free Survival (PFS).
!
Overall response rate (ORR) using RECIST v1.1 guidelines.
!
Overall Survival (OS).
3.3.
Exploratory Endpoints
!
Healthcare resource utilization during the study using a questionnaire.
!
Changes in the LCSS and EQ-5D.
!
 
!
 
 
!
Additional exploratory endpoints may be defined in the statistical analysis plan 
(SAP), if applicable.
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4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is a Phase IV, randomized, open-label, multicenter study of continuous weekly versus
weekly times three with one-week break nab-paclitaxel in combination with carboplatin as first-
line treatment in elderly subjects (≥ 70 years old) with advanced NSCLC who are not candidates 
for curative surgery or radiation therapy.
Subjects will be randomized 1:1 to receive one of the following treatments:
Arm A (21-day treatment cycle):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment cycle after 
completion of nab-paclitaxel infusion 
Arm B (21-day treatment followed by one-week break cycle, 28-day duration):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment  followed by one-week break cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment followed by 
one-week break cycle, after completion of nab-paclitaxel infusion 
The study will consist of a 28-day Screening Period, a Treatment Period, and a Follow-up
Period.
The Screening Period will start from signing the Informed Consent Form (ICF) until first dose of 
study drug. 
The Treatment Period will start from first dose of study drug until End-of-Treatment Visit 
(which is defined as visit with last dose of study drug).
Follow-up Period will start after End-of-Treatment visit.
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of 
consent, in accordance with local standard of care.
Tumor evaluations will be assessed locally and response (Complete Response (CR) or Partial 
Response (PR)) will be determined according to RECIST guidelines, Version 1.1. In both 
treatment arms, tumor assessments will be conducted at screening, every 42 days (-3/+7 days) 
(starting from Day 1 Cycle 1) until disease progression (even if treatment has been 
discontinued), withdrawal of consent, lost to follow-up, death or if clinically indicated while on 
treatment.
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Local laboratory test data for ANC, platelet count, hemoglobin and serum creatinine 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 AE, or SAE,
and the specific associated laboratory parameter(s) should be recorded in the laboratory 
assessments eCRF. Local safety laboratory data will also be the primary guide for eligibility and 
subject management. In addition, test results for tumor mutational status of genes including but 
not limited to EGFR, ALK, and KRAS will be collected and recorded on eCRF if these tests 
have been performed locally for routine diagnosis.  
4.1.1.
Follow-up Period
All subjects who discontinue from treatment for reasons other than withdrawal of consent or lost 
to follow-up, will enter the Follow-up Period. It will consist of a visit 28 days after treatment 
discontinuation following by follow-up for survival approximately every 90 days (+/- 14 days or 
when they are seen for routine care) by phone call or chart review for documentation of last 
contact for up to 6 months after the last subject is randomized or 192 PFS events have been 
observed, whichever comes later.
Those subjects entering the Follow-up Period without documented progression will continue to 
have CT scans in accordance with standard of care (at least every 90 days) until documented 
progression of disease, withdrawal of consent, lost to follow-up, death or study closure.
4.2.
Study Design Rationale
The nab-paclitaxel schedule used in Arm A is in accordance with pivotal trial CA031,
ie,100 mg/m2 administered once per week on Days 1, 8 and 15 combined with carboplatin 
AUC = 6 mg*min/mL administered on Day 1 every 21 days, as approved by the FDA.  The nab-
paclitaxel/carboplatin schedule used in Arm B is the same schedule as the current approved nab-
paclitaxel label with introduction of a one-week break following 21 days of treatment. This 
study will determine whether the one-week break can further improve tolerability without 
compromising efficacy (similar to the schedule advocated by Quoix, 2011) among elderly 
patients.  Reducing the rate of the most common AEs (Grade ≥ 3 myelosuppression toxicities 
and Grade ≥ 2 peripheral neuropathy) by 16% will be clinically meaningful as it can potentially 
improve tolerability, quality of life and allow subjects to receive treatment for a longer period of 
time.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
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Figure 1:
Overall Study Design
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nab-paclitaxel
Protocol ABI-007-NSCL-005
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ABI-007-NSCL-005 Final: 06 Mar 2014
4.3.
Study Duration 
Recruitment is expected to take approximately 24 months, and the analysis of PFS will be 
performed when approximately 192 PFS events have occurred, estimated as approximately 28
months from first subject randomized. The total length of this Phase IV study with follow-up is 
estimated to last approximately 3 years.
4.4.
End of Trial
The End of Trial is defined as either the:
!
date of the last visit of the last subject to complete the study, or 
!
the date of receipt of the last data point from the last subject that is required for primary, 
secondary and/or exploratory analysis, as pre-specified in the protocol and/or the SAP, 
whichever is the later date.
for 
or
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5.
TABLE OF EVENTS
Table 3:
Table of Events
Screening
/ Baseline
Treatment Perioda
Every cycle starting with Cycle 1
Follow-Up Period
Assessment
Day -28 
to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days) 
(counting from 
Day 1 Cycle 1)
End-of-
Treatment
Visit (last dose 
of study drug)
28-day Follow-up 
Visit (after last 
dose of study 
drug)
Survival Follow-Upb
Every 90 days (+/-
14 days) (after 28-
day follow-up visit)
Informed Consent
X
-
-
-
-
-
-
-
Medical History, Prior Medication and Procedures
X
-
-
-
-
-
-
-
CT Scan of Complete Chest (including base of neck 
and adrenal glands) and any other studies required 
for Tumor Imagingc
X
-
-
-
X c
X c
-
X c
Weight and Heightd
X
X
X
X
-
-
-
-
Body Surface Area (BSA) Calculationd
X
-
-
-
-
-
-
-
ECOG status
X
X
-
-
-
X
X
-
Concomitant Medication/Procedures
-
X
X
X
-
X
X
X
Peripheral Neuropathy Assessmente
X
X
X
X
-
X
X
-
Healthcare Resource Utilization Questionnaire
-
X
-
-
-
X
X
-
Hematologyf (ANC, platelet count, Hgb)
X
X
X
X
-
X
X
-
Serum Chemistryf (serum creatinine)
X
X
-
-
-
X
X
-
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nab-paclitaxel
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Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Final: 06 Mar 2014
Table 3:
Table of Events (Continued)
Screening
/ Baseline
Treatment Perioda
Every cycle starting with Cycle 1
Follow-Up Period
Assessment
Day -28 
to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days) 
(starting Day 1 
Cycle 1)
End-of-
Treatment
(last dose of 
study drug)
28-day Follow-up 
Visit (after last 
dose of study 
drug)
Survival Follow-Upb
Every 90 days (+/-
14 days) (after 28-
day follow-up visit)
Adverse Event Evaluation
After signing ICF and until 28 days after the last dose of study drug
nab-paclitaxel Administration/accountabilityg
-
X
X
X
-
-
-
-
Carboplatin Administration/accountabilityg
-
X
-
-
-
-
-
-
LCSS and EQ-5D
-
X
-
-
-
X
X
-
Survival phone call (or chart review for 
documentation of last contact or when they are seen 
for routine care
-
-
-
-
-
-
-
Xb
Electrocardiogram (ECG)
Will be done as per standard of care at screening, during the Treatment Period and as clinically indicated; however, results 
will not be routinely collected in the eCRFs. Results will be collected in the eCRFs as AE or SAE only if results are abnormal 
and clinically significant.
CT Scan of the Head or Brain Magnetic Resonance 
Imaging (MRI)
Bone Scan (X-rays if needed)
Physical Examination
Vital Signs
AE = Adverse Event; ANC = absolute neutrophil count; CT = Computed Tomography; ECOG = Eastern Cooperative Oncology Group; eCRF = electronic Case Report Form; EQ-
5D = EuroQol 5D; ICF = informed consent form; LCSS = Lung Cancer Symptom Scale; SAE = Serious Adverse Event.
a Treatment Period:  Arm A: nab-paclitaxel Days 1, 8, and 15 and carboplatin Day 1. Arm B: nab-paclitaxel Days 1, 8, and 15 and carboplatin Day 1 followed by one-week break.
b Every 90 (+/-14) days (from 28-day Follow-up Visit) or when they are seen for routine care for up to 6 months after the last subject is randomized or 192 PFS events have been 
observed, whichever comes later.
c All subjects must have a radiographically documented measurable tumor(s) by RECIST Version 1.1 criteria: CT scan of complete chest (including base of neck and adrenal 
glands) are performed at screening, every 42 days (-3/+7 days) thereafter (counting from Day 1 Cycle 1) until disease progression, withdrawal of consent, lost to follow-up, 
death and if clinically indicated while on treatment. The methods of assessment chosen at baseline to follow tumors are to remain consistent throughout study duration. Those 
subjects entering the Follow-up Period without documented progression will continue to have CT scans in accordance with standard of care (at least every 90 days) until 
documented progression of disease, withdrawal of consent, lost to follow-up, death or study closure.
d BSA will be calculated at screening and recalculated if body weight changes by more than 10% from previous assessment. Height will only be obtained at Screening Visit. 
Weight will be obtained at screening and every visit during the Treatment Period before administration of study drug, but will only be collected on the eCRF for the Screening 
Visit.
e The occurrence of peripheral neuropathy will be reported by the investigator per protocol as an AE or SAE.
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nab-paclitaxel
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Celgene Corporation
Confidential and Proprietary
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f Laboratory assessments will be done prior to each nab-paclitaxel treatment as per standard of care during the study and as clinically indicated. ANC, platelet count, hemoglobin
(Hgb) level and serum creatinine results will be collected in the eCRFs (all other routine laboratory test data except those mentioned above will not be collected in the eCRF
unless it is clinically significant, which will then be reported as AEs or SAEs, and the specific associated laboratory parameter(s) should be recorded on the laboratory 
assessments eCRF).
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6.
PROCEDURES
Subjects will be provided with a written ICF, given the opportunity to ask any questions 
concerning the study and will sign an ICF prior to participating in any study procedures. After 
giving written informed consent, subjects will undergo a Screening Period to be assessed for 
eligibility. All subjects who sign an ICF must be entered into the Interactive Randomization 
Technology (IRT) system immediately upon signature on the document. Subjects who do not 
meet the eligibility criteria will be considered screening failures and will not be eligible for the 
study. Subjects who screen fail may re-screen up to 2 times at any time and an ICF will need to 
be re-signed, as well as all screening procedures repeated (some procedures may not need to be 
done if previously done within 28 days prior to screening again). Subjects that have met all 
eligibility criteria after the Screening Period will be eligible to be randomized. 
6.1.
Medical History
Only clinically significant or ongoing medical conditions will be recorded at screening on the 
eCRF. 
6.2.
Prior and Concomitant Medications/Procedures
Prior medications are considered any medications stopped prior to the date of the first dose of 
study drug. Only prior medications/procedures (of clinically significant or ongoing medical 
conditions) within 28 days of time of signature on the ICF should be recorded. All NSCLC-
related prior medications/procedures (including radiation therapy) should be recorded regardless 
of time. 
Concomitant medications and procedures are considered any medications or procedures that 
were taken on or after the date of the first dose of study drug. All subjects will have concomitant 
medications and procedures (including radiation therapy) recorded from the time of signature on 
the ICF until the 28-day Follow-up Visit, for conditions that are clinically significant or ongoing. 
During the Follow-up Period only NSCLC-associated concomitant medications/procedures 
(including radiation therapy) will be recorded, ie, subsequent-line(s) of anti-cancer therapy.
6.3.
Computed Tomography (CT) Scan of Complete Chest (including 
base of neck and adrenal glands)
A CT scan of complete chest (including base of neck and adrenal glands) and any other studies 
required for tumor imaging will be done at screening, every 42 days (-3/+7 days) (starting from 
Day 1 Cycle 1) until treatment discontinuation or withdrawal of consent. Those subjects entering 
the Follow-up Period without documented progression will continue to have CT scans in 
accordance with standard of care (at least every 90 days) until documented progression of 
disease, withdrawal of consent, lost to follow-up, death or study closure. Additional CT scans
may be done at any time during the study if clinically indicated. All CT scans and reports should 
be archived at the site according to site regulations and copies provided to Sponsor if requested.
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nab-paclitaxel
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6.4.
Weight
Weight will be obtained at screening and at every visit during the Treatment Period before 
administration of study drug, but will only be collected on the eCRF for the Screening Visit.
Additional weights may be collected per local standards at any time during the study as needed.
6.5.
Body Surface Area (BSA) Calculation and Height
Height will be collected at screening only, and BSA will be calculated at screening of the study.
BSA will be recalculated if body weight changes by more than 10% from previous assessment.
6.6.
ECOG Performance Score
Eastern Cooperative Oncology Group performance score will be collected at screening, Day 1 of 
every treatment cycle, at the End-of-Treatment visit and at the 28-day Follow-up Visit. 
Additional ECOG assessments may be performed at any time during the study as clinically 
indicated.
6.7.
Peripheral Neuropathy Assessment
Peripheral neuropathy (sensory or motor) assessment will be done at screening, Day 1, 8, 15 of 
every treatment cycle, at the End-of-Treatment visit and at the 28-day Follow-up Visit. Changes 
in neuropathy grade from baseline will be reported as an AE as per Section 11. Additional 
peripheral neuropathy assessments may be done at any time during the study as clinically 
indicated.
6.8.
Adverse Event Reporting
Adverse events will be recorded from time of signature on the ICF until 28 days after the last 
dose of study drug, including any unscheduled visits. See Section 11 for details. 
6.9.
Lung Cancer Symptom Scale Questionnaire and EQ-5D
The LCSS and EQ-5D questionnaires will be used to measure quality of life (QoL) for subjects 
in the study. The LCSS is comprised of 9 questions to be completed by the subject using a visual 
analogue scale (VAS) to denote intensity of a symptom. The EQ-5D comprises 5 questions on 
mobility, self-care, usual activities, pain/discomfort, anxiety/depression and a VAS for overall 
QoL. These questionnaires will be completed at Day 1 of every Treatment Period, at the End-of-
Treatment Visit and at the 28-day Follow-up Visit.
6.10.
Healthcare Resource Utilization Questionnaire
A healthcare resource utilization questionnaire will be used to capture the additional use of 
healthcare resources, including hospitalizations, emergency room visits, doctor or nurse visits, 
procedures, and/or additional medication during the study period. The assessment will be 
completed at Day 1 of every treatment cycle, at the End-of-Treatment visit and at 28-day Follow-
up Visit. 
t.
ning, Day 1
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clinica
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time during
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comprised 
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ivit
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6.11.
Electrocardiogram
Electrocardiograms (ECGs) will be done per standard of care at screening, during the Treatment 
Period and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if 
results are abnormal, changed and clinically significant.
6.12.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI)
A CT scan of the head, or preferably brain MRI, will be done as per standard of care at 
screening, during the Treatment Period, and as clinically indicated. Results will be collected in 
the eCRFs as an AE or SAE only if the results are abnormal and clinically significant.
6.13.
Bone Scans and X-rays
Bone scans and x-rays will be done as per standard of care at screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if 
results are abnormal and clinically significant.
6.14.
Physical Examinations
Physical examinations will be done as per standard of care at screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if 
results are abnormal and clinically significant.
6.15.
Vital Signs
Vital signs will be done as per standard of care at screening, during the Treatment Period, and as 
clinically indicated. Results will be collected in the eCRFs as AE or SAE only if results are 
abnormal and clinically significant.
6.16.
Laboratory Assessments
Laboratory assessments will be done as indicated in Table 3 by local laboratories as per standard 
of care during the study and as clinically indicated. Local laboratory test data for ANC, platelet 
count and hemoglobin must be collected at screening, each visit before administration of study 
drug, at the End-of-Treatment visit and at the 28-day Follow-up Visit in the eCRF. Serum 
creatinine must be collected at screening, Day 1 of each cycle, at the End-of-Treatment visit and 
at the 28-day Follow-up Visit in the eCRF. Normal ranges for these selected parameters will be 
collected on the eCRF. All other laboratory test data, except those mentioned above, will not be 
collected routinely in the eCRF. Local safety laboratory data will also be the primary guide for 
eligibility and subject management. It is the responsibility of the investigator to assess the 
clinical significance of all abnormal values as defined by the reference ranges from the local 
laboratory. All clinically significant laboratory abnormalities (Section 11.3) are to be recorded as 
AEs on the AE eCRF, and the specific laboratory parameter(s) as well as the corresponding 
normal ranges should be recorded on the laboratory assessments eCRF. Clinically significant 
laboratory abnormalities at screening may result in subject ineligibility for the study and should 
not be captured as AE. Any abnormal values that persist should be followed at the discretion of 
the investigator. The investigator should file all copies of the reports, including faxes with the 
subject’s medical chart.
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6.17.
Tumor Tissue Sample Collection and Peripheral Blood Collection
(Exploratory Assessments) 
Provision of tumor tissue is mandatory for study enrollment, except when no tumor tissue is 
extant and this requirement would necessitate a new procedure such as a biopsy to collect it.  
 
 
 
 
 
 
 
 
 
 
 
 
 
In addition, test results for tumor mutational status of genes including but not limited to EGFR, 
ALK, and KRAS will be collected and recorded on eCRF if these tests have been performed
locally for routine diagnosis.
 
 
 
 
6.18.
Survival 
After the End-of-Treatment Visit, the subjects will have a 28-day Follow-up Visit followed by a
call or chart review for documentation of last contact approximately every 90 days (or when they 
are seen for routine care) for up to 6 months after the last subject is randomized or 192 PFS 
events have been observed, whichever comes later. The subjects will also be asked questions 
about other medications they may be taking for their NSCLC or their medical records will be 
reviewed to determine a last contact date for routine purposes. Those subjects entering the 
Follow-up Period without documented progression will continue to have CT scans in accordance 
with standard of care (at least every 90 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death or study closure.
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7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Elderly (≥70 years of age) male and female subjects with locally advanced or metastatic NSCLC 
with no prior chemotherapy for metastatic disease will be eligible for this study. The study will 
enroll approximately 284 subjects. The study will be conducted at approximately 65 sites in the 
United States.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be randomized in the study:
1. Age ≥ 70 years at the time of signing the ICF.
2. Understand and voluntarily provide written informed consent prior to the conduct of any 
study related assessments/procedures.  
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Histologically or cytologically confirmed locally advanced or metastatic NSCLC who are 
not candidates for curative surgery or radiation therapy.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease (defined by the presence of 
≥1 radiographically documented measurable lesion) (See Appendix A).
7. No prior chemotherapy for the treatment of metastatic disease. Adjuvant chemotherapy is 
permitted providing cytotoxic chemotherapy was completed 12 months prior to signing 
the ICF and without disease recurrence.
8. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
9. Platelets ≥ 100,000 cells/mm3.
10. Hemoglobin (Hgb) ≥ 9 g/dL.
11. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]), alanine
transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper limit of 
normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
12. Total bilirubin ≤ 1.5 mg/dL (unless there is a known history of Gilberts Syndrome).
13. Creatinine clearance (CrCl) > 40 mL/min calculated using Cockcroft-Gault equation (if 
renal impairment is suspected 24 hour urine collection for measurement is required).
14. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
15. Females who (1) have undergone hysterectomy (the surgical removal of the uterus) or 
bilateral oophorectomy (the surgical removal of both ovaries) or (2) have been naturally 
postmenopausal for at least 24 consecutive months (ie, has not had menses at any time 
during the preceding 24 consecutive months).
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15.5. F


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Male subjects must:
a.
Practice true abstinence* or agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the study, 
during dose interruptions and for at least 28 days following study drug 
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
≥4 weeks 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. Preexisting 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 a study drug: 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 allergy or hypersensitivity to nab-paclitaxel or carboplatin.
13. Currently enrolled in any other clinical protocol or investigational trial that involves
administration of experimental therapy and/or therapeutic devices.
                                               
* 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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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 randomization. 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 of 
which 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.
18. Females who (1) have not undergone hysterectomy (the surgical removal of the uterus) or 
bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been 
naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any 
time during the preceding 24 consecutive months).
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8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Study Drug(s)
Treatment
Subjects will receive open-label nab-paclitaxel and carboplatin during the Treatment Period of 
the study. The nab-paclitaxel and carboplatin are designated as noninvestigational products and 
investigative sites will use standard of care (commercially available) product via prescription.
The preparation for IV administration procedures should be followed as per approved 
Prescribing Information.
8.1.1.
nab-Paclitaxel
Each single-use 50 mL vial contains paclitaxel (100 mg) and approximately 900 mg human 
albumin as a stabilizer.
Unreconstituted nab-paclitaxel should be stored in accordance with the product label. 
Reconstituted nab-paclitaxel should be used immediately. If not used immediately, the vial of 
reconstituted nab-paclitaxel must be placed in its carton and be placed in a refrigerator at 2° to 
8°C (36° to 46°F) for a maximum of 8 hours. Both forms should be stored in an area free of 
environmental extremes and should be accessible only to study personnel.
Temperature records for nab-paclitaxel must be made available to Celgene or other Sponsor-
nominated monitoring teams for verification of proper study drug storage.
8.1.2.
Carboplatin
Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic
agent. The chemical name for carboplatin is platinum diammine [1,1-cyclobutane-
dicarboxylato (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 package insert. 
8.2.
Treatment Administration and Schedule
Approximately 284 subjects will be treated with nab-paclitaxel plus carboplatin until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of 
consent.
Treatment will commence on Day 1, in accordance with standard of care of first-line treatment of 
NSCLC: 
Arm A:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day treatment cycle,
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NSCLC


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!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment cycle, after 
completion of nab-paclitaxel infusion
OR
Arm B:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8 and 15 of each 
21-day treatment with one-week break cycle (ie, every 28 days),
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment with one-
week break cycle (ie, every 28 days), after completion of nab-paclitaxel infusion.
8.3.
Dose Modifications
Subjects who experience any of the adverse drug reactions in Table 4 will be dose reduced as per 
Table 4 during treatment. 
!
Do not administer nab-paclitaxel on Day 1 of a cycle until ANC is at least 
1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment 
until counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and 
platelet count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil 
count of at least 500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on 
Days 8 or 15 of the cycle. Upon resumption of dosing, permanently reduce nab-
paclitaxel and carboplatin doses as outlined in Table 4.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-
paclitaxel and carboplatin at reduced doses (Table 4) when peripheral neuropathy 
improves to Grade 1 or completely resolves.
Re-escalation is not permitted at any time. 
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Table 4:
Permanent Dose Reductions for Hematologic and Neurologic Toxicities and Dosing on the Study
Dose Modification During Treatment for A and B arms
Adverse Drug Reaction
Occurrence
nab-Paclitaxel Dose
(mg/m2)
Carboplatin Dose 
(AUC 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*
Sensory 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 twice, the subject should generally have treatment discontinued unless, at 
the discretion of the investigator, there is evidence of continuing benefit to the subject that outweighs the risk of recurrent toxicity. Re-Escalation is not 
permitted at anytime.
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8.4.
Method of Treatment Assignment
The Treatment Period of the study is open-label. Enrollment/randomization will occur via IRT 
system for all periods of the study. 
8.5.
Packaging and Labeling
nab-Paclitaxel and carboplatin are designated as noninvestigational products and investigative 
sites will use standard of care (commercially available) product via prescription.
8.6.
Study Drug Accountability and Disposal
nab-Paclitaxel and carboplatin are designated as noninvestigational products and investigative 
sites will use standard of care (commercially available) product via prescription. Procedures for 
proper handling and disposal of anticancer drug must comply with the relevant health, safety and 
environment regulations.
8.7.
Study Drug Compliance
Study drug will be administered only by study site personnel and accurate recording of all study 
drug 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 or carboplatin dosing only.
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel or carboplatin given to a subject, regardless of any associated adverse events or 
sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. See 
Section 11.1 for the reporting of adverse events associated with overdose.
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9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
Over the course of this study, additional medications may be required to manage aspects of the 
disease state of the subjects, including side effects from study treatments or disease recurrence. 
All supportive care (including but not limited to antiemetic medications, white blood cell (WBC)
growth factors, erythrocyte stimulating agents, zolendronic acid, and denosumab) is permitted
and may be administered at the discretion of the investigator, according to local guidelines. 
9.2.
Prohibited Concomitant Medications and Procedures
Other antineoplastic agents or Investigational Product than what is specified in the protocol are 
prohibited.
9.3.
Required Concomitant Medications and Procedures
Not applicable.
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10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the study are described 
below.  Additional analyses of these endpoints as well as exploratory endpoints or subgroup 
analyses will be described in detail in the SAP.  The SAP supersedes the analyses described in 
the protocol should there be differences between the two.
10.1.
Overview
Approximately 284 subjects will be randomized in a 1:1 ratio to two treatment arms (142 
subjects per group).  Arm A will receive nab-paclitaxel 100 mg/m2 administered on Days 1, 8 
and 15 followed by carboplatin AUC = 6 mg*min/mL on Day 1 of each 21-day treatment cycle. 
Arm B will receive the same treatment in the same schedule as that of Arm A during the first 21 
days of treatment, but followed by a one-week break prior to the start of next cycle (28-day 
duration). All subjects will receive the assigned study treatment until disease progression, 
unacceptable toxicity, death, lost to follow-up, or withdrawal of consent, in accordance of local 
standard of care.  A permuted-block randomization method will be employed, and the 
randomization will be carried out centrally using an IRT system. The randomization will be 
stratified based on the following 2 baseline or prognostic factors:
!
ECOG performance status (0 versus 1)
!
Histology (squamous cell carcinoma versus non-squamous cell carcinoma)
10.2.
Study Population Definitions
10.2.1.
Intent-to-treat Population
The primary efficacy analysis will be performed on the ITT population, which includes all 
randomized subjects regardless of whether the subject receives any study drug or has any 
efficacy assessments performed. 
10.2.2.
Per-protocol (PP) Population
The PP population is defined as all eligible subjects randomized who receive at least one dose of 
the study drug and have been treated in the arm they were assigned to. Additional analyses 
utilizing the PP population will be described in the SAP.
10.2.3.
Treated Population
The treated population will consist of all randomized subjects who receive at least one dose of 
study drug. The treatment groups for the safety analyses will be based on the treatment as 
received if different from the assigned treatment by randomization.
10.3.
Sample Size and Power Considerations
The primary objective of this study is to assess the safety and tolerability of nab-paclitaxel in 
combination with carboplatin administered in 21-day treatment cycles continuously or with a 
2
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one-week break in between cycles for the treatment of locally advanced or metastatic NSCLC in 
elderly subjects (≥ 70 years old). 
The primary study endpoint (also the primary safety endpoint) is the percentage of subjects with 
either peripheral neuropathy of Grade ≥2 or myelosuppression AEs of Grade ≥3 based on the 
local laboratory values for ANC, platelet count, and hemoglobin.  For the purpose of this 
protocol, this endpoint will be referred to as the percentage of subjects with Grade ≥2 peripheral 
neuropathy or Grade ≥3 myelosuppression laboratory adverse events.  
In Protocol CA031, the Phase 3 NSCLC study of the nab-paclitaxel development program, 
approximately 2% of the elderly subjects randomized discontinued from the study prior to 
receiving any study drug.  In addition, approximately 73% of the treated elderly subjects had 
AEs that fell in the category of AEs described above for the primary safety endpoint of the 
current study.  
The study is designed to detect a difference of 16 percentage points between the 2 treatment arms 
with respect to the primary safety endpoint with 80% power and a Type-I error of 5% (two-
sided), assuming the percentage of subjects with the AEs specified above is 73% for Arm A.  
Therefore, the current study is planned to randomize approximately 284 subjects to the 2 
treatment arms in a 1:1 ratio, with the expectation that approximately 278 subjects (139 per 
group) will receive at least one dose of study drug (as observed in CA031) and be included in the 
treated population for the analysis of the primary safety endpoint.
A non-binding interim analysis for futility with the primary safety endpoint will be conducted 
when approximately a total of 139 treated subjects have either completed 6 months of study 
treatment or discontinued from the study due to progression, adverse events, deaths, lost to 
follow up, or other reasons. The stopping rule and the final marginal significance level are 
determined based on the Gamma family spending function with parameter = -7 (Hwang, 1990) to
control the Type-II error rate at 20%. The study may be stopped early for futility if the treatment 
difference is between ± 0.4% (Z-score ± 0.054) given the interim analysis is performed at 50% 
information fraction.  
Progression free survival, OS, and ORR are the key efficacy endpoints of the study.  Since the 
primary research interest of this study is to evaluate the relative safety and toxicities of the 2 
treatment arms, the sample size was calculated based on the primary safety endpoint, the 
percentage of subjects with Grade ≥2 peripheral neuropathy or Grade ≥3 myelosuppression 
laboratory AEs, hence, the study is underpowered for the key efficacy endpoint, PFS, OS and 
ORR.  Consequently, a non-significant treatment difference in PFS, OS or ORR could simply be 
a function of the sample size and/or the lack of statistical power. Therefore, the assessments of 
all efficacy endpoints will be based on the point estimates and the associated 95% confidence 
intervals for the within-group parameters of interest and the between-group differences.  P-
values for between-group comparisons will be provided to indicate the strength of association 
only.  No multiplicity adjustment with the Type-I error rate will be made. 
Of note, based on the data from CA031 it is expected that approximately 67% of the 284
randomized subjects will have a PFS event during the study (ie, approximately 192 PFS events 
total).  With 192 PFS events, there is 73% power to detect a hazard ratio (HR) of 0.69 for PFS 
improvement with Arm B over Arm A and an overall Type-I error of 5% (two-sided).  Assuming 
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an exponential distribution with a median time to PFS of 5.8 months for Arm A and proportional 
hazards, a hazard ratio of 0.69 constitutes a 2.6 months improvement for Arm B.  
As an illustration for timeline projection, assuming an exponential distribution for PFS, a 24-
month recruitment period for 284 subjects, and a median PFS of approximately 5.8 months for 
Arm A, it will take approximately 28 months from the first subject randomized to observe 192 
PFS events.
The analysis of both the safety and efficacy endpoints for the clinical study report will be 
performed when approximately 192 PFS events have been observed.  No adjustment for the 
multiple treatment comparisons among the primary and secondary study endpoints will be made.  
Subjects will be followed for OS for at least 6 months after the last subject is randomized or 192 
PFS events have been observed, whichever comes later.
10.4.
Background and Demographic Characteristics
The baseline characteristics of all randomized subjects will be summarized. Subject’s age, 
height, weight, and baseline characteristics will be summarized using descriptive statistics, while 
gender, race and other categorical variables will be provided using frequency tabulations. 
Selected medical history data will be summarized using frequency tabulations by system organ 
class and preferred term.
10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both Treatment
and Follow-up Periods. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
10.6.
Safety Analysis
The treated population, which includes all randomized subjects who received at least one dose of 
study drug, will be the analysis population for all safety analyses.
The safety/tolerability of the two treatment arms will be monitored through continuous reporting 
and evaluated by the primary safety endpoint, adverse events and serious adverse events, 
abnormalities in ANC, platelet count and hemoglobin, and incidence of subjects experiencing 
dose modifications, dose interruptions, and/or premature discontinuation of study drug.
10.6.1.
Primary Safety Endpoint
The primary endpoint for this study is a composite safety endpoint, namely, the percentage of 
subjects who develop either peripheral neuropathy of Grade ≥2 or myelosuppression AEs of 
Grade ≥3 based on the local laboratory values for ANC, platelet count and hemoglobin.  The 
peripheral neuropathy events will be identified from the clinical AE dataset using the 
Standardised MedDRA Queries (SMQs). 
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The null (Ho) and alternative (Ha) hypotheses for this endpoint are as follows, where P is the rate 
of the AEs described for the primary safety endpoint: 
Ho:  P Arm B = P Arm A
Ha:  P Arm B ≠ P Arm A
The rate of the AEs described for the primary endpoint will be summarized within each 
treatment schedule by descriptive statistics. The treatment difference in the AE rate will be 
analyzed using a Mantel-Haenszel Chi-square test with ECOG performance status (0 versus 1)
and histology (squamous cell carcinoma versus non-squamous cell carcinoma) as the
stratification factors.  The ratio of the AE rates will be summarized along with the two-sided 
95% confidence interval (CI). 
10.6.2.
Adverse Events
Adverse events will be analyzed in terms of TEAEs, defined as any AE or SAE occurring or 
worsening on or after the first dose of the study drug through 28 days after the last dose of study 
drug.  In addition, any serious AE with an onset date more than 28 days after the last dose of 
study drug that is assessed by the investigator as related to study drug 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
Treatment-emergent adverse events, Grade 3 or higher TEAEs, serious AEs, TEAEs leading to
dose reduction, dose delay, and dose interruption, TEAEs leading to treatment discontinuation, 
and TEAEs with an outcome of death will be summarized per treatment arms by MedDRA 
system organ class and preferred terms.
Adverse events of special interest of the nab-paclitaxel plus carboplatin combination identified in 
previous studies in a similar population will be summarized in the same manner.
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, 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 for each treatment arm.  
All other laboratory parameters reported on the eCRFs will be summarized by descriptive 
statistics by visit and treatment if the number of subjects with data is adequate. In addition, NCI 
CTCAE v 4.0 grades for the reported parameters will be summarized, if applicable.  
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10.6.4.
Study Drug Exposure
The extent of exposure to the study drugs will be assessed based on the descriptive statistics on 
the number of cycles and study drug 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 by treatment 
arm. 
10.7.
Efficacy Analysis
10.7.1.
Key Efficacy Endpoints 
10.7.1.1.
Progression-free Survival
Progression-free survival is defined as the time from the date of randomization to the date of 
disease progression or death (any cause) on or prior to the data cutoff date for analyses, 
whichever 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 study therapy.
Subjects who do not have disease progression, or 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 randomization.
The null (Ho) and alternative (Ha) hypotheses for testing the PFS endpoint are: 
Ho: HR Arm B / Arm A = 1
Ha: HR Arm B / Arm A ≠ 1
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% CI) for each treatment schedule along with the hazard ratio 
estimated using Cox proportional hazards model (including two-sided 95% CI). The Kaplan-
Meier curve for PFS will be presented graphically for each treatment schedule.  P-value from a
stratified log-rank test will be reported as an indication for the strength of association for the 
difference between the two curves, where the strata include ECOG performance status (0 versus 
1) and histology (squamous versus non-squamous cell carcinoma), if the number of events in 
each cell is adequate.  
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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 for each treatment schedule. In addition, confirmatory and sensitivity analyses will be 
performed to further assess the impact of missed radiologic assessments. An additional analysis 
of PFS, where death or new treatment will be considered as an event, will be conducted to 
address the impact of second-line therapy. 
10.7.1.2.
Overall Survival
Overall survival is defined as the time between randomization and death. All deaths, regardless 
of the cause of death, will be included. All subjects who are lost to follow-up prior to the end of
the study or who are withdrawn from the study will be censored at the time of last contact. 
Subjects who are still receiving treatment as of the data cutoff date will be censored at the cutoff 
date. Overall survival will be analyzed similarly as PFS.
10.7.1.3.
Overall Response Rate 
Overall response rate is defined as the percent of subjects who had a radiologic complete or 
partial response according to RECIST Version 1.1 guidelines determined by the investigator and 
confirmed by repeat radiologic assessment performed no less than 28 days after the criteria for 
response were first met.  
Overall response rate for each treatment arm will be presented with the two-sided 95% CI.  
Relative treatment effect will be summarized by the difference in response rate and the 
associated two-sided 95% CI.  P-value from a Chi-square test will be reported to indicate the 
strength of association of the relative treatment effect.  
10.7.2.
Exploratory Endpoints
10.7.2.1.
Health Care Utilization and Quality of Life Questionnaire
The analysis of health care utilization and quality of life questionnaire data will be described in 
detail in the SAP.
 
