Conditions: Squamous Cell Carcinoma, Non-Small-Cell Lung
Keywords: Nab-paclitaxel Albumin bound paclitaxel Taxanes Maintenance trials Celgene Abraxane ABI-007 NSCLC Non-Small Cell Lung Cancer Cancer of the Lung Carcinoma, Squamous Cell Lung Neoplasms Abound.sqm
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 427
Healthy volunteers: no

Brief summary:
Maintenance treatment of advanced stage squamous cell NSCLC.

Phase III, randomized, open-label, multi-center study of nab-paclitaxel with best supportive care (BSC) or BSC alone as maintenance treatment after response or stable disease (SD) with nab-paclitaxel plus carboplatin as induction in subjects with stage IIIB/IV squamous cell NSCLC.

Subjects who discontinued treatment from the maintenance part for any reason other than withdrawal of consent, lost to follow-up, or death, were entered into a Follow-up period that had a visit 28 days after progression or discontinuation.

Those who entered Follow-up without progression continued with follow-up scans according to standard of care (SOC) until documentation of progression of disease. Additionally, subjects were followed for OS by phone approximately every 90 days for a minimum of 18 months, for up to approximately 5 years after the last subject was randomized.

Detailed description:
The sponsor used 15 Sep 2017 as the database cut-off date.

Arms:
arm 1: Dosing will occur in two phases - induction and maintenance. During induction, the subject will receive Abraxane plus carboplatin as standard of care. At the end of 4 cycles, if the subject has a complete response, partial response, or stable disease, he/she will continue on to the maintenance phase. Maintenance dosing on this arm includes Abraxane plus best supportive care. arm 2: Dosing will occur in two phases - induction and maintenance. During induction, the subject will receive Abraxane plus carboplatin as standard of care. At the end of 4 cycles, if the subject has a complete response, partial response, or stable disease, he/she will continue on to the maintenance phase. Maintenance dosing on this arm includes best supportive care only.

Interventions: intervention 1: Abraxane (Induction) intervention 2: Carboplatin (Induction) intervention 3: Abraxane (Maintenance) intervention 4: Best Supportive Care (Maintenance) intervention 5: Abraxane (Induction) intervention 6: Carboplatin (Induction) intervention 7: Best Supportive Care (Maintenance)
Intervention descriptions: intervention 1: 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 15 of each 21-day cycle, administered as standard of care intervention 2: 6 mg/min/mL IV on Day 1 of each 21-day cycle after completion of nab-paclitaxel infusion intervention 3: 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle, administered as standard of care intervention 4: The best palliative care per investigator (including but not limited to: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and/or focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis), excluding antineoplastic agents intervention 5: 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 15 of each 21-day cycle, administered as standard of care intervention 6: 6 mg/min/mL IV on Day 1 of each 21-day cycle after completion of nab-paclitaxel infusion, administered as standard of care intervention 7: The best palliative care per investigator (including but not limited to: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and/or focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis), excluding antineoplastic agents

Protocol document:
Prot_003.pdf: 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
TITLE PAGE
A PHASE III, RANDOMIZED, OPEN-LABEL, MULTI-
CENTER, SAFETY AND EFFICACY STUDY TO 
EVALUATE NAB-PACLITAXEL (ABRAXANE®) AS 
MAINTENANCE TREATMENT AFTER INDUCTION 
WITH NAB-PACLITAXEL PLUS CARBOPLATIN IN 
SUBJECTS WITH SQUAMOUS CELL NON-SMALL 
CELL LUNG CANCER (NSCLC)
INVESTIGATIONAL PRODUCT (IP):
nab-Paclitaxel (Abraxane®)
PROTOCOL NUMBER:
ABI-007-NSCL-003
ORIGINAL DATE FINAL:
27 Sep 2013
AMENDMENT 1 DATE FINAL:
28 Oct 2014
AMENDMENT 2 DATE FINAL:
07 May 2015
AMENDMENT 3 DATE FINAL:
13 Mar 2017
EudraCT NUMBER:
2014-003804-66
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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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
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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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name: _______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name: _______________________________________
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
PROTOCOL SUMMARY
Study Title
A Phase III, randomized, open-label, multi-center, safety and efficacy study to evaluate nab®-
paclitaxel1 (Abraxane) as maintenance treatment after induction with nab-paclitaxel plus 
carboplatin in subjects with squamous cell non-small cell lung cancer (NSCLC).
Indication
Maintenance treatment of squamous cell NSCLC.
Objectives
Primary
!
To evaluate progression free survival (PFS) with nab-paclitaxel as maintenance 
treatment after response or stable disease (SD) with nab-paclitaxel plus carboplatin in 
subjects with squamous cell NSCLC.
Secondary 
!
To evaluate the safety and tolerability of nab-paclitaxel as maintenance treatment 
after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous 
cell NSCLC.
!
To further assess the efficacy with nab-paclitaxel as maintenance treatment after
response or SD with nab-paclitaxel plus carboplatin in subjects with squamous cell 
NSCLC, as measured by secondary efficacy endpoints.
Exploratory 
!
To determine baseline tumor characteristics which predict response and resistance to 
nab-paclitaxel/carboplatin during the Induction part of the study. 
!
To determine what changes in peripheral tumor characteristics during treatment are 
associated with acquisition of resistance in the subjects who had initial clinical 
benefit.
!
To assess healthcare resource utilization during the Maintenance part of the study.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ5D).
Study Design
This is a Phase III, randomized, open-label, multi-center study of nab-paclitaxel or best 
supportive care (BSC) as maintenance treatment after response or SD with nab-paclitaxel plus 
carboplatin as induction in subjects with squamous cell NSCLC. Approximately 450 subjects
with stage IIIB or IV squamous cell NSCLC will be enrolled in the Induction part of the study to 
receive nab-paclitaxel plus carboplatin for 4 cycles. If after the 4 cycles, the subject has a 
complete response (CR), partial response (PR), or SD, they will be randomized (2:1) in the
Maintenance part of the study to receive nab-paclitaxel plus BSC or BSC alone. BSC is defined
                                               
1 nab® is a registered trademark of Celgene Corporation.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
as the best palliative care per investigator (including but not limited to: antibiotics, analgesics,
antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and/or focal 
external-beam radiation for control of pain, cough, dyspnea, or hemoptysis), excluding
antineoplastic agents. Approximately 216 subjects will be evaluable for the primary endpoint of 
PFS in maintenance.
Induction Part
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Approximately 450 subjects eligible for 
standard treatment with nab-paclitaxel plus carboplatin for 4 cycles will be enrolled, provided if 
all inclusion/exclusion criteria are met within a 28-day screening period prior to Cycle 1 Day 1.
Induction treatment will commence on Day 1: 
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD, and has met all eligibility criteria, they will continue on to the Maintenance part 
of the study. If the subject has radiological or clinical PD, they will be discontinued from the 
study and will not be followed.
Maintenance Part
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD without clinical progression, and has met all eligibility criteria, they will be 
randomized 2:1 to receive:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day cycle plus BSC until disease progression or unacceptable toxicity (see Section 8.3
for guidelines on starting dose for the Maintenance part of the study if the subject had 
dose reduced during the Induction part of the study)
OR
!
BSC until disease progression
Maintenance therapy should start at the time of randomization. If this is not possible, a maximum 
of 7 days will be allowed from the date of randomization to the start date of Maintenance 
therapy. Subjects must start Maintenance therapy no earlier than 21 days and no later than 35
days from Day 1 of the fourth cycle of Induction therapy.
Follow-up Period 
All subjects who discontinue from the Maintenance part of the study for any reason other than 
withdrawal of consent, lost to follow-up, or death, will enter the Follow-up period that will have 
a visit 28 days after progression or discontinuation.  Those subjects entering the follow up period 
without documented progression will continue to have CT scan in accordance with standard of 
care until documented progression of disease.  Additionally, subjects will be followed for overall 
survival (OS) by phone approximately every 90 days for up to 1.5 years after final analysis of 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
approximately 136 PFS events in which a total of 147 deaths are expected to be observed for the 
final OS analysis.
Study Population
Subjects with squamous cell NSCLC stage IIIB or IV with no prior chemotherapy for metastatic 
disease and ≥ 18 years old will be eligible for this study. The Induction part of the study will 
enroll approximately 450 subjects. Based on results from the nab-Paclitaxel Phase 3 NSCLC 
development study (Protocol CA031) it is estimated that approximately 216 subjects with CR, 
PR, or SD from the Induction part of the study will be randomized to the Maintenance part of the 
study. Enrollment into the Induction part of the study will be monitored and adjusted to ensure 
that approximately 216 subjects are randomized into the Maintenance part of the study.
Length of Study
The Induction part of the study will last approximately 36 months to enroll sufficient subjects for 
the Maintenance part of the study. The total length of this Phase III study with Induction, 
Maintenance, and Follow-up is estimated to last approximately 5 years.
Study Treatments
Induction 
The nab-paclitaxel and carboplatin treatments will not be supplied by Celgene during Induction 
in those countries where nab-paclitaxel plus carboplatin is available for the treatment of NSCLC. 
Investigative sites will use standard of care (commercially available) product via prescription in 
these countries.
In those countries where nab-paclitaxel plus carboplatin is not available for the treatment of 
NSCLC, or is available but designated as investigational product (IP) as per local regulations, 
both agents will be packaged and supplied by Celgene.  
Maintenance 
Subjects will be randomized to receive open-label nab-paclitaxel plus BSC or BSC during the 
Maintenance part of the study. The nab-paclitaxel used in the Maintenance part of the study will 
be packaged and supplied by Celgene Corporation.
Please see local prescribing information for Abraxane for detailed instructions on the
reconstitution, storage conditions, and IV administration of nab-paclitaxel.
Statistical Methods
Approximately 450 subjects will be enrolled in the open-label Induction part of the study. All 
subjects will receive nab-paclitaxel 100 mg/m2 administered weekly followed by carboplatin
AUC = 6 mg*min/mL on Day 1 of each cycle, repeated every 21 days, for 4 cycles.
At the end of Cycle 4, subjects who achieve a radiologically assessed complete response (CR), 
partial response (PR), or stable disease (SD) without clinical progression based on the 
Investigator’s evaluation using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 
guidelines will be further evaluated for their eligibility to participate in the Maintenance part of 
the study.  Approximately 216 subjects are expected to be randomized in the Maintenance part of 
the study.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
9
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
Similarly, the percentage of subjects manifesting a PFS event in the Maintenance part will be 
tracked on an ongoing basis.
Induction Part
Efficacy Analyses
All efficacy endpoints will be analyzed based on the intent-to-treat (ITT) population for the 
Induction part, which includes all enrolled subjects who received at least one dose of study 
treatment regardless of whether they have any efficacy assessments collected.
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Subjects will have CT scans performed at 
the end of Cycle 2 and 4. Subjects who attain a radiologically assessed CR, PR, or SD without 
clinical progression according to the investigator’s assessment of the scan performed at the end 
of Cycle 4, based on RECIST v1.1 (Eisenhauer, 2009) guidelines, and satisfy eligibility criteria 
will be eligible to be randomized in the Maintenance part.
The secondary objective of the Induction part is to estimate the Overall Response Rate (ORR, 
percent of subjects who have a CR or PR according to RECIST v1.1 guidelines as determined by 
the investigator and confirmed by repeat assessments performed no less than 28 days after the 
criteria for response were first met). Descriptive statistics along with appropriate point estimates
and associated two-sided 95% confidence interval will be calculated for this endpoint.
Safety Analyses
The safety population, includes all subjects enrolled who received at least 1 dose of study 
treatment, will be the analysis population for all safety analyses. Adverse events will be 
summarized by worst severity grade. Adverse events (AEs), as well as treatment-emergent AEs, 
will be summarized by system organ class, and preferred term. Adverse event severity/grade will 
be summarized by National Cancer Institute (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE) v4.0. 
Laboratory test results will not be collected in the eCRFs unless they are determined to be 
clinically significant laboratory abnormalities. Abnormal and clinically significant laboratory 
assessments at Screening will be recorded as medical history, and after Screening, as AE or 
serious adverse event (SAE). If a clinically significant laboratory abnormality is captured as 
medical history, AE, or SAE, the specific laboratory parameter(s) should be recorded on the 
laboratory assessments CRF.
Maintenance Part
Approximately 216 subjects will be randomized in the Maintenance part of the study. These 
subjects will be randomized in a 2:1 ratio to the nab-paclitaxel plus BSC and BSC alone groups, 
respectively. The nab-paclitaxel group will receive nab-paclitaxel 100 mg/m2 on Day 1 and 8 of 
each 21-day cycle plus BSC (the actual starting dose may be adjusted as specified in 
Section 8.3), while the BSC group will receive the standard BSC regimen. All subjects will 
receive the assigned regimen until disease progression or unacceptable toxicity.
Randomization will be stratified by the following 3 baseline and prognostic stratification factors:
Eastern Cooperative Oncology Group (ECOG) performance status at the end of the Induction 
part (0 vs. 1), tumor response to induction chemotherapy (CR/PR vs. SD), and disease stage 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
before administration of induction therapy (IIIB vs. IV). Tumor response to Induction part 
chemotherapy for stratification is the response assessed at the last CT scan before randomization. 
It is postulated that subjects will benefit from maintenance therapy with nab-paclitaxel, therefore 
a randomization ratio of 2:1 will reduce subject exposure to treatment with BSC alone while 
providing sufficient data for testing the treatment difference with respect to the primary endpoint, 
progression free survival.
Analysis of Progression Free Survival (PFS)
The Maintenance part of the study is designed to detect a hazard ratio (HR) of 0.60 for PFS 
improvement with the nab-paclitaxel plus BSC regimen over the BSC alone regimen with 80% 
power for a two-sided test conducted at a 5% level of significance. This hazard ratio of 0.60 
assumes an underlying exponential distribution for both treatment groups with a median time to 
PFS of 2 months for the BSC alone group and a median time to PFS of 3.33 months for the nab-
paclitaxel plus BSC group. Hence, the final analysis will be conducted after 136 PFS events (ie, 
events of disease progression or deaths from any cause) have occurred.
One non-binding interim analysis will be used to assess futility using the PFS endpoint only, and
is planned when approximately a total of 91 events have been observed. The study may be 
stopped early for futility only if the conditional power for PFS is < 10% under the assumed 
hazard ratio of 0.60, but there is no allowance to stop the study early to declare superior efficacy.
Analysis of Overall Survival (OS)
There will be two analyses for the OS endpoint, one of which involves an interim analysis that 
corresponds to the final analysis of PFS (approximately 136 PFS total events). However, OS 
collection may continue until 1.5 years after the final analysis of PFS with an expected number 
of total deaths of 147. The interim analysis for the OS endpoint will utilize a Lan-DeMets alpha-
spending function to account for the exact timing of the interim based upon the actual number of 
observed events with an O’Brien-Fleming boundary in order to perform an appropriate group-
sequential hypothesis testing procedure for a two-sided test conducted at a 5% level of 
significance.  
A step-down procedure from the PFS final analysis to this group sequential testing approach for 
OS will be used to address multiplicity of testing. 
OS analysis, the study may be stopped if the conditional power is below the threshold specified 
in the SAP.  
General Considerations for the Efficacy Analyses of PFS, OS, and ORR
The Maintenance part of the study starts on the date the subject is randomized to either of the 
treatment arms. All efficacy analyses in the Maintenance part will be based on the ITT 
population for the Maintenance part, which includes all randomized subjects regardless of 
whether they receive any IP or have any efficacy assessments collected. 
For the primary efficacy endpoint, PFS, the progressive disease component of this endpoint will 
be based on the investigator’s assessment of the subject’s radiologic response using RECIST 1.1 
guidelines. Baseline tumor measurements will be determined by the computed tomography (CT)-
scan performed less than 28 days before the first dose of nab-paclitaxel in the Induction part of 
the study. Progression-free survival (PFS) will be defined from the date of randomization to the 
start date of disease progression or date of subject death due to any cause, whichever occurs first.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
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.
The null (Ho) and alternative (Ha) hypotheses for the primary efficacy endpoint are: 
Ho: HR nab-paclitaxel plus best supportive care / best supportive care = 1
Ha: HR nab-paclitaxel plus best supportive care / best supportive care ≠1
Progression-free survival distributions will be summarized using a graphical display of the 
Kaplan-Meier product limit estimates by treatment group, median PFS time estimates (including 
two-sided 95% CI) by each treatment group, and with an estimated hazard ratio (including two-
sided 95% CI) from an unstratified Cox regression model. The hypothesis test of a hazard ratio 
of 1 with respect to the PFS distributions, as shown above, will be evaluated using a stratified 
log-rank test with the 3 baseline and prognostic factors described under the randomization 
scheme in Section 4.1.2. In addition to the stratified log-rank test, a stratified Cox regression 
model will be employed to evaluate the strength of the treatment effect using the estimated 
hazard ratio and corresponding 95% confidence interval.
The secondary efficacy endpoints include OS and ORR (percent of subjects who attain a CR or 
PR according to RECIST 1.1 guidelines as determined by the investigator and confirmed by 
repeat assessments performed no less than 28 days after the criteria for response are first met). 
Overall survival will be analyzed by the same method described for PFS, while ORR will be 
analyzed by a stratified Cochran-Mantel-Haenszel test at a nominal 5% level of significance.
If there exists unacceptable sparseness in some stratum cells (ie, a stratum cell that has less than 
5 BSC subject counts in the ITT population of the Maintenance part of the study), then an 
algorithm for collapsing some full strata will be employed until there are at least 5 BSC subjects 
in any given revised stratum cell. The initial stratum cells for the BSC treatment group will start 
out as 8 cells that represent all possible permutations of the 3 strata (baseline Eastern 
Cooperative Oncology Group [ECOG] performance status at the end of the Induction part [0 vs. 
1]; tumor response to induction chemotherapy [CR/PR vs. SD]; and disease stage before 
administration of induction therapy [IIIB vs. IV]). Hence, the 8 cells representing all possible 
permutations among the strata may be reduced down to either 4 cells (all possible permutations 
of just 2 relatively large strata), 2 cells (just 1 large stratum); or no strata at all when 
implementing the algorithm for the BSC group, the smallest treatment group based on the 2:1 
randomization. However, it is extremely unlikely that the algorithm will result in no stratum.
Once the revised strata have been determined through the algorithm, then it will be used 
consistently for all stratified analyses.
Safety Analyses
The safety population includes all randomized subjects. Adverse events will be summarized by 
worst severity grade. AEs, as well as treatment-emergent AEs, will be summarized by system 
organ class, and preferred term. Adverse event severity/grade will be summarized by NCI 
CTCAE v4.0.
Laboratory test results will not be collected in the eCRFs unless they are determined to be 
clinically significant laboratory abnormalities. Abnormal and clinically significant laboratory 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
12
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
assessments at Screening will be recorded as medical history, and after Screening, as AE or 
serious adverse event (SAE). If a clinically significant laboratory abnormality is captured as 
medical history, AE, or SAE, the specific laboratory parameter(s) should be recorded on the 
laboratory assessments CRF.
Data Monitoring Committee
An independent Data Monitoring Committee (DMC) will be established with the responsibilities 
for safeguarding the interests of study participants and monitoring the overall conduct of the 
study. Final recommendations of the DMC will reflect the judgment of the DMC members and 
will be considered advisory in nature to the Sponsor. The decision to implement the 
recommendations of the DMC will be made by the Sponsor, following consultation with the trial 
Coordinating Principal Investigator and Steering Committee. A DMC charter will be established.
&(/*(1(35235,(7$5<,1)250$7,21
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
13
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
1.
INTRODUCTION..................................................................................................20
1.1.
Non-small Cell Lung Cancer (NSCLC)...................................................................20
1.2.
nab-Paclitaxel.........................................................................................................20
1.3.
Rationale for Development of nab-Paclitaxel as Maintenance Treatment in 
Squamous Cell NSCLC ..........................................................................................23
2.
STUDY OBJECTIVES...........................................................................................24
2.1.
Primary Objective...................................................................................................24
2.2.
Secondary Objectives .............................................................................................24
2.3.
Exploratory Objectives ...........................................................................................24
3.
STUDY ENDPOINTS............................................................................................25
3.1.
Primary Endpoint....................................................................................................25
3.2.
Secondary Endpoints ..............................................................................................25
3.2.1.
Safety.....................................................................................................................25
3.2.2.
Efficacy..................................................................................................................25
3.3.
Exploratory Endpoints............................................................................................25
4.
OVERALL STUDY DESIGN ................................................................................26
4.1.
Study Design ..........................................................................................................26
4.1.1.
Induction Part.........................................................................................................26
4.1.2.
Maintenance Part....................................................................................................26
4.1.3.
Follow-up Period....................................................................................................27
4.2.
Study Design Rationale ..........................................................................................27
4.3.
Study Duration .......................................................................................................29
4.4.
End of Trial ............................................................................................................29
5.
TABLE OF EVENTS.............................................................................................30
6.
PROCEDURES......................................................................................................35
6.1.
Medical History......................................................................................................35
6.2.
Prior Medications/Procedures .................................................................................35
6.3.
Pregnancy Testing ..................................................................................................35
6.4.
Complete Chest Computed Tomography (CT) Scan (including adrenal 
gland) With and Without Contrast ..........................................................................36
20
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.......23
23
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TABLE 
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M
6.2.
6.2


EDMS Doc. Number: 
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Celgene Corporation
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
6.5.
Weight....................................................................................................................36
6.6.
Body Surface Area (BSA) Calculation and Height..................................................36
6.7.
ECOG Performance Score ......................................................................................36
6.8.
Concomitant Medications/Procedures.....................................................................36
6.9.
Peripheral Neuropathy Assessment.........................................................................36
6.10.
Adverse Event Reporting........................................................................................37
6.11.
Lung Cancer Symptom Scale Questionnaire and EQ5D..........................................37
6.12.
Healthcare Resource Utilization Questionnaire .......................................................37
6.13.
Electrocardiogram ..................................................................................................37
6.14.
CT Scan of Head or Brain Magnetic Resonance Imaging (MRI).............................37
6.15.
Bone Scans and X-rays...........................................................................................37
6.16.
Physical Examinations............................................................................................37
6.17.
Vital Signs..............................................................................................................38
6.18.
Laboratory Assessments .........................................................................................38
6.19.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) .....................................................................................38
6.20.
Survival..................................................................................................................39
7.
STUDY POPULATION.........................................................................................40
7.1.
Number of Subjects and Sites .................................................................................40
7.2.
Inclusion Criteria....................................................................................................40
7.3.
Exclusion Criteria...................................................................................................41
8.
DESCRIPTION OF STUDY TREATMENTS........................................................43
8.1.
Description of Investigational Product(s)................................................................43
8.1.1.
nab-Paclitaxel.........................................................................................................43
8.1.2.
Carboplatin.............................................................................................................43
8.2.
Treatment Administration and Schedule .................................................................44
8.3.
Dose Modifications.................................................................................................44
8.4.
Method of Treatment Assignment...........................................................................47
8.5.
Packaging and Labeling..........................................................................................47
8.6.
Investigational Product Accountability and Disposal ..............................................47
8.7.
Investigational Product Compliance........................................................................47
8.8.
Overdose ................................................................................................................47
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................49
&(/*(1(35235,(7$5<,1)250$7,21
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.......37
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8.6.
.6


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
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9.1.
Permitted Concomitant Medications and Procedures...............................................49
9.2.
Prohibited Concomitant Medications and Procedures..............................................49
9.3.
Required Concomitant Medications and Procedures................................................49
10.
STATISTICAL ANALYSES..................................................................................50
10.1.
Induction Part.........................................................................................................50
10.1.1.
Overview................................................................................................................50
10.1.2.
Study Population Definitions ..................................................................................50
10.1.2.1.
Intent-to-Treat Population.......................................................................................50
10.1.2.2.
Safety Population....................................................................................................50
10.1.3.
Sample Size and Power Considerations...................................................................50
10.1.4.
Background and Demographic Characteristics........................................................51
10.1.5.
Subject Disposition.................................................................................................51
10.1.6.
Efficacy Analysis....................................................................................................51
10.1.6.1.
Primary Purpose .....................................................................................................51
10.1.6.2.
Secondary Endpoints ..............................................................................................51
10.1.7.
Safety Analysis.......................................................................................................52
10.1.7.1.
Adverse Events.......................................................................................................52
10.1.7.2.
Laboratory Assessments .........................................................................................52
10.1.8.
Study Treatment Termination .................................................................................52
10.1.9.
Deaths ....................................................................................................................53
10.1.10.
Interim Analysis (Quality of Life Questionnaire and Biomarker Data)....................53
10.2.
Maintenance Part....................................................................................................53
10.2.1.
Overview................................................................................................................53
10.2.2.
Study Population Definitions ..................................................................................54
10.2.2.1.
Intent-to-Treat Population.......................................................................................54
10.2.2.2.
Response Evaluable Population ..............................................................................54
10.2.2.3.
Per-protocol (PP) Population ..................................................................................54
10.2.2.4.
Safety Population....................................................................................................54
10.2.3.
Sample Size and Power Considerations...................................................................54
10.2.4.
Background and Demographic Characteristics........................................................55
10.2.5.
Subject Disposition.................................................................................................55
10.2.6.
Efficacy Analysis....................................................................................................55
10.2.6.1.
Primary Endpoint....................................................................................................56
&(/*(1(35235,(7$5<,1)250$7,21
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10.2.4.
0.2.4.


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
10.2.6.2.
Secondary Endpoints ..............................................................................................57
10.2.6.3.
Exploratory Endpoints............................................................................................59
10.2.7.
Safety Analysis.......................................................................................................59
10.2.7.1.
Adverse Events.......................................................................................................59
10.2.7.2.
Laboratory Assessments .........................................................................................59
10.2.8.
Study Therapy Termination ....................................................................................60
10.2.9.
Deaths ....................................................................................................................60
10.2.10.
Interim Analysis .....................................................................................................60
10.3.
Data Monitoring Committee ...................................................................................61
10.4.
Scientific Steering Committee ................................................................................61
11.
ADVERSE EVENTS..............................................................................................62
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................62
11.2.
Evaluation of Adverse Events.................................................................................62
11.2.1.
Seriousness.............................................................................................................63
11.2.2.
Severity / Intensity..................................................................................................64
11.2.3.
Causality ................................................................................................................64
11.2.4.
Duration .................................................................................................................65
11.2.5.
Action Taken..........................................................................................................65
11.2.6.
Outcome.................................................................................................................65
11.3.
Abnormal Laboratory Values..................................................................................65
11.4.
Pregnancy...............................................................................................................65
11.4.1.
Females of Childbearing Potential ..........................................................................66
11.4.2.
Male Subjects.........................................................................................................66
11.5.
Reporting of Serious Adverse Events......................................................................66
11.5.1.
Safety Queries ........................................................................................................67
11.6.
Expedited Reporting of Adverse Events..................................................................67
12.
DISCONTINUATIONS .........................................................................................68
12.1.
Study Treatment Discontinuation............................................................................68
12.2.
Study Discontinuation ............................................................................................68
12.3.
Subject Replacement ..............................................................................................69
13.
EMERGENCY PROCEDURES.............................................................................70
13.1.
Emergency Contact.................................................................................................70
14.
REGULATORY CONSIDERATIONS...................................................................71
&(/*(1(35235,(7$5<,1)250$7,21
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2.2.
12.3.
2.3.


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
14.1.
Good Clinical Practice............................................................................................71
14.2.
Investigator Responsibilities ...................................................................................71
14.3.
Subject Information and Informed Consent.............................................................71
14.4.
Confidentiality........................................................................................................72
14.5.
Protocol Amendments.............................................................................................72
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................72
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................73
14.8.
Closure of the Study ...............................................................................................73
15.
DATA HANDLING AND RECORDKEEPING.....................................................74
15.1.
Data/Documents.....................................................................................................74
15.2.
Data Management...................................................................................................74
15.3.
Record Retention....................................................................................................74
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................76
16.1.
Study Monitoring and Source Data Verification......................................................76
16.2.
Audits and Inspections............................................................................................76
17.
PUBLICATIONS ...................................................................................................77
18.
REFERENCES.......................................................................................................78
19.
APPENDICES........................................................................................................80
Appendix A:
ECOG Performance Status Score.......................................................................80
&(/*(1(35235,(7$5<,1)250$7,21
..72
72
........
.......73
73
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..............
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.............
.............
tus Score
us Score


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
LIST OF TABLES
Table 1:
Blinded Radiology Assessment of Overall Response Rate (ITT Population) ...........22
Table 2:
Blinded Radiology Assessment of Response Rate for Patients with 
Squamous or Non-squamous Histologies (ITT Subgroups).....................................22
Table 3:
Table of Events – Induction....................................................................................30
Table 4:
Table of Events – Maintenance...............................................................................33
Table 5:
Permanent Dose Reductions for Hematologic and Non-Hematologic 
Toxicities on the Study ...........................................................................................46
&(/*(1(35235,(7$5<,1)250$7,21
3
........
.......46
46


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
19
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................28
&(/*(1(35235,(7$5<,1)250$7,21


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
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20
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer-related deaths (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 recent advances in identifying optimal chemotherapy regimens, patients with 
advanced NSCLC continue to have a poor prognosis (especially those without identifiable 
biomarkers), with only 10% to 15% of those treated still alive after 2 years of diagnosis.
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 vs 
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). 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).
1.2.
nab-Paclitaxel
nab-Paclitaxel has been developed to reduce the toxicities associated with Taxol and the 
Cremophor EL/ethanol vehicle while maintaining or improving the chemotherapeutic effect of 
the drug. 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 IV bags may be used for the IV administration of nab-paclitaxel.
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EDMS Doc. Number: 
nab-paclitaxel
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
nab-Paclitaxel for Injectable Suspension is approved under the trade name of ABRAXANE in 
the first-line setting in combination with carboplatin for patients with non-small cell lung cancer 
who are not candidates for curative surgery or radiation therapy in several countries (eg, US, 
Japan, Argentina, Australia, New Zealand, Ecuador, Chile and Guatemala). 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. nab-Paclitaxel is also 
approved for the treatment of patients with metastatic breast cancer and for the first-line 
treatment of metastatic adenocarcinoma of the pancreas.
The approval of nab-paclitaxel was based on the evaluation of Phase I and II data (Rizvi, 2008;
Socinski, 2010; Belani, 2008), as well as the pivotal Phase III study: A multicenter, randomized, 
open-label study was conducted in 1052 chemonaive patients 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 or development of an unacceptable toxicity. The primary 
efficacy outcome measure was overall response rate 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 
adenocarcinoma, 43% had squamous cell lung cancer, 76% were ECOG PS 1, and 73% were 
current or former smokers. Patients received a median of 6 cycles of treatment in both study 
arms. Patients in 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]. There was no statistically significant difference in the secondary endpoint
OS between the two study arms.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
Table 1:
Blinded Radiology Assessment of Overall Response Rate
(ITT Population)
Variable
Category/Statistic
ABI-007/
carboplatin
(N=521)
Taxol/
carboplatin
(N=531)
Response Rate 
Ratio
(pA/pT)
P-value
Patients with Confirmed Complete or Partial Overall Response
n (%)
170 (33%)
132 (25%)
1.313
0.005*
Confidence Interval (CI) a
28.6, 36.7
21.2, 28.5
1.082, 1.593
Complete Response
0
1 (< 1%)
Partial Response
170 (33%)
131 (25%)
Source Data on File.
a 95% CI of response rate and 95.1% CI of response rate ratio.
Note: P-value is based on a chi-square test.
* Indicates p-value < 0.049.
Per protocol, patients were stratified by NSCLC histology (squamous cell carcinoma vs
adenocarcinoma vs other histology). Subgroup analyses were performed to assess the influence 
of squamous vs non-squamous histology on the primary efficacy endpoint of overall response 
rate (the percentage of patients who achieved an objective confirmed CR or PR based on the 
blinded radiological review using RECIST response guidelines, Version 1.0). The proportion of 
patients with squamous cell carcinoma who responded was significantly higher for the 
ABI-007/carboplatin regimen relative to the Taxol/carboplatin regimen (41% vs 24%: pA/pT: 
1.680; p < 0.001). The proportion of patients with non-squamous cell carcinoma with a 
confirmed complete or partial overall response was comparable between the ABI-007 and 
Taxol/carboplatin arms (26% vs 25%: pA/pT: 1.034; p = 0.808).
Table 2:
Blinded Radiology Assessment of Response Rate for Patients with Squamous 
or Non-squamous Histologies (ITT Subgroups)
Prognostic Factor
Category/Statistic/N
ABI-007/
carboplatin
Taxol/
carboplatin
Response Rate 
Ratio (pA/pT)
P-value
Patients with Confirmed 
Complete or Partial Overall 
Response
Squamous cell carcinoma
94/229 (41%)
54/221 (24%)
1.680
< 0.001*
95% Confidence Interval
1.271, 2.221
Non-squamous cell carcinoma
76/292 (26%)
78/310 (25%)
1.034
0.808
95% Confidence Interval
0.788, 1.358
Abbreviations: ITT = intent-to-treat.
Note: P value is based on a chi-square test.
* Indicates p-value < 0.05.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
Adverse reactions were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. Patients in both treatment arms received a 
median of 6 cycles of treatment. The following common (≥ 10% incidence) adverse reactions 
were observed at a similar incidence in nab-paclitaxel plus carboplatin-treated and paclitaxel 
injection plus carboplatin-treated patients: 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).
Laboratory-detected abnormalities which occurred with a difference ≥5% for nab-paclitaxel plus 
carboplatin vs paclitaxel injection plus carboplatin (Grades 1-4 [and G3-4]) are: anemia (98% vs 
91% [28% vs 7%]), neutropenia (85% vs 83% [47% vs 58%]) and thrombocytopenia (68% vs 
55% [18% vs 9%]).  
1.3.
Rationale for Development of nab-Paclitaxel as Maintenance 
Treatment in Squamous Cell NSCLC
Although significant advances have been made in the treatment options and outcomes of patients 
with non-squamous NSCLC, progress for patients with squamous cell NSCLC has been 
disappointing. Furthermore, the data of maintenance therapy that resulted in the FDA approval of 
pemetrexed (Alimta) and erlotinib (Tarceva), seems to confer benefit (and choice) primarily for 
non-squamous NSCLC patients.
Both Alimta studies as well as the Tarceva study demonstrated an overall survival benefit with 
maintenance vs. placebo (Paz-Arez, 2012; Tarceva package insert). However, both of the Alimta 
maintenance studies showed benefit in non-squamous patients only. Whereas Tarceva showed
significant benefit in the non-squamous cell NSCLC patients, only modest improvement was 
observed in squamous cell NSCLC patients (Neal, 2010).
To date there have been no randomized studies showing benefit of maintenance therapy in 
squamous NSCLC patients. Therefore, there is still an unmet medical need for maintenance 
treatment in squamous cell NSCLC. 
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here is stil


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
2.
STUDY OBJECTIVES
2.1.
Primary Objective
The primary objective of the study is to evaluate PFS with nab-paclitaxel as maintenance 
treatment after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous 
cell NSCLC.
2.2.
Secondary Objectives 
The secondary objectives of the study are:
!
To evaluate the safety and tolerability of nab-paclitaxel as maintenance treatment 
after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous 
cell NSCLC.
!
To further assess the efficacy with nab-paclitaxel as maintenance treatment after 
response or SD with nab-paclitaxel plus carboplatin in subjects with squamous cell 
NSCLC, as measured by secondary efficacy endpoints.
2.3.
Exploratory Objectives
The exploratory objectives of the study are:
!
To determine baseline tumor characteristics which predict response and resistance to 
nab-paclitaxel/carboplatin during the Induction part of the study. 
!
To determine what changes in peripheral tumor characteristics during treatment are 
associated with acquisition of resistance in the subjects who had initial clinical 
benefit.
!
To assess healthcare resource utilization during the Maintenance part of the study.
!
To assess the LCSS and EQ5D.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
3.
STUDY ENDPOINTS
3.1.
Primary Endpoint
Progression free survival from randomization into the Maintenance part of the study.
3.2.
Secondary Endpoints
3.2.1.
Safety
Safety parameters including AEs and SAEs.
3.2.2.
Efficacy
!
Overall survival from randomization into the Maintenance part of the study.
!
Overall response rate during the Induction and Maintenance parts of the study.
!
PFS from Day 1 Cycle 1.
!
OS from Day 1 Cycle 1.
!
ORR in Maintenance Part beyond response in Induction Part.
!
Disease control rate during the Induction Part and over the entire study.
!
Time to response during the Induction Part and over the entire study, with and 
without the requirement of confirmation of response.
!
Duration of response over the entire study, with and without the requirement of 
confirmation of response.
3.3.
Exploratory Endpoints
!
The correlation between pretreatment tumor characteristics and response and 
resistance to the study treatment determined using next-generation sequencing 
methods, immunohistochemistry, or other analysis methods.
!
The association between the changes in tumor characteristics and the acquisition of 
resistance to therapy from plasma samples taken at treatment failure during 
Maintenance.
!
The association between DNA nucleotide polymorphisms in subject’s germ line DNA 
and association with treatment efficacy and or toxicity.
!
Healthcare resource utilization during the Maintenance part of the study using a 
questionnaire including hospitalizations, emergency room visits, doctor or nurse 
visits, procedures, and/or additional medication.
!
Change in the LCSS and EQ5D.
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que
v


EDMS Doc. Number: 
nab-paclitaxel
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is a Phase III, randomized, open-label, multi-center study of nab-paclitaxel plus BSC or 
BSC alone as maintenance treatment after response or SD with nab-paclitaxel plus carboplatin as 
induction in subjects with squamous cell NSCLC. Approximately 450 subjects with Stage 
IIIB/IV squamous cell NSCLC eligible to receive standard treatment of nab-paclitaxel plus 
carboplatin for 4 cycles will be enrolled in the Induction part of the study. If after the 4 cycles, 
the subject has a radiologically assessed CR, PR, or SD without clinical progression, they will be 
randomized (2:1) in the Maintenance part of the study to receive nab-paclitaxel plus BSC or 
BSC alone. BSC is defined as the best palliative care per investigator (including but not limited 
to: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional 
support, and/or focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis)
excluding antineoplastic agents. Approximately 216 subjects will be evaluable for the primary 
endpoint of PFS in maintenance.
4.1.1.
Induction Part
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Approximately 450 subjects eligible for 
standard treatment with nab-paclitaxel plus carboplatin for 4 cycles will be enrolled, provided if 
all inclusion/exclusion criteria are met within a 28-day screening period prior to Cycle 1 Day 1.
Induction treatment will commence on Cycle 1 Day 1: 
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD, and has met all eligibility criteria, they will continue on to the Maintenance part 
of the study. If the subject has radiological or clinical PD, they will be discontinued from the 
study and will not be followed.
4.1.2.
Maintenance Part
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD without clinical progression, they will be screened for eligibility over a 7-day 
period. Subjects (approximately 216) who satisfy all inclusion/exclusion criteria, will be 
randomized 2:1 to receive either:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day cycle plus BSC until disease progression (see Section 8.3 for guidelines on 
starting dose for the Maintenance part of the study if the subject had dose reduced 
during the Induction part of the study)
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EDMS Doc. Number: 
nab-paclitaxel
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
!
BSC until disease progression
Maintenance therapy should start at the time of randomization. If this is not possible, a maximum 
of 7 days will be allowed from the date of randomization to the start date of Maintenance 
therapy. Subjects must start Maintenance therapy no earlier than 21 days and no later than 35
days from Day 1 of the fourth cycle of Induction therapy. 
Randomization will be stratified by disease stage (IIIB vs IV), response in induction (CR/PR vs 
SD), and performance status (0 vs 1).
4.1.3.
Follow-up Period 
All subjects who discontinue from the Maintenance part of the study for any reason other than 
withdrawal of consent, lost to follow-up, or death, will enter the Follow-up period that will have 
a visit 28 days after progression or discontinuation. Those subjects entering the follow up period 
without documented progression will continue to have CT scans in accordance with standard of 
care until documented progression of disease. Additionally, subjects will be followed for OS by 
phone approximately every 90 days for up to approximately 1.5 years after final analysis of 
approximately 136 PFS events in which a total of 147 deaths are expected to be observed for the 
final OS analysis.
4.2.
Study Design Rationale
The results of promising activity with nab-paclitaxel in NSCLC, especially in squamous cell 
NSCLC, underscore the hypothesis for this Phase III study as a superiority trial to compare nab-
paclitaxel/BSC vs BSC as maintenance therapy in subjects with squamous cell NSCLC
(randomizing subjects with CR/PR/SD after Induction treatment with nab-paclitaxel/
carboplatin). The nab-paclitaxel regimen used for Induction will be in accordance with the FDA 
approved label, 100 mg/m2 administered once per week on Days 1, 8 and 15 of each 21-day
cycle with no break combined with carboplatin AUC = 6 mg*min/mL administered on Day 1 
every 21 days. Four cycles of doublet-chemotherapy is chosen as the cut-off, based on observed 
risk:benefit results that additional cycles of doublet chemotherapy did not confer significant 
advantages (Socinski, 2002); furthermore, 4 cycles of doublet-chemotherapy represents general 
trends of practice (Stinchcombe, 2009).
The nab-paclitaxel regimen used for Maintenance will be 100 mg/m2 administered on Days 1 
and 8 of each 21-day cycle until progression (the actual starting dose may be adjusted as 
specified in Section 8.3). The nab-paclitaxel dosing regimen was reduced to Days 1 and 8 of 
each 21-day cycle in the Maintenance part of the study to decrease potential toxicity and possibly 
optimize tolerability of treatment and drug exposure in subjects. Sufficient subjects will be
enrolled to provide adequate power to compare PFS. The safety and tolerability of nab-paclitaxel
will be assessed.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
Figure 1:
Overall Study Design
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EDMS Doc. Number: 
nab-paclitaxel
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
4.3.
Study Duration
The Induction part of the study will last approximately 36 months to randomize sufficient 
subjects for the Maintenance part of the study. The total length of this Phase III study with 
Induction, Maintenance, and Follow-up is estimated to last approximately 5 years.
4.4.
End of Trial
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
study, or the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol and/or the 
Statistical Analysis Plan (SAP), whichever is the later date.
&(/*(1(35235,(7$5<,1)250$7,21
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
5.
TABLE OF EVENTS
Table 3:
Table of Events – Induction
CYCLE 1 and 3 (21-day)
CYCLE 2 and 4 (21-day)
Assessment
Screening/
Baseline
(up to 28 
days)
Day 1
(C3: ±2 
days)
Day 8
(±2 days)
Day 15
(±2 days)
Day 1
(±2 days)
Day 8
(±2 days)
Day 15
(±2 days)
At the end 
of Cycles 2 
and 4 
(-3/+7 days)
Early
Treat-
ment 
Discon-
tinuation /
End of 4 
Cycles
Unsched-
uled
Informed Consent
X
-
-
-
-
-
-
-
-
-
Medical History
X
-
-
-
-
-
-
-
-
-
Prior Medication and Procedures
X
-
-
-
-
-
-
-
-
-
Serum β-hCGa
X
X
-
-
X
-
-
-
X
-
Complete Chest CT Scan (including 
adrenal gland) and any other studies 
required for tumor imagingb
X
-
-
-
-
-
X
X
Xc
Weight
X
X
X
X
X
X
X
-
X
Xc
Archived Tumor Tissue Sample for 
Biomarker (biopsy, surgical specimen, 
or other diagnostic tumor sample)
-
X (C1D1 
only)
-
-
-
-
-
-
-
-
Plasma for Biomarker Analyses 
-
X (C1D1 
only)
-
-
-
-
-
-
X
-
Blood for Pharmacogenomic Analyses
-
X (C1D1 
only)
-
-
-
-
-
-
-
-
Body Surface Area (BSA) Calculation 
and Heightd
X
-
-
-
-
-
-
-
-
Xc
ECOG status
X
X
-
-
X
-
-
-
X
Xc
Concomitant Medication/Procedures
X
X
X
X
X
X
X
-
X
Xc
Peripheral Neuropathy Assessmente
X
X
X
X
X
X
X
-
X
Xc
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
31
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
Table 3:
Table of Events – Induction (Continued)
CYCLE 1 and 3 (21-day)
CYCLE 2 and 4 (21-day)
Assessment
Screening/
Baseline 
(up to 28 
days)
Day 1
(C3: ±2 
days)
Day 8
(±2 days)
Day 15
(±2 days)
Day 1
(±2 days)
Day 8
(±2 days)
Day 15
(±2 days)
At the end 
of Cycle 2 
and 4 (-3/+7 
days)
Early 
Treat-
ment 
Discon-
tinuation / 
End of 4 
Cycles
Unsched-
uled
Hematology and Serum Chemistry f
X
X
X
X
X
X
X
-
Xc
X
Adverse Event Evaluation
X
X
X
X
X
X
X
-
X
Xc
nab-paclitaxel Administration
-
X
X
X
X
X
X
-
-
-
Carboplatin Administration
-
X
-
-
X
-
-
-
-
-
LCSS and EQ5D
-
X
-
-
X
-
-
-
X
-
Electrocardiogram (ECG)
X
-
-
-
-
-
-
-
-
Xc
CT Scan of Head or Brain 
Magnetic Resonance 
Imaging (MRI) g
X
-
-
-
-
-
-
-
-
Xc
Bone Scan (X-rays if 
needed)g
X
Xc
Physical Examination
X
-
-
-
-
-
-
-
X
Xc
Vital Signs
X
-
-
-
-
-
-
-
X
Xc
C3: Cycle 3, eCRF: electronic Case Report Form, C1D1: Cycle 1 Day 1, AE: Adverse Event, SAE: Serious Adverse Event, ECOG: Eastern Cooperative Oncology Group, CT: Computed Tomography, 
b-HCG: beta human chorionic gonadotropin, RECIST: Response Evaluation Criteria in Solid Tumors, LCSS: Lung Cancer Symptom Scale, EQ5D: EuroQol 5D.
a A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a Serum β-hCG pregnancy test must be performed to assess
eligibility at Screening/Baseline and within 72 hours of the first administration of study drug before beginning each new cycle. Note: the screening serum pregnancy test can be 
used as the test prior to Day 1 study therapy if it is performed within the 72-hour timeframe.
b All subjects must have a radiographically documented measurable tumor(s) by RECIST v1.1 criteria. Complete chest CT scan (including adrenal gland) is performed at
Screening, at the end of Cycles 2 and 4 during Induction part, early termination, and if clinically indicated while on-treatment. The methods of assessment chosen at baseline to 
follow tumors are to remain consistent throughout study duration. A CT scan with (if not contraindicated) and without contrast is preferred throughout the study. A CT scan with 
contrast only could be performed if not contraindicated per local site standard of practice, if the presence of liver metastasis can be assessed accurately. Scans will be archived as 
per institution standards.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
32
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
c If clinically indicated.
d BSA calculated at baseline and recalculated if body weight changes by more than 10% since baseline or since the previous visit when BSA was recalculated.
e The occurrence of peripheral neuropathy should be reported by the investigator as an AE or SAE.
f Laboratory assessments will be done prior to each treatment by local laboratories and as clinically indicated. The results from laboratory assessments will be captured as per 
Section 6.18.
g At Screening, if lesions are suspected.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
33
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
Table 4:
Table of Events – Maintenance
EVERY CYCLE
(21-day)
Assessment
Screening/ 
Baseline
(up to 14
days)
Day 1
(±2 days, 
except 1st
cycle)
Day 8a
(±2 days)
Every 42 
days
(-3/+7 days)
Early 
Treatment 
Discon-
tinuation /
Disease
Progression
28-day 
Follow-up 
visit
Survival 
(every 90 
days) up 
to as 
specified 
in Section 
6.20
Unsched-
uled
Serum β-hCG b
X
X
-
-
X
-
-
-
Complete Chest CT Scan (including adrenal 
gland) and any other studies required for 
tumor imaging c
Xd
-
-
X
X
-
-
Xe
Weight
X
X
X
-
X
X
-
Xe
Plasma for Biomarker Analyses
-
-
-
X
-
-
-
Body Surface Area (BSA) Calculation and 
Heightf
X
-
-
-
-
-
-
Xe
ECOG status
Xg
X
-
-
X
-
-
Xe
Concomitant Medication/Procedures
X
X
X
X
X
X
X
Xe
Peripheral Neuropathy Assessment h
X
X
X
-
X
X
-
Xe
Hematology and Serum Chemistry i
X
X
X
-
X
X
-
Xe
Adverse Event Evaluation
X
X
X
X
X
X
-
Xe
nab-paclitaxel Administration
-
X
X
-
-
-
-
Survival phone call 
-
-
-
-
-
-
X
-
Healthcare Resource Utilization 
Questionnaire
-
X
-
-
X
-
-
-
LCSS and EQ5D
-
X
-
-
X
-
-
-
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
34
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
Table 4:
Table of Events – Maintenance (Continued)
EVERY CYCLE
(21-day)
Assessment
Screening/ 
Baseline
(up to 14
days)
Day 1
(±2 days, 
except 1st
cycle)
Day 8
(±2 days)
Every 42 
days
(-3/+7 days)
Early 
Treatment 
Discon-
tinuation / 
Disease 
Progression
28-day 
Follow-up 
visit
Survival 
(every 90 
days) up 
to as 
specified 
in Section 
6.20
Unsched-
uled
Electrocardiogram (ECG)
Will be done as per standard of care during the study and as clinically indicated, however, results will not 
be routinely collected in the eCRFs. However, if abnormal and clinically significant results, will be collected as AE or SAE and if 
scans show documented progression of disease will be collected on eCRF.
CT Scan of Head or Brain Magnetic 
Resonance Imaging (MRI)
Bone Scan (X-rays if needed)
Physical Examination
Vital Signs
C1: Cycle 1, eCRF: electronic Case Report Form, AE: Adverse Event, SAE: Serious Adverse Event, ECOG: Eastern Cooperative Oncology Group, CT: Computed Tomography, b-HCG: beta human 
chorionic gonadotropin, LCSS: Lung Cancer Symptom Scale, EQ5D: EuroQol 5D.
a Adherence to Day 1 and 8 visits during Maintenance part is preferred and strongly encouraged. Per local standard of care assessment of Day 8 visit may be done over the phone 
for subjects randomized to BSC arm if there are no safety concerns.
b A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a Serum β-hCG pregnancy test must be performed to assess subject
eligibility at Screening/Baseline and within 72 hours of the first administration of study drug before beginning each new cycle. Note; the screening serum pregnancy test can be 
used as the test prior to Day 1 study therapy if it is performed within the 72-hour timeframe.
c Complete chest CT scan (including adrenal gland) is performed at baseline, every 42 days (-3/+7 days) while on-treatment (schedule based on calendar, not start of cycle), early 
termination, 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 until documented progression 
of disease. A CT scan with (if not contraindicated) and without contrast is preferred throughout the study. A CT scan with contrast only could be performed if not contraindicated 
per local site standard of practice if the presence of liver metastasis can be assessed accurately. Scans will be archived as per institution standards.
d Induction End of Cycle 4 information may serve as baseline for Maintenance.
e If clinically indicated.
f BSA calculated at baseline and recalculated if body weight changes by more than 10% since baseline or since the previous visit when BSA was recalculated.
g The ECOG performance status must be 0 or 1 for subjects to start maintenance treatment.
h The occurrence of peripheral neuropathy should be reported by the investigator as an AE or SAE.
i Laboratory assessments will be done prior to each nab-paclitaxel treatment by local laboratories as per standard of care during the study and as clinically indicated. The results 
from laboratory assessments will be captured as per Section 6.18.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
35
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
6.
PROCEDURES
Subjects will be provided with a written informed consent form (ICF), given the opportunity to 
ask any questions concerning the study, and will sign an ICF prior to participating in any study 
procedures. After giving written informed consent, subjects will undergo a screening period to be 
assessed for eligibility. All subjects who sign an ICF must be screened into the Interactive Voice 
Response System (IVRS) immediately upon signature on the document. Subjects who do not 
meet the inclusion/exclusion criteria will be considered screening failures and will not be eligible 
for the study. Subjects that have satisfied all eligibility criteria after the screening period will be 
eligible to be enrolled. Subjects who screen fail may re-screen up to 3 times and an ICF will need 
to be signed at each re-screen, 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).
A CT scan with (if not contraindicated) and without the contrast is preferred throughout the 
study.
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 (in this instance if only the CT scan with contrast 
is available, a CT scan without the contrast should be performed).
6.1.
Medical History
A complete medical history including, but not limited to, evaluation for past (up to 5 years) or 
present cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine, 
lymphatic, hematological, immunologic, dermatological, psychiatric, genitourinary, obstetrical, 
surgical history, smoking history, or any other diseases or disorders will be performed at 
Screening.
6.2.
Prior Medications/Procedures
All prior medications/procedures within 28 days of time of signature on the ICF should be 
recorded. All NSCLC-related prior medications/procedures should be recorded regardless of 
time.
6.3.
Pregnancy Testing
Serum pregnancy test with sensitivity of at least 25 mIU/mL is to be obtained in females of 
childbearing potential (FCBP) at Screening for Induction and Maintenance. A serum pregnancy 
test must be done within 72 hours prior to Cycle 1 Day 1 of starting study therapy, repeated 
before beginning each new cycle, and at discontinuation or end of treatment. The subject may 
not receive treatment until the investigator has verified that the result of the pregnancy test is 
negative. See inclusion criteria for pregnancy testing requirements. Any pregnancies that occur 
in women who have received study drug must be immediately reported to Celgene Drug Safety 
(See Section 11.4).
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
36
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
6.4.
Complete Chest Computed Tomography (CT) Scan (including 
adrenal gland) With and Without Contrast
Complete Chest CT Scan (including adrenal gland) and any other studies required for tumor 
imaging will be done at Screening, at the end of Cycles 2 and 4, and at Early Treatment 
Discontinuation during the Induction part of the study. During the Maintenance part of the study,
scans will be done every 42 days (-3/+7 days) (schedule for scans will be based on calendar, not 
start of cycle) and at Early Treatment Discontinuation/Disease Progression. Additional CTs may 
be done at any time during the study if clinically indicated. CT scans are preferred; however,
MRI would be acceptable. The same scanning modality for lesion assessment should be used 
throughout the study. A CT scan with (if not contraindicated) and without contrast is preferred
throughout the study. A CT scan with contrast only could be performed if not contraindicated per 
local site standard of practice, if the presence of liver metastasis can be assessed accurately. All 
scans and reports will be archived as per institution standards.
6.5.
Weight
Weight will be collected at every visit during the Induction and Maintenance parts of the study. 
Additional weights may be collected at any time during the study as needed.
6.6.
Body Surface Area (BSA) Calculation and Height
BSA and height will be collected and calculated at Screening during Induction and Maintenance 
parts of the study. BSA may be recalculated if body weight changes by more than 10% since 
baseline or since the previous visit when BSA was recalculated.
6.7.
ECOG Performance Score
ECOG performance score will be collected at Screening, Day 1 of every cycle and at Early 
Treatment Discontinuation/End of Cycle 4 during the Induction part of the study. During the 
Maintenance part of the study, ECOG performance score will be collected at Screening, Day 1 of 
every cycle, and at Early Treatment Discontinuation/Disease Progression. Additional ECOG may 
be collected at any time during the study as needed.
6.8.
Concomitant Medications/Procedures
All subjects will have concomitant medications and procedures recorded from the time of 
signature on the ICF until progression during the Induction part of the study or the 28-day 
follow-up visit during the Maintenance part of the study. Only NSCLC associated concomitant 
medications/procedures will be recorded, including BSC. During survival follow-up, anti-cancer 
treatment information will be collected, if available.
6.9.
Peripheral Neuropathy Assessment
Peripheral neuropathy assessment will be done from the time of signature on the ICF until 
progression during the Induction part of the study or the 28-day follow-up visit during the 
Maintenance part of the study. Additional peripheral neuropathy assessments may be done at any 
time during the study as needed.
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gr