10.8.
Study Therapy Termination
Reasons for stopping study therapy will be presented in listings and summarized by frequency of 
occurrence and corresponding percentage of occurrence.
10.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the study 
drug through 28 days post last dose of the study drug) 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).
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10.10.
Interim Analysis
A non-binding interim analysis for futility with the primary safety endpoint will be conducted 
when approximately a total of 139 treated subjects have either completed 6 months of study 
treatment or discontinued from the study due to progression, adverse events, deaths, lost to 
follow up, or other reasons. The stopping rule and the final marginal significance level are 
determined based on the Gamma family spending function with parameter = -7 (Hwang, 1990) to 
control the Type-II error rate at 20%. The study may be stopped early for futility if the treatment 
difference is between ± 0.4% (Z-score ± 0.054) given the interim analysis is performed at 50% 
information fraction.
10.11.
Scientific Steering Committee
The conduct of this study will be overseen by a Steering Committee. The Steering Committee 
will serve in an advisory capacity to the Sponsor. 
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11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the eCRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of NSCLC will not require reporting as 
an adverse event.
An overdose, accidental or intentional, whether or not it is associated with an AE, or abuse, 
withdrawal, sensitivity or toxicity to a study drug should be reported as an AE. If an overdose is 
associated with an AE, the overdose and adverse event should be reported as separate terms. See 
Section 8.8 for the definition of overdose.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for nab-paclitaxel, or 
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 
appropriate tests and procedures.
All AEs will be recorded by the investigator from the time the subject signs informed consent to
28 days after the last dose of study drug, and those SAEs made known to the investigator at any 
time thereafter that are suspected of being related to study drug. AEs and serious adverse events 
(SAEs) will be recorded on the AE page of the eCRF and in the subject’s source documents. All 
SAEs must be reported to Celgene Drug Safety within 24 hours of the investigator’s knowledge 
of the event by facsimile, or other appropriate method, using the SAE Report Form, or approved 
equivalent form.
11.2.
Evaluation of Adverse Events
A qualified investigator will evaluate all adverse events as to: 
11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
!
Results in death;
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!
Is life-threatening (ie, in the opinion of the investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the eCRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of or an elective procedure for a pre-existing condition 
unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
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For each SAE, the investigator will provide information on severity, start and stop dates, 
relationship to study drug, action taken regarding study drug, 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 National Cancer Institute (NCI) Common Terminology Criteria 
for Adverse Events (CTCAE, Version 4.0)
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Adverse events that are not defined in the NCI CTCAE should be evaluated for severity/intensity 
according to the following scale:
!
Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required
!
Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required
!
Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible
!
Grade 4 = Life threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable
!
Grade 5 = Death – the event results in death
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.
Seriousness, not severity, serves as a guide for defining regulatory obligations.
11.2.3.
Causality 
The investigator must determine the relationship between the administration of study drug 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 study drug
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 study drug caused the adverse event.  ‘Reasonable 
possibility’ means there is evidence to suggest a causal 
relationship between the study drug and the adverse event.
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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 study 
drug 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 study drug as a result of an AE or SAE, as 
applicable (eg, discontinuation or reduction of study drug, as appropriate) and report if 
concomitant and/or additional treatments were given for the event. 
11.2.6.
Outcome
The investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered or death (due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of study drug dose, or any other 
therapeutic intervention; or
!
is judged to be of significant clinical importance.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF. If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE.
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
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11.4.1.
Female Subjects
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 study drug, or within 3 months 
of the subject’s last dose of study drug, are considered immediately reportable events. Study drug
is to be discontinued immediately. The pregnancy, suspected pregnancy, or positive pregnancy 
test must be reported to Celgene Drug Safety immediately by facsimile, or other appropriate 
method, using the Pregnancy Initial Report Form, or approved equivalent form. The female 
subject should be referred to an obstetrician-gynecologist or another appropriate healthcare 
professional for further evaluation.
The investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the investigator
should report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate 
method, within 24 hours of the investigator’s knowledge of the event using the SAE Report 
Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the investigator suspects is 
related to the in utero exposure to the study drug should also be reported to Celgene Drug Safety 
by facsimile, or other appropriate method, within 24 hours of the investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving study drug
or within 3 months of the last dose of study drug, the male subject taking study drug should 
notify the investigator, and the pregnant female partner should be advised to call her healthcare 
provider immediately. If the male subject is receiving study drug, the study drug may need to be 
discontinued in the male subject, but may be resumed later at the discretion of the investigator
and medical monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The investigator is required to ensure that the data on these forms is accurate and consistent. This 
requirement applies to all SAEs (regardless of relationship to study drug) that occur during the 
study (from the time the subject signs informed consent to at least 28 days after the last dose of
study drug) and those made known to the investigator at anytime thereafter that are suspected of 
being related to study drug. SAEs occurring prior to treatment (after signing the ICF) will be 
captured.
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The SAE report should provide a detailed description of the SAE and include a concise summary
of hospital records and other relevant documents. If a subject died and an autopsy has been 
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available. Any follow-up data will be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety.
Where required by local legislation, the investigator is responsible for informing the Independent 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The investigator must keep copies of all SAE 
information on file including correspondence with Celgene and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than five (5) business 
days. Urgent queries (eg, missing causality assessment) may be handled by phone.
11.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to nab-paclitaxel 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 study drug in this study or in other 
studies that is both serious and unexpected (ie, SUSAR);
!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
The investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC. (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form/Completion Guidelines or to the Pregnancy Report Form/Completion Guidelines.
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12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the study 
drug:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent
!
Death
!
Lost to follow-up
!
Protocol violation
Prior to discontinuing a subject for disease progression, the investigator should contact and 
forward appropriate supporting documents to the Medical Monitor.
All subjects discontinued from study drug for any reason will have a treatment discontinuation 
visit at the time of discontinuation and should undergo treatment discontinuation procedures.
All subjects discontinued from nab-paclitaxel will be followed for a period of 28 days after last
dose of study drug for the collection of AEs.
Additionally subjects who withdraw from or discontinue treatment should be followed for 
progressive disease (if applicable), survival and any new anticancer therapy given.
The reason for treatment discontinuation should be recorded in the eCRF and in the source 
documents.
12.2.
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
study:
!
Withdrawal of consent
!
Death
!
Lost to follow-up
The following events may be considered sufficient reasons for discontinuing a subject from the 
study:
!
Adverse events(s)
!
Protocol violation
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. The investigator must notify the Medical Monitor immediately when a subject has 
been discontinued/withdrawn due to an AE (any unacceptable toxicity). All subjects who are 
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withdrawn from the study should complete all protocol-required evaluations scheduled for early 
termination at the time of withdrawal.
Since follow-up of subjects who discontinue prematurely is of particular importance, every 
attempt should be made to collect all survival information and NSCLC treatment/therapy, unless 
the subject has specifically withdrawn consent from further follow-up. The investigator must 
make every effort to obtain minimal information regarding the subject’s survival status before 
determining that the subject is lost to follow-up.
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.
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13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the investigator should contact the responsible Clinical Research
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page).This global Emergency 
Call Center is available 24 hours a day and 7 days a week. The representatives are responsible 
for obtaining your call-back information and contacting the on call Celgene/Contract Research 
Organization (CRO) Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
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14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative,
and investigator abide by Good Clinical Practice (GCP), as described in International Conference 
on Harmonization (ICH) Guideline E6 and in accordance with the general ethical principles 
outlined in the Declaration of Helsinki. The study will receive approval from an IRB/EC prior to 
commencement. The investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. Celgene staff or an authorized representative will evaluate and approve all 
investigators who in turn will select their staff.
The investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions. 
The investigator should maintain a list of sub-investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The investigator is responsible for keeping a record of all subjects who sign an ICF and are 
screened for entry into the study. Subjects who fail screening must have the reason(s) recorded in 
the subject’s source documents.
The investigator, or a designated member of the investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The investigator must ensure timely and accurate completion of eCRFs and queries.
14.3.
Subject Information and Informed Consent
The investigator must obtain informed consent of a legal representative prior to any study related 
procedures.
Documentation that informed consent occurred prior to the subject’s entry into the study and of 
the informed consent process should be recorded in the subject’s source documents including the 
date. The original ICF signed and dated by the subject and by the person consenting the subject 
prior to the subject’s entry into the study, must be maintained in the investigator’s study files and 
a copy given to the subject. In addition, if a protocol is amended and it impacts the content of the 
informed consent, the ICF must be revised. Subjects participating in the study when the amended 
protocol is implemented must be re-consented with the revised version of the ICF. The revised
ICF signed and dated by the subject and by the person consenting the subject must be maintained 
in the investigator’s study files and a copy given to the subject.
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14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
This documentation must also include a list of the members of the IRB/EC and their occupation 
and qualifications. If the IRB/EC will not disclose the names, occupations and qualifications of 
the committee members, it should be asked to issue a statement confirming that the composition 
of the committee is in accordance with GCP. For example, the IRB General Assurance Number 
may be accepted as a substitute for this list. Formal approval by the IRB/EC should mention the 
protocol title, number, amendment number (if applicable), study site (or region or area of 
jurisdiction, as applicable), and any other documents reviewed. It must mention the date on 
which the decision was made and must be officially signed by a committee member. Before the 
first subject is enrolled in the study, all ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
The investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a coordinating investigator and the IRB/EC. This statement also applies to any 
communication between the investigator (or coordinating investigator, if applicable) and 
regulatory authorities.
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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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15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The investigator must ensure that the records and documents pertaining to the conduct of the 
study and distribution of the study drug 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 eCRFs or CD-ROM.
15.2.
Data Management
Data will be 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 study drug. The investigator must retain 
these documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the investigator, Celgene, and their authorized 
representative(s);
!
List of sub-investigators and other appropriately qualified persons to whom the 
investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of eCRFs (if paper) and of documentation of corrections for all subjects;
!
Study drug accountability records;
!
Record of any body fluids or tissue samples retained;
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!
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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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, eCRFs, procedures for obtaining informed 
consent, record keeping, and reporting of AEs/SAEs with the investigator. Monitoring will 
include on-site visits with the investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, 
eCRFs, subject’s source documents, and all other study documentation will be
inspected/reviewed by the Celgene representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the eCRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the investigator and/or his/her staff. Any necessary 
corrections will be made directly to the eCRFs or via queries by the investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene. Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The investigator is required to permit direct access to the facilities where the study took place, 
source documents, eCRFs and applicable supporting records of subject participation for audits 
and inspections by IRB/IECs, regulatory authorities (eg, FDA, European Medicines Agency 
[EMA], Health Canada) and company authorized representatives. The investigator should make 
every effort to be available for the audits and/or inspections. If the investigator is contacted by 
any regulatory authority regarding an inspection, he/she should contact Celgene immediately.
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17.
PUBLICATIONS
The results of this study may be published in a medical publication, journal, or may be used for 
teaching purposes. Additionally, this study and its results may be submitted for inclusion in all 
appropriate health authority study registries, as well as publication on health authority study 
registry websites, as required by local health authority regulations. Selection of first authorship 
will be based on several considerations, including, but not limited to study participation, 
contribution to the protocol development, and analysis and input into the manuscript, related 
abstracts, and presentations in a study.


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18.
REFERENCES
Azzoli CG, Baker Jr. S, Temin S, Pao W, Aliff T, Brahmer J, et al. American Society of Clinical 
Oncology clinical practice guideline update on chemotherapy for Stage IV non-small-cell lung 
cancer. J Clin Oncol. 2009;27:6251-66.
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;26:468-73.
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.
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.
Hwang IK, Shih WJ, De Cani JS. Group sequential designs using a family of type I error
probability spending functions. Stat Med. 1990;9:1439-1445.
Lorenz W, Reimann HJ, Schmal A, Dormann P, Schwarz B, Neugebauer E, et al. Histamine 
release in dogs by Cremophor El and its derivatives: oxethylated oleic acid is the most effective 
constituent. Agents Actions 1977;7:63-7.
National Institute for Health & Clinical Excellence (NICE): The Diagnosis and Treatment of 
Lung Cancer: Methods, Evidence & Guidance, 2011.
Oken, MM, Creech, RH, Tormey, DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and 
Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol. 
1982;5(6):649-55.
Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, et al. Intergroupe Francophone 
de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared 
with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 
randomised, phase 3 trial. Lancet. 2011;378(9796):1079-88. 
Rizvi NA, Riely GJ, Azzoli CG, Miller VA, Ng KK, Fiore J, et al. Phase I/II trial of weekly 
intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with Stage IV 
non-small-cell lung cancer. J Clin Oncol. 2008;26(4):639-43.
Schiller JH, Gandara DR, Goss GD, Vokes EE.  Non-small-cell lung cancer: then and now. 
J Clin Oncol. 2013;31(8):981-3.
Socinski MA, Langer CJ, Okamoto I, Hon JK, Hirsh V, Dakhil SR, et al. Safety and efficacy of 
weekly nab®-paclitaxel in combination with carboplatin as first-line therapy in elderly patients 
with advanced non-small-cell lung cancer. Ann Oncol. 2013;24(2):314-21. 
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Socinski MA, Manikhas GM, Stroyakovsky DL, Makhson AN, Cheporov SV, Orlov SV, et al. A 
dose finding study of weekly and every-3-week nab-paclitaxel followed by carboplatin as 
first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol. 
2010;5(6):852-61.
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. 
Review.
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.
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19.
APPENDICES
Appendix A: Response Evaluation Criteria in Solid Tumors (RECIST), 
Version 1.1
Eligibility
!
Only subjects with measurable disease at baseline should be included in protocols 
where objective tumor response is the primary endpoint. 
∀
Measurable disease - the presence of at least one measurable lesion. If the 
measurable disease is restricted to a solitary lesion, its neoplastic nature should be 
confirmed by cytology/histology. 
∀
Measurable lesions - lesions that can be accurately measured in at least one 
dimension with a minimum size of: 10 mm by CT scan, 10 mm caliper 
measurement by clinical exam, 20 mm by chest X-ray.
∀
Non-measurable lesions - all other lesions, including small lesions (longest 
diameter < 10 mm or pathological lymph nodes with ≥10 mm to < 15 mm short 
axis) as well as truly non-measurable lesions ie, leptomeningeal disease, ascites, 
pleural/pericardial effusion, inflammatory breast disease, lymphangitis
involvement of skin or lung, abdominal masses/abdominal organomegaly 
identified by physical exam that is not measurable by reproducible imaging 
techniques.
!
All measurements should be taken and recorded in metric notation, using a ruler or 
calipers. All baseline evaluations should be performed as closely as possible to the 
beginning of treatment and never more than 28 days before the beginning of the 
treatment. 
!
The same method of assessment and the same technique should be used to 
characterize each identified and reported lesion at baseline and during follow-up. 
!
Clinical lesions will only be considered measurable when they are superficial (eg, 
skin nodules and palpable lymph nodes). For the case of skin lesions, documentation 
by color photography, including a ruler to estimate the size of the lesion, is 
recommended. 
Methods of Measurement 
!
CT and MRI are the best currently available and reproducible methods to measure 
target lesions selected for response assessment. Conventional CT and MRI should be 
performed with cuts of 10 mm or less in slice thickness contiguously. Spiral CT 
should be performed using a 5 mm contiguous reconstruction algorithm. This applies 
to tumors of the chest, abdomen and pelvis. Head and neck tumors and those of 
extremities usually require specific protocols.
!
Lesions on chest X-ray are acceptable as measurable lesions when they are clearly 
defined and surrounded by aerated lung. However, CT is preferable. 
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!
When the primary endpoint of the study is objective response evaluation, ultrasound 
should not be used to measure tumor lesions. It is, however, a possible alternative to 
clinical measurements of superficial palpable lymph nodes, subcutaneous lesions and 
thyroid nodules. Ultrasound might also be useful to confirm the complete 
disappearance of superficial lesions usually assessed by clinical examination.
!
The utilization of endoscopy and laparoscopy for objective tumor evaluation has not 
yet been fully and widely validated. Their uses in this specific context require 
sophisticated equipment and a high level of expertise that may only be available in 
some centers. Therefore, the utilization of such techniques for objective tumor 
response should be restricted to validation purposes in specialized centers. However, 
such techniques can be useful in confirming complete pathological response when 
biopsies are obtained.
!
Tumor markers alone cannot be used to assess response. If markers are initially above 
the upper normal limit, they must normalize for a subject to be considered in 
complete clinical response when all lesions have disappeared.
!
Cytology and histology can be used to differentiate between PR and CR in rare cases 
(eg, after treatment to differentiate between residual benign lesions and residual 
malignant lesions in tumor types such as germ cell tumors).
Baseline Documentation of “Target” and “Nontarget” Lesions
!
All measurable lesions up to a maximum of two lesions per organ and five lesions in 
total, representative of all involved organs should be identified as target lesions and
recorded and measured at baseline. 
!
Target lesions should be selected on the basis of their size (lesions with the longest 
diameter) and their suitability for accurate repeated measurements (either by imaging 
techniques or clinically). 
!
A sum of the longest diameter (LD) for all target lesions will be calculated and 
reported as the baseline sum LD. The baseline sum LD will be used as reference by 
which to characterize the objective tumor.
!
All other lesions (or sites of disease) should be identified as nontarget lesions and 
should also be recorded at baseline. Measurements of these lesions are not required, 
but the presence or absence of each should be noted throughout follow-up.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
70
ABI-007-NSCL-005 Final: 06 Mar 2014
Response Criteria
Table 5:
Evaluation of Target Lesions
Response
Criteria
Complete Response (CR):
Disappearance of all target lesions
Partial Response (PR):
At least a 30% decrease in the sum of the LD of target lesions, taking as 
reference the baseline sum LD
Progressive Disease (PD):
At least a 20% increase in the sum of diameters of target lesions, taking as 
reference the smallest sum on study (including baseline), in addition sum 
must demonstrate an absolute increase of at least 5 mm, or the appearance 
of one or more new lesions
Stable Disease (SD):
Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on 
study
Table 6:
Evaluation of Non-Target Lesions
Response
Criteria
Complete Response (CR):
Disappearance of all non-target lesions and normalization of tumor marker 
level
Incomplete Response/
Stable Disease (SD): 
Persistence of one or more non-target lesion(s) or/and maintenance of 
tumor marker level above the normal limits
Progressive Disease (PD):
Appearance of one or more new lesions and/or unequivocal progression of 
existing non-target lesionsa
a Although a clear progression of “nontarget” lesions only is exceptional, in such circumstances, the opinion of the 
treating physician should prevail and the progression status should be confirmed later on by the review panel (or 
study chair).
Evaluation of Best Overall Response
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for PD the smallest measurements recorded 
since the treatment started). In general, the subject's best response assignment will depend on the 
achievement of both measurement and confirmation criteria.
Target Lesions
Non-Target Lesions
New Lesions
Overall Response
CR
CR
No
CR
CR
Incomplete response/SD
No
PR
PR
Non-PD
No
PR
SD
Non-PD
No
SD
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
71
ABI-007-NSCL-005 Final: 06 Mar 2014
!
Subjects with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time should be 
classified as having “symptomatic deterioration”. Every effort should be made to 
document the objective progression even after discontinuation of treatment. 
!
In some circumstances it may be difficult to distinguish residual disease from normal
tissue. When the evaluation of complete response depends on this determination, it is 
recommended that the residual lesion be investigated (fine needle aspirate/biopsy) to 
confirm the complete response status.
Confirmation
!
The main goal of confirmation of objective response is to avoid overestimating the 
response rate observed. In cases where confirmation of response is not feasible, it 
should be made clear when reporting the outcome of such studies that the responses 
are not confirmed.
!
To be assigned a status of PR or CR, changes in tumor measurements must be 
confirmed by repeat assessments that should be performed no less than 28 days after 
the criteria for response are first met. Longer intervals as determined by the study 
protocol may also be appropriate. 
!
In the case of SD, follow-up measurements must have met the SD criteria at least 
once after study entry at a minimum interval (in general, not less than 6-8 weeks) that 
is defined in the study protocol.
Duration of Overall Response
!
The duration of overall response is measured from the time measurement criteria are 
met for CR or PR (whichever status is recorded first) until the first date that 
recurrence or PD is objectively documented, taking as reference for PD the smallest 
measurements recorded since the treatment started.
Duration of Stable Disease
!
SD is measured from the start of the treatment until the criteria for disease 
progression are met, taking as reference the smallest measurements recorded since the 
treatment started. 
!
The clinical relevance of the duration of SD varies for different tumor types and 
grades. Therefore, it is highly recommended that the protocol specify the minimal 
time interval required between two measurements for determination of SD. This time 
interval should take into account the expected clinical benefit that such a status may 
bring to the population under study. 
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
72
ABI-007-NSCL-005 Final: 06 Mar 2014
Appendix B: ECOG Performance Status Score
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5
Dead
Oken, 1982.
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Celgene Signing Page
This is a representation of an electronic record that was signed electronically in Livelink.
This page is the manifestation of the electronic signature(s) used in compliance with
the organizations electronic signature policies and procedures.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
TITLE PAGE
SAFETY AND EFFICACY OF nab®-PACLITAXEL 
(ABRAXANE®) IN COMBINATION WITH 
CARBOPLATIN AS FIRST LINE TREATMENT IN 
ELDERLY SUBJECTS WITH ADVANCED NON-SMALL 
CELL LUNG CANCER (NSCLC): A PHASE IV, 
RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY
(ABOUND.70+)
STUDY DRUG
nab®-paclitaxel (Abraxane®)
PROTOCOL NUMBER:
ABI-007-NSCL-005
ORIGINAL DATE FINAL:
06 Mar 2014
AMENDMENT 1 DATE FINAL:
09 Apr 2014
AMENDMENT 2 DATE FINAL:
05 Dec 2014
AMENDMENT 3 DATE FINAL:
17 Mar 2016
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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05 Dec
De
17
17 M
ou, your staff
ou, your staff
document is
cument 
may 
ma
Per
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(
1(
(/
(/


('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
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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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:
 
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
PROTOCOL SUMMARY
Study Title
Safety and efficacy of nab®-paclitaxel1 (Abraxane®) in combination with carboplatin as first line 
treatment in elderly subjects with advanced non-small cell lung cancer (NSCLC): A Phase IV, 
randomized, open-label, multicenter study (Abound.70+).
Indication
First-line treatment of advanced NSCLC in elderly subjects.
Objectives
Primary
!
To assess the safety and tolerability of continuous weekly versus weekly times three 
with one-week break nab-paclitaxel (Abraxane) in combination with carboplatin as 
first-line treatment for advanced NSCLC in elderly subjects (≥ 70 years old).
Secondary 
!
To evaluate the efficacy of nab-paclitaxel in combination with carboplatin in elderly 
subjects with advanced NSCLC.
Exploratory 
!
To assess healthcare resource utilization for the two nab-paclitaxel treatment arms.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ-5D) for the two nab-paclitaxel treatment arms.
!
 
 
!
 
Study Design
This is a Phase IV, randomized, open-label, multicenter study of continuous weekly versus 
weekly times three with one-week break nab-paclitaxel in combination with carboplatin as first-
line treatment in elderly subjects (≥ 70 years old) with advanced NSCLC who are not candidates 
for curative surgery or radiation therapy. Approximately 284 subjects with locally advanced or 
metastatic NSCLC will be randomized in this study to receive nab-paclitaxel in combination 
with carboplatin and will be randomized 1:1 into one of the two treatment arms prior to starting 
first dose of study drug. Randomization will be centralized and stratified by Eastern Cooperative 
Oncology Group (ECOG) performance status (0 versus 1, see Appendix A) and histology 
(squamous cell carcinoma versus non-squamous cell carcinoma).
The study will consist of a 28-day Screening Period, a Treatment Period, and a Follow-up 
Period.  
1 nab® is a registered trademark of Celgene Corporation.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of study drug.
The Treatment Period begins with the first dose of study drug as described in Section 8.  Subjects 
will receive one of the following treatments based on the randomization assignment:
Arm A (21-day treatment cycle):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment cycle,
!
Carboplatin area under the curve (AUC) = 6 mg*min/mL IV on Day 1 of each 21-day 
treatment cycle after completion of nab-paclitaxel infusion.
Arm B (21-day treatment followed by one-week break cycle, 28-day duration):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment  followed by one-week break cycle (i.e. every 28 
days),
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment followed by 
one-week break cycle (i.e. every 28 days), after completion of nab-paclitaxel 
infusion. 
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of 
consent, in accordance with local standard of care.
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
(v1.1) (Eisenhauer, 2009).
Local laboratory test data for absolute neutrophil count (ANC), platelet count, hemoglobin and 
serum creatinine will be collected in the electronic case report forms (eCRFs). All other 
laboratory test data, except those mentioned above, will not be collected routinely in the eCRF. 
All abnormal and clinically significant laboratory test results will be reported as adverse events 
(AEs) or serious adverse events (SAEs), and the specific associated laboratory parameter(s) 
should be recorded on the laboratory assessments eCRF. Local safety laboratory data will also be 
the primary guide for eligibility and subject management. In addition, test results for tumor 
mutational status of genes including but not limited to EGFR, ALK, and KRAS will be collected 
and recorded on eCRF if these tests have been performed locally for routine diagnosis.  
All subjects who discontinue from treatment for any reason other than withdrawal of consent or 
lost to follow-up will enter the Follow-up Period. It will consist of a visit 28 days after treatment 
discontinuation. Thereafter, subjects will be followed for survival approximately every 90 days 
(or when they are seen for routine care) by phone call or chart review for documentation of last 
contact for up to 6 months after the last subject is randomized or 192 progression-free survival 
(PFS) events have been observed, whichever comes later.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
Those subjects entering the Follow-up Period without documented progression will continue to 
have computed tomography (CT) scans in accordance with standard of care (at least every 90 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death or 
study closure. 
Study Population
Male and female subjects ≥ 70 years of age, with locally advanced or metastatic NSCLC 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.
Length of Study
The enrollment of 284 subjects on this study will take approximately 24 months. The total length 
of this Phase IV study with follow-up is estimated to be approximately 3 years.  
Study Treatments
Investigative sites will use standard of care (commercially available) product via prescription for 
nab-paclitaxel and carboplatin.
The preparation for IV administration procedures for nab-paclitaxel and carboplatin should be 
followed in accordance with the approved Prescribing Information for each drug.
Statistical Methods
Approximately 284 subjects will be randomized in a 1:1 ratio to one of two treatment arms 
(approximately 142 per arm).  Arm A will receive nab-paclitaxel 100 mg/m2 administered on 
Days 1, 8 and 15 in combination with carboplatin AUC = 6 mg*min/mL on Day 1 of each 21-
day treatment cycle, and Arm B will receive the same treatment in the same schedule as that of 
Arm A during the first 21 days, followed by a one-week break prior to the start of the next cycle
(28-day duration).  
Randomization will be stratified by ECOG performance status (0 versus 1) and histology 
(squamous cell carcinoma versus non-squamous cell carcinoma).  
The primary objective of this study is to assess the safety and tolerability of the two treatment 
arms for first-line treatment of locally advanced or metastatic NSCLC in elderly subjects ( ≥ 70 
years old).  The primary study endpoint, correspondingly, is the percentage of subjects with 
either peripheral neuropathy of Grade ≥ 2 or myelosuppression AEs Grade ≥ 3 based on the local 
laboratory values for ANC, platelet count, and hemoglobin, assessed using National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4.0). 
The peripheral neuropathy events will be identified from the clinical AE dataset using the 
Standardised MedDRA Queries (SMQs). For the purpose of this protocol, this endpoint will be 
referred to as the percentage of subjects with Grade ≥ 2 peripheral neuropathy or Grade ≥3 
myelosuppression laboratory adverse events.  
The study is designed to detect a difference of 16 percentage points between the 2 treatment arms 
with respect to the primary safety endpoint with 80% power and a Type-I error rate of 5% (two-
sided), assuming 139 of the 142 randomized subjects per arm will receive at least one dose of 
study drug and the percentage of the treated subjects with the AEs specified above is 73% for 
Arm A. 
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
9
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
A non-binding interim evaluation of dosing, primary safety endpoint, and efficacy data will be
conducted when approximately a total of 120 treated subjects have either completed 4 months of 
study treatment or discontinued study treatment due to progression, adverse events, deaths, lost 
to follow up, or other reasons. The Scientific Steering Committee (SSC) may recommend to stop 
the study early based on the study dosing data in relation to the primary hypothesis; or meeting 
of the futility criterion of the primary endpoint if the treatment difference (Arm B minus Arm A)
is ≥-0.2%, given the interim analysis of this endpoint is performed at 43% information fraction;
or the totality of the dosing, safety, and efficacy data as well as clinical significance.
Overview of Safety Assessment
The treated population, which includes all randomized subjects who received at least one dose of 
study drug, will be the analysis population for all safety analyses.  
The primary study endpoint (a composite safety endpoint) will be the percentage of subjects with 
Grade ≥ 2 peripheral neuropathy or Grade ≥ 3 myelosuppression laboratory adverse events.  
The null (Ho) and alternative (Ha) hypotheses for this endpoint are as follows, where P is the rate 
of the AEs described for the primary safety endpoint: 
Ho:  P Arm B = P Arm A
Ha:  P Arm B ≠ P Arm A
The AE rate of the primary study endpoint will be summarized within each treatment arm by 
descriptive statistics.  The treatment difference in the AE rate will be analyzed using a Mantel-
Haenszel Chi-square test with ECOG performance status (0 versus 1) and histology (squamous 
cell carcinoma versus non-squamous cell carcinoma) as the stratification factors.  The ratio of the 
AE rates will be summarized along with the two-sided 95% confidence interval (CI). 
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AE or SAE that begins or worsens in grade on or after the start of the study drug
through 28 days after the last dose of the study drug. Additionally, any SAE that occurs beyond 
this period of observation and is assessed by the investigator as related to the study drug, will be 
reported and analyzed.  
Treatment-emergent adverse events will be summarized by treatment arm by system organ class 
and preferred term. Grade 3 or higher TEAEs, SAEs, TEAEs leading to dose modification 
(reduction, delay not given, and interruption), TEAEs leading to treatment discontinuation, and 
TEAEs with an outcome of death will be summarized by treatment arm. Adverse events of 
special interest of the nab-paclitaxel and carboplatin combination identified in previous studies 
in a similar population will be summarized in the same manner. 
Laboratory parameters regularly collected on the eCRFs (ANC, platelets, hemoglobin, and serum 
creatinine) will be summarized by descriptive statistics by visit and treatment if the number of 
subjects with data is adequate.
Overview of Efficacy Assessment
All efficacy analyses will be based on the intent-to-treat (ITT) population, which includes all 
randomized subjects regardless of whether they receive any study drugs or have any efficacy 
assessments performed.  
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
10
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
Progression-free Survival (PFS) based on investigator’s assessment of the subject’s radiologic 
response using RECIST v1.1 guidelines, Overall Response Rate (ORR), and Overall Survival 
(OS) are the efficacy endpoints.  Since the primary research interest of this study is to evaluate 
the relative safety and toxicities of the two treatment arms, the sample size was calculated based 
on the primary safety endpoint, the percentage of subjects with Grade ≥ 2 peripheral neuropathy 
or Grade ≥ 3 myelosuppression laboratory adverse events.  Consequently, a statistically non-
significant treatment difference in PFS, ORR or OS could simply be a function of the sample 
size and/or the lack of statistical power. Therefore, the assessments of treatment differences in 
PFS and OS will be based on the hazard ratios and in ORR, the ratio of response rates, and the 
corresponding 95% confidence intervals. P-values for between-group comparisons will be 
provided to indicate the strength of association only.  No multiplicity adjustment with the Type-I 
error rate will be made. 
Progression-free survival is defined as the time from the randomization date to the start of 
disease progression or subject death from any cause, whichever occurs first. Subjects who do not 
have disease progression or have not died as of the data cutoff date for the statistical analysis will 
be censored at the time of the last radiologic assessment prior to the data cutoff date. Rules for 
censoring for missing visits and start of anticancer treatment are provided in Section 10. 
Progression-free survival will be summarized using the Kaplan-Meier method and by median 
PFS time (including two-sided 95% confidence interval [CI]) for each treatment arm along with 
the hazard ratio (including two-sided 95% CI) between treatment arms. The Kaplan-Meier curve 
for PFS will be presented graphically for each treatment arm. To illustrate the strength of 
association, the p-value for treatment difference in the curves will be reported from a stratified 
log-rank test with ECOG performance status (0 versus 1) and histology (squamous versus non-
squamous cell carcinoma) as the stratification factors.  
Of note, if recruitment is complete in 24 months, assuming that approximately 67% of the 284 
subjects randomized will experience a PFS event (approximately 192 PFS events total) within 28 
months from first subject randomized, there is 73% power to detect a hazard ratio (HR) of 0.69 
for PFS improvement with Arm B over Arm A and an overall Type-I error rate of 5% (two-
sided).  Assuming an exponential distribution with a median time to PFS of 5.8 months for Arm 
A and proportional hazards, a hazard ratio of 0.69 constitutes a 2.6 months improvement for Arm 
B. 
Overall response rate (percent of subjects who had a radiologic complete or partial response 
according to the investigator’s assessment of response based on RECIST v1.1 guidelines) and 
OS also will be assessed by descriptive statistics with the associated 95% CIs.  P-values from a 
Chi-square test and a stratified log-rank test will be provided to indicate the strength of 
association for the treatment differences in ORR and OS, respectively.  
The analyses of the safety and efficacy endpoints for the clinical study report will be performed 
after ~192 PFS events have been observed.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
11
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
1.
INTRODUCTION..................................................................................................18
1.1.
Non-small Cell Lung Cancer ..................................................................................18
1.2.
nab-Paclitaxel in NSCLC .......................................................................................19
1.3.
Rationale for Further Study of nab-Paclitaxel as First-line Treatment in 
Elderly Subjects with Advanced NSCLC................................................................20
2.
STUDY OBJECTIVES...........................................................................................22
2.1.
Primary Objectives .................................................................................................22
2.2.
Secondary Objective...............................................................................................22
2.3.
Exploratory Objectives ...........................................................................................22
3.
STUDY ENDPOINTS............................................................................................23
3.1.
Primary Endpoint....................................................................................................23
3.2.
Secondary Endpoints ..............................................................................................23
3.2.1.
Safety.....................................................................................................................23
3.2.2.
Efficacy..................................................................................................................23
3.3.
Exploratory Endpoints............................................................................................23
4.
OVERALL STUDY DESIGN ................................................................................24
4.1.
Study Design ..........................................................................................................24
4.1.1.
Follow-up Period....................................................................................................25
4.2.
Study Design Rationale ..........................................................................................25
4.3.
Study Duration .......................................................................................................27
4.4.
End of Trial ............................................................................................................27
5.
TABLE OF EVENTS.............................................................................................28
6.
PROCEDURES......................................................................................................31
6.1.
Medical History......................................................................................................31
6.2.
Prior and Concomitant Medications/Procedures......................................................31
6.3.
Computed Tomography (CT) Scan of Complete Chest (including base of 
neck and adrenal glands).........................................................................................31
6.4.
Weight....................................................................................................................32
6.5.
Body Surface Area (BSA) Calculation and Height..................................................32
6.6.
ECOG Performance Score ......................................................................................32
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4


('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
12
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
6.7.
Peripheral Neuropathy Assessment.........................................................................32
6.8.
Adverse Event Reporting........................................................................................32
6.9.
Lung Cancer Symptom Scale Questionnaire and EQ-5D.........................................32
6.10.
Healthcare Resource Utilization Questionnaire .......................................................32
6.11.
Electrocardiogram ..................................................................................................33
6.12.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI) .......................33
6.13.
Bone Scans and X-rays...........................................................................................33
6.14.
Physical Examinations............................................................................................33
6.15.
Vital Signs..............................................................................................................33
6.16.
Laboratory Assessments .........................................................................................33
6.17.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) .....................................................................................34
6.18.
Survival..................................................................................................................34
7.
STUDY POPULATION.........................................................................................35
7.1.
Number of Subjects and Sites .................................................................................35
7.2.
Inclusion Criteria....................................................................................................35
7.3.
Exclusion Criteria...................................................................................................36
8.
DESCRIPTION OF STUDY TREATMENTS........................................................38
8.1.
Description of Study Drug(s)..................................................................................38
8.1.1.
nab-Paclitaxel.........................................................................................................38
8.1.2.
Carboplatin.............................................................................................................38
8.2.
Treatment Administration and Schedule .................................................................38
8.3.
Dose Modifications.................................................................................................39
8.4.
Method of Treatment Assignment...........................................................................41
8.5.
Packaging and Labeling..........................................................................................41
8.6.
Study Drug Accountability and Disposal ................................................................41
8.7.
Study Drug Compliance..........................................................................................41
8.8.
Overdose ................................................................................................................41
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................42
9.1.
Permitted Concomitant Medications and Procedures...............................................42
9.2.
Prohibited Concomitant Medications and Procedures..............................................42
9.3.
Required Concomitant Medications and Procedures................................................42
10.
STATISTICAL ANALYSES..................................................................................43
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9.1