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
37
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
6.10.
Adverse Event Reporting
All subjects will have AEs 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. 
6.11.
Lung Cancer Symptom Scale Questionnaire and EQ5D
The Lung Cancer Symptom Scale (LCSS) and (EQ-5D) questionnaires will be used to measure 
quality of life (QoL) for subjects in the trial. The LCSS is a 9 question analysis the subject
completes using a visual analogue scale (VAS) to denote intensity of a symptom. The EQ-5D 
comprises 5 questions on mobility, self-care, usual activities, pain/discomfort, anxiety/depression 
and a VAS for overall QoL. These questionnaires will be completed at Day 1 of every cycle, and 
at Early Treatment Discontinuation/End of Cycle 4 during the Induction part of the study, during 
the Maintenance part of the study, at Day 1 of every cycle, and at progression of disease. The 
quality of life data generated from these questionnaires will be analyzed per the description in 
the SAP.
6.12.
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 cycle, and at progression of disease during the Maintenance part of 
the study.
6.13.
Electrocardiogram 
An Electrocardiogram (ECG) will be performed at screening and as clinically indicated;
however, normal and non-clinically significant results will not be collected in the eCRFs. If 
results are abnormal and clinically significant at Screening, they will be recorded as medical 
history. If results are abnormal and clinically significant after Screening, they will be recorded as 
AE or SAE).
6.14.
CT Scan of Head or Brain Magnetic Resonance Imaging (MRI)
CT scan of head or brain MRI will be performed at screening if lesions are suspected and as 
clinically indicated during the study; however, results will not be collected in the eCRFs. If scans 
show progression of disease, this information will be collected on the eCRF.
6.15.
Bone Scans and X-rays
Bone scans and x-rays will be performed at screening if lesions are suspected and as clinically 
indicated during the study; however, results will not be collected in the eCRFs. If scans show 
progression of disease, this information will be collected on the eCRF.
6.16.
Physical Examinations
Physical examinations will be performed at screening and treatment discontinuation and any 
other time as clinically indicated/per the institutional practice. However, results will not be 
routinely collected on the eCRFs.  If the findings are abnormal and clinically significant at 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
38
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
screening, they will be recorded as medical history, and if findings are abnormal and clinically 
significant after screening, they will be recorded as an AE or SAE.
6.17.
Vital Signs
Vital signs will be measured at screening, treatment discontinuation, and any other time as 
clinically indicated / standard of care for the institution. However, results will not be routinely 
collected on the eCRFs.  If the findings are abnormal and clinically significant at screening, they 
will be recorded as medical history, and if findings are abnormal and clinically significant after 
screening, they will be recorded as an AE or SAE.
6.18.
Laboratory Assessments
Laboratory assessments will be done prior to each nab-paclitaxel treatments by local laboratories 
as per standard of care during the study and as clinically indicated, however, results will not be 
collected in the eCRFs unless they are determined to be clinically significant laboratory 
abnormalities. 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. Abnormal and 
clinically significant laboratory assessments at Screening will be recorded as medical history, 
and after Screening, as AE or SAE (clinically significant laboratory abnormalities at Screening 
may result in a subject being ineligible for the study and should not be captured as an AE). If a 
clinically significant laboratory abnormality is captured as medical history, AE, or SAE, the 
specific laboratory parameter(s) should be recorded on the laboratory assessments CRF. Any 
abnormal values that persist should be followed at the discretion of the Investigator. The 
Investigator should file all copies of the reports, including faxes with the subject’s medical chart.
6.19.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) 
If archival tumor biopsy blocks or (preferably) surgical specimens from subjects with prior 
resections are available, 10 or more slides of at least 4 um thickness will be collected at Cycle 1 
Day 1 of Induction. Additionally, a core of an area representing viable tumor epithelium will be 
collected from the block. If the amount of tumor tissue available is not sufficient, fewer slides 
may be collected. 
If a fine needle aspirate (FNA) specimen is available, slides of at least 4 um thickness will be 
collected with the goal of obtaining at least 100,000 cells (preferably more) of material. If 
sufficient material cannot be collected, fewer slides/cells may be collected.
If only other types of diagnostic samples such as endoscopies, lavage, or sputum are available, 
this material should be optionally collected when possible, and collection is strongly encouraged 
when tissue such as endoscopy samples with multiple needle passes exists in quantities 
comparable to a core biopsy. In this instance, 10 slides and a core sample of tumor tissue should 
be collected as per biopsy and surgical samples above. 
Plasma for biomarker analyses will be collected on Day 1 of Cycle 1 during Induction and at 
progression during the Maintenance part of the study. When progression occurs during Induction 
and before Cycle 4, a plasma sample will be collected at the time of study withdrawal.
Peripheral blood will be collected for pharmacogenomic analyses on Cycle 1 Day 1 of Induction.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
Types of techniques planned to be used for tumor and blood analyses include:
!
Gene expression by RNA sequencing
!
Immunohistochemistry 
!
DNA sequencing
Details regarding the collection, storage, and shipment of the samples are given in the Laboratory 
Manual.
6.20.
Survival
After discontinuation from the Maintenance part of the study, the subjects will be followed for 
survival by phone approximately every 90 days for up to 1.5 years after final analysis of 
approximately 136 PFS events in which a total of 147 deaths are expected to be observed for the 
final OS analysis. The subjects will also be asked questions of other medications they may be 
taking for their NSCLC. 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
40
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Subjects with squamous cell NSCLC stage IIIB or IV with no prior chemotherapy for metastatic 
disease who are ≥ 18 years old will be eligible for this study. The Induction part of the study will 
enroll approximately 450 subjects. Based on results from the nab-Paclitaxel Phase 3 NSCLC 
development study (Protocol CA031) it is estimated that approximately 216 subjects with CR, 
PR, or SD from the Induction part of the study will be randomized to the Maintenance part of the 
study. Enrollment into the Induction part of the study will be monitored and adjusted to ensure 
that approximately 216 subjects are randomized into the Maintenance part of the study. The 
study will be conducted at approximately 120 sites in the United States and European Union 
(EU).
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the Induction and Maintenance parts 
of the study (except if specified at study entry only):
General and Demographics
1. Age ≥ 18 years of age at the time of signing the ICF.
2. Understand and voluntarily provide written consent to the ICF prior to conducting any 
study related assessments/procedures. 
3. Able to adhere to the study visit schedule and other protocol requirements
Disease Specific
4. Histologically or cytologically confirmed Stage IIIB or IV squamous cell NSCLC at 
study entry.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease at study entry (as defined by the 
RECIST v1.1 criteria).
7. No prior chemotherapy for the treatment of metastatic NSCLC at study entry. Adjuvant, 
neo-adjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic 
disease is permitted providing it was completed 12 months prior to starting the study 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 × ULN except in cases of Gilbert’s disease and liver metastases. 
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11. A
1. A


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
41
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
13. Creatinine ≤ 1.5 mg/dL.
14. Expected survival of > 12 weeks for the Induction part of the study.
15. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
16. For Maintenance part of the study, subjects must have received at least one dose of nab-
paclitaxel in each of the 4 cycles during Induction 
Pregnancy 
17. Females of childbearing potential [defined as a sexually mature woman who (1) have not 
undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy 
(the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for 
at least 24 consecutive months (ie, has had menses at any time during the preceding 24 
consecutive months)] must:
a.
agree to take a pregnancy test prior to starting study medication and throughout the 
study participation.
b. commit to complete abstinence from heterosexual contact, or agree to use medical 
doctor-approved contraception throughout the study without interruption, and while 
receiving study medication or for a longer period if required by local regulations.
Male subjects must:
c.
agree to complete abstinence from heterosexual contact or use a condom during 
sexual contact with a female of child bearing potential while receiving study 
medication and within 6 months after last dose of study medication, 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 into the Induction
and Maintenance parts of the study (except if specified at study entry only):
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 first dose of study drug).
2. Only evidence of disease is non-measurable at study entry.
3. Preexisting peripheral neuropathy of Grade 2, 3, or 4 (per CTCAE v4.0). For the 
Maintenance part of the study subjects with peripheral neuropathy of Grade 3 and higher 
are excluded.
4. Venous thromboembolism (VTE) within 1 month prior to signing ICF. If the subject has 
a history of VTE earlier 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.
5. Current congestive heart failure (New York Heart Association class II-IV).
6. 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 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
42
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
hypertension, clinically significant cardiac dysrhythmia or clinically significant ECG 
abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder.
7. Treatment with any investigational product within 28 days prior to signing ICF.
8. History of allergy or hypersensitivity to nab-paclitaxel or carboplatin.
9. Currently enrolled in any other clinical protocol or investigational trial that involved 
administration of experimental therapy and/or therapeutic devices.
10. Any other clinically significant medical condition and/or organ dysfunction that will 
interfere with the administration of the therapy according to this protocol.
11. 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 treatments should have been completed 6 
months prior to signing ICF.
12. 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.
13. Any condition, including the presence of laboratory abnormalities, that places the subject 
at unacceptable risk if he/she were to participate in the study.
14. Any condition that confounds the ability to interpret data from the study.
15. Pregnant and nursing females.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
43
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Investigational Product(s)
Induction 
The nab-paclitaxel and carboplatin treatments will not be supplied by Celgene during induction 
in those countries where nab-paclitaxel plus carboplatin is available for the treatment of NSCLC.  
Investigative sites will use standard of care (commercially available) product via prescription in 
these countries.
In those countries where nab-paclitaxel plus carboplatin is not available for the treatment of 
NSCLC, or is available but designated as investigational product (IP) as per local regulations
both agents will be packaged and supplied by Celgene.
Maintenance 
Subjects will be randomized to receive open-label nab-paclitaxel plus BSC or BSC during the 
Maintenance part of the study. The nab-paclitaxel used in the Maintenance part of the study is
designated as IP and will be packaged and supplied by Celgene Corporation. 
The preparation for IV administration procedures for IP should be followed as per Prescribing 
Information.
8.1.1.
nab-Paclitaxel
nab-Paclitaxel will be supplied by the Sponsor, Celgene Corporation, for the Maintenance part in 
all countries and for the Induction part if either not available or designated as IP in a country.
nab-Paclitaxel will be supplied in single-use vials in single count cartons. Each single-use 50 mL 
vial will contain paclitaxel (100 mg) and approximately 900 mg human albumin as a stabilizer.
Please see local prescribing information for Abraxane for detailed instructions on the
reconstitution, storage conditions and IV administration of nab-paclitaxel.
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 must 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 IP 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-cyclobutanedicarboxylato
(2-)0,0’]-,(SP-4-2). Carboplatin is a crystalline powder with the molecular formula of 
C6Hl2N204Pt and a molecular weight of 371.25. It is soluble in water at a rate of approximately 
14 mg/mL, and the pH of a 1% solution is 5 to 7. It is virtually insoluble in ethanol, acetone, and
dimethylacetamide.
For additional information about carboplatin storage, preparation, and administration please refer 
to the package insert. 
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meth


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
44
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
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.
Induction
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Approximately 450 subjects will be treated 
with nab-paclitaxel plus carboplatin for 4 cycles.
Induction treatment will commence on Day 1, in accordance with standard of care of 1st line 
treatment of metastatic NSCLC: 
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion
Maintenance Part
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD without clinical progression, they will be randomized 2:1 (approximately 216
subjects) to receive:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day cycle plus BSC until disease progression (the actual starting dose may be 
adjusted as specified in Section 8.3)
OR
!
BSC until disease progression
Maintenance therapy should start at the time of randomization. If this is not possible, a maximum 
of 7 days will be allowed from the date of randomization to the start date of Maintenance 
therapy. Subjects must start Maintenance therapy no earlier than 21 days and no later than 35
days from Day 1 of the fourth cycle of Induction therapy.
Subjects may receive BSC as needed per Investigator discretion and should be recorded.
All IP will be administered by the clinical site and administration will be documented in the 
study source record.
8.3.
Dose Modifications
Subjects will be evaluated for AEs at each visit with the NCI CTCAE v4.0 used as a guide for 
the grading of severity.  The dose of nab-paclitaxel and carboplatin for each subject will be 
modified following toxicity as described in Table 5.
Subjects who experience any of the adverse drug reactions in Table 5 will be dose reduced as per 
Table 5 during the Induction and Maintenance parts of the study. If a subject is dose reduced in 
the Induction part of the study, please refer to Table 5 for guidelines on dose and schedule for the 
Maintenance part of the study.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
45
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
!
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, on Day 1 of any 
cycle, withhold treatment until the ANC recovers to at least 1500 cells/mm3 and the 
platelet count recovers to at least 100,000 cells/mm3. On Days 8 and 15 the ANC 
should recover to at least 500 cells/mm3 and platelet count of at least 50,000 
cells/mm3. When dosing is resumed, the subject should be dosed at the next lower 
dose level of nab-paclitaxel and carboplatin as outlined in Table 5.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-
paclitaxel and carboplatin at reduced doses (Table 5) when peripheral neuropathy 
improves to Grade 1 or completely resolves.
&(/*(1(35235,(7$5<,1)250$7,21
pathy
pathy


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
46
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
Table 5:
Permanent Dose Reductions for Hematologic and Non-Hematologic Toxicities on the Study
Adverse Drug Reaction
Occurrence
nab-Paclitaxel 
Dose (mg/m2)
Carboplatin Dose 
(mg*min/mL)
Starting Dose Maintenance:
nab-paclitaxel Dose (mg/m2) Days 1 
and 8 of each 21-day Cycle
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
If subject at 100, 75 or 50 at end of 
Induction and ANC > 1500/mm3, will 
start at 100, 100 or 75 respectively 
during Maintenance
Second
50
3.0
Third
Discontinue Treatment*
Platelet count < 50,000/mm3
First
75
4.5
If subject at 100 or 75 at end of
Induction and platelet > 100,000/mm3, 
will start at 100 during Maintenance
Second
Discontinue Treatment*
Peripheral Neuropathy Grade 3 or 4
First
75
4.5
If subject at 100, 75 or 50 at end of
Induction and Grade 1 or no peripheral 
neuropathy, will start at 100, 100 or 75 
respectively during Maintenance
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
If subject at 100, 75 or 50 at end of
Induction and < a Grade 2 or none of 
the noted events, will start at 100, 100
or 75 respectively during Maintenance
Second
50
3.0
Third
Discontinue Treatment*
Grade 4 cutaneous toxicity, diarrhea or mucositis
First
Discontinue Treatment*
ANC: Absolute Neutrophil Count.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
47
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
8.4.
Method of Treatment Assignment
The Induction and Maintenance parts of the study are open-label. In the Maintenance part of the 
study, subjects will be randomized 2:1 to nab-paclitaxel plus BSC or BSC alone. 
Enrollment/randomization will occur via IVRS for all parts of the study. 
8.5.
Packaging and Labeling
The label(s) for IP (nab-paclitaxel) will include Sponsor name, address and telephone number, 
the protocol number, IP name, dosage form and strength (where applicable), amount of IP per 
container, lot number, expiry date (where applicable), medication identification/kit number, 
dosing instructions, storage conditions, and required caution statements and/or regulatory 
statements as applicable. Additional information may be included on the label as applicable per 
local regulations.
8.6.
Investigational Product Accountability and Disposal
Celgene (or designee) will review with the Investigator and relevant site personnel the process 
for IP return, disposal, and/or destruction including responsibilities for the site vs. Celgene (or 
designee).
Celgene will instruct the Investigator on the return, disposal and/or destruction of IP and/or 
medical device materials if applicable. Only completely unused IP vials should be retained by 
the site until a representative from Celgene or other Celgene-designated personnel have 
completed an inventory. Partially used and completely used vials should be destroyed according 
to local guidelines, and disposition should be recorded on the Investigational Drug 
Accountability Record Form.
The investigator, or designee, shall record the dispensing of IP to subjects in an IP accountability 
record. The IP record will be made available to Celgene, or other authorized Celgene-designated 
monitoring personnel for the purpose of accounting for the IP supply. Inspections of the IP 
supply for inventory purposes and assurance of proper storage will be conducted as necessary. 
Any significant discrepancy will be recorded and reported to Celgene or their designee and a 
plan for resolution will be documented.
Investigational product will not be loaned or dispensed by the investigator to another investigator 
or site. Under certain circumstances, and with sponsor permission, cooperative groups may 
manage IP between locations within their network as clinical trial agreement and local guidelines 
permit.
8.7.
Investigational Product Compliance
All IP will be administered only by study site personnel and accurate recording of all IP 
administration will be made in the appropriate section of the subject’s eCRF and source 
documents.
8.8.
Overdose
Overdose, as defined for this protocol, refers to nab-paclitaxel or carboplatin dosing only.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
48
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel or carboplatin to a given subject, regardless of any associated adverse events or 
sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified
rate. 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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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
49
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
All supportive care is permitted. 
9.2.
Prohibited Concomitant Medications and Procedures
Other antineoplastic agents or IP other than what is specified in the protocol is prohibited.
9.3.
Required Concomitant Medications and Procedures
Not applicable.
&(/*(1(35235,(7$5<,1)250$7,21


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
50
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the Induction and 
Maintenance parts of the study are described below by study part. Although some definitions for 
the efficacy and safety endpoints, and the analysis populations are the same for both parts of the 
study, they are repeated in the respective section to ensure that each part is self-contained.
Furthermore, while key analyses for the primary and key secondary endpoints are described in 
this section, additional analyses of these endpoints as well as exploratory endpoints will be 
described in detail in the SAP.
10.1.
Induction Part
10.1.1.
Overview
This is an open-label, single-arm, Induction part of the study. Subjects receiving nab-paclitaxel 
100 mg/m2 administered weekly followed by carboplatin at AUC = 6 mg*min/mL on Day 1 of 
each cycle, repeated every 21 days, for 4 cycles will be enrolled. Subjects will have CT scans 
performed at the end of Cycle 2 and Cycle 4. At the end of the 4 cycles, subjects who achieve a 
radiologically assessed CR, PR, or SD without clinical progression based on the Investigator’s 
evaluation using RECIST 1.1 guidelines, and meet inclusion/exclusion criteria will be 
randomized in the Maintenance part of the study.
An independent DMC will be established to monitor the study conduct. Details will be provided 
in the DMC charter.
10.1.2.
Study Population Definitions
10.1.2.1.
Intent-to-Treat Population
The primary efficacy analysis will be performed on the ITT population, which includes all 
enrolled subjects who received at least one dose of study treatment regardless of whether they 
have any efficacy assessments collected.
10.1.2.2.
Safety Population
The safety population will be the analysis population for all safety/ tolerability analyses. The 
safety population includes all subjects enrolled who received at least 1 dose of study treatment. 
Only subjects with clear documentation that no study treatment was administered will be 
excluded from the safety population. 
10.1.3.
Sample Size and Power Considerations
Approximately up to 450 subjects will be enrolled in the Induction part of the study. This sample 
size would provide approximately 216 subjects eligible for randomization in the Maintenance 
part.  
In the nab-Paclitaxel Phase 3 NSCLC development study (Protocol CA031), 42% (13/31) and 
63% (125/198) of the squamous subjects from the North American and ex-North American sites, 
respectively, were progression free after 4 cycles of treatment and remained in the study in Cycle 
5 and beyond. It is assumed that approximately 50% (225/450) of the subjects in the Induction 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
51
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
part of this study will meet the radiologic and clinical progression free criteria at the end of 
Cycle 4. Furthermore, it is expected that approximately 4% of these 225 subjects will not meet 
the other inclusion/exclusion criteria for the Maintenance part, yielding a total of approximately 
216 subjects entering the Maintenance part of the study.
The actual number of subjects enrolling into the Induction part, and then being randomized in the 
Maintenance part of the study will be monitored on an ongoing basis and adjusted accordingly to 
ensure that the targeted number of required PFS events for the Maintenance part is attained.
Enrollment of the Induction part, therefore, could be discontinued early or extended beyond the 
planned number of 450 subjects.
The sample size in the Induction part of the study does not support any pre-defined hypothesis 
and hence power is not relevant for this part of the study. Sample sizes for this part of the study 
are based on the pragmatic requirements for achieving the necessary PFS events in the 
Maintenance part of the study. (See Section 10.2.3). 
10.1.4.
Background and Demographic Characteristics
The baseline characteristics of all subjects enrolled 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. Medical 
history data will be summarized using frequency tabulations by system organ class and preferred 
term.
10.1.5.
Subject Disposition
Subject disposition including the number and percent of subjects enrolled, randomized, treated, 
and the primary reason for discontinuation of therapy will be summarized by study site. Protocol 
deviations will be summarized using frequency tabulations.
10.1.6.
Efficacy Analysis
10.1.6.1.
Primary Purpose
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. There is no formal inferential testing
statistical analysis planned for this purpose. Subjects who attain a radiologically assessed CR, 
PR, or SD without clinical progression according to the investigator’s assessment of the scan 
performed at the end of Cycle 4, based on RECIST 1.1 guidelines, and satisfy the 
inclusion/exclusion criteria will be eligible to be randomized into the Maintenance part of the 
study.  
10.1.6.2.
Secondary Endpoints
10.1.6.2.1. Overall Response Rate 
The percentage of subjects who achieve an overall complete or partial response (ORR) according 
to RECIST 1.1 guidelines as determined by the investigator and confirmed by repeat assessments 
performed no less than 28 days after the criteria for response were first met will be calculated.
The associated two-sided 95% CI of the ORR will be presented.
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0.1.6.2.1
he p


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
52
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
Given that the confirmation CT-scan for the ORR could be taken after the start of the 
Maintenance part in which subjects will be receiving either nab-paclitaxel plus BSC or BSC
alone, the ORR will be reported for all subjects enrolled as 1 group, and also by the Maintenance 
treatment regimen, if necessary.
It is important to note that the Induction part is analogous to a 4-cycle fixed duration study with 
all subjects exiting this part prior to or at the end of Cycle 4. Therefore, the analysis results for 
all secondary efficacy endpoints should be interpreted accordingly.
10.1.7.
Safety Analysis
All subjects who take at least 1 dose of nab-paclitaxel will be included in the safety analyses. 
Adverse events will be summarized by worst severity grade. AEs, as well as treatment-emergent 
AEs, will be summarized by system organ class, and preferred term. nab-Paclitaxel-related 
adverse events, adverse events leading to death or to discontinuation from treatment, events 
classified as CTCAE Grade 3 or Grade 4, and serious adverse events, and adverse events of 
special interest will be summarized separately.
Cross tabulations will be provided to summarize frequencies of abnormalities.
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.
10.1.7.1.
Adverse Events
Adverse events will be coded using the Medical Dictionary for Drug Regulatory Activities 
(MedDRA).
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AEs that began or worsened in grade after the start of nab-paclitaxel to the start of 
the Maintenance part for those who randomize in the Maintenance part, or until 28 days after the 
last dose of study drug for those who do not randomize in the Maintenance part. 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 summarized by system organ class, relative and absolute frequency, 
severity/grade based on the NCI CTCAE version 4.0 and relationship to treatment. Study 
medication-related AEs, SAEs, and events leading to discontinuation or death will be listed 
separately.
10.1.7.2.
Laboratory Assessments
Laboratory test results will not be collected in the eCRFs unless they are determined to be 
clinically significant laboratory abnormalities. Abnormal and clinically significant laboratory 
assessments at Screening will be recorded as medical history, and after Screening, as AE or SAE. 
If a clinically significant laboratory abnormality is captured as medical history, AE, or SAE, the 
specific laboratory parameter(s) should be recorded on the laboratory assessments CRF.
10.1.8.
Study Treatment Termination
Reasons for stopping study treatment during the Induction part will be summarized in listings by 
frequency of occurrence and corresponding percentage of occurrence.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
53
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
10.1.9.
Deaths
Deaths reported during treatment (defined as deaths after the start of nab-paclitaxel to the start of 
the Maintenance part for those who are randomized in the Maintenance part, or through end of 
treatment of nab-paclitaxel for those who are not randomized in the Maintenance part) will be 
summarized by frequency of occurrence and corresponding percentage by cause of death per 
period.
10.1.10.
Interim Analysis (Quality of Life Questionnaire and Biomarker Data)
For administrative purposes (eg, planning of new studies, publication of data) the LCSS, EQ-5D 
measurements and biomarker data collected during the Induction part will be summarized using 
descriptive statistics when approximately 50, 100, 200 and all subjects, respectively, have either 
discontinued during or completed the Induction part of the study.
10.2.
Maintenance Part
10.2.1.
Overview
This is the open-label, randomized, Maintenance part of the study for the evaluation of the 
benefit of a maintenance treatment after an initial 4 cycles of Induction treatment for subjects 
with squamous NSCLC.
Approximately 216 radiologic and clinical progression free subjects from the Induction part will 
be randomized in the Maintenance part. These subjects will be randomized in a 2:1 ratio to the 
nab-paclitaxel plus BSC and BSC alone groups, respectively. The nab-paclitaxel group will 
receive nab-paclitaxel 100 mg/m2 on Day 1 and 8 of each 21-day cycle plus BSC (the actual 
starting dose may be adjusted as specified in Section 8.3), while the BSC group will receive the 
standard BSC. All subjects will receive the assigned regimen until disease progression or 
unacceptable toxicity.
A permuted-block randomization method and an Interactive Voice Response System (IVRS) will 
be utilized to ensure a central randomization. The randomization will be stratified based on 
following 3 baseline and prognostic factors:
!
ECOG performance status at the end of the Induction part (0 vs. 1)
!
Tumor response to induction chemotherapy (CR or PR vs. SD), and 
!
Disease stage before administration of induction therapy (IIIB vs. IV).
Tumor response to Induction part chemotherapy for stratification is the response assessed at the 
last CT scan before randomization.
It is hypothesized that subjects will benefit from maintenance treatment with nab-paclitaxel. A
randomization ratio of 2:1 will, therefore, minimize subject exposure to treatment with BSC only 
while providing sufficient data for testing the treatment difference with respect to the primary 
endpoint, PFS, in the Maintenance part of the study. 
A DMC will be used to monitor the study conduct. Details will be provided in the DMC charter.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
10.2.2.
Study Population Definitions
10.2.2.1.
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 IP or has any efficacy 
assessments collected. 
10.2.2.2.
Response Evaluable Population
Response evaluable population includes all randomized subjects who meet eligibility criteria, 
take at least one dose of IP or on BSC and have at least one baseline and post baseline efficacy 
assessment. The response evaluable population may be used for additional analyses which will 
be described in the SAP.
10.2.2.3.
Per-protocol (PP) Population
The PP population is defined as all subjects randomized in the Maintenance part who receive at 
least one dose of the study therapy or on BSC arm and do not have any known major protocol 
deviations and fulfill the study enrollment criteria. The PP population may be used for additional 
analyses which will be described in the SAP.
10.2.2.4.
Safety Population
The safety population includes all randomized subjects and will be the population for all safety 
analyses.
10.2.3.
Sample Size and Power Considerations
Progression free survival is the primary endpoint while OS and ORR are the secondary endpoints 
in this part of the study.  
One non-binding interim analysis for PFS with early stopping rule for futility only will be 
conducted when approximately 91 events are observed. The study may be stopped for futility 
only if conditional power is < 10% under the assumed design hazard ratio of 0.60, but there is no 
allowance to stop the study early to declare superior efficacy.
The final analysis of the primary endpoint will be performed when approximately 136 PFS 
events have been observed. A total of approximately 216 subjects will need to be randomized 
assuming an approximate 36 months accrual period and an approximate 2 months follow-up and 
an approximate 9% per month dropout rate.
Analysis of Progression Free Survival (PFS)
The Maintenance part of the study is designed to detect a hazard ratio (HR) of 0.60 for PFS 
improvement with the nab-paclitaxel plus BSC regimen over the BSC alone regimen. There is an 
80% power to detect a hazard ratio of 0.60 using a two-sided test conducted at the 5% level of 
significance. This hazard ratio of 0.60 assumes an underlying exponential distribution for both 
treatment groups with a median time to PFS of 2 months for the BSC alone group and a median 
time to PFS of 3.33 months for the nab-paclitaxel plus BSC group. Hence, the final analysis will 
be conducted after 136 PFS events (ie, events of disease progression or deaths from any cause) 
have occurred.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
55
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
The required number of PFS events and power calculation were obtained from 
 
Analysis of Overall Survival (OS)
There will be two analyses for the OS endpoint, one of which involves an interim analysis that 
corresponds to the final analysis of PFS (approximately 136 PFS total events with a 
corresponding total of 92 deaths). However, OS collection may continue until 1.5 years after the 
final analysis of PFS in which a total of 147 total deaths are expected to be observed. The interim 
analysis for the OS endpoint will utilize a Lan-DeMets alpha-spending function to account for 
the exact timing of the interim based upon the actual number of observed events with an 
O’Brien-Fleming boundary in order to perform an appropriate group-sequential hypothesis 
testing procedure at the 5% level of significance (two-sided).  
Assuming an underlying exponential distribution for both treatment groups with median OS 
times of 7.2 and 10.3 months for the BSC alone and nab-paclitaxel plus BSC regimens, 
respectively, there is 53% power to detect a hazard ratio of 0.70 using this two-sided group 
sequential testing procedure at an overall 5% level of significance, provided that the study has an 
opportunity to continue up to 147 observed events.
A step-down procedure from the PFS final analysis to this group sequential testing approach for 
OS will be used to address multiplicity of testing.
OS analysis, the study may be stopped if the conditional power is below the threshold specified 
in the SAP.  
The required number of OS events and power calculation were obtained from 
 
10.2.4.
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. 
Medical history data will be summarized using frequency tabulations by system organ class and 
preferred term.
10.2.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both treatments 
and follow-up parts. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
10.2.6.
Efficacy Analysis
While some efficacy analyses are described in this section, additional analyses may be specified 
in the SAP.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
56
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
10.2.6.1.
Primary Endpoint 
The primary endpoint, PFS, will be based on investigator’s assessment of response using 
RECIST 1.1 guidelines. Baseline tumor measurements will be determined from the radiology 
evaluation performed within 28 days of the start of Induction therapy. Time to Progression will 
be calculated from the date of randomization (start of Maintenance part) to the first date of 
progressive disease or death from any cause.  
Progression-free survival will be summarized using Kaplan-Meier methods. 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. In the event 
that a new anticancer treatment occurs prior to documented progression, the subject will be 
censored at the time 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 time 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 time of the last radiologic 
assessment where the subject was documented to be progression-free prior to the first of the two 
missing visits.
The null (Ho) and alternative (Ha) hypotheses for testing the primary efficacy endpoint are: 
Ho: HR nab-paclitaxel plus best supportive care/ best supportive care = 1
Ha: HR nab-paclitaxel plus best supportive care/ best supportive care ≠1 
Progression-free survival distributions will be summarized using a graphical display of the 
Kaplan-Meier product limit estimates by treatment group, median PFS time estimates (including 
two-sided 95% CI) by each treatment group, and with an estimated hazard ratio (including two-
sided 95% CI) from an unstratified Cox regression model. The hypothesis test of a hazard ratio 
of 1 with respect to the PFS distributions, as shown above, will be evaluated using a stratified 
log-rank test with the 3 baseline and prognostic factors described under the randomization 
scheme in Section 4.1.2. In addition to the stratified log-rank test, a stratified Cox regression 
model will be employed to evaluate the strength of the treatment effect using the estimated 
hazard ratio and corresponding 95% confidence interval.
Pooling of Sparse Strata
If there exists unacceptable sparseness in some stratum cells (ie, a stratum cell that has less than 
5 BSC subject counts in the ITT population of the Maintenance part of the study), then an 
algorithm for collapsing some full strata will be employed until there are at least 5 BSC subjects 
in any given revised stratum cell. The initial stratum cells for the BSC treatment group will start 
out as 8 cells that represent all possible permutations of the 3 strata (baseline Eastern 
Cooperative Oncology Group [ECOG] performance status at the end of the Induction part [0 vs. 
1]; tumor response to induction chemotherapy [CR/PR vs. SD]; and disease stage before 
administration of induction therapy [IIIB vs. IV]). Hence, the 8 cells representing all possible 
permutations among the strata may be reduced down to either 4 cells (all possible permutations 
of just 2 relatively large strata), 2 cells (just 1 large stratum); or no strata at all when 
implementing the algorithm for the BSC group, the smallest treatment group based on the 2:1 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
57
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
randomization. However, it is extremely unlikely that the algorithm will result in no stratum. 
Once the revised strata have been determined through the algorithm, then it will be used 
consistently for all stratified analyses.  
Sensitivity and Supplemental Analyses
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 regimen. In addition, sensitivity analyses will be performed to 
further assess the impact of missed radiologic assessments. An additional analysis of PFS, where 
new treatment will be considered as an event, will be conducted to address the impact of second 
line therapy. 
10.2.6.2.
Secondary Endpoints
Key secondary efficacy endpoints include OS and ORR (percent of subjects who had a 
radiologic complete or partial response according to RECIST 1.1 guidelines determined by the 
investigator and confirmed by repeat assessments performed no less than 28 days after the 
criteria for response were first met). 
10.2.6.2.1. 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 trial or who are withdrawn from the trial 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 cut-off date. 
Overall survival will be analyzed in the same manner as PFS (primary endpoint), including the 
stratification variables.
10.2.6.2.2. Overall Response Rate 
The percentage of randomized subjects having an overall confirmed CR or PR based on the 
investigator’s assessment using RECIST 1.1 guidelines over the entire study (Induction and 
Maintenance) will be calculated (scans will be performed every 42 days [-3/+7 days] and 
confirmation scan will be performed no less than 4 weeks after the criteria for response were first 
met). Baseline tumor measurements will be determined from the radiology evaluation performed 
within 28 days of the start of Induction therapy.
The two-sided 95% CI of the response rates will be presented. Relative response rates between 
treatment regimens will be tested using a stratified Cochran-Mantel-Haenszel chi-square test at a 
two-sided 5% significance level.  The stratification variables for the analysis will be the same as 
the PFS analysis (primary endpoint).
10.2.6.2.3. Disease Control Rate
Disease Control rate (ie, SD for ≥ 6 weeks or confirmed CR or PR) over the entire study will be 
analyzed in the same manner as overall response rate. Baseline tumor measurements will be 
determined from the radiology evaluation performed within 28 days of the start of Induction 
therapy.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
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58
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
10.2.6.2.4. Progression Free Survival From Day 1 Cycle 1
Additional analyses of PFS calculated from the date of the first dose of Induction therapy will be 
conducted using the same statistical methods described for PFS measured from the date of 
randomization above.
10.2.6.2.5. Overall Survival from Day 1 Cycle 1
Additional analyses of OS calculated from the date of the first dose of induction therapy will be 
conducted using the same statistical methods described for OS calculated from the date of 
randomization above.
10.2.6.2.6. Overall Response Rate in Maintenance Part Beyond Response in Induction Part
Tumor reductions during maintenance treatment beyond the response to induction therapy will 
be explored by the percentage of randomized subjects achieving an overall confirmed CR or PR
compared with the radiologic assessment before randomization (ie, using end of cycle 4 CT-scan 
as the baseline measurement) according to the investigator’s evaluation using RECIST 1.1 
guidelines.
The two-sided 95% CI of the response rates will be presented. Differences in response rates 
between treatment regimens may be tested using chi-square test at a two-sided 5% significance 
level.
10.2.6.2.7. Time to Response During the Induction Part and Over the Entire Study, With 
and Without the Requirement of Confirmation of Response
Time to response is defined as the time from Day 1 Cycle 1 to the first occurrence of confirmed 
response (CR or PR). Time to response will be summarized with descriptive statistics. Only 
subjects with a CR or PR as a best overall confirmed response during induction will be included 
in this analysis.
The same analysis will be performed for time to response without confirmation of response.
10.2.6.2.8. Duration of Response Over the Entire Study, With and Without the 
Requirement of Confirmation of Response
For subjects who had a confirmed CR or PR, the duration of overall response is measured from 
the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first 
date that recurrent or progressive disease is radiologically documented (taking as reference for 
progressive disease the smallest measurements recorded on study).
Subjects who are non-responders (ie, do not achieve at least a PR) will be excluded from this 
analysis. Subjects who do not have PD after the response will be censored on the date of last 
tumor assessment. If a subject died before PD, then the subject will be censored on the date of 
death.
The duration of response 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 stratified Cox 
proportional hazard model. For this analysis, the stratification factors will be the same as those 
used in the primary efficacy analysis, if stratum sizes are sufficient.
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d


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
59
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
The same analysis will be performed for duration of response without confirmation of response.
10.2.6.3.
Exploratory Endpoints
10.2.6.3.1. Health Care Utilization and Quality of Life Questionnaire
The analysis of health care utilization and quality of life questionnaire will be described in detail 
in the SAP.
10.2.6.3.2. Biomarkers and Pharmacogenomic Data
Statistical analysis of the biomarkers and pharmacogenomic data collected from the plasma and 
blood samples will be covered under a separate SAP from that mentioned above.
10.2.7.
Safety Analysis
Adverse events will be summarized by worst severity grade. AEs, as well as treatment-emergent 
AEs, will be summarized by system organ class, and preferred term. IP-related adverse events, 
adverse events leading to death or to discontinuation from treatment, events classified as CTCAE 
Grade 3 or Grade 4 (or moderate/severe if other rating scale is used), and serious adverse events, 
and adverse events of special interest will be summarized separately.
Cross tabulations will be provided to summarize frequencies of abnormalities.
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. 
10.2.7.1.
Adverse Events
Adverse events will be analyzed in terms of TEAEs, defined as any AE occurring or worsening 
on or after the date of randomization through 28 days after the last administration of the study 
regimen. In addition, any AE with an onset date more than 28 days after the last dose of IP that is 
assessed by the investigator as related to study drug will be considered a TEAE. They will be 
summarized by system organ class, relative and absolute frequency, severity grade based on the 
NCI CTCAE version 4.0 and relationship to treatment. Study medication-related AEs, SAEs, and 
events leading to discontinuation or death will be listed separately. 
AEs will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA).
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.
Since laboratory test data will not be collected routinely in the eCRFs, this will not be analyzed.
10.2.7.2.
Laboratory Assessments
Laboratory tests will be performed weekly prior to nab-paclitaxel administration, as per standard 
of care during the study and as clinically indicated. Laboratory test results will not be collected 
in the eCRFs unless they are determined to be clinically significant laboratory abnormalities.
Abnormal and clinically significant laboratory assessments at Screening will be recorded as 
medical history, and after Screening, as AE or SAE. If a clinically significant laboratory 
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Labora
ca


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
60
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
abnormality is captured as medical history, AE, or SAE, the specific laboratory parameter(s) 
should be recorded on the laboratory assessments CRF.
10.2.8.
Study Therapy Termination
Reasons for stopping study therapy will be summarized in listings by frequency of occurrence 
and corresponding percentage of occurrence per study part (Induction and Maintenance) and 
combined.
10.2.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the study 
Maintenance regimen through 28 days after the last dose of the study Maintenance regimen) 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).
Deaths occurring during the entire study (Induction and Maintenance parts) will also be 
summarized similarly.
10.2.10.
Interim Analysis
Progression Free Survival (PFS)
One non-binding interim analysis will be used to assess futility using the PFS endpoint only, and 
is planned when approximately a total of 91 events have been observed. The study may be 
stopped early for futility only if the conditional power for PFS is < 10% under the assumed 
design hazard ratio of 0.60, but there is no allowance to stop the study early to declare superior 
efficacy.
The final analysis of PFS will be performed when approximately 136 PFS events have been 
observed, provided the study is not terminated early due to futility or other administrative 
reasons.
An observed hazard ratio at the interim of greater than or equal to 0.94 corresponds to the 
conditional power boundary of less than or equal to 10%. These boundaries were calculated 
using 
Overall Survival (OS)
The interim analysis for the OS endpoint will utilize a Lan-DeMets alpha-spending function to 
account for the exact timing of the interim based upon the actual number of observed events with 
an O’Brien-Fleming boundary in order to perform an appropriate group-sequential hypothesis 
testing procedure at the 5% level of significance (two-sided). 
Assuming an underlying exponential distribution for both treatment groups with median OS 
times of 7.2 and 10.3 months for the BSC alone and nab-paclitaxel plus BSC regimens, 
respectively, there is 53% power to detect a hazard ratio of 0.70 using this two-sided group 
sequential testing procedure at an overall 5% level of significance, provided that study has an 
opportunity to continue up to 147 observed events.
The two-sided nominal value p-value stopping boundary for first interim analysis is 0.009, while 
the final two-sided nominal p-value stopping boundary is 0.047. These stopping boundaries and 
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35


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
61
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
previous power calculation for the OS endpoint were calculated using 
 
OS analysis, the study may be stopped if the conditional power is below the threshold specified 
in the SAP.
10.3.
Data Monitoring Committee
An independent DMC will be established with the responsibilities for safeguarding the interests 
of study participants and monitoring the overall conduct of the study. Final recommendations of 
the DMC will reflect the judgment of the DMC members and will be considered advisory in 
nature to the Sponsor. The decision to implement the recommendations of the DMC will be 
made by the Sponsor, following consultation with the coordinating PI and Steering Committee.
A DMC charter will be established.
10.4.
Scientific Steering Committee
The conduct of this trial will be overseen by a Steering Committee. The Steering Committee will 
serve in an advisory capacity to the Sponsor. 
Note: the Steering Committee is separate from the Data Monitoring Committee described in 
Section 10.3.
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teering
ng Commi
g Comm


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
62
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the CRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of squamous cell NSCLC will not 
require reporting as an adverse event. However, signs and symptoms (events) related to disease 
progression may be reported as adverse events. If reported, events of disease progression for 
squamous cell NSCLC disease under the study (including deaths due to disease progression for 
indications that are considered to be fatal) will be assessed as expected AEs and will not be 
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 an IP 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 other appropriate tests and 
procedures.
All AEs will be recorded by the Investigator from the time the subject signs informed consent to
28 days after the last dose of IP or the End of Study Treatment Visit, whichever is longer, and
those SAEs made known to the investigator at any time thereafter that are suspected of being 
related to IP. AEs and serious adverse events (SAEs) will be recorded on the AE page of the 
CRF and in the subject’s source documents. All SAEs must be reported to Celgene Drug Safety 
within 24 hours of the Investigator’s knowledge of the event by facsimile, or other appropriate 
method, using the SAE Report Form, or approved equivalent form.
11.2.
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to: 
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E
A quali
A qual


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
63
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
!
Results in death;
!
Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the CRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of a pre-existing condition unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
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be
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
64
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to IP, action taken regarding IP, and outcome.
11.2.2.
Severity / Intensity
For both AEs and SAEs, the Investigator must assess the severity/intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current active minor version of 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 IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
The temporal relationship of the adverse event to IP 
administration makes a causal relationship unlikely or 
remote, or other medications, therapeutic interventions, or 
underlying conditions provide a sufficient explanation for the 
observed event.
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Not su
Not su


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
65
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
Suspected:
The temporal relationship of the adverse event to IP 
administration makes a causal relationship possible, and other 
medications, therapeutic interventions, or underlying conditions 
do not provide a sufficient explanation for the observed event.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP 
that has not been manufactured or provided by Celgene, please provide the name of the 
manufacturer when reporting the event.
11.2.4.
Duration
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event.
11.2.5.
Action Taken
The Investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(eg, discontinuation or reduction of IP, as appropriate) and report if concomitant and/or 
additional treatments were given for the event. 
11.2.6.
Outcome
The investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered (death due to another cause) or death 
(due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or
!
is judged to be of significant clinical importance.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the CRF. If the abnormality was not a 
part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE. If 
possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
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4


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
66
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
11.4.1.
Females of Childbearing Potential
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on IP, or within 28 days of the 
subject’s last dose of IP, are considered immediately reportable events. IP is to be discontinued 
immediately. The pregnancy, suspected pregnancy, or positive pregnancy test must be reported 
to Celgene Drug Safety immediately by facsimile, or other appropriate method, using the 
Pregnancy Initial Report Form, or approved equivalent form. The female subject should be 
referred to an obstetrician-gynecologist, preferably one experienced in reproductive toxicity for 
further evaluation and counseling.
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 or therapeutic abortion), the 
Investigator should report the abnormal outcome as an AE. If the abnormal outcome meets any 
of the serious criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or 
other appropriate method, within 24 hours of the Investigator’s knowledge of the event using the 
SAE Report Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the Investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the Investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving IP or within
6 months of the last dose of IP, the male subject taking IP should notify the Investigator, and the 
pregnant female partner should be advised to call her healthcare provider immediately. The IP 
may need to be discontinued in the male subject, but may be resumed later at the discretion of 
the Investigator and medical monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The Investigator is required to ensure that the data on these forms is accurate and consistent. This 
requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent to at least 28 days after the last dose of IP or 
End of Study Treatment Visit, whichever is later) and those made known to the Investigator at 
any time thereafter that are suspected of being related to IP. SAEs occurring prior to treatment 
will be captured.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
67
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
The SAE report should provide a detailed description of the SAE and include summaries 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 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 Abraxane and Investigator 
Brochure. For the purpose of regulatory reporting in the EEA, Celgene Drug Safety will 
determine the expectedness of events suspected of being related to the other IP, carboplatin,
based on the EU Summary of Product Characteristics (SmPC). 
For countries within the European Economic Area (EEA), Celgene or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 
presentation of adverse reaction reports arising from clinical trials on IP for human use 
(ENTR/CT3) and also in accordance with country-specific requirements.
Celgene or its authorized representative shall notify the Investigator of the following 
information: 
!
Any AE suspected of being related to the use of IP in this study or in other studies 
that is both serious and unexpected (ie, SUSAR);
!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC. (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report
Form/Completion Guidelines or to the Pregnancy Report Form/Completion Guidelines.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
68
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the IP:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent
!
Death
!
Lost to follow-up
!
Protocol violation
All subjects discontinued from nab-paclitaxel for any reason will have a treatment 
discontinuation visit at the time of nab-paclitaxel discontinuation and should undergo early 
termination procedures.
All subjects discontinued from nab-paclitaxel will be followed for a period of 28 days after PFS 
or early discontinuation, or until the date of the last study visit, whichever is longer.
Additionally, subjects who withdraw from or complete treatment should not be withdrawn from 
the study (unless specifically requested) and should be followed up for progressive disease, 
survival and any new therapy given.
The reason for treatment discontinuation should be recorded in the eCRF and in the source 
documents.
The decision to discontinue a subject remains the responsibility of the treating physician, which 
will not be delayed or refused by the Sponsor. However, prior to discontinuing a subject, the 
Investigator may contact the Medical Monitor and forward appropriate supporting documents for 
review and discussion.
12.2.
Study Discontinuation
The following are considered sufficient reasons for discontinuing a subject from the study:
!
Withdrawal of consent (decision form the subject not to provide follow-up 
information)
!
Death
!
Lost to follow-up
The following may be considered a sufficient reason for discontinuing a subject from the study:
!
Protocol violation
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. The Investigator must notify the Medical Monitor immediately when a subject has 
been discontinued/withdrawn due to an AE (any unacceptable toxicity). All subjects who are 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
69
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
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 the subject lost to follow-up.
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.
&(/*(1(35235,(7$5<,1)250$7,21


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
70
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
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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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
71
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
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 Council for
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 CRFs 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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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
72
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the Investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the Investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the Investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
IP can only be supplied to an Investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
Celgene or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB/EC should mention the protocol title, number, amendment number 
(if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
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EDMS Doc. Number: 
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Celgene Corporation
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the Investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
74
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and the distribution of the IP are complete, accurate, filed and retained. Examples of source 
documents include: hospital records; clinic and office charts; laboratory notes; memoranda; 
subject’s diaries or evaluation checklists; dispensing records; recorded data from automated 
instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy, and the laboratories, as 
well as copies of CRFs or CD-ROM.
15.2.
Data Management
Data will be entered into the clinical database per Celgene Standard Operating Procedures 
(SOPs). This data will be electronically verified through use of programmed edit checks 
specified by the clinical team. Discrepancies in the data will be brought to the attention of the 
clinical team, and investigational site personnel, if necessary. Resolutions to these issues will be 
reflected in the database. An audit trail within the system will track all changes made to the data.
15.3.
Record Retention
Essential documents must be retained by the Investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IP. The investigator must retain these 
documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the Investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the Investigator, Celgene, and their authorized 
representative(s);
!
List of Sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of CRFs (if paper) and of documentation of corrections for all subjects;
!
IP accountability records;
!
Record of any body fluids or tissue samples retained;
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
75
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
!
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
tion of 
tion of 


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
76
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
16.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative
for compliance with applicable government regulations with respect to current GCP and standard 
operating procedures.
16.1.
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study. All aspects of the study are reviewed with the Investigator and the staff at a study 
initiation visit and/or at an investigator meeting. Prior to enrolling subjects into the study, a 
Celgene representative will review the protocol, CRFs, procedures for obtaining informed 
consent, record keeping, and reporting of AEs/SAEs with the Investigator. Monitoring will 
include on-site visits with the Investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, IP
storage area, CRFs, subject’s source documents, and all other study documentation will be
inspected/reviewed by the Celgene representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the CRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff. Any necessary
corrections will be made directly to the CRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene. Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, CRFs and applicable supporting records of 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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EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
77
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
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 and order of 
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 the study.
&(/*(1(35235,(7$5<,1)250$7,21


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
78
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
18.
REFERENCES
Azzoli CG, Baker Jr. S, Temin S, 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, 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 
Onc. 2008;26:468-473.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response 
evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 
Jan;45(2):228-47.
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):1590-1598.
Lorenz W, Reimann HJ, Schmal A, et al. Histamine release in dogs by Cremophor El and its 
derivatives: oxethylated oleic acid is the most effective constituent. Agents Actions 
1997;7:63-67.
Lung Cancer Awareness. Global Lung Cancer Coalition Website. 
http://www.lungcancercoalition.org/en/pages/about/awareness. Accessed July 12, 2013.
National Institute for Health & Clinical Excellence: The Diagnosis and Treatment of Lung 
Cancer: Methods, Evidence & Guidance, 2011.
Neal, JW. The SATURN trial: the value of maintenance erlotinib in patients with non-small-cell
lung cancer. Future Oncol. 2010 Dec;6(12):1827-1832.
O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979 
Sep;35(3):549-556.
Oken, MM, Creech, RH, Tormey, DC, et al. Toxicity And Response Criteria Of The Eastern 
Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982.
Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus best 
supportive care versus placebo plus best supportive care after induction therapy with pemetrexed 
plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a 
double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55.
Rizvi NA, Riely GJ, Azzoli CG, 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):639-643.
Schell MJ, Peterman A, et al. Phase III trial comparing a defined duration of therapy versus 
continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell 
lung cancer. J Clin Oncol. 2002;20(5):1335-1343.
Socinski M, Manikhas GM, Stroyakovsky DL, 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):852-861.
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ponse
onse
ncer. 2009
cer. 2009
backs and 
acks and
(13)
(13):1590
:1590
Cremophor
emoph
Agents Act
gents Acti
ite.
te.
i
nessss. Acces
Acce
e Diag
iagnosi
nos
ntenance
enance er
827
827-1832.
-1832.
ting proced
ting proced
, DC,
, DC, et ala
Am J Clin
Am J Clin
Dediu M, e
ediu M, 
placebo plu
placebo pl
anced non
anced non
se 3, rando
se 3, rando
ely GJ, Azz
ely GJ, Az
ound paclit
und paclit
J Clin Onc
J Clin Onc
ell MJ,
ell MJ, Pet
Pet
continuous 
ontinuous 
lung can
ung ca


EDMS Doc. Number: 
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
79
ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
Stinchcombe TE, Socinski MA. Current treatments for advanced stage non-small cell lung 
cancer. Proc Am Thorac Soc. 2009;6(2):233-241.
Weiss RB, Donehower RC, Wiernik PH, et al. Hypersensitivity reactions from Taxol. J Clin 
Oncol. 1990;8(7):1263-1268.


EDMS Doc. Number: 
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Protocol ABI-007-NSCL-003
Celgene Corporation
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ABI-007-NSCL-003 Amendment 3 Final: 13 Mar 2017
19.
APPENDICES
Appendix A:
ECOG Performance Status Score
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5
Dead
Oken, 1982.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
TITLE PAGE
A PHASE III, RANDOMIZED, OPEN-LABEL, MULTI-
CENTER, SAFETY AND EFFICACY STUDY TO 
EVALUATE NAB-PACLITAXEL (ABRAXANE®) AS 
MAINTENANCE TREATMENT AFTER INDUCTION 
WITH NAB-PACLITAXEL PLUS CARBOPLATIN IN 
SUBJECTS WITH SQUAMOUS CELL NON-SMALL 
CELL LUNG CANCER (NSCLC)
INVESTIGATIONAL PRODUCT (IP):
nab-Paclitaxel (Abraxane®)
PROTOCOL NUMBER:
ABI-007-NSCL-003
ORIGINAL DATE FINAL:
27 Sep 2013
AMENDMENT 1 DATE FINAL:
28 Oct 2014
AMENDMENT 2 DATE FINAL:
07 May 2015
EudraCT NUMBER:
2014-003804-66
IND NUMBER:
114882
SPONSOR NAME / ADDRESS:
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board. The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations.
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information:
Name:
Title:
Address: 
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
Phone:
 
E-mail:
Contact Information:
Name:
Title:
Address: 
Celgene Corporation
86 Morris  Avenue
Summit, NJ 07901
Phone:
E-mail:
Note: The back-up 24 hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls.
Back-up 24 Hour Global Emergency Contact Call Center:
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
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-003
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
PROTOCOL SUMMARY
Study Title
A Phase III, randomized, open-label, multi-center, safety and efficacy study to evaluate nab®-
paclitaxel1 (Abraxane) as maintenance treatment after induction with nab-paclitaxel plus 
carboplatin in subjects with squamous cell non-small cell lung cancer (NSCLC).
Indication
Maintenance treatment of squamous cell NSCLC.
Objectives
Primary
!
To evaluate progression free survival (PFS) with nab-paclitaxel as maintenance 
treatment after response or stable disease (SD) with nab-paclitaxel plus carboplatin in 
subjects with squamous cell NSCLC.
Secondary 
!
To evaluate the safety and tolerability of nab-paclitaxel as maintenance treatment 
after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous 
cell NSCLC.
!
To further assess the efficacy with nab-paclitaxel as maintenance treatment after
response or SD with nab-paclitaxel plus carboplatin in subjects with squamous cell 
NSCLC, as measured by secondary efficacy endpoints.
Exploratory 
!
To determine baseline tumor characteristics which predict response and resistance to 
nab-paclitaxel/carboplatin during the Induction part of the study. 
!
To determine what changes in peripheral tumor characteristics during treatment are 
associated with acquisition of resistance in the subjects who had initial clinical 
benefit.
!
To assess healthcare resource utilization during the Maintenance part of the study.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ5D).
Study Design
This is a Phase III, randomized, open-label, multi-center study of nab-paclitaxel or best 
supportive care (BSC) as maintenance treatment after response or SD with nab-paclitaxel plus 
carboplatin as induction in subjects with squamous cell NSCLC. Approximately 540 subjects
with stage IIIB or IV squamous cell NSCLC will be enrolled in the Induction part of the study to 
receive nab-paclitaxel plus carboplatin for 4 cycles. If after the 4 cycles, the subject has a 
complete response (CR), partial response (PR), or SD, they will be randomized (2:1) in the
                                               
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
Maintenance part of the study to receive nab-paclitaxel plus BSC or BSC alone. BSC is defined
as the best palliative care per investigator (including but not limited to: antibiotics, analgesics,
antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and/or focal 
external-beam radiation for control of pain, cough, dyspnea, or hemoptysis), excluding
antineoplastic agents. Approximately 260 subjects will be evaluable for the primary endpoint of 
PFS in maintenance.
Induction Part
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Approximately 540 subjects eligible for 
standard treatment with nab-paclitaxel plus carboplatin for 4 cycles will be enrolled, provided if 
all inclusion/exclusion criteria are met within a 28-day screening period prior to Cycle 1 Day 1.
Induction treatment will commence on Day 1: 
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD, and has met all eligibility criteria, they will continue on to the Maintenance part 
of the study. If the subject has radiological or clinical PD, they will be discontinued from the 
study and will not be followed.
Maintenance Part
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD without clinical progression, and has met all eligibility criteria, they will be 
randomized 2:1 to receive:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day cycle plus BSC until disease progression or unacceptable toxicity (see Section 8.3
for guidelines on starting dose for the Maintenance part of the study if the subject had 
dose reduced during the Induction part of the study)
OR
!
BSC until disease progression
Maintenance therapy should start at the time of randomization. If this is not possible, a maximum 
of 7 days will be allowed from the date of randomization to the start date of Maintenance 
therapy. Subjects must start Maintenance therapy no earlier than 21 days and no later than 35
days from Day 1 of the fourth cycle of Induction therapy.
Follow-up Period 
All subjects who discontinue from the Maintenance part of the study for any reason other than 
withdrawal of consent, lost to follow-up, or death, will enter the Follow-up period that will have 
a visit 28 days after progression or discontinuation.   Those subjects entering the follow up 
period without documented progression will continue to have CT scan in accordance with 
standard of care until documented progression of disease.  Additionally, subjects will be 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
followed for overall survival (OS) by phone approximately every 90 days for up to 1.5 years
after final analysis of approximately 182 PFS events or approximately 218 deaths have been 
observed for the final OS analysis, whichever is earlier.
Study Population
Subjects with squamous cell NSCLC stage IIIB or IV with no prior chemotherapy for metastatic 
disease and ≥ 18 years old will be eligible for this study. The Induction part of the study will 
enroll approximately 540 subjects. Based on results from the nab-Paclitaxel Phase 3 NSCLC 
development study (Protocol CA031) it is estimated that approximately 260 subjects with CR, 
PR, or SD from the Induction part of the study will be randomized to the Maintenance part of the 
study. Enrollment into the Induction part of the study will be monitored and adjusted to ensure 
that approximately 260 subjects are randomized into the Maintenance part of the study.
Length of Study
The Induction part of the study will last approximately 36 months to enroll sufficient subjects for 
the Maintenance part of the study. The total length of this Phase III study with Induction, 
Maintenance, and Follow-up is estimated to last approximately 5 years.
Study Treatments
Induction 
The nab-paclitaxel and carboplatin treatments will not be supplied by Celgene during Induction 
in those countries where nab-paclitaxel plus carboplatin is available for the treatment of NSCLC. 
Investigative sites will use standard of care (commercially available) product via prescription in 
these countries.
In those countries where nab-paclitaxel plus carboplatin is not available for the treatment of 
NSCLC, or is available but designated as investigational product (IP) as per local regulations, 
both agents will be packaged and supplied by Celgene.  
Maintenance 
Subjects will be randomized to receive open-label nab-paclitaxel plus BSC or BSC during the 
Maintenance part of the study. The nab-paclitaxel used in the Maintenance part of the study will 
be packaged and supplied by Celgene Corporation.
Please see local prescribing information for Abraxane for detailed instructions on the
reconstitution, storage conditions, and IV administration of nab-paclitaxel.
Statistical Methods
Approximately 540 subjects will be enrolled in the open-label Induction part of the study. All 
subjects will receive nab-paclitaxel 100 mg/m2 administered weekly followed by carboplatin
AUC = 6 mg*min/mL on Day 1 of each cycle, repeated every 21 days, for 4 cycles.
At the end of Cycle 4, subjects who achieve a radiologically assessed complete response (CR), 
partial response (PR), or stable disease (SD) without clinical progression based on the 
Investigator’s evaluation using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 
guidelines will be further evaluated for their eligibility to participate in the Maintenance part of 
the study.  Approximately 260 subjects are expected to be randomized in the Maintenance part of 
the study.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
9
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
The actual number of subjects that will be enrolled in the Induction part will be monitored and 
adjusted to ensure that the target number of subjects for the Maintenance part is attained.
Similarly, the percentage of subjects manifesting a PFS event in the Maintenance part will be 
tracked on an ongoing basis. If the observed percentage of subjects with a PFS event is trending 
lower than the assumed 70%, the number of subjects enrolled in the Induction and Maintenance 
parts will be increased to ensure that at least 182 PFS events will be observed within the 
anticipated duration of the study.
Induction Part
Efficacy Analyses
All efficacy endpoints will be analyzed based on the intent-to-treat (ITT) population for the 
Induction part, which includes all enrolled subjects who received at least one dose of study 
treatment regardless of whether they have any efficacy assessments collected.
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Subjects will have CT scans performed at 
the end of Cycle 2 and 4. Subjects who attain a radiologically assessed CR, PR, or SD without 
clinical progression according to the investigator’s assessment of the scan performed at the end 
of Cycle 4, based on RECIST v1.1 (Eisenhauer, 2009) guidelines, and satisfy eligibility criteria 
will be eligible to be randomized in the Maintenance part.
The secondary objective of the Induction part is to estimate the Overall Response Rate (ORR, 
percent of subjects who have a CR or PR according to RECIST v1.1 guidelines as determined by 
the investigator and confirmed by repeat assessments performed no less than 28 days after the 
criteria for response were first met). Descriptive statistics (point estimate and the associated two-
sided 95% confidence interval) will be calculated for this endpoint.
Safety Analyses
The safety population, includes all subjects enrolled who received at least 1 dose of study 
treatment, will be the analysis population for all safety analyses. Adverse events will be 
summarized by worst severity grade. Adverse events (AEs), as well as treatment-emergent AEs, 
will be summarized by system organ class, and preferred term. Adverse event severity/grade will 
be summarized by National Cancer Institute (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE) v4.0. 
Laboratory test results will not be collected in the eCRFs unless they are determined to be 
clinically significant laboratory abnormalities. Abnormal and clinically significant laboratory 
assessments at Screening will be recorded as medical history, and after Screening, as AE or 
serious adverse event (SAE). If a clinically significant laboratory abnormality is captured as 
medical history, AE, or SAE, the specific laboratory parameter(s) should be recorded on the 
laboratory assessments CRF.
Maintenance Part
Approximately 260 subjects will be randomized in the Maintenance part of the study. These 
subjects will be randomized in a 2:1 ratio to the nab-paclitaxel plus BSC and BSC alone groups, 
respectively. The nab-paclitaxel group will receive nab-paclitaxel 100 mg/m2 on Day 1 and 8 of 
each 21-day cycle plus BSC (the actual starting dose may be adjusted as specified in 
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Section 8.3), while the BSC group will receive the standard BSC regimen. All subjects will 
receive the assigned regimen until disease progression or unacceptable toxicity.
Randomization will be stratified by the following 3 baseline and prognostic stratification factors:
Eastern Cooperative Oncology Group (ECOG) performance status at the end of the Induction 
part (0 vs. 1), tumor response to induction chemotherapy (CR/PR vs. SD), and disease stage 
before administration of induction therapy (IIIB vs. IV). Tumor response to Induction part 
chemotherapy for stratification is the response assessed at the last CT scan before randomization. 
It is postulated that subjects will benefit from maintenance therapy with nab-paclitaxel, therefore 
a randomization ratio of 2:1 will reduce subject exposure to treatment with BSC alone while 
providing sufficient data for testing the treatment difference with respect to the primary endpoint, 
progression free survival.
The Maintenance part of the study is designed to detect a hazard ratio (HR) of 0.60 for PFS 
improvement with the nab-paclitaxel plus BSC regimen over the BSC alone regimen with 90% 
power and an overall type-I error rate of 5% (two-sided). The final analysis will be conducted 
after approximately 182 PFS events (ie, events of disease progression or deaths from any cause) 
have occurred. Assuming an exponential distribution with a median time to PFS of 2 months for 
the BSC alone group and proportional hazards, a hazard ratio of 0.60 constitutes a 1.33 months 
improvement for the nab-paclitaxel plus BSC group over that of the BSC alone group.
A non-binding interim analysis for futility with PFS will be planned at approximately 91 events.
The stopping rules and the final marginal significance level are determined based on O'Brien-
Fleming type boundaries (O’Brien, 1979). The study may be stopped early for futility if the 
conditional power is < 10%.
There will be 2 analyses for the OS endpoint. The interim analysis (non-binding) of OS will be 
conducted based on the number of deaths observed at the time of the final PFS analysis.
However, all subjects will continue to be followed for OS up to 1.5 years after final analysis of
approximately 182 PFS events or approximately 218 deaths have been observed for the final OS
analysis, whichever is earlier. The marginal significance levels for OS are determined based on 
O'Brien-Fleming type boundaries and will be adjusted based on the actual number of deaths 
observed at each stage.  
A Step-down procedure from PFS to OS will be used to control the family-wise two-sided Type-
I error rate to 5%.
Efficacy Analyses
The Maintenance part of the study starts on the date the subject is randomized to either of the 
treatment arms. All efficacy analyses in the Maintenance part will be based on the ITT 
population for the Maintenance part, which includes all randomized subjects regardless of 
whether they receive any IP or have any efficacy assessments collected. 
The primary efficacy endpoint is PFS based on investigator’s assessment of the subject’s 
radiologic response using RECIST 1.1 guidelines. Baseline tumor measurements will be 
determined by the computed tomography (CT)-scan performed less than 28 days before the first 
dose of nab-paclitaxel in the Induction part of the study. Progression-free survival will be 
counted from the date of randomization 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 
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('06'RF1XPEHU
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radiologic assessment prior to the data cutoff date. Rules for censoring for missing visits and 
start of anticancer treatment are provided in Section 10.
The null (Ho) and alternative (Ha) hypotheses for the primary efficacy endpoint are: 
Ho: HR nab-paclitaxel plus best supportive care / best supportive care = 1
Ha: HR nab-paclitaxel plus best supportive care / best supportive care ≠1
Progression-free survival will be summarized using the Kaplan-Meier method and by median 
PFS time (including two-sided 95% CI) for each treatment regimen along with the hazard ratio 
(including two-sided 95% CI). The Kaplan-Meier curve for PFS will be presented graphically for 
each treatment regimen and differences in the curves will be tested using a stratified log-rank test 
with the 3 baseline and prognostic factors described above.
Secondary efficacy endpoints include OS and ORR (percent of subjects who attain a CR or PR 
according to RECIST 1.1 guidelines as determined by the investigator and confirmed by repeat 
assessments performed no less than 28 days after the criteria for response are first met). Overall 
survival will be analyzed by the same method described for PFS, while ORR will be analyzed by 
chi-square test.
Safety Analyses
The safety population includes all randomized subjects. Adverse events will be summarized by 
worst severity grade. AEs, as well as treatment-emergent AEs, will be summarized by system 
organ class, and preferred term. Adverse event severity/grade will be summarized by NCI 
CTCAE v4.0.
Laboratory test results will not be collected in the eCRFs unless they are determined to be 
clinically significant laboratory abnormalities. Abnormal and clinically significant laboratory 
assessments at Screening will be recorded as medical history, and after Screening, as AE or 
serious adverse event (SAE). If a clinically significant laboratory abnormality is captured as 
medical history, AE, or SAE, the specific laboratory parameter(s) should be recorded on the 
laboratory assessments CRF.
Data Monitoring Committee
An independent Data Monitoring Committee (DMC) will be established with the responsibilities 
for safeguarding the interests of study participants and monitoring the overall conduct of the 
study. Final recommendations of the DMC will reflect the judgment of the DMC members and 
will be considered advisory in nature to the Sponsor. The decision to implement the 
recommendations of the DMC will be made by the Sponsor, following consultation with the trial 
Coordinating Principal Investigator and Steering Committee. A DMC charter will be established.
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('06'RF1XPEHU
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ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
1.
INTRODUCTION..................................................................................................19
1.1.
Non-small Cell Lung Cancer (NSCLC)...................................................................19
1.2.
nab-Paclitaxel.........................................................................................................19
1.3.
Rationale for Development of nab-Paclitaxel as Maintenance Treatment in 
Squamous Cell NSCLC ..........................................................................................22
2.
STUDY OBJECTIVES...........................................................................................23
2.1.
Primary Objective...................................................................................................23
2.2.
Secondary Objectives .............................................................................................23
2.3.
Exploratory Objectives ...........................................................................................23
3.
STUDY ENDPOINTS............................................................................................24
3.1.
Primary Endpoint....................................................................................................24
3.2.
Secondary Endpoints ..............................................................................................24
3.2.1.
Safety.....................................................................................................................24
3.2.2.
Efficacy..................................................................................................................24
3.3.
Exploratory Endpoints............................................................................................24
4.
OVERALL STUDY DESIGN ................................................................................25
4.1.
Study Design ..........................................................................................................25
4.1.1.
Induction Part.........................................................................................................25
4.1.2.
Maintenance Part....................................................................................................25
4.1.3.
Follow-up Period....................................................................................................26
4.2.
Study Design Rationale ..........................................................................................26
4.3.
Study Duration .......................................................................................................28
4.4.
End of Trial ............................................................................................................28
5.
TABLE OF EVENTS.............................................................................................29
6.
PROCEDURES......................................................................................................34
6.1.
Medical History......................................................................................................34
6.2.
Prior Medications/Procedures .................................................................................34
6.3.
Pregnancy Testing ..................................................................................................34
6.4.
Complete Chest Computed Tomography (CT) Scan (including adrenal 
gland) With and Without Contrast ..........................................................................35
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6.2.
6.2


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6.5.
Weight....................................................................................................................35
6.6.
Body Surface Area (BSA) Calculation and Height..................................................35
6.7.
ECOG Performance Score ......................................................................................35
6.8.
Concomitant Medications/Procedures.....................................................................35
6.9.
Peripheral Neuropathy Assessment.........................................................................35
6.10.
Adverse Event Reporting........................................................................................36
6.11.
Lung Cancer Symptom Scale Questionnaire and EQ5D..........................................36
6.12.
Healthcare Resource Utilization Questionnaire .......................................................36
6.13.
Electrocardiogram ..................................................................................................36
6.14.
CT Scan of Head or Brain Magnetic Resonance Imaging (MRI).............................36
6.15.
Bone Scans and X-rays...........................................................................................36
6.16.
Physical Examinations............................................................................................36
6.17.
Vital Signs..............................................................................................................37
6.18.
Laboratory Assessments .........................................................................................37
6.19.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) .....................................................................................37
6.20.
Survival..................................................................................................................38
7.
STUDY POPULATION.........................................................................................39
7.1.
Number of Subjects and Sites .................................................................................39
7.2.
Inclusion Criteria....................................................................................................39
7.3.
Exclusion Criteria...................................................................................................40
8.
DESCRIPTION OF STUDY TREATMENTS........................................................42
8.1.
Description of Investigational Product(s)................................................................42
8.1.1.
nab-Paclitaxel.........................................................................................................42
8.1.2.
Carboplatin.............................................................................................................42
8.2.
Treatment Administration and Schedule .................................................................43
8.3.
Dose Modifications.................................................................................................43
8.4.
Method of Treatment Assignment...........................................................................46
8.5.
Packaging and Labeling..........................................................................................46
8.6.
Investigational Product Accountability and Disposal ..............................................46
8.7.
Investigational Product Compliance........................................................................46
8.8.
Overdose ................................................................................................................46
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................48
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('06'RF1XPEHU
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9.1.
Permitted Concomitant Medications and Procedures...............................................48
9.2.
Prohibited Concomitant Medications and Procedures..............................................48
9.3.
Required Concomitant Medications and Procedures................................................48
10.
STATISTICAL ANALYSES..................................................................................49
10.1.
Induction Part.........................................................................................................49
10.1.1.
Overview................................................................................................................49
10.1.2.
Study Population Definitions ..................................................................................49
10.1.2.1.
Intent-to-Treat Population.......................................................................................49
10.1.2.2.
Safety Population....................................................................................................49
10.1.3.
Sample Size and Power Considerations...................................................................49
10.1.4.
Background and Demographic Characteristics........................................................50
10.1.5.
Subject Disposition.................................................................................................50
10.1.6.
Efficacy Analysis....................................................................................................51
10.1.6.1.
Primary Purpose .....................................................................................................51
10.1.6.2.
Secondary Endpoints ..............................................................................................51
10.1.7.
Safety Analysis.......................................................................................................51
10.1.7.1.
Adverse Events.......................................................................................................51
10.1.7.2.
Laboratory Assessments .........................................................................................52
10.1.8.
Study Treatment Termination .................................................................................52
10.1.9.
Deaths ....................................................................................................................52
10.1.10.
Interim Analysis (Quality of Life Questionnaire and Biomarker Data)....................52
10.2.
Maintenance Part....................................................................................................52
10.2.1.
Overview................................................................................................................52
10.2.2.
Study Population Definitions ..................................................................................53
10.2.2.1.
Intent-to-Treat Population.......................................................................................53
10.2.2.2.
Response Evaluable Population ..............................................................................53
10.2.2.3.
Per-protocol (PP) Population ..................................................................................53
10.2.2.4.
Safety Population....................................................................................................53
10.2.3.
Sample Size and Power Considerations...................................................................54
10.2.4.
Background and Demographic Characteristics........................................................55
10.2.5.
Subject Disposition.................................................................................................55
10.2.6.
Efficacy Analysis....................................................................................................55
10.2.6.1.
Primary Endpoint....................................................................................................55
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0.2.4.


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10.2.6.2.
Key Secondary Endpoints.......................................................................................56
10.2.6.3.
Other Secondary Efficacy Endpoints.......................................................................57
10.2.6.4.
Exploratory Endpoints............................................................................................57
10.2.7.
Safety Analysis.......................................................................................................57
10.2.7.1.
Adverse Events.......................................................................................................57
10.2.7.2.
Laboratory Assessments .........................................................................................58
10.2.8.
Study Therapy Termination ....................................................................................58
10.2.9.
Deaths ....................................................................................................................58
10.2.10.
Interim Analysis .....................................................................................................58
10.3.
Data Monitoring Committee ...................................................................................59
10.4.
Scientific Steering Committee ................................................................................59
11.
ADVERSE EVENTS..............................................................................................60
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................60
11.2.
Evaluation of Adverse Events.................................................................................60
11.2.1.
Seriousness.............................................................................................................61
11.2.2.
Severity / Intensity..................................................................................................62
11.2.3.
Causality ................................................................................................................62
11.2.4.
Duration .................................................................................................................63
11.2.5.
Action Taken..........................................................................................................63
11.2.6.
Outcome.................................................................................................................63
11.3.
Abnormal Laboratory Values..................................................................................63
11.4.
Pregnancy...............................................................................................................63
11.4.1.
Females of Childbearing Potential ..........................................................................64
11.4.2.
Male Subjects.........................................................................................................64
11.5.
Reporting of Serious Adverse Events......................................................................64
11.5.1.
Safety Queries ........................................................................................................65
11.6.
Expedited Reporting of Adverse Events..................................................................65
12.
DISCONTINUATIONS .........................................................................................66
12.1.
Study Treatment Discontinuation............................................................................66
12.2.
Study Discontinuation ............................................................................................66
12.3.
Subject Replacement ..............................................................................................67
13.
EMERGENCY PROCEDURES.............................................................................68
13.1.
Emergency Contact.................................................................................................68
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2.2.


('06'RF1XPEHU
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Protocol ABI-007-NSCL-003
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14.
REGULATORY CONSIDERATIONS...................................................................69
14.1.
Good Clinical Practice............................................................................................69
14.2.
Investigator Responsibilities ...................................................................................69
14.3.
Subject Information and Informed Consent.............................................................69
14.4.
Confidentiality........................................................................................................70
14.5.
Protocol Amendments.............................................................................................70
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................70
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................71
14.8.
Closure of the Study ...............................................................................................71
15.
DATA HANDLING AND RECORDKEEPING.....................................................72
15.1.
Data/Documents .....................................................................................................72
15.2.
Data Management...................................................................................................72
15.3.
Record Retention....................................................................................................72
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................74
16.1.
Study Monitoring and Source Data Verification......................................................74
16.2.
Audits and Inspections............................................................................................74
17.
PUBLICATIONS ...................................................................................................75
18.
REFERENCES.......................................................................................................76
19.
APPENDICES........................................................................................................78
Appendix A: ECOG Performance Status Score .........................................................................78
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
17
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
LIST OF TABLES
Table 1:
Blinded Radiology Assessment of Overall Response Rate  (ITT Population) ..........21
Table 2:
Blinded Radiology Assessment of Response Rate for Patients with 
Squamous or Non-squamous Histologies (ITT Subgroups).....................................21
Table 3:
Table of Events – Induction....................................................................................29
Table 4:
Table of Events – Maintenance...............................................................................32
Table 5:
Permanent Dose Reductions for Hematologic and Non-Hematologic 
Toxicities on the Study ...........................................................................................45
Table 6:
Precision of the Estimate for a Proportion Given a Sample Size of 540...................50
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2
........
.......45
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.............
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LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................27
&(/*(1(35235,(7$5<,1)250$7,21


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1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer-related deaths (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 recent advances in identifying optimal chemotherapy regimens, patients with 
advanced NSCLC continue to have a poor prognosis (especially those without identifiable 
biomarkers), with only 10% to 15% of those treated still alive after 2 years of diagnosis.
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 vs
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). 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).
1.2.
nab-Paclitaxel
nab-Paclitaxel has been developed to reduce the toxicities associated with Taxol and the 
Cremophor EL/ethanol vehicle while maintaining or improving the chemotherapeutic effect of 
the drug. The Cremophor EL-free medium enables nab-paclitaxelto be given in a shorter 
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1.2.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
20
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
duration without the need for premedication to prevent solvent-related hypersensitivity reactions.
In addition, standard tubing and IV bags may be used for the IV administration of nab-paclitaxel.
nab-Paclitaxel for Injectable Suspension is approved under the trade name of ABRAXANE in 
the first-line setting in combination with carboplatin for patients with non-small cell lung cancer 
who are not candidates for curative surgery or radiation therapy in several countries (eg, US, 
Japan,  Argentina, Australia, New Zealand, Ecuador, Chile and Guatemala). 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. nab-Paclitaxel is also 
approved for the treatment of patients with metastatic breast cancer and for the first-line 
treatment of metastatic adenocarcinoma of the pancreas.
The approval of nab-paclitaxel was based on the evaluation of Phase I and II data (Rizvi, 2008;
Socinski, 2010; Belani, 2008), as well as the pivotal Phase III study: A multicenter, randomized, 
open-label study was conducted in 1052 chemonaive patients 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 or development of an unacceptable toxicity. The primary 
efficacy outcome measure was overall response rate 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 
adenocarcinoma, 43% had squamous cell lung cancer, 76% were ECOG PS 1, and 73% were 
current or former smokers. Patients received a median of 6 cycles of treatment in both study 
arms. Patients in 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]. There was no statistically significant difference in the secondary endpoint
OS between the two study arms.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
21
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
Table 1:
Blinded Radiology Assessment of Overall Response Rate 
(ITT Population)
Variable
Category/Statistic
ABI-007/
carboplatin
(N=521)
Taxol/
carboplatin
(N=531)
Response Rate 
Ratio
(pA/pT)
P-value
Patients with Confirmed Complete or Partial Overall Response
n (%)
170 (33%)
132 (25%)
1.313
0.005*
Confidence Interval (CI) a
28.6, 36.7
21.2, 28.5
1.082, 1.593
Complete Response
0
1 (< 1%)
Partial Response
170 (33%)
131 (25%)
Source Data on File
a 95% CI of response rate and 95.1% CI of response rate ratio.
Note: P-value is based on a chi-square test.
* Indicates p-value < 0.049
Per protocol, patients were stratified by NSCLC histology (squamous cell carcinoma vs
adenocarcinoma vs other histology). Subgroup analyses were performed to assess the influence 
of squamous vs non-squamous histology on the primary efficacy endpoint of overall response 
rate (the percentage of patients who achieved an objective confirmed CR or PR based on the 
blinded radiological review using RECIST response guidelines, Version 1.0). The proportion of 
patients with squamous cell carcinoma who responded was significantly higher for the 
ABI-007/carboplatin regimen relative to the Taxol/carboplatin regimen (41% vs 24%: pA/pT: 
1.680; p < 0.001). The proportion of patients with non-squamous cell carcinoma with a 
confirmed complete or partial overall response was comparable between the ABI-007 and 
Taxol/carboplatin arms (26% vs 25%: pA/pT: 1.034; p = 0.808).
Table 2:
Blinded Radiology Assessment of Response Rate for Patients with Squamous 
or Non-squamous Histologies (ITT Subgroups)
Prognostic Factor
Category/Statistic/N
ABI-007/
carboplatin
Taxol/
carboplatin
Response Rate 
Ratio (pA/pT)
P-value
Patients with Confirmed Complete 
or Partial Overall Response
Squamous cell carcinoma
94/229 (41%)
54/221 (24%)
1.680
< 0.001*
95% Confidence Interval
1.271, 2.221
Non-squamous cell carcinoma
76/292 (26%)
78/310 (25%)
1.034
0.808
95% Confidence Interval
0.788, 1.358
Abbreviations: ITT = intent-to-treat
Note: P value is based on a chi-square test.
* Indicates p-value < 0.05.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
22
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
Adverse reactions were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. Patients in both treatment arms received a 
median of 6 cycles of treatment. The following common (≥ 10% incidence) adverse reactions 
were observed at a similar incidence in nab-paclitaxel plus carboplatin-treated and paclitaxel 
injection plus carboplatin-treated patients: 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).
Laboratory-detected abnormalities which occurred with a difference ≥5% for nab-paclitaxel plus 
carboplatin vs paclitaxel injection plus carboplatin (Grades1-4 [and G3-4]) are: anemia (98% vs 
91% [28% vs 7%]), neutropenia (85% vs 83% [47% vs 58%]) and thrombocytopenia (68% vs 
55% [18% vs 9%]).  
1.3.
Rationale for Development of nab-Paclitaxel as Maintenance 
Treatment in Squamous Cell NSCLC
Although significant advances have been made in the treatment options and outcomes of patients 
with non-squamous NSCLC, progress for patients with squamous cell NSCLC has been 
disappointing. Furthermore, the data of maintenance therapy that resulted in the FDA approval of 
pemetrexed (Alimta) and erlotinib (Tarceva), seems to confer benefit (and choice) primarily for 
non-squamous NSCLC patients.
Both Alimta studies as well as the Tarceva study demonstrated an overall survival benefit with 
maintenance vs. placebo (Paz-Arez, 2012; Tarceva package insert). However, both of the Alimta 
maintenance studies showed benefit in non-squamous patients only. Whereas Tarceva showed
significant benefit in the non-squamous cell NSCLC patients, only modest improvement was 
observed in squamous cell NSCLC patients (Neal, 2010).
To date there have been no randomized studies showing benefit of maintenance therapy in 
squamous NSCLC patients. Therefore, there is still an unmet medical need for maintenance 
treatment in squamous cell NSCLC. 
us 
us 
vs 
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% vs
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udies showi
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there is st
here is stil


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
23
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
2.
STUDY OBJECTIVES
2.1.
Primary Objective
The primary objective of the study is to evaluate PFS with nab-paclitaxel as maintenance 
treatment after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous 
cell NSCLC.
2.2.
Secondary Objectives 
The secondary objectives of the study are:
!
To evaluate the safety and tolerability of nab-paclitaxel as maintenance treatment 
after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous 
cell NSCLC.
!
To further assess the efficacy with nab-paclitaxel as maintenance treatment after 
response or SD with nab-paclitaxel plus carboplatin in subjects with squamous cell 
NSCLC, as measured by secondary efficacy endpoints.
2.3.
Exploratory Objectives
The exploratory objectives of the study are:
!
To determine baseline tumor characteristics which predict response and resistance to 
nab-paclitaxel/carboplatin during the Induction part of the study. 
!
To determine what changes in peripheral tumor characteristics during treatment are 
associated with acquisition of resistance in the subjects who had initial clinical 
benefit.
!
To assess healthcare resource utilization during the Maintenance part of the study.
!
To assess the LCSS and EQ5D.
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nduction 
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resistance 
source utili
urce utili
and EQ5D
and EQ5


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
24
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
3.
STUDY ENDPOINTS
3.1.
Primary Endpoint
Progression free survival from randomization into the Maintenance part of the study.
3.2.
Secondary Endpoints
3.2.1.
Safety
Safety parameters including AEs and SAEs.
3.2.2.
Efficacy
!
Overall survival from randomization into the Maintenance part of the study.
!
Overall response rate during the Induction and Maintenance parts of the study.
!
Disease control rate over the entire study.
3.3.
Exploratory Endpoints
!
The correlation between pretreatment tumor characteristics and response and 
resistance to the study treatment determined using next-generation sequencing 
methods, immunohistochemistry, or other analysis methods.
!
The association between the changes in tumor characteristics and the acquisition of 
resistance to therapy from plasma samples taken at treatment failure during 
Maintenance.
!
The association between DNA nucleotide polymorphisms in subject’s germ line DNA 
and association with treatment efficacy and or toxicity.
!
Healthcare resource utilization during the Maintenance part of the study using a 
questionnaire including hospitalizations, emergency room visits, doctor or nurse 
visits, procedures, and/or additional medication.
!
Change in the LCSS and EQ5D.
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the study
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the LCS


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
25
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is a Phase III, randomized, open-label, multi-center study of nab-paclitaxel plus BSC or 
BSC alone as maintenance treatment after response or SD with nab-paclitaxel plus carboplatin as 
induction in subjects with squamous cell NSCLC. Approximately 540 subjects with Stage 
IIIB/IV squamous cell NSCLC eligible to receive standard treatment of nab-paclitaxel plus 
carboplatin for 4 cycles will be enrolled in the Induction part of the study. If after the 4 cycles, 
the subject has a radiologically assessed CR, PR, or SD without clinical progression, they will be 
randomized (2:1) in the Maintenance part of the study to receive nab-paclitaxel plus BSC or 
BSC alone. BSC is defined as the best palliative care per investigator (including but not limited 
to: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional 
support, and/or focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis)
excluding antineoplastic agents. Approximately 260 subjects will be evaluable for the primary 
endpoint of PFS in maintenance.
4.1.1.
Induction Part
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Approximately 540 subjects eligible for 
standard treatment with nab-paclitaxel plus carboplatin for 4 cycles will be enrolled, provided if 
all inclusion/exclusion criteria are complied within a 28-day screening period prior to Cycle 1 
Day 1.
Induction treatment will commence on Cycle 1 Day 1: 
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD, and has met all eligibility criteria, they will continue on to the Maintenance part 
of the study. If the subject has radiological or clinical PD, they will be discontinued from the 
study and will not be followed.
4.1.2.
Maintenance Part
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD without clinical progression, they will be screened for eligibility over a 7-day 
period. Subjects (approximately 260) who satisfy all inclusion/exclusion criteria, will be 
randomized 2:1 to receive either:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day cycle plus BSC until disease progression (see Section 8.3 for guidelines on 
starting dose for the Maintenance part of the study if the subject had dose reduced 
during the Induction part of the study)
cles,
les,
ey will be
will b
BSC or 
BSC or 
ut not limit
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Day 1: 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
26
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
OR
!
BSC until disease progression
Maintenance therapy should start at the time of randomization. If this is not possible, a maximum 
of 7 days will be allowed from the date of randomization to the start date of Maintenance 
therapy. Subjects must start Maintenance therapy no earlier than 21 days and no later than 35
days from Day 1 of the fourth cycle of Induction therapy. 
Randomization will be stratified by disease stage (IIIB vs IV), response in induction (CR/PR vs 
SD), and performance status (0 vs 1).
4.1.3.
Follow-up Period 
All subjects who discontinue from the Maintenance part of the study for any reason other than 
withdrawal of consent, lost to follow-up, or death, will enter the Follow-up period that will have 
a visit 28 days after progression or discontinuation. Those subjects entering the follow up period 
without documented progression will continue to have CT scans in accordance with standard of 
care until documented progression of disease. Additionally, subjects will be followed for OS by 
phone approximately every 90 days for up to 1.5 year after final analysis of approximately 182 
PFS events or approximately 218 deaths have been observed for the final OS analysis, whichever 
is earlier.
4.2.
Study Design Rationale
The results of promising activity with nab-paclitaxel in NSCLC, especially in squamous cell 
NSCLC, underscore the hypothesis for this Phase III study as a superiority trial to compare nab-
paclitaxel/BSC vs BSC as maintenance therapy in subjects with squamous cell NSCLC
(randomizing subjects with CR/PR/SD after Induction treatment with nab-paclitaxel/
carboplatin). The nab-paclitaxel regimen used for Induction will be in accordance with the FDA 
approved label, 100 mg/m2 administered once per week on Days 1, 8 and 15 of each 21-day
cycle with no break combined with carboplatin AUC = 6 mg*min/mL administered on Day 1 
every 21 days. Four cycles of doublet-chemotherapy is chosen as the cut-off, based on observed 
risk:benefit results that additional cycles of doublet chemotherapy did not confer significant 
advantages (Socinski, 2002); furthermore, 4 cycles of doublet-chemotherapy represents general 
trends of practice (Stinchcombe, 2009).
The nab-paclitaxel regimen used for Maintenance will be 100 mg/m2 administered on Days 1 
and 8 of each 21-day cycle until progression (the actual starting dose may be adjusted as 
specified in Section 8.3). The nab-paclitaxel dosing regimen was reduced to Days 1 and 8 of 
each 21-day cycle in the Maintenance part of the study to decrease potential toxicity and possibly 
optimize tolerability of treatment and drug exposure in subjects. Sufficient subjects will be
enrolled to provide adequate power to compare PFS. The safety and tolerability of nab-paclitaxel
will be assessed.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
27
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
Figure 1:
Overall Study Design
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
28
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
4.3.
Study Duration
The Induction part of the study will last approximately 36 months to randomize sufficient 
subjects for the Maintenance part of the study. The total length of this Phase III study with 
Induction, Maintenance, and Follow-up is estimated to last approximately 5 years.
4.4.
End of Trial
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
study, or the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol and/or the 
Statistical Analysis Plan (SAP), whichever is the later date.
&(/*(1(35235,(7$5<,1)250$7,21
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
29
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
5.
TABLE OF EVENTS
Table 3:
Table of Events – Induction
CYCLE 1 and 3 (21-day)
CYCLE 2 and 4 (21-day)
Assessment
Screening/
Baseline
(up to 28 
days)
Day 1
(C3: ±2 
days)
Day 8
(±2 days)
Day 15
(±2 days)
Day 1
(±2 days)
Day 8
(±2 days)
Day 15
(±2 days)
At the end 
of Cycles 2 
and 4 
(-3/+7 days)
Early
Treat-
ment 
Discon-
tinuation /
End of 4 
Cycles
Unsched-
uled
Informed Consent
X
-
-
-
-
-
-
-
-
-
Medical History
X
-
-
-
-
-
-
-
-
-
Prior Medication and Procedures
X
-
-
-
-
-
-
-
-
-
Serum β-hCGa
X
X
-
-
X
-
-
-
X
-
Complete Chest CT Scan (including 
adrenal gland) with and without contrast
and any other studies required for tumor 
imagingb
X
-
-
-
-
-
X
X
Xc
Weight
X
X
X
X
X
X
X
-
X
Xc
Archived Tumor Tissue Sample for 
Biomarker (biopsy, surgical specimen, 
or other diagnostic tumor sample)
-
X (C1D1 
only)
-
-
-
-
-
-
-
-
Plasma for Biomarker Analyses 
-
X (C1D1 
only)
-
-
-
-
-
-
X
-
Blood for PharmacogenomicAnalyses
-
X (C1D1 
only)
-
-
-
-
-
-
-
-
Body Surface Area (BSA) Calculation 
and Heightd
X
-
-
-
-
-
-
-
-
Xc
ECOG status
X
X
-
-
X
-
-
-
X
Xc
Concomitant Medication/Procedures
X
X
X
X
X
X
X
-
X
Xc
Peripheral Neuropathy Assessmente
X
X
X
X
X
X
X
-
X
Xc
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
30
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
Table 3:
Table of Events – Induction (Continued)
CYCLE 1 and 3 (21-day)
CYCLE 2 and 4 (21-day)
Assessment
Screening/
Baseline 
(up to 28 
days)
Day 1
(C3: ±2 
days)
Day 8
(±2 days)
Day 15
(±2 days)
Day 1
(±2 days)
Day 8
(±2 days)
Day 15
(±2 days)
At the end 
of Cycle 2 
and 4 (-3/+7 
days)
Early 
Treat-
ment 
Discon-
tinuation / 
End of 4 
Cycles
Unsched-
uled
Hematology and Serum Chemistry f
X
X
X
X
X
X
X
-
Xc
X
Adverse Event Evaluation
X
X
X
X
X
X
X
-
X
Xc
nab-paclitaxel Administration
-
X
X
X
X
X
X
-
-
-
Carboplatin Administration
-
X
-
-
X
-
-
-
-
-
LCSS and EQ5D
-
X
-
-
X
-
-
-
X
-
Electrocardiogram (ECG)
X
-
-
-
-
-
-
-
-
Xc
CT Scan of Head or Brain 
Magnetic Resonance 
Imaging (MRI) g
X
-
-
-
-
-
-
-
-
Xc
Bone Scan (X-rays if 
needed)g
X
Xc
Physical Examination
X
-
-
-
-
-
-
-
X
Xc
Vital Signs
X
-
-
-
-
-
-
-
X
Xc
C3: Cycle 3, eCRF: electronic Case Report Form, C1D1: Cycle 1 Day 1, AE: Adverse Event, SAE: Serious Adverse Event, ECOG: Eastern Cooperative Oncology Group, CT: Computed Tomography, 
b-HCG: beta human chorionic gonadotropin, RECIST: Response Evaluation Criteria in Solid Tumors, LCSS: Lung Cancer Symptom Scale, EQ5D: EuroQol 5D
a A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a Serum β-hCG pregnancy test must be performed to assess
eligibility at Screening/Baseline and within 72 hours of the first administration of study drug before beginning each new cycle. Note: the screening serum pregnancy test can be 
used as the test prior to Day 1 study therapy if it is performed within the 72-hour timeframe.
b All subjects must have a radiographically documented measurable tumor(s) by RECIST v1.1 criteria: Complete chest CT scan (including adrenal gland) with and without 
contrast are performed at Screening, at the end of Cycles 2 and 4 during Induction part, early termination, and if clinically indicated while on-treatment. The methods of 
assessment chosen at baseline to follow tumors are to remain consistent throughout study duration. Scans will be archived as per institution standards. CT scan with (if not 
contraindicated) and without contrast is required at Screening and preferably throughout the study. At subsequent assessments the CT scan with contrast only could be performed 
if not contraindicated per local site standard of practice, if the presence of liver metastasis can be assessed accurately.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
31
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
c If clinically indicated.
d BSA calculated at baseline and recalculated if body weight changes by more than 10% since baseline or since the previous visit when BSA was recalculated.
e The occurrence of peripheral neuropathy should be reported by the investigator as an AE or SAE.
f Laboratory assessments will be done prior to each treatment by local laboratories and as clinically indicated. The results from laboratory assessments will be captured as per 
Section 6.18.
g At Screening, if lesions are suspected.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
32
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
Table 4:
Table of Events – Maintenance
EVERY CYCLE
(21-day)
Assessment
Screening/ 
Baseline
(up to 14
days)
Day 1
(±2 days, 
except 1st
cycle)
Day 8
(±2 days)
Every 42 
days
(-3/+7 days)
Early 
Treatment 
Discon-
tinuation /
Disease
Progression
28-day 
Follow-up 
visit
Survival 
(every 90 
days) up 
to as 
specified 
in Section 
6.20
Unsched-
uled
Serum β-hCGa
X
X
-
-
X
-
-
-
Complete Chest CT Scan (including adrenal 
gland) with and without contrast and any other 
studies required for tumor imaging b
Xc
-
-
X
X
-
-
Xd
Weight
X
X
X
-
X
X
-
Xd
Plasma for Biomarker Analyses
-
-
-
X
-
-
-
Body Surface Area (BSA) Calculation and 
Heighte
X
-
-
-
-
-
-
Xd
ECOG status
Xf
X
-
-
X
-
-
Xd
Concomitant Medication/Procedures
X
X
X
X
X
X
X
Xd
Peripheral Neuropathy Assessmentg
X
X
X
-
X
X
-
Xd
Hematology and Serum Chemistry h
X
X
X
-
X
X
-
Xd
Adverse Event Evaluation
X
X
X
X
X
X
-
Xd
nab-paclitaxel Administration
-
X
X
-
-
-
-
Survival phone call 
-
-
-
-
-
-
X
-
Healthcare Resource Utilization 
Questionnaire
-
X
-
-
X
-
-
-
LCSS and EQ5D
-
X
-
-
X
-
-
-
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
33
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
Table 4:
Table of Events – Maintenance (Continued)
EVERY CYCLE
(21-day)
Assessment
Screening/ 
Baseline
(up to 14
days)
Day 1
(±2 days, 
except 1st
cycle)
Day 8
(±2 days)
Every 42 
days
(-3/+7 days)
Early 
Treatment 
Discon-
tinuation / 
Disease 
Progression
28-day 
Follow-up 
visit
Survival 
(every 90 
days) up 
to as 
specified 
in Section 
6.20
Unsched-
uled
Electrocardiogram (ECG)
Will be done as per standard of care during the study and as clinically indicated, however, results will not 
be routinely collected in the eCRFs. However, if abnormal and clinically significant results, will be collected as AE or SAE and if 
scans show documented progression of disease will be collected on eCRF.
CT Scan of Head or Brain Magnetic 
Resonance Imaging (MRI)
Bone Scan (X-rays if needed)
Physical Examination
Vital Signs
C1: Cycle 1, eCRF: electronic Case Report Form, AE: Adverse Event, SAE: Serious Adverse Event, ECOG: Eastern Cooperative Oncology Group, CT: Computed Tomography, b-HCG: beta human 
chorionic gonadotropin, LCSS: Lung Cancer Symptom Scale, EQ5D: EuroQol 5D 
a A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a Serum β-hCG pregnancy test must be performed to assess subject
eligibility at Screening/Baseline and within 72 hours of the first administration of study drug before beginning each new cycle. Note; the screening serum pregnancy test can be 
used as the test prior to Day 1 study therapy if it is performed within the 72-hour timeframe.
b Complete chest CT scan (including adrenal gland) with and without contrast is performed at baseline, every 42 days (-3/+7 days) while on-treatment (schedule based on calendar, 
not start of cycle), early termination, and if clinically indicated while on-treatment. The methods of assessment chosen at baseline to follow tumors are to remain consistent 
throughout study duration. Scans will be archived as per institution standards. Those subjects entering the follow up period without documented progression will continue to 
have CT scans in accordance with standard of care until documented progression of disease. A CT scan with (if not contraindicated) and without contrast is preferred throughout 
the study. During Maintenance the CT scan with contrast only could be performed if not contraindicated per local site standard of practice if the presence of liver metastasis can 
be assessed accurately.
c Induction End of Cycle 4 information may serve as baseline for Maintenance.
d If clinically indicated.
e BSA calculated at baseline and recalculated if body weight changes by more than 10% since baseline or since the previous visit when BSA was recalculated.
f The ECOG performance status must be 0 or 1 for subjects to start maintenance treatment.
g The occurrence of peripheral neuropathy should be reported by the investigator as an AE or SAE.
h Laboratory assessments will be done prior to each nab-paclitaxel treatment by local laboratories as per standard of care during the study and as clinically indicated. The results 
from laboratory assessments will be captured as per Section 6.18.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
34
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
6.
PROCEDURES
Subjects will be provided with a written informed consent form (ICF), given the opportunity to 
ask any questions concerning the study, and will sign an ICF prior to participating in any study 
procedures. After giving written informed consent, subjects will undergo a screening period to be 
assessed for eligibility. All subjects who sign an ICF must be screened into the Interactive Voice 
Response System (IVRS) immediately upon signature on the document. Subjects who do not 
meet the inclusion/exclusion criteria will be considered screening failures and will not be eligible 
for the study. Subjects that have satisfied all eligibility criteria after the screening period will be 
eligible to be enrolled. Subjects who screen fail may re-screen up to 3 times and an ICF will need 
to be signed at each re-screen, 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).
A CT scan with (if not contraindicated) and without the contrast is required at Screening and 
preferably throughout the study.
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 (in this instance if only the CT scan with contrast 
is available, a CT scan without the contrast should be performed). 
6.1.
Medical History
A complete medical history including, but not limited to, evaluation for past (up to 5 years) or 
present cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine, 
lymphatic, hematological, immunologic, dermatological, psychiatric, genitourinary, obstetrical, 
surgical history, smoking history, or any other diseases or disorders will be performed at 
Screening. 
6.2.
Prior Medications/Procedures
All prior medications/procedures within 28 days of time of signature on the ICF should be 
recorded. All NSCLC-related prior medications/procedures should be recorded regardless of 
time.
6.3.
Pregnancy Testing
Serum pregnancy test with sensitivity of at least 25 mIU/mL is to be obtained in females of 
childbearing potential (FCBP) at Screening for Induction and Maintenance. A serum pregnancy 
test must be done within 72 hours prior to Cycle 1 Day 1 of starting study therapy, repeated 
before beginning each new cycle, and at discontinuation or end of treatment. The subject may 
not receive treatment until the investigator has verified that the result of the pregnancy test is 
negative. See inclusion criteria for pregnancy testing requirements. Any pregnancies that occur 
in women who have received study drug must be immediately reported to Celgene Drug Safety 
(See Section 11.4).
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ble
ill be
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will
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ocedures 
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t Screening
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local stand
ocal stan
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ace pr or
only
nly the C
ed
ed). 
ed to,
ed to, evalu
va
nal, renal, h
al, renal, h
matological,
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her disease
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rocedu
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nancy Tes
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
35
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
6.4.
Complete Chest Computed Tomography (CT) Scan (including 
adrenal gland) With and Without Contrast
Complete Chest CT Scan (including adrenal gland) with and without contrast and any other 
studies required for tumor imaging will be done at Screening, at the end of Cycles 2 and 4, and at 
Early Treatment Discontinuation during the Induction part of the study. During the Maintenance 
part of the study, scans will be done every 42 days (-3/+7 days) (schedule for scans will be based 
on calendar, not start of cycle) and at Early Treatment Discontinuation/Disease Progression.
Additional CTs may be done at any time during the study if clinically indicated. CT scans are 
preferred, however MRI would be acceptable. The same scanning modality for lesion assessment 
should be used throughout the study. All scans and reports should be archived as per institution 
standards. A CT scan with (if not contraindicated) and without contrast is required at Screening 
and preferably throughout the study. At subsequent assessments the CT scan with contrast only 
could be performed if not contraindicated per local site standard of practice, if the presence of 
liver metastasis can be assessed accurately.
6.5.
Weight
Weight will be collected at every visit during the Induction and Maintenance parts of the study. 
Additional weights may be collected at any time during the study as needed.
6.6.
Body Surface Area (BSA) Calculation and Height
BSA and height will be collected and calculated at Screening during Induction and Maintenance 
parts of the study. BSA may be recalculated if body weight changes by more than 10% since 
baseline or since the previous visit when BSA was recalculated.
6.7.
ECOG Performance Score
ECOG performance score will be collected at Screening, Day 1 of every cycle and at Early 
Treatment Discontinuation/End of Cycle 4 during the Induction part of the study. During the 
Maintenance part of the study, ECOG performance score will be collected at Screening, Day 1 of 
every cycle, and at Early Treatment Discontinuation/Disease Progression. Additional ECOG may 
be collected at any time during the study as needed.
6.8.
Concomitant Medications/Procedures
All subjects will have concomitant medications and procedures recorded from the time of 
signature on the ICF until progression during the Induction part of the study or the 28-day 
follow-up visit during the Maintenance part of the study. Only NSCLC associated concomitant 
medications/procedures will be recorded, including BSC. During survival follow-up, anti-cancer 
treatment information will be collected, if available.
6.9.
Peripheral Neuropathy Assessment
Peripheral neuropathy assessment will be done from the time of signature on the ICF until 
progression during the Induction part of the study or the 28-day follow-up visit during the 
Maintenance part of the study. Additional peripheral neuropathy assessments may be done at any 
time during the study as needed.
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sment 
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he presenc
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aintenance 
intenance
dy as
y as neede
n and Hei
n and Hei
reening du
reening du
y weight ch
weight ch
y
was recalcu
was recalc
re
re
ected at S
ected a
Cycle 4 du
ycle 4 du
ECOG perf
ECOG perf
atment Dis
atment Dis
uring the st
ng the st
mitant M
itant M
l have conc
l have conc
the ICF
the ICF un
un
visit durin
isit durin
tioions/proce
/proce
ment infor
ent infor
6.9.
6.
ipi