('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
13
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
10.1.
Overview................................................................................................................43
10.2.
Study Population Definitions ..................................................................................43
10.2.1.
Intent-to-treat Population........................................................................................43
10.2.2.
Per-protocol (PP) Population ..................................................................................43
10.2.3.
Treated Population..................................................................................................43
10.3.
Sample Size and Power Considerations...................................................................43
10.4.
Background and Demographic Characteristics........................................................45
10.5.
Subject Disposition.................................................................................................45
10.6.
Safety Analysis.......................................................................................................45
10.6.1.
Primary Safety Endpoint.........................................................................................45
10.6.2.
Adverse Events.......................................................................................................46
10.6.3.
Laboratory Assessments .........................................................................................46
10.6.4.
Study Drug Exposure..............................................................................................46
10.7.
Efficacy Analysis....................................................................................................47
10.7.1.
Efficacy Endpoints .................................................................................................47
10.7.1.1.
Progression-free Survival........................................................................................47
10.7.1.2.
Overall Survival .....................................................................................................48
10.7.1.3.
Overall Response Rate............................................................................................48
10.7.2.
Exploratory Endpoints............................................................................................48
10.7.2.1.
Health Care Utilization and Quality of Life Questionnaire......................................48
10.8.
Study Therapy Termination ....................................................................................48
10.9.
Deaths ....................................................................................................................48
10.10.
Interim Analysis .....................................................................................................49
10.10.1.
Interim Evaluation of Dosing, Safety and Efficacy..................................................49
10.10.2.
Interim Analysis of Quality of Life Questionnaire Data ..........................................49
10.11.
Scientific Steering Committee ................................................................................49
11.
ADVERSE EVENTS..............................................................................................50
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................50
11.2.
Evaluation of Adverse Events.................................................................................50
11.2.1.
Seriousness.............................................................................................................50
11.2.2.
Severity / Intensity..................................................................................................52
11.2.3.
Causality ................................................................................................................52
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523


('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
14
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
11.2.4.
Duration .................................................................................................................53
11.2.5.
Action Taken..........................................................................................................53
11.2.6.
Outcome.................................................................................................................53
11.3.
Abnormal Laboratory Values..................................................................................53
11.4.
Pregnancy...............................................................................................................53
11.4.1.
Female Subjects......................................................................................................54
11.4.2.
Male Subjects.........................................................................................................54
11.5.
Reporting of Serious Adverse Events......................................................................54
11.5.1.
Safety Queries ........................................................................................................55
11.6.
Expedited Reporting of Adverse Events..................................................................55
12.
DISCONTINUATIONS .........................................................................................56
12.1.
Study Treatment Discontinuation............................................................................56
12.2.
Study Discontinuation ............................................................................................56
12.3.
Subject Replacement ..............................................................................................57
13.
EMERGENCY PROCEDURES.............................................................................58
13.1.
Emergency Contact.................................................................................................58
14.
REGULATORY CONSIDERATIONS...................................................................59
14.1.
Good Clinical Practice............................................................................................59
14.2.
Investigator Responsibilities ...................................................................................59
14.3.
Subject Information and Informed Consent.............................................................59
14.4.
Confidentiality........................................................................................................60
14.5.
Protocol Amendments.............................................................................................60
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................60
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................61
14.8.
Closure of the Study ...............................................................................................61
15.
DATA HANDLING AND RECORDKEEPING.....................................................62
15.1.
Data/Documents .....................................................................................................62
15.2.
Data Management...................................................................................................62
15.3.
Record Retention....................................................................................................62
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................64
16.1.
Study Monitoring and Source Data Verification......................................................64
16.2.
Audits and Inspections............................................................................................64
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
15
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
17.
PUBLICATIONS ...................................................................................................65
18.
REFERENCES.......................................................................................................66
19.
APPENDICES........................................................................................................68
Appendix A:
ECOG Performance Status Score.......................................................................68
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
16
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
LIST OF TABLES
Table 1:
Blinded Radiology Assessment of Overall Response Rate (ITT Population) ...........20
Table 3:
Table of Events.......................................................................................................28
Table 4:
Permanent Dose Reductions for Hematologic and Neurologic Toxicities and 
Dosing on the Study ...............................................................................................40
&(/*(1(35235,(7$5<,1)250$7,21
.40
40


('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
17
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................26
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
18
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer
Lung cancer is the leading cause of cancer-related deaths among men and women worldwide, 
with 1.2 million new cases diagnosed each year. Non-small cell lung cancer (NSCLC) is the 
most common type of lung cancer, accounting for 80% of all new cases. There are an estimated 
1.1 million lives lost per year (approximately 500,000 in the United States [US] and European 
Union [EU] alone) due to NSCLC. Smoking is the causative factor for up to 85% of cases 
(http://www.lungcancercoalition.org/en/pages/about/awareness).
The majority of patients are not diagnosed until the tumor has progressed beyond the primary 
site. Despite step-wise advances in patient selection, targeted agents and optimizing
chemotherapy regimens, patients with advanced NSCLC continue to have an unmet medical 
need (Schiller, 2013).
Platinum-containing chemotherapy regimens remain the standard first-line treatment in the 
majority of patients, in the US and Japan. In the EU, a third-generation chemotherapeutic agent 
(docetaxel, gemcitabine, paclitaxel, or vinorelbine), most commonly gemcitabine or vinorelbine, 
plus a platinum drug is used for advanced NSCLC (NICE, 2011). For first-line therapy in 
patients with Stage IV NSCLC and good performance status, the American Society of Clinical 
Oncology (ASCO) clinical practice guideline recommends treatment with a platinum-based 
two-drug combination of cytotoxic drugs (Azzoli, 2009). A trend that is becoming more 
prevalent is personalized NSCLC treatment based on tumor histology (squamous versus 
non-squamous), on molecular characteristics of the tumor, and on the patient’s clinical status 
using agents targeting specific receptors and kinases and pathways (ie, epidermal growth factor 
receptor [EGFR], echinoderm microtubule-associated protein-like 4 [EML4] and anaplastic 
lymphoma kinase [ALK] fusion protein).
In advanced NSCLC, the prevalently used combination of solvent-based 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, and requires the use of specialized infusion sets and in-line 
filters that do not contain di[2-ethylhexyl] phthalate (DEHP).
Compared with solvent-based paclitaxel, nab-paclitaxel exhibits 10-fold higher mean Cmax of 
free paclitaxel, delivers 33% higher drug concentration to tumors in preclinical xenograft 
he primary
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
19
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
models, and demonstrates enhanced transport across endothelial cell monolayers (Desai, 2006; 
Gardner, 2008). The Cremophor EL-free medium enables nab-paclitaxelto be given in a shorter 
duration without the need for premedication to prevent solvent-related hypersensitivity reactions. 
In addition, standard tubing and intravenous (IV) bags may be used for the IV administration of 
nab-paclitaxel. 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. 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.
1.2.
nab-Paclitaxel in NSCLC
The Food and Drug Administration (FDA) approval of nab-paclitaxel 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. 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%), see Table 1].
Non-inferiority analysis of overall survival (OS) demonstrated that nab-paclitaxel/carboplatin
(nab-p/C) treatment is not inferior to solvent-based paclitaxel/carboplatin (sb-P/C) treatment.  
Overall survival in the nab-paclitaxel arm was 12.1 months versus 11.2 months in the control 
arm (p = 0.271; HR = 0.922).  Toxicities, particularly neuropathy and neutropenia were less 
pronounced using nab-paclitaxel in the dose and schedule employed.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
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Table 1:
Blinded Radiology Assessment of Overall Response Rate (ITT Population)
Variable
Category/Statistic
nab-Paclitaxel/
Carboplatin
(N=521)
sb-Paclitaxel/
Carboplatin
(N=531)
Response Rate 
Ratio
(pA/pT)a
p-value
Patients with Confirmed Complete or Partial Overall Response
n (%)
170 (33%)
132 (25%)
1.313
0.005*
Confidence Interval (CI) b
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%)
a PA/PT equals response rate of nab-paclitaxel/response rate of sb paclitaxel.
b 95% CI of response rate and 95.1% CI of response rate ratio.
* Indicates p-value < 0.049.Note: P-value is based on a chi-square test.
Source: Data on File.
Adverse events were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. The following common (≥ 10% incidence) 
adverse events were observed at a similar incidence in nab-paclitaxel and paclitaxel 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).
1.3.
Rationale for Further Study of nab-Paclitaxel as First-line Treatment 
in Elderly Subjects with Advanced NSCLC
The tolerability of doublet chemotherapy in elderly patients with advanced NSCLC is an
important therapeutic consideration, whereby the landmark IFCT 0501 reported that first-line sb-
paclitaxel given weekly three weeks out of four coupled with carboplatin every 4 weeks (i.e.
21days of treatment followed by one-week break) improved efficacy over single-agent 
chemotherapy (either gemcitabine or vinorelbine) in patients 70 years or older with advanced 
NSCLC.  The results demonstrated that doublet chemotherapy was feasible in this elderly
population with an acceptable toxicity profile, when sb-paclitaxel/carboplatin was given as 21
days of treatment followed by one-week rest. The combination also resulted in a significant 
improvement in OS (median, 10.3 versus 6.2 months; HR = 0.639, 95% CI:0.52-0.79, p <
0.0001), with 1-year survival rates of 45.1% versus 26.9% for doublet therapy and monotherapy.  
This prospective trial set a standard, against which doublet-regimens must be measured in the 
elderly population with advanced NSCLC.
In the CA031 study of nab-paclitaxel (Abraxane) in combination with carboplatin, patients were 
stratified by age (< 70 years old versus ≥ 70 years old). Fifteen percent of ITT patients were 
elderly (≥70 years: nab-paclitaxel, n = 74: sb-paclitaxel, n = 82). Baseline characteristics were 
generally well balanced between treatment arms in elderly population, and subgroup analyses 
were performed to assess the influence of age on the primary efficacy endpoint of overall 
response rate as well as PFS and OS (Socinski, 2013). 
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
Of note, the post-hoc analysis of the CA031 trial showed marked improvement in survival in the 
nab-paclitaxel/carboplatin arm. Amongst 156 elderly (≥70 years of age) subjects randomized on 
the study, OS was 19.9 months versus 10.4 months (HR: 0.583, p = 0.009) in favor of the nab-
p/C arm compared to sb-p/C. The proportion of patients who had complete or partial response 
were consistently higher in all age stratum groups for the nab-paclitaxel/carboplatin regimen 
relative to the sb-paclitaxel/carboplatin regimen (in patients ≥ 70 years of age 34% versus 24% 
respectively, ratio of rates 1.385, p = 0.196, 
).
 
 
 
Although it was a statistically significant treatment effect in favor of nab-paclitaxel in the elderly 
subgroup from CA031 trial, 46% of patients in the nab-paclitaxel/carboplatin arm experienced 
dose reductions or dose delays. Approximately 92% of dose modifications and reductions were 
due to AEs. The most common clinical AEs in this subgroup were hematologic Grade ≥ 3 
neutropenia (45%), anemia (22%) and thrombocytopenia (19%). Approximately 18% of the 
elderly population in the CA031 trial had Grade ≥ 2 peripheral neuropathy. Despite that,
approximately 10% more elderly patients in the nab-paclitaxel arm were able to receive second-
line therapy compared to sb-paclitaxel (61% versus 50%, respectively), possibly because they 
may have been in better shape due to a better tolerated first-line regimen with nab-paclitaxel or 
better disease and symptom control as demonstrated as improvement in ORR.
The results from the elderly subset in CA031 trial showed the combination of nab-paclitaxel and 
carboplatin to be particularly promising. We hypothesize that the tolerability can be improved 
further by introducing a one week break at the end of each treatment cycle (similar to the 
schedule advocated by Quoix, 2011) among elderly patients.  Reducing the rate of the most 
common AEs (Grade ≥ 3 myelosuppression toxicities and Grade ≥ 2 peripheral neuropathy) by 
16% will be clinically meaningful as it can potentially improve tolerability, quality of life and 
allow patients to receive treatment for a longer period of time, without necessarily compromising 
efficacy.  
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
22
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
2.
STUDY OBJECTIVES
2.1.
Primary Objectives 
!
To assess the safety and tolerability of continuous weekly versus weekly times three 
with one-week break nab-paclitaxel (Abraxane) in combination with carboplatin as 
first-line treatment for advanced NSCLC in elderly subjects (≥ 70 years old).
2.2.
Secondary Objective
!
To evaluate the efficacy of nab-paclitaxel in combination with carboplatin in elderly 
subjects with advanced NSCLC.
2.3.
Exploratory Objectives
!
To assess healthcare resource utilization for the two nab-paclitaxel treatment arms.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ-5D) for the two nab-paclitaxel treatment arms.
!
 
 
!
 
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
23
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
3.
STUDY ENDPOINTS
3.1.
Primary Endpoint
!
The primary study endpoint is the percentage of subjects with either peripheral 
neuropathy of Grade ≥ 2 or myelosuppression AEs of Grade ≥ 3 based on the local 
laboratory values for ANC, platelet count, and hemoglobin. All AEs will be graded 
using NCI CTCAE v4.0.  
3.2.
Secondary Endpoints
The secondary endpoints are: 
3.2.1.
Safety
!
The type, frequency, and severity of AEs and SAEs. 
!
Discontinuation rate.
!
Dose intensity administered.
!
The incidence of dose reduction and dose delay.
3.2.2.
Efficacy
!
Progression-free Survival (PFS).
!
Overall response rate (ORR) using RECIST v1.1 guidelines.
!
Overall Survival (OS).
3.3.
Exploratory Endpoints
!
Healthcare resource utilization during the study using a questionnaire.
!
Changes in the LCSS and EQ-5D.
!
 
 
 
!
 
!
Additional exploratory endpoints may be defined in the statistical analysis plan 
(SAP), if applicable.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
24
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is a Phase IV, randomized, open-label, multicenter study of continuous weekly versus
weekly times three with one-week break nab-paclitaxel in combination with carboplatin as first-
line treatment in elderly subjects (≥ 70 years old) with advanced NSCLC who are not candidates 
for curative surgery or radiation therapy.
Subjects will be randomized 1:1 to receive one of the following treatments:
Arm A (21-day treatment cycle):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment cycle after 
completion  of nab-paclitaxel infusion 
Arm B (21-day treatment followed by one-week break cycle, 28-day duration):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment  followed by one-week break cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment followed by 
one-week break cycle, after completion of nab-paclitaxel infusion 
The study will consist of a 28-day Screening Period, a Treatment Period, and a Follow-up 
Period.
The Screening Period will start from signing the Informed Consent Form (ICF) until first dose of 
study drug. 
The Treatment Period will start from first dose of study drug until End-of-Treatment Visit 
(which is defined as visit with last dose of study drug).
Follow-up Period will start after End-of-Treatment visit.
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of 
consent, in accordance with local standard of care.
Tumor evaluations will be assessed locally and response (Complete Response [CR] or Partial 
Response [PR]) will be determined according to RECIST guidelines, Version 1.1. In both 
treatment arms, tumor assessments will be conducted at screening and every 42 days (-3/+7
days) (starting from Day 1 Cycle 1) until disease progression, withdrawal of consent, lost to 
follow-up, death, or if clinically indicated while on treatment.
Local laboratory test data for ANC, platelet count, hemoglobin and serum creatinine will be 
collected in the eCRFs. All other routine laboratory test data except those mentioned above will 
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
25
ABI-007-NSCL-005 Amendment 3.0 Final:17 Mar 2016
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 AE, or SAE, 
and the specific associated laboratory parameter(s) should be recorded in the laboratory 
assessments eCRF. Local safety laboratory data will also be the primary guide for eligibility and 
subject management. In addition, test results for tumor mutational status of genes including but 
not limited to EGFR, ALK, and KRAS will be collected and recorded on eCRF if these tests 
have been performed locally for routine diagnosis.  
4.1.1.
Follow-up Period
All subjects who discontinue from treatment for reasons other than withdrawal of consent or lost 
to follow-up will enter the Follow-up Period. It will consist of a visit 28 days after treatment 
discontinuation following by follow-up for survival approximately every 90 days (+/- 14 days or 
when they are seen for routine care) by phone call or chart review for documentation of last 
contact for up to 6 months after the last subject is randomized or 192 PFS events have been 
observed, whichever comes later.
Those subjects entering the Follow-up Period without documented progression will continue to 
have CT scans in accordance with standard of care (at least every 90 days) until documented 
progression of disease, withdrawal of consent, lost to follow-up, death, or study closure.
4.2.
Study Design Rationale
The nab-paclitaxel schedule used in Arm A is in accordance with pivotal trial CA031,
ie,100 mg/m2 administered once per week on Days 1, 8 and 15 combined with carboplatin 
AUC = 6 mg*min/mL administered on Day 1 every 21 days, as approved by the FDA.  The nab-
paclitaxel/carboplatin schedule used in Arm B is the same schedule as the current approved nab-
paclitaxel label with introduction of a one-week break following 21 days of treatment. This 
study will determine whether the one-week break can further improve tolerability without 
compromising efficacy (similar to the schedule advocated by Quoix, 2011) among elderly 
patients.  Reducing the rate of the most common AEs (Grade ≥ 3 myelosuppression toxicities 
and Grade ≥ 2 peripheral neuropathy) by 16% will be clinically meaningful as it can potentially 
improve tolerability, quality of life and allow subjects to receive treatment for a longer period of 
time.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
26
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
Figure 1:
Overall Study Design
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
27
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
4.3.
Study Duration
Recruitment is expected to take approximately 24 months, and the analysis of PFS will be 
performed when approximately 192 PFS events have occurred, estimated as approximately 28
months from first subject randomized. The total length of this Phase IV study with follow-up is 
estimated to last approximately 3 years.
4.4.
End of Trial
The End of Trial is defined as either the:
!
date of the last visit of the last subject to complete the study, or 
!
the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol
and/or the SAP, whichever is the later date.
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-005
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Confidential and Proprietary
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ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
5.
TABLE OF EVENTS
Table 3:
Table of Events
Screening
/ Baseline
Treatment Perioda
Every cycle starting with Cycle 1
Follow-Up Period
Assessment
Day -28 
to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days) 
(counting from 
Day 1 Cycle 1)
End-of-
Treatment
Visit (last dose 
of study drug)
28-day Follow-up 
Visit (after last 
dose of study 
drug)
Survival Follow-Upb
Every 90 days (+/-
14 days) (after 28-
day follow-up visit)
Informed Consent
X
-
-
-
-
-
-
-
Medical History, Prior Medication and Procedures
X
-
-
-
-
-
-
-
CT Scan of Complete Chest (including base of neck 
and adrenal glands) and any other studies required 
for Tumor Imagingc
X
-
-
-
X c
X c
-
X c
Weight and Heightd
X
X
X
X
-
-
-
-
Body Surface Area (BSA) Calculationd
X
-
-
-
-
-
-
-
ECOG status
X
X
-
-
-
X
X
-
Concomitant Medication/Procedures
-
X
X
X
-
X
X
X
Peripheral Neuropathy Assessmente
X
X
X
X
-
X
X
-
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-
X
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X
X
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X
X
X
X
-
X
X
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X
X
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X
X
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
29
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
Table 3:
Table of Events (Continued)
Screening
/ Baseline
Treatment Perioda
Every cycle starting with Cycle 1
Follow-Up Period
Assessment
Day -28 
to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days) 
(starting Day 1 
Cycle 1)
End-of-
Treatment
(last dose of 
study drug)
28-day Follow-up 
Visit (after last 
dose of study 
drug)
Survival Follow-Upb
Every 90 days (+/-
14 days) (after 28-
day follow-up visit)
Blood for Pharmacogenomic Analyses
-
X
(C1D1 only)
-
-
-
-
-
-
Adverse Event Evaluation
After signing ICF and until 28 days after the last dose of study drug
nab-paclitaxel Administration/accountabilityg
-
X
X
X
-
-
-
-
Carboplatin Administration/accountabilityg
-
X
-
-
-
-
-
-
LCSS and EQ-5D
-
X
-
-
-
X
X
-
Survival phone call (or chart review for 
documentation of last contact or when they are seen 
for routine care
-
-
-
-
-
-
-
Xb
Electrocardiogram (ECG)
Will be done as per standard of care at screening, during the Treatment Period and as clinically indicated; however, results 
will not be routinely collected in the eCRFs. Results will be collected in the eCRFs as AE or SAE only if results are abnormal 
and clinically significant.
CT Scan of the Head or Brain Magnetic Resonance 
Imaging (MRI)
Bone Scan (X-rays if needed)
Physical Examination
Vital Signs
AE = Adverse Event; ANC = absolute neutrophil count; C1D1 = Cycle 1, Day 1; CT = Computed Tomography; ECOG = Eastern Cooperative Oncology Group; eCRF =
electronicCase Report Form; EQ-5D = EuroQol 5D; ICF = informed consent form; LCSS = Lung Cancer Symptom Scale; SAE = Serious Adverse Event; RECIST=Response 
Evaluation Criteria in Solid Tumors; PFS=Progression Free Survival.
a Treatment Period:  Arm A: nab-paclitaxel Days 1, 8, and 15 and carboplatin Day 1. Arm B: nab-paclitaxel Days 1, 8, and 15 and carboplatin Day 1 followed by one-week break.
b Every 90 (+/-14) days (from 28-day Follow-up Visit) or when they are seen for routine care for up to 6 months after the last subject is randomized or 192 PFS events have been 
observed, whichever comes later.
c All subjects must have a radiographically documented measurable tumor(s) by RECIST Version 1.1 criteria: CT scan of complete chest (including base of neck and adrenal 
glands) are performed at screening, every 42 days (-3/+7 days) thereafter (counting from Day 1 Cycle 1) until disease progression, withdrawal of consent, lost to follow-up, 
death and if clinically indicated while on treatment. The methods of assessment chosen at baseline to follow tumors are to remain consistent throughout study duration. Those 
subjects entering the Follow-up Period without documented progression will continue to have CT scans in accordance with standard of care (at least every 90 days) until 
documented progression of disease, withdrawal of consent, lost to follow-up, death or study closure.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
30
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
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 recalculated. Height 
will only be obtained at Screening Visit. Weight will be obtained at screening and every visit during the Treatment Period before administration of study drug, but will only be 
collected on the eCRF for the Screening Visit.
e The occurrence of peripheral neuropathy will be reported by the investigator per protocol as an AE or SAE.
f Laboratory assessments will be done prior to each nab-paclitaxel treatment as per standard of care during the study and as clinically indicated. ANC, platelet count, hemoglobin
(Hgb) level and serum creatinine results will be collected in the eCRFs (all other routine laboratory test data except those mentioned above will not be collected in the eCRF
unless it is clinically significant, which will then be reported as AEs or SAEs, and the specific associated laboratory parameter(s) should be recorded on the laboratory 
assessments eCRF).
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
31
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
6.
PROCEDURES
Subjects will be provided with a written ICF, given the opportunity to ask any questions 
concerning the study and will sign an ICF prior to participating in any study procedures. Serum 
Chemistry assessments or CT scans performed in accordance with the local standard of care 
within 28 days before the first dose of study drug, even if they took place prior to signing of the 
ICF, can be used for the screening assessment. After giving written informed consent, subjects 
will undergo a Screening Period to be assessed for eligibility. All subjects who sign an ICF must 
be entered into the Interactive Randomization Technology (IRT) system immediately upon 
signature on the document. Subjects who do not meet the eligibility criteria will be considered 
screening failures and will not be eligible for the study. Subjects who screen fail may re-screen 
up to 2 times at any time and an ICF will need to be re-signed, as well as all screening 
procedures repeated (some procedures may not need to be done if previously done within 28 
days prior to screening again). Subjects that have met all eligibility criteria after the Screening 
Period will be eligible to be randomized. 
6.1.
Medical History
Only clinically significant or ongoing medical conditions will be recorded at screening on the 
eCRF. 
6.2.
Prior and Concomitant Medications/Procedures
Prior medications are defined as all medications that were started before the date of the first dose 
of study drug. Only prior medications/procedures (of clinically significant or ongoing medical 
conditions) within 28 days of the time of signature on the ICF should be recorded. All NSCLC-
related prior medications/procedures (including radiation therapy) should be recorded regardless 
of time. 
Concomitant medications are considered 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. All 
subjects will have concomitant medications and procedures (including radiation therapy) 
recorded from the time of signature on the ICF until the 28-day Follow-up Visit, for conditions 
that are clinically significant or ongoing. During the Follow-up Period only NSCLC-associated 
concomitant medications/procedures (including radiation therapy) will be recorded, ie, 
subsequent-line(s) of anti-cancer therapy.
6.3.
Computed Tomography (CT) Scan of Complete Chest (including 
base of neck and adrenal glands)
A CT scan of complete chest (including base of neck and adrenal glands) and any other studies 
required for tumor imaging will be done at screening, every 42 days (-3/+7 days) (starting from 
Day 1 Cycle 1) until treatment discontinuation or withdrawal of consent. Those subjects entering 
the Follow-up Period without documented progression will continue to have CT scans in 
accordance with standard of care (at least every 90 days) until documented progression of 
disease, withdrawal of consent, lost to follow-up, death or study closure. Additional CT scans
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one wit
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s/Proced
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at were sta
at were sta
res
es (of
(of clini
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f
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nature on t
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
32
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
may be done at any time during the study if clinically indicated. All CT scans and reports should 
be archived at the site according to site regulations and copies provided to Sponsor if requested.
6.4.
Weight
Weight will be obtained at screening and at every visit during the Treatment Period before 
administration of study drug, but will only be collected on the eCRF for the Screening Visit.
Additional weights may be collected per local standards at any time during the study as needed.
6.5.
Body Surface Area (BSA) Calculation and Height
Height will be collected at screening only, and BSA will be calculated at screening of the study. 
BSA will be recalculated if body weight changes by more than 10% during the study.
6.6.
ECOG Performance Score
Eastern Cooperative Oncology Group performance score will be collected at screening, Day 1 of 
every treatment cycle, at the End-of-Treatment visit and at the 28-day Follow-up Visit. 
Additional ECOG assessments may be performed at any time during the study as clinically 
indicated.
6.7.
Peripheral Neuropathy Assessment
Peripheral neuropathy (sensory or motor) assessment will be done at screening, Day 1, 8, 15 of 
every treatment cycle, at the End-of-Treatment visit and at the 28-day Follow-up Visit. Changes 
in neuropathy grade from baseline will be reported as an AE as per Section 11. Additional 
peripheral neuropathy assessments may be done at any time during the study as clinically 
indicated.
6.8.
Adverse Event Reporting
Adverse events will be recorded from time of signature on the ICF until 28 days after the last 
dose of study drug, including any unscheduled visits. See Section 11 for details. 
6.9.
Lung Cancer Symptom Scale Questionnaire and EQ-5D
The LCSS and EQ-5D questionnaires will be used to measure quality of life (QoL) for subjects 
in the study. The LCSS is comprised of 9 questions to be completed by the subject using a visual 
analogue scale (VAS) to denote intensity of a symptom. The EQ-5D comprises 5 questions on 
mobility, self-care, usual activities, pain/discomfort, anxiety/depression and a VAS for overall 
QoL. These questionnaires will be completed at Day 1 of every Treatment Period, at the End-of-
Treatment Visit and at the 28-day Follow-up Visit.
6.10.
Healthcare Resource Utilization Questionnaire
A healthcare resource utilization questionnaire will be used to capture the additional use of 
healthcare resources, including hospitalizations, emergency room visits, doctor or nurse visits, 
procedures, and/or additional medication during the study period. The assessment will be 
completed at Day 1 of every treatment cycle, at the End-of-Treatment visit and at 28-day Follow-
up Visit. 
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
33
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
6.11.
Electrocardiogram
Electrocardiograms (ECGs) will be done per standard of care at screening, during the Treatment 
Period and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if 
results are abnormal, changed, and clinically significant.
6.12.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI)
A CT scan of the head, or preferably brain MRI, will be done as per standard of care at 
screening, during the Treatment Period, and as clinically indicated. Results will be collected in 
the eCRFs as an AE or SAE only if the results are abnormal and clinically significant.
6.13.
Bone Scans and X-rays
Bone scans and x-rays will be done as per standard of care at screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if 
results are abnormal and clinically significant.
6.14.
Physical Examinations
Physical examinations will be done as per standard of care at screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if 
results are abnormal and clinically significant.
6.15.
Vital Signs
Vital signs will be done as per standard of care at screening, during the Treatment Period, and as 
clinically indicated. Results will be collected in the eCRFs as AE or SAE only if results are 
abnormal and clinically significant.
6.16.
Laboratory Assessments
Laboratory assessments will be done as indicated in Table 3 by local laboratories as per standard 
of care during the study and as clinically indicated. Local laboratory test data for ANC, platelet 
count and hemoglobin must be collected at screening, each visit before administration of study 
drug, at the End-of-Treatment visit and at the 28-day Follow-up Visit in the eCRF. Serum 
creatinine must be collected at screening, Day 1 of each cycle, at the End-of-Treatment visit and 
at the 28-day Follow-up Visit in the eCRF. Normal ranges for these selected parameters will be 
collected on the eCRF. All other laboratory test data, except those mentioned above, will not be 
collected routinely in the eCRF. Local safety laboratory data will also be the primary guide for 
eligibility and subject management. It is the responsibility of the investigator to assess the 
clinical significance of all abnormal values as defined by the reference ranges from the local 
laboratory. All clinically significant laboratory abnormalities (Section 11.3) are to be recorded as 
AEs on the AE eCRF, and the specific laboratory parameter(s) as well as the corresponding 
normal ranges should be recorded on the laboratory assessments eCRF. Clinically significant 
laboratory abnormalities at screening may result in subject ineligibility for the study and should 
not be captured as AE. Any abnormal values that persist should be followed at the discretion of 
the investigator. The investigator should file all copies of the reports, including faxes with the 
subject’s medical chart.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
34
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
6.17.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) 
Provision of tumor tissue is mandatory for study enrollment, except when no tumor tissue is 
extant and this requirement would necessitate a new procedure such as a biopsy to collect it.  
 
 
 
 
 
 
 
 
 
 
 
In addition, test results for tumor mutational status of genes including but not limited to EGFR, 
ALK, and KRAS will be collected and recorded on eCRF if these tests have been performed
locally for routine diagnosis.
 