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
36
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
6.10.
Adverse Event Reporting
All subjects will have AEs 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. 
6.11.
Lung Cancer Symptom Scale Questionnaire and EQ5D
The Lung Cancer Symptom Scale (LCSS) and (EQ-5D) questionnaires will be used to measure 
quality of life (QoL) for subjects in the trial. The LCSS is a 9 question analysis the subject
completes using a visual analogue scale (VAS) to denote intensity of a symptom. The EQ-5D 
comprises 5 questions on mobility, self-care, usual activities, pain/discomfort, anxiety/depression 
and a VAS for overall QoL. These questionnaires will be completed at Day 1 of every cycle, and 
at Early Treatment Discontinuation/End of Cycle 4 during the Induction part of the study, during 
the Maintenance part of the study, at Day 1 of every cycle, and at progression of disease. The 
quality of life data generated from these questionnaires will be analyzed per the description in 
the SAP.
6.12.
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 cycle, and at progression of disease during the Maintenance part of 
the study.
6.13.
Electrocardiogram 
An Electrocardiogram (ECG) will be performed at screening and as clinically indicated;
however, normal and non-clinically significant results will not be collected in the eCRFs. If 
results are abnormal and clinically significant at Screening, they will be recorded as medical 
history. If results are abnormal and clinically significant after Screening, they will be recorded as 
AE or SAE).
6.14.
CT Scan of Head or Brain Magnetic Resonance Imaging (MRI)
CT scan of head or brain MRI will be performed at screening if lesions are suspected and as 
clinically indicated during the study; however, results will not be collected in the eCRFs. If scans 
show progression of disease, this information will be collected on the eCRF.
6.15.
Bone Scans and X-rays
Bone scans and x-rays will be performed at screening if lesions are suspected and as clinically 
indicated during the study; however, results will not be collected in the eCRFs. If scans show 
progression of disease, this information will be collected on the eCRF.
6.16.
Physical Examinations
Physical examinations will be performed at screening and treatment discontinuation and any 
other time as clinically indicated/per the institutional practice. However, results will not be 
routinely collected on the eCRFs.   If the findings are abnormal and clinically significant at 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
37
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
screening, they will be recorded as medical history, and if findings are abnormal and clinically 
significant after screening, they will be recorded as an AE or SAE.
6.17.
Vital Signs
Vital signs will be measured at screening, treatment discontinuation, and any other time as 
clinically indicated / standard of care for the institution. However, results will not be routinely 
collected on the eCRFs.   If the findings are abnormal and clinically significant at screening, they 
will be recorded as medical history, and if findings are abnormal and clinically significant after 
screening, they will be recorded as an AE or SAE.
6.18.
Laboratory Assessments
Laboratory assessments will be done prior to each nab-paclitaxel treatments by local laboratories 
as per standard of care during the study and as clinically indicated, however, results will not be 
collected in the eCRFs unless they are determined to be clinically significant laboratory 
abnormalities. 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. Abnormal and 
clinically significant laboratory assessments at Screening will be recorded as medical history, 
and after Screening, as AE or SAE (clinically significant laboratory abnormalities at Screening 
may result in a subject being ineligible for the study and should not be captured as an AE). If a 
clinically significant laboratory abnormality is captured as medical history, AE, or SAE, the 
specific laboratory parameter(s) should be recorded on the laboratory assessments CRF. Any 
abnormal values that persist should be followed at the discretion of the Investigator. The 
Investigator should file all copies of the reports, including faxes with the subject’s medical chart.
6.19.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) 
If archival tumor biopsy blocks or (preferably) surgical specimens from subjects with prior 
resections are available, 10 or more slides of at least 4 um thickness will be collected at Cycle 1 
Day 1 of Induction. Additionally a core of an area representing viable tumor epithelium will be 
collected from the block. If the amount of tumor tissue available is not sufficient, fewer slides 
may be collected. 
If a fine needle aspirate (FNA) specimen is available, slides of at least 4 um thickness will be 
collected with the goal of obtaining at least 100,000 cells (preferably more) of material. If 
sufficient material cannot be collected, fewer slides/cells may be collected.
If only other types of diagnostic samples such as endoscopies, lavage, or sputum are available, 
this material should be optionally collected when possible, and collection is strongly encouraged 
when tissue such as endoscopy samples with multiple needle passes exists in quantities 
comparable to a core biopsy. In this instance, 10 slides and a core sample of tumor tissue should 
be collected as per biopsy and surgical samples above. 
Plasma for biomarker analyses will be collected on Day 1 of Cycle 1 during Induction and at 
progression during the Maintenance part of the study. When progression occurs during Induction 
and before Cycle 4, a plasma sample will be collected at the time of study withdrawal.
Peripheral blood will be collected for pharmacogenomic analyses on Cycle 1 Day 1 of Induction.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
38
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
Types of techniques planned to be used for tumor and blood analyses include:
!
Gene expression by RNA sequencing
!
Immunohistochemistry 
!
DNA sequencing
Details regarding the collection, storage, and shipment of the samples are given in the Laboratory 
Manual.
6.20.
Survival
After discontinuation from the Maintenance part of the study, the subjects will be followed for 
survival by phone approximately every 90 days for up to 1.5 year after final analysis of 
approximately 182 PFS events, or approximately 218 deaths have been observed for the final OS 
analysis, whichever is earlier. The subjects will also be asked questions of other medications they 
may be taking for their NSCLC. 
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owed for 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Subjects with squamous cell NSCLC stage IIIB or IV with no prior chemotherapy for metastatic 
disease who are ≥ 18 years old will be eligible for this study. The Induction part of the study will 
enroll approximately 540 subjects. Based on results from the nab-Paclitaxel Phase 3 NSCLC 
development study (Protocol CA031) it is estimated that approximately 260 subjects with CR, 
PR, or SD from the Induction part of the study will be randomized to the Maintenance part of the 
study. Enrollment into the Induction part of the study will be monitored and adjusted to ensure 
that approximately 260 subjects are randomized into the Maintenance part of the study. The 
study will be conducted at approximately 120 sites in the United States and European Union 
(EU).
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the Induction and Maintenance parts 
of the study (except if specified at study entry only):
General and Demographics
1. Age ≥ 18 years of age at the time of signing the ICF.
2. Understand and voluntarily provide written consent to the ICF prior to conducting any 
study related assessments/procedures. 
3. Able to adhere to the study visit schedule and other protocol requirements
Disease Specific
4. Histologically or cytologically confirmed Stage IIIB or IV squamous cell NSCLC at 
study entry.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease at study entry (as defined by the 
RECIST v1.1 criteria).
7. No prior chemotherapy for the treatment of metastatic NSCLC at study entry. Adjuvant, 
neo-adjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic 
disease is permitted providing it was completed 12 months prior to starting the study 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.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
40
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
12. Total bilirubin ≤ 1.5 × ULN except in cases of Gilbert’s disease and liver metastases. 
13. Creatinine ≤ 1.5 mg/dL.
14. Expected survival of > 12 weeks for the Induction part of the study.
15. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
16. For Maintenance part of the study, subjects must have received at least one dose of nab-
paclitaxel in each of the 4 cycles during Induction 
Pregnancy 
17. Females of childbearing potential [defined as a sexually mature woman who (1) have not 
undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy 
(the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for 
at least 24 consecutive months (ie, has had menses at any time during the preceding 24 
consecutive months)] must:
a.
agree to take a pregnancy test prior to starting study medication and throughout the 
study participation.
b. commit to complete abstinence from heterosexual contact, or agree to use medical 
doctor-approved contraception throughout the study without interruption, and while 
receiving study medication or for a longer period if required by local regulations.
Male subjects must:
c.
agree to complete abstinence from heterosexual contact or use a condom during 
sexual contact with a female of child bearing potential while receiving study 
medication and within 6 months after last dose of study medication, 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 into the Induction
and Maintenance parts of the study (except if specified at study entry only):
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 first dose of study drug).
2. Only evidence of disease is non-measurable at study entry.
3. Preexisting peripheral neuropathy of Grade 2, 3, or 4 (per CTCAE v4.0). For the 
Maintenance part of the study subjects with peripheral neuropathy of Grade 3 and higher 
are excluded.
4. Venous thromboembolism (VTE) within 1 month prior to signing ICF. If the subject has 
a history of VTE earlier 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.
5. Current congestive heart failure (New York Heart Association class II-IV).
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
41
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
6. 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.
7. Treatment with any investigational product within 28 days prior to signing ICF.
8. History of allergy or hypersensitivity to nab-paclitaxel or carboplatin.
9. Currently enrolled in any other clinical protocol or investigational trial that involved 
administration of experimental therapy and/or therapeutic devices.
10. Any other clinically significant medical condition and/or organ dysfunction that will 
interfere with the administration of the therapy according to this protocol.
11. 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 treatments should have been completed 6 
months prior to signing ICF.
12. 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.
13. Any condition, including the presence of laboratory abnormalities, that places the subject 
at unacceptable risk if he/she were to participate in the study.
14. Any condition that confounds the ability to interpret data from the study.
15. Pregnant and nursing females.
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at will
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males.


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
42
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Investigational Product(s)
Induction 
The nab-paclitaxel and carboplatin treatments will not be supplied by Celgene during induction 
in those countries where nab-paclitaxel plus carboplatin is available for the treatment of NSCLC.  
Investigative sites will use standard of care (commercially available) product via prescription in 
these countries.
In those countries where nab-paclitaxel plus carboplatin is not available for the treatment of 
NSCLC, or is available but designated as investigational product (IP) as per local regulations
both agents will be packaged and supplied by Celgene.
Maintenance 
Subjects will be randomized to receive open-label nab-paclitaxel plus BSC or BSC during the 
Maintenance part of the study. The nab-paclitaxel used in the Maintenance part of the study is
designated as IP and will be packaged and supplied by Celgene Corporation. 
The preparation for IV administration procedures for IP should be followed as per Prescribing
Information.
8.1.1.
nab-Paclitaxel
nab-Paclitaxel will be supplied by the Sponsor, Celgene Corporation, for the Maintenance part in 
all countries and for the Induction part if either not available or designated as IP in a country.
nab-Paclitaxel will be supplied in single-use vials in single count cartons. Each single-use 50 mL 
vial will contain paclitaxel (100 mg) and approximately 900 mg human albumin as a stabilizer.
Please see local prescribing information for Abraxane for detailed instructions on the
reconstitution, storage conditions and IV administration of nab-paclitaxel.
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 must 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 IP 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-cyclobutanedicarboxylato
(2-)0,0’]-,(SP-4-2). Carboplatin is a crystalline powder with the molecular formula of 
C6Hl2N204Pt and a molecular weight of 371.25. It is soluble in water at a rate of approximately 
14 mg/mL, and the pH of a 1% solution is 5 to 7. It is virtually insoluble in ethanol, acetone, and
dimethylacetamide.
For additional information about carboplatin storage, preparation, and administration please refer 
to the package insert. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
43
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
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.
Induction
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Approximately 540 subjects will be treated 
with nab-paclitaxel plus carboplatin for 4 cycles.
Induction treatment will commence on Day 1, in accordance with standard of care of 1st line 
treatment of metastatic NSCLC: 
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion
Maintenance Part
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD without clinical progression, they will be randomized 2:1 (approximately 260
subjects) to receive:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day cycle plus BSC until disease progression (the actual starting dose may be 
adjusted as specified in Section 8.3)
OR
!
BSC until disease progression
Maintenance therapy should start at the time of randomization. If this is not possible, a maximum 
of 7 days will be allowed from the date of randomization to the start date of Maintenance 
therapy. Subjects must start Maintenance therapy no earlier than 21 days and no later than 35
days from Day 1 of the fourth cycle of Induction therapy.
Subjects may receive BSC as needed per Investigator discretion and should be recorded.
All IP will be administered by the clinical site and administration will be documented in the 
study source record.
8.3.
Dose Modifications
Subjects will be evaluated for AEs at each visit with the NCI CTCAE v4.0 used as a guide for 
the grading of severity.  The dose of nab-paclitaxel and carboplatin for each subject will be 
modified following toxicity as described in Table 5.
Subjects who experience any of the adverse drug reactions in Table 5 will be dose reduced as per 
Table 5 during the Induction and Maintenance parts of the study. If a subject is dose reduced in 
the Induction part of the study, please refer to Table 5 for guidelines on dose and schedule for the 
Maintenance part of the study.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
44
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
!
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, on Day 1 of any 
cycle, withhold treatment until the ANC recovers to at least 1500 cells/mm3 and the 
platelet count recovers to at least 100,000 cells/mm3. On Days 8 and 15 the ANC 
should recover to at least 500 cells/mm3 and platelet count of at least 50,000 
cells/mm3. When dosing is resumed, the subject should be dosed at the next lower 
dose level of nab-paclitaxel and carboplatin as outlined in Table 5.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-
paclitaxel and carboplatin at reduced doses (Table 5) when peripheral neuropathy 
improves to Grade 1 or completely resolves.
&(/*(1(35235,(7$5<,1)250$7,21
pathy
pathy


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
45
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
Table 5:
Permanent Dose Reductions for Hematologic and Non-Hematologic Toxicities on the Study
Adverse Drug Reaction
Occurrence
nab-Paclitaxel 
Dose (mg/m2)
Carboplatin Dose 
(mg*min/mL)
Starting Dose Maintenance:
nab-paclitaxel Dose (mg/m2) Days 1 
and 8 of each 21-day Cycle
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
If subject at 100, 75 or 50 at end of 
Induction and ANC > 1500/mm3, will 
start at 100, 100 or 75 respectively 
during Maintenance
Second
50
3.0
Third
Discontinue Treatment*
Platelet count < 50,000/mm3
First
75
4.5
If subject at 100 or 75 at end of
Induction and platelet > 100,000/mm3, 
will start at 100 during Maintenance
Second
Discontinue Treatment*
Peripheral Neuropathy Grade 3 or 4
First
75
4.5
If subject at 100, 75 or 50 at end of
Induction and Grade 1 or no peripheral 
neuropathy, will start at 100, 100 or 75 
respectively during Maintenance
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
If subject at 100, 75 or 50 at end of
Induction and <  a Grade 2 or none of 
the noted events, will start at 100, 100
or 75 respectively during Maintenance
Second
50
3.0
Third
Discontinue Treatment*
Grade 4 cutaneous toxicity, diarrhea or mucositis
First
Discontinue Treatment*
ANC: Absolute Neutrophil Count
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
46
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
8.4.
Method of Treatment Assignment
The Induction and Maintenance parts of the study are open-label. In the Maintenance part of the 
study, subjects will be randomized 2:1 to nab-paclitaxel plus BSC or BSC alone. 
Enrollment/randomization will occur via IVRS for all parts of the study. 
8.5.
Packaging and Labeling
The label(s) for IP (nab-paclitaxel) will include Sponsor name, address and telephone number, 
the protocol number, IP name, dosage form and strength (where applicable), amount of IP per 
container, lot number, expiry date (where applicable), medication identification/kit number, 
dosing instructions, storage conditions, and required caution statements and/or regulatory 
statements as applicable. Additional information may be included on the label as applicable per 
local regulations.
8.6.
Investigational Product Accountability and Disposal
Celgene (or designee) will review with the Investigator and relevant site personnel the process 
for IP return, disposal, and/or destruction including responsibilities for the site vs. Celgene (or 
designee).
Celgene will instruct the Investigator on the return, disposal and/or destruction of IP and/or 
medical device materials if applicable. Only completely unused IP vials should be retained by 
the site until a representative from Celgene or other Celgene-designated personnel have 
completed an inventory. Partially used an completely used vials should be destroyed according to 
local guidelines, and disposition should be recorded on the Investigational Drug Accountability 
Record Form.
The investigator, or designee, shall record the dispensing of IP to subjects in an IP accountability 
record. The IP record will be made available to Celgene, or other authorized Celgene-designated 
monitoring personnel for the purpose of accounting for the IP supply. Inspections of the IP 
supply for inventory purposes and assurance of proper storage will be conducted as necessary. 
Any significant discrepancy will be recorded and reported to Celgene or their designee and a 
plan for resolution will be documented.
Investigational product will not be loaned or dispensed by the investigator to another investigator 
or site. Under certain circumstances, and with sponsor permission, cooperative groups may 
manage IP between locations within their network as clinical trial agreement and local guidelines 
permit.
8.7.
Investigational Product Compliance
All IP will be administered only by study site personnel and accurate recording of all IP 
administration will be made in the appropriate section of the subject’s eCRF and source 
documents.
8.8.
Overdose
Overdose, as defined for this protocol, refers to nab-paclitaxel or carboplatin dosing only.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
47
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel or carboplatin to a given subject, regardless of any associated adverse events or 
sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. See 
Section 11.1 for the reporting of adverse events associated with overdose.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
48
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
All supportive care is permitted. 
9.2.
Prohibited Concomitant Medications and Procedures
Other antineoplastic agents or IP other than what is specified in the protocol is prohibited.
9.3.
Required Concomitant Medications and Procedures
Not applicable.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
49
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the Induction and 
Maintenance parts of the study are described below by study part. Although some definitions for 
the efficacy and safety endpoints, and the analysis populations are the same for both parts of the 
study, they are repeated in the respective section to ensure that each part is self-contained.
Furthermore, while key analyses for the primary and key secondary endpoints are described in 
this section, additional analyses of these endpoints as well as exploratory endpoints will be 
described in details in the SAP.
10.1.
Induction Part
10.1.1.
Overview
This is the open-label, single-arm, Induction part of the study. Subjects receiving nab-paclitaxel 
100 mg/m2 administered weekly followed by carboplatin at AUC = 6 mg*min/mL on Day 1 of 
each cycle, repeated every 21 days, for 4 cycles will be enrolled. Subjects will have CT scans 
performed at the end of Cycle 2 and Cycle 4. At the end of the 4 cycles, subjects who achieve a 
radiologically assessed CR, PR, or SD without clinical progression based on the Investigator’s 
evaluation using RECIST 1.1 guidelines, and meet inclusion/exclusion criteria will be 
randomized in the Maintenance part of the study.
An independent DMC will be established to monitor the study conduct. Details will be provided 
in the DMC charter.
10.1.2.
Study Population Definitions
10.1.2.1.
Intent-to-Treat Population
The primary efficacy analysis will be performed on the ITT population, which includes all 
enrolled subjects who received at least one dose of study treatment regardless of whether they
have any efficacy assessments collected.
10.1.2.2.
Safety Population
The safety population will be the analysis population for all safety/ tolerability analyses. The 
safety population includes all subjects enrolled who received at least 1 dose of study treatment. 
Only subjects with clear documentation that no study treatment was administered will be 
excluded from the safety population. 
10.1.3.
Sample Size and Power Considerations
Approximately 540 subjects will be enrolled in the Induction part of the study. This sample size 
is expected to provide approximately 260 subjects eligible for randomization in the Maintenance 
part.   
In the nab-Paclitaxel Phase 3 NSCLC development study (Protocol CA031), 42% (13/31) and 
63% (125/198) of the squamous subjects from the North American and ex-North American sites, 
respectively, were progression free after 4 cycles of treatment and remained in the study in Cycle 
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iviving
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nab
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
50
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
5 and beyond. To be conservative, it is assumed that approximately 50% (270/540) of the 
subjects in the Induction part of this study will meet the radiologic and clinical progression free 
criteria at the end of Cycle 4. Furthermore, it is expected that approximately 4% of these 270
subjects will not meet the other inclusion/exclusion criteria for the Maintenance part, yielding a 
total of approximately 260 subjects entering the Maintenance part of the study.
The actual number of subjects that will be enrolled in the Induction part will be monitored on an 
ongoing basis and adjusted to ensure that the target number of subjects for the Maintenance part 
is attained. Enrollment of the Induction part, therefore, could be discontinued early or extended 
beyond the planned number of 540 subjects.
The ORR is the secondary endpoint in the Induction part. The point estimate and the associated 
two-sided 95% confidence interval will be calculated for this endpoint. No multiplicity 
adjustment will be made for this endpoint as no formal inferential testing will be performed.
The percentage of subjects with an AE of Grade 3 or higher peripheral neuropathy will be 
captured along with the associated two-sided 95% confidence interval without inferential testing.
Table 6 below demonstrates the precision of the estimate for a proportion that can be attained 
given a sample size of 540. For example, for a hypothetical ORR rate of 40% at the end of Cycle 
4, the half-width of the associated two-sided 95% confidence interval will be 4.1%, and the 
estimated 95% confidence interval will be (35.9%, 44.1%).
Table 6:
Precision of the Estimate for a Proportion Given a Sample Size of 540
Endpoint
Hypothetical Event Rate
Half Widtha of 
95% Confidence 
Interval
two-sided 95% 
Confidence Intervala
Overall Response Rate
35%
4.0%
(31.0% to 39.0%)
40%
4.1%
(35.9% to 44.1%)
45%
4.2%
(40.8% to 49.2%)
Peripheral Neuropathy
≥ Grade 3
5%
1.8%
(3.2% to 6.8%)
10%
2.5%
(7.5% to 12.5%)
15%
3.0%
(12.0% to 18.0%)
a Estimated based on normal approximation.
10.1.4.
Background and Demographic Characteristics
The baseline characteristics of all subjects enrolled 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. Medical 
history data will be summarized using frequency tabulations by system organ class and preferred 
term.
10.1.5.
Subject Disposition
Subject disposition including the number and percent of subjects enrolled, randomized, treated, 
and the primary reason for discontinuation of therapy will be summarized by study site. Protocol 
deviations will be summarized using frequency tabulations.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
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10.1.6.
Efficacy Analysis
10.1.6.1.
Primary Purpose
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. There is no formal inferential testing
statistical analysis planned for this purpose. Subjects who attain a radiologically assessed CR, 
PR, or SD without clinical progression according to the investigator’s assessment of the scan 
performed at the end of Cycle 4, based on RECIST 1.1 guidelines, and satisfy the 
inclusion/exclusion criteria will be eligible to be randomized into the Maintenance part of the 
study.  
10.1.6.2.
Secondary Endpoints
10.1.6.2.1. Overall Response Rate 
The percentage of subjects who achieve an overall complete or partial response (ORR) according 
to RECIST 1.1 guidelines as determined by the investigator and confirmed by repeat assessments 
performed no less than 28 days after the criteria for response were first met will be calculated.
The associated two-sided 95% CI of the ORR will be presented.
Given that the confirmation CT-scan for the ORR could be taken after the start of the 
Maintenance part in which subjects will be receiving either nab-paclitaxel plus BSC or BSC
alone, the ORR will be reported for all subjects enrolled as 1 group, and also by the Maintenance 
treatment regimen, if necessary.
It is important to note that the Induction part is analogous to a 4-cycle fixed duration study with 
all subjects exiting this part prior to or at the end of Cycle 4. Therefore, the analysis results for 
all secondary efficacy endpoints should be interpreted accordingly.
10.1.7.
Safety Analysis
All subjects who take at least 1 dose of nab-paclitaxel will be included in the safety analyses. 
Adverse events will be summarized by worst severity grade. AEs, as well as treatment-emergent 
AEs, will be summarized by system organ class, and preferred term. nab-Paclitaxel-related 
adverse events, adverse events leading to death or to discontinuation from treatment, events 
classified as CTCAE Grade 3 or Grade 4, and serious adverse events, and adverse events of 
special interest will be summarized separately.
Cross tabulations will be provided to summarize frequencies of abnormalities.
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.
10.1.7.1.
Adverse Events
Adverse events will be coded using the Medical Dictionary for Drug Regulatory Activities 
(MedDRA).
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AEs that began or worsened in grade after the start of nab-paclitaxel to the start of 
the Maintenance part for those who randomize in the Maintenance part, or until 28 days after the 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
last dose of study drug for those who do not randomize in the Maintenance part. 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 summarized by system organ class, relative and absolute frequency, 
severity/grade based on the NCI CTCAE version 4.0 and relationship to treatment. Study 
medication-related AEs, SAEs, and events leading to discontinuation or death will be listed 
separately.
10.1.7.2.
Laboratory Assessments
Laboratory test results will not be collected in the eCRFs unless they are determined to be 
clinically significant laboratory abnormalities. Abnormal and clinically significant laboratory 
assessments at Screening will be recorded as medical history, and after Screening, as AE or SAE. 
If a clinically significant laboratory abnormality is captured as medical history, AE, or SAE, the 
specific laboratory parameter(s) should be recorded on the laboratory assessments CRF.
10.1.8.
Study Treatment Termination
Reasons for stopping study treatment during the Induction part will be summarized in listings by 
frequency of occurrence and corresponding percentage of occurrence.
10.1.9.
Deaths
Deaths reported during treatment (defined as deaths after the start of nab-paclitaxel to the start of 
the Maintenance part for those who are randomized in the Maintenance part, or through end of
treatment of nab-paclitaxel for those who are not randomized in the Maintenance part) will be 
summarized by frequency of occurrence and corresponding percentage by cause of death per 
period.
10.1.10.
Interim Analysis (Quality of Life Questionnaire and Biomarker Data)
For administrative purposes (eg, planning of new studies, publication of data) the LCSS, EQ-5D 
measurements and biomarker data collected during the Induction part will be summarized using 
descriptive statistics when approximately 50, 100, 200, 400, and all subjects, respectively, have 
either discontinued during or completed the Induction part of the study.
10.2.
Maintenance Part
10.2.1.
Overview
This is the open-label, randomized, Maintenance part of the study for the evaluation of the 
benefit of a maintenance treatment after an initial 4 cycles of Induction treatment for subjects 
with squamous NSCLC.
Approximately 260 radiologic and clinical progression free subjects from the Induction part will 
be randomized in the Maintenance part. These subjects will be randomized in a 2:1 ratio to the 
nab-paclitaxel plus BSC and BSC alone groups, respectively. The nab-paclitaxel group will 
receive nab-paclitaxel 100 mg/m2 on Day 1 and 8 of each 21-day cycle plus BSC (the actual 
starting dose may be adjusted as specified in Section 8.3), while the BSC group will receive the 
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('06'RF1XPEHU
nab-paclitaxel
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Confidential and Proprietary
53
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
standard BSC. All subjects will receive the assigned regimen until disease progression or 
unacceptable toxicity.
A permuted-block randomization method and an Interactive Voice Response System (IVRS) will 
be utilized to ensure a central randomization. The randomization will be stratified based on 
following 3 baseline and prognostic factors:
!
ECOG performance status at the end of the Induction part (0 vs. 1)
!
Tumor response to induction chemotherapy (CR or PR vs. SD), and 
!
Disease stage before administration of induction therapy (IIIB vs. IV).
Tumor response to Induction part chemotherapy for stratification is the response assessed at the 
last CT scan before randomization.
It is hypothesized that subjects will benefit from maintenance treatment with nab-paclitaxel. A
randomization ratio of 2:1 will, therefore, minimize subject exposure to treatment with BSC only 
while providing sufficient data for testing the treatment difference with respect to the primary 
endpoint, PFS, in the Maintenance part of the study. 
A DMC will be used to monitor the study conduct. Details will be provided in the DMC charter.
10.2.2.
Study Population Definitions
10.2.2.1.
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 IP or has any efficacy 
assessments collected. 
10.2.2.2.
Response Evaluable Population
Response evaluable population includes all randomized subjects who meet eligibility criteria, 
take at least one dose of IP or on BSC and have at least one baseline and post baseline efficacy 
assessment. The response evaluable population may be used for additional analyses which will 
be described in the SAP.
10.2.2.3.
Per-protocol (PP) Population
The PP population is defined as all subjects randomized in the Maintenance part who receive at 
least one dose of the study therapy and do not have any known major protocol deviations and 
fulfill the study enrollment criteria. The PP population may be used for additional analyses 
which will be described in the SAP.
10.2.2.4.
Safety Population
The safety population includes all randomized subjects and will be the population for all safety 
analyses.
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.2.4.
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afety
analyse
nalyse


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
54
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
10.2.3.
Sample Size and Power Considerations
Progression free survival is the primary endpoint while OS and ORR are the secondary endpoints 
in this part of the study.  
One non-binding interim analysis for PFS with early stopping rule for futility will be conducted 
when approximately 91 events are observed. The study may be stopped for futility if conditional 
power is < 10%.
The final analysis of the primary endpoint will be performed when approximately 182 PFS 
events have been observed. A total of approximately 260 subjects will need to be randomized 
assuming an approximate 36 months accrual period and an approximate 2 months follow-up and 
an approximate 9% per year dropout rate.
This study is designed to provide approximately 90% power to detect a HR of 0.60 for PFS 
improvement with nab-paclitaxel plus BSC over BSC alone with a two-sided 5% significance 
level. Assuming an exponential distribution with a median time to PFS of 2 months for the BSC 
alone and proportional hazard, a hazard ratio of 0.60 constitutes an approximate 1.33 months 
increase in median PFS or a 40% hazard risk reduction by the nab-paclitaxel plus BSC regimen 
over that of the BSC alone.
There will be 2 analyses for the OS endpoint. The interim analysis (non-binding) of OS will be 
conducted based on the number of deaths observed at the time of the final PFS analysis. 
However, all subjects will continue to be followed for OS up to 1.5 years after final analysis of 
approximately 182 PFS events or approximately 218 deaths have been observed for the final OS 
analysis, whichever is earlier. The marginal significance levels for OS will be adjusted according 
to O’Brien-Fleming type boundary based on the actual number of deaths observed at each stage.
For example, if 163 and 218 deaths (~75% information) are observed by the time of the interim 
and final analyses of OS, respectively, the marginal critical values will be p ≤0.01106 and p ≤
0.04794, correspondingly.
Assuming an exponential distribution, proportional hazards, and median OS times of 7.2 and 
10.30 months for the BSC alone and nab-paclitaxel plus BSC regimens, respectively, this design 
provides 70% marginal power to detect a hazard ratio of 0.70 between the 2 maintenance 
regimens with an overall two-sided 5% significance level.
A step-down procedure from PFS to OS will be used to control family-wise Type-I error rate to 
5%. That is, OS will be tested only if the nab-paclitaxel plus BSC regimen demonstrates 
superiority over the BSC alone with PFS. 
As an illustration for timeline projection, assuming an exponential distribution for PFS, a 36-
month recruitment period for 260 subjects, and a median PFS of approximately 2.0 months for 
the BSC alone, it will take approximately 23 months from the first subject randomized to observe 
91 PFS events for the interim analysis. The final analysis of PFS (with 182 events) is estimated 
to take place at approximately 15 months after that, which is approximately 2 months after the 
last subject randomized.  
Assuming an exponential distribution for OS and a median OS of 7.2 months for the BSC arm, it 
will take approximately an additional 1.5 years follow-up after the final analysis of PFS to 
observe a total of 218 death events in the entire Maintenance part.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
55
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
10.2.4.
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. 
Medical history data will be summarized using frequency tabulations by system organ class and 
preferred term.
10.2.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both treatments 
and follow-up parts. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
10.2.6.
Efficacy Analysis
While key analyses are described in this section, additional analyses will be specified in the SAP.
10.2.6.1.
Primary Endpoint 
The primary endpoint, PFS, will be based on investigator’s assessment of response using 
RECIST 1.1 guidelines. Baseline tumor measurements will be determined from the radiology 
evaluation performed within 28 days of the start of Induction therapy. Time to Progression will 
be calculated from the date of randomization (start of Maintenance part) to the first date of 
progressive disease or death from any cause.  
Progression-free survival will be summarized using Kaplan-Meier methods. 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. In the event 
that a new anticancer treatment occurs prior to documented progression, the subject will be 
censored at the time 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 time 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 time of the last radiologic 
assessment where the subject was documented to be progression-free prior to the first of the two 
missing visits.
The null (Ho) and alternative (Ha) hypotheses for testing the primary efficacy endpoint are: 
Ho: HR nab-paclitaxel plus best supportive care/ best supportive care = 1
Ha: HR nab-paclitaxel plus best supportive care/ best supportive care ≠1 
Progression-free survival will be summarized by median PFS time (including two-sided 95% CI) 
for each treatment regimen 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 regimen and differences in the curves will be tested using the 
stratified log-rank test, where the strata include ECOG performance status at the end of the 
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('06'RF1XPEHU
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56
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Induction part (0 vs.1), tumor response to induction chemotherapy (CR or PR vs. SD), and 
disease stage before administration of induction therapy (IIIB vs. IV), if the number of events in 
each cell is adequate. Other factors may be included if indicated by the actual population 
enrolled.
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 regimen. 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. 
Additional analyses of PFS calculated from the date of the first dose of Induction therapy will be 
conducted using the same statistical methods described for PFS measured from the date of 
randomization above.
10.2.6.2.
Key Secondary Endpoints
Key secondary efficacy endpoints include OS and ORR (percent of subjects who had a 
radiologic complete or partial response according to RECIST 1.1 guidelines determined by the 
investigator and confirmed by repeat assessments performed no less than 28 days after the 
criteria for response were first met). 
10.2.6.2.1. 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 trial or who are withdrawn from the trial 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 cut-off date. 
Overall survival will be analyzed similarly as PFS.
Additional analyses of OS calculated from the date of the first dose of induction therapy will be 
conducted using the same statistical methods described for OS calculated from the date of 
randomization above.
10.2.6.2.2. Overall Response Rate 
The percentage of randomized subjects having an overall confirmed CR or PR based on the 
investigator’s assessment using RECIST 1.1 guidelines over the entire study (Induction and 
Maintenance) will be calculated (scans will be performed every 42 days [-3/+7 days] and 
confirmation scan will be performed no less than 4 weeks after the criteria for response were first 
met). Baseline tumor measurements will be determined from the radiology evaluation performed 
within 28 days of the start of Induction therapy.
The two-sided 95% CI of the response rates will be presented. Differences in response rates 
between treatment regimens will be tested using chi-square test at a two-sided 5% significance 
level.  
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
57
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
10.2.6.3.
Other Secondary Efficacy Endpoints
10.2.6.3.1. Disease Control Rate
Disease Control rate (ie, SD for ≥ 6 weeks or confirmed CR or PR) over the entire study will be 
analyzed in the same manner as overall response rate. Baseline tumor measurements will be 
determined from the radiology evaluation performed within 28 days of the start of Induction 
therapy.
10.2.6.4.
Exploratory Endpoints
10.2.6.4.1. Overall Response Rate in Maintenance Part 
Tumor reductions during maintenance treatment beyond the response to induction therapy will 
be explored by the percentage of randomized subjects achieving an overall confirmed CR or PR
compared with the radiologic assessment before randomization (i.e, using end of cycle 4 CT-
scan as the baseline measurement) according to the investigator’s evaluation using RECIST 1.1 
guidelines.  
The two-sided 95% CI of the response rates will be presented. Differences in response rates 
between treatment regimens may be tested using chi-square test at a two-sided 5% significance 
level.
10.2.6.4.2. Health Care Utilization and Quality of Life Questionnaire
The analysis of health care utilization and quality of life questionnaire will be described in detail 
in the SAP.
10.2.6.4.3. Biomarkers and Pharmacogenomic Data
Statistical analysis of the biomarkers and pharmacogenomic data collected from the plasma and 
blood samples will be covered under a separate SAP from that mentioned above.
10.2.7.
Safety Analysis
Adverse events will be summarized by worst severity grade. AEs, as well as treatment-emergent 
AEs, will be summarized by system organ class, and preferred term. IP-related adverse events, 
adverse events leading to death or to discontinuation from treatment, events classified as CTCAE 
Grade 3 or Grade 4 (or moderate/severe if other rating scale is used), and serious adverse events, 
and adverse events of special interest will be summarized separately.
Cross tabulations will be provided to summarize frequencies of abnormalities.
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. 
10.2.7.1.
Adverse Events
Adverse events will be analyzed in terms of TEAEs, defined as any AE occurring or worsening 
on or after the date of randomization through 28 days after the last administration of the study 
regimen. In addition, any AE with an onset date more than 28 days after the last dose of IP that is 
assessed by the investigator as related to study drug will be considered a TEAE. They will be 
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ve


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
58
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
summarized by system organ class, relative and absolute frequency, severity grade based on the 
NCI CTCAE version 4.0 and relationship to treatment. Study medication-related AEs, SAEs, and 
events leading to discontinuation or death will be listed separately. 
AEs will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA).
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.
Since laboratory test data will not be collected routinely in the eCRFs, this will not be analyzed.
10.2.7.2.
Laboratory Assessments
Laboratory tests will be performed weekly prior to nab-paclitaxel administration, as per standard 
of care during the study and as clinically indicated. Laboratory test results will not be collected 
in the eCRFs unless they are determined to be clinically significant laboratory abnormalities.
Abnormal and clinically significant laboratory assessments at Screening will be recorded as 
medical history, and after Screening, as AE or SAE. If a clinically significant laboratory 
abnormality is captured as medical history, AE, or SAE, the specific laboratory parameter(s) 
should be recorded on the laboratory assessments CRF.
10.2.8.
Study Therapy Termination
Reasons for stopping study therapy will be summarized in listings by frequency of occurrence 
and corresponding percentage of occurrence per study part (Induction and Maintenance) and 
combined.
10.2.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the study 
Maintenance regimen through 28 days after the last dose of the study Maintenance regimen) 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).
Deaths occurring during the entire study (Induction and Maintenance parts) will also be 
summarized similarly.
10.2.10.
Interim Analysis
There will be one non-binding interim analysis for futility for the primary endpoint, PFS, when 
approximately 91 events (50% information) have been observed. Futility may be declared and 
the study discontinued if the conditional power at the interim analysis is < 10%.  The final 
analysis of PFS will be performed when approximately 182 PFS events have been observed.
There will be two analyses for the secondary OS endpoint. The interim analysis of OS (for 
efficacy) will be conducted based on the number of deaths observed up to the time of the final 
PFS analysis. The final OS analysis will be performed after approximately 218 deaths have been 
observed, if applicable.  
A Step-down procedure from PFS to OS will be used to control the family-wise two-sided Type-
I error rate to 5%.
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Celgene Corporation
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59
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
The marginal significance level for OS will be adjusted according to O'Brien-Fleming type of 
boundary. The nominal two-sided p-values for declaring superiority will be calculated using the 
statistical software 
 The analysis and boundaries will be adjusted 
based on the actual number of deaths observed.
10.3.
Data Monitoring Committee
An independent DMC will be established with the responsibilities for safeguarding the interests 
of study participants and monitoring the overall conduct of the study. Final recommendations of 
the DMC will reflect the judgment of the DMC members and will be considered advisory in 
nature to the Sponsor. The decision to implement the recommendations of the DMC will be 
made by the Sponsor, following consultation with the coordinating PI and Steering Committee.
A DMC charter will be established.
10.4.
Scientific Steering Committee
The conduct of this trial will be overseen by a Steering Committee. The Steering Committee will 
serve in an advisory capacity to the Sponsor. 
Note: the Steering Committee is separate from the Data Monitoring Committee described in 
Section 10.3.
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Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
60
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the CRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of squamous cell NSCLC will not 
require reporting as an adverse event. However, signs and symptoms (events) related to disease 
progression may be reported as adverse events. If reported, events of disease progression for 
squamous cell NSCLC disease under the study (including deaths due to disease progression for 
indications that are considered to be fatal) will be assessed as expected AEs and will not be 
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 an IP 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 other appropriate tests and 
procedures.
All AEs will be recorded by the Investigator from the time the subject signs informed consent to
28 days after the last dose of IP or the End of Study Visit, whichever is longer, and those SAEs 
made known to the investigator at any time thereafter that are suspected of being related to IP.
AEs and serious adverse events (SAEs) will be recorded on the AE page of the CRF and in the
subject’s source documents. All SAEs must be reported to Celgene Drug Safety within 24 hours 
of the Investigator’s knowledge of the event by facsimile, or other appropriate method, using the 
SAE Report Form, or approved equivalent form.
11.2.
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to: 
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Celgene Corporation
Confidential and Proprietary
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11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
!
Results in death;
!
Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the CRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of a pre-existing condition unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
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Celgene Corporation
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If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to IP, action taken regarding IP, and outcome.
11.2.2.
Severity / Intensity
For both AEs and SAEs, the Investigator must assess the severity/intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current active minor version of 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 IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
The temporal relationship of the adverse event to IP 
administration makes a causal relationship unlikely or 
remote, or other medications, therapeutic interventions, or 
underlying conditions provide a sufficient explanation for the 
observed event.
Suspected:
The temporal relationship of the adverse event to IP 
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Celgene Corporation
Confidential and Proprietary
63
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
administration makes a causal relationship possible, and other 
medications, therapeutic interventions, or underlying conditions 
do not provide a sufficient explanation for the observed event.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP 
that has not been manufactured or provided by Celgene, please provide the name of the 
manufacturer when reporting the event.
11.2.4.
Duration
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event.
11.2.5.
Action Taken
The Investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(eg, discontinuation or reduction of IP, as appropriate) and report if concomitant and/or 
additional treatments were given for the event. 
11.2.6.
Outcome
The investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered (death due to another cause) or death 
(due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or
!
is judged to be of significant clinical importance.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the CRF. If the abnormality was not a 
part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE. If 
possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
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Celgene Corporation
Confidential and Proprietary
64
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
11.4.1.
Females of Childbearing Potential
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on IP, or within 28 days of the 
subject’s last dose of IP, are considered immediately reportable events. IP is to be discontinued 
immediately. The pregnancy, suspected pregnancy, or positive pregnancy test must be reported 
to Celgene Drug Safety immediately by facsimile, or other appropriate method, using the 
Pregnancy Initial Report Form, or approved equivalent form. The female subject should be 
referred to an obstetrician-gynecologist, preferably one experienced in reproductive toxicity for 
further evaluation and counseling.
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 or therapeutic abortion), the 
Investigator should report the abnormal outcome as an AE. If the abnormal outcome meets any 
of the serious criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or 
other appropriate method, within 24 hours of the Investigator’s knowledge of the event using the 
SAE Report Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the Investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the Investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving IP or within 
6 months of the last dose of IP, the male subject taking IP should notify the Investigator, and the 
pregnant female partner should be advised to call her healthcare provider immediately. The IP 
may need to be discontinued in the male subject, but may be resumed later at the discretion of 
the Investigator and medical monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The Investigator is required to ensure that the data on these forms is accurate and consistent. This 
requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent to at least 28 days after the last dose of IP or 
End of Study Visit, whichever is later) and those made known to the Investigator at anytime 
thereafter that are suspected of being related to IP. SAEs occurring prior to treatment will be 
captured.
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
65
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
The SAE report should provide a detailed description of the SAE and include summaries 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 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 Abraxane and Investigator 
Brochure. For the purpose of regulatory reporting in the EEA, Celgene Drug Safety will 
determine the expectedness of events suspected of being related to the other IP, carboplatin,
based on the EU Summary of Product Characteristics (SmPC). 
For countries within the European Economic Area (EEA), Celgene or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 
presentation of adverse reaction reports arising from clinical trials on IP for human use 
(ENTR/CT3) and also in accordance with country-specific requirements.
Celgene or its authorized representative shall notify the Investigator of the following 
information: 
!
Any AE suspected of being related to the use of IP in this study or in other studies 
that is both serious and unexpected (ie, SUSAR);
!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC. (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form/Completion Guidelines or to the Pregnancy Report Form/Completion Guidelines.
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66
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12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the IP:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent
!
Death
!
Lost to follow-up
!
Protocol violation
All subjects discontinued from nab-paclitaxel for any reason will have a treatment 
discontinuation visit at the time of nab-paclitaxel discontinuation and should undergo early 
termination procedures.
All subjects discontinued from nab-paclitaxel will be followed for a period of 28 days after PFS
or early discontinuation, or until the date of the last study visit (whichever is longer) for the 
collection of AEs.
Additionally subjects who withdraw from or complete treatment should not be withdrawn from 
the study (unless specifically requested) and should be followed up for progressive disease, 
survival and any new therapy given.
The reason for treatment discontinuation should be recorded in the eCRF and in the source 
documents.
The decision to discontinue a subject remains the responsibility of the treating physician, which 
will not be delayed or refused by the Sponsor. However, prior to discontinuing a subject, the 
Investigator may contact the Medical Monitor and forward appropriate supporting documents for 
review and discussion
12.2.
Study Discontinuation
The following are considered sufficient reasons for discontinuing a subject from the study:
!
Withdrawal of consent (decision form the subject not to provide follow-up 
information)
!
Death
!
Lost to follow-up
The following may be considered a sufficient reason for discontinuing a subject from the study:
!
Protocol violation
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. The Investigator must notify the Medical Monitor immediately when a subject has 
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67
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
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 the subject lost to follow-up.
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.
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68
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page).This global Emergency 
Call Center is available 24 hours a day and 7 days a week. The representatives are responsible 
for obtaining your call-back information and contacting the on call Celgene/Contract Research 
Organization (CRO) Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
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Celgene Corporation
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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 CRFs 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-003
Celgene Corporation
Confidential and Proprietary
70
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the Investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the Investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the Investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
IP can only be supplied to an Investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
Celgene or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB/EC should mention the protocol title, number, amendment number 
(if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
arch
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or written ap
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or a form 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
71
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the Investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
e;e;
ed risk to su
ed risk to su
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
72
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and the distribution of the IP are complete, accurate, filed and retained. Examples of source 
documents include: hospital records; clinic and office charts; laboratory notes; memoranda; 
subject’s diaries or evaluation checklists; dispensing records; recorded data from automated 
instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy, and the laboratories, as 
well as copies of CRFs or CD-ROM.
15.2.
Data Management
Data will be entered into the clinical database per Celgene Standard Operating Procedures 
(SOPs). This data will be electronically verified through use of programmed edit checks 
specified by the clinical team. Discrepancies in the data will be brought to the attention of the 
clinical team, and investigational site personnel, if necessary. Resolutions to these issues will be 
reflected in the database. An audit trail within the system will track all changes made to the data.
15.3.
Record Retention
Essential documents must be retained by the Investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IP. The investigator must retain these 
documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the Investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the Investigator, Celgene, and their authorized 
representative(s);
!
List of Sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of CRFs (if paper) and of documentation of corrections for all subjects;
!
IP accountability records;
!
Record of any body fluids or tissue samples retained;
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
73
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
!
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The Investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.
The Investigator must obtain approval in writing from Celgene prior to destruction of any 
records. If the Investigator is unable to meet this obligation, the Investigator must ask Celgene 
for permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.
&(/*(1(35235,(7$5<,1)250$7,21
e
ities.
ties.
destruction
destruction


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
74
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
16.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative
for compliance with applicable government regulations with respect to current GCP and standard 
operating procedures.
16.1.
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study. All aspects of the study are reviewed with the Investigator and the staff at a study 
initiation visit and/or at an investigator meeting. Prior to enrolling subjects into the study, a 
Celgene representative will review the protocol, CRFs, procedures for obtaining informed 
consent, record keeping, and reporting of AEs/SAEs with the Investigator. Monitoring will 
include on-site visits with the Investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, IP
storage area, CRFs, subject’s source documents, and all other study documentation will be
inspected/reviewed by the Celgene representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the CRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff. Any necessary 
corrections will be made directly to the CRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene. Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, CRFs and applicable supporting records of 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-003
Celgene Corporation
Confidential and Proprietary
75
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
17.
PUBLICATIONS
The results of this study may be published in a medical publication, journal, or may be used for 
teaching purposes. Additionally, this study and its results may be submitted for inclusion in all 
appropriate health authority study registries, as well as publication on health authority study 
registry websites, as required by local health authority regulations. Selection and order of  
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 the study.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
76
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
18.
REFERENCES
Azzoli CG, Baker Jr. S, Temin S, 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, 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 
Onc. 2008;26:468-473.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response 
evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 
Jan;45(2):228-47.
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):1590-1598.
Lorenz W, Reimann HJ, Schmal A, et al. Histamine release in dogs by Cremophor El and its 
derivatives: oxethylated oleic acid is the most effective constituent. Agents Actions 
1997;7:63-67.
Lung Cancer Awareness. Global Lung Cancer Coalition Website. 
http://www.lungcancercoalition.org/en/pages/about/awareness. Accessed July 12, 2013.
National Institute for Health & Clinical Excellence: The Diagnosis and Treatment of Lung 
Cancer: Methods, Evidence & Guidance, 2011.
Neal, JW. The SATURN trial: the value of maintenance erlotinib in patients with non-small-cell
lung cancer. Future Oncol. 2010 Dec;6(12):1827-1832.
O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979 
Sep;35(3):549-556.
Oken, MM, Creech, RH, Tormey, DC, et al. Toxicity And Response Criteria Of The Eastern 
Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982.
Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus best 
supportive care versus placebo plus best supportive care after induction therapy with pemetrexed 
plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a 
double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55.
Rizvi NA, Riely GJ, Azzoli CG, 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):639-643.
Schell MJ, Peterman A, et al. Phase III trial comparing a defined duration of therapy versus 
continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell 
lung cancer. J Clin Oncol. 2002;20(5):1335-1343.
&(/*(1(35235,(7$5<,1)250$7,21
response
response
J Cancer. 20
Cancer. 2
awbacks an
awbacks a
;37
37(13)
(13):15
by Cremop
y Cremop
nt. Agents A
Agents A
Website.
bsite.
areness
areness. Ac
A
The
The Diag
iag
ma
maint
intenanc
nan
2):1827
2):1827-18
18
testing pro
testing p
mey, DC, 
mey, DC, e
oup.
up. Am J C
Am J 
s F, Dediu 
s F, Dediu 
sus place
s placebo
bo
advanced 
advanced 
phase 3, ra
hase 3, r
, Ri
Rielyly GJ, 
GJ,
n-bound pa
bound pa
erer. J Clin O
J Clin O
Schell MJ,
Schell MJ,
continu
ontinu


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
77
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
Socinski M, Manikhas GM, Stroyakovsky DL, 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):852-861.
Stinchcombe TE, Socinski MA. Current treatments for advanced stage non-small cell lung 
cancer. Proc Am Thorac Soc. 2009;6(2):233-241.
Weiss RB, Donehower RC, Wiernik PH, et al. Hypersensitivity reactions from Taxol. J Clin 
Oncol. 1990;8(7):1263-1268.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
78
ABI-007-NSCL-003 Amendment 2 Final: 07 May 2015
19.
APPENDICES
Appendix A: ECOG Performance Status Score
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5
Dead
Oken, 1982.
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This is a representation of an electronic record that was signed electronically in Livelink.
This page is the manifestation of the electronic signature(s) used in compliance with
the organizations electronic signature policies and procedures.
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-003 Final: 27 Sep 2013
TITLE PAGE
A PHASE III, RANDOMIZED, OPEN-LABEL, CROSS-
OVER, MULTI-CENTER, SAFETY AND EFFICACY 
STUDY TO EVALUATE NAB-PACLITAXEL 
(ABRAXANE®) AS MAINTENANCE TREATMENT 
AFTER INDUCTION WITH NAB-PACLITAXEL PLUS 
CARBOPLATIN IN SUBJECTS WITH SQUAMOUS 
CELL NON-SMALL CELL LUNG CANCER (NSCLC)
INVESTIGATIONAL PRODUCT (IP):
nab-Paclitaxel (Abraxane®)
PROTOCOL NUMBER:
ABI-007-NSCL-003
DATE FINAL:
27 Sep 2013
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-003
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-003 Final: 27 Sep 2013
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information:
Name:
Title:
Address: 
Celgene Corporation
86 Summit Avenue
Summit, NJ 07901
Phone:
 
E-mail:
Contact Information:
Name:
Title:
Address: 
Celgene Corporation
86 Summit 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-003
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-003 Final: 27 Sep 2013
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-003
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-003 Final: 27 Sep 2013
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-003
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-003 Final: 27 Sep 2013
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-003
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-003 Final: 27 Sep 2013
PROTOCOL SUMMARY
Study Title
A Phase III, randomized, open-label, cross-over, multi-center, safety and efficacy study to 
evaluate nab-paclitaxel (Abraxane) as maintenance treatment after induction with nab-paclitaxel
plus carboplatin in subjects with squamous cell non-small cell lung cancer (NSCLC).
Indication
Maintenance treatment of squamous cell NSCLC.
Objectives
Primary
!
To evaluate progression free survival (PFS) with nab-paclitaxel as maintenance 
treatment after response or stable disease (SD) with nab-paclitaxel plus carboplatin in 
subjects with squamous cell NSCLC.
Secondary 
!
To evaluate the safety and tolerability of nab-paclitaxel as maintenance treatment 
after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous 
cell NSCLC.
!
To further assess the efficacy with nab-paclitaxel as maintenance treatment after
response or SD with nab-paclitaxel plus carboplatin in subjects with squamous cell 
NSCLC, as measured by secondary efficacy endpoints.
Exploratory 
!
To determine baseline tumor characteristics which predict response and resistance to 
nab-paclitaxel/carboplatin during the Induction part of the study. 
!
To determine what changes in peripheral tumor characteristics during treatment are 
associated with acquisition of resistance in the subjects who had initial clinical 
benefit.
!
To evaluate the safety and efficacy of nab-paclitaxel as Cross-over treatment after 
progression during the Maintenance part of the study in subjects with squamous cell 
NSCLC. 
!
To assess healthcare resource utilization during the Maintenance part of the study.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ5D).
Study Design
This is a Phase III, randomized, open-label, cross-over, multi-center study of nab-paclitaxel or 
best supportive care (BSC) as maintenance treatment after response or SD with nab-paclitaxel
plus carboplatin as induction in subjects with squamous cell NSCLC. Approximately 540
subjects with stage IIIB or IV squamous cell NSCLC will be enrolled in the Induction part of the 
maintenan
maintenan
xel
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changes
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cquisitioion 
te the safet
te the saf
ssion durin
sion durin
CLC
CLC. . 
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Sel
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his is
his is


nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-003 Final: 27 Sep 2013
study to receive nab-paclitaxel plus carboplatin for 4 cycles. If after the 4 cycles, the subject has 
a complete response (CR), partial response (PR), or SD, they will be randomized (2:1) in the 
Maintenance part of the study to receive nab-paclitaxel plus BSC or BSC alone. BSC is defined 
as the best palliative care per investigator (including but not limited to: antibiotics, analgesics, 
antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and/or focal 
external-beam radiation for control of pain, cough, dyspnea, or hemoptysis), excluding
antineoplastic agents. Approximately 260 subjects will be evaluable for the primary endpoint of 
PFS in maintenance. Once a subject in the BSC arm during the Maintenance part of the study 
experiences radiologic progression of disease, they will be eligible to cross-over to receive nab-
paclitaxel.
Induction Part
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Approximately 540 subjects eligible for 
standard treatment with nab-paclitaxel plus carboplatin for 4 cycles will be enrolled, provided if 
all inclusion/exclusion criteria are met within a 28-day screening period prior to Cycle 1 Day 1.
Induction treatment will commence on Day 1: 
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD, and has met all eligibility criteria, they will continue on to the Maintenance part 
of the study. If the subject has radiological or clinical PD, they will be discontinued from the 
study and will not be followed.
Maintenance Part
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD without clinical progression, and has met all eligibility criteria, they will be 
randomized 2:1 to receive:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day cycle plus BSC until disease progression or unacceptable toxicity (see Section 8.3
for guidelines on starting dose for the Maintenance part of the study if the subject had 
dose reduced during the Induction part of the study)
OR
!
BSC until disease progression
Maintenance therapy should start at the time of randomization. If this is not possible, a maximum 
of 7 days will be allowed from the date of randomization to the start date of Maintenance 
therapy. Subjects must start Maintenance therapy no earlier than 21 days and no later than 35
days from Day 1 of the fourth cycle of Induction therapy.
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-003 Final: 27 Sep 2013
Cross-over 
A subject in the BSC alone arm during the Maintenance part of the study who experiences 
radiological progression of disease, will be eligible to cross-over to receive nab-paclitaxel
100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle until unacceptable 
toxicity or discontinuation for any other reason, if the benefit : risk is considered appropriate by 
the treating investigator (see Section 8.3 for guidelines on starting dose for the Cross-over part of 
the study if the subject had dose reduced during the Induction part of the study, and Sections 7.2
and 7.3 for eligibility criteria).
Follow-up Period 
All subjects who discontinue from the Maintenance or Cross-over parts of the study for any 
reason other than withdrawal of consent, lost to follow-up, or death, will enter the Follow-up 
period that will have a visit 28 days after progression or discontinuation.   Those subjects 
entering the follow up period without documented progression will continue to have CT scan in 
accordance with standard of care until documented progression of disease.  Additionally, 
subjects will be followed for overall survival (OS) by phone approximately every 90 days for up 
to 1.5 years after final analysis of approximately 182 PFS events or approximately 218 deaths 
have been observed for the final OS analysis, whichever is earlier.
Study Population
Subjects with squamous cell NSCLC stage IIIB or IV with no prior chemotherapy for metastatic 
disease and ≥ 18 years old will be eligible for this study. The Induction part of the study will 
enroll approximately 540 subjects. Based on results from the nab-Paclitaxel Phase 3 NSCLC 
development study (Protocol CA031) it is estimated that approximately 260 subjects with CR, 
PR, or SD from the Induction part of the study will be randomized to the Maintenance part of the 
study. Enrollment into the Induction part of the study will be monitored and adjusted to ensure 
that approximately 260 subjects are randomized into the Maintenance part of the study.
Length of Study
The Induction part of the study will last approximately 36 months to enroll sufficient subjects for 
the Maintenance part of the study. The total length of this Phase III study with Induction, 
Maintenance, Cross-over, and Follow-up is estimated to last approximately 5 years.
Study Treatments
Induction 
The nab-paclitaxel and carboplatin treatments are designated as non-investigational products
during induction and will not be supplied by Celgene. Investigative sites will use standard of care 
(commercially available) product via prescription.
Maintenance and Cross-over
Subjects will be randomized to receive open-label nab-paclitaxel plus BSC or BSC during the 
Maintenance part of the study. Subjects will receive open-label nab-paclitaxel during the Cross-
over part of the study. The nab-paclitaxel used in the Maintenance and Cross-over parts of the 
study is designated as investigational product (IP) and will be packaged and supplied by Celgene 
Corporation.
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
9
ABI-007-NSCL-003 Final: 27 Sep 2013
The preparation for IV administration procedures for IP should be followed as per package 
insert.
Statistical Methods
Approximately 540 subjects will be enrolled in the open-label Induction part of the study. All 
subjects will receive nab-paclitaxel 100 mg/m2 administered weekly followed by carboplatin
AUC = 6 mg*min/mL on Day 1 of each cycle, repeated every 21 days, for 4 cycles.
At the end of Cycle 4, subjects who achieve a radiologically assessed complete response (CR), 
partial response (PR), or stable disease (SD) without clinical progression based on the 
Investigator’s evaluation using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 
guidelines will be further evaluated for their eligibility to participate in the Maintenance part of 
the study.  Approximately 260 subjects are expected to be randomized in the Maintenance part of 
the study.
The actual number of subjects that will be enrolled in the Induction part will be monitored and 
adjusted to ensure that the target number of subjects for the Maintenance part is attained.
Similarly, the percentage of subjects manifesting a PFS event in the Maintenance part will be 
tracked on an ongoing basis. If the observed percentage of subjects with a PFS event is trending 
lower than the assumed 70%, the number of subjects enrolled in the Induction and Maintenance 
parts will be increased to ensure that at least 182 PFS events will be observed within the 
anticipated duration of the study.
Induction Part
Efficacy Analyses
All efficacy endpoints will be analyzed based on the intent-to-treat (ITT) population, which 
includes all subjects who are enrolled regardless of whether the subjects receive any nab-
paclitaxel or have any efficacy assessments collected.
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Subjects will have CT scans performed 
every 42 days (-3/+7 days). Subjects who attain a radiologically assessed CR, PR, or SD without 
clinical progression according to the investigator’s assessment of the scan performed at the end 
of Cycle 4, based on RECIST 1.1 guidelines, and satisfy eligibility criteria will be eligible to be 
randomized in the Maintenance part.
The secondary objective of the Induction part is to estimate the Overall Response Rate (ORR, 
percent of subjects who have a CR or PR according to RECIST 1.1 guidelines as determined by 
the investigator and confirmed by repeat assessments performed no less than 28 days after the 
criteria for response were first met). Descriptive statistics (point estimate and the associated two-
sided 95% confidence interval) will be calculated for this endpoint.
Safety Analyses
The safety population, includes all subjects enrolled who received at least 1 dose of study 
treatment, will be the analysis population for all safety analyses. Adverse events will be 
summarized by worst severity grade. Adverse events (AEs), as well as treatment-emergent AEs, 
will be summarized by system organ class, and preferred term. Adverse event severity/grade will 
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
10
ABI-007-NSCL-003 Final: 27 Sep 2013
be summarized by National Cancer Institute (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE) v4.0. 
Laboratory test results will not be collected in the eCRFs unless they are determined to be 
clinically significant laboratory abnormalities. Abnormal and clinically significant laboratory 
assessments at Screening will be recorded as medical history, and after Screening, as AE or 
serious adverse event (SAE). If a clinically significant laboratory abnormality is captured as 
medical history, AE, or SAE, the specific laboratory parameter(s) should be recorded on the 
laboratory assessments CRF.
Maintenance Part
Approximately 260 subjects will be randomized in the Maintenance part of the study. These 
subjects will be randomized in a 2:1 ratio to the nab-paclitaxel plus BSC and BSC alone groups, 
respectively. The nab-paclitaxel group will receive nab-paclitaxel 100 mg/m2 on Day 1 and 8 of 
each 21-day cycle plus BSC (the actual starting dose may be adjusted as specified in Section 
8.3), while the BSC group will receive the standard BSC regimen. All subjects will receive the 
assigned regimen until disease progression or unacceptable toxicity. Subjects in the BSC alone 
group who have radiologic progression will be eligible to crossover and receive the nab-
paclitaxel regimen until unacceptable toxicity or discontinuation for any other reason, if the 
benefit:risk is considered appropriate by the treating investigator.
Randomization will be stratified by the following 3 baseline and prognostic stratification factors:
Eastern Cooperative Oncology Group (ECOG) performance status at the end of the Induction 
part (0 vs. 1), tumor response to induction chemotherapy (CR/PR vs. SD), and disease stage 
before administration of induction therapy (IIIB vs. IV). It is postulated that subjects will benefit 
from maintenance therapy with nab-paclitaxel, therefore a randomization ratio of 2:1 will reduce 
subject exposure to treatment with BSC alone while providing sufficient data for testing the 
treatment difference with respect to the primary endpoint, progression free survival.
The Maintenance part of the study is designed to detect a hazard ratio (HR) of 0.60 for PFS 
improvement with the nab-paclitaxel plus BSC regimen over the BSC alone regimen with 90% 
power and an overall type-I error rate of 5% (two-sided). The final analysis will be conducted 
after approximately 182 PFS events (ie, events of disease progression or deaths from any cause) 
have occurred. Assuming an exponential distribution with a median time to PFS of 2 months for 
the BSC alone group and proportional hazards, a hazard ratio of 0.60 constitutes a 1.33 months 
improvement for the nab-paclitaxel plus BSC group over that of the BSC alone group.
A non-binding interim analysis for futility with PFS will be planned at approximately 91 events.
The stopping rules and the final marginal significance level are determined based on O'Brien-
Fleming type boundaries (O’Brien, 1979). The study may be stopped early for futility if the 
conditional power is < 10%.
There will be 2 analyses for the OS endpoint. The interim analysis (non-binding) of OS will be 
conducted based on the number of deaths observed at the time of the final PFS analysis.
However, all subjects will continue to be followed for OS up to 1.5 years after final analysis of
approximately 182 PFS events or approximately 218 deaths have been observed for the final OS
analysis, whichever is earlier. The marginal significance levels for OS are determined based on 
O'Brien-Fleming type boundaries and will be adjusted based on the actual number of deaths 
observed at each stage.  
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
11
ABI-007-NSCL-003 Final: 27 Sep 2013
A Step-down procedure from PFS to OS will be used to control the family-wise two-sided Type-
I error rate to 5%.
Efficacy Analyses
The Maintenance part of the study starts on the date the subject is randomized to either of the 
treatment arms. All efficacy analyses in the Maintenance part will be based on the ITT 
population, which includes all randomized subjects regardless of whether they receive any IP or 
have any efficacy assessments collected. 
The primary efficacy endpoint is PFS based on investigator’s assessment of the subject’s 
radiologic response using RECIST 1.1 guidelines. Baseline tumor measurements will be 
determined by the computed tomography (CT)-scan performed less than 28 days before the first 
dose of nab-paclitaxel in the Induction part of the study. Progression-free survival will be 
counted from the date of randomization 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.
The null (Ho) and alternative (Ha) hypotheses for the primary efficacy endpoint are: 
Ho: HR nab-paclitaxel plus best supportive care / best supportive care = 1
Ha: HR nab-paclitaxel plus best supportive care / best supportive care ≠1
Progression-free survival will be summarized using the Kaplan-Meier method and by median 
PFS time (including two-sided 95% CI) for each treatment regimen along with the hazard ratio 
(including two-sided 95% CI). The Kaplan-Meier curve for PFS will be presented graphically for 
each treatment regimen and differences in the curves will be tested using a stratified log-rank test 
with the 3 baseline and prognostic factors described above.
Secondary efficacy endpoints include OS and ORR (percent of subjects who attain a CR or PR 
according to RECIST 1.1 guidelines as determined by the investigator and confirmed by repeat 
assessments performed no less than 28 days after the criteria for response are first met). Overall 
survival will be analyzed by the same method described for PFS, while ORR will be analyzed by 
chi-square test.
Safety Analyses
The safety population includes all randomized subjects in the BSC alone arm and those who
receive at least one dose of nab-paclitaxel in the nab-paclitaxel plus BSC arm in the Maintenance 
part of the study. Adverse events will be summarized by worst severity grade. AEs, as well as 
treatment-emergent AEs, will be summarized by system organ class, and preferred term. Adverse 
event severity/grade will be summarized by NCI CTCAE v4.0.
Laboratory test results will not be collected in the eCRFs unless they are determined to be 
clinically significant laboratory abnormalities. Abnormal and clinically significant laboratory 
assessments at Screening will be recorded as medical history, and after Screening, as AE or 
serious adverse event (SAE). If a clinically significant laboratory abnormality is captured as 
medical history, AE, or SAE, the specific laboratory parameter(s) should be recorded on the 
laboratory assessments CRF.
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Data Monitoring Committee
An independent Data Monitoring Committee (DMC) will be established with the responsibilities 
for safeguarding the interests of study participants and monitoring the overall conduct of the 
study. Final recommendations of the DMC will reflect the judgment of the DMC members and 
will be considered advisory in nature to the Sponsor. The decision to implement the 
recommendations of the DMC will be made by the Sponsor, following consultation with the trial 
Coordinating Principal Investigator and Steering Committee. A DMC charter will be established.
&(/*(1(35235,(7$5<,1)250$7,21


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TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
1.
INTRODUCTION..................................................................................................20
1.1.
Non-small Cell Lung Cancer (NSCLC)...................................................................20
1.2.
nab-Paclitaxel.........................................................................................................20
1.3.
Rationale for Development of nab-Paclitaxel as Maintenance Treatment in 
Squamous Cell NSCLC ..........................................................................................23
2.
STUDY OBJECTIVES...........................................................................................24
2.1.
Primary Objective...................................................................................................24
2.2.
Secondary Objectives .............................................................................................24
2.3.
Exploratory Objectives ...........................................................................................24
3.
STUDY ENDPOINTS............................................................................................25
3.1.
Primary Endpoint....................................................................................................25
3.2.
Secondary Endpoints ..............................................................................................25
3.2.1.
Safety.....................................................................................................................25
3.2.2.
Efficacy..................................................................................................................25
3.3.
Exploratory Endpoints............................................................................................25
4.
OVERALL STUDY DESIGN ................................................................................26
4.1.
Study Design ..........................................................................................................26
4.1.1.
Induction Part.........................................................................................................26
4.1.2.
Maintenance Part....................................................................................................26
4.1.3.
Cross-over..............................................................................................................27
4.1.4.
Follow-up Period....................................................................................................27
4.2.
Study Design Rationale ..........................................................................................27
4.3.
Study Duration .......................................................................................................30
4.4.
End of Trial ............................................................................................................30
5.
TABLE OF EVENTS.............................................................................................31
6.
PROCEDURES......................................................................................................35
6.1.
Medical History......................................................................................................35
6.2.
Prior Medications/Procedures .................................................................................35
6.3.
Pregnancy Testing ..................................................................................................35
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6.1.
6.1


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6.4.
Complete Chest Computed Tomography (CT) Scan (including adrenal 
gland) With and Without Contrast ..........................................................................35
6.5.
Weight....................................................................................................................36
6.6.
Body Surface Area (BSA) Calculation and Height..................................................36
6.7.
ECOG Performance Score ......................................................................................36
6.8.
Concomitant Medications/Procedures.....................................................................36
6.9.
Peripheral Neuropathy Assessment.........................................................................36
6.10.
Adverse Event Reporting........................................................................................36
6.11.
Lung Cancer Symptom Scale Questionnaire and EQ5D..........................................36
6.12.
Healthcare Resource Utilization Questionnaire .......................................................37
6.13.
Electrocardiogram ..................................................................................................37
6.14.
CT Scan of Head or Brain Magnetic Resonance Imaging (MRI).............................37
6.15.
Bone Scans and X-rays...........................................................................................37
6.16.
Physical Examinations............................................................................................37
6.17.
Vital Signs..............................................................................................................37
6.18.
Laboratory Assessments .........................................................................................38
6.19.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) .....................................................................................38
6.20.
Survival..................................................................................................................39
7.
STUDY POPULATION.........................................................................................40
7.1.
Number of Subjects and Sites .................................................................................40
7.2.
Inclusion Criteria....................................................................................................40
7.3.
Exclusion Criteria...................................................................................................41
8.
DESCRIPTION OF STUDY TREATMENTS........................................................43
8.1.
Description of Investigational Product(s)................................................................43
8.1.1.
nab-Paclitaxel.........................................................................................................43
8.1.2.
Carboplatin.............................................................................................................43
8.2.
Treatment Administration and Schedule .................................................................44
8.3.
Dose Modifications.................................................................................................45
8.4.
Method of Treatment Assignment...........................................................................47
8.5.
Packaging and Labeling..........................................................................................47
8.6.
Investigational Product Accountability and Disposal ..............................................47
8.7.
Investigational Product Compliance........................................................................47
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8.4.
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5


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8.8.
Overdose ................................................................................................................47
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................49
9.1.
Permitted Concomitant Medications and Procedures...............................................49
9.2.
Prohibited Concomitant Medications and Procedures..............................................49
9.3.
Required Concomitant Medications and Procedures................................................49
10.
STATISTICAL ANALYSES..................................................................................50
10.1.
Induction Part.........................................................................................................50
10.1.1.
Overview................................................................................................................50
10.1.2.
Study Population Definitions ..................................................................................50
10.1.2.1.
Intent-to-Treat Population.......................................................................................50
10.1.2.2.
Safety Population....................................................................................................50
10.1.3.
Sample Size and Power Considerations...................................................................50
10.1.4.
Background and Demographic Characteristics........................................................51
10.1.5.
Subject Disposition.................................................................................................52
10.1.6.
Efficacy Analysis....................................................................................................52
10.1.6.1.
Primary Purpose .....................................................................................................52
10.1.6.2.
Secondary Endpoints ..............................................................................................52
10.1.7.
Safety Analysis.......................................................................................................52
10.1.7.1.
Adverse Events.......................................................................................................53
10.1.7.2.
Laboratory Assessments .........................................................................................53
10.1.8.
Study Treatment Termination .................................................................................53
10.1.9.
Deaths ....................................................................................................................53
10.2.
Maintenance Part....................................................................................................53
10.2.1.
Overview................................................................................................................53
10.2.2.
Study Population Definitions ..................................................................................54
10.2.2.1.
Intent-to-Treat Population.......................................................................................54
10.2.2.2.
Response Evaluable Population ..............................................................................54
10.2.2.3.
Per-protocol (PP) Population ..................................................................................54
10.2.2.4.
Safety Population....................................................................................................54
10.2.3.
Sample Size and Power Considerations...................................................................54
10.2.4.
Background and Demographic Characteristics........................................................55
10.2.5.
Subject Disposition.................................................................................................56
10.2.6.
Efficacy Analysis....................................................................................................56
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10.2.3.
0.2.3.


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10.2.6.1.
Primary Endpoint....................................................................................................56
10.2.6.2.
Key Secondary Endpoints.......................................................................................57
10.2.6.3.
Other Secondary Efficacy Endpoints.......................................................................57
10.2.6.4.
Exploratory Endpoints............................................................................................58
10.2.7.
Safety Analysis.......................................................................................................58
10.2.7.1.
Adverse Events.......................................................................................................59
10.2.7.2.
Laboratory Assessments .........................................................................................59
10.2.8.
Study Therapy Termination ....................................................................................59
10.2.9.
Deaths ....................................................................................................................59
10.2.10.
Interim Analysis .....................................................................................................59
10.3.
Data Monitoring Committee ...................................................................................60
10.4.
Scientific Steering Committee ................................................................................60
11.
ADVERSE EVENTS..............................................................................................61
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................61
11.2.
Evaluation of Adverse Events.................................................................................61
11.2.1.
Seriousness.............................................................................................................61
11.2.2.
Severity / Intensity..................................................................................................63
11.2.3.
Causality ................................................................................................................63
11.2.4.
Duration .................................................................................................................64
11.2.5.
Action Taken..........................................................................................................64
11.2.6.
Outcome.................................................................................................................64
11.3.
Abnormal Laboratory Values..................................................................................64
11.4.
Pregnancy...............................................................................................................64
11.4.1.
Females of Childbearing Potential: .........................................................................64
11.4.2.
Male Subjects.........................................................................................................65
11.5.
Reporting of Serious Adverse Events......................................................................65
11.5.1.
Safety Queries ........................................................................................................66
11.6.
Expedited Reporting of Adverse Events..................................................................66
12.
DISCONTINUATIONS .........................................................................................67
12.1.
Study Treatment Discontinuation............................................................................67
12.2.
Study Discontinuation ............................................................................................67
12.3.
Subject Replacement ..............................................................................................68
13.
EMERGENCY PROCEDURES.............................................................................69
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12.1.
2.1.


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13.1.
Emergency Contact.................................................................................................69
14.
REGULATORY CONSIDERATIONS...................................................................70
14.1.
Good Clinical Practice............................................................................................70
14.2.
Investigator Responsibilities ...................................................................................70
14.3.
Subject Information and Informed Consent.............................................................70
14.4.
Confidentiality........................................................................................................71
14.5.
Protocol Amendments.............................................................................................71
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................71
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................72
14.8.
Closure of the Study ...............................................................................................72
15.
DATA HANDLING AND RECORDKEEPING.....................................................73
15.1.
Data/Documents .....................................................................................................73
15.2.
Data Management...................................................................................................73
15.3.
Record Retention....................................................................................................73
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................75
16.1.
Study Monitoring and Source Data Verification......................................................75
16.2.
Audits and Inspections............................................................................................75
17.
PUBLICATIONS ...................................................................................................76
18.
REFERENCES.......................................................................................................77
19.
APPENDICES........................................................................................................79
Appendix A: Response Evaluation Criteria in Solid Tumors (RECIST 1.1)...............................79
Appendix B: ECOG Performance Status Score..........................................................................83
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LIST OF TABLES
Table 1:
Blinded Radiology Assessment of Overall Response Rate  (ITT Population) ..........22
Table 2:
Blinded Radiology Assessment of Response Rate for Patients with 
Squamous or Non-squamous Histologies (ITT Subgroups).....................................22
Table 3:
Table of Events – Induction....................................................................................31
Table 4:
Table of Events – Maintenance and Cross-over.......................................................33
Table 5:
Permanent Dose Reductions for Hematologic and Neurologic Adverse 
Events and Dosing for Maintenance and Cross-over Parts of the Study...................46
Table 6:
Precision of the Estimate for a Proportion Given a Sample Size of 540...................51
Table 7:
Evaluation of Target Lesions ..................................................................................81
Table 8:
Evaluation of Non-target Lesions............................................................................81
3
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LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................29
&(/*(1(35235,(7$5<,1)250$7,21


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1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer-related deaths (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 recent advances in identifying optimal chemotherapy regimens, patients with 
advanced NSCLC continue to have a poor prognosis (especially those without identifiable 
biomarkers), with only 10% to 15% of those treated still alive after 2 years of diagnosis.
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 vs 
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). 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).
1.2.
nab-Paclitaxel
nab-Paclitaxel has been developed to reduce the toxicities associated with Taxol and the 
Cremophor EL/ethanol vehicle while maintaining or improving the chemotherapeutic effect of 
the drug. The Cremophor EL-free medium enables nab-paclitaxelto be given in a shorter 
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duration without the need for premedication to prevent solvent-related hypersensitivity reactions.
In addition, standard tubing and 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, pancreatic cancer and NSCLC. For NSCLC in the US, nab-Paclitaxel is approved for the 
treatment of patients with locally advanced or metastatic NSCLC, as first-line treatment in 
combination with carboplatin, in patients 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.
The Food and Drug Administration (FDA) approval of nab-paclitaxel was based on the 
evaluation of Phase I and II data (Rizvi, 2008; Socinski, 2010; Belani, 2008), as well as the 
pivotal Phase III study: A multicenter, randomized, open-label study was conducted in 1052 
chemonaive patients 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 or development of an unacceptable toxicity. The primary efficacy outcome measure 
was overall response rate 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 adenocarcinoma, 43% had 
squamous cell lung cancer, 76% were ECOG PS 1, and 73% were current or former smokers. 
Patients received a median of 6 cycles of treatment in both study arms. Patients in 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]. There 
was no statistically significant difference in the secondary endpoint OS between the two study 
arms.
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Table 1:
Blinded Radiology Assessment of Overall Response Rate 
(ITT Population)
Variable
Category/Statistic
ABI-007/
carboplatin
(N=521)
Taxol/
carboplatin
(N=531)
Response Rate 
Ratio
(pA/pT)
P-value
Patients with Confirmed Complete or Partial Overall Response
n (%)
170 (33%)
132 (25%)
1.313
0.005*
Confidence Interval (CI) a
28.6, 36.7
21.2, 28.5
1.082, 1.593
Complete Response
0
1 (< 1%)
Partial Response
170 (33%)
131 (25%)
Source Data on File
a 95% CI of response rate and 95.1% CI of response rate ratio.
Note: P-value is based on a chi-square test.
* Indicates p-value < 0.049
Per protocol, patients were stratified by NSCLC histology (squamous cell carcinoma vs
adenocarcinoma vs other histology). Subgroup analyses were performed to assess the influence 
of squamous vs non-squamous histology on the primary efficacy endpoint of overall response 
rate (the percentage of patients who achieved an objective confirmed CR or PR based on the 
blinded radiological review using RECIST response guidelines, Version 1.0). The proportion of 
patients with squamous cell carcinoma who responded was significantly higher for the 
ABI-007/carboplatin regimen relative to the Taxol/carboplatin regimen (41% vs 24%: pA/pT: 
1.680; p < 0.001). The proportion of patients with non-squamous cell carcinoma with a 
confirmed complete or partial overall response was comparable between the ABI-007 and 
Taxol/carboplatin arms (26% vs 25%: pA/pT: 1.034; p = 0.808).
Table 2:
Blinded Radiology Assessment of Response Rate for Patients with Squamous 
or Non-squamous Histologies (ITT Subgroups)
Prognostic Factor
Category/Statistic/N
ABI-007/
carboplatin
Taxol/
carboplatin
Response Rate 
Ratio (pA/pT)
P-value
Patients with Confirmed Complete 
or Partial Overall Response
Squamous cell carcinoma
94/229 (41%)
54/221 (24%)
1.680
< 0.001*
95% Confidence Interval
1.271, 2.221
Non-squamous cell carcinoma
76/292 (26%)
78/310 (25%)
1.034
0.808
95% Confidence Interval
0.788, 1.358
Abbreviations: ITT = intent-to-treat
Note: P value is based on a chi-square test.
* Indicates p-value < 0.05.
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
23
ABI-007-NSCL-003 Final: 27 Sep 2013
Adverse reactions were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. Patients in both treatment arms received a 
median of 6 cycles of treatment. The following common (≥ 10% incidence) adverse reactions 
were observed at a similar incidence in nab-paclitaxel plus carboplatin-treated and paclitaxel 
injection plus carboplatin-treated patients: 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).
Laboratory-detected abnormalities which occurred with a difference ≥5% for nab-paclitaxel plus 
carboplatin vs paclitaxel injection plus carboplatin (Grades1-4 [and G3-4]) are: anemia (98% vs 
91% [28% vs 7%]), neutropenia (85% vs 83% [47% vs 58%]) and thrombocytopenia (68% vs 
55% [18% vs 9%]).  
1.3.
Rationale for Development of nab-Paclitaxel as Maintenance 
Treatment in Squamous Cell NSCLC
Although significant advances have been made in the treatment options and outcomes of patients 
with non-squamous NSCLC, progress for patients with squamous cell NSCLC has been 
disappointing. Furthermore, the data of maintenance therapy that resulted in the FDA approval of 
pemetrexed (Alimta) and erlotinib (Tarceva), seems to confer benefit (and choice) primarily for 
non-squamous NSCLC patients.
Both Alimta studies as well as the Tarceva study demonstrated an overall survival benefit with 
maintenance vs. placebo (Paz-Arez, 2012; Tarceva package insert). However, both of the Alimta 
maintenance studies showed benefit in non-squamous patients only. Whereas Tarceva showed
significant benefit in the non-squamous cell NSCLC patients, only modest improvement was 
observed in squamous cell NSCLC patients (Neal, 2010).
To date there have been no randomized studies showing benefit of maintenance therapy in 
squamous NSCLC patients. Therefore, there is still an unmet medical need for maintenance 
treatment in squamous cell NSCLC. 
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there is st
here is stil


nab-paclitaxel
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2.
STUDY OBJECTIVES
2.1.
Primary Objective
The primary objective of the study is to evaluate PFS with nab-paclitaxel as maintenance 
treatment after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous 
cell NSCLC.
2.2.
Secondary Objectives 
The secondary objectives of the study are:
!
To evaluate the safety and tolerability of nab-paclitaxel as maintenance treatment 
after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous 
cell NSCLC.
!
To further assess the efficacy with nab-paclitaxel as maintenance treatment after 
response or SD with nab-paclitaxel plus carboplatin in subjects with squamous cell 
NSCLC, as measured by secondary efficacy endpoints.
2.3.
Exploratory Objectives
The exploratory objectives of the study are:
!
To determine baseline tumor characteristics which predict response and resistance to 
nab-paclitaxel/carboplatin during the Induction part of the study. 
!
To determine what changes in peripheral tumor characteristics during treatment are 
associated with acquisition of resistance in the subjects who had initial clinical 
benefit.
!
To evaluate the safety and efficacy of nab-paclitaxel as cross-over (re-induction)
treatment after progression during the Maintenance part of the study in subjects with 
squamous cell NSCLC. 
!
To assess healthcare resource utilization during the Maintenance part of the study.
!
To assess the LCSS and EQ5D.
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treatment 
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which
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resistance 
and efficacy
and efficacy
ression dur
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SCLC
SCLC. 
ltlthcare
hcare res
r
s the LCSS
the LCSS


nab-paclitaxel
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3.
STUDY ENDPOINTS
3.1.
Primary Endpoint
Progression free survival from randomization into the Maintenance part of the study.
3.2.
Secondary Endpoints
3.2.1.
Safety
Safety parameters including AEs and SAEs.
3.2.2.
Efficacy
!
Overall survival from randomization into the Maintenance part of the study.
!
Overall response rate during the Induction and Maintenance parts of the study.
3.3.
Exploratory Endpoints
!
Overall response rate and disease control rate of subjects in the Cross-over part of the 
study.
!
The correlation between pretreatment tumor characteristics and response and 
resistance to the study treatment determined using next-generation sequencing 
methods, immunohistochemistry, or other analysis methods.
!
The association between the changes in tumor characteristics and the acquisition of 
resistance to therapy from plasma samples taken at treatment failure during 
Maintenance.
!
The relationships between variants in subject pharmacogenomics, such as 
polymorphisms in enzymes involved in drug metabolism, and treatment efficacy and 
toxicity. 
!
Healthcare resource utilization during the Maintenance part of the study using a 
questionnaire including hospitalizations, emergency room visits, doctor or nurse 
visits, procedures, and/or additional medication.
!
Change in the LCSS and EQ5D.
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the study
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ange in the 
nge in th


nab-paclitaxel
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Confidential and Proprietary
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4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is a Phase III, randomized, open-label, cross-over, multi-center study of nab-paclitaxel plus 
BSC or BSC alone as maintenance treatment after response or SD with nab-paclitaxel plus 
carboplatin as induction in subjects with squamous cell NSCLC. Approximately 540 subjects 
with Stage IIIB/IV squamous cell NSCLC eligible to receive standard treatment of nab-paclitaxel
plus carboplatin for 4 cycles will be enrolled in the Induction part of the study. If after the 4 
cycles, the subject has a radiologically assessed CR, PR, or SD without clinical progression, they 
will be randomized (2:1) in the Maintenance part of the study to receive nab-paclitaxel plus BSC 
or BSC alone. BSC is defined as the best palliative care per investigator (including but not 
limited to: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, 
nutritional support, and/or focal external-beam radiation for control of pain, cough, dyspnea, or 
hemoptysis) excluding antineoplastic agents. Approximately 260 subjects will be evaluable for 
the primary endpoint of PFS in maintenance. Once a subject in the BSC arm during the 
Maintenance part of the study experiences radiologic progression of disease, they will be eligible 
to cross-over to receive nab-paclitaxel.
4.1.1.
Induction Part
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Approximately 540 subjects eligible for 
standard treatment with nab-paclitaxel plus carboplatin for 4 cycles will be enrolled, provided if 
all inclusion/exclusion criteria are complied within a 28-day screening period prior to Cycle 1 
Day 1.
Induction treatment will commence on Cycle 1 Day 1: 
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD, and has met all eligibility criteria, they will continue on to the Maintenance part 
of the study. If the subject has radiological or clinical PD, they will be discontinued from the 
study and will not be followed.
4.1.2.
Maintenance Part
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD without clinical progression, they will be screened for eligibility over a 7-day 
period. Subjects (approximately 260) who satisfy all inclusion/exclusion criteria, will be 
randomized 2:1 to receive either:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day cycle plus BSC until disease progression (see Section 8.3 for guidelines on 
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-003 Final: 27 Sep 2013
starting dose for the Maintenance part of the study if the subject had dose reduced 
during the Induction part of the study)
OR
!
BSC until disease progression
Maintenance therapy should start at the time of randomization. If this is not possible, a maximum 
of 7 days will be allowed from the date of randomization to the start date of Maintenance 
therapy. Subjects must start Maintenance therapy no earlier than 21 days and no later than 35
days from Day 1 of the fourth cycle of Induction therapy. 
Randomization will be stratified by disease stage (IIIB vs IV), response in induction (CR/PR vs 
SD), and performance status (0 vs 1).
4.1.3.
Cross-over 
A subject in the BSC arm during the Maintenance part of the study who experiences radiological 
progression of disease, will be eligible to cross-over to receive nab-paclitaxel 100 mg/m2 IV 
infusion over 30 minutes on Days 1 and 8 of each 21-day cycle until unacceptable toxicity or 
discontinuation for any other reason, if the benefit : risk is considered appropriate by the treating 
investigator (see Section 8.3 for guidelines on starting dose for the Cross-over part of the study if 
the subject had dose reduced during the Induction part of the study, and Sections 7.2 and 7.3 for 
eligibility). 
4.1.4.
Follow-up Period 
All subjects who discontinue from the Maintenance or Cross-over parts of the study for any 
reason other than withdrawal of consent, lost to follow-up, or death, will enter the Follow-up 
period that will have a visit 28 days after progression or discontinuation. Those subjects entering 
the follow up period without documented progression will continue to have CT scans in 
accordance with standard of care until documented progression of disease. Additionally, subjects 
will be followed for OS by phone approximately every 90 days for up to 1.5 year after final 
analysis of approximately 182 PFS events or approximately 218 deaths have been observed for 
the final OS analysis, whichever is earlier.
4.2.
Study Design Rationale
The results of promising activity with nab-paclitaxel in NSCLC, especially in squamous cell 
NSCLC, underscore the hypothesis for this Phase III study as a superiority trial to compare nab-
paclitaxel/BSC vs BSC as maintenance therapy in subjects with squamous cell NSCLC
(randomizing subjects with CR/PR/SD after Induction treatment with nab-paclitaxel/
carboplatin). The nab-paclitaxel regimen used for Induction will be in accordance with the FDA 
approved label, 100 mg/m2 administered once per week on Days 1, 8 and 15 of each 21-day
cycle with no break combined with carboplatin AUC = 6 mg*min/mL administered on Day 1 
every 21 days. Four cycles of doublet-chemotherapy is chosen as the cut-off, based on observed 
risk:benefit results that additional cycles of doublet chemotherapy did not confer significant 
advantages (Socinski, 2002); furthermore, 4 cycles of doublet-chemotherapy represents general 
trends of practice (Stinchcombe, 2009).
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-003 Final: 27 Sep 2013
The nab-paclitaxel regimen used for Maintenance will be 100 mg/m2 administered on Days 1 and 
8 of each 21-day cycle until progression (the actual starting dose may be adjusted as specified in 
Section 8.3). The nab-paclitaxel dosing regimen was reduced to Days 1 and 8 of each 21-day 
cycle in the Maintenance part of the study to decrease potential toxicity and possibly optimize 
tolerability of treatment and drug exposure in subjects. Sufficient subjects will be enrolled to 
provide adequate power to compare PFS. The safety and tolerability of nab-paclitaxel will be 
assessed.
&(/*(1(35235,(7$5<,1)250$7,21


nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
29
ABI-007-NSCL-003 Final: 27 Sep 2013
Figure 1:
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
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4.3.
Study Duration 
The Induction part of the study will last approximately 36 months to randomize sufficient 
subjects for the Maintenance part of the study. The total length of this Phase III study with 
Induction, Maintenance, Cross-over, and Follow-up is estimated to last approximately 5 years.
4.4.
End of Trial
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
study, or the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol and/or the 
Statistical Analysis Plan (SAP), whichever is the later date.
&(/*(1(35235,(7$5<,1)250$7,21
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nab-paclitaxel
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5.
TABLE OF EVENTS
Table 3:
Table of Events – Induction
CYCLE 1 and 3 (21-day)
CYCLE 2 and 4 (21-day)
Assessment
Screening/
Baseline
(up to 28 
days)
Day 1
(C3: ±2 
days)
Day 8
(±2 days)
Day 15
(±2 days)
Day 1
(±2 days)
Day 8
(±2 days)
Day 15
(±2 days)
Every 42 
days
(-3/+7 days)
Early
Treat-
ment 
Discon-
tinuation /
End of 4 
Cycles
Unsched-
uled
Informed Consent
X
-
-
-
-
-
-
-
-
-
Medical History
X
-
-
-
-
-
-
-
-
-
Prior Medication and Procedures
X
-
-
-
-
-
-
-
-
-
Serum β-hCGb
X
X
-
-
X
-
-
-
X
-
Complete Chest CT Scan (including 
adrenal gland) with contrast and any 
other studies required for tumor 
imagingc
X
-
-
-
-
-
X
X
Xa
Weight
X
X
X
X
X
X
X
-
X
Xa
Archived Tumor Tissue Sample for 
Biomarker (biopsy, surgical specimen, 
or other diagnostic tumor sample)
-
X (C1D1 
only)
-
-
-
-
-
-
-
-
Plasma for Biomarker Analyses 
-
X (C1D1 
only)
-
-
-
-
-
-
X
-
Blood for Pharmacogenomic Analyses
-
X (C1D1 
only)
-
-
-
-
-
-
-
-
Body Surface Area (BSA) Calculation 
and Heightd
X
-
-
-
-
-
-
-
-
Xa
ECOG status
X
X
-
-
X
-
-
-
X
Xa
Concomitant Medication/Procedures
X
X
X
X
X
X
X
X
X
Xa
Peripheral Neuropathy Assessmente
X
X
X
X
X
X
X
-
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nab-paclitaxel
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ABI-007-NSCL-003 Final: 27 Sep 2013
Table 3:
Table of Events – Induction (Continued)
CYCLE 1 and 3 (21-day)
CYCLE 2 and 4 (21-day)
Assessment
Screening/
Baseline 
(up to 28 
days)
Day 1
(C3: ±2 
days)
Day 8
(±2 days)
Day 15
(±2 days)
Day 1
(±2 days)
Day 8
(±2 days)
Day 15
(±2 days)
Every 42 
days
(-3/+7 days)
Early 
Treat-
ment 
Discon-
tinuation / 
End of 4 
Cycles
Unsched-
uled
Hematology and Serum Chemistry f
X
X
X
X
X
X
X
-
Xa
X
Adverse Event Evaluation
X
X
X
X
X
X
X
X
X
Xa
nab-paclitaxel Administration
-
X
X
X
X
X
X
-
-
-
Carboplatin Administration
-
X
-
-
X
-
-
-
-
-
LCSS and EQ5D
-
X
-
-
X
-
-
-
X
-
Electrocardiogram (ECG)
Will be done as per standard of care during the study and as clinically indicated, however results will not 
be routinely collected in the eCRFs, However if abnormal and clinically significant results, will be collected as AE or SAE and if scans 
show documented progression of disease will be collected on eCRF.
CT Scan of Head or Brain Magnetic 
Resonance Imaging (MRI)
Bone Scan (X-rays if needed)
Physical Examination
Vital Signs
C3: Cycle 3, eCRF: electronic Case Report Form, C1D1: Cycle 1 Day 1, AE: Adverse Event, SAE: Serious Adverse Event, ECOG: Eastern Cooperative Oncology Group, CT: Computed Tomography, 
b-HCG: beta human chorionic gonadotropin, RECIST: Response Evaluation Criteria in Solid Tumors, LCSS: Lung Cancer Symptom Scale, EQ5D: EuroQol 5D
a If clinically indicated.
b A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a Serum β-hCG pregnancy test must be performed to assess
eligibility at Screening/Baseline and within 72 hours of the first administration of study drug before beginning each new cycle. Note: the screening serum pregnancy test can be 
used as the test prior to Day 1 study therapy if it is performed within the 72-hour timeframe.
c All subjects must have a radiographically documented measurable tumor(s) by RECIST criteria: Complete chest CT scan (including adrenal gland) with and without contrast are
performed at Screening, every 42 days (-3/+7 days) while on-treatment (schedule based on calendar, not start of cycle), early termination, and if clinically indicated while on-
treatment. The methods of assessment chosen at baseline to follow tumors are to remain consistent throughout study duration. Scans will be archived as per institution standards.
d BSA calculated at baseline and recalculated if body weight changes by more than 10% from baseline.
e The occurrence of peripheral neuropathy should be reported by the investigator per protocol as an AE or SAE.
f Laboratory assessments will be done prior to each nab-paclitaxel treatment by local laboratories as per standard of care during the study and as clinically indicated. The results 
from laboratory assessments will be captured as per Section 6.18.
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
33
ABI-007-NSCL-003 Final: 27 Sep 2013
Table 4:
Table of Events – Maintenance and Cross-over
EVERY CYCLE
(21-day)
Assessment
Screening/ 
Baseline
(up to 14
days)
Day 1
(±2 days, 
except 1st
cycle)
Day 8
(±2 days)
Every 42 
days
(-3/+7 days)
Early 
Treatment 
Discon-
tinuation /
Disease
Progression
28-day 
Follow-up 
visit
Survival 
(every 90 
days) up 
to as 
specified 
in Section 
6.20
Unsched-
uled
Serum β-hCGb
X
X
-
-
X
-
-
-
Complete Chest CT Scan (including adrenal 
gland) with contrast and any other studies 
required for tumor imaging c
Xg
-
-
X
X
-
-
Xa
Weight
X
X
X
-
X
X
-
Xa
Plasma for Biomarker Analyses
-
-
-
X
-
-
-
Body Surface Area (BSA) Calculation and 
Heightd
X
-
-
-
-
-
-
Xa
ECOG status
Xf
X
-
-
X
-
-
Xa
Concomitant Medication/Procedures
X
X
X
X
X
X
X
Xa
Peripheral Neuropathy Assessmente
X
X
X
-
X
X
-
Xa
Hematology and Serum Chemistry h
X
X
X
-
X
X
-
Xa
Adverse Event Evaluation
X
X
X
X
X
X
-
Xa
nab-paclitaxel Administration
-
X
X
-
-
-
-
Survival phone call 
-
-
-
-
-
-
X
-
Healthcare Resource Utilization 
Questionnaire
-
X
-
-
X
-
-
-
LCSS and EQ5D
-
X
-
-
X
-
-
-
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
34
ABI-007-NSCL-003 Final: 27 Sep 2013
Table 4:
Table of Events – Maintenance and Cross-over (Continued)
EVERY CYCLE
(21-day)
Assessment
Screening/ 
Baseline
(up to 14
days)
Day 1
(±2 days, 
except 1st
cycle)
Day 8
(±2 days)
Every 42 
days
(-3/+7 days)
Early 
Treatment 
Discon-
tinuation / 
Disease 
Progression
28-day 
Follow-up 
visit
Survival 
(every 90 
days) up 
to as 
specified 
in Section 
6.20
Unsched-
uled
Electrocardiogram (ECG)
Will be done as per standard of care during the study and as clinically indicated, however results will not 
be routinely collected in the eCRFs, However if abnormal and clinically significant results, will be collected as AE or SAE and if 
scans show documented progression of disease will be collected on eCRF.
CT Scan of Head or Brain Magnetic 
Resonance Imaging (MRI)
Bone Scan (X-rays if needed)
Physical Examination
Vital Signs
C1: Cycle 1, eCRF: electronic Case Report Form, AE: Adverse Event, SAE: Serious Adverse Event, ECOG: Eastern Cooperative Oncology Group, CT: Computed Tomography, b-HCG: beta human 
chorionic gonadotropin, LCSS: Lung Cancer Symptom Scale, EQ5D: EuroQol 5D 
a If clinically indicated.
b A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a Serum β-hCG pregnancy test must be performed to assess subject
eligibility at Screening/Baseline and within 72 hours of the first administration of study drug before beginning each new cycle. Note; the screening serum pregnancy test can be 
used as the test prior to Day 1 study therapy if it is performed within the 72-hour timeframe.
c Complete chest CT scan (including adrenal gland) with and without contrast is performed at baseline, every 42 days (-3/+7 days) while on-treatment (schedule based on calendar, 
not start of cycle), early termination, and if clinically indicated while on-treatment. The methods of assessment chosen at baseline to follow tumors are to remain consistent 
throughout study duration. Scans will be archived as per institution standards. Those subjects entering the follow up period without documented progression will continue to 
have CT scans in accordance with standard of care until documented progression of disease.
d BSA calculated at baseline and recalculated if body weight changes by more than 10% from baseline.
e The occurrence of peripheral neuropathy should be reported by the investigator per protocol as an AE or SAE.
f The ECOG performance status must be 0 or 1 for subjects to start maintenance treatment.
g Induction End of Cycle 4 information may serve as baseline for Maintenance.
h Laboratory assessments will be done prior to each nab-paclitaxel treatment by local laboratories as per standard of care during the study and as clinically indicated. The results 
from laboratory assessments will be captured as per Section 6.18.
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-003 Final: 27 Sep 2013
6.
PROCEDURES
Subjects will be provided with a written informed consent form (ICF), given the opportunity to 
ask any questions concerning the study, and will sign an ICF prior to participating in any study 
procedures. After giving written informed consent, subjects will undergo a screening period to be 
assessed for eligibility. All subjects who sign an ICF must be screened into the Interactive Voice 
Response System (IVRS) immediately upon signature on the document. Subjects who do not 
meet the inclusion/exclusion criteria will be considered screening failures and will not be eligible 
for the study. Subjects that have satisfied all eligibility criteria after the screening period will be 
eligible to be enrolled. Subjects who screen fail may re-screen up to 3 times and an ICF will need 
to be signed at each re-screen, 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).
6.1.
Medical History
A complete medical history including, but not limited to, evaluation for past (up to 5 years) or 
present cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine, 
lymphatic, hematological, immunologic, dermatological, psychiatric, genitourinary, obstetrical, 
surgical history or any other diseases or disorders will be performed at Screening. 
6.2.
Prior Medications/Procedures
All prior medications/procedures within 28 days of time of signature on the ICF should be 
recorded. All NSCLC-related prior medications/procedures should be recorded regardless of 
time.
6.3.
Pregnancy Testing
Serum pregnancy test with sensitivity of at least 25 mIU/mL is to be obtained in females of 
childbearing potential (FCBP) at Screening for Induction, Maintenance and Cross-over. A serum 
pregnancy test must be done within 72 hours prior to Cycle 1 Day 1 of starting study therapy, 
repeated before beginning each new cycle, and at discontinuation or end of treatment. The 
subject may not receive treatment until the investigator has verified that the result of the 
pregnancy test is negative. See inclusion criteria for pregnancy testing requirements. Any 
pregnancies that occur in women who have received study drug must be immediately reported to 
Celgene Drug Safety (See Section 11.4).
6.4.
Complete Chest Computed Tomography (CT) Scan (including 
adrenal gland) With and Without Contrast
Complete Chest CT Scan (including adrenal gland) with and without contrast and any other 
studies required for tumor imaging will be done at Screening, every 42 days (-3/+7 days) 
(schedule for scans will be based on calendar, not start of cycle), and at Early Treatment 
Discontinuation/End of Cycle 4 during the Induction part of the study. During the Maintenance 
and Cross-over parts of the study scans will be done every 42 days (-3/+7 days) (schedule for 
scans will be based on calendar, not start of cycle) and at Early Treatment 
Discontinuation/Disease Progression. Additional CTs may be done at any time during the study 
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
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if clinically indicated. CT scans are preferred, however MRI would be acceptable. The same 
scanning modality for lesion assessment should be used throughout the study. All scans and 
reports should be archived as per institution standards.
6.5.
Weight
Weight will be collected at every visit during the Induction, Maintenance, and Cross-over parts 
of the study. Additional weights may be collected at any time during the study as needed.
6.6.
Body Surface Area (BSA) Calculation and Height
BSA and height will be collected and calculated at Screening during Induction, Maintenance, 
and Cross-over parts of the study. BSA may be recalculated if body weight changes by more 
than 10% from baseline.
6.7.
ECOG Performance Score
ECOG performance score will be collected at Screening, Day 1 of every cycle and at Early 
Treatment Discontinuation/End of Cycle 4 during the Induction part of the study. During the 
Maintenance and Cross-over parts of the study, ECOG performance score will be collected at 
Screening, Day 1 of every cycle, and at Early Treatment Discontinuation/Disease Progression. 
Additional ECOG may be collected at any time during the study as needed.
6.8.
Concomitant Medications/Procedures
All subjects will have concomitant medications and procedures recorded from the time of 
signature on the ICF until progression during the Induction part of the study or the 28-day 
follow-up visit during the Maintenance part of the study or after Cross-over. Only NSCLC 
associated concomitant medications/procedures will be recorded, including BSC. During 
survival follow-up, anti-cancer treatment information will be collected, if available.
6.9.
Peripheral Neuropathy Assessment
Peripheral neuropathy assessment will be done from the time of signature on the ICF until 
progression during the Induction part of the study or the 28-day follow-up visit during the 
Maintenance part of the study or after Cross-over. Additional peripheral neuropathy assessments 
may be done at any time during the study as needed.
6.10.
Adverse Event Reporting
All subjects will have AEs recorded from time of signature on the ICF until progression during 
the Induction part of the study or the 28 days after the last dose of study drug during the 
Maintenance part of the study or after Cross-over, including any unscheduled visits. See 
Section 11 for details. 
6.11.
Lung Cancer Symptom Scale Questionnaire and EQ5D
The Lung Cancer Symptom Scale (LCSS) and (EQ-5D) questionnaires will be used to measure 
quality of life (QoL) for subjects in the trial. The LCSS is a 9 question analysis the subject
completes using a visual analogue scale (VAS) to denote intensity of a symptom. The EQ-5D 
ance
nce, , 
by more
by more
y cycle
ycle and 
an
of the study
of the stud
ce score wi
e score w
ntinuat
inua ion/D
tudy
udy as nee
as nee
y
res
re
nd procedur
nd procedur
he Induct
Inductioio
of the study
of the stud
edures
edures will
will
nt informa
t informa
opathy As
opathy A
ment will b
ment w
duct
ductioion par
n 
e study
e stud or r
y
time d
me durin
urin
d
dverse Ev
verse E
cts will hav
will hav
duction part
duction part
ntenance p
ntenance p
ecti
ection
on 11
11 f
11.
11


nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
37
ABI-007-NSCL-003 Final: 27 Sep 2013
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 cycle, and 
at Early Treatment Discontinuation/End of Cycle 4 during the Induction part of the study. During 
the Maintenance and Cross-over parts of the study, at Day 1 of every cycle, and at progression of 
disease. The quality of life data generated from these questionnaires will be analyzed per the 
description in the SAP.
6.12.
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 cycle, and at progression of disease during the Maintenance and 
Cross-over parts of the study.
6.13.
Electrocardiogram 
Electrocardiograms (ECGs) will be done as per standard of care during the study and as 
clinically indicated, however results will not be collected in the eCRFs (if results are abnormal 
and clinically significant at Screening, they will be recorded as medical history, and if results are 
abnormal and clinically significant after Screening, they will be recorded as AE or SAE).
6.14.
CT Scan of Head or Brain Magnetic Resonance Imaging (MRI)
CT scan of head or brain MRI will be done as per standard of care during the study and as 
clinically indicated, however results will not be collected in the eCRFs. If scans show  
progression of disease, this information will be collected on eCRF.
6.15.
Bone Scans and X-rays
Bone scans and x-rays will be done as per standard of care during the study and as clinically 
indicated, however results will not be collected in the eCRFs. If scans show progression of 
disease, this information will be collected on eCRF.
6.16.
Physical Examinations
Physical examinations will be done as per standard of care during the study and as clinically 
indicated, however results will not be collected in the eCRFs (if results are abnormal and 
clinically significant at Screening, they will be recorded as medical history, and if results are 
abnormal and clinically significant after Screening, they will be recorded as AE or SAE).
6.17.
Vital Signs
Vital signs will be done as per standard of care during the study and as clinically indicated, 
however results will not be collected in the eCRFs (if results are abnormal and clinically 
significant at Screening, they will be recorded as medical history, and if results are abnormal and 
clinically significant after Screening, they will be recorded as AE or SAE). 
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
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6.18.
Laboratory Assessments
Laboratory assessments will be done prior to each nab-paclitaxel treatments by local laboratories 
as per standard of care during the study and as clinically indicated, however results will not be 
collected in the eCRFs unless they are determined to be clinically significant laboratory 
abnormalities. 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. Abnormal and 
clinically significant laboratory assessments at Screening will be recorded as medical history, 
and after Screening, as AE or SAE (clinically significant laboratory abnormalities at Screening 
may result in a subject being ineligible for the study and should not be captured as an AE). If a 
clinically significant laboratory abnormality is captured as medical history, AE, or SAE, the 
specific laboratory parameter(s) should be recorded on the laboratory assessments CRF. Any 
abnormal values that persist should be followed at the discretion of the Investigator. The 
Investigator should file all copies of the reports, including faxes with the subject’s medical chart.
6.19.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) 
If archival tumor biopsy blocks or (preferably) surgical specimens from subjects with prior 
resections are available, 10 or more slides of at least 4 um thickness will be collected at Cycle 1 
Day 1 of Induction. Additionally a core of an area representing viable tumor epithelium be 
collected from the block. If the amount of tumor tissue available is not sufficient, fewer slides 
may be collected. 
If a fine needle aspirate (FNA) specimen is available, slides of at least 4 um thickness will be 
collected with the goal of obtaining at least 100,000 cells (preferably more) of material. If 
sufficient material cannot be collected, fewer slides/cells may be collected.
If only other types of diagnostic samples such as endoscopies, lavage, or sputum are available, 
this material should be optionally collected when possible, and collection is strongly encouraged 
when tissue such as endoscopy samples with multiple needle passes exists in quantities 
comparable to a core biopsy. In this instance, 10 slides and a core sample of tumor tissue should 
be collected as per biopsy and surgical samples above. 
Plasma for biomarker analyses will be collected on Day 1 of Cycle 1 during Induction and at 
progression during the Maintenance and Cross-over parts of the study. When progression occurs 
during Induction and before Cycle 4, a plasma sample will be collected at the time of study 
withdrawal.
Peripheral blood will be collected for pharmacogenomic analyses on Cycle 1 Day 1 of Induction.
This sample will be collected in a CPT tube and shipped on dry ice to the central lab for 
processing to Peripheral Blood Mononuclear Cells (PBMC) and stored as a frozen pellet.
Types of techniques planned to be used for tumor and blood analyses include:
!
Gene expression by RNA sequencing
!
Immunohistochemistry 
!
DNA sequencing
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nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-003 Final: 27 Sep 2013
Details regarding the collection, storage, and shipment of the samples are given in the Laboratory 
Manual.
6.20.
Survival
After discontinuation from the Maintenance or Cross-over part of the study, the subjects will be 
followed for survival by phone approximately every 90 days for up to 1.5 year after final 
analysis of approximately 182 PFS events, or approximately 218 deaths have been observed for 
the final OS analysis, whichever is earlier. The subjects will also be asked questions of other 
medications they may be taking for their NSCLC. 
&(/*(1(35235,(7$5<,1)250$7,21


nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-003 Final: 27 Sep 2013
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Subjects with squamous cell NSCLC stage IIIB or IV with no prior chemotherapy for metastatic 
disease who are ≥ 18 years old will be eligible for this study. The Induction part of the study will 
enroll approximately 540 subjects. Based on results from the nab-Paclitaxel Phase 3 NSCLC 
development study (Protocol CA031) it is estimated that approximately 260 subjects with CR, 
PR, or SD from the Induction part of the study will be randomized to the Maintenance part of the 
study. Enrollment into the Induction part of the study will be monitored and adjusted to ensure 
that approximately 260 subjects are randomized into the Maintenance part of the study. The 
study will be conducted at approximately 120 sites in the United States.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the Induction, Maintenance, and 
Cross-over parts of the study (except if specified at study entry only):
General and Demographics
1. Age ≥ 18 years of age at the time of signing the ICF.
2. Understand and voluntarily provide written consent to the ICF prior to conducting any 
study related assessments/procedures. 
3. Able to adhere to the study visit schedule and other protocol requirements
Disease Specific
4. Histologically or cytologically confirmed Stage IIIB or IV squamous cell NSCLC at 
study entry.
5. No prior history of other malignancies, except basal cell carcinoma of the skin, squamous 
cell carcinoma of the skin, or carcinoma in situ of the cervix.
6. Radiographically documented measurable disease at study entry (as defined in Appendix 
A; lesions in previously irradiated areas [or areas with local therapy] should not be 
selected as target lesions, unless there has been demonstrated progression in the lesion).
7. No prior chemotherapy for the treatment of metastatic disease at study entry. Adjuvant
chemotherapy is permitted providing cytotoxic chemotherapy was completed 12 months 
prior to starting the study 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.
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nab-paclitaxel
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Celgene Corporation
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ABI-007-NSCL-003 Final: 27 Sep 2013
12. Total bilirubin ≤ 1.5 × ULN except in cases of Gilbert’s disease and liver metastases. 
13. Creatinine ≤ 1.5 mg/dL.
14. Expected survival of > 12 weeks for the Induction part of the study.
15. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
16. For Maintenance part of the study, subjects must have received at least one dose of nab-
paclitaxel in each of the 4 cycles during Induction 
Pregnancy 
17. Females of childbearing potential [defined as a sexually mature woman who (1) have not 
undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy 
(the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for 
at least 24 consecutive months (ie, has had menses at any time during the preceding 24 
consecutive months)] must:
a.
Have a negative pregnancy test as verified by the study doctor prior to starting study 
therapy. She must agree to ongoing pregnancy testing during the course of the study, 
and after end of study therapy. This applies even if the subject practices true 
abstinence* from heterosexual contact.
b. Either commit to true abstinence* from heterosexual contact (which must be reviewed 
on a monthly basis) or agree to use, and be able to comply with, effective 
contraception without interruption, 28 days prior to starting study drug, during the 
study therapy (including dose interruptions), and for 3 months after discontinuation of 
study therapy. 
Male subjects must:
c.
practice true abstinence* or agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the study, 
during dose interruptions and for at least 3 months following study drug 
discontinuation, even if he has undergone a successful vasectomy. 
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic 
abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception].
18. Females must abstain from breastfeeding during study participation and 3 months after IP 
discontinuation.
7.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment into the Induction, 
Maintenance, or Cross-over parts of the study (except if specified at study entry only):
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 ≥
42 days prior to signing ICF).
2. Only evidence of disease is non-measurable at study entry.
3. Preexisting peripheral neuropathy of Grade 2, 3, or 4 (per CTCAE v4.0).
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4. Venous thromboembolism within 6 months prior to signing ICF.
5. Current congestive heart failure (New York Heart Association class II-IV).
6. Myocardial infarction (MI) within 6 months prior to signing ICF.
7. Treatment with any investigational product within 28 days prior to signing ICF.
8. History of allergy or hypersensitivity to nab-paclitaxel or carboplatin.
9. Currently enrolled in any other clinical protocol or investigational trial that involved 
administration of experimental therapy and/or therapeutic devices.
10. Any other clinically significant medical condition and/or organ dysfunction that will 
interfere with the administration of the therapy according to this protocol.
11. Any condition including the presence of laboratory abnormalities, which places the 
subject at unacceptable risk if he/she were to participate in the study.
12. Any condition that confounds the ability to interpret data from the study.
13. Pregnant and nursing females.
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nab-paclitaxel
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ABI-007-NSCL-003 Final: 27 Sep 2013
8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Investigational Product(s)
Induction 
Subjects will receive open-label nab-paclitaxel and carboplatin during the Induction part of the 
study as non-investigational products and will not be supplied by Celgene. Investigative sites 
will use standard of care (commercially available) product via prescription.
Maintenance and Cross-over
Subjects will be randomized to receive nab-paclitaxel plus BSC or BSC alone during the 
Maintenance part of the study. Once a subject in the BSC alone arm during the Maintenance part 
of the study experiences radiologic progression of disease, they will be eligible to cross-over to 
receive nab-paclitaxel. The nab-paclitaxel used in the Maintenance and Cross-over parts of the 
study is designated as IP and will be packaged and supplied by Celgene Corporation. 
The preparation for IV administration procedures should be followed as per package insert.
8.1.1.
nab-Paclitaxel
nab-Paclitaxel will be supplied by the Sponsor, Celgene Corporation, for the Maintenance and 
Cross-over parts of the study in single-use vials in single count cartons. Each single-use 50 mL 
vial will contain paclitaxel (100 mg) and approximately 900 mg human albumin as a stabilizer.
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, the time of reconstitution should be recorded to 
ensure compliance with the 8 hour requirement. Both forms should be stored in an area free of 
environmental extremes and must 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-cyclobutanedicarboxylato
(2-)0,0’]-,(SP-4-2). Carboplatin is a crystalline powder with the molecular formula of 
C6Hl2N204Pt and a molecular weight of 371.25. It is soluble in water at a rate of approximately 
14 mg/mL, and the pH of a 1% solution is 5 to 7. It is virtually insoluble in ethanol, acetone, and
dimethylacetamide.
For additional information about carboplatin storage, preparation, and administration please refer 
to the package insert. 
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8.2.
Treatment Administration and Schedule
Induction
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Approximately 540 subjects will be treated 
with nab-paclitaxel plus carboplatin for 4 cycles.
Induction treatment will commence on Day 1, in accordance with standard of care of 1st line 
treatment of metastatic NSCLC: 
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-Paclitaxel infusion
Maintenance Part
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD without clinical progression, they will be randomized 2:1 (approximately 260
subjects) to receive:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day cycle plus BSC until disease progression (the actual starting dose may be 
adjusted as specified in Section 8.3)
OR
!
BSC until disease progression
Maintenance therapy should start at the time of randomization. If this is not possible, a maximum 
of 7 days will be allowed from the date of randomization to the start date of Maintenance 
therapy. Subjects must start Maintenance therapy no earlier than 21 days and no later than 35
days from Day 1 of the fourth cycle of Induction therapy.
Cross-over Part
A subject in the BSC arm during the Maintenance part of the study experiences radiologic 
progression of disease, they will be eligible to cross-over to receive nab-paclitaxel 100 mg/m2 IV 
infusion over 30 minutes on Days 1 and 8 of each 21-day cycle until unacceptable toxicity or 
discontinuation for any other reason, if the benefit : risk is considered appropriate by the treating 
investigator (see Section 8.3 for guidelines on starting dose for the Cross-over part of the study if 
the subject had dose reduced during the Induction part of the study, and Sections 7.2 and 7.3 for 
eligibility). 
Subjects may receive BSC as needed per Investigator discretion and should be recorded.
All IP will be administered by the clinical site and administration will be documented in the 
study source record.
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nab-paclitaxel
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8.3.
Dose Modifications
Subjects will be evaluated for AEs at each visit with the NCI CTCAE v4.0 used as a guide for 
the grading of severity.  The dose of nab-paclitaxel and carboplatin for each subject will be 
modified following toxicity as described in Table 5.
Subjects who experience any of the adverse drug reactions in Table 5 will be dose reduced as per 
Table 5 during the Induction, Maintenance, or Cross-over parts of the study. If a subject is dose 
reduced in the Induction part of the study, please refer to Table 5 for guidelines on dose and 
schedule for the Maintenance and Cross-over parts of the study.
!
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, on Day 1 of any 
cycle, withhold treatment until the ANC recovers to at least 1500 cells/mm3 and the 
platelet count recovers to at least 100,000 cells/mm3. On Days 8 and 15 the ANC 
should recover to at least 500 cells/mm3 and platelet count of at least 50,000 
cells/mm3. When dosing is resumed, the subject should be dosed at the next lower 
dose level of nab-paclitaxel and carboplatin as outlined in Table 5.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-
paclitaxel and carboplatin at reduced doses (Table 5) when peripheral neuropathy 
improves to Grade 1 or completely resolves.
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Table 5:
Permanent Dose Reductions for Hematologic and Neurologic Adverse Events and Dosing for Maintenance and 
Cross-over Parts of the Study
Dose Modification During Induction, Maintenance and Cross-over
Starting Dose 
Maintenance
Starting Dose 
Cross-over
Adverse Drug Reaction
Occurrence
Weekly nab-
paclitaxel Dose 
(mg/m2)
Every 21-Days
Carboplatin 
Dose (AUC 
mg•min/mL)
nab-paclitaxel 
Dose (mg/m2) 
Days 1 and 8 of 
each 21-day 
Cycle
nab-paclitaxel 
Dose (mg/m2) 
Days 1 and 8 of 
each 21-day Cycle
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
If subject at 100, 75 or 50 at end of
Induction and ANC > 1500/mm3, will 
start at 100, 100 or 75 respectively
during Maintenance and Cross-over
Second
50
3
Third
Discontinue Treatment
Platelet count < 50,000/mm3
First
75
4.5
If subject at 100 or 75 at end of
Induction and platelet > 100,000/mm3, 
will start at 100 during Maintenance 
and Cross-over 
Second
Discontinue Treatment
Sensory Neuropathy Grade 3 or 4
First
75
4.5
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Induction and Grade 1 or no peripheral 
neuropathy, will start at 100, 100 or 75
respectively during Maintenance and 
Cross-over
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50
3
Third
Discontinue Treatment
ANC: Absolute Neutrophil Count
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8.4.
Method of Treatment Assignment
The Induction, Maintenance and Cross-over parts of the study are open-label. In the Maintenance 
part of the study, subjects will be randomized 2:1 to nab-paclitaxel plus BSC or BSC alone. 
Enrollment/randomization will occur via IVRS for all parts of the study. 
8.5.
Packaging and Labeling
The label(s) for IP (nab-paclitaxel) will include Sponsor name, address and telephone number, 
the protocol number, IP name, dosage form and strength (where applicable), amount of IP per 
container, lot number, expiry date (where applicable), medication identification/kit number, 
dosing instructions, storage conditions, and required caution statements and/or regulatory 
statements as applicable. Additional information may be included on the label as applicable per 
local regulations.
8.6.
Investigational Product Accountability and Disposal
Celgene (or designee) will review with the Investigator and relevant site personnel the process 
for IP return, disposal, and/or destruction including responsibilities for the site vs. Celgene (or 
designee).
Celgene will instruct the Investigator on the return, disposal and/or destruction of IP and/or 
medical device materials if applicable. Only completely unused IP vials should be retained by 
the site until a representative from Celgene or other Celgene-designated personnel have 
completed an inventory. Partially used an completely used vials should be destroyed according to 
local guidelines, and disposition should be recorded on the Investigational Drug Accountability 
Record Form.
The investigator, or designee, shall record the dispensing of IP to subjects in an IP accountability 
record. The IP record will be made available to Celgene, or other authorized Celgene-designated 
monitoring personnel for the purpose of accounting for the IP supply. Inspections of the IP 
supply for inventory purposes and assurance of proper storage will be conducted as necessary. 
Any significant discrepancy will be recorded and reported to Celgene or their designee and a 
plan for resolution will be documented.
Investigational product will not be loaned or dispensed by the investigator to another investigator 
or site. Under certain circumstances, and with sponsor permission, cooperative groups may 
manage IP between locations within their network as clinical trial agreement and local guidelines 
permit.
8.7.
Investigational Product Compliance
All IP will be administered only by study site personnel and accurate recording of all IP 
administration will be made in the appropriate section of the subject’s eCRF and source 
documents.
8.8.
Overdose
Overdose, as defined for this protocol, refers to nab-paclitaxel or carboplatin dosing only.
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nab-paclitaxel
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Celgene Corporation
Confidential and Proprietary
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On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel or carboplatin to a given subject, regardless of any associated adverse events or 
sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. See 
Section 11.1 for the reporting of adverse events associated with overdose.
&(/*(1(35235,(7$5<,1)250$7,21


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9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
All supportive care is permitted. 
9.2.
Prohibited Concomitant Medications and Procedures
Other antineoplastic agents or IP other than what is specified in the protocol is prohibited.
9.3.
Required Concomitant Medications and Procedures
Not applicable.
&(/*(1(35235,(7$5<,1)250$7,21


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10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the Induction and 
Maintenance parts of the study are described below by study part. Although some definitions for 
the efficacy and safety endpoints, and the analysis populations are the same for both parts of the 
study, they are repeated in the respective section to ensure that each part is self-contained.
Furthermore, while key analyses for the primary and key secondary endpoints are described in 
this section, additional analyses of these endpoints as well as exploratory endpoints will be 
described in details in the SAP.
10.1.
Induction Part
10.1.1.
Overview
This is the open-label, single-arm, Induction part of the study. Subjects receiving nab-paclitaxel 
100 mg/m2 administered weekly followed by carboplatin at AUC = 6 mg*min/mL on Day 1 of 
each cycle, repeated every 21 days, for 4 cycles will be enrolled. Subjects will have CT scans 
performed every 42 days (-3/+7 days). At the end of the 4 cycles, subjects who achieve a 
radiologically assessed CR, PR, or SD without clinical progression based on the Investigator’s 
evaluation using RECIST 1.1 guidelines, and meet inclusion/exclusion criteria will be 
randomized in the Maintenance part of the study.
An independent DMC will be established to monitor the study conduct. Details will be provided 
in the DMC charter.
10.1.2.
Study Population Definitions
10.1.2.1.
Intent-to-Treat Population
The primary efficacy analysis will be performed on the ITT population, which includes all 
enrolled subjects regardless of whether the subject receives any dose of nab-paclitaxel or has any 
efficacy assessments collected.
10.1.2.2.
Safety Population
The safety population will be the analysis population for all safety/ tolerability analyses. The 
safety population includes all subjects enrolled who received at least 1 dose of study treatment. 
Only subjects with clear documentation that no study treatment was administered will be 
excluded from the safety population. 
10.1.3.
Sample Size and Power Considerations
Approximately 540 subjects will be enrolled in the Induction part of the study. This sample size 
is expected to provide approximately 260 subjects eligible for randomization in the Maintenance 
part.   
In the nab-Paclitaxel Phase 3 NSCLC development study (Protocol CA031), 42% (13/31) and 
63% (125/198) of the squamous subjects from the North American and ex-North American sites, 
respectively, were progression free after 4 cycles of treatment and remained in the study in Cycle 
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art.


nab-paclitaxel
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5 and beyond. To be conservative, it is assumed that approximately 50% (270/540) of the 
subjects in the Induction part of this study will meet the radiologic and clinical progression free 
criteria at the end of Cycle 4. Furthermore, it is expected that approximately 4% of these 270
subjects will not meet the other inclusion/exclusion criteria for the Maintenance part, yielding a 
total of approximately 260 subjects entering the Maintenance part of the study.
The actual number of subjects that will be enrolled in the Induction part will be monitored on an 
ongoing basis and adjusted to ensure that the target number of subjects for the Maintenance part 
is attained. Enrollment of the Induction part, therefore, could be discontinued early or extended 
beyond the planned number of 540 subjects.
The ORR is the secondary endpoint in the Induction part. The point estimate and the associated 
two-sided 95% confidence interval will be calculated for this endpoint. No multiplicity 
adjustment will be made for this endpoint as no formal inferential testing will be performed.
The percentage of subjects with an AE of Grade 3 or higher peripheral neuropathy will be 
captured along with the associated two-sided 95% confidence interval without inferential testing.
Table 6 below demonstrates the precision of the estimate for a proportion that can be attained 
given a sample size of 540. For example, for a hypothetical ORR rate of 40% at the end of Cycle 
4, the half-width of the associated two-sided 95% confidence interval will be 4.1%, and the 
estimated 95% confidence interval will be (35.9%, 44.1%).
Table 6:
Precision of the Estimate for a Proportion Given a Sample Size of 540
Endpoint
Hypothetical Event Rate
Half Widtha of 
95% Confidence 
Interval
two-sided 95% 
Confidence Intervala
Overall Response Rate
35%
4.0%
(31.0% to 39.0%)
40%
4.1%
(35.9% to 44.1%)
45%
4.2%
(40.8% to 49.2%)
Peripheral Neuropathy
≥ Grade 3
5%
1.8%
(3.2% to 6.8%)
10%
2.5%
(7.5% to 12.5%)
15%
3.0%
(12.0% to 18.0%)
a Estimated based on normal approximation.
10.1.4.
Background and Demographic Characteristics
The baseline characteristics of all subjects enrolled 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. Medical 
history data will be summarized using frequency tabulations by system organ class and preferred 
term.
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10.1.5.
Subject Disposition
Subject disposition including the number and percent of subjects enrolled, randomized, treated, 
and the primary reason for discontinuation of therapy will be summarized by study site. Protocol 
deviations will be summarized using frequency tabulations.
10.1.6.
Efficacy Analysis
10.1.6.1.
Primary Purpose
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. There is no formal statistical analysis 
planned for this purpose. Subjects who attain a radiologically assessed CR, PR, or SD without 
clinical progression according to the investigator’s assessment of the scan performed at the end 
of Cycle 4, based on RECIST 1.1 guidelines, and satisfy the inclusion/exclusion criteria will be 
eligible to be randomized into the Maintenance part of the study.  
10.1.6.2.
Secondary Endpoints
10.1.6.2.1. Overall Response Rate 
The percentage of subjects who achieve an overall complete or partial response (ORR) according 
to RECIST 1.1 guidelines as determined by the investigator and confirmed by repeat assessments 
performed no less than 28 days after the criteria for response were first met will be calculated.
The associated two-sided 95% CI of the ORR will be presented.
Given that the confirmation CT-scan for the ORR could be taken after the start of the 
Maintenance part in which subjects will be receiving either nab-paclitaxel plus BSC or BSC
alone, the ORR will be reported for all subjects enrolled as 1 group, and also by the Maintenance 
treatment regimen, if necessary.
It is important to note that the Induction part is analogous to a 4-cycle fixed duration study with 
all subjects exiting this part prior to or at the end of Cycle 4. Therefore, the analysis results for 
all secondary efficacy endpoints should be interpreted accordingly.
10.1.7.
Safety Analysis
All subjects who take at least 1 dose of nab-paclitaxel will be included in the safety analyses. 
Adverse events will be summarized by worst severity grade. AEs, as well as treatment-emergent 
AEs, will be summarized by system organ class, and preferred term. nab-Paclitaxel-related 
adverse events, adverse events leading to death or to discontinuation from treatment, events 
classified as CTCAE Grade 3 or Grade 4, and serious adverse events, and events of interest will 
be summarized separately.
Cross tabulations will be provided to summarize frequencies of abnormalities.
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.
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10.1.7.1.
Adverse Events
Adverse events will be coded using the Medical Dictionary for Drug Regulatory Activities 
(MedDRA).
Adverse events will be analyzed in terms of treatment emergent adverse events (TEAEs), defined 
as any AEs that began or worsened in grade after the start of nab-paclitaxel to the start of the 
Maintenance part for those who randomize in the Maintenance part, or through end of treatment 
of nab-paclitaxel for those who do not randomize in the Maintenance part. 
Adverse events will be summarized by system organ class, relative and absolute frequency, 
severity/grade based on the NCI CTCAE version 4.0 and relationship to treatment. Study 
medication-related AEs, SAEs, and events leading to discontinuation or death will be listed 
separately.
10.1.7.2.
Laboratory Assessments
Laboratory test results will not be collected in the eCRFs unless they are determined to be 
clinically significant laboratory abnormalities. Abnormal and clinically significant laboratory 
assessments at Screening will be recorded as medical history, and after Screening, as AE or SAE. 
If a clinically significant laboratory abnormality is captured as medical history, AE, or SAE, the 
specific laboratory parameter(s) should be recorded on the laboratory assessments CRF.
10.1.8.
Study Treatment Termination
Reasons for stopping study treatment during the Induction part will be summarized in listings by 
frequency of occurrence and corresponding percentage of occurrence.
10.1.9.
Deaths
Deaths reported during treatment (defined as deaths after the start of nab-paclitaxel to the start of 
the Maintenance part for those who are randomized in the Maintenance part, or through end of 
treatment of nab-paclitaxel for those who are not randomized in the Maintenance part) will be 
summarized by frequency of occurrence and corresponding percentage by cause of death per 
period.
10.2.
Maintenance Part
10.2.1.
Overview
This is the open-label, randomized, Maintenance part of the study for the evaluation of the 
benefit of a maintenance treatment after an initial 4 cycles of Induction treatment for subjects 
with squamous NSCLC.
Approximately 260 radiologic and clinical progression free subjects from the Induction part will 
be randomized in the Maintenance part. These subjects will be randomized in a 2:1 ratio to the 
nab-paclitaxel plus BSC and BSC alone groups, respectively. The nab-paclitaxel group will 
receive nab-paclitaxel 100 mg/m2 on Day 1 and 8 of each 21-day cycle plus BSC (the actual 
starting dose may be adjusted as specified in Section 8.3), while the BSC group will receive the 
standard BSC. All subjects will receive the assigned regimen until disease progression or 
unacceptable toxicity. Subjects in the BSC alone group who have radiologic progression will be 
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eligible to crossover and receive the nab-paclitaxel regimen until unacceptable toxicity or 
discontinuation for any other reason.
A permuted-block randomization method and an Interactive Voice Response System (IVRS) will 
be utilized to ensure a central randomization. The randomization will be stratified based on 
following 3 baseline and prognostic factors:
!
ECOG performance status at the end of the Induction part (0 vs. 1)
!
Tumor response to induction chemotherapy (CR or PR vs. SD), and 
!
Disease stage before administration of induction therapy (IIIB vs. IV).
It is hypothesized that subjects will benefit from maintenance treatment with nab-paclitaxel. A
randomization ratio of 2:1 will, therefore, minimize subject exposure to treatment with BSC only 
while providing sufficient data for testing the treatment difference with respect to the primary 
endpoint, PFS, in the Maintenance part of the study. 
A DMC will be used to monitor the study conduct. Details will be provided in the DMC charter.
10.2.2.
Study Population Definitions
10.2.2.1.
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 IP or has any efficacy 
assessments collected. 
10.2.2.2.
Response Evaluable Population
Response evaluable population includes all randomized subjects who meet eligibility criteria, 
take at least one dose of IP or on BSC and have at least one baseline and post baseline efficacy 
assessment. The response evaluable population may be used for additional analyses which will 
be described in the SAP.
10.2.2.3.
Per-protocol (PP) Population
The PP population is defined as all subjects randomized in the Maintenance part who receive at 
least one dose of the study therapy and do not have any known major protocol deviations and 
fulfill the study enrollment criteria. The PP population may be used for additional analyses 
which will be described in the SAP.
10.2.2.4.
Safety Population
The safety population includes all randomized subjects in the BSC alone arm and those who
receive at least one dose of nab-paclitaxel in the nab-paclitaxel plus BSC arm in the Maintenance 
part of the study. The safety population will be the population for all safety analyses.
10.2.3.
Sample Size and Power Considerations
Progression free survival is the primary endpoint while OS and ORR are the secondary endpoints 
in this part of the study.  
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One non-binding interim analysis for PFS with early stopping rule for futility will be conducted 
when approximately 91 events are observed. The study may be stopped for futility if conditional 
power is < 10%.
The final analysis of the primary endpoint will be performed when approximately 182 PFS 
events have been observed. A total of approximately 260 subjects will need to be randomized 
assuming an approximate 36 months accrual period and an approximate 2 months follow-up and 
an approximate 9% per year dropout rate.
This study is designed to provide approximately 90% power to detect a HR of 0.60 for PFS 
improvement with nab-paclitaxel plus BSC over BSC alone with a two-sided 5% significance 
level. Assuming an exponential distribution with a median time to PFS of 2 months for the BSC 
alone and proportional hazard, a hazard ratio of 0.60 constitutes an approximate 1.33 months 
increase in median PFS or a 40% hazard risk reduction by the nab-paclitaxel plus BSC regimen 
over that of the BSC alone.
There will be 2 analyses for the OS endpoint. The interim analysis (non-binding) of OS will be 
conducted based on the number of deaths observed at the time of the final PFS analysis. 
However, all subjects will continue to be followed for OS up to 1.5 years after final analysis of 
approximately 182 PFS events or approximately 218 deaths have been observed for the final OS 
analysis, whichever is earlier. The marginal significance levels for OS will be adjusted according 
to O’Brien-Fleming type boundary based on the actual number of deaths observed at each stage.
For example, if 163 and 218 deaths (~75% information) are observed by the time of the interim 
and final analyses of OS, respectively, the marginal critical values will be p ≤0.01106 and p ≤
0.04794, correspondingly.
Assuming an exponential distribution, proportional hazards, and median OS times of 7.2 and 
10.30 months for the BSC alone and nab-paclitaxel plus BSC regimens, respectively, this design 
provides 70% marginal power to detect a hazard ratio of 0.70 between the 2 maintenance 
regimens with an overall two-sided 5% significance level.
A step-down procedure from PFS to OS will be used to control family-wise Type-I error rate to 
5%. That is, OS will be tested only if the nab-paclitaxel plus BSC regimen demonstrates 
superiority over the BSC alone with PFS. 
As an illustration for timeline projection, assuming an exponential distribution for PFS, a 36-
month recruitment period for 260 subjects, and a median PFS of approximately 2.0 months for 
the BSC alone, it will take approximately 23 months from the first subject randomized to observe 
91 PFS events for the interim analysis. The final analysis of PFS (with 182 events) is estimated 
to take place at approximately 15 months after that, which is approximately 2 months after the 
last subject randomized.  
Assuming an exponential distribution for OS and a median OS of 7.2 months for the BSC arm, it 
will take approximately an additional 1.5 years follow-up after the final analysis of PFS to 
observe a total of 218 death events in the entire Maintenance part.
10.2.4.
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. 
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Medical history data will be summarized using frequency tabulations by system organ class and 
preferred term.
10.2.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both treatments 
and follow-up parts. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
10.2.6.
Efficacy Analysis
While key analyses are described in this section, additional analyses will be specified in the SAP.
10.2.6.1.
Primary Endpoint 
The primary endpoint, PFS, will be based on investigator’s assessment of response using 
RECIST 1.1 guidelines. Baseline tumor measurements will be determined from the radiology 
evaluation performed within 28 days of the start of Induction therapy. Time to Progression will 
be calculated from the date of randomization (start of Maintenance part) to the first date of 
progressive disease or death from any cause.  
Progression-free survival will be summarized using Kaplan-Meier methods. 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. In the event 
that a new anticancer treatment occurs prior to documented progression, the subject will be 
censored at the time 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 time 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 time of the last radiologic 
assessment where the subject was documented to be progression-free prior to the first of the two 
missing visits.
The null (Ho) and alternative (Ha) hypotheses for testing the primary efficacy endpoint are: 
Ho: HR nab-paclitaxel plus best supportive care/ best supportive care = 1
Ha: HR nab-paclitaxel plus best supportive care/ best supportive care ≠1 
Progression-free survival will be summarized by median PFS time (including two-sided 95% CI) 
for each treatment regimen 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 regimen and differences in the curves will be tested using the 
stratified log-rank test, where the strata include ECOG performance status at the end of the 
Induction part (0 vs.1), tumor response to induction chemotherapy (CR or PR vs. SD), and 
disease stage before administration of induction therapy (IIIB vs. IV), if the number of events in 
each cell is adequate. Other factors may be included if indicated by the actual population 
enrolled.
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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 regimen. 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. 
Additional analyses of PFS calculated from the date of the first dose of Induction therapy will be 
conducted using the same statistical methods described for PFS measured from the date of 
randomization above.
10.2.6.2.
Key Secondary Endpoints
Key secondary efficacy endpoints include OS and ORR (percent of subjects who had a 
radiologic complete or partial response according to RECIST 1.1 guidelines determined by the 
investigator and confirmed by repeat assessments performed no less than 28 days after the 
criteria for response were first met). 
10.2.6.2.1. 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 trial or who are withdrawn from the trial 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 cut-off date. 
Overall survival will be analyzed similarly as PFS.
Additional analyses of OS calculated from the date of the first dose of induction therapy will be 
conducted using the same statistical methods described for OS calculated from the date of 
randomization above.
10.2.6.2.2. Overall Response Rate 
The percentage of randomized subjects having an overall confirmed CR or PR based on the 
investigator’s assessment using RECIST 1.1 guidelines over the entire study (Induction and 
Maintenance) will be calculated (scans will be performed every 42 days [-3/+7 days] and 
confirmation scan will be performed no less than 4 weeks after the criteria for response were first 
met). Baseline tumor measurements will be determined from the radiology evaluation performed 
within 28 days of the start of Induction therapy.
The two-sided 95% CI of the response rates will be presented. Differences in response rates 
between treatment regimens will be tested using chi-square test at a two-sided 5% significance 
level.  
10.2.6.3.
Other Secondary Efficacy Endpoints
10.2.6.3.1. Disease Control Rate
Disease Control rate (ie, SD for ≥ 6 weeks or confirmed CR or PR) over the entire study will be 
analyzed in the same manner as overall response rate. Baseline tumor measurements will be 
determined from the radiology evaluation performed within 28 days of the start of Induction 
therapy.
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0.2.6.


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10.2.6.4.
Exploratory Endpoints
10.2.6.4.1. Overall Response Rate in Maintenance Part 
Tumor reductions during maintenance treatment beyond the response to induction therapy will 
be explored by the percentage of randomized subjects achieving an overall confirmed CR or PR
compared with the radiologic assessment before randomization (i.e, using end of cycle 4 CT-
scan as the baseline measurement) according to the investigator’s evaluation using RECIST 1.1 
guidelines.  
The two-sided 95% CI of the response rates will be presented. Differences in response rates 
between treatment regimens may be tested using chi-square test at a two-sided 5% significance 
level.
10.2.6.4.2. Response Rate Subsequent to Cross-over to nab-Paclitaxel Regimen
The number and percentage of subjects from the BSC group who cross over to the nab-paclitaxel 
plus BSC regimen after radiologic disease progression, who subsequently achieve CR or PR will 
be estimated with the associated two-sided 95% confidence interval.
For this endpoint, baseline tumor measurements will be determined from the radiologic 
evaluation that renders the subject as having progressive disease by the investigator prior to 
crossing over to receive the nab-paclitaxel plus BSC regimen.
10.2.6.4.3. Health Care Utilization and Quality of Life Questionnaire
The analysis of health care utilization and quality of life questionnaire will be described in detail 
in the SAP.
10.2.6.4.4. Biomarkers and Pharmacogenomic Data
Statistical analysis of the biomarkers and pharmacogenomic data collected from the plasma and 
blood samples will be covered under a separate SAP from that mentioned above.
10.2.7.
Safety Analysis
All subjects in the BSC arm and all subjects who take at least 1 dose of nab-paclitaxel in the nab-
paclitaxel plus BSC in the Maintenance part will be included in the safety analyses. Adverse 
events will be summarized by worst severity grade. AEs, as well as treatment-emergent AEs, 
will be summarized by system organ class, and preferred term. IP-related adverse events, adverse 
events leading to death or to discontinuation from treatment, events classified as CTCAE Grade 
3 or Grade 4 (or moderate/severe if other rating scale is used), and serious adverse events, and 
events of interest will be summarized separately.
Cross tabulations will be provided to summarize frequencies of abnormalities.
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. 
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10.2.7.1.
Adverse Events
Adverse events will be analyzed in terms of TEAEs, defined as any AE occurring or worsening 
on or after the first treatment of the study regimen of the Maintenance part through 28 days after 
the last dose of study regimen administration. In addition, any AE with an onset date more than 
28 days after the last dose of IP that is assessed by the investigator as related to study drug will 
be considered a TEAE. They will be summarized by system organ class, relative and absolute 
frequency, severity grade based on the NCI CTCAE version 4.0 and relationship to treatment. 
Study medication-related AEs, SAEs, and events leading to discontinuation or death will be 
listed separately. 
AEs will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA, 
Version 16.0). 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.
Since laboratory test data will not be collected routinely in the eCRFs, this will not be analyzed.
10.2.7.2.
Laboratory Assessments
Laboratory tests will be performed weekly prior to nab-paclitaxel administration, as per standard 
of care during the study and as clinically indicated. Laboratory test results will not be collected 
in the eCRFs unless they are determined to be clinically significant laboratory abnormalities.
Abnormal and clinically significant laboratory assessments at Screening will be recorded as 
medical history, and after Screening, as AE or SAE. If a clinically significant laboratory 
abnormality is captured as medical history, AE, or SAE, the specific laboratory parameter(s) 
should be recorded on the laboratory assessments CRF.
10.2.8.
Study Therapy Termination
Reasons for stopping study therapy will be summarized in listings by frequency of occurrence 
and corresponding percentage of occurrence per study part (Induction and Maintenance) and 
combined.
10.2.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the study 
Maintenance regimen through 28 days after the last dose of the study Maintenance regimen) 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).
Deaths occurring during the entire study (Induction and Maintenance parts) will also be 
summarized similarly.
10.2.10.
Interim Analysis
There will be one non-binding interim analysis for futility for the primary endpoint, PFS, when 
approximately 91 events (50% information) have been observed. Futility may be declared and 
the study discontinued if the conditional power at the interim analysis is < 10%.  The final 
analysis of PFS will be performed when approximately 182 PFS events have been observed.
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There will be two analyses for the secondary OS endpoint. The interim analysis of OS (for 
efficacy) will be conducted based on the number of deaths observed up to the time of the final 
PFS analysis. The final OS analysis will be performed after approximately 218 deaths have been 
observed, if applicable.  
A Step-down procedure from PFS to OS will be used to control the family-wise two-sided Type-
I error rate to 5%.
The marginal significance level for OS will be adjusted according to O'Brien-Fleming type of 
boundary. The nominal two-sided p-values for declaring superiority will be calculated using the 
statistical software 
. The analysis and boundaries will be adjusted 
based on the actual number of deaths observed.
10.3.
Data Monitoring Committee
An independent DMC will be established with the responsibilities for safeguarding the interests 
of study participants and monitoring the overall conduct of the study. Final recommendations of 
the DMC will reflect the judgment of the DMC members and will be considered advisory in 
nature to the Sponsor. The decision to implement the recommendations of the DMC will be 
made by the Sponsor, following consultation with the coordinating PI and Steering Committee.
A DMC charter will be established.
10.4.
Scientific Steering Committee
The conduct of this trial will be overseen by a Steering Committee. The Steering Committee will 
serve in an advisory capacity to the Sponsor. 
Note: the Steering Committee is separate from the Data Monitoring Committee described in 
Section 10.3.
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11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the CRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of squamous cell NSCLC will not 
require reporting as an adverse event.
An overdose, accidental or intentional, whether or not it is associated with an AE, or abuse, 
withdrawal, sensitivity or toxicity to an IP 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 other appropriate tests and 
procedures.
All AEs will be recorded by the Investigator from the time the subject signs informed consent to
28 days after the last dose of IP or the End of Study Visit, whichever is longer, and those SAEs 
made known to the investigator at any time thereafter that are suspected of being related to IP.
AEs and serious adverse events (SAEs) will be recorded on the AE page of the CRF and in the 
subject’s source documents. All SAEs must be reported to Celgene Drug Safety within 24 hours 
of the Investigator’s knowledge of the event by facsimile, or other appropriate method, using the 
SAE Report Form, or approved equivalent form.
11.2.
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to: 
11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
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11.2.1.
1.2.1.
ser


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!
Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the CRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of a pre-existing condition unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to IP, action taken regarding IP, and outcome.
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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 IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
The temporal relationship of the adverse event to IP 
administration makes a causal relationship unlikely or 
remote, or other medications, therapeutic interventions, or 
underlying conditions provide a sufficient explanation for the 
observed event.
Suspected:
The temporal relationship of the adverse event to IP 
administration makes a causal relationship possible, and other 
medications, therapeutic interventions, or underlying conditions 
do not provide a sufficient explanation for the observed event.
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If an event is assessed as suspected of being related to a comparator, ancillary or additional IP 
that has not been manufactured or provided by Celgene, please provide the name of the 
manufacturer when reporting the event.
11.2.4.
Duration
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event.
11.2.5.
Action Taken
The Investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(eg, discontinuation or reduction of IP, as appropriate) and report if concomitant and/or 
additional treatments were given for the event. 
11.2.6.
Outcome
The investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered (death due to another cause) or death 
(due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or
!
is judged to be of significant clinical importance.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the CRF. If the abnormality was not a 
part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE. If 
possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
11.4.1.
Females of Childbearing Potential:
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on IP, or within 3 months of the 
subject’s last dose of IP, are considered immediately reportable events. IP is to be discontinued 
immediately. The pregnancy, suspected pregnancy, or positive pregnancy test must be reported 
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11.4.1.
1.4.1.