 
 
 
 
 
6.18.
Survival 
After the End-of-Treatment Visit, the subjects will have a 28-day Follow-up Visit followed by a 
call or chart review for documentation of last contact approximately every 90 days (or when they 
are seen for routine care) for up to 6 months after the last subject is randomized or 192 PFS 
events have been observed, whichever comes later. The subjects will also be asked questions 
about other medications they may be taking for their NSCLC or their medical records will be 
reviewed to determine a last contact date for routine purposes. Those subjects entering the 
Follow-up Period without documented progression will continue to have CT scans in accordance 
with standard of care (at least every 90 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death or study closure.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
35
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Elderly (≥70 years of age) male and female subjects with locally advanced or metastatic NSCLC 
with no prior chemotherapy for metastatic disease will be eligible for this study. The study will 
enroll approximately 284 subjects. The study will be conducted at approximately 65 sites in the 
United States.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be randomized in the study:
1. Age ≥ 70 years at the time of signing the ICF.
2. Understand and voluntarily provide written informed consent prior to the conduct of any 
study related assessments/procedures.  
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Histologically or cytologically confirmed locally advanced or metastatic NSCLC who are 
not candidates for curative surgery or radiation therapy.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease per RECIST v1.1.
7. No prior chemotherapy for the treatment of metastatic NSCLC. Adjuvant chemotherapy, 
neo-adjuvant chemotherapy, or chemoradiotherapy with curative intent of non-metastatic 
disease is permitted providing that it was completed 12 months prior to signing the ICF
and without disease recurrence. Patients with previously known EGFR mutation or ALK 
gene translocation must have failed or had intolerance to one treatment with EGFR 
tyrosine kinase inhibitor or ALK inhibitor therapy, respectively.
8. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
9. Platelets ≥ 100,000 cells/mm3. 
10. Hemoglobin (Hgb) ≥ 9 g/dL.
11. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]), alanine
transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper limit of 
normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
12. Total bilirubin ≤ 1.5 mg/dL (unless there is a known history of Gilberts Syndrome).
13. Creatinine clearance (CrCl) > 40 mL/min calculated using Cockcroft-Gault equation (if 
renal impairment is suspected 24 hour urine collection for measurement is required).
14. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
15. Females who (1) have undergone hysterectomy (the surgical removal of the uterus) or 
bilateral oophorectomy (the surgical removal of both ovaries) or (2) have been naturally 
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
36
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
postmenopausal for at least 24 consecutive months (ie, has not had menses at any time 
during the preceding 24 consecutive months). Male subjects must:
a.
Practice true abstinence or agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the 
study, during dose interruptions, and for 6 months following study drug 
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
≥4 weeks 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. Preexisting 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 study drug, 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 (VTE) within 1 month prior to signing ICF. If the subject has 
a history of VTE more than 1 month prior to signing the ICF, the event should be 
resolved, stable, and without clinically significant bleeding, such as hematuria, 
gastrointestinal bleeding, or hemoptysis.
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 a study drug: 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.
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.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
37
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
13. History of allergy or hypersensitivity to nab-paclitaxel or carboplatin.
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 randomization. Exceptions are 
malignancies with a negligible risk of metastasis or death (eg, expected 5-year OS > 
90%) that were treated with an expected curative outcome such as: 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 of which 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.
19. Females who (1) have not undergone hysterectomy (the surgical removal of the uterus) or 
bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been 
naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any 
time during the preceding 24 consecutive months).
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
38
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Study Drug(s)
Treatment
Subjects will receive open-label nab-paclitaxel and carboplatin during the Treatment Period of 
the study. Investigative sites will use standard of care (commercially available) product via 
prescription for nab-paclitaxel and carboplatin.
The preparation for IV administration procedures should be followed as per approved 
Prescribing Information. 
8.1.1.
nab-Paclitaxel
Each single-use 50 mL vial contains paclitaxel (100 mg) and approximately 900 mg human 
albumin as a stabilizer.
Unreconstituted nab-paclitaxel should be stored in accordance with the product label. 
Reconstituted nab-paclitaxel should be used immediately. Both forms should be stored in an area 
free of environmental extremes and should be accessible only to study personnel. Reconstitution 
and administration should follow local prescribing information and local practice. Temperature 
records for nab-paclitaxel must be made available to Celgene or other Sponsor- nominated 
monitoring teams for verification of proper study drug storage.
8.1.2.
Carboplatin
Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic 
agent. The chemical name for carboplatin is platinum diammine [1,1-
cyclobutane-dicarboxylato (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 package insert. 
8.2.
Treatment Administration and Schedule
Following administration of nab-paclitaxel, the intravenous line should be flushed with sodium 
chloride 9 mg/mL (0.9%) solution for injection to ensure administration of the complete dose, 
according to local practice.
Approximately 284 subjects will be treated with nab-paclitaxel plus carboplatin until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of 
consent. 
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900 mg hu
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
Treatment will commence on Day 1, in accordance with standard of care of first-line treatment of 
NSCLC: 
Arm A:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day treatment cycle,
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment cycle, after 
completion of nab-paclitaxel infusion
OR
Arm B:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day treatment with one-week break cycle (i.e. every 28 days),
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment with one-
week break cycle (i.e. every 28 days), after completion of nab-paclitaxel infusion.
8.3.
Dose Modifications
Subjects who experience any of the adverse drug reactions in Table 4 will be dose reduced as per 
Table 4 during treatment. 
!
Do not administer nab-paclitaxel on Day 1 of a cycle until ANC is at least 
1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment 
until counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and 
platelet count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil 
count of at least 500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on 
Days 8 or 15 of the cycle. Upon resumption of dosing, permanently reduce nab-
paclitaxel and carboplatin doses as outlined in Table 4.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-
paclitaxel and carboplatin at reduced doses (Table 4) when peripheral neuropathy 
improves to Grade 1 or completely resolves.
Re-escalation is not permitted at any time. 
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
40
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
Table 4:
Permanent Dose Reductions for Hematologic and Neurologic Toxicities and Dosing on the Study
Dose Modification During Treatment for A and B arms
Adverse Drug Reaction
Occurrence
nab-Paclitaxel Dose 
(mg/m2)
Carboplatin Dose 
(AUC 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*
Sensory 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 twice, the subject should generally have treatment discontinued unless, at 
the discretion of the investigator, there is evidence of continuing benefit to the subject that outweighs the risk of recurrent toxicity. Re-Escalation is not 
permitted at anytime.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
41
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
8.4.
Method of Treatment Assignment
The Treatment Period of the study is open-label. Enrollment/randomization will occur via IRT 
system for all periods of the study. 
8.5.
Packaging and Labeling
Investigative sites will use standard of care (commercially available) product via prescription for 
nab-paclitaxel and carboplatin.
8.6.
Study Drug Accountability and Disposal
Investigative sites will use standard of care (commercially available) product via prescription for 
nab-paclitaxel and carboplatin. Accurate recordings of all study drug administration should be 
made.
Procedures for proper handling and disposal of anticancer drug must comply with the relevant 
health, safety, and environment regulations.
8.7.
Study Drug Compliance
Study drug will be administered only by study site personnel and accurate recording of all study 
drug 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 or carboplatin dosing only.
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel or carboplatin given to a subject, regardless of any associated adverse events or 
sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate. For nab-paclitaxel, an infusion completed in less than 25 minutes may increase Cmax by 
approximately 20%; therefore, a nab-paclitaxel infusion completed in less than 25 minutes will 
meet the infusion rate criterion for an overdose.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. See 
Section 11.1 for the reporting of adverse events associated with overdose.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
42
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
Over the course of this study, additional medications may be required to manage aspects of the 
disease state of the subjects, including side effects from study treatments or disease recurrence. 
All supportive care (including but not limited to antiemetic medications, white blood cell (WBC)
growth factors, erythrocyte stimulating agents, zolendronic acid, and denosumab) is permitted
and may be administered at the discretion of the investigator, according to local guidelines. 
9.2.
Prohibited Concomitant Medications and Procedures
Other antineoplastic agents or Investigational Product than what is specified in the protocol are 
prohibited.
9.3.
Required Concomitant Medications and Procedures
Not applicable.
&(/*(1(35235,(7$5<,1)250$7,21
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
43
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
10.
STATISTICAL ANALYSES
Statistical analyses for the primary and 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 284 subjects will be randomized in a 1:1 ratio to two treatment arms (142 
subjects per group).  Arm A will receive nab-paclitaxel 100 mg/m2 administered on Days 1, 8 
and 15 followed by carboplatin AUC = 6 mg*min/mL on Day 1 of each 21-day treatment cycle. 
Arm B will receive the same treatment in the same schedule as that of Arm A during the first 21 
days of treatment, but followed by a one-week break prior to the start of next cycle (28-day 
duration). All subjects will receive the assigned study treatment until disease progression,
unacceptable toxicity, death, lost to follow-up, or withdrawal of consent, in accordance of local 
standard of care.  A permuted-block randomization method will be employed, and the 
randomization will be carried out centrally using an IRT system. The randomization will be 
stratified based on the following 2 baseline or prognostic factors: 
!
ECOG performance status (0 versus 1)
!
Histology (squamous cell carcinoma versus non-squamous cell carcinoma)
10.2.
Study Population Definitions
10.2.1.
Intent-to-treat Population
The primary efficacy analysis will be performed on the ITT population, which includes all 
randomized subjects regardless of whether the subject receives any study drug or has any 
efficacy assessments performed. 
10.2.2.
Per-protocol (PP) Population
The PP population is defined as all eligible subjects randomized who receive at least one dose of 
the study drug and have been treated in the arm they were assigned to. Additional analyses 
utilizing the PP population will be described in the SAP.
10.2.3.
Treated Population
The treated population will consist of all randomized subjects who receive at least one dose of 
study drug. The treatment groups for the safety analyses will be based on the treatment as 
received if different from the assigned treatment by randomization.
10.3.
Sample Size and Power Considerations
The primary objective of this study is to assess the safety and tolerability of nab-paclitaxel in 
combination with carboplatin administered in 21-day treatment cycles continuously or with a 
&(/*(1(35235,(7$5<,1)250$7,21
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1, 8
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received if 
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
44
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
one-week break in between cycles for the treatment of locally advanced or metastatic NSCLC in 
elderly subjects (≥ 70 years old).  
The primary study endpoint (also the primary safety endpoint) is the percentage of subjects with 
either peripheral neuropathy of Grade ≥ 2 or myelosuppression AEs of Grade ≥ 3 based on the 
local laboratory values for ANC, platelet count, and hemoglobin.  For the purpose of this 
protocol, this endpoint will be referred to as the percentage of subjects with Grade ≥ 2 peripheral 
neuropathy or Grade ≥ 3 myelosuppression laboratory adverse events.  
In Protocol CA031, the Phase 3 NSCLC study of the nab-paclitaxel development program, 
approximately 2% of the elderly subjects randomized discontinued from the study prior to 
receiving any study drug.  In addition, approximately 73% of the treated elderly subjects had 
AEs that fell in the category of AEs described above for the primary safety endpoint of the 
current study.  
The study is designed to detect a difference of 16 percentage points between the 2 treatment arms 
with respect to the primary safety endpoint with 80% power and a Type-I error of 5% (two-
sided), assuming the percentage of subjects with the AEs specified above is 73% for Arm A.  
Therefore, the current study is planned to randomize approximately 284 subjects to the 2 
treatment arms in a 1:1 ratio, with the expectation that approximately 278 subjects (139 per 
group) will receive at least one dose of study drug (as observed in CA031) and be included in the 
treated population for the analysis of the primary safety endpoint.
A non-binding interim evaluation of dosing, primary safety endpoint, and efficacy data will be 
conducted when approximately a total of 120 treated subjects have either completed 4 months of 
study treatment or discontinued treatment due to progression, adverse events, deaths, lost to 
follow up, or other reasons. The stopping rule and the final marginal significance level for this 
endpoint are determined based on the Gamma family spending function with parameter = -7 
(Hwang, 1990) to control the Type-II error rate at 20%.  Futility criterion for this endpoint is met 
if the treatment difference (Arm B minus Arm A) is ≥-0.2%, given the interim analysis of this 
endpoint is performed at 43% information fraction.  
Progression free survival, OS, and ORR are the efficacy endpoints of the study.  Since the 
primary research interest of this study is to evaluate the relative safety and toxicities of the 2 
treatment arms, the sample size was calculated based on the primary safety endpoint, the 
percentage of subjects with Grade ≥2 peripheral neuropathy or Grade ≥3 myelosuppression 
laboratory AEs, hence, the study is underpowered for the efficacy endpoint, PFS, OS and ORR.  
Consequently, a non-significant treatment difference in PFS, OS or ORR could simply be a 
function of the sample size and/or the lack of statistical power. Therefore, the assessments of all 
efficacy endpoints will be based on the point estimates and the associated 95% confidence 
intervals for the within-group parameters of interest and the between-group differences.  P-
values for between-group comparisons will be provided to indicate the strength of association 
only.  No multiplicity adjustment with the Type-I error rate will be made. 
Of note, based on the data from CA031 it is expected that approximately 67% of the 284
randomized subjects will have a PFS event during the study (i.e. approximately 192 PFS events 
total).  With 192 PFS events, there is 73% power to detect a hazard ratio (HR) of 0.69 for PFS 
improvement with Arm B over Arm A and an overall Type-I error of 5% (two-sided).  Assuming 
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
45
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
an exponential distribution with a median time to PFS of 5.8 months for Arm A and proportional 
hazards, a hazard ratio of 0.69 constitutes a 2.6 months improvement for Arm B.  
As an illustration for timeline projection, assuming an exponential distribution for PFS, a 24-
month recruitment period for 284 subjects, and a median PFS of approximately 5.8 months for 
Arm A, it will take approximately 28 months from the first subject randomized to observe 192 
PFS events.
The analysis of both the safety and efficacy endpoints for the clinical study report will be 
performed when approximately 192 PFS events have been observed.  No adjustment for the 
multiple treatment comparisons among the primary and secondary study endpoints will be made.  
Subjects will be followed for OS for at least 6 months after the last subject is randomized or 192 
PFS events have been observed, whichever comes later.
10.4.
Background and Demographic Characteristics
The baseline characteristics of all randomized subjects will be summarized. Subject’s age, 
height, weight, and baseline characteristics will be summarized using descriptive statistics, while 
gender, race and other categorical variables will be provided using frequency tabulations. 
Selected medical history data will be summarized using frequency tabulations by system organ 
class and preferred term.
10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both Treatment
and Follow-up Periods. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
10.6.
Safety Analysis
The treated population, which includes all randomized subjects who received at least one dose of 
study drug, will be the analysis population for all safety analyses.
The safety/tolerability of the two treatment arms will be monitored through continuous reporting 
and evaluated by the primary safety endpoint, adverse events and serious adverse events, 
abnormalities in ANC, platelet count and hemoglobin, and incidence of subjects experiencing 
dose modifications, dose interruptions, and/or premature discontinuation of study drug.
10.6.1.
Primary Safety Endpoint
The primary endpoint for this study is a composite safety endpoint, namely, the percentage of 
subjects who develop either peripheral neuropathy of Grade ≥ 2 or myelosuppression AEs of 
Grade ≥ 3 based on the local laboratory values for ANC, platelet count and hemoglobin.  The 
peripheral neuropathy events will be identified from the clinical AE dataset using the 
Standardised MedDRA Queries (SMQs). 
made.
ade.
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or 192
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udes all ran
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population
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e two treat
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mary safet
mary safe
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s, dose inte
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
46
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
The null (Ho) and alternative (Ha) hypotheses for this endpoint are as follows, where P is the rate 
of the AEs described for the primary safety endpoint: 
Ho:  P Arm B = P Arm A
Ha:  P Arm B ≠ P Arm A
The rate of the AEs described for the primary endpoint will be summarized within each 
treatment schedule by descriptive statistics. The treatment difference in the AE rate will be 
analyzed using a Mantel-Haenszel Chi-square test with ECOG performance status (0 versus 1) 
and histology (squamous cell carcinoma versus non-squamous cell carcinoma) as the 
stratification factors.  The ratio of the AE rates will be summarized along with the two-sided 
95% confidence interval (CI). 
10.6.2.
Adverse Events
Adverse events will be analyzed in terms of TEAEs, defined as any AE or SAE occurring or 
worsening on or after the first dose of the study drug through 28 days after the last dose of study 
drug.  In addition, any serious AE with an onset date more than 28 days after the last dose of 
study drug that is assessed by the investigator as related to study drug 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
Treatment-emergent adverse events, Grade 3 or higher TEAEs, serious AEs, TEAEs leading to 
dose reduction, dose delay, and dose interruption, TEAEs leading to treatment discontinuation, 
and TEAEs with an outcome of death will be summarized per treatment arms by MedDRA 
system organ class and preferred terms. 
Adverse events of special interest of the nab-paclitaxel plus carboplatin combination identified in 
previous studies in a similar population will be summarized in the same manner.
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
Laboratory parameters regularly collected on the eCRFs (ANC, platelets, hemoglobin, and serum 
creatinine) will be summarized by descriptive statistics by visit and treatment if the number of 
subjects with data is adequate. Clinically significant laboratory abnormalities will be reported 
and summarized as adverse events.
10.6.4.
Study Drug Exposure
The extent of exposure to the study drugs will be assessed based on the descriptive statistics on 
the number of cycles and study drug doses administered, cumulative dose, average dose 
intensity, and percentage of protocol dose administered.  The incidences of nab-paclitaxel and/or 
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10.6.4.
0.6.4.


('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
47
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
carboplatin dose reductions, dose interruptions, and dose delays will be summarized by treatment 
arm. 
10.7.
Efficacy Analysis
10.7.1.
Efficacy Endpoints 
10.7.1.1.
Progression-free Survival
Progression-free survival is defined as the time from the date of randomization to the date of 
disease progression or death (any cause) on or prior to the data cutoff date for analyses, 
whichever 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 study therapy. 
Subjects who do not have disease progression and are alive as of the data cutoff date for the 
statistical analysis will be censored at the date of the last radiologic assessment prior to the data 
cutoff date.  Similarly, subjects who discontinue from the study prior to disease progression or 
death will be censored at the date of the last radiologic assessment prior to the data cutoff date.  
In the event that a new anticancer treatment occurs prior to documented progression, the subject 
will be censored at the date of the last radiologic assessment where the subject was documented 
to be progression-free prior to the new anticancer treatment. Subjects with a single missing 
radiologic assessment prior to a visit with documented disease progression (or death) will be 
analyzed as a PFS event at the date of the radiologic assessment that shows progression or death 
(whichever is earlier). Subjects with two or more missing radiologic assessments prior to a visit 
with documented disease progression (or death) will be censored at the date of the last radiologic 
assessment where the subject was documented to be progression-free prior to the first of the two 
missing visits.  Subjects who do not die within the first two scheduled tumor assessments and do 
not have any post-baseline radiologic tumor assessment before the data cutoff date, will be 
censored on the date of randomization. 
The null (Ho) and alternative (Ha) hypotheses for testing the PFS endpoint are: 
Ho: HR Arm B / Arm A = 1
Ha: HR Arm B / Arm A ≠ 1
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% CI) for each treatment schedule along with the hazard ratio 
estimated using Cox proportional hazards model (including two-sided 95% CI). The Kaplan-
Meier curve for PFS will be presented graphically for each treatment schedule.  P-value from a 
stratified log-rank test will be reported as an indication for the strength of association for the 
difference between the two curves, where the strata include ECOG performance status (0 versus 
1) and histology (squamous versus non-squamous cell carcinoma), if the number of events in 
each cell is adequate.  
To assess the impact on PFS of radiologic assessments not occurring at the regularly scheduled 
assessment times, the frequency of these unscheduled/off-scheduled assessments will be 
presented for each treatment schedule. In addition, confirmatory and sensitivity analyses will be 
performed to further assess the impact of missed radiologic assessments. An additional analysis 
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Celgene Corporation
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ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
of PFS, where death or new treatment will be considered as an event, will be conducted to 
address the impact of second-line therapy. 
10.7.1.2.
Overall Survival
Overall survival is defined as the time between randomization and death. All deaths, regardless 
of the cause of death, will be included. All subjects who are lost to follow-up prior to the end of
the study or who are withdrawn from the study will be censored at the time of last contact. 
Subjects who are still receiving treatment as of the data cutoff date will be censored at the cutoff 
date. Overall survival will be analyzed similarly as PFS.
10.7.1.3.
Overall Response Rate 
Overall response rate is defined as the percent of subjects who had a radiologic complete or 
partial response according to RECIST Version 1.1 guidelines determined by the investigator and 
confirmed by repeat radiologic assessment performed no less than 28 days after the criteria for 
response were first met.
Overall response rate for each treatment arm will be presented with the two-sided 95% CI.  
Relative treatment effect will be summarized by the difference in response rate and the 
associated two-sided 95% CI.  P-value from a Chi-square test will be reported to indicate the 
strength of association of the relative treatment effect.  
10.7.2.
Exploratory Endpoints
10.7.2.1.
Health Care Utilization and Quality of Life Questionnaire
The analysis of health care utilization and quality of life questionnaire data will be described in 
detail in the SAP. 
  
10.8.
Study Therapy Termination
Reasons for stopping study therapy will be presented in listings and summarized by frequency of 
occurrence and corresponding percentage of occurrence.
10.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the study 
drug through 28 days post last dose of the study drug) 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). 
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Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
10.10.
Interim Analysis
10.10.1.
Interim Evaluation of Dosing, Safety and Efficacy
A non-binding interim evaluation of dosing, primary safety endpoint, and efficacy data will be 
conducted when approximately a total of 120 treated subjects have either completed 4 months of 
study treatment or discontinued study treatment due to progression, adverse events, deaths, lost 
to follow up, or other reasons. The interim evaluation will be conducted by an independent 
statistician and the results will be reviewed by the SSC. The SSC may recommend to stop the 
study early based on the study dosing data in relation to the primary hypothesis, or meeting of 
the futility criterion of the primary endpoint (if the treatment difference [Arm B minus Arm A] is 
≥-0.2% given the interim analysis of this endpoint is performed at 43% information fraction), or 
totality of the dosing, safety, and efficacy data as well as clinical significance. 
10.10.2.
Interim Analysis of Quality of Life Questionnaire Data
For administrative purposes (eg, planning of new studies, publication of data) the LCSS and EQ-
5D measurements will be summarized for the two treatment groups combined using descriptive 
statistics when approximately 50, 100, 150, and all subjects, respectively, have completed four 
cycles of treatment or discontinued treatment.
10.11.
Scientific Steering Committee
The conduct of this study will be overseen by a Steering Committee. The Steering Committee 
will serve in an advisory capacity to the Sponsor. 
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
50
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the eCRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of NSCLC will not require reporting as 
an adverse event. However, signs and symptoms (events) related to PD may be reported as 
adverse events. If reported, events of PD for NSCLC (including deaths due to PD for indications
that are considered to be fatal) will be assessed as expected adverse events, and will not be 
reported as expedited safety reports to regulatory authorities.
An overdose, accidental or intentional, whether or not it is associated with an AE, or abuse, 
withdrawal, sensitivity or toxicity to a study drug should be reported as an AE. If an overdose is 
associated with an AE, the overdose and adverse event should be reported as separate terms. See 
Section 8.8 for the definition of overdose.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for nab-paclitaxel, or 
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 
appropriate tests and procedures.
All AEs will be recorded by the investigator from the time the subject signs informed consent to
28 days after the last dose of study drug, and those SAEs made known to the investigator at any 
time thereafter that are suspected of being related to study drug. AEs and serious adverse events 
(SAEs) will be recorded on the AE page of the eCRF and in the subject’s source documents. All 
SAEs must be reported to Celgene Drug Safety within 24 hours of the investigator’s knowledge 
of the event by facsimile, or other appropriate method, using the SAE Report Form, or approved 
equivalent form.
11.2.
Evaluation of Adverse Events
A qualified investigator will evaluate all adverse events as to: 
11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
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Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
!
Results in death;
!
Is life-threatening (ie, in the opinion of the investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the eCRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of or an elective procedure for a pre-existing condition 
unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
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Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
52
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
For each SAE, the investigator will provide information on severity, start and stop dates, 
relationship to study drug, action taken regarding study drug, 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 National Cancer Institute (NCI) Common Terminology Criteria 
for Adverse Events (CTCAE, Version 4.0)
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Adverse events that are not defined in the NCI CTCAE should be evaluated for severity/intensity 
according to the following scale:
!
Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required
!
Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required
!
Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible
!
Grade 4 = Life threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable
!
Grade 5 = Death – the event results in death
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.
Seriousness, not severity, serves as a guide for defining regulatory obligations.
11.2.3.
Causality 
The investigator must determine the relationship between the administration of study drug 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 study drug 
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 study drug caused the adverse event.  ‘Reasonable 
possibility’ means there is evidence to suggest a causal 
relationship between the study drug and the adverse event.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
53
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
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 study 
drug 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 study drug as a result of an AE or SAE, as 
applicable (eg, discontinuation or reduction of study drug, as appropriate) and report if 
concomitant and/or additional treatments were given for the event. 
11.2.6.
Outcome
The investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered or death (due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of study drug dose, or any other 
therapeutic intervention; or
!
is judged to be of significant clinical importance.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF. If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE.
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
54
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
11.4.1.
Female Subjects
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 study drug, or within 28 days
of the subject’s last dose of study drug, are considered immediately reportable events. Study drug 
is to be discontinued immediately. The pregnancy, suspected pregnancy, or positive pregnancy 
test must be reported to Celgene Drug Safety immediately by facsimile, or other appropriate 
method, using the Pregnancy Initial Report Form, or approved equivalent form. The female 
subject should be referred to an obstetrician-gynecologist or another appropriate healthcare 
professional for further evaluation.
The investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the investigator
should report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate 
method, within 24 hours of the investigator’s knowledge of the event using the SAE Report 
Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the investigator suspects is 
related to the in utero exposure to the study drug should also be reported to Celgene Drug Safety 
by facsimile, or other appropriate method, within 24 hours of the investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving study drug
or within 6 months of the last dose of study drug, the male subject taking study drug should 
notify the investigator, and the pregnant female partner should be advised to call her healthcare 
provider immediately. If the male subject is receiving study drug, the study drug may need to be 
discontinued in the male subject, but may be resumed later at the discretion of the investigator
and Medical Monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The investigator is required to ensure that the data on these forms is accurate and consistent. This 
requirement applies to all SAEs (regardless of relationship to study drug) that occur during the 
study (from the time the subject signs informed consent to at least 28 days after the last dose of
study drug) and those made known to the investigator at anytime thereafter that are suspected of 
being related to study drug. SAEs occurring prior to treatment (after signing the ICF) will be 
captured.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
55
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
The SAE report should provide a detailed description of the SAE and include a concise summary 
of hospital records and other relevant documents. If a subject died and an autopsy has been 
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available. Any follow-up data will be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety.
Where required by local legislation, the investigator is responsible for informing the Independent 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The investigator must keep copies of all SAE 
information on file including correspondence with Celgene and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than five (5) business 
days. Urgent queries (eg, missing causality assessment) may be handled by phone.
11.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to nab-paclitaxel 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 study drug 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-005
Celgene Corporation
Confidential and Proprietary
56
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the study 
drug:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent 
!
Death
!
Lost to follow-up
!
Protocol violation
The decision to discontinue a subject remains the responsibility of the treating physician, which 
will not be delayed or refused by the sponsor. However, prior to discontinuing a subject, the 
investigator may contact the Medical Monitor and forward appropriate supporting documents for 
review and discussion.
All subjects discontinued from study drug for any reason will have a treatment discontinuation 
visit at the time of discontinuation and should undergo treatment discontinuation procedures.
All subjects discontinued from nab-paclitaxel will be followed for a period of 28 days after last 
dose of study drug for the collection of AEs.
Additionally subjects who withdraw from or discontinue treatment should be followed for 
progressive disease (if applicable), survival and any new anticancer therapy given.
The reason for treatment discontinuation should be recorded in the eCRF and in the source 
documents.
12.2.
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
study:
!
Withdrawal of consent
!
Death
!
Lost to follow-up
The following events may be considered sufficient reasons for discontinuing a subject from the 
study:
!
Adverse events(s)
!
Protocol violation
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
57
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. The investigator must notify the Medical Monitor immediately when a subject has 
been discontinued/withdrawn due to an AE (any unacceptable toxicity). All subjects who are 
withdrawn from the study should complete all protocol-required evaluations scheduled for early 
termination at the time of withdrawal.
Since follow-up of subjects who discontinue prematurely is of particular importance, every 
attempt should be made to collect all survival information and NSCLC treatment/therapy, unless 
the subject has specifically withdrawn consent from further follow-up. The investigator must 
make every effort to obtain minimal information regarding the subject’s survival status before 
determining that the subject is lost to follow-up.
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.
&(/*(1(35235,(7$5<,1)250$7,21
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
58
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the investigator should contact the responsible Clinical Research 
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page).This global Emergency 
Call Center is available 24 hours a day and 7 days a week. The representatives are responsible 
for obtaining your call-back information and contacting the on call 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. 
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not be
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
59
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, 
and investigator abide by Good Clinical Practice (GCP), as described in International Conference 
on Harmonization (ICH) Guideline E6 and in accordance with the general ethical principles 
outlined in the Declaration of Helsinki. The study will receive approval from an IRB/EC prior to 
commencement. The investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. Celgene staff or an authorized representative will evaluate and approve all 
investigators who in turn will select their staff.
The investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions. 
The investigator should maintain a list of sub-investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The investigator is responsible for keeping a record of all subjects who sign an ICF and are 
screened for entry into the study. Subjects who fail screening must have the reason(s) recorded in 
the subject’s source documents.
The investigator, or a designated member of the investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The investigator must ensure timely and accurate completion of eCRFs and queries.
14.3.
Subject Information and Informed Consent
The investigator must obtain informed consent of the subject and/or the subject’s legal 
representative prior to any study-related procedures.
Documentation that informed consent occurred prior to the subject’s entry into the study and of 
the informed consent process should be recorded in the subject’s source documents including the 
date. The original ICF signed and dated by the subject and by the person consenting the subject 
prior to the subject’s entry into the study, must be maintained in the investigator’s study files and 
a copy given to the subject. In addition, if a protocol is amended and it impacts the content of the 
informed consent, the ICF must be revised. Subjects participating in the study when the amended 
protocol is implemented must be re-consented with the revised version of the ICF. The revised 
ICF signed and dated by the subject and by the person consenting the subject must be maintained 
in the investigator’s study files and a copy given to the subject.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
60
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
This documentation must also include a list of the members of the IRB/EC and their occupation 
and qualifications. If the IRB/EC will not disclose the names, occupations and qualifications of 
the committee members, it should be asked to issue a statement confirming that the composition 
of the committee is in accordance with GCP. For example, the IRB General Assurance Number 
may be accepted as a substitute for this list. Formal approval by the IRB/EC should mention the 
protocol title, number, amendment number (if applicable), study site (or region or area of 
jurisdiction, as applicable), and any other documents reviewed. It must mention the date on 
which the decision was made and must be officially signed by a committee member. Before the 
first subject is enrolled in the study, all ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
The investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a coordinating investigator and the IRB/EC. This statement also applies to any 
communication between the investigator (or coordinating investigator, if applicable) and 
regulatory authorities.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
61
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
62
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The investigator must ensure that the records and documents pertaining to the conduct of the 
study and distribution of the study drug 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 eCRFs or CD-ROM.
15.2.
Data Management
Data will be 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 study drug. The investigator must retain 
these documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the investigator, Celgene, and their authorized 
representative(s);
!
List of sub-investigators and other appropriately qualified persons to whom the 
investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of eCRFs (if paper) and of documentation of corrections for all subjects;
!
Study drug accountability records;
!
Record of any body fluids or tissue samples retained;
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
63
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
!
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The investigator must notify 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-005
Celgene Corporation
Confidential and Proprietary
64
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
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, eCRFs, procedures for obtaining informed 
consent, record keeping, and reporting of AEs/SAEs with the investigator. Monitoring will 
include on-site visits with the investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, 
eCRFs, subject’s source documents, and all other study documentation will be 
inspected/reviewed by the Celgene representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the eCRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the investigator and/or his/her staff. Any necessary 
corrections will be made directly to the eCRFs or via queries by the investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene. Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The investigator is required to permit direct access to the facilities where the study took place, 
source documents, eCRFs and applicable supporting records of subject participation for audits 
and inspections by IRB/IECs, regulatory authorities (eg, FDA, European Medicines Agency 
[EMA], Health Canada) and company authorized representatives. The investigator should make 
every effort to be available for the audits and/or inspections. If the investigator is contacted by 
any regulatory authority regarding an inspection, he/she should contact Celgene immediately.
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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
65
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
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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('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
66
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
18.
REFERENCES
Azzoli CG, Baker Jr. S, Temin S, Pao W, Aliff T, Brahmer J, et al. American Society of Clinical 
Oncology clinical practice guideline update on chemotherapy for Stage IV non-small-cell lung 
cancer. J Clin Oncol. 2009;27:6251-66.
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;26:468-73.
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, Dancey J, et al. New 
response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J 
Cancer. 2009 Jan;45(2):228-47. 
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 
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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.
Hwang IK, Shih WJ, De Cani JS. Group sequential designs using a family of type I error
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Lorenz W, Reimann HJ, Schmal A, Dormann P, Schwarz B, Neugebauer E, et al. Histamine 
release in dogs by Cremophor El and its derivatives: oxethylated oleic acid is the most effective 
constituent. Agents Actions 1977;7:63-7.
National Institute for Health & Clinical Excellence (NICE): The Diagnosis and Treatment of 
Lung Cancer: Methods, Evidence & Guidance, 2011.
Oken, MM, Creech, RH, Tormey, DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and 
Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol. 
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Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, et al. Intergroupe Francophone 
de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared 
with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 
randomised, phase 3 trial. Lancet. 2011;378(9796):1079-88. 
Rizvi NA, Riely GJ, Azzoli CG, Miller VA, Ng KK, Fiore J, et al. Phase I/II trial of weekly 
intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with Stage IV 
non-small-cell lung cancer. J Clin Oncol. 2008;26(4):639-43.
Schiller JH, Gandara DR, Goss GD, Vokes EE.  Non-small-cell lung cancer: then and now. 
J Clin Oncol. 2013;31(8):981-3.
&(/*(1(35235,(7$5<,1)250$7,21
eated 
ated
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
 Cremopho
Cremop
on.n Eur J C
Eur J 
uential desi
uential desi
1990;9:143
1990;9:143
ormann P, 
ormann P, 
d i
d its deriva
ts deriv
i
7;7:63
7;7:63-7.
-7.
& Clinical
Clinic
Evidence &
Evidenc
RH, Torme
RH, Torm
Of The Ea
Of The Ea
55.
55.
alcman G, 
alcman G, 
érologie Th
érologie T
monotherap
onother
ndo
domised, 
mised, 
Ri
Rizvi NA
zvi NA
rav
ra


('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
67
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
Socinski MA, Langer CJ, Okamoto I, Hon JK, Hirsh V, Dakhil SR, et al. Safety and efficacy of 
weekly nab®-paclitaxel in combination with carboplatin as first-line therapy in elderly patients 
with advanced non-small-cell lung cancer. Ann Oncol. 2013;24(2):314-21. 
Socinski MA, Manikhas GM, Stroyakovsky DL, Makhson AN, Cheporov SV, Orlov SV, et al. A 
dose finding study of weekly and every-3-week nab-paclitaxel followed by carboplatin as 
first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol. 
2010;5(6):852-61.
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. 
Review.
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.
&(/*(1(35235,(7$5<,1)250$7,21
latatioion n
):665
):665-85.
85
Sparreboom
parreboom
lasma phar
asma pha
18-24.
-24.
Trump DL
Trump DL
(7):1263
(7):1263-8.
-8


('06'RF1XPEHU
nab®-Paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
68
ABI-007-NSCL-005 Amendment 3.0 Final: 17 Mar 2016
19.
APPENDICES
Appendix A: ECOG Performance Status Score
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5
Dead
Oken, 1982.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
TITLE PAGE
SAFETY AND EFFICACY OF nab-PACLITAXEL 
(ABRAXANE®) IN COMBINATION WITH 
CARBOPLATIN AS FIRST LINE TREATMENT IN 
ELDERLY SUBJECTS WITH ADVANCED NON-SMALL 
CELL LUNG CANCER (NSCLC): A PHASE IV, 
RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY
(ABOUND.70+)
STUDY DRUG
nab-Paclitaxel (Abraxane®)
PROTOCOL NUMBER:
ABI-007-NSCL-005
ORIGINAL DATE FINAL:
06 Mar 2014
AMENDMENT 1 DATE FINAL:
09 Apr 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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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 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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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 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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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 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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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:
 
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
PROTOCOL SUMMARY
Study Title
Safety and efficacy of nab-paclitaxel (Abraxane) in combination with carboplatin as first line 
treatment in elderly subjects with advanced non-small cell lung cancer (NSCLC): A Phase IV, 
randomized, open-label, multicenter study (Abound.70+).
Indication
First-line treatment of advanced NSCLC in elderly subjects.
Objectives
Primary
!
To assess the safety and tolerability of continuous weekly versus weekly times three 
with one-week break nab-paclitaxel (Abraxane) in combination with carboplatin as 
first-line treatment for advanced NSCLC in elderly subjects (≥ 70 years old).
Secondary 
!
To evaluate the efficacy of nab-paclitaxel in combination with carboplatin in elderly 
subjects with advanced NSCLC.
Exploratory 
!
To assess healthcare resource utilization for the two nab-paclitaxel treatment arms.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ-5D) for the two nab-paclitaxel treatment arms.
!
 
 
!
 