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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, preferably one experienced in reproductive toxicity for 
further evaluation and counseling.
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 or therapeutic abortion), the 
Investigator should report the abnormal outcome as an AE. If the abnormal outcome meets any 
of the serious criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or 
other appropriate method, within 24 hours of the Investigator’s knowledge of the event using the 
SAE Report Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the Investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the Investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving IP or within 
3 months of the last dose of IP, the male subject taking IP should notify the Investigator, and the 
pregnant female partner should be advised to call her healthcare provider immediately. The IP 
may need to be discontinued in the male subject, but may be resumed later at the discretion of 
the Investigator and medical monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The Investigator is required to ensure that the data on these forms is accurate and consistent. This 
requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent to at least 28 days after the last dose of IP or 
End of Study Visit, whichever is later) and those made known to the Investigator at anytime 
thereafter that are suspected of being related to IP. SAEs occurring prior to treatment will be 
captured.
The SAE report should provide a detailed description of the SAE and include summaries 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.
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Where required by local legislation, the Investigator is responsible for informing the IRB/EC of 
the SAE and providing them with all relevant initial and follow-up information about the event. 
The Investigator must keep copies of all SAE information on file including correspondence with 
Celgene and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than five (5) business 
days. Urgent queries (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 Abraxane and Investigator 
Brochure. For the purpose of regulatory reporting in the EEA, Celgene Drug Safety will 
determine the expectedness of events suspected of being related to the other IP, carboplatin,
based on the EU Summary of Product Characteristics (SmPC). 
For countries within the European Economic Area (EEA), Celgene or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 
presentation of adverse reaction reports arising from clinical trials on IP for human use 
(ENTR/CT3) and also in accordance with country-specific requirements.
Celgene or its authorized representative shall notify the Investigator of the following 
information: 
!
Any AE suspected of being related to the use of IP in this study or in other studies 
that is both serious and unexpected (ie, SUSAR);
!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC. (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form/Completion Guidelines or to the Pregnancy Report Form/Completion Guidelines.
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12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the IP:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent
!
Death
!
Lost to follow-up
!
Protocol violation
All subjects discontinued from nab-paclitaxel for any reason will have a treatment 
discontinuation visit at the time of nab-paclitaxel discontinuation and should undergo early 
termination procedures.
All subjects discontinued from nab-paclitaxel will be followed for a period of 28 days after PFS 
or early discontinuation, or until the date of the last study visit (whichever is longer) for the 
collection of AEs.
Additionally subjects who withdraw from or complete treatment should not be withdrawn from 
the study (unless specifically requested) and should be followed up for progressive disease, 
survival and any new therapy given.
The reason for treatment discontinuation should be recorded in the eCRF and in the source 
documents.
12.2.
Study Discontinuation
The following are considered sufficient reasons for discontinuing a subject from the study:
!
Withdrawal of consent (decision form the subject not to provide follow-up 
information)
!
Death
!
Lost to follow-up
The following may be considered a sufficient reason for discontinuing a subject from the study:
!
Protocol violation
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. 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.
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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 the subject 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 CRFs 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.
IP can only be supplied to an Investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
Celgene or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB/EC should mention the protocol title, number, amendment number 
(if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
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The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the Investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
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15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and the distribution of the IP are complete, accurate, filed and retained. Examples of source 
documents include: hospital records; clinic and office charts; laboratory notes; memoranda; 
subject’s diaries or evaluation checklists; dispensing records; recorded data from automated 
instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy, and the laboratories, as 
well as copies of CRFs or CD-ROM.
15.2.
Data Management
Data will be entered into the clinical database per Celgene Standard Operating Procedures 
(SOPs). This data will be electronically verified through use of programmed edit checks 
specified by the clinical team. Discrepancies in the data will be brought to the attention of the 
clinical team, and investigational site personnel, if necessary. Resolutions to these issues will be 
reflected in the database. An audit trail within the system will track all changes made to the data.
15.3.
Record Retention
Essential documents must be retained by the Investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IP. The investigator must retain these 
documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the Investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the Investigator, Celgene, and their authorized 
representative(s);
!
List of Sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of CRFs (if paper) and of documentation of corrections for all subjects;
!
IP accountability records;
!
Record of any body fluids or tissue samples retained;
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!
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, CRFs, procedures for obtaining informed 
consent, record keeping, and reporting of AEs/SAEs with the Investigator. Monitoring will 
include on-site visits with the Investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, IP
storage area, CRFs, subject’s source documents, and all other study documentation will be
inspected/reviewed by the Celgene representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the CRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff. Any necessary 
corrections will be made directly to the CRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene. Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, CRFs and applicable supporting records of 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 and order of  
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 the study.
&(/*(1(35235,(7$5<,1)250$7,21


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18.
REFERENCES
Azzoli CG, Baker Jr. S, Temin S, 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, 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 
Onc. 2008;26:468-473.
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):1590-1598.
Lorenz W, Reimann HJ, Schmal A, et al. Histamine release in dogs by Cremophor El and its 
derivatives: oxethylated oleic acid is the most effective constituent. Agents Actions 
1997;7:63-67.
Lung Cancer Awareness. Global Lung Cancer Coalition Website. 
http://www.lungcancercoalition.org/en/pages/about/awareness. Accessed July 12, 2013.
National Institute for Health & Clinical Excellence: The Diagnosis and Treatment of Lung 
Cancer: Methods, Evidence & Guidance, 2011.
Neal, JW. The SATURN trial: the value of maintenance erlotinib in patients with non-small-cell
lung cancer. Future Oncol. 2010 Dec;6(12):1827-1832.
O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979 
Sep;35(3):549-556.
Oken, MM, Creech, RH, Tormey, DC, et al. Toxicity And Response Criteria Of The Eastern 
Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982.
Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus best 
supportive care versus placebo plus best supportive care after induction therapy with pemetrexed 
plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a 
double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55.
Rizvi NA, Riely GJ, Azzoli CG, 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):639-643.
Schell MJ, Peterman A, et al. Phase III trial comparing a defined duration of therapy versus 
continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell 
lung cancer. J Clin Oncol. 2002;20(5):1335-1343.
Socinski M, Manikhas GM, Stroyakovsky DL, 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):852-861.
Stinchcombe TE, Socinski MA. Current treatments for advanced stage non-small cell lung 
cancer. Proc Am Thorac Soc. 2009;6(2):233-241.
&(/*(1(35235,(7$5<,1)250$7,21
and 
nd 
590
90-1598.
1598
phor El
hor El and
an
Act
Actioions
ns
ccessed Ju
cessed Ju
gnosis and 
nosis and
ce
ce erl
erlotinib
otinib
832.
32
ocedure for
cedure fo
t al
t al. Toxi
Tox c
Clin Oncol
Clin On
M, et al.
M, et al. M
o plus best 
o plus best
non
non-squam
squam
andomised 
andomise
, Azzo
Azzoli CG
li CG
paclitaxel as
aclitaxel a
Onc
Oncol
ol. 200
20
J, Peterm
Peterman
an
uous therap
uous therap
g cancer.
g cancer. J C
J
Socinski M
Socinski M
week na
week n


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Weiss RB, Donehower RC, Wiernik PH, et al. Hypersensitivity reactions from Taxol. J Clin 
Oncol. 1990;8(7):1263-1268.
&(/*(1(35235,(7$5<,1)250$7,21


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19.
APPENDICES
Appendix A: Response Evaluation Criteria in Solid Tumors (RECIST 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 longest diameter # 20 mm using conventional techniques or # 10 
mm with spiral CT scan.
∀
Non-measurable lesions - all other lesions, including small lesions (longest 
diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan), 
ie, bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusion, 
inflammatory breast disease, lymphangitis cutis/pulmonis, cystic lesions, and also 
abdominal masses that are not confirmed and followed by 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 five lesions per organ and 10 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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Response Criteria
Table 7:
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 the LD of target lesions, taking as 
reference the smallest sum LD recorded since the treatment started 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 LD since the treatment 
started
Table 8:
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 lesions
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
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Yes
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!
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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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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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
1
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
TITLE PAGE
A PHASE III, RANDOMIZED, OPEN-LABEL, MULTI-
CENTER, SAFETY AND EFFICACY STUDY TO 
EVALUATE NAB-PACLITAXEL (ABRAXANE®) AS 
MAINTENANCE TREATMENT AFTER INDUCTION 
WITH NAB-PACLITAXEL PLUS CARBOPLATIN IN 
SUBJECTS WITH SQUAMOUS CELL NON-SMALL 
CELL LUNG CANCER (NSCLC)
INVESTIGATIONAL PRODUCT (IP):
nab-Paclitaxel (Abraxane®)
PROTOCOL NUMBER:
ABI-007-NSCL-003
ORIGINAL DATE FINAL:
27 Sep 2013
AMENDMENT 1 DATE FINAL:
28 Oct 2014
EudraCT NUMBER:
2014-003804-66
IND NUMBER:
114882
SPONSOR NAME / ADDRESS:
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board. The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations.
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
2
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 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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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
3
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
4
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 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-003
Celgene Corporation
Confidential and Proprietary
5
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 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-003
Celgene Corporation
Confidential and Proprietary
6
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
PROTOCOL SUMMARY
Study Title
A Phase III, randomized, open-label, multi-center, safety and efficacy study to evaluate nab-
paclitaxel (Abraxane) as maintenance treatment after induction with nab-paclitaxel plus 
carboplatin in subjects with squamous cell non-small cell lung cancer (NSCLC).
Indication
Maintenance treatment of squamous cell NSCLC.
Objectives
Primary
!
To evaluate progression free survival (PFS) with nab-paclitaxel as maintenance 
treatment after response or stable disease (SD) with nab-paclitaxel plus carboplatin in 
subjects with squamous cell NSCLC.
Secondary 
!
To evaluate the safety and tolerability of nab-paclitaxel as maintenance treatment 
after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous 
cell NSCLC.
!
To further assess the efficacy with nab-paclitaxel as maintenance treatment after
response or SD with nab-paclitaxel plus carboplatin in subjects with squamous cell 
NSCLC, as measured by secondary efficacy endpoints.
Exploratory 
!
To determine baseline tumor characteristics which predict response and resistance to 
nab-paclitaxel/carboplatin during the Induction part of the study. 
!
To determine what changes in peripheral tumor characteristics during treatment are 
associated with acquisition of resistance in the subjects who had initial clinical 
benefit.
!
To assess healthcare resource utilization during the Maintenance part of the study.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ5D).
Study Design
This is a Phase III, randomized, open-label, multi-center study of nab-paclitaxel or best 
supportive care (BSC) as maintenance treatment after response or SD with nab-paclitaxel plus 
carboplatin as induction in subjects with squamous cell NSCLC. Approximately 540 subjects
with stage IIIB or IV squamous cell NSCLC will be enrolled in the Induction part of the study to 
receive nab-paclitaxel plus carboplatin for 4 cycles. If after the 4 cycles, the subject has a 
complete response (CR), partial response (PR), or SD, they will be randomized (2:1) in the 
Maintenance part of the study to receive nab-paclitaxel plus BSC or BSC alone. BSC is defined 
as the best palliative care per investigator (including but not limited to: antibiotics, analgesics, 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
7
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and/or focal 
external-beam radiation for control of pain, cough, dyspnea, or hemoptysis), excluding
antineoplastic agents. Approximately 260 subjects will be evaluable for the primary endpoint of 
PFS in maintenance.
Induction Part
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Approximately 540 subjects eligible for 
standard treatment with nab-paclitaxel plus carboplatin for 4 cycles will be enrolled, provided if 
all inclusion/exclusion criteria are met within a 28-day screening period prior to Cycle 1 Day 1.
Induction treatment will commence on Day 1: 
!
nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion over 30 minutes on Days 1, 8, 
and 15 of each 21-day cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD, and has met all eligibility criteria, they will continue on to the Maintenance part 
of the study. If the subject has radiological or clinical PD, they will be discontinued from the 
study and will not be followed.
Maintenance Part
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD without clinical progression, and has met all eligibility criteria, they will be 
randomized 2:1 to receive:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day cycle plus BSC until disease progression or unacceptable toxicity (see Section 8.3
for guidelines on starting dose for the Maintenance part of the study if the subject had 
dose reduced during the Induction part of the study)
OR
!
BSC until disease progression
Maintenance therapy should start at the time of randomization. If this is not possible, a maximum 
of 7 days will be allowed from the date of randomization to the start date of Maintenance 
therapy. Subjects must start Maintenance therapy no earlier than 21 days and no later than 35
days from Day 1 of the fourth cycle of Induction therapy.
Follow-up Period 
All subjects who discontinue from the Maintenance part of the study for any reason other than 
withdrawal of consent, lost to follow-up, or death, will enter the Follow-up period that will have 
a visit 28 days after progression or discontinuation.   Those subjects entering the follow up 
period without documented progression will continue to have CT scan in accordance with 
standard of care until documented progression of disease.  Additionally, subjects will be 
followed for overall survival (OS) by phone approximately every 90 days for up to 1.5 years
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
8
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
after final analysis of approximately 182 PFS events or approximately 218 deaths have been 
observed for the final OS analysis, whichever is earlier.
Study Population
Subjects with squamous cell NSCLC stage IIIB or IV with no prior chemotherapy for metastatic 
disease and ≥ 18 years old will be eligible for this study. The Induction part of the study will 
enroll approximately 540 subjects. Based on results from the nab-Paclitaxel Phase 3 NSCLC 
development study (Protocol CA031) it is estimated that approximately 260 subjects with CR, 
PR, or SD from the Induction part of the study will be randomized to the Maintenance part of the 
study. Enrollment into the Induction part of the study will be monitored and adjusted to ensure 
that approximately 260 subjects are randomized into the Maintenance part of the study.
Length of Study
The Induction part of the study will last approximately 36 months to enroll sufficient subjects for 
the Maintenance part of the study. The total length of this Phase III study with Induction, 
Maintenance, and Follow-up is estimated to last approximately 5 years.
Study Treatments
Induction 
The nab-paclitaxel and carboplatin treatments will not be supplied by Celgene during Induction 
in those countries where nab-paclitaxel plus carboplatin is available for the treatment of NSCLC. 
Investigative sites will use standard of care (commercially available) product via prescription in 
these countries.
In those countries where nab-paclitaxel plus carboplatin is not available for the treatment of 
NSCLC, both agents will be designated as investigational product (IP) and will be packaged and 
supplied by Celgene.  
Maintenance 
Subjects will be randomized to receive open-label nab-paclitaxel plus BSC or BSC during the 
Maintenance part of the study. The nab-paclitaxel used in the Maintenance part of the study will 
be packaged and supplied by Celgene Corporation.
Please see local prescribing information for Abraxane for detailed instructions on the
reconstitution, storage conditions, and IV administration of nab-paclitaxel.
Statistical Methods
Approximately 540 subjects will be enrolled in the open-label Induction part of the study. All 
subjects will receive nab-paclitaxel 100 mg/m2 administered weekly followed by carboplatin
AUC = 6 mg*min/mL on Day 1 of each cycle, repeated every 21 days, for 4 cycles.
At the end of Cycle 4, subjects who achieve a radiologically assessed complete response (CR), 
partial response (PR), or stable disease (SD) without clinical progression based on the 
Investigator’s evaluation using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 
guidelines will be further evaluated for their eligibility to participate in the Maintenance part of 
the study.  Approximately 260 subjects are expected to be randomized in the Maintenance part of 
the study.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
9
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
The actual number of subjects that will be enrolled in the Induction part will be monitored and 
adjusted to ensure that the target number of subjects for the Maintenance part is attained.
Similarly, the percentage of subjects manifesting a PFS event in the Maintenance part will be 
tracked on an ongoing basis. If the observed percentage of subjects with a PFS event is trending 
lower than the assumed 70%, the number of subjects enrolled in the Induction and Maintenance 
parts will be increased to ensure that at least 182 PFS events will be observed within the 
anticipated duration of the study.
Induction Part
Efficacy Analyses
All efficacy endpoints will be analyzed based on the intent-to-treat (ITT) population, which 
includes all subjects who are enrolled regardless of whether the subjects receive any nab-
paclitaxel or have any efficacy assessments collected.
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Subjects will have CT scans performed at 
the end of Cycle 2 and 4. Subjects who attain a radiologically assessed CR, PR, or SD without 
clinical progression according to the investigator’s assessment of the scan performed at the end 
of Cycle 4, based on RECIST v1.1 (Eisenhauer, 2009) guidelines, and satisfy eligibility criteria 
will be eligible to be randomized in the Maintenance part.
The secondary objective of the Induction part is to estimate the Overall Response Rate (ORR, 
percent of subjects who have a CR or PR according to RECIST v1.1 guidelines as determined by 
the investigator and confirmed by repeat assessments performed no less than 28 days after the 
criteria for response were first met). Descriptive statistics (point estimate and the associated two-
sided 95% confidence interval) will be calculated for this endpoint.
Safety Analyses
The safety population, includes all subjects enrolled who received at least 1 dose of study 
treatment, will be the analysis population for all safety analyses. Adverse events will be 
summarized by worst severity grade. Adverse events (AEs), as well as treatment-emergent AEs, 
will be summarized by system organ class, and preferred term. Adverse event severity/grade will 
be summarized by National Cancer Institute (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE) v4.0. 
Laboratory test results will not be collected in the eCRFs unless they are determined to be 
clinically significant laboratory abnormalities. Abnormal and clinically significant laboratory 
assessments at Screening will be recorded as medical history, and after Screening, as AE or 
serious adverse event (SAE). If a clinically significant laboratory abnormality is captured as 
medical history, AE, or SAE, the specific laboratory parameter(s) should be recorded on the 
laboratory assessments CRF.
Maintenance Part
Approximately 260 subjects will be randomized in the Maintenance part of the study. These 
subjects will be randomized in a 2:1 ratio to the nab-paclitaxel plus BSC and BSC alone groups, 
respectively. The nab-paclitaxel group will receive nab-paclitaxel 100 mg/m2 on Day 1 and 8 of 
each 21-day cycle plus BSC (the actual starting dose may be adjusted as specified in Section 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
10
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
8.3), while the BSC group will receive the standard BSC regimen. All subjects will receive the 
assigned regimen until disease progression or unacceptable toxicity.
Randomization will be stratified by the following 3 baseline and prognostic stratification factors:
Eastern Cooperative Oncology Group (ECOG) performance status at the end of the Induction 
part (0 vs. 1), tumor response to induction chemotherapy (CR/PR vs. SD), and disease stage 
before administration of induction therapy (IIIB vs. IV). It is postulated that subjects will benefit 
from maintenance therapy with nab-paclitaxel, therefore a randomization ratio of 2:1 will reduce 
subject exposure to treatment with BSC alone while providing sufficient data for testing the 
treatment difference with respect to the primary endpoint, progression free survival.
The Maintenance part of the study is designed to detect a hazard ratio (HR) of 0.60 for PFS 
improvement with the nab-paclitaxel plus BSC regimen over the BSC alone regimen with 90% 
power and an overall type-I error rate of 5% (two-sided). The final analysis will be conducted 
after approximately 182 PFS events (ie, events of disease progression or deaths from any cause) 
have occurred. Assuming an exponential distribution with a median time to PFS of 2 months for 
the BSC alone group and proportional hazards, a hazard ratio of 0.60 constitutes a 1.33 months 
improvement for the nab-paclitaxel plus BSC group over that of the BSC alone group.
A non-binding interim analysis for futility with PFS will be planned at approximately 91 events.
The stopping rules and the final marginal significance level are determined based on O'Brien-
Fleming type boundaries (O’Brien, 1979). The study may be stopped early for futility if the 
conditional power is < 10%.
There will be 2 analyses for the OS endpoint. The interim analysis (non-binding) of OS will be 
conducted based on the number of deaths observed at the time of the final PFS analysis.
However, all subjects will continue to be followed for OS up to 1.5 years after final analysis of
approximately 182 PFS events or approximately 218 deaths have been observed for the final OS
analysis, whichever is earlier. The marginal significance levels for OS are determined based on 
O'Brien-Fleming type boundaries and will be adjusted based on the actual number of deaths 
observed at each stage.  
A Step-down procedure from PFS to OS will be used to control the family-wise two-sided Type-
I error rate to 5%.
Efficacy Analyses
The Maintenance part of the study starts on the date the subject is randomized to either of the 
treatment arms. All efficacy analyses in the Maintenance part will be based on the ITT 
population, which includes all randomized subjects regardless of whether they receive any IP or 
have any efficacy assessments collected. 
The primary efficacy endpoint is PFS based on investigator’s assessment of the subject’s 
radiologic response using RECIST 1.1 guidelines. Baseline tumor measurements will be 
determined by the computed tomography (CT)-scan performed less than 28 days before the first 
dose of nab-paclitaxel in the Induction part of the study. Progression-free survival will be 
counted from the date of randomization 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.
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The null (Ho) and alternative (Ha) hypotheses for the primary efficacy endpoint are: 
Ho: HR nab-paclitaxel plus best supportive care / best supportive care = 1
Ha: HR nab-paclitaxel plus best supportive care / best supportive care ≠1
Progression-free survival will be summarized using the Kaplan-Meier method and by median 
PFS time (including two-sided 95% CI) for each treatment regimen along with the hazard ratio 
(including two-sided 95% CI). The Kaplan-Meier curve for PFS will be presented graphically for 
each treatment regimen and differences in the curves will be tested using a stratified log-rank test 
with the 3 baseline and prognostic factors described above.
Secondary efficacy endpoints include OS and ORR (percent of subjects who attain a CR or PR 
according to RECIST 1.1 guidelines as determined by the investigator and confirmed by repeat 
assessments performed no less than 28 days after the criteria for response are first met). Overall 
survival will be analyzed by the same method described for PFS, while ORR will be analyzed by 
chi-square test.
Safety Analyses
The safety population includes all randomized subjects in the BSC alone arm and those who
receive at least one dose of nab-paclitaxel in the nab-paclitaxel plus BSC arm in the 
Maintenance part of the study. Adverse events will be summarized by worst severity grade. AEs, 
as well as treatment-emergent AEs, will be summarized by system organ class, and preferred 
term. Adverse event severity/grade will be summarized by NCI CTCAE v4.0.
Laboratory test results will not be collected in the eCRFs unless they are determined to be 
clinically significant laboratory abnormalities. Abnormal and clinically significant laboratory 
assessments at Screening will be recorded as medical history, and after Screening, as AE or 
serious adverse event (SAE). If a clinically significant laboratory abnormality is captured as 
medical history, AE, or SAE, the specific laboratory parameter(s) should be recorded on the 
laboratory assessments CRF.
Data Monitoring Committee
An independent Data Monitoring Committee (DMC) will be established with the responsibilities 
for safeguarding the interests of study participants and monitoring the overall conduct of the 
study. Final recommendations of the DMC will reflect the judgment of the DMC members and 
will be considered advisory in nature to the Sponsor. The decision to implement the 
recommendations of the DMC will be made by the Sponsor, following consultation with the trial 
Coordinating Principal Investigator and Steering Committee. A DMC charter will be established.
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TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
1.
INTRODUCTION..................................................................................................19
1.1.
Non-small Cell Lung Cancer (NSCLC)...................................................................19
1.2.
nab-Paclitaxel.........................................................................................................19
1.3.
Rationale for Development of nab-Paclitaxel as Maintenance Treatment in 
Squamous Cell NSCLC ..........................................................................................22
2.
STUDY OBJECTIVES...........................................................................................23
2.1.
Primary Objective...................................................................................................23
2.2.
Secondary Objectives .............................................................................................23
2.3.
Exploratory Objectives ...........................................................................................23
3.
STUDY ENDPOINTS............................................................................................24
3.1.
Primary Endpoint....................................................................................................24
3.2.
Secondary Endpoints ..............................................................................................24
3.2.1.
Safety.....................................................................................................................24
3.2.2.
Efficacy..................................................................................................................24
3.3.
Exploratory Endpoints............................................................................................24
4.
OVERALL STUDY DESIGN ................................................................................25
4.1.
Study Design ..........................................................................................................25
4.1.1.
Induction Part.........................................................................................................25
4.1.2.
Maintenance Part....................................................................................................25
4.1.3.
Follow-up Period....................................................................................................26
4.2.
Study Design Rationale ..........................................................................................26
4.3.
Study Duration .......................................................................................................28
4.4.
End of Trial ............................................................................................................28
5.
TABLE OF EVENTS.............................................................................................29
6.
PROCEDURES......................................................................................................34
6.1.
Medical History......................................................................................................34
6.2.
Prior Medications/Procedures .................................................................................34
6.3.
Pregnancy Testing ..................................................................................................34
6.4.
Complete Chest Computed Tomography (CT) Scan (including adrenal 
gland) With and Without Contrast ..........................................................................34
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6.2


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6.5.
Weight....................................................................................................................35
6.6.
Body Surface Area (BSA) Calculation and Height..................................................35
6.7.
ECOG Performance Score ......................................................................................35
6.8.
Concomitant Medications/Procedures.....................................................................35
6.9.
Peripheral Neuropathy Assessment.........................................................................35
6.10.
Adverse Event Reporting........................................................................................35
6.11.
Lung Cancer Symptom Scale Questionnaire and EQ5D..........................................35
6.12.
Healthcare Resource Utilization Questionnaire .......................................................36
6.13.
Electrocardiogram ..................................................................................................36
6.14.
CT Scan of Head or Brain Magnetic Resonance Imaging (MRI).............................36
6.15.
Bone Scans and X-rays...........................................................................................36
6.16.
Physical Examinations............................................................................................36
6.17.
Vital Signs..............................................................................................................36
6.18.
Laboratory Assessments .........................................................................................37
6.19.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) .....................................................................................37
6.20.
Survival..................................................................................................................38
7.
STUDY POPULATION.........................................................................................39
7.1.
Number of Subjects and Sites .................................................................................39
7.2.
Inclusion Criteria....................................................................................................39
7.3.
Exclusion Criteria...................................................................................................40
8.
DESCRIPTION OF STUDY TREATMENTS........................................................42
8.1.
Description of Investigational Product(s)................................................................42
8.1.1.
nab-Paclitaxel.........................................................................................................42
8.1.2.
Carboplatin.............................................................................................................42
8.2.
Treatment Administration and Schedule .................................................................43
8.3.
Dose Modifications.................................................................................................43
8.4.
Method of Treatment Assignment...........................................................................46
8.5.
Packaging and Labeling..........................................................................................46
8.6.
Investigational Product Accountability and Disposal ..............................................46
8.7.
Investigational Product Compliance........................................................................46
8.8.
Overdose ................................................................................................................46
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................48
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9.1.
Permitted Concomitant Medications and Procedures...............................................48
9.2.
Prohibited Concomitant Medications and Procedures..............................................48
9.3.
Required Concomitant Medications and Procedures................................................48
10.
STATISTICAL ANALYSES..................................................................................49
10.1.
Induction Part.........................................................................................................49
10.1.1.
Overview................................................................................................................49
10.1.2.
Study Population Definitions ..................................................................................49
10.1.2.1.
Intent-to-Treat Population.......................................................................................49
10.1.2.2.
Safety Population....................................................................................................49
10.1.3.
Sample Size and Power Considerations...................................................................49
10.1.4.
Background and Demographic Characteristics........................................................50
10.1.5.
Subject Disposition.................................................................................................50
10.1.6.
Efficacy Analysis....................................................................................................51
10.1.6.1.
Primary Purpose .....................................................................................................51
10.1.6.2.
Secondary Endpoints ..............................................................................................51
10.1.7.
Safety Analysis.......................................................................................................51
10.1.7.1.
Adverse Events.......................................................................................................51
10.1.7.2.
Laboratory Assessments .........................................................................................52
10.1.8.
Study Treatment Termination .................................................................................52
10.1.9.
Deaths ....................................................................................................................52
10.2.
Maintenance Part....................................................................................................52
10.2.1.
Overview................................................................................................................52
10.2.2.
Study Population Definitions ..................................................................................53
10.2.2.1.
Intent-to-Treat Population.......................................................................................53
10.2.2.2.
Response Evaluable Population ..............................................................................53
10.2.2.3.
Per-protocol (PP) Population ..................................................................................53
10.2.2.4.
Safety Population....................................................................................................53
10.2.3.
Sample Size and Power Considerations...................................................................53
10.2.4.
Background and Demographic Characteristics........................................................54
10.2.5.
Subject Disposition.................................................................................................55
10.2.6.
Efficacy Analysis....................................................................................................55
10.2.6.1.
Primary Endpoint....................................................................................................55
10.2.6.2.
Key Secondary Endpoints.......................................................................................56
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10.2.6.3.
Other Secondary Efficacy Endpoints.......................................................................56
10.2.6.4.
Exploratory Endpoints............................................................................................57
10.2.7.
Safety Analysis.......................................................................................................57
10.2.7.1.
Adverse Events.......................................................................................................57
10.2.7.2.
Laboratory Assessments .........................................................................................58
10.2.8.
Study Therapy Termination ....................................................................................58
10.2.9.
Deaths ....................................................................................................................58
10.2.10.
Interim Analysis .....................................................................................................58
10.3.
Data Monitoring Committee ...................................................................................59
10.4.
Scientific Steering Committee ................................................................................59
11.
ADVERSE EVENTS..............................................................................................60
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................60
11.2.
Evaluation of Adverse Events.................................................................................60
11.2.1.
Seriousness.............................................................................................................61
11.2.2.
Severity / Intensity..................................................................................................62
11.2.3.
Causality ................................................................................................................62
11.2.4.
Duration .................................................................................................................63
11.2.5.
Action Taken..........................................................................................................63
11.2.6.
Outcome.................................................................................................................63
11.3.
Abnormal Laboratory Values..................................................................................63
11.4.
Pregnancy...............................................................................................................63
11.4.1.
Females of Childbearing Potential ..........................................................................64
11.4.2.
Male Subjects.........................................................................................................64
11.5.
Reporting of Serious Adverse Events......................................................................64
11.5.1.
Safety Queries ........................................................................................................65
11.6.
Expedited Reporting of Adverse Events..................................................................65
12.
DISCONTINUATIONS .........................................................................................66
12.1.
Study Treatment Discontinuation............................................................................66
12.2.
Study Discontinuation ............................................................................................66
12.3.
Subject Replacement ..............................................................................................67
13.
EMERGENCY PROCEDURES.............................................................................68
13.1.
Emergency Contact.................................................................................................68
14.
REGULATORY CONSIDERATIONS...................................................................69
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2.3.


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14.1.
Good Clinical Practice............................................................................................69
14.2.
Investigator Responsibilities ...................................................................................69
14.3.
Subject Information and Informed Consent.............................................................69
14.4.
Confidentiality........................................................................................................70
14.5.
Protocol Amendments.............................................................................................70
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................70
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................71
14.8.
Closure of the Study ...............................................................................................71
15.
DATA HANDLING AND RECORDKEEPING.....................................................72
15.1.
Data/Documents .....................................................................................................72
15.2.
Data Management...................................................................................................72
15.3.
Record Retention....................................................................................................72
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................74
16.1.
Study Monitoring and Source Data Verification......................................................74
16.2.
Audits and Inspections............................................................................................74
17.
PUBLICATIONS ...................................................................................................75
18.
REFERENCES.......................................................................................................76
19.
APPENDICES........................................................................................................78
Appendix A: ECOG Performance Status Score .........................................................................78
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..70
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('06'RF1XPEHU
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Celgene Corporation
Confidential and Proprietary
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ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
LIST OF TABLES
Table 1:
Blinded Radiology Assessment of Overall Response Rate (ITT Population) ..........21
Table 2:
Blinded Radiology Assessment of Response Rate for Patients with 
Squamous or Non-squamous Histologies (ITT Subgroups).....................................21
Table 3:
Table of Events – Induction....................................................................................29
Table 4:
Table of Events – Maintenance...............................................................................32
Table 5:
Permanent Dose Reductions for Hematologic and Non-Hematologic 
Toxicities on the Study ...........................................................................................45
Table 6:
Precision of the Estimate for a Proportion Given a Sample Size of 540...................50
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2
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.......45
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('06'RF1XPEHU
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Celgene Corporation
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LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................27
&(/*(1(35235,(7$5<,1)250$7,21


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1.
INTRODUCTION
1.1.
Non-small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer-related deaths (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 recent advances in identifying optimal chemotherapy regimens, patients with 
advanced NSCLC continue to have a poor prognosis (especially those without identifiable 
biomarkers), with only 10% to 15% of those treated still alive after 2 years of diagnosis.
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 vs 
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). 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).
1.2.
nab-Paclitaxel
nab-Paclitaxel has been developed to reduce the toxicities associated with Taxol and the 
Cremophor EL/ethanol vehicle while maintaining or improving the chemotherapeutic effect of 
the drug. The Cremophor EL-free medium enables nab-paclitaxelto be given in a shorter 
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duration without the need for premedication to prevent solvent-related hypersensitivity reactions.
In addition, standard tubing and IV bags may be used for the IV administration of nab-paclitaxel.
nab-Paclitaxel for Injectable Suspension is approved under the trade name of ABRAXANE in 
the first-line setting in combination with carboplatin for patients with non-small cell lung cancer 
who are not candidates for curative surgery or radiation therapy in several countries (e.g. US, 
Japan,  Argentina, Australia, New Zealand, Ecuador, Chile and Guatemala). 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. nab-Paclitaxel is also 
approved for the treatment of patients with metastatic breast cancer and for the first-line 
treatment of metastatic adenocarcinoma of the pancreas.
The approval of nab-paclitaxel was based on the evaluation of Phase I and II data (Rizvi, 2008;
Socinski, 2010; Belani, 2008), as well as the pivotal Phase III study: A multicenter, randomized, 
open-label study was conducted in 1052 chemonaive patients 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 or development of an unacceptable toxicity. The primary 
efficacy outcome measure was overall response rate 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 
adenocarcinoma, 43% had squamous cell lung cancer, 76% were ECOG PS 1, and 73% were 
current or former smokers. Patients received a median of 6 cycles of treatment in both study 
arms. Patients in 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]. There was no statistically significant difference in the secondary endpoint
OS between the two study arms.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
21
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
Table 1:
Blinded Radiology Assessment of Overall Response Rate 
(ITT Population)
Variable
Category/Statistic
ABI-007/
carboplatin
(N=521)
Taxol/
carboplatin
(N=531)
Response Rate 
Ratio
(pA/pT)
P-value
Patients with Confirmed Complete or Partial Overall Response
n (%)
170 (33%)
132 (25%)
1.313
0.005*
Confidence Interval (CI) a
28.6, 36.7
21.2, 28.5
1.082, 1.593
Complete Response
0
1 (< 1%)
Partial Response
170 (33%)
131 (25%)
Source Data on File
a 95% CI of response rate and 95.1% CI of response rate ratio.
Note: P-value is based on a chi-square test.
* Indicates p-value < 0.049
Per protocol, patients were stratified by NSCLC histology (squamous cell carcinoma vs
adenocarcinoma vs other histology). Subgroup analyses were performed to assess the influence 
of squamous vs non-squamous histology on the primary efficacy endpoint of overall response 
rate (the percentage of patients who achieved an objective confirmed CR or PR based on the 
blinded radiological review using RECIST response guidelines, Version 1.0). The proportion of 
patients with squamous cell carcinoma who responded was significantly higher for the 
ABI-007/carboplatin regimen relative to the Taxol/carboplatin regimen (41% vs 24%: pA/pT: 
1.680; p < 0.001). The proportion of patients with non-squamous cell carcinoma with a 
confirmed complete or partial overall response was comparable between the ABI-007 and 
Taxol/carboplatin arms (26% vs 25%: pA/pT: 1.034; p = 0.808).
Table 2:
Blinded Radiology Assessment of Response Rate for Patients with Squamous 
or Non-squamous Histologies (ITT Subgroups)
Prognostic Factor
Category/Statistic/N
ABI-007/
carboplatin
Taxol/
carboplatin
Response Rate 
Ratio (pA/pT)
P-value
Patients with Confirmed Complete 
or Partial Overall Response
Squamous cell carcinoma
94/229 (41%)
54/221 (24%)
1.680
< 0.001*
95% Confidence Interval
1.271, 2.221
Non-squamous cell carcinoma
76/292 (26%)
78/310 (25%)
1.034
0.808
95% Confidence Interval
0.788, 1.358
Abbreviations: ITT = intent-to-treat
Note: P value is based on a chi-square test.
* Indicates p-value < 0.05.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
22
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
Adverse reactions were assessed in 514 nab-paclitaxel/carboplatin-treated patients and 524 
paclitaxel injection/carboplatin-treated patients. Patients in both treatment arms received a 
median of 6 cycles of treatment. The following common (≥ 10% incidence) adverse reactions 
were observed at a similar incidence in nab-paclitaxel plus carboplatin-treated and paclitaxel 
injection plus carboplatin-treated patients: 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).
Laboratory-detected abnormalities which occurred with a difference ≥5% for nab-paclitaxel plus 
carboplatin vs paclitaxel injection plus carboplatin (Grades1-4 [and G3-4]) are: anemia (98% vs 
91% [28% vs 7%]), neutropenia (85% vs 83% [47% vs 58%]) and thrombocytopenia (68% vs 
55% [18% vs 9%]).  
1.3.
Rationale for Development of nab-Paclitaxel as Maintenance 
Treatment in Squamous Cell NSCLC
Although significant advances have been made in the treatment options and outcomes of patients 
with non-squamous NSCLC, progress for patients with squamous cell NSCLC has been 
disappointing. Furthermore, the data of maintenance therapy that resulted in the FDA approval of 
pemetrexed (Alimta) and erlotinib (Tarceva), seems to confer benefit (and choice) primarily for 
non-squamous NSCLC patients.
Both Alimta studies as well as the Tarceva study demonstrated an overall survival benefit with 
maintenance vs. placebo (Paz-Arez, 2012; Tarceva package insert). However, both of the Alimta 
maintenance studies showed benefit in non-squamous patients only. Whereas Tarceva showed
significant benefit in the non-squamous cell NSCLC patients, only modest improvement was 
observed in squamous cell NSCLC patients (Neal, 2010).
To date there have been no randomized studies showing benefit of maintenance therapy in 
squamous NSCLC patients. Therefore, there is still an unmet medical need for maintenance 
treatment in squamous cell NSCLC. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
23
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
2.
STUDY OBJECTIVES
2.1.
Primary Objective
The primary objective of the study is to evaluate PFS with nab-paclitaxel as maintenance 
treatment after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous 
cell NSCLC.
2.2.
Secondary Objectives 
The secondary objectives of the study are:
!
To evaluate the safety and tolerability of nab-paclitaxel as maintenance treatment 
after response or SD with nab-paclitaxel plus carboplatin in subjects with squamous 
cell NSCLC.
!
To further assess the efficacy with nab-paclitaxel as maintenance treatment after 
response or SD with nab-paclitaxel plus carboplatin in subjects with squamous cell 
NSCLC, as measured by secondary efficacy endpoints.
2.3.
Exploratory Objectives
The exploratory objectives of the study are:
!
To determine baseline tumor characteristics which predict response and resistance to 
nab-paclitaxel/carboplatin during the Induction part of the study. 
!
To determine what changes in peripheral tumor characteristics during treatment are 
associated with acquisition of resistance in the subjects who had initial clinical 
benefit.
!
To assess healthcare resource utilization during the Maintenance part of the study.
!
To assess the LCSS and EQ5D.
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and EQ5D
and EQ5


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
24
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
3.
STUDY ENDPOINTS
3.1.
Primary Endpoint
Progression free survival from randomization into the Maintenance part of the study.
3.2.
Secondary Endpoints
3.2.1.
Safety
Safety parameters including AEs and SAEs.
3.2.2.
Efficacy
!
Overall survival from randomization into the Maintenance part of the study.
!
Overall response rate during the Induction and Maintenance parts of the study.
3.3.
Exploratory Endpoints
!
The correlation between pretreatment tumor characteristics and response and 
resistance to the study treatment determined using next-generation sequencing 
methods, immunohistochemistry, or other analysis methods.
!
The association between the changes in tumor characteristics and the acquisition of 
resistance to therapy from plasma samples taken at treatment failure during 
Maintenance.
!
The association between DNA nucleotide polymorphisms in subject’s germ line DNA 
and association with treatment efficacy and or toxicity.
!
Healthcare resource utilization during the Maintenance part of the study using a 
questionnaire including hospitalizations, emergency room visits, doctor or nurse 
visits, procedures, and/or additional medication.
!
Change in the LCSS and EQ5D.
the study
the study
parts of the 
arts of 
eri
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ng next
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and/or add
and/or add
LCSS
LCSS and


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
25
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is a Phase III, randomized, open-label, multi-center study of nab-paclitaxel plus BSC or 
BSC alone as maintenance treatment after response or SD with nab-paclitaxel plus carboplatin as 
induction in subjects with squamous cell NSCLC. Approximately 540 subjects with Stage 
IIIB/IV squamous cell NSCLC eligible to receive standard treatment of nab-paclitaxel plus 
carboplatin for 4 cycles will be enrolled in the Induction part of the study. If after the 4 cycles, 
the subject has a radiologically assessed CR, PR, or SD without clinical progression, they will be 
randomized (2:1) in the Maintenance part of the study to receive nab-paclitaxel plus BSC or 
BSC alone. BSC is defined as the best palliative care per investigator (including but not limited 
to: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional 
support, and/or focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis)
excluding antineoplastic agents. Approximately 260 subjects will be evaluable for the primary 
endpoint of PFS in maintenance.
4.1.1.
Induction Part
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Approximately 540 subjects eligible for 
standard treatment with nab-paclitaxel plus carboplatin for 4 cycles will be enrolled, provided if 
all inclusion/exclusion criteria are complied within a 28-day screening period prior to Cycle 1 
Day 1.
Induction treatment will commence on Cycle 1 Day 1: 
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD, and has met all eligibility criteria, they will continue on to the Maintenance part 
of the study. If the subject has radiological or clinical PD, they will be discontinued from the 
study and will not be followed.
4.1.2.
Maintenance Part
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD without clinical progression, they will be screened for eligibility over a 7-day 
period. Subjects (approximately 260) who satisfy all inclusion/exclusion criteria, will be 
randomized 2:1 to receive either:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day cycle plus BSC until disease progression (see Section 8.3 for guidelines on 
starting dose for the Maintenance part of the study if the subject had dose reduced 
during the Induction part of the study)
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
26
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
OR
!
BSC until disease progression
Maintenance therapy should start at the time of randomization. If this is not possible, a maximum 
of 7 days will be allowed from the date of randomization to the start date of Maintenance 
therapy. Subjects must start Maintenance therapy no earlier than 21 days and no later than 35
days from Day 1 of the fourth cycle of Induction therapy. 
Randomization will be stratified by disease stage (IIIB vs IV), response in induction (CR/PR vs 
SD), and performance status (0 vs 1).
4.1.3.
Follow-up Period 
All subjects who discontinue from the Maintenance part of the study for any reason other than 
withdrawal of consent, lost to follow-up, or death, will enter the Follow-up period that will have 
a visit 28 days after progression or discontinuation. Those subjects entering the follow up period
without documented progression will continue to have CT scans in accordance with standard of 
care until documented progression of disease. Additionally, subjects will be followed for OS by 
phone approximately every 90 days for up to 1.5 year after final analysis of approximately 182 
PFS events or approximately 218 deaths have been observed for the final OS analysis, whichever 
is earlier.
4.2.
Study Design Rationale
The results of promising activity with nab-paclitaxel in NSCLC, especially in squamous cell 
NSCLC, underscore the hypothesis for this Phase III study as a superiority trial to compare nab-
paclitaxel/BSC vs BSC as maintenance therapy in subjects with squamous cell NSCLC
(randomizing subjects with CR/PR/SD after Induction treatment with nab-paclitaxel/
carboplatin). The nab-paclitaxel regimen used for Induction will be in accordance with the FDA 
approved label, 100 mg/m2 administered once per week on Days 1, 8 and 15 of each 21-day
cycle with no break combined with carboplatin AUC = 6 mg*min/mL administered on Day 1 
every 21 days. Four cycles of doublet-chemotherapy is chosen as the cut-off, based on observed 
risk:benefit results that additional cycles of doublet chemotherapy did not confer significant 
advantages (Socinski, 2002); furthermore, 4 cycles of doublet-chemotherapy represents general 
trends of practice (Stinchcombe, 2009).
The nab-paclitaxel regimen used for Maintenance will be 100 mg/m2 administered on Days 1 
and 8 of each 21-day cycle until progression (the actual starting dose may be adjusted as 
specified in Section 8.3). The nab-paclitaxel dosing regimen was reduced to Days 1 and 8 of 
each 21-day cycle in the Maintenance part of the study to decrease potential toxicity and possibly 
optimize tolerability of treatment and drug exposure in subjects. Sufficient subjects will be
enrolled to provide adequate power to compare PFS. The safety and tolerability of nab-paclitaxel
will be assessed.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
27
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
Figure 1:
Overall Study Design
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
28
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
4.3.
Study Duration
The Induction part of the study will last approximately 36 months to randomize sufficient 
subjects for the Maintenance part of the study. The total length of this Phase III study with 
Induction, Maintenance, and Follow-up is estimated to last approximately 5 years.
4.4.
End of Trial
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
study, or the date of receipt of the last data point from the last subject that is required for 
primary, secondary and/or exploratory analysis, as pre-specified in the protocol and/or the 
Statistical Analysis Plan (SAP), whichever is the later date.
&(/*(1(35235,(7$5<,1)250$7,21
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
29
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
5.
TABLE OF EVENTS
Table 3:
Table of Events – Induction
CYCLE 1 and 3 (21-day)
CYCLE 2 and 4 (21-day)
Assessment
Screening/
Baseline
(up to 28 
days)
Day 1
(C3: ±2 
days)
Day 8
(±2 days)
Day 15
(±2 days)
Day 1
(±2 days)
Day 8
(±2 days)
Day 15
(±2 days)
At the end 
of Cycles 2 
and 4 
(-3/+7 days)
Early
Treat-
ment 
Discon-
tinuation /
End of 4 
Cycles
Unsched-
uled
Informed Consent
X
-
-
-
-
-
-
-
-
-
Medical History
X
-
-
-
-
-
-
-
-
-
Prior Medication and Procedures
X
-
-
-
-
-
-
-
-
-
Serum β-hCGa
X
X
-
-
X
-
-
-
X
-
Complete Chest CT Scan (including 
adrenal gland) with contrast and any 
other studies required for tumor 
imagingb
X
-
-
-
-
-
X
X
Xc
Weight
X
X
X
X
X
X
X
-
X
Xc
Archived Tumor Tissue Sample for 
Biomarker (biopsy, surgical specimen, 
or other diagnostic tumor sample)
-
X (C1D1 
only)
-
-
-
-
-
-
-
-
Plasma for Biomarker Analyses 
-
X (C1D1 
only)
-
-
-
-
-
-
X
-
Blood for PharmacogenomicAnalyses
-
X (C1D1 
only)
-
-
-
-
-
-
-
-
Body Surface Area (BSA) Calculation 
and Heightd
X
-
-
-
-
-
-
-
-
Xc
ECOG status
X
X
-
-
X
-
-
-
X
Xc
Concomitant Medication/Procedures
X
X
X
X
X
X
X
-
X
Xc
Peripheral Neuropathy Assessmente
X
X
X
X
X
X
X
-
X
Xc
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
30
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
Table 3:
Table of Events – Induction (Continued)
CYCLE 1 and 3 (21-day)
CYCLE 2 and 4 (21-day)
Assessment
Screening/
Baseline 
(up to 28 
days)
Day 1
(C3: ±2 
days)
Day 8
(±2 days)
Day 15
(±2 days)
Day 1
(±2 days)
Day 8
(±2 days)
Day 15
(±2 days)
At the end 
of Cycle 2 
and 4 (-3/+7 
days)
Early 
Treat-
ment 
Discon-
tinuation / 
End of 4 
Cycles
Unsched-
uled
Hematology and Serum Chemistry f
X
X
X
X
X
X
X
-
Xc
X
Adverse Event Evaluation
X
X
X
X
X
X
X
-
X
Xc
nab-paclitaxel Administration
-
X
X
X
X
X
X
-
-
-
Carboplatin Administration
-
X
-
-
X
-
-
-
-
-
LCSS and EQ5D
-
X
-
-
X
-
-
-
X
-
Electrocardiogram (ECG)
X
-
-
-
-
-
-
-
-
Xc
CT Scan of Head or Brain 
Magnetic Resonance 
Imaging (MRI) g
X
-
-
-
-
-
-
-
-
Xc
Bone Scan (X-rays if 
needed)g
X
Xc
Physical Examination
X
-
-
-
-
-
-
-
X
Xc
Vital Signs
X
-
-
-
-
-
-
-
X
Xc
C3: Cycle 3, eCRF: electronic Case Report Form, C1D1: Cycle 1 Day 1, AE: Adverse Event, SAE: Serious Adverse Event, ECOG: Eastern Cooperative Oncology Group, CT: Computed Tomography, 
b-HCG: beta human chorionic gonadotropin, RECIST: Response Evaluation Criteria in Solid Tumors, LCSS: Lung Cancer Symptom Scale, EQ5D: EuroQol 5D
a A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a Serum β-hCG pregnancy test must be performed to assess
eligibility at Screening/Baseline and within 72 hours of the first administration of study drug before beginning each new cycle. Note: the screening serum pregnancy test can be 
used as the test prior to Day 1 study therapy if it is performed within the 72-hour timeframe.
b All subjects must have a radiographically documented measurable tumor(s) by RECIST v1.1 criteria: Complete chest CT scan (including adrenal gland) with and without 
contrast are performed at Screening, at the end of Cycles 2 and 4 during Induction part, early termination, and if clinically indicated while on-treatment. The methods of 
assessment chosen at baseline to follow tumors are to remain consistent throughout study duration. Scans will be archived as per institution standards.
c If clinically indicated.
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, at the end of
the end of
follow tumors
follow tumor


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
31
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
d BSA calculated at baseline and recalculated if body weight changes by more than 10% since baseline or since the previous visit when BSA was recalculated.
e The occurrence of peripheral neuropathy should be reported by the investigator as an AE or SAE.
f Laboratory assessments will be done prior to each treatment by local laboratories and as clinically indicated. The results from laboratory assessments will be captured as per 
Section 6.18.
g At Screening, if lesions are suspected.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
32
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
Table 4:
Table of Events – Maintenance
EVERY CYCLE
(21-day)
Assessment
Screening/ 
Baseline
(up to 14
days)
Day 1
(±2 days, 
except 1st
cycle)
Day 8
(±2 days)
Every 42 
days
(-3/+7 days)
Early 
Treatment 
Discon-
tinuation /
Disease
Progression
28-day 
Follow-up 
visit
Survival 
(every 90 
days) up 
to as 
specified 
in Section 
6.20
Unsched-
uled
Serum β-hCGa
X
X
-
-
X
-
-
-
Complete Chest CT Scan (including adrenal 
gland) with contrast and any other studies 
required for tumor imaging b
Xc
-
-
X
X
-
-
Xd
Weight
X
X
X
-
X
X
-
Xd
Plasma for Biomarker Analyses
-
-
-
X
-
-
-
Body Surface Area (BSA) Calculation and 
Heighte
X
-
-
-
-
-
-
Xd
ECOG status
Xf
X
-
-
X
-
-
Xd
Concomitant Medication/Procedures
X
X
X
X
X
X
X
Xd
Peripheral Neuropathy Assessmentg
X
X
X
-
X
X
-
Xd
Hematology and Serum Chemistry h
X
X
X
-
X
X
-
Xd
Adverse Event Evaluation
X
X
X
X
X
X
-
Xd
nab-paclitaxel Administration
-
X
X
-
-
-
-
Survival phone call 
-
-
-
-
-
-
X
-
Healthcare Resource Utilization 
Questionnaire
-
X
-
-
X
-
-
-
LCSS and EQ5D
-
X
-
-
X
-
-
-
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
33
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
Table 4:
Table of Events – Maintenance (Continued)
EVERY CYCLE
(21-day)
Assessment
Screening/ 
Baseline
(up to 14
days)
Day 1
(±2 days, 
except 1st
cycle)
Day 8
(±2 days)
Every 42 
days
(-3/+7 days)
Early 
Treatment 
Discon-
tinuation / 
Disease 
Progression
28-day 
Follow-up 
visit
Survival 
(every 90 
days) up 
to as 
specified 
in Section 
6.20
Unsched-
uled
Electrocardiogram (ECG)
Will be done as per standard of care during the study and as clinically indicated, however results will not 
be routinely collected in the eCRFs. However if abnormal and clinically significant results, will be collected as AE or SAE and if 
scans show documented progression of disease will be collected on eCRF.
CT Scan of Head or Brain Magnetic 
Resonance Imaging (MRI)
Bone Scan (X-rays if needed)
Physical Examination
Vital Signs
C1: Cycle 1, eCRF: electronic Case Report Form, AE: Adverse Event, SAE: Serious Adverse Event, ECOG: Eastern Cooperative Oncology Group, CT: Computed Tomography, b-HCG: beta human 
chorionic gonadotropin, LCSS: Lung Cancer Symptom Scale, EQ5D: EuroQol 5D 
a A pregnancy test is required for women of child-bearing potential only. For women of child-bearing potential a Serum β-hCG pregnancy test must be performed to assess subject
eligibility at Screening/Baseline and within 72 hours of the first administration of study drug before beginning each new cycle. Note; the screening serum pregnancy test can be 
used as the test prior to Day 1 study therapy if it is performed within the 72-hour timeframe.
b Complete chest CT scan (including adrenal gland) with and without contrast is performed at baseline, every 42 days (-3/+7 days) while on-treatment (schedule based on calendar, 
not start of cycle), early termination, and if clinically indicated while on-treatment. The methods of assessment chosen at baseline to follow tumors are to remain consistent 
throughout study duration. Scans will be archived as per institution standards. Those subjects entering the follow up period without documented progression will continue to 
have CT scans in accordance with standard of care until documented progression of disease.
c Induction End of Cycle 4 information may serve as baseline for Maintenance.
d If clinically indicated.
e BSA calculated at baseline and recalculated if body weight changes by more than 10% since baseline or since the previous visit when BSA was recalculated.
f The ECOG performance status must be 0 or 1 for subjects to start maintenance treatment.
g The occurrence of peripheral neuropathy should be reported by the investigator as an AE or SAE.
h Laboratory assessments will be done prior to each nab-paclitaxel treatment by local laboratories as per standard of care during the study and as clinically indicated. The results 
from laboratory assessments will be captured as per Section 6.18.
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ECOG: East
men of child
men of child
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on of study 
72
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
34
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
6.
PROCEDURES
Subjects will be provided with a written informed consent form (ICF), given the opportunity to 
ask any questions concerning the study, and will sign an ICF prior to participating in any study 
procedures. After giving written informed consent, subjects will undergo a screening period to be 
assessed for eligibility. All subjects who sign an ICF must be screened into the Interactive Voice 
Response System (IVRS) immediately upon signature on the document. Subjects who do not 
meet the inclusion/exclusion criteria will be considered screening failures and will not be eligible 
for the study. Subjects that have satisfied all eligibility criteria after the screening period will be 
eligible to be enrolled. Subjects who screen fail may re-screen up to 3 times and an ICF will need 
to be signed at each re-screen, 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).
Serum Chemistry or CT scans performed in accordance with the local standard of care within 28 
days before first dose of study drug , and prior to signing the ICF, can be used for the screening 
assessment.
6.1.
Medical History
A complete medical history including, but not limited to, evaluation for past (up to 5 years) or 
present cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine, 
lymphatic, hematological, immunologic, dermatological, psychiatric, genitourinary, obstetrical, 
surgical history, smoking history, or any other diseases or disorders will be performed at 
Screening. 
6.2.
Prior Medications/Procedures
All prior medications/procedures within 28 days of time of signature on the ICF should be 
recorded. All NSCLC-related prior medications/procedures should be recorded regardless of 
time.
6.3.
Pregnancy Testing
Serum pregnancy test with sensitivity of at least 25 mIU/mL is to be obtained in females of 
childbearing potential (FCBP) at Screening for Induction and Maintenance. A serum pregnancy 
test must be done within 72 hours prior to Cycle 1 Day 1 of starting study therapy, repeated 
before beginning each new cycle, and at discontinuation or end of treatment. The subject may 
not receive treatment until the investigator has verified that the result of the pregnancy test is 
negative. See inclusion criteria for pregnancy testing requirements. Any pregnancies that occur 
in women who have received study drug must be immediately reported to Celgene Drug Safety 
(See Section 11.4).
6.4.
Complete Chest Computed Tomography (CT) Scan (including 
adrenal gland) With and Without Contrast
Complete Chest CT Scan (including adrenal gland) with and without contrast and any other 
studies required for tumor imaging will be done at Screening, at the end of Cycles 2 and 4, and at 
Early Treatment Discontinuation during the Induction part of the study. During the Maintenance 
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ill be
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ocedures 
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n).).
d of care w
d of care w
sed for the 
sed for the
uat
uatioion n fo
for p
hepat
epatic, neu
ic, n
l, psychia
, psychiatrt
es or di
es or disord
sord
res
res
28
28 day
days of
edicati
edications/
o
sting
sting
ith sensit
ith sensitiv
l ( (FCBP
FCBP) a
wi
within 72 h
thin 72 h
i
ng each new
g each new
eatmen
eatmentn un
u
See inclusi
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Section
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&
6.4.
6.4


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
35
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
part of the study, scans will be done every 42 days (-3/+7 days) (schedule for scans will be based 
on calendar, not start of cycle) and at Early Treatment Discontinuation/Disease Progression.
Additional CTs may be done at any time during the study if clinically indicated. CT scans are 
preferred, however MRI would be acceptable. The same scanning modality for lesion assessment 
should be used throughout the study. All scans and reports should be archived as per institution 
standards.
6.5.
Weight
Weight will be collected at every visit during the Induction and Maintenance parts of the study. 
Additional weights may be collected at any time during the study as needed.
6.6.
Body Surface Area (BSA) Calculation and Height
BSA and height will be collected and calculated at Screening during Induction and Maintenance 
parts of the study. BSA may be recalculated if body weight changes by more than 10% since 
baseline or since the previous visit when BSA was recalculated.
6.7.
ECOG Performance Score
ECOG performance score will be collected at Screening, Day 1 of every cycle and at Early 
Treatment Discontinuation/End of Cycle 4 during the Induction part of the study. During the 
Maintenance part of the study, ECOG performance score will be collected at Screening, Day 1 of 
every cycle, and at Early Treatment Discontinuation/Disease Progression. Additional ECOG may 
be collected at any time during the study as needed.
6.8.
Concomitant Medications/Procedures
All subjects will have concomitant medications and procedures recorded from the time of 
signature on the ICF until progression during the Induction part of the study or the 28-day 
follow-up visit during the Maintenance part of the study. Only NSCLC associated concomitant 
medications/procedures will be recorded, including BSC. During survival follow-up, anti-cancer 
treatment information will be collected, if available.
6.9.
Peripheral Neuropathy Assessment
Peripheral neuropathy assessment will be done from the time of signature on the ICF until 
progression during the Induction part of the study or the 28-day follow-up visit during the 
Maintenance part of the study. Additional peripheral neuropathy assessments may be done at any 
time during the study as needed.
6.10.
Adverse Event Reporting
All subjects will have AEs 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. 
6.11.
Lung Cancer Symptom Scale Questionnaire and EQ5D
The Lung Cancer Symptom Scale (LCSS) and (EQ-5D) questionnaires will be used to measure 
quality of life (QoL) for subjects in the trial. The LCSS is a 9 question analysis the subject
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dy.
and
and Mainte
Main
e than 10%
than 10%
 of every c
of eve
tion part of
ion part of
will be col
will be col
Disease Prog
Disease Pro
rocedure
rocedure
atatioions and 
ns and 
during the
during the
ance part of
ce part o
ecorded
ecorded, in
, in
co
collected
llected i
l Neuropa
l Neuro
hy assessm
assessm
y
ng the Ind
ng the Indu
d
part of the 
art of the
g the study
the study
Adv
Ad
All
All subjects
subjects
dose of s
dose of s


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
36
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
completes using a visual analogue scale (VAS) to denote intensity of a symptom. The EQ-5D 
comprises 5 questions on mobility, self-care, usual activities, pain/discomfort, anxiety/depression 
and a VAS for overall QoL. These questionnaires will be completed at Day 1 of every cycle, and 
at Early Treatment Discontinuation/End of Cycle 4 during the Induction part of the study, during 
the Maintenance part of the study, at Day 1 of every cycle, and at progression of disease. The 
quality of life data generated from these questionnaires will be analyzed per the description in 
the SAP.
6.12.
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 cycle, and at progression of disease during the Maintenance part of 
the study.
6.13.
Electrocardiogram 
An Electrocardiogram (ECG) will be performed at screening and as clinically indicated;
however, normal and non-clinically significant results will not be collected in the eCRFs. If 
results are abnormal and clinically significant at Screening, they will be recorded as medical 
history. If results are abnormal and clinically significant after Screening, they will be recorded as 
AE or SAE).
6.14.
CT Scan of Head or Brain Magnetic Resonance Imaging (MRI)
CT scan of head or brain MRI will be performed at screening if lesions are suspected and as 
clinically indicated during the study; however, results will not be collected in the eCRFs. If scans 
show progression of disease, this information will be collected on the eCRF.
6.15.
Bone Scans and X-rays
Bone scans and x-rays will be performed at screening if lesions are suspected and as clinically 
indicated during the study; however, results will not be collected in the eCRFs. If scans show 
progression of disease, this information will be collected on the eCRF.
6.16.
Physical Examinations
Physical examinations will be performed at screening and treatment discontinuation and any 
other time as clinically indicated/per the institutional practice. However, results will not be 
routinely collected on the eCRFs.   If the findings are abnormal and clinically significant at 
screening, they will be recorded as medical history, and if findings are abnormal and clinically 
significant after screening, they will be recorded as an AE or SAE.
6.17.
Vital Signs
Vital signs will be measured at screening, treatment discontinuation, and any other time as 
clinically indicated / standard of care for the institution. However, results will not be routinely 
collected on the eCRFs.   If the findings are abnormal and clinically significant at screening, they 
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6.17.
.17.