Study Design
This is a Phase IV, randomized, open-label, multicenter study of continuous weekly versus 
weekly times three with one-week break nab-paclitaxel in combination with carboplatin as first-
line treatment in elderly subjects (≥ 70 years old) with advanced NSCLC who are not candidates 
for curative surgery or radiation therapy. Approximately 284 subjects with locally advanced or 
metastatic NSCLC will be randomized in this study to receive nab-paclitaxel in combination 
with carboplatin and will be randomized 1:1 into one of the two treatment arms prior to starting 
first dose of study drug. Randomization will be centralized and stratified by Eastern Cooperative 
Oncology Group (ECOG) performance status (0 versus 1, see Appendix A) and histology 
(squamous cell carcinoma versus non-squamous cell carcinoma).
The study will consist of a 28-day Screening Period, a Treatment Period and a Follow-up Period.  
 randomize
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
The Screening Period for eligibility determination begins upon subject written informed consent.  
All screening assessments must be completed within 28 days prior to first dose of study drug.
The Treatment Period begins with the first dose of study drug as described in Section 8.  Subjects 
will receive one of the following treatments based on the randomization assignment:
Arm A (21-day treatment cycle):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment cycle,
!
Carboplatin area under the curve (AUC) = 6 mg*min/mL IV on Day 1 of each 21-day 
treatment cycle after completion of nab-paclitaxel infusion.
Arm B (21-day treatment followed by one-week break cycle, 28-day duration):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment  followed by one-week break cycle (i.e. every 28 
days),
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment followed by 
one-week break cycle (i.e. every 28 days), after completion of nab-paclitaxel 
infusion. 
No additional anticancer agents are allowed during study treatment.  All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of 
consent, in accordance with local standard of care.
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
(v1.1) (Eisenhauer, 2009).
Local laboratory test data for absolute neutrophil count (ANC), platelet count, hemoglobin and 
serum creatinine will be collected in the electronic case report forms (eCRFs). All other 
laboratory test data, except those mentioned above, will not be collected routinely in the eCRF. 
All abnormal and clinically significant laboratory test results will be reported as adverse events 
(AEs) or serious adverse events (SAEs), and the specific associated laboratory parameter(s) 
should be recorded on the laboratory assessments eCRF. Local safety laboratory data will also be 
the primary guide for eligibility and subject management. In addition, test results for tumor 
mutational status of genes including but not limited to EGFR, ALK, and KRAS will be collected 
and recorded on eCRF if these tests have been performed locally for routine diagnosis.  
All subjects who discontinue from treatment for any reason other than withdrawal of consent or
lost to follow-up will enter the Follow-up Period. It will consist of a visit 28 days after treatment 
discontinuation. Thereafter, subjects will be followed for survival approximately every 90 days 
(or when they are seen for routine care) by phone call or chart review for documentation of last 
contact for up to 6 months after the last subject is randomized or 192 progression-free survival 
(PFS) events have been observed, whichever comes later.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
Those subjects entering the Follow-up Period without documented progression will continue to 
have computed tomography (CT) scans in accordance with standard of care (at least every 90 
days) until documented progression of disease, withdrawal of consent, lost to follow-up, death or 
study closure. 
Study Population
Male and female subjects ≥ 70 years of age, with locally advanced or metastatic NSCLC 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.
Length of Study
The enrollment of 284 subjects on this study will take approximately 24 months. The total length 
of this Phase IV study with follow-up is estimated to be approximately 3 years.  
Study Treatments
nab-Paclitaxel and carboplatin are designated as non-investigational products and investigative 
sites will use standard of care (commercially available) product via routine prescription.
The preparation for IV administration procedures for nab-paclitaxel and carboplatin should be 
followed in accordance with the approved Prescribing Information for each drug.
Statistical Methods
Approximately 284 subjects will be randomized in a 1:1 ratio to one of two treatment arms 
(approximately 142 per arm).  Arm A will receive nab-paclitaxel 100 mg/m2 administered on 
Days 1, 8 and 15 in combination with carboplatin AUC = 6 mg*min/mL on Day 1 of each 21-
day treatment cycle, and Arm B will receive the same treatment in the same schedule as that of 
Arm A during the first 21 days, followed by a one-week break prior to the start of the next cycle
(28-day duration).  
Randomization will be stratified by ECOG performance status (0 versus 1) and histology 
(squamous cell carcinoma versus non-squamous cell carcinoma).
The primary objective of this study is to assess the safety and tolerability of the two treatment 
arms for first-line treatment of locally advanced or metastatic NSCLC in elderly subjects ( ≥ 70 
years old).  The primary study endpoint, correspondingly, is the percentage of subjects with 
either peripheral neuropathy of Grade ≥2 or myelosuppression AEs Grade ≥3 based on the local
laboratory values for ANC, platelet count, and hemoglobin, assessed using National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4.0). 
The peripheral neuropathy events will be identified from the clinical AE dataset using the 
Standardised MedDRA Queries (SMQs). For the purpose of this protocol, this endpoint will be 
referred to as the percentage of subjects with Grade ≥2 peripheral neuropathy or Grade ≥3 
myelosuppression laboratory adverse events.  
The study is designed to detect a difference of 16 percentage points between the 2 treatment arms
with respect to the primary safety endpoint with 80% power and a Type-I error rate of 5% (two-
sided), assuming 139 of the 142 randomized subjects per arm will receive at least one dose of 
study drug and the percentage of the treated subjects with the AEs specified above is 73% for 
Arm A.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
9
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
A non-binding interim analysis for futility with the primary safety endpoint will be conducted 
when approximately a total of 139 treated subjects have either completed 6 months of study 
treatment or discontinued from the study due to progression, adverse events, deaths, lost to 
follow up, or other reasons. The study may be stopped early for futility if the treatment 
difference is between ± 0.4%, given the interim analysis is performed at 50% information 
fraction. 
Overview of Safety Assessment
The treated population, which includes all randomized subjects who received at least one dose of 
study drug, will be the analysis population for all safety analyses.  
The primary study endpoint (a composite safety endpoint) will be the percentage of subjects with 
Grade ≥2 peripheral neuropathy or Grade ≥3 myelosuppression laboratory adverse events.  
The null (Ho) and alternative (Ha) hypotheses for this endpoint are as follows, where P is the rate 
of the AEs described for the primary safety endpoint: 
Ho:  P Arm B = P Arm A
Ha:  P Arm B ≠ P Arm A
The AE rate of the primary study endpoint will be summarized within each treatment arm by 
descriptive statistics.  The treatment difference in the AE rate will be analyzed using a Mantel-
Haenszel Chi-square test with ECOG performance status (0 versus 1) and histology (squamous 
cell carcinoma versus non-squamous cell carcinoma) as the stratification factors.  The ratio of the 
AE rates will be summarized along with the two-sided 95% confidence interval (CI). 
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AE or SAE that begins or worsens in grade on or after the start of the study drug
through 28 days after the last dose of the study drug. Additionally, any SAE that occurs beyond 
this period of observation and is assessed by the investigator as related to the study drug, will be 
reported and analyzed.  
Treatment-emergent adverse events will be summarized by treatment arm by system organ class
and preferred term. Grade 3 or higher TEAEs, SAEs, TEAEs leading to dose modification 
(reduction, delay not given, and interruption), TEAEs leading to treatment discontinuation, and 
TEAEs with an outcome of death will be summarized by treatment arm. Adverse events of 
special interest of the nab-paclitaxel and carboplatin combination identified in previous studies
in a similar population will be summarized in the same manner.
In order to investigate the maximal degree of myelosuppression, ANC, platelet count, and 
hemoglobin will be summarized by the most severe grade in each treatment cycle and by the 
most severe grade during the study using NCI CTCAE v4.0. 
Overview of Efficacy Assessment
All efficacy analyses will be based on the intent-to-treat (ITT) population, which includes all 
randomized subjects regardless of whether they receive any study drugs or have any efficacy 
assessments performed.  
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
10
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Progression-free Survival (PFS) based on investigator’s assessment of the subject’s radiologic 
response using RECIST v1.1 guidelines, Overall Response Rate (ORR), and Overall Survival 
(OS) are the key efficacy endpoints.  Since the primary research interest of this study is to 
evaluate the relative safety and toxicities of the two treatment arms, the sample size was
calculated based on the primary safety endpoint, the percentage of subjects with Grade ≥2
peripheral neuropathy or Grade ≥3 myelosuppression laboratory adverse events.  Consequently, 
a statistically non-significant treatment difference in PFS, ORR or OS could simply be a function 
of the sample size and/or the lack of statistical power. Therefore, the assessments of treatment 
differences in PFS and OS will be based on the hazard ratios and in ORR, the ratio of response 
rates, and the corresponding 95% confidence intervals. P-values for between-group comparisons 
will be provided to indicate the strength of association only.  No multiplicity adjustment with the 
Type-I error rate will be made. 
Progression-free survival is defined as the time from the randomization date to the start of 
disease progression or subject death from any cause, whichever occurs first. Subjects who do not 
have disease progression or have not died as of the data cutoff date for the statistical analysis will 
be censored at the time of the last radiologic assessment prior to the data cutoff date. Rules for 
censoring for missing visits and start of anticancer treatment are provided in Section 10. 
Progression-free survival will be summarized using the Kaplan-Meier method and by median 
PFS time (including two-sided 95% confidence interval [CI]) for each treatment arm along with 
the hazard ratio (including two-sided 95% CI) between treatment arms. The Kaplan-Meier curve 
for PFS will be presented graphically for each treatment arm. To illustrate the strength of 
association, the p-value for treatment difference in the curves will be reported from a stratified 
log-rank test with ECOG performance status (0 versus 1) and histology (squamous versus non-
squamous cell carcinoma) as the stratification factors.  
Of note, if recruitment is complete in 24 months, assuming that approximately 67% of the 284 
subjects randomized will experience a PFS event (approximately 192 PFS events total) within 28
months from first subject randomized, there is 73% power to detect a hazard ratio (HR) of 0.69 
for PFS improvement with Arm B over Arm A and an overall Type-I error rate of 5% (two-
sided).  Assuming an exponential distribution with a median time to PFS of 5.8 months for Arm 
A and proportional hazards, a hazard ratio of 0.69 constitutes a 2.6 months improvement for Arm 
B. 
Overall response rate (percent of subjects who had a radiologic complete or partial response 
according to the investigator’s assessment of response based on RECIST v1.1 guidelines) and 
OS also will be assessed by descriptive statistics with the associated 95% CIs.  P-values from a 
Chi-square test and a stratified log-rank test will be provided to indicate the strength of 
association for the treatment differences in ORR and OS, respectively.  
The analyses of the safety and efficacy endpoints for the clinical study report will be performed 
after ~192 PFS events have been observed.
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PF


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TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
1.
INTRODUCTION..................................................................................................18
1.1.
Non-small Cell Lung Cancer ..................................................................................18
1.2.
nab-Paclitaxel in NSCLC .......................................................................................19
1.3.
Rationale for Further Study of nab-Paclitaxel as First-line Treatment in 
Elderly Subjects with Advanced NSCLC................................................................20
2.
STUDY OBJECTIVES...........................................................................................22
2.1.
Primary Objectives .................................................................................................22
2.2.
Secondary Objective...............................................................................................22
2.3.
Exploratory Objectives ...........................................................................................22
3.
STUDY ENDPOINTS............................................................................................23
3.1.
Primary Endpoint....................................................................................................23
3.2.
Secondary Endpoints ..............................................................................................23
3.2.1.
Safety.....................................................................................................................23
3.2.2.
Efficacy..................................................................................................................23
3.3.
Exploratory Endpoints............................................................................................23
4.
OVERALL STUDY DESIGN ................................................................................24
4.1.
Study Design ..........................................................................................................24
4.1.1.
Follow-up Period....................................................................................................25
4.2.
Study Design Rationale ..........................................................................................25
4.3.
Study Duration .......................................................................................................27
4.4.
End of Trial ............................................................................................................27
5.
TABLE OF EVENTS.............................................................................................28
6.
PROCEDURES......................................................................................................31
6.1.
Medical History......................................................................................................31
6.2.
Prior and Concomitant Medications/Procedures......................................................31
6.3.
Computed Tomography (CT) Scan of Complete Chest (including base of 
neck and adrenal glands).........................................................................................31
6.4.
Weight....................................................................................................................32
6.5.
Body Surface Area (BSA) Calculation and Height..................................................32
6.6.
ECOG Performance Score ......................................................................................32
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Medical 
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3.3.
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4


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6.7.
Peripheral Neuropathy Assessment.........................................................................32
6.8.
Adverse Event Reporting........................................................................................32
6.9.
Lung Cancer Symptom Scale Questionnaire and EQ-5D.........................................32
6.10.
Healthcare Resource Utilization Questionnaire .......................................................32
6.11.
Electrocardiogram ..................................................................................................33
6.12.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI) .......................33
6.13.
Bone Scans and X-rays...........................................................................................33
6.14.
Physical Examinations............................................................................................33
6.15.
Vital Signs..............................................................................................................33
6.16.
Laboratory Assessments .........................................................................................33
6.17.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) .....................................................................................34
6.18.
Survival..................................................................................................................34
7.
STUDY POPULATION.........................................................................................36
7.1.
Number of Subjects and Sites .................................................................................36
7.2.
Inclusion Criteria....................................................................................................36
7.3.
Exclusion Criteria...................................................................................................37
8.
DESCRIPTION OF STUDY TREATMENTS........................................................39
8.1.
Description of Study Drug(s)..................................................................................39
8.1.1.
nab-Paclitaxel.........................................................................................................39
8.1.2.
Carboplatin.............................................................................................................39
8.2.
Treatment Administration and Schedule .................................................................39
8.3.
Dose Modifications.................................................................................................40
8.4.
Method of Treatment Assignment...........................................................................42
8.5.
Packaging and Labeling..........................................................................................42
8.6.
Study Drug Accountability and Disposal ................................................................42
8.7.
Study Drug Compliance..........................................................................................42
8.8.
Overdose ................................................................................................................42
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................43
9.1.
Permitted Concomitant Medications and Procedures...............................................43
9.2.
Prohibited Concomitant Medications and Procedures..............................................43
9.3.
Required Concomitant Medications and Procedures................................................43
10.
STATISTICAL ANALYSES..................................................................................44
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9.1.
9.1


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10.1.
Overview................................................................................................................44
10.2.
Study Population Definitions ..................................................................................44
10.2.1.
Intent-to-treat Population........................................................................................44
10.2.2.
Per-protocol (PP) Population ..................................................................................44
10.2.3.
Treated Population..................................................................................................44
10.3.
Sample Size and Power Considerations...................................................................44
10.4.
Background and Demographic Characteristics........................................................46
10.5.
Subject Disposition.................................................................................................46
10.6.
Safety Analysis.......................................................................................................46
10.6.1.
Primary Safety Endpoint.........................................................................................46
10.6.2.
Adverse Events.......................................................................................................47
10.6.3.
Laboratory Assessments .........................................................................................47
10.6.4.
Study Drug Exposure..............................................................................................48
10.7.
Efficacy Analysis....................................................................................................48
10.7.1.
Key Efficacy Endpoints..........................................................................................48
10.7.1.1.
Progression-free Survival........................................................................................48
10.7.1.2.
Overall Survival .....................................................................................................49
10.7.1.3.
Overall Response Rate............................................................................................49
10.7.2.
Exploratory Endpoints............................................................................................49
10.7.2.1.
Health Care Utilization and Quality of Life Questionnaire......................................49
10.8.
Study Therapy Termination ....................................................................................49
10.9.
Deaths ....................................................................................................................49
10.10.
Interim Analysis .....................................................................................................50
10.11.
Scientific Steering Committee ................................................................................50
11.
ADVERSE EVENTS..............................................................................................51
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................51
11.2.
Evaluation of Adverse Events.................................................................................51
11.2.1.
Seriousness.............................................................................................................51
11.2.2.
Severity / Intensity..................................................................................................53
11.2.3.
Causality ................................................................................................................53
11.2.4.
Duration .................................................................................................................54
11.2.5.
Action Taken..........................................................................................................54
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1.2.1.
11.2.2.
1.2.2.
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11.2.6.
Outcome.................................................................................................................54
11.3.
Abnormal Laboratory Values..................................................................................54
11.4.
Pregnancy...............................................................................................................54
11.4.1.
Female Subjects......................................................................................................55
11.4.2.
Male Subjects.........................................................................................................55
11.5.
Reporting of Serious Adverse Events......................................................................55
11.5.1.
Safety Queries ........................................................................................................56
11.6.
Expedited Reporting of Adverse Events..................................................................56
12.
DISCONTINUATIONS .........................................................................................57
12.1.
Study Treatment Discontinuation............................................................................57
12.2.
Study Discontinuation ............................................................................................57
12.3.
Subject Replacement ..............................................................................................58
13.
EMERGENCY PROCEDURES.............................................................................59
13.1.
Emergency Contact.................................................................................................59
14.
REGULATORY CONSIDERATIONS...................................................................60
14.1.
Good Clinical Practice............................................................................................60
14.2.
Investigator Responsibilities...................................................................................60
14.3.
Subject Information and Informed Consent.............................................................60
14.4.
Confidentiality........................................................................................................61
14.5.
Protocol Amendments.............................................................................................61
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................61
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................62
14.8.
Closure of the Study ...............................................................................................62
15.
DATA HANDLING AND RECORDKEEPING.....................................................63
15.1.
Data/Documents .....................................................................................................63
15.2.
Data Management...................................................................................................63
15.3.
Record Retention....................................................................................................63
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................65
16.1.
Study Monitoring and Source Data Verification......................................................65
16.2.
Audits and Inspections............................................................................................65
17.
PUBLICATIONS ...................................................................................................66
18.
REFERENCES.......................................................................................................67
5
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16.1.
6
2


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19.
APPENDICES........................................................................................................69
Appendix A:
ECOG Performance Status Score.......................................................................69
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LIST OF TABLES
Table 1:
Blinded Radiology Assessment of Overall Response Rate (ITT Population) ...........20
Table 3:
Table of Events.......................................................................................................28
Table 4:
Permanent Dose Reductions for Hematologic and Neurologic Toxicities and 
Dosing on the Study ...............................................................................................41
&(/*(1(35235,(7$5<,1)250$7,21
.41
41


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


nab-paclitaxel
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1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer
Lung cancer is the leading cause of cancer-related deaths among men and women worldwide, 
with 1.2 million new cases diagnosed each year. Non-small cell lung cancer (NSCLC) is the 
most common type of lung cancer, accounting for 80% of all new cases. There are an estimated 
1.1 million lives lost per year (approximately 500,000 in the United States [US] and European 
Union [EU] alone) due to NSCLC. Smoking is the causative factor for up to 85% of cases 
(http://www.lungcancercoalition.org/en/pages/about/awareness).
The majority of patients are not diagnosed until the tumor has progressed beyond the primary 
site. Despite step-wise advances in patient selection, targeted agents and optimizing
chemotherapy regimens, patients with advanced NSCLC continue to have an unmet medical 
need (Schiller, 2013).
Platinum-containing chemotherapy regimens remain the standard first-line treatment in the 
majority of patients, in the US and Japan. In the EU, a third-generation chemotherapeutic agent 
(docetaxel, gemcitabine, paclitaxel, or vinorelbine), most commonly gemcitabine or vinorelbine, 
plus a platinum drug is used for advanced NSCLC (NICE, 2011). For first-line therapy in 
patients with Stage IV NSCLC and good performance status, the American Society of Clinical 
Oncology (ASCO) clinical practice guideline recommends treatment with a platinum-based 
two-drug combination of cytotoxic drugs (Azzoli, 2009). A trend that is becoming more 
prevalent is personalized NSCLC treatment based on tumor histology (squamous versus
non-squamous), on molecular characteristics of the tumor, and on the patient’s clinical status 
using agents targeting specific receptors and kinases and pathways (ie, epidermal growth factor 
receptor [EGFR], echinoderm microtubule-associated protein-like 4 [EML4] and anaplastic 
lymphoma kinase [ALK] fusion protein).
In advanced NSCLC, the prevalently used combination of solvent-based 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, and requires the use of specialized infusion sets and in-line 
filters that do not contain di[2-ethylhexyl] phthalate (DEHP).
Compared with solvent-based paclitaxel, nab-paclitaxel exhibits 10-fold higher mean Cmax of 
free paclitaxel, delivers 33% higher drug concentration to tumors in preclinical xenograft 
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perio


nab-paclitaxel
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models, and demonstrates enhanced transport across endothelial cell monolayers (Desai, 2006; 
Gardner, 2008). The Cremophor EL-free medium enables nab-paclitaxelto be given in a shorter
duration without the need for premedication to prevent solvent-related hypersensitivity reactions.
In addition, standard tubing and intravenous (IV) bags may be used for the IV administration of 
nab-paclitaxel. 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. 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.
1.2.
nab-Paclitaxel in NSCLC
The Food and Drug Administration (FDA) approval of nab-paclitaxel 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. 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%), see Table 1].
Non-inferiority analysis of overall survival (OS) demonstrated that nab-paclitaxel/carboplatin
(nab-p/C) treatment is not inferior to solvent-based paclitaxel/carboplatin (sb-P/C) treatment. 
Overall survival in the nab-paclitaxel arm was 12.1 months versus 11.2 months in the control 
arm (p = 0.271; HR = 0.922).  Toxicities, particularly neuropathy and neutropenia were less 
pronounced using nab-paclitaxel in the dose and schedule employed.
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unced usin


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Table 1:
Blinded Radiology Assessment of Overall Response Rate (ITT Population)
Variable
Category/Statistic
nab-Paclitaxel/
Carboplatin
(N=521)
sb-Paclitaxel/
Carboplatin
(N=531)
Response Rate 
Ratio
(pA/pT)a
p-value
Patients with Confirmed Complete or Partial Overall Response
n (%)
170 (33%)
132 (25%)
1.313
0.005*
Confidence Interval (CI) b
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%)
a PA/PT equals response rate of nab-paclitaxel/response rate of sb paclitaxel.
b 95% CI of response rate and 95.1% CI of response rate ratio.
* Indicates p-value < 0.049.Note: P-value is based on a chi-square test.
Source: Data on File.
Adverse events were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. The following common (≥ 10% incidence) 
adverse events were observed at a similar incidence in nab-paclitaxel and paclitaxel 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).
1.3.
Rationale for Further Study of nab-Paclitaxel as First-line Treatment 
in Elderly Subjects with Advanced NSCLC
The tolerability of doublet chemotherapy in elderly patients with advanced NSCLC is an
important therapeutic consideration, whereby the landmark IFCT 0501 reported that first-line sb-
paclitaxel given weekly three weeks out of four coupled with carboplatin every 4 weeks (i.e.
21days of treatment followed by one-week break) improved efficacy over single-agent 
chemotherapy (either gemcitabine or vinorelbine) in patients 70 years or older with advanced 
NSCLC. The results demonstrated that doublet chemotherapy was feasible in this elderly
population with an acceptable toxicity profile, when sb-paclitaxel/carboplatin was given as 21
days of treatment followed by one-week rest. The combination also resulted in a significant 
improvement in OS (median, 10.3 versus 6.2 months; HR = 0.639, 95% CI:0.52-0.79, p <
0.0001), with 1-year survival rates of 45.1% versus 26.9% for doublet therapy and monotherapy.  
This prospective trial set a standard, against which doublet-regimens must be measured in the 
elderly population with advanced NSCLC.
In the CA031 study of nab-paclitaxel (Abraxane) in combination with carboplatin, patients were 
stratified by age (< 70 years old versus ≥ 70 years old). Fifteen percent of ITT patients were 
elderly (≥70 years: nab-paclitaxel, n = 74: sb-paclitaxel, n = 82). Baseline characteristics were 
generally well balanced between treatment arms in elderly population, and subgroup analyses 
were performed to assess the influence of age on the primary efficacy endpoint of overall 
response rate as well as PFS and OS (Socinski, 2013). 
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
Of note, the post-hoc analysis of the CA031 trial showed marked improvement in survival in the 
nab-paclitaxel/carboplatin arm. Amongst 156 elderly (≥70 years of age) subjects randomized on 
the study, OS was 19.9 months versus 10.4 months (HR: 0.583, p = 0.009) in favor of the nab-
p/C arm compared to sb-p/C. The proportion of patients who had complete or partial response 
were consistently higher in all age stratum groups for the nab-paclitaxel/carboplatin regimen 
relative to the sb-paclitaxel/carboplatin regimen (in patients ≥ 70 years of age 34% versus 24% 
respectively, ratio of rates 1.385, p = 0.196, 
).
 
 
 
Although it was a statistically significant treatment effect in favor of nab-paclitaxel in the elderly 
subgroup from CA031 trial, 46% of patients in the nab-paclitaxel/carboplatin arm experienced 
dose reductions or dose delays. Approximately 92% of dose modifications and reductions were 
due to AEs. The most common clinical AEs in this subgroup were hematologic Grade ≥ 3 
neutropenia (45%), anemia (22%) and thrombocytopenia (19%). Approximately 18% of the 
elderly population in the CA031 trial had Grade ≥ 2 peripheral neuropathy. Despite that,
approximately 10% more elderly patients in the nab-paclitaxel arm were able to receive second-
line therapy compared to sb-paclitaxel (61% versus 50%, respectively), possibly because they 
may have been in better shape due to a better tolerated first-line regimen with nab-paclitaxel or 
better disease and symptom control as demonstrated as improvement in ORR.
The results from the elderly subset in CA031 trial showed the combination of nab-paclitaxel and 
carboplatin to be particularly promising. We hypothesize that the tolerability can be improved 
further by introducing a one week break at the end of each treatment cycle (similar to the 
schedule advocated by Quoix, 2011) among elderly patients.  Reducing the rate of the most 
common AEs (Grade ≥ 3 myelosuppression toxicities and Grade ≥ 2 peripheral neuropathy) by 
16% will be clinically meaningful as it can potentially improve tolerability, quality of life and 
allow patients to receive treatment for a longer period of time, without necessarily compromising 
efficacy.  
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
22
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
2.
STUDY OBJECTIVES
2.1.
Primary Objectives 
!
To assess the safety and tolerability of continuous weekly versus weekly times three 
with one-week break nab-paclitaxel (Abraxane) in combination with carboplatin as 
first-line treatment for advanced NSCLC in elderly subjects (≥ 70 years old).
2.2.
Secondary Objective
!
To evaluate the efficacy of nab-paclitaxel in combination with carboplatin in elderly 
subjects with advanced NSCLC.
2.3.
Exploratory Objectives
!
To assess healthcare resource utilization for the two nab-paclitaxel treatment arms.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ-5D) for the two nab-paclitaxel treatment arms.
!
 
 
!
 
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
23
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
3.
STUDY ENDPOINTS
3.1.
Primary Endpoint
!
The primary study endpoint is the percentage of subjects with either peripheral 
neuropathy of Grade ≥2 or myelosuppression AEs of Grade ≥3 based on the local
laboratory values for ANC, platelet count, and hemoglobin. All AEs will be graded 
using NCI CTCAE v4.0. 
3.2.
Secondary Endpoints
The secondary endpoints are: 
3.2.1.
Safety
!
The type, frequency, and severity of AEs and SAEs. 
!
Discontinuation rate.
!
Dose intensity administered.
!
The incidence of dose reduction and dose delay.
3.2.2.
Efficacy
!
Progression-free Survival (PFS).
!
Overall response rate (ORR) using RECIST v1.1 guidelines.
!
Overall Survival (OS).
3.3.
Exploratory Endpoints
!
Healthcare resource utilization during the study using a questionnaire.
!
Changes in the LCSS and EQ-5D.
!
 
!
 
 
!
Additional exploratory endpoints may be defined in the statistical analysis plan 
(SAP), if applicable.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
24
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is a Phase IV, randomized, open-label, multicenter study of continuous weekly versus
weekly times three with one-week break nab-paclitaxel in combination with carboplatin as first-
line treatment in elderly subjects (≥ 70 years old) with advanced NSCLC who are not candidates 
for curative surgery or radiation therapy.
Subjects will be randomized 1:1 to receive one of the following treatments:
Arm A (21-day treatment cycle):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment cycle after 
completion of nab-paclitaxel infusion 
Arm B (21-day treatment followed by one-week break cycle, 28-day duration):
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment  followed by one-week break cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment followed by 
one-week break cycle, after completion of nab-paclitaxel infusion 
The study will consist of a 28-day Screening Period, a Treatment Period, and a Follow-up
Period.
The Screening Period will start from signing the Informed Consent Form (ICF) until first dose of 
study drug. 
The Treatment Period will start from first dose of study drug until End-of-Treatment Visit 
(which is defined as visit with last dose of study drug).
Follow-up Period will start after End-of-Treatment visit.
No additional anticancer agents are allowed during study treatment. All supportive care
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of 
consent, in accordance with local standard of care.
Tumor evaluations will be assessed locally and response (Complete Response [CR] or Partial 
Response [PR]) will be determined according to RECIST guidelines, Version 1.1. In both 
treatment arms, tumor assessments will be conducted at screening, every 42 days (-3/+7 days) 
(starting from Day 1 Cycle 1) until disease progression (even if treatment has been 
discontinued), withdrawal of consent, lost to follow-up, death or if clinically indicated while on 
treatment.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
25
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
Local laboratory test data for ANC, platelet count, hemoglobin and serum creatinine 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 AE, or SAE, 
and the specific associated laboratory parameter(s) should be recorded in the laboratory 
assessments eCRF. Local safety laboratory data will also be the primary guide for eligibility and 
subject management. In addition, test results for tumor mutational status of genes including but 
not limited to EGFR, ALK, and KRAS will be collected and recorded on eCRF if these tests 
have been performed locally for routine diagnosis.  
4.1.1.
Follow-up Period
All subjects who discontinue from treatment for reasons other than withdrawal of consent or lost 
to follow-up, will enter the Follow-up Period. It will consist of a visit 28 days after treatment 
discontinuation following by follow-up for survival approximately every 90 days (+/- 14 days or 
when they are seen for routine care) by phone call or chart review for documentation of last 
contact for up to 6 months after the last subject is randomized or 192 PFS events have been 
observed, whichever comes later.
Those subjects entering the Follow-up Period without documented progression will continue to 
have CT scans in accordance with standard of care (at least every 90 days) until documented 
progression of disease, withdrawal of consent, lost to follow-up, death or study closure.
4.2.
Study Design Rationale
The nab-paclitaxel schedule used in Arm A is in accordance with pivotal trial CA031,
ie,100 mg/m2 administered once per week on Days 1, 8 and 15 combined with carboplatin 
AUC = 6 mg*min/mL administered on Day 1 every 21 days, as approved by the FDA.  The nab-
paclitaxel/carboplatin schedule used in Arm B is the same schedule as the current approved nab-
paclitaxel label with introduction of a one-week break following 21 days of treatment. This 
study will determine whether the one-week break can further improve tolerability without 
compromising efficacy (similar to the schedule advocated by Quoix, 2011) among elderly 
patients.  Reducing the rate of the most common AEs (Grade ≥ 3 myelosuppression toxicities 
and Grade ≥ 2 peripheral neuropathy) by 16% will be clinically meaningful as it can potentially 
improve tolerability, quality of life and allow subjects to receive treatment for a longer period of 
time.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
26
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
Figure 1:
Overall Study Design
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
27
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
4.3.
Study Duration
Recruitment is expected to take approximately 24 months, and the analysis of PFS will be 
performed when approximately 192 PFS events have occurred, estimated as approximately 28
months from first subject randomized. The total length of this Phase IV study with follow-up is 
estimated to last approximately 3 years.
4.4.
End of Trial
The End of Trial is defined as either the:
!
date of the last visit of the last subject to complete the study, or 
!
the date of receipt of the last data point from the last subject that is required for primary, 
secondary and/or exploratory analysis, as pre-specified in the protocol and/or the SAP, 
whichever is the later date.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
28
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
5.
TABLE OF EVENTS
Table 3:
Table of Events
Screening
/ Baseline
Treatment Perioda
Every cycle starting with Cycle 1
Follow-Up Period
Assessment
Day -28 
to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days) 
(counting from 
Day 1 Cycle 1)
End-of-
Treatment
Visit (last dose 
of study drug)
28-day Follow-up 
Visit (after last 
dose of study 
drug)
Survival Follow-Upb
Every 90 days (+/-
14 days) (after 28-
day follow-up visit)
Informed Consent
X
-
-
-
-
-
-
-
Medical History, Prior Medication and Procedures
X
-
-
-
-
-
-
-
CT Scan of Complete Chest (including base of neck 
and adrenal glands) and any other studies required 
for Tumor Imagingc
X
-
-
-
X c
X c
-
X c
Weight and Heightd
X
X
X
X
-
-
-
-
Body Surface Area (BSA) Calculationd
X
-
-
-
-
-
-
-
ECOG status
X
X
-
-
-
X
X
-
Concomitant Medication/Procedures
-
X
X
X
-
X
X
X
Peripheral Neuropathy Assessmente
X
X
X
X
-
X
X
-
Healthcare Resource Utilization Questionnaire
-
X
-
-
-
X
X
-
Hematologyf (ANC, platelet count, Hgb)
X
X
X
X
-
X
X
-
Serum Chemistryf (serum creatinine)
X
X
-
-
-
X
X
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
29
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
Table 3:
Table of Events (Continued)
Screening
/ Baseline
Treatment Perioda
Every cycle starting with Cycle 1
Follow-Up Period
Assessment
Day -28 
to
Day -1
Day 1
( ±2 days)
Day 8
(±2 
days)
Day 15
(±2 
days)
Every 42 days 
(-3/+7 days) 
(starting Day 1 
Cycle 1)
End-of-
Treatment
(last dose of 
study drug)
28-day Follow-up 
Visit (after last 
dose of study 
drug)
Survival Follow-Upb
Every 90 days (+/-
14 days) (after 28-
day follow-up visit)
Blood for Pharmacogenomic Analyses
-
X
(C1D1 only)
-
-
-
-
-
-
Adverse Event Evaluation
After signing ICF and until 28 days after the last dose of study drug
nab-paclitaxel Administration/accountabilityg
-
X
X
X
-
-
-
-
Carboplatin Administration/accountabilityg
-
X
-
-
-
-
-
-
LCSS and EQ-5D
-
X
-
-
-
X
X
-
Survival phone call (or chart review for 
documentation of last contact or when they are seen 
for routine care
-
-
-
-
-
-
-
Xb
Electrocardiogram (ECG)
Will be done as per standard of care at screening, during the Treatment Period and as clinically indicated; however, results 
will not be routinely collected in the eCRFs. Results will be collected in the eCRFs as AE or SAE only if results are abnormal 
and clinically significant.
CT Scan of the Head or Brain Magnetic Resonance 
Imaging (MRI)
Bone Scan (X-rays if needed)
Physical Examination
Vital Signs
AE = Adverse Event; ANC = absolute neutrophil count; C1D1 = Cycle 1, Day 1; CT = Computed Tomography; ECOG = Eastern Cooperative Oncology Group; eCRF = electronic 
Case Report Form; EQ-5D = EuroQol 5D; ICF = informed consent form; LCSS = Lung Cancer Symptom Scale; SAE = Serious Adverse Event.
a Treatment Period:  Arm A: nab-paclitaxel Days 1, 8, and 15 and carboplatin Day 1. Arm B: nab-paclitaxel Days 1, 8, and 15 and carboplatin Day 1 followed by one-week break.
b Every 90 (+/-14) days (from 28-day Follow-up Visit) or when they are seen for routine care for up to 6 months after the last subject is randomized or 192 PFS events have been 
observed, whichever comes later.
c All subjects must have a radiographically documented measurable tumor(s) by RECIST Version 1.1 criteria: CT scan of complete chest (including base of neck and adrenal 
glands) are performed at screening, every 42 days (-3/+7 days) thereafter (counting from Day 1 Cycle 1) until disease progression, withdrawal of consent, lost to follow-up, 
death and if clinically indicated while on treatment. The methods of assessment chosen at baseline to follow tumors are to remain consistent throughout study duration. Those 
subjects entering the Follow-up Period without documented progression will continue to have CT scans in accordance with standard of care (at least every 90 days) until 
documented progression of disease, withdrawal of consent, lost to follow-up, death or study closure.
d BSA will be calculated at screening and recalculated if body weight changes by more than 10% during the study. Height will only be obtained at Screening Visit. Weight will be 
obtained at screening and every visit during the Treatment Period before administration of study drug, but will only be collected on the eCRF for the Screening Visit.
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Celgene Corporation
Confidential and Proprietary
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e The occurrence of peripheral neuropathy will be reported by the investigator per protocol as an AE or SAE.
f Laboratory assessments will be done prior to each nab-paclitaxel treatment as per standard of care during the study and as clinically indicated. ANC, platelet count, hemoglobin
(Hgb) level and serum creatinine results will be collected in the eCRFs (all other routine laboratory test data except those mentioned above will not be collected in the eCRF
unless it is clinically significant, which will then be reported as AEs or SAEs, and the specific associated laboratory parameter(s) should be recorded on the laboratory 
assessments eCRF).
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
6.
PROCEDURES
Subjects will be provided with a written ICF, given the opportunity to ask any questions 
concerning the study and will sign an ICF prior to participating in any study procedures. After 
giving written informed consent, subjects will undergo a Screening Period to be assessed for 
eligibility. All subjects who sign an ICF must be entered into the Interactive Randomization 
Technology (IRT) system immediately upon signature on the document. Subjects who do not 
meet the eligibility criteria will be considered screening failures and will not be eligible for the 
study. Subjects who screen fail may re-screen up to 2 times at any time and an ICF will need to 
be re-signed, as well as all screening procedures repeated (some procedures may not need to be 
done if previously done within 28 days prior to screening again). Subjects that have met all 
eligibility criteria after the Screening Period will be eligible to be randomized. 
6.1.
Medical History
Only clinically significant or ongoing medical conditions will be recorded at screening on the 
eCRF. 
6.2.
Prior and Concomitant Medications/Procedures
Prior medications are considered any medications stopped prior to the date of the first dose of 
study drug. Only prior medications/procedures (of clinically significant or ongoing medical 
conditions) within 28 days of time of signature on the ICF should be recorded. All NSCLC-
related prior medications/procedures (including radiation therapy) should be recorded regardless 
of time. 
Concomitant medications and procedures are considered any medications or procedures that 
were taken on or after the date of the first dose of study drug. All subjects will have concomitant 
medications and procedures (including radiation therapy) recorded from the time of signature on 
the ICF until the 28-day Follow-up Visit, for conditions that are clinically significant or ongoing. 
During the Follow-up Period only NSCLC-associated concomitant medications/procedures 
(including radiation therapy) will be recorded, ie, subsequent-line(s) of anti-cancer therapy.
6.3.
Computed Tomography (CT) Scan of Complete Chest (including 
base of neck and adrenal glands)
A CT scan of complete chest (including base of neck and adrenal glands) and any other studies 
required for tumor imaging will be done at screening, every 42 days (-3/+7 days) (starting from 
Day 1 Cycle 1) until treatment discontinuation or withdrawal of consent. Those subjects entering 
the Follow-up Period without documented progression will continue to have CT scans in 
accordance with standard of care (at least every 90 days) until documented progression of 
disease, withdrawal of consent, lost to follow-up, death or study closure. Additional CT scans
may be done at any time during the study if clinically indicated. All CT scans and reports should 
be archived at the site according to site regulations and copies provided to Sponsor if requested.
e
ed to
d to
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nab-paclitaxel
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Celgene Corporation
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6.4.
Weight
Weight will be obtained at screening and at every visit during the Treatment Period before 
administration of study drug, but will only be collected on the eCRF for the Screening Visit.
Additional weights may be collected per local standards at any time during the study as needed.
6.5.
Body Surface Area (BSA) Calculation and Height
Height will be collected at screening only, and BSA will be calculated at screening of the study.
BSA will be recalculated if body weight changes by more than 10% during the study.
6.6.
ECOG Performance Score
Eastern Cooperative Oncology Group performance score will be collected at screening, Day 1 of 
every treatment cycle, at the End-of-Treatment visit and at the 28-day Follow-up Visit. 
Additional ECOG assessments may be performed at any time during the study as clinically 
indicated.
6.7.
Peripheral Neuropathy Assessment
Peripheral neuropathy (sensory or motor) assessment will be done at screening, Day 1, 8, 15 of 
every treatment cycle, at the End-of-Treatment visit and at the 28-day Follow-up Visit. Changes 
in neuropathy grade from baseline will be reported as an AE as per Section 11. Additional 
peripheral neuropathy assessments may be done at any time during the study as clinically 
indicated.
6.8.
Adverse Event Reporting
Adverse events will be recorded from time of signature on the ICF until 28 days after the last 
dose of study drug, including any unscheduled visits. See Section 11 for details. 
6.9.
Lung Cancer Symptom Scale Questionnaire and EQ-5D
The LCSS and EQ-5D questionnaires will be used to measure quality of life (QoL) for subjects 
in the study. The LCSS is comprised of 9 questions to be completed by the subject using a visual 
analogue scale (VAS) to denote intensity of a symptom. The EQ-5D comprises 5 questions on 
mobility, self-care, usual activities, pain/discomfort, anxiety/depression and a VAS for overall 
QoL. These questionnaires will be completed at Day 1 of every Treatment Period, at the End-of-
Treatment Visit and at the 28-day Follow-up Visit.
6.10.
Healthcare Resource Utilization Questionnaire
A healthcare resource utilization questionnaire will be used to capture the additional use of 
healthcare resources, including hospitalizations, emergency room visits, doctor or nurse visits, 
procedures, and/or additional medication during the study period. The assessment will be 
completed at Day 1 of every treatment cycle, at the End-of-Treatment visit and at 28-day Follow-
up Visit. 
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nab-paclitaxel
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Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
6.11.
Electrocardiogram
Electrocardiograms (ECGs) will be done per standard of care at screening, during the Treatment 
Period and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if 
results are abnormal, changed and clinically significant.
6.12.
CT Scan of the Head or Brain Magnetic Resonance Imaging (MRI)
A CT scan of the head, or preferably brain MRI, will be done as per standard of care at 
screening, during the Treatment Period, and as clinically indicated. Results will be collected in 
the eCRFs as an AE or SAE only if the results are abnormal and clinically significant.
6.13.
Bone Scans and X-rays
Bone scans and x-rays will be done as per standard of care at screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if 
results are abnormal and clinically significant.
6.14.
Physical Examinations
Physical examinations will be done as per standard of care at screening, during the Treatment 
Period, and as clinically indicated. Results will be collected in the eCRFs as AE or SAE only if 
results are abnormal and clinically significant.
6.15.
Vital Signs
Vital signs will be done as per standard of care at screening, during the Treatment Period, and as 
clinically indicated. Results will be collected in the eCRFs as AE or SAE only if results are 
abnormal and clinically significant.
6.16.
Laboratory Assessments
Laboratory assessments will be done as indicated in Table 3 by local laboratories as per standard 
of care during the study and as clinically indicated. Local laboratory test data for ANC, platelet 
count and hemoglobin must be collected at screening, each visit before administration of study 
drug, at the End-of-Treatment visit and at the 28-day Follow-up Visit in the eCRF. Serum 
creatinine must be collected at screening, Day 1 of each cycle, at the End-of-Treatment visit and 
at the 28-day Follow-up Visit in the eCRF. Normal ranges for these selected parameters will be 
collected on the eCRF. All other laboratory test data, except those mentioned above, will not be 
collected routinely in the eCRF. Local safety laboratory data will also be the primary guide for 
eligibility and subject management. It is the responsibility of the investigator to assess the 
clinical significance of all abnormal values as defined by the reference ranges from the local 
laboratory. All clinically significant laboratory abnormalities (Section 11.3) are to be recorded as 
AEs on the AE eCRF, and the specific laboratory parameter(s) as well as the corresponding 
normal ranges should be recorded on the laboratory assessments eCRF. Clinically significant 
laboratory abnormalities at screening may result in subject ineligibility for the study and should 
not be captured as AE. Any abnormal values that persist should be followed at the discretion of 
the investigator. The investigator should file all copies of the reports, including faxes with the 
subject’s medical chart.
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Confidential and Proprietary
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6.17.
Tumor Tissue Sample Collection and Peripheral Blood Collection
(Exploratory Assessments) 
Provision of tumor tissue is mandatory for study enrollment, except when no tumor tissue is 
extant and this requirement would necessitate a new procedure such as a biopsy to collect it.  
 
 
 
 
 
 
 
 
 
 
 
 
 
In addition, test results for tumor mutational status of genes including but not limited to EGFR, 
ALK, and KRAS will be collected and recorded on eCRF if these tests have been performed
locally for routine diagnosis.
 
 
 
 
 
 
6.18.
Survival 
After the End-of-Treatment Visit, the subjects will have a 28-day Follow-up Visit followed by a 
call or chart review for documentation of last contact approximately every 90 days (or when they 
are seen for routine care) for up to 6 months after the last subject is randomized or 192 PFS 
events have been observed, whichever comes later. The subjects will also be asked questions 
about other medications they may be taking for their NSCLC or their medical records will be 
reviewed to determine a last contact date for routine purposes. Those subjects entering the 
Follow-up Period without documented progression will continue to have CT scans in accordance 
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
35
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
with standard of care (at least every 90 days) until documented progression of disease, 
withdrawal of consent, lost to follow-up, death or study closure.
&(/*(1(35235,(7$5<,1)250$7,21


nab-paclitaxel
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Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Elderly (≥70 years of age) male and female subjects with locally advanced or metastatic NSCLC 
with no prior chemotherapy for metastatic disease will be eligible for this study. The study will 
enroll approximately 284 subjects. The study will be conducted at approximately 65 sites in the 
United States.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be randomized in the study:
1. Age ≥ 70 years at the time of signing the ICF.
2. Understand and voluntarily provide written informed consent prior to the conduct of any 
study related assessments/procedures.  
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Histologically or cytologically confirmed locally advanced or metastatic NSCLC who are 
not candidates for curative surgery or radiation therapy.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease (defined by the presence of 
≥1 radiographically documented measurable lesion).
7. No prior chemotherapy for the treatment of metastatic disease. Adjuvant chemotherapy is 
permitted providing cytotoxic chemotherapy was completed 12 months prior to signing 
the ICF and without disease recurrence.
8. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
9. Platelets ≥ 100,000 cells/mm3.
10. Hemoglobin (Hgb) ≥ 9 g/dL.
11. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]), alanine
transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper limit of 
normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
12. Total bilirubin ≤ 1.5 mg/dL (unless there is a known history of Gilberts Syndrome).
13. Creatinine clearance (CrCl) > 40 mL/min calculated using Cockcroft-Gault equation (if 
renal impairment is suspected 24 hour urine collection for measurement is required).
14. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
15. Females who (1) have undergone hysterectomy (the surgical removal of the uterus) or 
bilateral oophorectomy (the surgical removal of both ovaries) or (2) have been naturally 
postmenopausal for at least 24 consecutive months (ie, has not had menses at any time 
during the preceding 24 consecutive months).
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15.5. F


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Male subjects must:
a.
Practice true abstinence* or agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the study, 
during dose interruptions and for at least 28 days following study drug 
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
≥4 weeks 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. Preexisting 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 a study drug: 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 allergy or hypersensitivity to nab-paclitaxel or carboplatin.
13. Currently enrolled in any other clinical protocol or investigational trial that involves
administration of experimental therapy and/or therapeutic devices.
                                               
* 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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Celgene Corporation
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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 randomization. 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 of 
which 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.
18. Females who (1) have not undergone hysterectomy (the surgical removal of the uterus) or 
bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been 
naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any 
time during the preceding 24 consecutive months).
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8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Study Drug(s)
Treatment
Subjects will receive open-label nab-paclitaxel and carboplatin during the Treatment Period of 
the study. The nab-paclitaxel and carboplatin are designated as noninvestigational products and 
investigative sites will use standard of care (commercially available) product via prescription.
The preparation for IV administration procedures should be followed as per approved 
Prescribing Information.
8.1.1.
nab-Paclitaxel
Each single-use 50 mL vial contains paclitaxel (100 mg) and approximately 900 mg human 
albumin as a stabilizer.
Unreconstituted nab-paclitaxel should be stored in accordance with the product label. 
Reconstituted nab-paclitaxel should be used immediately. If not used immediately, the vial of 
reconstituted nab-paclitaxel must be placed in its carton and be placed in a refrigerator at 2° to 
8°C (36° to 46°F) for a maximum of 8 hours. Both forms should be stored in an area free of 
environmental extremes and should be accessible only to study personnel.
Temperature records for nab-paclitaxel must be made available to Celgene or other Sponsor-
nominated monitoring teams for verification of proper study drug storage.
8.1.2.
Carboplatin
Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic
agent. The chemical name for carboplatin is platinum diammine [1,1-cyclobutane-
dicarboxylato (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 package insert. 
8.2.
Treatment Administration and Schedule
Approximately 284 subjects will be treated with nab-paclitaxel plus carboplatin until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of 
consent.
Treatment will commence on Day 1, in accordance with standard of care of first-line treatment of 
NSCLC: 
Arm A:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day treatment cycle,
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment cycle, after 
completion of nab-paclitaxel infusion
OR
Arm B:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8 and 15 of each 
21-day treatment with one-week break cycle (i.e. every 28 days),
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment with one-
week break cycle (i.e. every 28 days), after completion of nab-paclitaxel infusion.
8.3.
Dose Modifications
Subjects who experience any of the adverse drug reactions in Table 4 will be dose reduced as per 
Table 4 during treatment. 
!
Do not administer nab-paclitaxel on Day 1 of a cycle until ANC is at least 
1500 cells/mm3 and platelet count is at least 100,000 cells/mm3.
!
In subjects who develop severe neutropenia or thrombocytopenia withhold treatment 
until counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and 
platelet count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil 
count of at least 500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on 
Days 8 or 15 of the cycle. Upon resumption of dosing, permanently reduce nab-
paclitaxel and carboplatin doses as outlined in Table 4.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-
paclitaxel and carboplatin at reduced doses (Table 4) when peripheral neuropathy 
improves to Grade 1 or completely resolves.
Re-escalation is not permitted at any time. 
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nab-paclitaxel
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Table 4:
Permanent Dose Reductions for Hematologic and Neurologic Toxicities and Dosing on the Study
Dose Modification During Treatment for A and B arms
Adverse Drug Reaction
Occurrence
nab-Paclitaxel Dose
(mg/m2)
Carboplatin Dose 
(AUC 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*
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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 twice, the subject should generally have treatment discontinued unless, at 
the discretion of the investigator, there is evidence of continuing benefit to the subject that outweighs the risk of recurrent toxicity. Re-Escalation is not 
permitted at anytime.
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8.4.
Method of Treatment Assignment
The Treatment Period of the study is open-label. Enrollment/randomization will occur via IRT 
system for all periods of the study. 
8.5.
Packaging and Labeling
nab-Paclitaxel and carboplatin are designated as noninvestigational products and investigative 
sites will use standard of care (commercially available) product via prescription.
8.6.
Study Drug Accountability and Disposal
nab-Paclitaxel and carboplatin are designated as noninvestigational products and investigative 
sites will use standard of care (commercially available) product via prescription. Procedures for 
proper handling and disposal of anticancer drug must comply with the relevant health, safety and 
environment regulations.
8.7.
Study Drug Compliance
Study drug will be administered only by study site personnel and accurate recording of all study 
drug 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 or carboplatin dosing only.
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel or carboplatin given to a subject, regardless of any associated adverse events or 
sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. See 
Section 11.1 for the reporting of adverse events associated with overdose.
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9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
Over the course of this study, additional medications may be required to manage aspects of the 
disease state of the subjects, including side effects from study treatments or disease recurrence. 
All supportive care (including but not limited to antiemetic medications, white blood cell (WBC)
growth factors, erythrocyte stimulating agents, zolendronic acid, and denosumab) is permitted
and may be administered at the discretion of the investigator, according to local guidelines. 
9.2.
Prohibited Concomitant Medications and Procedures
Other antineoplastic agents or Investigational Product than what is specified in the protocol are 
prohibited.
9.3.
Required Concomitant Medications and Procedures
Not applicable.
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10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the study are described 
below.  Additional analyses of these endpoints as well as exploratory endpoints or subgroup 
analyses will be described in detail in the SAP.  The SAP supersedes the analyses described in 
the protocol should there be differences between the two.
10.1.
Overview
Approximately 284 subjects will be randomized in a 1:1 ratio to two treatment arms (142 
subjects per group).  Arm A will receive nab-paclitaxel 100 mg/m2 administered on Days 1, 8 
and 15 followed by carboplatin AUC = 6 mg*min/mL on Day 1 of each 21-day treatment cycle. 
Arm B will receive the same treatment in the same schedule as that of Arm A during the first 21 
days of treatment, but followed by a one-week break prior to the start of next cycle (28-day 
duration). All subjects will receive the assigned study treatment until disease progression, 
unacceptable toxicity, death, lost to follow-up, or withdrawal of consent, in accordance of local 
standard of care.  A permuted-block randomization method will be employed, and the 
randomization will be carried out centrally using an IRT system. The randomization will be 
stratified based on the following 2 baseline or prognostic factors:
!
ECOG performance status (0 versus 1)
!
Histology (squamous cell carcinoma versus non-squamous cell carcinoma)
10.2.
Study Population Definitions
10.2.1.
Intent-to-treat Population
The primary efficacy analysis will be performed on the ITT population, which includes all 
randomized subjects regardless of whether the subject receives any study drug or has any 
efficacy assessments performed. 
10.2.2.
Per-protocol (PP) Population
The PP population is defined as all eligible subjects randomized who receive at least one dose of 
the study drug and have been treated in the arm they were assigned to. Additional analyses 
utilizing the PP population will be described in the SAP.
10.2.3.
Treated Population
The treated population will consist of all randomized subjects who receive at least one dose of 
study drug. The treatment groups for the safety analyses will be based on the treatment as 
received if different from the assigned treatment by randomization.
10.3.
Sample Size and Power Considerations
The primary objective of this study is to assess the safety and tolerability of nab-paclitaxel in 
combination with carboplatin administered in 21-day treatment cycles continuously or with a 
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one-week break in between cycles for the treatment of locally advanced or metastatic NSCLC in 
elderly subjects (≥ 70 years old). 
The primary study endpoint (also the primary safety endpoint) is the percentage of subjects with 
either peripheral neuropathy of Grade ≥2 or myelosuppression AEs of Grade ≥3 based on the 
local laboratory values for ANC, platelet count, and hemoglobin.  For the purpose of this 
protocol, this endpoint will be referred to as the percentage of subjects with Grade ≥2 peripheral 
neuropathy or Grade ≥3 myelosuppression laboratory adverse events.  
In Protocol CA031, the Phase 3 NSCLC study of the nab-paclitaxel development program, 
approximately 2% of the elderly subjects randomized discontinued from the study prior to 
receiving any study drug.  In addition, approximately 73% of the treated elderly subjects had 
AEs that fell in the category of AEs described above for the primary safety endpoint of the 
current study.  
The study is designed to detect a difference of 16 percentage points between the 2 treatment arms 
with respect to the primary safety endpoint with 80% power and a Type-I error of 5% (two-
sided), assuming the percentage of subjects with the AEs specified above is 73% for Arm A.  
Therefore, the current study is planned to randomize approximately 284 subjects to the 2 
treatment arms in a 1:1 ratio, with the expectation that approximately 278 subjects (139 per 
group) will receive at least one dose of study drug (as observed in CA031) and be included in the 
treated population for the analysis of the primary safety endpoint.
A non-binding interim analysis for futility with the primary safety endpoint will be conducted 
when approximately a total of 139 treated subjects have either completed 6 months of study 
treatment or discontinued from the study due to progression, adverse events, deaths, lost to 
follow up, or other reasons. The stopping rule and the final marginal significance level are 
determined based on the Gamma family spending function with parameter = -7 (Hwang, 1990) to
control the Type-II error rate at 20%. The study may be stopped early for futility if the treatment 
difference is between ± 0.4% (Z-score ± 0.054) given the interim analysis is performed at 50% 
information fraction.  
Progression free survival, OS, and ORR are the key efficacy endpoints of the study.  Since the 
primary research interest of this study is to evaluate the relative safety and toxicities of the 2 
treatment arms, the sample size was calculated based on the primary safety endpoint, the 
percentage of subjects with Grade ≥2 peripheral neuropathy or Grade ≥3 myelosuppression 
laboratory AEs, hence, the study is underpowered for the key efficacy endpoint, PFS, OS and 
ORR.  Consequently, a non-significant treatment difference in PFS, OS or ORR could simply be 
a function of the sample size and/or the lack of statistical power. Therefore, the assessments of 
all efficacy endpoints will be based on the point estimates and the associated 95% confidence 
intervals for the within-group parameters of interest and the between-group differences.  P-
values for between-group comparisons will be provided to indicate the strength of association 
only.  No multiplicity adjustment with the Type-I error rate will be made. 
Of note, based on the data from CA031 it is expected that approximately 67% of the 284
randomized subjects will have a PFS event during the study (i.e. approximately 192 PFS events 
total).  With 192 PFS events, there is 73% power to detect a hazard ratio (HR) of 0.69 for PFS 
improvement with Arm B over Arm A and an overall Type-I error of 5% (two-sided).  Assuming 
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an exponential distribution with a median time to PFS of 5.8 months for Arm A and proportional 
hazards, a hazard ratio of 0.69 constitutes a 2.6 months improvement for Arm B.  
As an illustration for timeline projection, assuming an exponential distribution for PFS, a 24-
month recruitment period for 284 subjects, and a median PFS of approximately 5.8 months for 
Arm A, it will take approximately 28 months from the first subject randomized to observe 192 
PFS events.
The analysis of both the safety and efficacy endpoints for the clinical study report will be 
performed when approximately 192 PFS events have been observed.  No adjustment for the 
multiple treatment comparisons among the primary and secondary study endpoints will be made.  
Subjects will be followed for OS for at least 6 months after the last subject is randomized or 192 
PFS events have been observed, whichever comes later.
10.4.
Background and Demographic Characteristics
The baseline characteristics of all randomized subjects will be summarized. Subject’s age, 
height, weight, and baseline characteristics will be summarized using descriptive statistics, while 
gender, race and other categorical variables will be provided using frequency tabulations. 
Selected medical history data will be summarized using frequency tabulations by system organ 
class and preferred term.
10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both Treatment
and Follow-up Periods. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
10.6.
Safety Analysis
The treated population, which includes all randomized subjects who received at least one dose of 
study drug, will be the analysis population for all safety analyses.
The safety/tolerability of the two treatment arms will be monitored through continuous reporting 
and evaluated by the primary safety endpoint, adverse events and serious adverse events, 
abnormalities in ANC, platelet count and hemoglobin, and incidence of subjects experiencing 
dose modifications, dose interruptions, and/or premature discontinuation of study drug.
10.6.1.
Primary Safety Endpoint
The primary endpoint for this study is a composite safety endpoint, namely, the percentage of 
subjects who develop either peripheral neuropathy of Grade ≥2 or myelosuppression AEs of 
Grade ≥3 based on the local laboratory values for ANC, platelet count and hemoglobin.  The 
peripheral neuropathy events will be identified from the clinical AE dataset using the 
Standardised MedDRA Queries (SMQs). 
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The null (Ho) and alternative (Ha) hypotheses for this endpoint are as follows, where P is the rate 
of the AEs described for the primary safety endpoint: 
Ho:  P Arm B = P Arm A
Ha:  P Arm B ≠ P Arm A
The rate of the AEs described for the primary endpoint will be summarized within each 
treatment schedule by descriptive statistics. The treatment difference in the AE rate will be 
analyzed using a Mantel-Haenszel Chi-square test with ECOG performance status (0 versus 1)
and histology (squamous cell carcinoma versus non-squamous cell carcinoma) as the
stratification factors.  The ratio of the AE rates will be summarized along with the two-sided 
95% confidence interval (CI). 
10.6.2.
Adverse Events
Adverse events will be analyzed in terms of TEAEs, defined as any AE or SAE occurring or 
worsening on or after the first dose of the study drug through 28 days after the last dose of study 
drug.  In addition, any serious AE with an onset date more than 28 days after the last dose of 
study drug that is assessed by the investigator as related to study drug 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
Treatment-emergent adverse events, Grade 3 or higher TEAEs, serious AEs, TEAEs leading to
dose reduction, dose delay, and dose interruption, TEAEs leading to treatment discontinuation, 
and TEAEs with an outcome of death will be summarized per treatment arms by MedDRA 
system organ class and preferred terms.
Adverse events of special interest of the nab-paclitaxel plus carboplatin combination identified in 
previous studies in a similar population will be summarized in the same manner.
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, 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 for each treatment arm.  
All other laboratory parameters reported on the eCRFs will be summarized by descriptive 
statistics by visit and treatment if the number of subjects with data is adequate. In addition, NCI 
CTCAE v 4.0 grades for the reported parameters will be summarized, if applicable.  
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10.6.4.
Study Drug Exposure
The extent of exposure to the study drugs will be assessed based on the descriptive statistics on 
the number of cycles and study drug 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 by treatment 
arm. 
10.7.
Efficacy Analysis
10.7.1.
Key Efficacy Endpoints 
10.7.1.1.
Progression-free Survival
Progression-free survival is defined as the time from the date of randomization to the date of 
disease progression or death (any cause) on or prior to the data cutoff date for analyses, 
whichever 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 study therapy.
Subjects who do not have disease progression, or 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 randomization.
The null (Ho) and alternative (Ha) hypotheses for testing the PFS endpoint are: 
Ho: HR Arm B / Arm A = 1
Ha: HR Arm B / Arm A ≠ 1
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% CI) for each treatment schedule along with the hazard ratio 
estimated using Cox proportional hazards model (including two-sided 95% CI). The Kaplan-
Meier curve for PFS will be presented graphically for each treatment schedule.  P-value from a
stratified log-rank test will be reported as an indication for the strength of association for the 
difference between the two curves, where the strata include ECOG performance status (0 versus 
1) and histology (squamous versus non-squamous cell carcinoma), if the number of events in 
each cell is adequate.  
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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 for each treatment schedule. In addition, confirmatory and sensitivity analyses will be 
performed to further assess the impact of missed radiologic assessments. An additional analysis 
of PFS, where death or new treatment will be considered as an event, will be conducted to 
address the impact of second-line therapy. 
10.7.1.2.
Overall Survival
Overall survival is defined as the time between randomization and death. All deaths, regardless 
of the cause of death, will be included. All subjects who are lost to follow-up prior to the end of
the study or who are withdrawn from the study will be censored at the time of last contact. 
Subjects who are still receiving treatment as of the data cutoff date will be censored at the cutoff 
date. Overall survival will be analyzed similarly as PFS.
10.7.1.3.
Overall Response Rate 
Overall response rate is defined as the percent of subjects who had a radiologic complete or 
partial response according to RECIST Version 1.1 guidelines determined by the investigator and 
confirmed by repeat radiologic assessment performed no less than 28 days after the criteria for 
response were first met.  
Overall response rate for each treatment arm will be presented with the two-sided 95% CI.  
Relative treatment effect will be summarized by the difference in response rate and the 
associated two-sided 95% CI.  P-value from a Chi-square test will be reported to indicate the 
strength of association of the relative treatment effect.  
10.7.2.
Exploratory Endpoints
10.7.2.1.
Health Care Utilization and Quality of Life Questionnaire
The analysis of health care utilization and quality of life questionnaire data will be described in 
detail in the SAP.
 
10.8.
Study Therapy Termination
Reasons for stopping study therapy will be presented in listings and summarized by frequency of 
occurrence and corresponding percentage of occurrence.
10.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the study 
drug through 28 days post last dose of the study drug) 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).
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10.10.
Interim Analysis
A non-binding interim analysis for futility with the primary safety endpoint will be conducted 
when approximately a total of 139 treated subjects have either completed 6 months of study 
treatment or discontinued from the study due to progression, adverse events, deaths, lost to 
follow up, or other reasons. The stopping rule and the final marginal significance level are 
determined based on the Gamma family spending function with parameter = -7 (Hwang, 1990) to 
control the Type-II error rate at 20%. The study may be stopped early for futility if the treatment 
difference is between ± 0.4% (Z-score ± 0.054) given the interim analysis is performed at 50% 
information fraction.
10.11.
Scientific Steering Committee
The conduct of this study will be overseen by a Steering Committee. The Steering Committee 
will serve in an advisory capacity to the Sponsor. 
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11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the eCRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of NSCLC will not require reporting as 
an adverse event.
An overdose, accidental or intentional, whether or not it is associated with an AE, or abuse, 
withdrawal, sensitivity or toxicity to a study drug should be reported as an AE. If an overdose is 
associated with an AE, the overdose and adverse event should be reported as separate terms. See 
Section 8.8 for the definition of overdose.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for nab-paclitaxel, or 
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 
appropriate tests and procedures.
All AEs will be recorded by the investigator from the time the subject signs informed consent to
28 days after the last dose of study drug, and those SAEs made known to the investigator at any 
time thereafter that are suspected of being related to study drug. AEs and serious adverse events 
(SAEs) will be recorded on the AE page of the eCRF and in the subject’s source documents. All 
SAEs must be reported to Celgene Drug Safety within 24 hours of the investigator’s knowledge 
of the event by facsimile, or other appropriate method, using the SAE Report Form, or approved 
equivalent form.
11.2.
Evaluation of Adverse Events
A qualified investigator will evaluate all adverse events as to: 
11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
!
Results in death;
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!
Is life-threatening (ie, in the opinion of the investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the eCRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of or an elective procedure for a pre-existing condition 
unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
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For each SAE, the investigator will provide information on severity, start and stop dates, 
relationship to study drug, action taken regarding study drug, 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 National Cancer Institute (NCI) Common Terminology Criteria 
for Adverse Events (CTCAE, Version 4.0)
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
Adverse events that are not defined in the NCI CTCAE should be evaluated for severity/intensity 
according to the following scale:
!
Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required
!
Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required
!
Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible
!
Grade 4 = Life threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable
!
Grade 5 = Death – the event results in death
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.
Seriousness, not severity, serves as a guide for defining regulatory obligations.
11.2.3.
Causality 
The investigator must determine the relationship between the administration of study drug 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 study drug
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 study drug caused the adverse event.  ‘Reasonable 
possibility’ means there is evidence to suggest a causal 
relationship between the study drug and the adverse event.
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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 study 
drug 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 study drug as a result of an AE or SAE, as 
applicable (eg, discontinuation or reduction of study drug, as appropriate) and report if 
concomitant and/or additional treatments were given for the event. 
11.2.6.
Outcome
The investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered or death (due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of study drug dose, or any other 
therapeutic intervention; or
!
is judged to be of significant clinical importance.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF. If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE.
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
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11.4.1.
Female Subjects
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 study drug, or within 3 months 
of the subject’s last dose of study drug, are considered immediately reportable events. Study drug
is to be discontinued immediately. The pregnancy, suspected pregnancy, or positive pregnancy 
test must be reported to Celgene Drug Safety immediately by facsimile, or other appropriate 
method, using the Pregnancy Initial Report Form, or approved equivalent form. The female 
subject should be referred to an obstetrician-gynecologist or another appropriate healthcare 
professional for further evaluation.
The investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the investigator
should report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate 
method, within 24 hours of the investigator’s knowledge of the event using the SAE Report 
Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the investigator suspects is 
related to the in utero exposure to the study drug should also be reported to Celgene Drug Safety 
by facsimile, or other appropriate method, within 24 hours of the investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving study drug
or within 3 months of the last dose of study drug, the male subject taking study drug should 
notify the investigator, and the pregnant female partner should be advised to call her healthcare 
provider immediately. If the male subject is receiving study drug, the study drug may need to be 
discontinued in the male subject, but may be resumed later at the discretion of the investigator
and medical monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The investigator is required to ensure that the data on these forms is accurate and consistent. This 
requirement applies to all SAEs (regardless of relationship to study drug) that occur during the 
study (from the time the subject signs informed consent to at least 28 days after the last dose of
study drug) and those made known to the investigator at anytime thereafter that are suspected of 
being related to study drug. SAEs occurring prior to treatment (after signing the ICF) will be 
captured.
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The SAE report should provide a detailed description of the SAE and include a concise summary
of hospital records and other relevant documents. If a subject died and an autopsy has been 
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available. Any follow-up data will be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety.
Where required by local legislation, the investigator is responsible for informing the Independent 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The investigator must keep copies of all SAE 
information on file including correspondence with Celgene and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than five (5) business 
days. Urgent queries (eg, missing causality assessment) may be handled by phone.
11.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to nab-paclitaxel 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 study drug in this study or in other 
studies that is both serious and unexpected (ie, SUSAR);
!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
The investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC. (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form/Completion Guidelines or to the Pregnancy Report Form/Completion Guidelines.
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12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the study 
drug:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent
!
Death
!
Lost to follow-up
!
Protocol violation
Prior to discontinuing a subject for disease progression, the investigator should contact and 
forward appropriate supporting documents to the Medical Monitor.
All subjects discontinued from study drug for any reason will have a treatment discontinuation 
visit at the time of discontinuation and should undergo treatment discontinuation procedures.
All subjects discontinued from nab-paclitaxel will be followed for a period of 28 days after last
dose of study drug for the collection of AEs.
Additionally subjects who withdraw from or discontinue treatment should be followed for 
progressive disease (if applicable), survival and any new anticancer therapy given.
The reason for treatment discontinuation should be recorded in the eCRF and in the source 
documents.
12.2.
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
study:
!
Withdrawal of consent
!
Death
!
Lost to follow-up
The following events may be considered sufficient reasons for discontinuing a subject from the 
study:
!
Adverse events(s)
!
Protocol violation
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. The investigator must notify the Medical Monitor immediately when a subject has 
been discontinued/withdrawn due to an AE (any unacceptable toxicity). All subjects who are 
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withdrawn from the study should complete all protocol-required evaluations scheduled for early 
termination at the time of withdrawal.
Since follow-up of subjects who discontinue prematurely is of particular importance, every 
attempt should be made to collect all survival information and NSCLC treatment/therapy, unless 
the subject has specifically withdrawn consent from further follow-up. The investigator must 
make every effort to obtain minimal information regarding the subject’s survival status before 
determining that the subject is lost to follow-up.
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.
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13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the investigator should contact the responsible Clinical Research
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page).This global Emergency 
Call Center is available 24 hours a day and 7 days a week. The representatives are responsible 
for obtaining your call-back information and contacting the on call Celgene/Contract Research 
Organization (CRO) Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
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14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative,
and investigator abide by Good Clinical Practice (GCP), as described in International Conference 
on Harmonization (ICH) Guideline E6 and in accordance with the general ethical principles 
outlined in the Declaration of Helsinki. The study will receive approval from an IRB/EC prior to 
commencement. The investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. Celgene staff or an authorized representative will evaluate and approve all 
investigators who in turn will select their staff.
The investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions. 
The investigator should maintain a list of sub-investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The investigator is responsible for keeping a record of all subjects who sign an ICF and are 
screened for entry into the study. Subjects who fail screening must have the reason(s) recorded in 
the subject’s source documents.
The investigator, or a designated member of the investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The investigator must ensure timely and accurate completion of eCRFs and queries.
14.3.
Subject Information and Informed Consent
The investigator must obtain informed consent of a legal representative prior to any study related 
procedures.
Documentation that informed consent occurred prior to the subject’s entry into the study and of 
the informed consent process should be recorded in the subject’s source documents including the 
date. The original ICF signed and dated by the subject and by the person consenting the subject 
prior to the subject’s entry into the study, must be maintained in the investigator’s study files and 
a copy given to the subject. In addition, if a protocol is amended and it impacts the content of the 
informed consent, the ICF must be revised. Subjects participating in the study when the amended 
protocol is implemented must be re-consented with the revised version of the ICF. The revised
ICF signed and dated by the subject and by the person consenting the subject must be maintained 
in the investigator’s study files and a copy given to the subject.
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14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
This documentation must also include a list of the members of the IRB/EC and their occupation 
and qualifications. If the IRB/EC will not disclose the names, occupations and qualifications of 
the committee members, it should be asked to issue a statement confirming that the composition 
of the committee is in accordance with GCP. For example, the IRB General Assurance Number 
may be accepted as a substitute for this list. Formal approval by the IRB/EC should mention the 
protocol title, number, amendment number (if applicable), study site (or region or area of 
jurisdiction, as applicable), and any other documents reviewed. It must mention the date on 
which the decision was made and must be officially signed by a committee member. Before the 
first subject is enrolled in the study, all ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
The investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a coordinating investigator and the IRB/EC. This statement also applies to any 
communication between the investigator (or coordinating investigator, if applicable) and 
regulatory authorities.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
62
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
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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jects.
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medical or 
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
63
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The investigator must ensure that the records and documents pertaining to the conduct of the 
study and distribution of the study drug 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 eCRFs or CD-ROM.
15.2.
Data Management
Data will be 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 study drug. The investigator must retain 
these documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the investigator, Celgene, and their authorized 
representative(s);
!
List of sub-investigators and other appropriately qualified persons to whom the 
investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of eCRFs (if paper) and of documentation of corrections for all subjects;
!
Study drug accountability records;
!
Record of any body fluids or tissue samples retained;
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
64
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
!
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.
The investigator must obtain approval in writing from Celgene prior to destruction of any 
records. If the investigator is unable to meet this obligation, the investigator must ask Celgene
for permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.
&(/*(1(35235,(7$5<,1)250$7,21
ities.
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destruction
destruction


nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
65
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 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, eCRFs, procedures for obtaining informed 
consent, record keeping, and reporting of AEs/SAEs with the investigator. Monitoring will 
include on-site visits with the investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, 
eCRFs, subject’s source documents, and all other study documentation will be
inspected/reviewed by the Celgene representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the eCRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the investigator and/or his/her staff. Any necessary 
corrections will be made directly to the eCRFs or via queries by the investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene. Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The investigator is required to permit direct access to the facilities where the study took place, 
source documents, eCRFs and applicable supporting records of subject participation for audits 
and inspections by IRB/IECs, regulatory authorities (eg, FDA, European Medicines Agency 
[EMA], Health Canada) and company authorized representatives. The investigator should make 
every effort to be available for the audits and/or inspections. If the investigator is contacted by 
any regulatory authority regarding an inspection, he/she should contact Celgene immediately.
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nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
66
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
17.
PUBLICATIONS
The results of this study may be published in a medical publication, journal, or may be used for 
teaching purposes. Additionally, this study and its results may be submitted for inclusion in all 
appropriate health authority study registries, as well as publication on health authority study 
registry websites, as required by local health authority regulations. Selection of first authorship 
will be based on several considerations, including, but not limited to study participation, 
contribution to the protocol development, and analysis and input into the manuscript, related 
abstracts, and presentations in a study.


nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
67
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
18.
REFERENCES
Azzoli CG, Baker Jr. S, Temin S, Pao W, Aliff T, Brahmer J, et al. American Society of Clinical 
Oncology clinical practice guideline update on chemotherapy for Stage IV non-small-cell lung 
cancer. J Clin Oncol. 2009;27:6251-66.
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;26:468-73.
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, Dancey J, et al. New 
response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J 
Cancer. 2009 Jan;45(2):228-47. 
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.
Hwang IK, Shih WJ, De Cani JS. Group sequential designs using a family of type I error
probability spending functions. Stat Med. 1990;9:1439-45.
Lorenz W, Reimann HJ, Schmal A, Dormann P, Schwarz B, Neugebauer E, et al. Histamine 
release in dogs by Cremophor El and its derivatives: oxethylated oleic acid is the most effective 
constituent. Agents Actions 1977;7:63-7.
National Institute for Health & Clinical Excellence (NICE): The Diagnosis and Treatment of 
Lung Cancer: Methods, Evidence & Guidance, 2011.
Oken, MM, Creech, RH, Tormey, DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and 
Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol. 
1982;5(6):649-55.
Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, et al. Intergroupe Francophone 
de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared 
with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 
randomised, phase 3 trial. Lancet. 2011;378(9796):1079-88. 
Rizvi NA, Riely GJ, Azzoli CG, Miller VA, Ng KK, Fiore J, et al. Phase I/II trial of weekly 
intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with Stage IV 
non-small-cell lung cancer. J Clin Oncol. 2008;26(4):639-43.
Schiller JH, Gandara DR, Goss GD, Vokes EE.  Non-small-cell lung cancer: then and now. 
J Clin Oncol. 2013;31(8):981-3.
&(/*(1(35235,(7$5<,1)250$7,21
ated 
ate
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 
Eur J C
uential desi
uential desi
1990;9:143
1990;9:143
ormann P, 
ormann P, 
nd its deriv
d its deriv
7;7:63
7;7:63-7.
-7.
& Clinical
& Clinic
Evidence &
Evidenc
RH, Torme
RH, Torm
Of The Ea
Of The Ea
55.
55.
alcman G, 
alcman G, 
érologie Th
érologie T
monotherap
onother
ndo
domised, 
mised, 
Ri
Rizvi NA
zvi NA
rav
ra


nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
68
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
Socinski MA, Langer CJ, Okamoto I, Hon JK, Hirsh V, Dakhil SR, et al. Safety and efficacy of 
weekly nab®-paclitaxel in combination with carboplatin as first-line therapy in elderly patients 
with advanced non-small-cell lung cancer. Ann Oncol. 2013;24(2):314-21. 
Socinski MA, Manikhas GM, Stroyakovsky DL, Makhson AN, Cheporov SV, Orlov SV, et al. A 
dose finding study of weekly and every-3-week nab-paclitaxel followed by carboplatin as 
first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol. 
2010;5(6):852-61.
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. 
Review.
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.
&(/*(1(35235,(7$5<,1)250$7,21
latatioion
):665
):665-85.
85
Sparreboom
parreboom
lasma phar
asma pha
18-24.
-24.
Trump DL
Trump DL
(7):1263
(7):1263-8.
-8


nab-paclitaxel
Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
69
ABI-007-NSCL-005 Amendment 1.0 Final: 09 Apr 2014
19.
APPENDICES
Appendix A: ECOG Performance Status Score
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up 
and about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of waking 
hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5
Dead
Oken, 1982.
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This is a representation of an electronic record that was signed electronically in Livelink.
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the organizations electronic signature policies and procedures.
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
1
STATISTICAL ANALYSIS PLAN
SAFETY AND EFFICACY OF nab-PACLITAXEL (ABRAXANE®) IN COMBINATION 
WITH CARBOPLATIN AS FIRST LINE TREATMENT IN ELDERLY SUBJECTS WITH 
ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC): A PHASE IV, 
RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY
(ABOUND.70+)
STUDY DRUG:
nab-Paclitaxel
PROTOCOL NUMBER:
ABI-007-NSCL-005
DATE FINAL:
24JUN2016
AMENDMENT 3 DATE FINAL:
17MAR2016
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.
&(/*(1(35235,(7$5<,1)250$7,21
6
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repared b
half o
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6 Mo
Sum
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formation c
formation 
except to t
except to t
disclosed 
disclosed 
regu
regu
inf
in
35
35
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35


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
2
HISTORY OF AMENDMENTS
Amendment 
number
Date of 
amendment
Significant amendments and 
rationales
Impact to statistical 
analysis and descriptions
1
29 MAR 
2017
One progression-free censoring 
rule was removed. According to 
this rule, subjects who discontinued 
treatment due to symptomatic 
deterioration prior to a tumor 
assessment showing disease 
progression were censored at the 
date of the last progression-free 
tumor assessment prior to treatment 
discontinuation. 
The rule was removed in order to 
be consistent with Celgene 
standards.
After removing the 
censoring rule, tumor 
assessment showing 
disease progression will be 
an event regardless of the 
reason for treatment 
discontinuation unless 
other censoring rules apply 
(e.g., if the tumor 
assessment occurs after 
initiation of subsequent 
anti-cancer therapy).
The overall survival censoring 
rules were simplified in order to 
use the data cutoff date as the date 
of censoring for all subjects with 
ongoing study participation as of 
the data cutoff.
All subjects were closely followed 
for vital status and study
discontinuation as part of data 
cleaning activities in preparation 
for the CSR database lock. 
Therefore it can be assumed that all 
subjects who have died or 
discontinued from the study as of 
the CSR data cutoff date have been 
identified and recorded 
accordingly. This makes it 
unnecessary to search the database 
for the last known alive date.
For the CSR analysis, all 
subjects for whom the 
database does not hold a 
death date nor a study 
discontinuation date will 
be censored as of the data 
cutoff date rather than the 
last data point in the 
database. 
Updates were made throughout to 
reflect early termination of 
enrollment and resultant shortening 
of timelines and decrease in overall 
sample size. Description of clinical 
cutoff for CSR analysis and OS 
update were added.
The number of subjects 
randomized was 143, 
compared to the original 
plan for 284 subjects. 
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
4
TABLE OF CONTENTS
STATISTICAL ANALYSIS PLAN ............................................................................................1
HISTORY OF AMENDMENTS.................................................................................................2
SIGNATURE PAGE...................................................................................................................3
TABLE OF CONTENTS............................................................................................................4
LIST OF TABLES......................................................................................................................8
LIST OF FIGURES ....................................................................................................................9
1.
LIST OF ABBREVIATIONS.................................................................................10
TABLE 1: ABBREVIATIONS AND SPECIALIST TERMS....................................................10
2.
INTRODUCTION..................................................................................................12
3.
STUDY OBJECTIVES...........................................................................................13
3.1.
Primary Objective...................................................................................................13
3.2.
Secondary Objective...............................................................................................13
3.3.
Exploratory Objectives ...........................................................................................13
4.
INVESTIGATIONAL PLAN .................................................................................14
4.1.
Overall Study Design and Plan ...............................................................................14
FIGURE 1: STUDY SCHEMATIC FOR ABI-007-NSCL-005 .................................................16
4.2.
Study Endpoints .....................................................................................................16
4.2.1.
Primary Endpoint....................................................................................................16
4.2.2.
Secondary Endpoints ..............................................................................................16
4.2.3.
Exploratory Endpoint(s)..........................................................................................17
4.3.
Stratification, Randomization, and Blinding............................................................17
4.4.
Sample Size Determination.....................................................................................17
5.
GENERAL STATISTICAL CONSIDERATIONS .................................................19
5.1.
Reporting Conventions ...........................................................................................19
5.2.
Analysis Populations ..............................................................................................20
5.2.1.
Intent-to-Treat Population.......................................................................................20
5.2.2.
Treated Population..................................................................................................20
5.2.3.
Per-Protocol Populations ........................................................................................20
6.
SUBJECT DISPOSITION......................................................................................22
7.
PROTOCOL DEVIATIONS/VIOLATIONS ..........................................................24
8.
DEMOGRAPHICS AND BASELINE CHARACTERISTICS................................25
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5.2.3.
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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8.1.
Demographics.........................................................................................................25
8.2.
Baseline Characteristics..........................................................................................25
8.3.
Medical History......................................................................................................25
8.4.
Lung Cancer History...............................................................................................25
8.5.
Prior and Concomitant Therapy for NSCLC ...........................................................26
8.5.1.
Prior Systemic Anti-cancer Therapies.....................................................................26
8.5.2.
Prior Radiation Therapy..........................................................................................26
8.5.3.
Prior Non-small Cell Lung Cancer Surgeries ..........................................................27
8.5.4.
Concomitant Radiation and Procedures/Surgeries...................................................27
8.6.
Prior and Concomitant Medications........................................................................27
8.6.1.
Prior Medications ...................................................................................................27
8.6.2.
Concomitant Medications .......................................................................................27
9.
STUDY TREATMENTS AND EXTENT OF EXPOSURE....................................28
9.1.
Treatment and Cycle Start and End Dates ...............................................................28
9.2.
Dosing Period for Each Study Drug........................................................................28
TABLE 2: CALCULATION OF DOSING PERIOD FOR EACH STUDY DRUG 
BASED ON CYCLE DAY NUMBER OF LAST DOSE OF THE STUDY 
DRUG ....................................................................................................................29
9.3.
Treatment Duration.................................................................................................30
9.4.
Cumulative Dose ....................................................................................................30
9.5.
Dose Intensity.........................................................................................................30
9.6.
Percentage of Protocol Dose ...................................................................................30
9.7.
Exposure, Dose Reduction, Delay, and Skipped Doses ...........................................31
10.
SAFETY ANALYSIS ............................................................................................32
10.1.
Primary Safety Endpoint.........................................................................................33
10.2.
Adverse Events.......................................................................................................33
10.3.
Peripheral Neuropathy............................................................................................35
10.4.
Adverse Events of Special Interest..........................................................................35
10.5.
Clinical Laboratory Evaluations..............................................................................36
11.
EFFICACY ANALYSIS ........................................................................................37
11.1.
Multiplicity.............................................................................................................37
11.2.
Analysis of Efficacy Endpoints...............................................................................37
11.2.1.
Progression-free Survival........................................................................................37
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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TABLE 3: CENSORING RULES FOR PFS .............................................................................39
11.2.2.
Overall Survival .....................................................................................................42
11.2.3.
Overall Response Rate and Tumor Response ..........................................................42
11.3.
Subgroup Analysis..................................................................................................43
11.4.
Exploratory analysis ...............................................................................................43
11.4.1.
Healthcare utilization..............................................................................................43
11.4.2.
Quality of Life Analysis..........................................................................................43
12.
FOLLOW UP TREATMENTS...............................................................................46
13.
INTERIM ANALYSIS...........................................................................................47
13.1.
Interim Evaluation of Dosing, Safety and Efficacy..................................................47
13.2.
Interim Analysis of Quality of Life Questionnaire Data ..........................................47
14.
CHANGES TO THE STATISTICAL ANALYSES SECTION OF THE 
PROTOCOL...........................................................................................................48
15.
REFERENCES.......................................................................................................49
16.
APPENDICES........................................................................................................50
16.1.
Handling of Dates...................................................................................................50
CALCULATION USING DATES..........................................................................................50
WEEKS = DAYS /7..................................................................................................................51
MONTHS = DAYS /30.4375....................................................................................................51
16.2.
Date Imputation Guideline......................................................................................51
16.2.1.
Impute Missing Dates for Adverse Events/ Prior or Concomitant 
Medications............................................................................................................51
INCOMPLETE END DATE.......................................................................................................52
MISSING DAY ONLY................................................................................................................52
16.3.
Relative Day Ranges for CT-Scans.........................................................................52
TABLE 4: RELATIVE DAY RANGES FOR CT SCANS ........................................................52
16.4.
Treatment-emergent Adverse Events of Special Interest..........................................53
TABLE 5: TREATMENT-EMERGENT ADVERSE EVENTS OF SPECIAL 
INTEREST FILE AND DATES.............................................................................53
16.5.
MedDRA Versions and Dates.................................................................................53
TABLE 6 GIVES THE MEDDRA VERSIONS USED IN THIS STUDY AND THE
DATES OF IMPLEMENTATION. ........................................................................53
TABLE 6: MEDDRA VERSIONS AND DATES.....................................................................53
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-005
Celgene Corporation
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16.6.
RECIST 1.1 Best Overall Response with Confirmation of Complete and 
Partial Response .....................................................................................................53
TABLE 7 GIVES THE INTERPRETATION OF BEST OVERALL RESPONSE WITH 
THE REQUIREMENT OF CONFIRMATION OF CR AND PR BASED 
ON THE RECIST 1.1 CRITERIA (EISENHAUER) AS APPLICABLE TO 
THIS STUDY.........................................................................................................53
TABLE 7: RECIST 1.1 BEST OVERALL RESPONSE WITH CONFIRMATION OF 
COMPLETE AND PARTIAL RESPONSE............................................................53
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
8
LIST OF TABLES
Table 1: Abbreviations and Specialist Terms.............................................................................10
Table 2: Calculation of Dosing Period for Each Study Drug Based on Cycle Day 
Number of Last Dose of the Study Drug .................................................................29
Table 3: Censoring Rules for PFS .............................................................................................39
Table 4: Relative Day Ranges for CT Scans..............................................................................52
Table 5: Treatment-emergent Adverse Events of Special Interest File and Dates.......................53
Table 6: MedDRA Versions and Dates......................................................................................53
Table 7: RECIST 1.1 Best Overall Response with Confirmation of Complete and Partial 
Response ................................................................................................................53
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-005
Celgene Corporation
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9
LIST OF FIGURES
Figure 1: Study Schematic for ABI-007-NSCL-005 ..................................................................16
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
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1.
LIST OF ABBREVIATIONS
Table 1: Abbreviations and Specialist Terms
ADT
Analysis date
AE
Adverse event
AESI
Adverse event of Special Interest
ALK
Anaplastic lymphoma kinase
ANC
Absolute neutrophil count
AUC
Area under the curve
BMI
Body mass index
BSA
Body surface area
CI
Confidence interval
CR
Complete response
CRF
Case report form
CSR
Clinical study report
CT
Computerized tomography
CTCAE
Common Terminology Criteria for Adverse Events
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EGFR
Epidermal growth factor receptor 
EQ-5D-5L
EuroQoL Group 5-Dimension
FNC
Fine needle cytology
HR
Hazard ratio
IRT
Interactive Randomization Technology
ITT
Intent-to-treat
IV
Intravenous
IVRS
Interactive voice response system
KRAS
Kirsten rat sarcoma
LCSS
Lung Cancer Symptom Scale
MedDRA
Medical Dictionary for Regulatory Activities
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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NCI
National Cancer Institute
NSCLC
Non-small cell lung cancer
ORR
Overall response rate
OS
Overall survival
PD
Progressive disease
PFS
Progression-free survival
PN
Peripheral neuropathy 
PP
Per protocol
PR
Partial response
PT
Preferred term
RECIST
Response evaluation criteria in solid tumors
SAE
Serious adverse event
SAP
Statistical analysis plan
SD
Stable disease
SI
International System of Units (Le Système International d’unités)
SMQ
Standardized MedDRA query
SOC
System organ class
SSC
Scientific steering committee
STDEV
Standard deviation
TEAE
Treatment-emergent adverse event
UE
Unevaluable
US
United States
VAS
Visual analog scale
WHO
World Health Organization
WHO-DDE
World Health Organization Drug Dictionary Enhanced
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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2.
INTRODUCTION
This statistical analysis plan (SAP) describes the analyses and data presentations for Celgene’s 
protocol ABI-007-NSCL-005 “SAFETY AND EFFICACY OF nab-PACLITAXEL 
(ABRAXANE®) IN COMBINATION WITH CARBOPLATIN AS FIRST LINE 
TREATMENT IN ELDERLY SUBJECTS WITH ADVANCED NON-SMALL CELL LUNG 
CANCER (NSCLC): A PHASE IV, RANDOMIZED, OPEN-LABEL, MULTICENTER 
STUDY (ABOUND.70+)” which was issued on 06MAR2014 (amended 09APR2014 and 
05DEC2014). It contains definitions of analysis populations, derived variables and statistical 
methods for the analysis of efficacy and safety.
These analyses include one (1) non-binding interim analysis and one final clinical study report 
(CSR) analysis. After the conclusion of survival follow-up, the overall survival (OS) analysis 
and relevant safety and efficacy analyses will be updated. Throughout this SAP, the treatment 
arms will be referred to as Arm A (21-day cycle) and Arm B (28-day cycle). 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 for the 
interim/final analysis. All statistical analyses detailed in this SAP will be conducted using SAS® 
Version 9.2 or higher.
A non-binding interim analysis will be conducted when approximately a total of 120 treated 
subjects have either completed 4 months of study treatment or discontinued from the study due 
to disease progression, adverse events, death, lost to follow up, or other reasons. 
The clinical cutoff date for the final analysis will be on November 20, 2016. Subjects will be 
followed for OSuntil approximately September 29, 2017, which is the anticipated cutoff date for 
the updated OS analysis.
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Celgene Corporation
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3.
STUDY OBJECTIVES
3.1.
Primary Objective
The primary objective is as follows:
!
To assess the safety and tolerability of continuous weekly versus weekly times three 
with one-week break nab-paclitaxel (Abraxane) in combination with carboplatin as 
first-line treatment for advanced non-small cell lung cancer (NSCLC) in elderly 
subjects (≥ 70 years old).
3.2.
Secondary Objective
The secondary objective is as follows:
!
To evaluate the efficacy of nab-paclitaxel in combination with carboplatin in elderly 
subjects with advanced NSCLC.
3.3.
Exploratory Objectives
The exploratory objectives are as follows:
!
To assess healthcare resource utilization for the two nab-paclitaxel treatment arms.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ-5D) for the two nab-paclitaxel treatment arms.
!
 
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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4.
INVESTIGATIONAL PLAN
4.1.
Overall Study Design and Plan
This is a Phase IV, randomized, open-label, multicenter study of continuous weekly versus
weekly times three with one-week break nab-paclitaxel in combination with carboplatin as first
line treatment in elderly subjects (≥ 70 years old) with advanced NSCLC who are not candidates
for curative surgery or radiation therapy.
Approximately 143 subjects (originally planned to be 284 subjects), stratified by ECOG 
performance status and histology, will be randomized 1:1 to one of the following treatment arms:
Arm A (21-day treatment cycle):
!
nab-Paclitaxel 100 mg/m² intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment cycle
!
Carboplatin area under the curve (AUC) = 6 mg*min/mL IV on Day 1 of each 21-day 
treatment cycle after completion of nab-paclitaxel infusion
Arm B (21-day treatment followed by one-week break cycle, 28-day duration):
!
nab-Paclitaxel 100 mg/m² intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day treatment followed by one-week break cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day treatment followed by 
one-week break cycle, after completion of nab-paclitaxel infusion
The study will consist of a 28-day Screening Period, a Treatment Period, and a Follow-up 
Period.
The Screening Period will start from signing the Informed Consent Form until Day 1 of
treatment (defined in Section 9.1).
The Treatment Period will start on Day 1 of treatment and will end on the treatment end date
(defined in Section 9.1).
The Follow-up Period will start the day after the treatment end date.
No additional anticancer agents are allowed during study treatment. All supportive care 
(including but not limited to growth factors, antiemetics, analgesics, zolendronic acid, 
denosumab) is permitted as per the investigator’s discretion and should be administered 
according to local institutional practice. Subjects will continue treatment until disease 
progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of 
consent, in accordance with local standard of care.
Local laboratory test data for absolute neutrophil count (ANC), platelet count, hemoglobin,
serum creatinine and baseline creatinine clearance will be collected in the electronic case report 
forms (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(s) 
should be recorded in the laboratory assessments eCRF. Local safety laboratory data will also be 
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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the primary guide for eligibility and subject management. In addition, test results for tumor 
mutational status of genes including but not limited to FGFR. EGFR, ALK, and KRAS will be 
collected and recorded on eCRF, if these tests have been performed locally for routine diagnosis. 
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 Tumors 
(RECIST) guidelines, Version 1.1 (Eisenhauer, et al., 2009). In both treatment arms, tumor 
assessments will be conducted at Screening, every 42 days (-3/+7 days) (starting from Day 1 
Cycle 1) until disease progression, withdrawal of consent, lost to follow-up, death or if clinically 
indicated while on treatment.
All subjects who discontinue from treatment for reasons other than withdrawal of consent or lost 
to follow-up, will enter the Follow-up Period. It will consist of a visit 28 days after treatment 
discontinuation. Thereafter, subjects will be followed for survival approximately every 90 days 
(+/- 14 days or when they are seen for routine care) by phone call or chart review for 
documentation of last contact for up to 6 months after the last subject is randomized or after 192 
PFS events have been observed, whichever comes later.
Those subjects entering the Follow-up Period without documented progression will continue to 
have CT scans in accordance with standard of care (at least every 90 days) until documented 
progression of disease, withdrawal of consent, lost to follow-up, death or study closure. 
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-005
4.2.
Study Endpoints
4.2.1.
Primary Endpoint
The primary study endpoint is the percentage of subjects with either peripheral neuropathy of 
Grade ≥ 2 or myelosuppression AEs of Grade ≥ 3 based on the local laboratory values for ANC, 
platelet count, and hemoglobin. All AEs will be graded using National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.
4.2.2.
Secondary Endpoints
Secondary endpoints are as follows:
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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4.2.2.1.
Safety
!
The type, frequency, and severity of AEs and SAEs
!
Discontinuation rate
!
Dose intensity administered
!
The incidence of dose reduction and dose delay
4.2.2.2.
Efficacy
!
Progression-free survival (PFS)
!
Overall survival (OS)
!
Overall response rate (ORR) 
4.2.3.
Exploratory Endpoint(s)
!
Healthcare resource utilization during the study using a questionnaire.
!
Changes in the LCSS and EQ-5D.
!
 
 
!
 
4.3.
Stratification, Randomization, and Blinding
Randomization will be carried out centrally using an Interactive Randomization Technology 
(IRT) system. Treatment assignment follows a 1:1 ratio between two treatment arms. 
Randomization method is based on permutated-block randomization. Randomization will be
stratified by the following factors: 
1. Eastern Cooperative Oncology Group (ECOG) performance status (0 versus 1) at 
screening
2. Histology (squamous cell carcinoma versus non-squamous cell carcinoma)
The study is open label due to the differences in scheduling the treatments.
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 administered in 21-day treatment cycles continuously or with a 
one-week break in between cycles for the treatment of locally advanced or metastatic NSCLC in 
elderly subjects (≥ 70 years old).
The primary study endpoint (also the primary safety endpoint) is the percentage of subjects with 
either peripheral neuropathy of Grade ≥ 2 or myelosuppression AEs of Grade ≥ 3 based on the 
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-005
Celgene Corporation
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18
local laboratory values for ANC, platelet count, and hemoglobin. For the purpose of this 
protocol, this endpoint will be referred to as the percentage of subjects with Grade ≥ 2 peripheral 
neuropathy or Grade ≥ 3 myelosuppression laboratory adverse events. In Protocol CA031, the 
Phase 3 NSCLC study of the nab-paclitaxel development program, approximately 2% of the 
elderly subjects randomized discontinued from the study prior to receiving any study drug. In 
addition, approximately 73% of the treated elderly subjects had AEs that fell in the category of 
AEs described above for the primary safety endpoint of the current study.
The study is designed to detect a difference of 16 percentage points between the 2 treatment arms 
with respect to the primary safety endpoint with 80% power and a Type-I error of 5% (two-
sided), assuming the percentage of subjects with the AEs specified above is 73% for Arm A. 
Therefore, the current study is planned to randomize approximately 284 subjects to the 2 
treatment arms in a 1:1 ratio, with the expectation that approximately 278 subjects (139 per
group) will receive at least one dose of study drug (as observed in CA031) and be included in the 
treated population for the analysis of the primary safety endpoint.
A non-binding interim evaluation of dosing, primary safety endpoint, and efficacy data will be 
conducted when approximately a total of 120 treated subjects have either completed 4 months of 
study treatment or discontinued treatment due to progression, adverse events, deaths, lost to 
follow up, or other reasons. The stopping rule and the final marginal significance level for this 
endpoint are determined based on the Gamma family spending function with parameter = -7 
(Hwang, 1990) to control the Type-II error rate at 20%. Futility criterion for this endpoint is met 
if the treatment difference (Arm B minus Arm A) is ≥ -0.2%, given the interim analysis of this 
endpoint is performed at 43% information fraction.
Progression free survival, OS, and ORR are the efficacy endpoints of the study. Since the 
primary research interest of this study is to evaluate the relative safety and toxicities of the 2 
treatment arms, the sample size was calculated based on the primary safety endpoint, the 
percentage of subjects with Grade ≥ 2 peripheral neuropathy or Grade ≥ 3 myelosuppression 
laboratory AEs, hence, the study is underpowered for the efficacy endpoints, PFS, OS and ORR. 
Consequently, a non-significant treatment difference in PFS, OS or ORR could simply be a 
function of the sample size and/or the lack of statistical power. Therefore, the assessments of all 
efficacy endpoints will be based on the point estimates and the associated 95% confidence 
intervals for the within-group parameters of interest and the between-group differences. P-values 
for between-group comparisons will be provided to indicate the strength of association only. No 
multiplicity adjustment with the Type-I error rate will be made.
Of note, based on the data from CA031 it is expected that approximately 67% of the 284 
randomized subjects will have a PFS event during the study (i.e., approximately 192 PFS events 
total). With 192 PFS events, there is 73% power to detect a hazard ratio (HR) of 0.69 for PFS 
improvement with Arm B over Arm A and an overall Type-I error of 5% (two-sided). Assuming 
an exponential distribution with a median time to PFS of 5.8 months for Arm A and proportional 
hazards, a hazard ratio of 0.69 constitutes a 2.6 months improvement for Arm B.
The analysis of both the safety and efficacy endpoints for the clinical study report will be 
performed on data collected through 20NOV2016. No adjustment for the multiple treatment 
comparisons among the primary and secondary study endpoints will be made. Subjects will be 
followed for OS until approximately 29SEP2017.
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he an
f


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
Confidential and Proprietary
19
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;
!
All stratified efficacy analyses will use the stratification factors for randomization
including histology (squamous cell carcinoma versus non-squamous cell carcinoma) 
and ECOG performance status at randomization (0 versus 1);  
!
The statistical test of the treatment effect with respect to the primary endpoint will be 
interpreted based on the stopping boundaries determined at the pre-specified interim 
analyses and the final analysis;
!
All other statistical tests of the treatment effect will be performed at significance level 
of 0.050 for 2-sided tests. Testing of interactions will be performed at the 0.100 
significance level;
!
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 (CIs) will be presented as 2-sided 95% CIs unless specified 
differently for a given analysis;
!
Summary statistics will consist of the number and percentage of subjects (or cycles, if 
appropriate) in each category for discrete variables, and the sample size, mean, 
standard deviation, 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 randomized treatment arm, 
study site, subject, and date of procedure or event;
!
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, with the exception 
&(/*(1(35235,(7$5<,1)250$7,21
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discrete var
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entage is in
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(XX.X%)
(XX.X%)
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All lili
stu
stu
!


nab-Paclitaxel (Abraxane®)
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of lab data, where the value with the worst CTC grade is the baseline. For subjects 
who were not treated, the baseline will be the last non-missing value obtained on or 
prior to the randomization date; 
!
Partial dates will be imputed based on the rules specified in Appendix 16.2; 
!
All laboratory data will be reported using international system of units (SI); 
!
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. The similar approach will be used for summaries of ECOG 
performance status and peripheral neuropathy (PN) grades; 
!
SAS® Version 9.2 (or higher) will be the statistical software package used to produce 
all data summaries, listings, graphs, and statistical analyses. 
5.2.
Analysis Populations
The number of subjects included in each of the populations described below will be summarized 
based on the number of subjects randomized.
5.2.1.
Intent-to-Treat Population
The primary efficacy analysis will be performed on the intent-to-treat (ITT) population, which 
includes all randomized subjects regardless of whether the subject receives any study drug or has 
any efficacy assessments performed. Unless otherwise specified, the ITT population will be the 
analysis population for all efficacy analyses.
5.2.2.
Treated Population
The treated population includes all subjects who are randomized and receive at least one dose of 
study drug. If a subject consistently receives study drug other than the subject’s randomized 
treatment assignment, and if the change in dosing schedule was not due to TEAEs, then the 
subject is assigned to the treatment arm reflecting the treatment that the subject actually received 
during the study. 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.
5.2.3.
Per-Protocol Populations
The per-protocol (PP) populations are defined to include all eligible subjects randomized who 
receive at least one dose of the study drug; have been treated in the arm they were assigned to; 
and do not have any relevant protocol deviations. Additionally, for the per protocol safety 
analysis, subjects must have at least one post-baseline hematology panel that includes ANC, 
platelet, and hemoglobin. For the efficacy per-protocol analysis, subjects must have at least one 
post-baseline radiologic evaluation. The per-protocol population will be finalized before 
database lock.
&(/*(1(35235,(7$5<,1)250$7,21
and 
and
f ECOG 
ECOG 
sed to prod
ed to prod
d below w
below w
int
intent
ent-toto-t
her the subj
her the su
rwi
rwise speci
se spec
subject
ubjects wh
s w
tly 
ly receive
receive
he change i
he change
eatment arm
atment ar
 otherwise 
otherwis
ety y analyse
analys
be excluded
be exclude
er
er-Protoco
Protoco
protocol (
protocol (P
ve at least o
ve at least
d do not ha
do not ha
analysis
nalysis, s
latel
ateletet


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The PP populations will be used in a replication of the primary safety analysis and efficacy 
analyses of PFS, OS, and ORR. 


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6.
SUBJECT DISPOSITION
The total number of subjects screened will be presented, and subjects with screen failure and 
reasons for screen failure will be summarized by frequency and percentage of total number of 
subjects screened.
The number and percentage of subjects screened will be summarized by their eligibility or non-
eligibility for the study, and the number of subjects randomized under each protocol amendment 
will be summarized by treatment arm. Subjects enrolled by site will be presented.
The number and percentage of subjects who are randomized and treated, discontinued treatment, 
and discontinued the study will be presented for the ITT population by treatment arm and for all 
subjects combined. Reasons for treatment discontinuation will be summarized in the subject 
disposition table 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
Reasons for study discontinuation will be summarized in the subject disposition table with the 
following categories:
!
Screen failure
!
Death
!
Adverse event
!
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 
&(/*(1(35235,(7$5<,1)250$7,21
ment,
ment,
d for all
for all
subject
subject
be summar
e summa
ntnt
awal by sub
wal by sub
t to follow 
t to follow
Study
Study term
term
y
!
Protoc
rotoc
!
O


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-005
Celgene Corporation
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Period, and all deaths will be summarized by frequency of occurrence and corresponding 
percentage by cause of death per period (during treatment or follow-up). Cause of death will be 
categorized by both the categories on the death eCRF and by coded cause of death.
The number of subjects who entered the post-treatment follow-up period and the number of 
subjects who are in survival follow-up at the time of analysis will be presented.
Listings will be provided for discontinued subjects with reason for treatment discontinuation and 
reason for study discontinuation, for subjects randomized but not treated, 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.
A summary and by-subject listing of subjects with protocol deviations and violations in the ITT 
population will be provided. 
Protocol deviations and violations will be reviewed before database lock, and subjects with 
relevant protocol violations will be excluded from the per protocol population (defined in 
Section 5.2.3).  
&(/*(1(35235,(7$5<,1)250$7,21


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 the ITT population by 
treatment arm and overall. Individual subject listings will be provided to support the summary 
tables.
8.1.
Demographics
Age (years), height (cm), weight (kg), body mass index (BMI), body surface area (BSA) (m²) at 
baseline will be summarized descriptively. Sex, age category (70-74 years, 75-79 years, 80-84
years, 85-89 years, ≥90 years), race, and ethnicity will be summarized by frequency counts.
Age will be calculated as follows: age = greatest integer ∀[(informed consent date – date of birth 
+ 1) / 365.25]. 
BMI will be calculated as follows: BMI = weight in kg / (height in m)2.
BSA will be calculated as follows: BSA m2 = 0.007184 × (weight in kg)0.425 × (height in cm)0.725.
8.2.
Baseline Characteristics
The number and percentage of subjects in each of the following categories will be presented:
1. ECOG performance status at randomization (0 versus 1)
2. Histology (squamous cell carcinoma versus non-squamous cell carcinoma)
3. Physician assessment of peripheral neuropathy at baseline
4. Creatinine clearance at screening (< 45 mL/min versus ≥ 45 mL/min).
8.3.
Medical History
A summary of medical and surgical history will be coded using MedDRA version 18.0 or higher
and presented by system and organ class (SOC) and preferred term (PT). A similar summary will 
be generated for the currently active abnormalities only, by SOC and PT.
8.4.
Lung Cancer History
The following items will be summarized for lung cancer history:
o
Confirmed histology  (squamous, adenocarcinoma, large cell, other) 
Squamous cell histology type (papillary, clear cell, basaloid, and other)
o
Adenocarcinoma cell type (acinar, papillary, bronchioloalveolar carcinoma, 
solid adenocarcinoma with mucin, adenocarcinoma with mixed subtypes, and 
other)
!
The time from specimen collection date to randomization date in months, defined as 
(first dose date – specimen collection date + 1)/ 30.4375
!
Method of specimen collection (biopsy, surgical specimen, FNC, other)
!
Additional histology markers
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at
84
nts.
datate of 
e of biri
25 × (
× (heig
h
ng categori
ng catego
sus 1)
1)
n-
n-squam
squamou
ou
pathy at bas
pathy at ba
5 mL/min
5 mL/min
al history
history
l
w
y
gan cl
gan class (S
ass (S
y act
y active abn
ive abn
ncer Histo
ncer Hist
s will
s will b
l e su
e s
o
Confir
Conf
Squ
Squ
o


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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26
!
Stage at enrollment
!
Mutational gene status (FGFR, KRAS, EGFR, ALK, other)
!
Number of prior cancer surgeries from non-small cell lung cancer
!
Time from latest prior cancer surgery to randomization date in months
!
Number of prior systemic anti-cancer therapies for non-small cell lung cancer
!
Time from latest systemic anti-cancer therapy to randomization date in months
!
Number of prior radiation therapies
!
Time from latest radiation therapy to randomization date in months
!
Time from latest lung cancer treatment (last to occur of systemic anti-cancer therapy, 
radiation, or cancer surgery) to randomization date in months.
Subject listings will be provided for all of the above, as well as date of specimen collection.
In the event that there is a record of a screening-period radiological assessment confirming lung 
cancer that is earlier than specimen collection date, the date of the radiological assessment will 
be used in place of the specimen collection date.
8.5.
Prior and Concomitant Therapy for NSCLC
Any therapies administered for NSCLC will be summarized separately.
Therapies administered during the follow up period are described in Section 12.
8.5.1.
Prior Systemic Anti-cancer Therapies
Prior systemic therapies (e.g. chemotherapy) will be coded to therapeutic drug classes and 
generic drug names using the World Health Organization (WHO) Drug Dictionary Enhanced 
version WHO-DDE Q3 2014 or later. The number of subjects with prior systemic anti-cancer 
therapies (including EGFR TKI and ALK rearrangement inhibitors) and number of cycles (where 
known) will be summarized by drug class and therapy. The best response for all prior treatments 
by subject will be summarized by treatment arm.
Prior systemic anti-cancer therapies will be listed. The duration, whether the number of cycles is 
known, the number of cycles (if known), and the best response will be presented in the listing.
8.5.2.
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 type 
and 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.
&(/*(1(35235,(7$5<,1)250$7,21
cancer thera
ancer ther
cimen colle
imen colle
essment co
essment c
adioiolologigical
SCLC
CLC
arized sepa
arized sepa
od are descr
od are des
erapies
erapies
apy
apy) will b
) will
y
Healt
Health Org
h O
er. The nu
e nu
I and ALK 
and ALK 
by drug cla
by drug cla
rized by tre
rized by tre
ancer therap
ncer ther
r of cy
r of cycles 
cles 
rior Radia
rior Radia
ber and per
r and per
ubjects with
bjects with
treatme
treatmentnt
percentage
percentage
known) 
known
tin


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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8.5.3.
Prior Non-small Cell Lung Cancer Surgeries
The number and percentage of subjects who had any prior non-small cell lung cancer surgery 
will be presented by system organ class and preferred term. Prior surgeries will be listed.
8.5.4.
Concomitant Radiation and Procedures/Surgeries
Concomitant procedures are considered any procedures that occurred on or after the date of 
randomization. The number of subjects having concomitant radiation therapy, concomitant 
surgeries or procedures performed will be summarized in separate tables.
Concomitant radiation therapy, surgeries and procedures will be listed.
8.6.
Prior and Concomitant Medications
Medications reported on the Prior and Concomitant medications CRF pages will be coded to 
therapeutic drug classes and generic drug names using the WHO drug dictionary version WHO-
DDE Q3 2014 or later. Medications initiated prior to 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.
8.6.1.
Prior Medications
Prior medications are defined as all medications that were started before the date of 
randomization. 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 ITT population.
8.6.2.
Concomitant Medications
Concomitant medications are any non-study medications that were taken on or after the date of 
randomization 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 will be presented for 
the ITT population.
&(/*(1(35235,(7$5<,1)250$7,21
ll be coded
l be code
nary
nary v
y ersrsioi
atm
atment and
ent 
comitant m
comitant m
e started be
started
percentage 
percentage 
onary therap
nary therap
TT populat
TT popul
study
study med
med
days after t
ays after
er and perce
r and perce
herapeutic 
herapeut


nab-Paclitaxel (Abraxane®)
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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 administered by treatment arm.
9.1.
Treatment and Cycle Start and End Dates
Planned cycle lengths are 21 days (Arm A) and 28 days (Arm B). Day 1 of treatment is the first 
day any study drug is administered to a subject. 
The first day of a cycle is the first Day 1 carboplatin administration as recorded on the eCRF. 
The end of a cycle is the day before the first day of the next cycle. The treatment end date and 
the end date of the last cycle will be calculated as follows:
!
For subjects who discontinue prior to the clinical cutoff date, the treatment end date is 
the date of treatment discontinuation from the treatment disposition form in the 
eCRF.
!
For subjects who are still ongoing at the time of study closure or clinical cutoff, the 
treatment end date is the maximum of the end dates of the nab-paclitaxel and 
carboplatin dosing periods (see Section 9.2).
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 duration for subjects who are still on treatment at the time of study closure or clinical 
cutoff. 
Conceptually, the dosing period for a study drug is the time period in weeks starting at the first 
dose of any study drug and ending a protocol- and subject-specific number of days after the last 
dose of the specific study drug, depending on the dosing schedule for the treatment arm and the 
subject’s status. Ending the dosing period on the date of last dose would lead to an 
overestimation of the dose intensity. Similarly, ending the dosing period on the date of treatment 
discontinuation, if such date closely follows the 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.
The specific calculations of the dosing period for each study drug and arm are given in Table 2
below:
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CRF.
RF.
date and 
ate and 
eatment en
atment en
ioion n fo
form
rm i
m
osure or cli
ure or cli
f the
he nab-p
and will be
and will b
ng period 
ng period w
n treatmen
n treatmen
tudy drug
udy drug
a protocol
protocol
depending o
depending 
osing peri
osing perio
intensit
ntensi y. S
date closel
date close
oioid such ov
d such o
w for the ca
for the ca
e aligned w
e aligned
ds beyo
ds beyond t
nd 
me circum
e circum
specific cal
specific ca
low:
low:


nab-Paclitaxel (Abraxane®)
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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
Arm
nab-Paclitaxel
Carboplatin
Last dose 
record is D1 
Last dose 
record is D8
Last dose 
record is D15
Last dose record is D1
Arm A (21-day cycle)
min{study day of death date, max[study day of 
treatment discontinuation date, study day of date 
of last dose of nab-paclitaxel + 6]}
min{study day of death 
date, max[study day of 
treatment discontinuation 
date, study day of date of 
last dose of carboplatin 
+20]}
Arm B (28-day cycle)
min {study day 
of death date, 
max[study day 
of treatment 
discontinuation 
date, study day 
of date of last 
dose of nab-
paclitaxel + 
8.33]}
min {study day 
of death date, 
max[study day 
of treatment 
discontinuation 
date, study day 
of date of last 
dose of nab-
paclitaxel + 
10.67]}
min {death 
date, 
max[treatment 
discontinuation 
date, date of 
last dose of 
nab-paclitaxel 
+ 13]}
min{study day of death 
date, max[study day of 
treatment discontinuation 
date, study day of date of 
last dose of carboplatin + 
27]}
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pri
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35235
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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30
For the dosing period calculations, the date of last dose is the latest record on the exposure eCRF 
for the respective study drug regardless of the actual dose or whether the dose was administered.
9.3.
Treatment Duration
For a given study drug, treatment duration (in weeks) is defined as: 
[(Treatment end date as defined in Section 9.1) – (Day 1 of treatment) + 1]/7. 
Cycle duration is defined as the time period from Day 1 of each cycle to the day prior to Day 1 
of subsequent cycle. For the last cycle, the end date is the treatment end date and will be used in 
the calculation of duration of the last cycle. 
Descriptive statistics will be provided for treatment duration, and cycle duration for both nab-
paclitaxel and carboplatin. Number of subjects will also be tabulated by total number of cycles 
received for both nab-paclitaxel and carboplatin.
9.4.
Cumulative Dose
Cumulative dose is defined as the sum of the values entered on the dose assigned field on the 
exposure eCRF for visits at which actual dose administered > 0 mg, taken across the study in 
mg/m² for nab-paclitaxel or mg*min/mL for carboplatin. Cumulative dose will be computed 
separately for nab-paclitaxel and carboplatin. Only doses that were actually administered will be 
included in the cumulative dose. Descriptive statistics will be presented for cumulative dose 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 for that study drug. 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].
Dose intensity will be presented by study drug 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 for Arm A (21 day cycle) are as follows:
!
nab-Paclitaxel: 100 mg/m2/wk (100 mg/m2 on days 1, 8, and 15 of each 3 week cycle)
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!
Carboplatin: 2 mg*min/mL/wk (6 mg*min/mL  on day 1 of each 3 week cycle)
The protocol weekly doses for Arm B (28 day cycle) are as follows:
!
nab-Paclitaxel: 75 mg/m2/wk (100 mg/m2 on days 1, 8, and 15 for each 4 week cycle)
!
Carboplatin: 1.5 mg*min/mL/wk (6 mg*min/mL on day 1 of each 4 week cycle)
Percentage of protocol dose for carboplatin and nab-paclitaxel will be categorized into <70%, 
≥70% to < 80%, and ≥80 to <90% and ≥90%, and frequency counts will be provided for the 
treated population.
9.7.
Exposure, Dose Reduction, Delay, and Skipped Doses
Dose reduction is defined as when the assigned dose at any visit after Cycle 1 Day 1 is at a lower 
dose level than the assigned dose at the previous dosing visit. In addition, a Cycle 1 Day 1 
assigned dose that is lower than 100 mg/m2 for nab-paclitaxel or AUC 6 for carboplatin is 
considered a dose reduction.
Dose delay is defined as when the scheduled dose is administered greater than or equal to 3 days 
after the scheduled dosing date.
Treatment exposure, dose reductions and delays, and doses not administered will be summarized 
as follows:
!
Number of cycles and doses administered;
!
Number and percentage of subjects with at least 1 dose reduction, number of dose 
reductions, and reasons (adverse event or other) for reduction, by cycle and overall;
!
Number and percentage of subjects with at least one dose delay, number of dose 
delays, by cycle and overall;
!
Number and percentage of subjects with at least 1 dose not administered, number of 
doses not administered, and reasons (adverse event or other) for dose not 
administered, by cycle and overall.
The reason for dose reduction will be summarized using the data in the “reason for dose 
adjustment” field in the exposure CRF for identified dose reductions. 
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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.
Of note, the primary objectives of this study regard safety endpoints.
&(/*(1(35235,(7$5<,1)250$7,21


nab-Paclitaxel (Abraxane®)
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10.1.
Primary Safety Endpoint
The primary endpoint for this study is a composite safety endpoint, namely, the percentage of 
subjects who develop treatment-emergent peripheral neuropathy of Grade ≥ 2 or treatment-
emergent myelosuppression AEs of Grade ≥ 3 based on the local laboratory values for ANC, 
platelet count and hemoglobin (with lower values corresponding to higher grades). The 
peripheral neuropathy events will be identified from the clinical AE dataset using the adverse 
events MedDRA preferred terms that are identified with adverse events of special interest 
category equal to “Peripheral Neuropathy” in the embedded spreadsheet in Appendix 16.4.
The myelosuppression AEs of grade ≥ 3 will be identified from the local laboratory values for 
ANC, platelet count and hemoglobin, which will be graded according to the NCI CTCAE 
Version 4.0. The specific cutoff values to identify myelosuppression AEs for the primary 
endpoint are as follows:
!
Absolute neutrophils < 1,000 cells/mm3 (which is equivalent to < 1.0 x 10^9 /L and < 1.0 
x 10^3/mm^3);
!
Hemoglobin < 8 g/dL (which is equivalent to < 80 g/L);
!
Platelets <50,000 cells/mm3 (which is equivalent to < 50.0 x 10^9 /L and < 50.0 x 
10^3/mm^3);
The null (Ho) and alternative (Ha) hypotheses for this endpoint are as follows, where P is the rate 
of the AEs described for the primary safety endpoint: 
Ho:  P Arm B = P Arm A
Ha:  P Arm B ≠ P Arm A
The rate of the AEs described for the primary endpoint will be estimated within each treatment 
arm and presented with two-sided 95% confidence intervals. The treatment difference in the AE 
rate will be analyzed using a Cochran-Mantel-Haenszel Chi-square test (Mantel, 1959) with 
ECOG performance status at randomization (0 versus 1) and histology (squamous cell carcinoma 
versus non-squamous cell carcinoma) as the stratification factors.  The ratio of the AE rates will 
be estimated along with the two-sided 95% confidence interval (CI). If stratum cell sizes are too 
small based on the Mantel-Fleiss criterion (Mantel, 1980) a Pearson Chi-square test will be used 
instead.
10.2.
Adverse Events
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), which 
are defined as any AEs that begin or worsen on or after the first dose date through 28 days after 
the last dose of study drug recorded on the treatment disposition CRF. In addition, any SAE with 
an onset date more than 28 days after last dose of study drug that is assessed by the investigator 
as related to study drug will be considered a TEAE. All AEs will be coded using the Medical 
Dictionary for Regulatory Affairs® (MedDRA) dictionary Version 18.0 or above. Appendix 16.5
gives the dates of application of new versions of MedDRA. The severity will be graded based on 
NCI CTCAE Version 4.0.
The following rules will be implemented for cycle calculations:
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!
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.
!
All TEAEs which start after Day 1 of last cycle will be included only in the last cycle.
For the summary of treatment-related AEs, a treatment-related TEAE is defined as an adverse 
event which was considered to be related, reported as “suspected” in eCRF, to either component 
of combination drugs. Additionally, for related AEs reported as “suspected” in eCRF to each 
individual drug, nab-Paclitaxel or Carboplatin will be summarized for each study drug. If a 
subject experiences multiple occurrences of the same AE with different relationship to study 
medication categories, the subject will be counted once, as a relationship category of treatment 
related. 
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 preferred term (system organ class), then the subject will be counted only 
once for that preferred term (system organ class). 
The incidence of TEAEs will be summarized by MedDRA system organ class (SOC) and 
preferred term (PT). The intensity of AEs will be graded 1 to 5 according to the National Cancer 
Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. For all other 
AEs not described in the CTCAE criteria, the intensity will be assessed by the investigator as 
mild (grade 1), moderate (grade 2), severe (grade 3), life-threatening (grade 4) or death (grade 5). 
Tables summarizing the incidence of TEAEs by treatment arm and overall will be generated for 
each of the following:
!
Overall summary of TEAEs;
!
All TEAEs by MedDRA system organ class and preferred term;
!
All Grade 3/4 and Grade 5TEAEs by MedDRA system organ class and preferred 
term;
!
Treatment-related TEAEs by MedDRA system organ class and preferred term;
!
Grade 3/4 and Grade 5 treatment-related TEAEs by MedDRA system organ class and 
preferred term;
!
Serious TEAEs by MedDRA system organ class and preferred term;
!
Treatment-related serious TEAE;
!
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 study drug interrupted;
!
Treatment-related TEAEs with action of study drug dose reduced or study drug 
interrupted;
!
TEAEs with fatal outcome;
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nab-Paclitaxel (Abraxane®)
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!
Treatment-related TEAEs with fatal outcome;
!
All death within 28 days of last dose with cause of death; 
!
Most frequent TEAEs ( ≥ 5% in either arm; sorted by Preferred Term, without SOC)
!
TEAEs for the following baseline subgroups (provided the number of subjects are 
sufficient): 
#
Age (70-74 years,  ≥75 years); 
#
Sex (male and female); 
#
Race
Listings for treatment-emergent and non-treatment-emergent AEs, and treatment-emergent and 
non-treatment-emergent serious AEs will be provided. 
10.3.
Peripheral Neuropathy
Peripheral neuropathy (PN) events will be collected on the Assessment of Peripheral Neuropathy 
eCRF reported as AEs and will be included in analyses described in Section 10.2. A summary of 
PN grade by treatment arm and cycle will be provided based on the eCRF data. In addition, time 
from first dose to the first occurrence or worsening of peripheral neuropathy and time from 
occurrence or worsening to improvement in peripheral neuropathy will be presented by treatment 
arm as follows:
!
Time to first onset of grade 3 or higher peripheral neuropathy;
!
Time to improvement of grade 3 or higher peripheral neuropathy by at least 1 grade;
!
Time to improvement of grade 3 or higher peripheral neuropathy to grade 1 or better.
Summaries of time to first onset will present summary statistics for those subjects who 
experienced peripheral neuropathy of the relevant grade. There will be no censoring. 
Summaries of time to improvement will include only subjects who experienced peripheral 
neuropathy of the relevant grades. Subjects who do not experience improvement will be censored 
at the last time the subject is evaluated for adverse events. Kaplan Meier methods will be used to 
attain the median and 95% confidence interval.
10.4.
Adverse Events of Special Interest
The adverse events of special interest (AESI) listed in Appendix 16.4 will be summarized.
The following summaries will be provided for AESI: 
!
AESI by MedDRA system organ class and preferred term; 
!
All grade 3 or higher AESI by MedDRA system organ class and preferred term;
!
AESI with action of study drug withdrawn; 
!
AESI with action of study drug dose reduced or study drug interrupted;
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!
AESI by age group for risks specific to safety in patients older than 75 years (70-74
years,  ≥75 years).
In addition to the above, the following time to event analyses will be performed for each class of 
AE of special interest (with the exception of hypersensitivity):
!
Time to first onset of grade 3 or higher;
!
Time to improvement of grade 3 or higher by at least 1 grade;
!
Time to improvement of grade 3 or higher to grade 1 or better;
Summaries of time to first onset will present summary statistics for those subjects who 
experienced AESI of the relevant grade. There will be no censoring.
Summaries of time to improvement will be presented for AESI categories in which at least 20 
subjects experienced an event. The summaries will include only subjects who experienced AESI
of the relevant grades. Subjects who do not experience improvement will be censored at the last 
time the subject is evaluated for adverse events. Kaplan Meier methods will be used to attain the 
median and 95% confidence interval.
10.5.
Clinical Laboratory Evaluations
All laboratory data will be listed.  Laboratory parameters regularly collected on the eCRFs 
(ANC, platelets, hemoglobin, and serum creatinine) will be summarized by descriptive statistics 
by visit and treatment if the number of subjects with data is adequate. Local laboratory values for 
ANC, platelets, and hemoglobin that meet the CTCAE criteria for grade 3 or higher 
myelosuppression will be identified as described in section 10.1.
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11.
EFFICACY ANALYSIS
Note that the primary objective of this study is safety. All efficacy evaluations will be conducted 
using the ITT population. Supportive analysis of the efficacy endpoints PFS, OS, and ORR using 
the PP population will be conducted for the final analysis. The assessments of all efficacy 
endpoints will be based on the point estimates and the associated 95% confidence intervals for 
the within-group parameters of interest and the between-group differences.  P-values for 
between-group comparisons will be provided to indicate the strength of association only.
Listings will be provided for all endpoints. 
Confirmation of response is required for some efficacy analyses. Confirmation of response will 
be determined based on the RECIST 1.1 criteria. Confirmed complete or partial response will be 
declared if the criteria for response are met at two consecutive radiological assessments at least 
28 days apart, or if two assessments meeting the criteria for response are separated by a single 
assessment with overall response of Not Evaluable. The specific sequences of responses and the 
best confirmed overall response associated with those sequences are presented in Table 7 in 
Appendix 16.6.
For all efficacy evaluations that make use of tumor assessment data, post-baseline tumor 
assessments that occur after the initiation of subsequent anti-cancer therapy will be excluded. 
11.1.
Multiplicity
No formal adjustment will be made for testing multiple endpoints. Adjustments made based on 
the interim analysis are described in Section 13.
11.2.
Analysis of Efficacy Endpoints
11.2.1.
Progression-free Survival
Progression-free survival (PFS) will be analyzed using the p-value from the stratified log-rank 
test of PFS based on the ITT population and will be considered the primary efficacy analysis, 
with the unstratified analysis considered a supporting analysis.
PFS is defined as the time in months from the date of randomization 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 Table 3: Censoring Rules for PFS).Subjects who do not have disease 
progression and have not died, regardless of whether they discontinued treatment, will be 
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censored at the date of last tumor assessment, on or prior to the clinical cutoff date that the 
subject was progression-free. The calculation of PFS is a two-step process:
!
Determination of date of disease progression, which is recorded on the Overall 
Response eCRF at the first tumor assessment when the overall tumor response is 
“Progressive Disease” 
!
Calculation of duration from randomization to disease progression, death, or 
censoring date as described below in Table 3
&(/*(1(35235,(7$5<,1)250$7,21


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Table 3: Censoring Rules for PFS
&(/*(1(35235,(7$5<,1)250$7,21


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Situation on or before Clinical Data 
Cutoff Date for CSR
Analysis Date 
Censored or 
Event
Disease progression, and time interval 
between progression date and 
previous tumor assessment date with 
progression-free response is less than 
or equal to 91 days
Date of disease progression 
recorded at the first tumor 
assessment with overall response 
of PD
Event
Disease progression, and time interval 
between the progression date and the 
previous tumor assessment date with 
progression-free response is greater 
than 91 days.
Latest of:
!
the last 
progression-free 
assessment date
!
randomization 
date
Censored
Death without any post-baseline 
radiological assessment, and time 
interval between death date and 
randomization date is less than or 
equal to 91 days
Death date
Event
Death before documented progression, 
and time interval between death date 
and previous tumor assessment date 
with progression-free response is less 
than or equal to 91 days
Death date
Event
Death without any post-baseline 
radiological assessment, and time 
interval between death date and 
randomization date is greater than 91
days
Randomization date
Censored
Death before documented progression, 
and time interval between death date 
and previous tumor assessment date 
with progression-free response is 
greater than 91 days
The last progression-free 
assessment date
Censored
No death or disease progression and 
no subsequent anti-cancer therapy 
(i.e., systemic anti-cancer therapy, 
anti-cancer surgery, curative 
radiotherapy).
Latest of 
!
the last progression-free 
assessment date
!
randomization date
Censored
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Subsequent anti-cancer treatment (i.e., 
systemic anti-cancer therapy, anti-
cancer surgery, curative radiotherapy) 
started prior to progression
Latest of 
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start of anti-cancer 
treatment
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Note: Progression-free response refers to a response that was neither progressive disease 
(PD) nor un-evaluable (UE). 
Progression-free survival is calculated as follows:
PFS = (Analysis date defined above – randomization date + 1)/30.4375
The null (Ho) and alternative (Ha) hypotheses for testing the PFS endpoint are: 
Ho: HR Arm B / Arm A = 1
Ha: HR Arm B / Arm A ≠ 1
Progression-free survival will be summarized using Kaplan-Meier methods with median PFS 
time (including two-sided 95% CI) for each treatment arm. The associated hazard ratio and two-
sided 95% CI will be estimated using a stratified Cox proportional hazards model (Cox, 1972). 
The stratification factors are ECOG performance status at randomization (0 versus 1) and 
histology (squamous versus non-squamous cell carcinoma). The Kaplan-Meier curve for PFS 
will be presented graphically for each treatment arm. PFS rates, including two-sided 95% CIs,
will be provided for every 2 months relative to randomization (Greenwood’s formula, 
Klein, 2003). The p-value from a stratified log-rank test (
Klein 2003) will be reported as an indication of the strength of association for the difference 
between the two curves.
To assess the impact on PFS of radiologic assessments not occurring at the regularly scheduled 
assessment times, sensitivity analyses will be performed where subjects with events and 
censorings that occur at a time other than the regularly scheduled visit assessment will have PFS 
time based on the date of the next regularly scheduled assessment rather than the actual off-
schedule date. Methods similar to the primary analysis will be used to estimate the median PFS 
along with HRs.
An additional analysis of PFS will be performed using the European Medicines Agency 
methodology for analysis of a PFS endpoint. Similar to the approach described above, PFS will 
be defined as the time from the randomization date to the start of disease progression or subject
death (any cause), 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.
An additional analysis of PFS, where the initiation of a subsequent treatment will be considered 
as an event, will be conducted to address the impact of second-line therapy.
PFS will be analyzed on the ITT and PP populations.
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11.2.2.
Overall Survival
Overall survival (OS) is defined as the time in months between randomization and death. Thus, it 
is calculated as follows
OS = (date of death – date of randomization + 1) /30.4375
All deaths prior to the data cutoff date, regardless of the cause of death, will be included. All 
subjects who are lost to follow-up prior to the data cutoff date will be censored at the last known 
alive date as recorded on the survival follow-up eCRF page. Subjects who are not lost-to-follow-
up and are still active on the study, whether on treatment or in follow-up, as of the data cutoff 
date, will be censored at the cutoff date. Subjects who have discontinued participation in the 
study will be censored at the study discontinuation date. 
Overall survival will be analyzed similarly to PFS on the ITT and PP populations and presented 
for each treatment arm.
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 new cancer therapy. 
11.2.3.
Overall Response Rate and Tumor Response
Overall response rate (ORR) is defined as the percent of all ITT subjects who had a radiologic 
complete response (CR) or partial response (PR) compared to baseline (radiographic evaluation 
on the day of or within 28 days prior to randomization) according to RECIST Version 1.1 
guidelines determined by the investigator; confirmed by repeat radiologic assessment performed 
no less than 28 days after the criteria for response were first met; and occurring between Day 1 
of treatment and the start of subsequent anti-cancer therapy, death, or study discontinuation.  
ORR for each treatment arm will be presented with the two-sided 95% CI. The relative treatment 
effect will be estimated by the response rate ratio (ORR in Arm B/ORR in Arm A) and the 
associated two-sided 95% CI.  The p-value from a Cochran-Mantel-Haenszel Chi-square test,
stratified by ECOG status and histology, will be reported.
As a supportive analysis, the percentage of subjects that achieve an overall complete or partial 
response based on investigator’s assessment of response using RECIST 1.1 guideline, regardless 
of confirmation status, will also be summarized with 2-sided 95% exact confidence interval for 
each treatment regimen.
The number and percentage of subjects with a tumor response of complete response (CR), partial 
response (PR), stable disease (SD), progressive disease (PD), unevaluable (UE) and the 
corresponding 95% CI will be presented for each protocol-specified CT scan (Week 6, Week 12, 
etc. ). For CT scans that do not fall on those exact dates, the windows given in Section 16.3 will 
be used to determine the week. 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 Section 16.3.
Subjects who do not have post-baseline tumor assessments will be presented in a separate row. 
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11.3.
Subgroup Analysis
PFS, OS, and ORR will all be analyzed within the following subgroups (with subgroup data 
based on the clinical database). Subgroup factors will not be used as stratification factors or
regression adjustment covariates for relevant analyses, but otherwise these analyses will parallel 
the analyses for the endpoint performed on the whole population:  
!
Age (70 – 74 years, 75 – 79 years, ≥80 years)
!
ECOG status at randomization (0 versus 1);
!
Histology (squamous versus non-squamous);
!
Sex (male versus female); 
The p-value from the treatment-by-subgroup interaction term in the Cox model will be presented 
for all subgroups. A forest plot will be provided displaying the HRs and corresponding 95% CIs 
for PFS and OS for each subgroup. These HRs and 95% CIs will be obtained from Cox 
proportional hazards models using only subjects in the relevant subgroup. 
11.4.
Exploratory analysis
11.4.1.
Healthcare utilization
Frequency tabulation 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 by treatment arm.
11.4.2.
Quality of Life Analysis
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 index score that is derived from the 5 
questions. These questionnaires will be completed at Day 1 of every cycle, at End of Treatment, 
and at the 28-day follow-up visit. Baseline scores are defined as scores captured on Day 1 (first 
dose date). In the case of multiple assessments on Day 1, the later assessment will be used. 
Missing baseline scores will not be imputed. In the case of multiple assessments at post-baseline 
assessments, the later assessment will be used.
11.4.2.1.
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
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!
Blood in sputum
!
Pain
In addition, it measures how bad a subject’s symptoms are, how much it has affected normal 
activities, and quality of life. 
The LCSS consists of two scales: one to be filled out by the subject and one by the health care 
provider. For this study, only the portion filled out by the subject will be used. The subject will 
respond to each of the 9 items using marks on a 100 mm visual analog scale (VAS). For analysis 
and presentation purposes, the scores will be presented such that 0 mm corresponds to the worst 
possible health state and 100 mm corresponds to the best possible health state.
The average of the VAS score of all 9 items 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 
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 ITT population at every time point at which the instrument is 
given. In addition, the change from baseline to the best LCSS score during treatment, defined as 
the maximum LCSS score reported between Cycle 2 Day 1 through the end of treatment visit, 
will be presented. Finally, the change from baseline to the last LCSS score during treatment, 
defined as the LCSS score at the end of treatment visit or the last reported on-treatment LCSS 
score before clinical cutoff for subjects who have not had an end of treatment visit, will be 
presented.
Statistical comparisons will be made between the treatment arms for change from baseline to last 
administration and best score using analysis of covariance. Histology (squamous cell carcinoma 
versus non-squamous cell carcinoma) and ECOG status (0 versus 1) at screening will be the 
covariates.
11.4.2.2.
EQ-5D-5L
The EQ-5D-5L has been designed as an international, standardized, generic instrument for 
describing and valuing health-related quality of life. It contains only the domains common to 
generic health status measures, contains the minimum number of questions for each domain, was 
designed for ease of self-administration, and produces a single index for analysis. 
Five dimensions are covered by the EQ-5D-5L:
!
Mobility
!
Self-care
!
Usual Activities
!
Pain/Discomfort
!
Anxiety/Depression
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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.  
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 will be presented for 
each dimension for the ITT population. 
The utility score and change from baseline in the utility score will be summarized for each time 
point at which the instrument is given for the ITT population. In addition, the change from 
baseline to the best utility score reported during treatment, defined as the maximum utility score 
reported between Cycle 2 Day 1through the end of treatment visit, will be presented. Finally, the 
change from baseline to the last 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 to the best utility
score reported during treatment, defined as the maximum VAS reported between Cycle 2 Day 
1through the end of treatment visit, will be presented. Finally, the change from baseline to the 
last reported overall score, either 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.
Statistical comparisons will be made between the treatment arms for change from baseline to the 
best and last utility score and VAS using analysis of covariance. Histology (squamous cell 
carcinoma versus non-squamous cell carcinoma) and ECOG status (0 versus 1) at screening will 
be the covariates.
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12.
FOLLOW UP TREATMENTS
Follow up anti-cancer treatments will be coded to therapeutic drug classes and generic drug 
names using the World Health Organization (WHO) Drug Dictionary Enhanced version WHO-
DDE Q3 2013 or later. Combinations of treatments will be classified into regimens. 
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, which 
is defined as the time interval from the date of last dose of study drug to the date that the first 
subsequent systemic anti-cancer therapy is initiated. Subjects who don’t have a subsequent
therapy and have not died as of the cutoff date for the statistical analysis will be censored at the 
last follow up date. Subjects who die before initiating a new 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 for each treatment arm; the associated 
hazard ratio with two-sided 95% confidence interval will be estimated using a non-stratified Cox 
proportional hazard model (Cox, 1972).
Time to second-line therapy will be summarized for all discontinued subjects, and for subjects 
who discontinued due to disease progression and subjects who discontinued for reasons other 
than disease progression.
The duration, whether the number of cycles is known, the number of cycles (if known), and the 
best response for all subsequent anti-cancer treatments will all be presented in a listing. These 
follow up treatments will be summarized by treatment arm and ATC class and preferred term. In 
addition, the following summaries by treatment arm will be generated:
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will


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13.
INTERIM ANALYSIS
13.1.
Interim Evaluation of Dosing, Safety and Efficacy
A non-binding interim evaluation of dosing, primary safety endpoint, and efficacy data will be
conducted when approximately a total of 120 treated subjects have either completed 4 months of
study treatment or discontinued study treatment due to progression, adverse events, deaths, lost
to follow up, or other reasons. The interim evaluation will be conducted by an independent
statistician and the results will be reviewed by the SSC. The SSC may recommend to stop the
study early based on the study dosing data in relation to the primary hypothesis, or meeting of
the futility criterion of the primary endpoint (if the treatment difference [Arm B minus Arm A] is
≥-0.2% given the interim analysis of this endpoint is performed at 43% information fraction), or
totality of the dosing, safety, and efficacy data as well as clinical significance.
13.2.
Interim Analysis of Quality of Life Questionnaire Data
For administrative purposes (eg, planning of new studies, publication of data) the LCSS and EQ-
5D measurements will be summarized for the two treatment groups combined using descriptive 
statistics when approximately 50, 100, 150, and all subjects, respectively, have completed four 
cycles of treatment or discontinued treatment.
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14.
CHANGES TO THE STATISTICAL ANALYSES SECTION OF 
THE PROTOCOL
The study was originally planned to enroll 284 subjects but stopped early due to futility criterion 
being met. The actual number randomized was 143.
The PFS censoring rules given in protocol section 10.7.1 are elaborated with clarification of
derivation rules in section 11.2.1 of this document.
The following secondary efficacy endpoint was added to further characterize the ORR endpoint:
!
ORR without the requirement of confirmation of response.
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15.
REFERENCES
Cox, D., 1972. Regression Models and Life-Tables. Journal of the Royal Statisticial Society, 
Series B, 34(2), pp. 187-220.
Eisenhauer, E. et al., 2009. New response evaluation criteria in solid tumours: Revised RECIST 
guideline (version 1.1). European Journal of Cancer, Volume 45, pp. 228-247.
Hwang, I. K., Shih, W. J. & De Cani, J. S., 1990. Group sequential designs using a family of 
Type I error probability spending functions. Statistics in Medicine, Volume 9, pp. 1439-1445.
Klein J.P. and Moeschberger M.L. Survival Analysis: Techniques for Censored and Truncated
Data, 2nd ed. Springer, 2003.
Mantel N. and Fleiss J.L., 1980. Minimum Expected Cell Size Requirements for the Mantel-
Haenszel One-Degree-of-Freedom Chi-Square Test and a Related Rapid Procedure. American 
Journal of Epidemiology, Volume 112, pp. 129-134.
Mantel N. and Haenszel W., 1959. Statistical aspects of the analysis of data from retrospective 
studies of disease. Journal of the National Cancer Institute Volume 22 (4), pp. 719–748.
Ulm K., 1990. Simple Method to Calculate the Confidence Interval of a Standardized Mortality 
Ratio (SMR). American Journal of Epidemiology, Volume 131(2), pp. 373-375.
y of
o
-1445.
1445.
and Truncat
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ments for th
nts fo
pid Procedu
pid Procedu
e analysis o
e analysis 
ute
ute Vo
Volulum
Confidenc
Confidenc
ology
ology, Vol
 Vol


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16.
APPENDICES
16.1.
Handling of Dates 
Dates will be stored as numeric variables in the SAS analysis files and reported in 
DDMMMYYYY format (i.e., 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 CRF 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 (egg, for duration or cycle assignment, etc). However, in listings, log dates will 
be shown as recorded without imputation.
!
Milestone Dates are dates of protocol milestones such as randomization, study drug 
start date, study drug termination date, study closure date, etc.  They should not be 
missing if the milestone occurs for a subject.  They will not be imputed.
!
Outcome Dates are dates corresponding to study endpoints such as survival, 
progression, etc.  In most cases they are derived either from a milestone (egg, the 
survival date is derived from the death date), or a procedure date (egg, 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 (egg, 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: 
ns, 
s, 
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marked as
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They
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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. 
!
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
16.2.
Date Imputation Guideline
16.2.1.
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 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 
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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 
!
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16.3.
Relative Day Ranges for CT-Scans
Table 4: Relative Day Ranges for CT Scans
Study 
Week
Relative Days in 
Study
6
2 - 63
12
64 - 105
18
106 - 147
24
148 - 189
30
190 - 231
36
232 - 273
42
274 - 315
48
316 - 357
54
358 - 399
60
400 - 441
66
442 - 483
72
484 - 525
78
526 - 567
84
568 - 609
90
610 - 651
96
652 - 693
102
694 - 735
108
736 - 777
114
778 - 819
120
820 - 861
126
862 - 903
132
904 – 945
138
946 - 987
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6 - 147
6 - 147
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148 - 189
148 - 189
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190 - 2
190 - 2
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232
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35
35
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48
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54
54
23
60
60
52
3
6
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3


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
53
16.4.
Treatment-emergent Adverse Events of Special Interest
Table 5 below provides the spreadsheets of adverse events of special interest that were used for 
data summaries up to the dates provided.
Table 5: Treatment-emergent Adverse Events of Special Interest File and Dates
For reports dated: 
File
MedDRA version
June 2015 – 01May2016
ABRAXANE 
ABI-007-NSCL-005_V1
18.0
02May2016 – present
ABRAXANE 
ABI-007-NSCL-005_V
19.0
16.5.
MedDRA Versions and Dates
Table 6 gives the MedDRA versions used in this study and the dates of implementation.
Table 6: MedDRA Versions and Dates
For reports dated: 
MedDRA version
04May2015 – 01May2016
18.0
02May2016 – present
19.0
16.6.
RECIST 1.1 Best Overall Response with Confirmation of Complete 
and Partial Response
Table 7 gives the interpretation of best overall response with the requirement of confirmation of 
CR and PR based on the RECIST 1.1 criteria (Eisenhauer) as applicable to this study.
Table 7: RECIST 1.1 Best Overall Response with Confirmation of Complete and Partial 
Response
Overall response 
First time point
Overall response
Subsequent time point
Best overall response
CR
CR
CR
CR
PR
SD, PD or PRa
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Over
Over
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udy
udy and the
and th
y
DRA versio
RA versi
5,(
8.0
8.0
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19.0
19.0
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35
35
35
35
ST 1.1 Be
ST 1.1 Be
Partial R
Partial R
es the interp
es the inter
PR based o
based 
e 7: RECI
REC
&(
&


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-005
Celgene Corporation
Confidential and Proprietary
54
CR
SD
SD
CR
PD
SD 
CR
NE
SD 
PR
CR
PR
PR
PR
PR
PR
SD
SD
PR
PD
SD 
PR
NE
SD 
NE
NE
NE
[a] If a CR is truly met at first time point, then any disease seen at a subsequent time point, 
event disease meeting PR criteria relative to baseline, makes the disease PD at that time 
point.
Subjects with at least one post-baseline tumor assessment who do not experience any of the 
scenarios in Table 7: RECIST 1.1 Best Overall Response with Confirmation of Complete and 
Partial Responsewill have the following rules applied:
!
SD followed by PD will be classified as SD
!
SD followed by SD will be classified as SD
!
SD followed by NE is SD
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nt,
me
me
$
50$
nce any o
e any of
n of Co
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mp