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
37
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
will be recorded as medical history, and if findings are abnormal and clinically significant after 
screening, they will be recorded as an AE or SAE.
6.18.
Laboratory Assessments
Laboratory assessments will be done prior to each nab-paclitaxel treatments by local laboratories 
as per standard of care during the study and as clinically indicated, however results will not be 
collected in the eCRFs unless they are determined to be clinically significant laboratory 
abnormalities. 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. Abnormal and 
clinically significant laboratory assessments at Screening will be recorded as medical history, 
and after Screening, as AE or SAE (clinically significant laboratory abnormalities at Screening 
may result in a subject being ineligible for the study and should not be captured as an AE). If a 
clinically significant laboratory abnormality is captured as medical history, AE, or SAE, the 
specific laboratory parameter(s) should be recorded on the laboratory assessments CRF. Any 
abnormal values that persist should be followed at the discretion of the Investigator. The 
Investigator should file all copies of the reports, including faxes with the subject’s medical chart.
6.19.
Tumor Tissue Sample Collection and Peripheral Blood Collection 
(Exploratory Assessments) 
If archival tumor biopsy blocks or (preferably) surgical specimens from subjects with prior 
resections are available, 10 or more slides of at least 4 um thickness will be collected at Cycle 1 
Day 1 of Induction. Additionally a core of an area representing viable tumor epithelium will be 
collected from the block. If the amount of tumor tissue available is not sufficient, fewer slides 
may be collected. 
If a fine needle aspirate (FNA) specimen is available, slides of at least 4 um thickness will be 
collected with the goal of obtaining at least 100,000 cells (preferably more) of material. If 
sufficient material cannot be collected, fewer slides/cells may be collected.
If only other types of diagnostic samples such as endoscopies, lavage, or sputum are available, 
this material should be optionally collected when possible, and collection is strongly encouraged 
when tissue such as endoscopy samples with multiple needle passes exists in quantities 
comparable to a core biopsy. In this instance, 10 slides and a core sample of tumor tissue should 
be collected as per biopsy and surgical samples above.
Plasma for biomarker analyses will be collected on Day 1 of Cycle 1 during Induction and at 
progression during the Maintenance part of the study. When progression occurs during Induction 
and before Cycle 4, a plasma sample will be collected at the time of study withdrawal.
Peripheral blood will be collected for pharmacogenomic analyses on Cycle 1 Day 1 of Induction.
Types of techniques planned to be used for tumor and blood analyses include:
!
Gene expression by RNA sequencing
!
Immunohistochemistry 
!
DNA sequencing
tory
ory,
creening
creening
an AE).
an AE). If a
If 
or SAE, th
or SAE, th
ments CRF.
ments CRF.
est
estigator. T
igator. T
e subject’s
e subject
heral Bloo
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s frf
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um thickne
epresent
epresenting
i
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east 100,00
ast 100,0
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samples su
samples su
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py sampl
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opsy and 
arker analy
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
38
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
Details regarding the collection, storage, and shipment of the samples are given in the Laboratory 
Manual.
6.20.
Survival
After discontinuation from the Maintenance part of the study, the subjects will be followed for 
survival by phone approximately every 90 days for up to 1.5 year after final analysis of 
approximately 182 PFS events, or approximately 218 deaths have been observed for the final OS 
analysis, whichever is earlier. The subjects will also be asked questions of other medications they 
may be taking for their NSCLC. 
&(/*(1(35235,(7$5<,1)250$7,21
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
39
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Subjects with squamous cell NSCLC stage IIIB or IV with no prior chemotherapy for metastatic 
disease who are ≥ 18 years old will be eligible for this study. The Induction part of the study will 
enroll approximately 540 subjects. Based on results from the nab-Paclitaxel Phase 3 NSCLC 
development study (Protocol CA031) it is estimated that approximately 260 subjects with CR, 
PR, or SD from the Induction part of the study will be randomized to the Maintenance part of the 
study. Enrollment into the Induction part of the study will be monitored and adjusted to ensure 
that approximately 260 subjects are randomized into the Maintenance part of the study. The 
study will be conducted at approximately 120 sites in the United States and European Union 
(EU).
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the Induction and Maintenance parts 
of the study (except if specified at study entry only):
General and Demographics
1. Age ≥ 18 years of age at the time of signing the ICF.
2. Understand and voluntarily provide written consent to the ICF prior to conducting any 
study related assessments/procedures. 
3. Able to adhere to the study visit schedule and other protocol requirements
Disease Specific
4. Histologically or cytologically confirmed Stage IIIB or IV squamous cell NSCLC at 
study entry.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease at study entry (as defined by the 
RECIST v1.1 criteria).
7. No prior chemotherapy for the treatment of metastatic disease at study entry. Adjuvant
chemotherapy is permitted providing cytotoxic chemotherapy was completed 12 months 
prior to starting the study 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 × ULN except in cases of Gilbert’s disease and liver metastases. 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
40
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
13. Creatinine ≤ 1.5 mg/dL.
14. Expected survival of > 12 weeks for the Induction part of the study.
15. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
16. For Maintenance part of the study, subjects must have received at least one dose of nab-
paclitaxel in each of the 4 cycles during Induction 
Pregnancy 
17. Females of childbearing potential [defined as a sexually mature woman who (1) have not 
undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy 
(the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for 
at least 24 consecutive months (ie, has had menses at any time during the preceding 24 
consecutive months)] must:
a.
agree to take a pregnancy test prior to starting study medication and throughout the 
study participation.
b. commit to complete abstinence from heterosexual contact, or agree to use medical 
doctor-approved contraception throughout the study without interruption, and while 
receiving study medication or for a longer period if required by local regulations.
Male subjects must:
c.
agree to complete abstinence from heterosexual contact or use a condom during 
sexual contact with a female of child bearing potential while receiving study 
medication and within 6 months after last dose of study medication, even if he has 
undergone a successful vasectomy.
18. Females must abstain from breastfeeding during study participation and for 3 months 
after IP discontinuation. Women must not be breastfeeding .
7.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment into the Induction
and Maintenance parts of the study (except if specified at study entry only):
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 first dose of study drug).
2. Only evidence of disease is non-measurable at study entry.
3. Preexisting peripheral neuropathy of Grade 2, 3, or 4 (per CTCAE v4.0).
4. Venous thromboembolism within 6 months prior to signing ICF.
5. Current congestive heart failure (New York Heart Association class II-IV).
6. 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.
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not 
not
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
41
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
7. Treatment with any investigational product within 28 days prior to signing ICF.
8. History of allergy or hypersensitivity to nab-paclitaxel or carboplatin.
9. Currently enrolled in any other clinical protocol or investigational trial that involved 
administration of experimental therapy and/or therapeutic devices.
10. Any other clinically significant medical condition and/or organ dysfunction that will 
interfere with the administration of the therapy according to this protocol.
11. 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 treatments that
should have been completed 6 months prior to signing ICF.
12. 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.
13. Any condition, including the presence of laboratory abnormalities, that places the subject 
at unacceptable risk if he/she were to participate in the study.
14. Any condition that confounds the ability to interpret data from the study.
15. Pregnant and nursing females.
&(/*(1(35235,(7$5<,1)250$7,21
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
42
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Investigational Product(s)
Induction 
The nab-paclitaxel and carboplatin treatments will not be supplied by Celgene during induction 
in those countries where nab-paclitaxel plus carboplatin is available for the treatment of NSCLC.  
Investigative sites will use standard of care (commercially available) product via prescription in 
these countries.
In those countries where nab-paclitaxel plus carboplatin is not available for the treatment of 
NSCLC, both agents will be designated as investigational product (IP) and will be packaged and 
supplied by Celgene.
Maintenance 
Subjects will be randomized to receive open-label nab-paclitaxel plus BSC or BSC during the 
Maintenance part of the study. The nab-paclitaxel used in the Maintenance part of the study is
designated as IP and will be packaged and supplied by Celgene Corporation. 
The preparation for IV administration procedures for IP should be followed as per Prescribing 
Information.
8.1.1.
nab-Paclitaxel
nab-Paclitaxel will be supplied by the Sponsor, Celgene Corporation, for the Maintenance part in 
all countries and for the Induction part if not available in a country. nab-Paclitaxel will be 
supplied in single-use vials in single count cartons. Each single-use 50 mL vial will contain 
paclitaxel (100 mg) and approximately 900 mg human albumin as a stabilizer.
Please see local prescribing information for Abraxane for detailed instructions on the
reconstitution, storage conditions and IV administration of nab-paclitaxel.
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 must 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 IP 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-cyclobutanedicarboxylato
(2-)0,0’]-,(SP-4-2). Carboplatin is a crystalline powder with the molecular formula of 
C6Hl2N204Pt and a molecular weight of 371.25. It is soluble in water at a rate of approximately 
14 mg/mL, and the pH of a 1% solution is 5 to 7. It is virtually insoluble in ethanol, acetone, and
dimethylacetamide.
For additional information about carboplatin storage, preparation, and administration please refer 
to the package insert. 
C. . 
n inin
ment of 
nt of 
packaged a
ackaged
BSC or BSC
BSC or B
enance pa
nance partr
Corporati
rporation
o
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llo
Celgene Co
elgene Co
vailable
vailable inin
cartons. Ea
artons. E
900 m
00 mg hum
g h
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atioion fo
for Ab
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and IV ad
and IV ad
xel should b
xel should b
xel should 
xel should 
extremes an
extremes a
ds for 
ds for nab
nab
itoring team
itoring team
Carbopla
Carbopla
plplatatini is a p
s a p
ent. The che
nt. The che
(2-)-)0,0’]
0,0’]- (
C6Hl2N
m


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
43
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
8.2.
Treatment Administration and Schedule
Induction
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. Approximately 540 subjects will be treated
with nab-paclitaxel plus carboplatin for 4 cycles.
Induction treatment will commence on Day 1, in accordance with standard of care of 1st line 
treatment of metastatic NSCLC: 
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion
Maintenance Part
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed
CR, PR, or SD without clinical progression, they will be randomized 2:1 (approximately 260
subjects) to receive:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day cycle plus BSC until disease progression (the actual starting dose may be 
adjusted as specified in Section 8.3)
OR
!
BSC until disease progression
Maintenance therapy should start at the time of randomization. If this is not possible, a maximum 
of 7 days will be allowed from the date of randomization to the start date of Maintenance 
therapy. Subjects must start Maintenance therapy no earlier than 21 days and no later than 35
days from Day 1 of the fourth cycle of Induction therapy.
Subjects may receive BSC as needed per Investigator discretion and should be recorded.
All IP will be administered by the clinical site and administration will be documented in the 
study source record.
8.3.
Dose Modifications
Subjects will be evaluated for AEs at each visit with the NCI CTCAE v4.0 used as a guide for 
the grading of severity.  The dose of nab-paclitaxel and carboplatin for each subject will be 
modified following toxicity as described in Table 5.
Subjects who experience any of the adverse drug reactions in Table 5 will be dose reduced as per 
Table 5 during the Induction and Maintenance parts of the study. If a subject is dose reduced in 
the Induction part of the study, please refer to Table 5 for guidelines on dose and schedule for the 
Maintenance part of the study.
!
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. 
each
ach
er com
er complet
ple
m
diol
ologi
ogical
c ly
2:1 (approx
2:1 (appro
utes
utes on Da
on D
he actual st
e actual s
e of random
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nce ther
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be evaluate
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of severit
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Table
Table 5 dur
dur
the Indu
e Ind
ain


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
44
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
!
In subjects who develop severe neutropenia or thrombocytopenia, on Day 1 of any 
cycle, withhold treatment until the ANC recovers to at least 1500 cells/mm3 and the 
platelet count recovers to at least 100,000 cells/mm3. On Days 8 and 15 the ANC 
should recover to at least 500 cells/mm3 and platelet count of at least 50,000 
cells/mm3. When dosing is resumed, the subject should be dosed at the next lower 
dose level of nab-paclitaxel and carboplatin as outlined in Table 5.
!
Withhold nab-paclitaxel for Grade 3 or 4 peripheral neuropathy. Resume nab-
paclitaxel and carboplatin at reduced doses (Table 5) when peripheral neuropathy 
improves to Grade 1 or completely resolves.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
45
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
Table 5:
Permanent Dose Reductions for Hematologic and Non-Hematologic Toxicities on the Study
Adverse Drug Reaction
Occurrence
nab-Paclitaxel 
Dose (mg/m2)
Carboplatin Dose 
(mg*min/mL)
Starting Dose Maintenance:
nab-paclitaxel Dose (mg/m2) Days 1 
and 8 of each 21-day Cycle
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
If subject at 100, 75 or 50 at end of 
Induction and ANC > 1500/mm3, will 
start at 100, 100 or 75 respectively 
during Maintenance
Second
50
3.0
Third
Discontinue Treatment*
Platelet count < 50,000/mm3
First
75
4.5
If subject at 100 or 75 at end of
Induction and platelet > 100,000/mm3, 
will start at 100 during Maintenance
Second
Discontinue Treatment*
Peripheral Neuropathy Grade 3 or 4
First
75
4.5
If subject at 100, 75 or 50 at end of
Induction and Grade 1 or no peripheral 
neuropathy, will start at 100, 100 or 75 
respectively during Maintenance
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
If subject at 100, 75 or 50 at end of
Induction and <  a Grade 2 or none of 
the noted events, will start at 100, 100
or 75 respectively during Maintenance
Second
50
3.0
Third
Discontinue Treatment*
Grade 4 cutaneous toxicity, diarrhea or mucositis
First
Discontinue Treatment*
ANC: Absolute Neutrophil Count
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
46
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
8.4.
Method of Treatment Assignment
The Induction and Maintenance parts of the study are open-label. In the Maintenance part of the 
study, subjects will be randomized 2:1 to nab-paclitaxel plus BSC or BSC alone. 
Enrollment/randomization will occur via IVRS for all parts of the study. 
8.5.
Packaging and Labeling
The label(s) for IP (nab-paclitaxel) will include Sponsor name, address and telephone number, 
the protocol number, IP name, dosage form and strength (where applicable), amount of IP per 
container, lot number, expiry date (where applicable), medication identification/kit number, 
dosing instructions, storage conditions, and required caution statements and/or regulatory 
statements as applicable. Additional information may be included on the label as applicable per 
local regulations.
8.6.
Investigational Product Accountability and Disposal
Celgene (or designee) will review with the Investigator and relevant site personnel the process 
for IP return, disposal, and/or destruction including responsibilities for the site vs. Celgene (or 
designee).
Celgene will instruct the Investigator on the return, disposal and/or destruction of IP and/or 
medical device materials if applicable. Only completely unused IP vials should be retained by 
the site until a representative from Celgene or other Celgene-designated personnel have 
completed an inventory. Partially used an completely used vials should be destroyed according to 
local guidelines, and disposition should be recorded on the Investigational Drug Accountability 
Record Form.
The investigator, or designee, shall record the dispensing of IP to subjects in an IP accountability 
record. The IP record will be made available to Celgene, or other authorized Celgene-designated 
monitoring personnel for the purpose of accounting for the IP supply. Inspections of the IP 
supply for inventory purposes and assurance of proper storage will be conducted as necessary. 
Any significant discrepancy will be recorded and reported to Celgene or their designee and a 
plan for resolution will be documented.
Investigational product will not be loaned or dispensed by the investigator to another investigator 
or site. Under certain circumstances, and with sponsor permission, cooperative groups may 
manage IP between locations within their network as clinical trial agreement and local guidelines 
permit.
8.7.
Investigational Product Compliance
All IP will be administered only by study site personnel and accurate recording of all IP 
administration will be made in the appropriate section of the subject’s eCRF and source 
documents.
8.8.
Overdose
Overdose, as defined for this protocol, refers to nab-paclitaxel or carboplatin dosing only.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
47
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel or carboplatin to a given subject, regardless of any associated adverse events or 
sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate.
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. See 
Section 11.1 for the reporting of adverse events associated with overdose.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
48
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
All supportive care is permitted. 
9.2.
Prohibited Concomitant Medications and Procedures
Other antineoplastic agents or IP other than what is specified in the protocol is prohibited.
9.3.
Required Concomitant Medications and Procedures
Not applicable.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
49
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the Induction and 
Maintenance parts of the study are described below by study part. Although some definitions for 
the efficacy and safety endpoints, and the analysis populations are the same for both parts of the 
study, they are repeated in the respective section to ensure that each part is self-contained.
Furthermore, while key analyses for the primary and key secondary endpoints are described in 
this section, additional analyses of these endpoints as well as exploratory endpoints will be 
described in details in the SAP.
10.1.
Induction Part
10.1.1.
Overview
This is the open-label, single-arm, Induction part of the study. Subjects receiving nab-paclitaxel 
100 mg/m2 administered weekly followed by carboplatin at AUC = 6 mg*min/mL on Day 1 of 
each cycle, repeated every 21 days, for 4 cycles will be enrolled. Subjects will have CT scans 
performed every 42 days (-3/+7 days). At the end of the 4 cycles, subjects who achieve a 
radiologically assessed CR, PR, or SD without clinical progression based on the Investigator’s 
evaluation using RECIST 1.1 guidelines, and meet inclusion/exclusion criteria will be 
randomized in the Maintenance part of the study.
An independent DMC will be established to monitor the study conduct. Details will be provided 
in the DMC charter.
10.1.2.
Study Population Definitions
10.1.2.1.
Intent-to-Treat Population
The primary efficacy analysis will be performed on the ITT population, which includes all 
enrolled subjects regardless of whether the subject receives any dose of nab-paclitaxel or has any 
efficacy assessments collected.
10.1.2.2.
Safety Population
The safety population will be the analysis population for all safety/ tolerability analyses. The 
safety population includes all subjects enrolled who received at least 1 dose of study treatment. 
Only subjects with clear documentation that no study treatment was administered will be 
excluded from the safety population. 
10.1.3.
Sample Size and Power Considerations
Approximately 540 subjects will be enrolled in the Induction part of the study. This sample size 
is expected to provide approximately 260 subjects eligible for randomization in the Maintenance 
part.   
In the nab-Paclitaxel Phase 3 NSCLC development study (Protocol CA031), 42% (13/31) and 
63% (125/198) of the squamous subjects from the North American and ex-North American sites, 
respectively, were progression free after 4 cycles of treatment and remained in the study in Cycle 
&(/*(1(35235,(7$5<,1)250$7,21
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.
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art.


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
50
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
5 and beyond. To be conservative, it is assumed that approximately 50% (270/540) of the 
subjects in the Induction part of this study will meet the radiologic and clinical progression free 
criteria at the end of Cycle 4. Furthermore, it is expected that approximately 4% of these 270
subjects will not meet the other inclusion/exclusion criteria for the Maintenance part, yielding a 
total of approximately 260 subjects entering the Maintenance part of the study.
The actual number of subjects that will be enrolled in the Induction part will be monitored on an 
ongoing basis and adjusted to ensure that the target number of subjects for the Maintenance part 
is attained. Enrollment of the Induction part, therefore, could be discontinued early or extended
beyond the planned number of 540 subjects.
The ORR is the secondary endpoint in the Induction part. The point estimate and the associated 
two-sided 95% confidence interval will be calculated for this endpoint. No multiplicity 
adjustment will be made for this endpoint as no formal inferential testing will be performed.
The percentage of subjects with an AE of Grade 3 or higher peripheral neuropathy will be 
captured along with the associated two-sided 95% confidence interval without inferential testing.
Table 6 below demonstrates the precision of the estimate for a proportion that can be attained 
given a sample size of 540. For example, for a hypothetical ORR rate of 40% at the end of Cycle 
4, the half-width of the associated two-sided 95% confidence interval will be 4.1%, and the 
estimated 95% confidence interval will be (35.9%, 44.1%).
Table 6:
Precision of the Estimate for a Proportion Given a Sample Size of 540
Endpoint
Hypothetical Event Rate
Half Widtha of 
95% Confidence 
Interval
two-sided 95% 
Confidence Intervala
Overall Response Rate
35%
4.0%
(31.0% to 39.0%)
40%
4.1%
(35.9% to 44.1%)
45%
4.2%
(40.8% to 49.2%)
Peripheral Neuropathy
≥ Grade 3
5%
1.8%
(3.2% to 6.8%)
10%
2.5%
(7.5% to 12.5%)
15%
3.0%
(12.0% to 18.0%)
a Estimated based on normal approximation.
10.1.4.
Background and Demographic Characteristics
The baseline characteristics of all subjects enrolled 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. Medical 
history data will be summarized using frequency tabulations by system organ class and preferred 
term.
10.1.5.
Subject Disposition
Subject disposition including the number and percent of subjects enrolled, randomized, treated, 
and the primary reason for discontinuation of therapy will be summarized by study site. Protocol 
deviations will be summarized using frequency tabulations.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
51
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
10.1.6.
Efficacy Analysis
10.1.6.1.
Primary Purpose
The main purpose of the Induction part is to identify those subjects who are eligible for 
randomization in the Maintenance part of the study. There is no formal statistical analysis 
planned for this purpose. Subjects who attain a radiologically assessed CR, PR, or SD without 
clinical progression according to the investigator’s assessment of the scan performed at the end 
of Cycle 4, based on RECIST 1.1 guidelines, and satisfy the inclusion/exclusion criteria will be 
eligible to be randomized into the Maintenance part of the study.  
10.1.6.2.
Secondary Endpoints
10.1.6.2.1. Overall Response Rate 
The percentage of subjects who achieve an overall complete or partial response (ORR) according 
to RECIST 1.1 guidelines as determined by the investigator and confirmed by repeat assessments 
performed no less than 28 days after the criteria for response were first met will be calculated.
The associated two-sided 95% CI of the ORR will be presented.
Given that the confirmation CT-scan for the ORR could be taken after the start of the 
Maintenance part in which subjects will be receiving either nab-paclitaxel plus BSC or BSC
alone, the ORR will be reported for all subjects enrolled as 1 group, and also by the Maintenance 
treatment regimen, if necessary.
It is important to note that the Induction part is analogous to a 4-cycle fixed duration study with 
all subjects exiting this part prior to or at the end of Cycle 4. Therefore, the analysis results for 
all secondary efficacy endpoints should be interpreted accordingly.
10.1.7.
Safety Analysis
All subjects who take at least 1 dose of nab-paclitaxel will be included in the safety analyses. 
Adverse events will be summarized by worst severity grade. AEs, as well as treatment-emergent 
AEs, will be summarized by system organ class, and preferred term. nab-Paclitaxel-related 
adverse events, adverse events leading to death or to discontinuation from treatment, events 
classified as CTCAE Grade 3 or Grade 4, and serious adverse events, and events of interest will 
be summarized separately.
Cross tabulations will be provided to summarize frequencies of abnormalities.
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.
10.1.7.1.
Adverse Events
Adverse events will be coded using the Medical Dictionary for Drug Regulatory Activities 
(MedDRA).
Adverse events will be analyzed in terms of treatment-emergent adverse events (TEAEs), 
defined as any AEs that began or worsened in grade after the start of nab-paclitaxel to the start of 
the Maintenance part for those who randomize in the Maintenance part, or until 28 days after the 
last dose of study drug for those who do not randomize in the Maintenance part. In addition, any 
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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 summarized by system organ class, relative and absolute frequency, 
severity/grade based on the NCI CTCAE version 4.0 and relationship to treatment. Study 
medication-related AEs, SAEs, and events leading to discontinuation or death will be listed 
separately.
10.1.7.2.
Laboratory Assessments
Laboratory test results will not be collected in the eCRFs unless they are determined to be 
clinically significant laboratory abnormalities. Abnormal and clinically significant laboratory 
assessments at Screening will be recorded as medical history, and after Screening, as AE or SAE. 
If a clinically significant laboratory abnormality is captured as medical history, AE, or SAE, the 
specific laboratory parameter(s) should be recorded on the laboratory assessments CRF.
10.1.8.
Study Treatment Termination
Reasons for stopping study treatment during the Induction part will be summarized in listings by 
frequency of occurrence and corresponding percentage of occurrence.
10.1.9.
Deaths
Deaths reported during treatment (defined as deaths after the start of nab-paclitaxel to the start of 
the Maintenance part for those who are randomized in the Maintenance part, or through end of 
treatment of nab-paclitaxel for those who are not randomized in the Maintenance part) will be 
summarized by frequency of occurrence and corresponding percentage by cause of death per 
period.
10.2.
Maintenance Part
10.2.1.
Overview
This is the open-label, randomized, Maintenance part of the study for the evaluation of the 
benefit of a maintenance treatment after an initial 4 cycles of Induction treatment for subjects 
with squamous NSCLC.
Approximately 260 radiologic and clinical progression free subjects from the Induction part will 
be randomized in the Maintenance part. These subjects will be randomized in a 2:1 ratio to the 
nab-paclitaxel plus BSC and BSC alone groups, respectively. The nab-paclitaxel group will 
receive nab-paclitaxel 100 mg/m2 on Day 1 and 8 of each 21-day cycle plus BSC (the actual 
starting dose may be adjusted as specified in Section 8.3), while the BSC group will receive the 
standard BSC. All subjects will receive the assigned regimen until disease progression or 
unacceptable toxicity.
A permuted-block randomization method and an Interactive Voice Response System (IVRS) will 
be utilized to ensure a central randomization. The randomization will be stratified based on 
following 3 baseline and prognostic factors:
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ECOG performance status at the end of the Induction part (0 vs. 1)
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!
Tumor response to induction chemotherapy (CR or PR vs. SD), and 
!
Disease stage before administration of induction therapy (IIIB vs. IV).
It is hypothesized that subjects will benefit from maintenance treatment with nab-paclitaxel. A
randomization ratio of 2:1 will, therefore, minimize subject exposure to treatment with BSC only 
while providing sufficient data for testing the treatment difference with respect to the primary 
endpoint, PFS, in the Maintenance part of the study. 
A DMC will be used to monitor the study conduct. Details will be provided in the DMC charter.
10.2.2.
Study Population Definitions
10.2.2.1.
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 IP or has any efficacy 
assessments collected. 
10.2.2.2.
Response Evaluable Population
Response evaluable population includes all randomized subjects who meet eligibility criteria, 
take at least one dose of IP or on BSC and have at least one baseline and post baseline efficacy 
assessment. The response evaluable population may be used for additional analyses which will 
be described in the SAP.
10.2.2.3.
Per-protocol (PP) Population
The PP population is defined as all subjects randomized in the Maintenance part who receive at 
least one dose of the study therapy and do not have any known major protocol deviations and 
fulfill the study enrollment criteria. The PP population may be used for additional analyses 
which will be described in the SAP.
10.2.2.4.
Safety Population
The safety population includes all randomized subjects in the BSC alone arm and those who
receive at least one dose of nab-paclitaxel in the nab-paclitaxel plus BSC arm in the 
Maintenance part of the study. The safety population will be the population for all safety 
analyses.
10.2.3.
Sample Size and Power Considerations
Progression free survival is the primary endpoint while OS and ORR are the secondary endpoints 
in this part of the study.  
One non-binding interim analysis for PFS with early stopping rule for futility will be conducted 
when approximately 91 events are observed. The study may be stopped for futility if conditional 
power is < 10%.
The final analysis of the primary endpoint will be performed when approximately 182 PFS 
events have been observed. A total of approximately 260 subjects will need to be randomized 
r.
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-003
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assuming an approximate 36 months accrual period and an approximate 2 months follow-up and 
an approximate 9% per year dropout rate.
This study is designed to provide approximately 90% power to detect a HR of 0.60 for PFS 
improvement with nab-paclitaxel plus BSC over BSC alone with a two-sided 5% significance 
level. Assuming an exponential distribution with a median time to PFS of 2 months for the BSC 
alone and proportional hazard, a hazard ratio of 0.60 constitutes an approximate 1.33 months 
increase in median PFS or a 40% hazard risk reduction by the nab-paclitaxel plus BSC regimen 
over that of the BSC alone.
There will be 2 analyses for the OS endpoint. The interim analysis (non-binding) of OS will be 
conducted based on the number of deaths observed at the time of the final PFS analysis. 
However, all subjects will continue to be followed for OS up to 1.5 years after final analysis of 
approximately 182 PFS events or approximately 218 deaths have been observed for the final OS 
analysis, whichever is earlier. The marginal significance levels for OS will be adjusted according 
to O’Brien-Fleming type boundary based on the actual number of deaths observed at each stage.
For example, if 163 and 218 deaths (~75% information) are observed by the time of the interim 
and final analyses of OS, respectively, the marginal critical values will be p ≤0.01106 and p ≤
0.04794, correspondingly.
Assuming an exponential distribution, proportional hazards, and median OS times of 7.2 and 
10.30 months for the BSC alone and nab-paclitaxel plus BSC regimens, respectively, this design 
provides 70% marginal power to detect a hazard ratio of 0.70 between the 2 maintenance 
regimens with an overall two-sided 5% significance level.
A step-down procedure from PFS to OS will be used to control family-wise Type-I error rate to 
5%. That is, OS will be tested only if the nab-paclitaxel plus BSC regimen demonstrates 
superiority over the BSC alone with PFS. 
As an illustration for timeline projection, assuming an exponential distribution for PFS, a 36-
month recruitment period for 260 subjects, and a median PFS of approximately 2.0 months for 
the BSC alone, it will take approximately 23 months from the first subject randomized to observe 
91 PFS events for the interim analysis. The final analysis of PFS (with 182 events) is estimated 
to take place at approximately 15 months after that, which is approximately 2 months after the 
last subject randomized.  
Assuming an exponential distribution for OS and a median OS of 7.2 months for the BSC arm, it 
will take approximately an additional 1.5 years follow-up after the final analysis of PFS to 
observe a total of 218 death events in the entire Maintenance part.
10.2.4.
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. 
Medical history data will be summarized using frequency tabulations by system organ class and 
preferred term.
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10.2.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both treatments 
and follow-up parts. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
10.2.6.
Efficacy Analysis
While key analyses are described in this section, additional analyses will be specified in the SAP.
10.2.6.1.
Primary Endpoint 
The primary endpoint, PFS, will be based on investigator’s assessment of response using 
RECIST 1.1 guidelines. Baseline tumor measurements will be determined from the radiology 
evaluation performed within 28 days of the start of Induction therapy. Time to Progression will 
be calculated from the date of randomization (start of Maintenance part) to the first date of 
progressive disease or death from any cause.  
Progression-free survival will be summarized using Kaplan-Meier methods. 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. In the event 
that a new anticancer treatment occurs prior to documented progression, the subject will be 
censored at the time 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 time 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 time of the last radiologic 
assessment where the subject was documented to be progression-free prior to the first of the two 
missing visits.
The null (Ho) and alternative (Ha) hypotheses for testing the primary efficacy endpoint are: 
Ho: HR nab-paclitaxel plus best supportive care/ best supportive care = 1
Ha: HR nab-paclitaxel plus best supportive care/ best supportive care ≠1 
Progression-free survival will be summarized by median PFS time (including two-sided 95% CI) 
for each treatment regimen 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 regimen and differences in the curves will be tested using the 
stratified log-rank test, where the strata include ECOG performance status at the end of the 
Induction part (0 vs.1), tumor response to induction chemotherapy (CR or PR vs. SD), and 
disease stage before administration of induction therapy (IIIB vs. IV), if the number of events in 
each cell is adequate. Other factors may be included if indicated by the actual population 
enrolled.
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 regimen. In addition, confirmatory and sensitivity analyses will be 
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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. 
Additional analyses of PFS calculated from the date of the first dose of Induction therapy will be 
conducted using the same statistical methods described for PFS measured from the date of 
randomization above.
10.2.6.2.
Key Secondary Endpoints
Key secondary efficacy endpoints include OS and ORR (percent of subjects who had a 
radiologic complete or partial response according to RECIST 1.1 guidelines determined by the 
investigator and confirmed by repeat assessments performed no less than 28 days after the 
criteria for response were first met). 
10.2.6.2.1. 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 trial or who are withdrawn from the trial 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 cut-off date. 
Overall survival will be analyzed similarly as PFS.
Additional analyses of OS calculated from the date of the first dose of induction therapy will be 
conducted using the same statistical methods described for OS calculated from the date of 
randomization above.
10.2.6.2.2. Overall Response Rate 
The percentage of randomized subjects having an overall confirmed CR or PR based on the 
investigator’s assessment using RECIST 1.1 guidelines over the entire study (Induction and 
Maintenance) will be calculated (scans will be performed every 42 days [-3/+7 days] and 
confirmation scan will be performed no less than 4 weeks after the criteria for response were first 
met). Baseline tumor measurements will be determined from the radiology evaluation performed 
within 28 days of the start of Induction therapy.
The two-sided 95% CI of the response rates will be presented. Differences in response rates 
between treatment regimens will be tested using chi-square test at a two-sided 5% significance 
level.  
10.2.6.3.
Other Secondary Efficacy Endpoints
10.2.6.3.1. Disease Control Rate
Disease Control rate (ie, SD for ≥ 6 weeks or confirmed CR or PR) over the entire study will be 
analyzed in the same manner as overall response rate. Baseline tumor measurements will be 
determined from the radiology evaluation performed within 28 days of the start of Induction 
therapy.
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10.2.6.4.
Exploratory Endpoints
10.2.6.4.1. Overall Response Rate in Maintenance Part 
Tumor reductions during maintenance treatment beyond the response to induction therapy will 
be explored by the percentage of randomized subjects achieving an overall confirmed CR or PR
compared with the radiologic assessment before randomization (i.e, using end of cycle 4 CT-
scan as the baseline measurement) according to the investigator’s evaluation using RECIST 1.1 
guidelines.  
The two-sided 95% CI of the response rates will be presented. Differences in response rates 
between treatment regimens may be tested using chi-square test at a two-sided 5% significance 
level.
10.2.6.4.2. Health Care Utilization and Quality of Life Questionnaire
The analysis of health care utilization and quality of life questionnaire will be described in detail 
in the SAP.
10.2.6.4.3. Biomarkers and Pharmacogenomic Data
Statistical analysis of the biomarkers and pharmacogenomic data collected from the plasma and 
blood samples will be covered under a separate SAP from that mentioned above.
10.2.7.
Safety Analysis
All subjects in the BSC arm and all subjects who take at least 1 dose of nab-paclitaxel in the 
nab-paclitaxel plus BSC in the Maintenance part will be included in the safety analyses. Adverse 
events will be summarized by worst severity grade. AEs, as well as treatment-emergent AEs, 
will be summarized by system organ class, and preferred term. IP-related adverse events, adverse 
events leading to death or to discontinuation from treatment, events classified as CTCAE Grade 
3 or Grade 4 (or moderate/severe if other rating scale is used), and serious adverse events, and 
events of interest will be summarized separately.
Cross tabulations will be provided to summarize frequencies of abnormalities.
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. 
10.2.7.1.
Adverse Events
Adverse events will be analyzed in terms of TEAEs, defined as any AE occurring or worsening 
on or after the first treatment of the study regimen of the Maintenance part through 28 days after 
the last dose of study regimen administration. In addition, any AE with an onset date more than 
28 days after the last dose of IP that is assessed by the investigator as related to study drug will 
be considered a TEAE. They will be summarized by system organ class, relative and absolute 
frequency, severity grade based on the NCI CTCAE version 4.0 and relationship to treatment. 
Study medication-related AEs, SAEs, and events leading to discontinuation or death will be 
listed separately. 
AEs will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA).
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
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('06'RF1XPEHU
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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.
Since laboratory test data will not be collected routinely in the eCRFs, this will not be analyzed.
10.2.7.2.
Laboratory Assessments
Laboratory tests will be performed weekly prior to nab-paclitaxel administration, as per standard 
of care during the study and as clinically indicated. Laboratory test results will not be collected 
in the eCRFs unless they are determined to be clinically significant laboratory abnormalities.
Abnormal and clinically significant laboratory assessments at Screening will be recorded as 
medical history, and after Screening, as AE or SAE. If a clinically significant laboratory 
abnormality is captured as medical history, AE, or SAE, the specific laboratory parameter(s) 
should be recorded on the laboratory assessments CRF.
10.2.8.
Study Therapy Termination
Reasons for stopping study therapy will be summarized in listings by frequency of occurrence 
and corresponding percentage of occurrence per study part (Induction and Maintenance) and 
combined.
10.2.9.
Deaths
Deaths reported during treatment (defined as deaths from the first administration of the study 
Maintenance regimen through 28 days after the last dose of the study Maintenance regimen) 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).
Deaths occurring during the entire study (Induction and Maintenance parts) will also be 
summarized similarly.
10.2.10.
Interim Analysis
There will be one non-binding interim analysis for futility for the primary endpoint, PFS, when 
approximately 91 events (50% information) have been observed. Futility may be declared and 
the study discontinued if the conditional power at the interim analysis is < 10%.  The final 
analysis of PFS will be performed when approximately 182 PFS events have been observed.
There will be two analyses for the secondary OS endpoint. The interim analysis of OS (for 
efficacy) will be conducted based on the number of deaths observed up to the time of the final 
PFS analysis. The final OS analysis will be performed after approximately 218 deaths have been 
observed, if applicable.  
A Step-down procedure from PFS to OS will be used to control the family-wise two-sided Type-
I error rate to 5%.
The marginal significance level for OS will be adjusted according to O'Brien-Fleming type of 
boundary. The nominal two-sided p-values for declaring superiority will be calculated using the 
statistical software 
 The analysis and boundaries will be adjusted 
based on the actual number of deaths observed.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
59
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
10.3.
Data Monitoring Committee
An independent DMC will be established with the responsibilities for safeguarding the interests 
of study participants and monitoring the overall conduct of the study. Final recommendations of 
the DMC will reflect the judgment of the DMC members and will be considered advisory in 
nature to the Sponsor. The decision to implement the recommendations of the DMC will be 
made by the Sponsor, following consultation with the coordinating PI and Steering Committee.
A DMC charter will be established.
10.4.
Scientific Steering Committee
The conduct of this trial will be overseen by a Steering Committee. The Steering Committee will 
serve in an advisory capacity to the Sponsor. 
Note: the Steering Committee is separate from the Data Monitoring Committee described in 
Section 10.3.
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11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria in Section 11.3), regardless of 
etiology. Any worsening (ie, any clinically significant adverse change in the frequency or 
intensity of a pre-existing condition) should be considered an AE. A diagnosis or syndrome 
should be recorded on the AE page of the CRF rather than the individual signs or symptoms of 
the diagnosis or syndrome. 
For the purposes of this study, progressive disease (PD) of squamous cell NSCLC will not 
require reporting as an adverse event. However, signs and symptoms (events) related to disease 
progression may be reported as adverse events. If reported, events of disease progression for 
squamous cell NSCLC disease under the study (including deaths due to disease progression for 
indications that are considered to be fatal) will be assessed as expected AEs and will not be 
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 an IP 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 other appropriate tests and 
procedures.
All AEs will be recorded by the Investigator from the time the subject signs informed consent to
28 days after the last dose of IP or the End of Study Visit, whichever is longer, and those SAEs 
made known to the investigator at any time thereafter that are suspected of being related to IP.
AEs and serious adverse events (SAEs) will be recorded on the AE page of the CRF and in the 
subject’s source documents. All SAEs must be reported to Celgene Drug Safety within 24 hours
of the Investigator’s knowledge of the event by facsimile, or other appropriate method, using the 
SAE Report Form, or approved equivalent form.
11.2.
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to: 
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11.2.


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Celgene Corporation
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11.2.1.
Seriousness 
A serious adverse event (SAE) is any AE occurring at any dose that:
!
Results in death;
!
Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate 
risk of death from the AE);
!
Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);
!
Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);
!
Is a congenital anomaly/birth defect;
!
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
Events not considered to be SAEs are hospitalizations for:
!
A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE. 
!
Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.
!
The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.
!
A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.
!
Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the CRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of a pre-existing condition unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
62
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to IP, action taken regarding IP, and outcome.
11.2.2.
Severity / Intensity
For both AEs and SAEs, the Investigator must assess the severity/intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current active minor version of 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 IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
The temporal relationship of the adverse event to IP
administration makes a causal relationship unlikely or 
remote, or other medications, therapeutic interventions, or 
underlying conditions provide a sufficient explanation for the 
observed event.
Suspected:
The temporal relationship of the adverse event to IP 
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Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
63
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
administration makes a causal relationship possible, and other 
medications, therapeutic interventions, or underlying conditions 
do not provide a sufficient explanation for the observed event.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP 
that has not been manufactured or provided by Celgene, please provide the name of the 
manufacturer when reporting the event.
11.2.4.
Duration
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event.
11.2.5.
Action Taken
The Investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(eg, discontinuation or reduction of IP, as appropriate) and report if concomitant and/or 
additional treatments were given for the event. 
11.2.6.
Outcome
The investigator will report the outcome of the event for both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered (death due to another cause) or death 
(due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:
!
results in discontinuation from the study;
!
requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or
!
is judged to be of significant clinical importance.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the CRF. If the abnormality was not a 
part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE. If 
possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
64
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
11.4.1.
Females of Childbearing Potential
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on IP, or within 28 days of the 
subject’s last dose of IP, are considered immediately reportable events. IP is to be discontinued 
immediately. The pregnancy, suspected pregnancy, or positive pregnancy test must be reported 
to Celgene Drug Safety immediately by facsimile, or other appropriate method, using the 
Pregnancy Initial Report Form, or approved equivalent form. The female subject should be 
referred to an obstetrician-gynecologist, preferably one experienced in reproductive toxicity for 
further evaluation and counseling.
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 or therapeutic abortion), the 
Investigator should report the abnormal outcome as an AE. If the abnormal outcome meets any 
of the serious criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or 
other appropriate method, within 24 hours of the Investigator’s knowledge of the event using the 
SAE Report Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the Investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the Investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject becomes pregnant while the subject is receiving IP or within 
6 months of the last dose of IP, the male subject taking IP should notify the Investigator, and the 
pregnant female partner should be advised to call her healthcare provider immediately. The IP 
may need to be discontinued in the male subject, but may be resumed later at the discretion of 
the Investigator and medical monitor.
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in
addition to being recorded on the AE page/screen of the eCRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. This 
instruction pertains to initial SAE reports as well as any follow-up reports.
The Investigator is required to ensure that the data on these forms is accurate and consistent. This 
requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent to at least 28 days after the last dose of IP or 
End of Study Visit, whichever is later) and those made known to the Investigator at anytime 
thereafter that are suspected of being related to IP. SAEs occurring prior to treatment will be 
captured.
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
65
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
The SAE report should provide a detailed description of the SAE and include summaries 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 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 Abraxane and Investigator 
Brochure. For the purpose of regulatory reporting in the EEA, Celgene Drug Safety will 
determine the expectedness of events suspected of being related to the other IP, carboplatin,
based on the EU Summary of Product Characteristics (SmPC). 
For countries within the European Economic Area (EEA), Celgene or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 
presentation of adverse reaction reports arising from clinical trials on IP for human use 
(ENTR/CT3) and also in accordance with country-specific requirements.
Celgene or its authorized representative shall notify the Investigator of the following 
information: 
!
Any AE suspected of being related to the use of IP in this study or in other studies 
that is both serious and unexpected (ie, SUSAR);
!
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC. (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form/Completion Guidelines or to the Pregnancy Report Form/Completion Guidelines.
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('06'RF1XPEHU
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Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
66
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
12.
DISCONTINUATIONS
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the IP:
!
Adverse Event(s)
!
Disease progression
!
Withdrawal of consent
!
Death
!
Lost to follow-up
!
Protocol violation
All subjects discontinued from nab-paclitaxel for any reason will have a treatment 
discontinuation visit at the time of nab-paclitaxel discontinuation and should undergo early 
termination procedures.
All subjects discontinued from nab-paclitaxel will be followed for a period of 28 days after PFS 
or early discontinuation, or until the date of the last study visit (whichever is longer) for the 
collection of AEs.
Additionally subjects who withdraw from or complete treatment should not be withdrawn from 
the study (unless specifically requested) and should be followed up for progressive disease, 
survival and any new therapy given.
The reason for treatment discontinuation should be recorded in the eCRF and in the source 
documents.
The decision to discontinue a subject remains the responsibility of the treating physician, which 
will not be delayed or refused by the Sponsor. However, prior to discontinuing a subject, the 
Investigator may contact the Medical Monitor and forward appropriate supporting documents for 
review and discussion
12.2.
Study Discontinuation
The following are considered sufficient reasons for discontinuing a subject from the study:
!
Withdrawal of consent (decision form the subject not to provide follow-up 
information)
!
Death
!
Lost to follow-up
The following may be considered a sufficient reason for discontinuing a subject from the study:
!
Protocol violation
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. The Investigator must notify the Medical Monitor immediately when a subject has 
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
67
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
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 the subject lost to follow-up.
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
68
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 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-003
Celgene Corporation
Confidential and Proprietary
69
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 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 CRFs 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-003
Celgene Corporation
Confidential and Proprietary
70
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the Investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the Investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval.
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the Investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
IP can only be supplied to an Investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
Celgene or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB/EC should mention the protocol title, number, amendment number 
(if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
arch
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
71
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.
14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:
!
Information on serious or unexpected adverse events as soon as possible; 
!
Periodic reports on the progress of the study;
!
Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the Investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
!
Unsatisfactory enrollment;
!
GCP noncompliance;
!
Inaccurate or incomplete data collection;
!
Falsification of records;
!
Failure to adhere to the study protocol.
&(/*(1(35235,(7$5<,1)250$7,21
e;e;
ed risk to su
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reasonable
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
72
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and the distribution of the IP are complete, accurate, filed and retained. Examples of source 
documents include: hospital records; clinic and office charts; laboratory notes; memoranda; 
subject’s diaries or evaluation checklists; dispensing records; recorded data from automated 
instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy, and the laboratories, as 
well as copies of CRFs or CD-ROM.
15.2.
Data Management
Data will be entered into the clinical database per Celgene Standard Operating Procedures 
(SOPs). This data will be electronically verified through use of programmed edit checks 
specified by the clinical team. Discrepancies in the data will be brought to the attention of the 
clinical team, and investigational site personnel, if necessary. Resolutions to these issues will be 
reflected in the database. An audit trail within the system will track all changes made to the data.
15.3.
Record Retention
Essential documents must be retained by the Investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IP. The investigator must retain these 
documents for the time period described above or according to local laws or requirements, 
whichever is longer. Essential documents include, but are not limited to, the following:
!
Signed ICFs for all subjects;
!
Subject identification code list, screening log (if applicable), and enrollment log;
!
Record of all communications between the Investigator and the IRB/EC;
!
Composition of the IRB/EC;
!
Record of all communications between the Investigator, Celgene, and their authorized 
representative(s);
!
List of Sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;
!
Copies of CRFs (if paper) and of documentation of corrections for all subjects;
!
IP accountability records;
!
Record of any body fluids or tissue samples retained;
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
73
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
!
All other source documents (subject records, hospital records, laboratory records, 
etc.); 
!
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The Investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.
The Investigator must obtain approval in writing from Celgene prior to destruction of any 
records. If the Investigator is unable to meet this obligation, the Investigator must ask Celgene 
for permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.
&(/*(1(35235,(7$5<,1)250$7,21
e
ities.
ties.
destruction
destruction


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
74
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
16.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative
for compliance with applicable government regulations with respect to current GCP and standard 
operating procedures.
16.1.
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study. All aspects of the study are reviewed with the Investigator and the staff at a study 
initiation visit and/or at an investigator meeting. Prior to enrolling subjects into the study, a 
Celgene representative will review the protocol, CRFs, procedures for obtaining informed 
consent, record keeping, and reporting of AEs/SAEs with the Investigator. Monitoring will
include on-site visits with the Investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, IP
storage area, CRFs, subject’s source documents, and all other study documentation will be
inspected/reviewed by the Celgene representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the CRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff. Any necessary 
corrections will be made directly to the CRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene. Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations.
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, CRFs and applicable supporting records of 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.
&(/*(1(35235,(7$5<,1)250$7,21
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('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
75
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 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 and order of  
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 the study.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
76
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
18.
REFERENCES
Azzoli CG, Baker Jr. S, Temin S, 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, 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 
Onc. 2008;26:468-473.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response 
evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 
Jan;45(2):228-47.
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):1590-1598.
Lorenz W, Reimann HJ, Schmal A, et al. Histamine release in dogs by Cremophor El and its 
derivatives: oxethylated oleic acid is the most effective constituent. Agents Actions 
1997;7:63-67.
Lung Cancer Awareness. Global Lung Cancer Coalition Website. 
http://www.lungcancercoalition.org/en/pages/about/awareness. Accessed July 12, 2013.
National Institute for Health & Clinical Excellence: The Diagnosis and Treatment of Lung 
Cancer: Methods, Evidence & Guidance, 2011.
Neal, JW. The SATURN trial: the value of maintenance erlotinib in patients with non-small-cell
lung cancer. Future Oncol. 2010 Dec;6(12):1827-1832.
O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979 
Sep;35(3):549-556.
Oken, MM, Creech, RH, Tormey, DC, et al. Toxicity And Response Criteria Of The Eastern 
Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982.
Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus best 
supportive care versus placebo plus best supportive care after induction therapy with pemetrexed 
plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a 
double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55.
Rizvi NA, Riely GJ, Azzoli CG, 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):639-643.
Schell MJ, Peterman A, et al. Phase III trial comparing a defined duration of therapy versus 
continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell 
lung cancer. J Clin Oncol. 2002;20(5):1335-1343.
response
response
J Cancer. 20
Cancer. 2
awbacks an
awbacks a
;37
37(13)
(13):15
by Cremop
y Cremop
nt. Agents A
Agents A
Websi
bsite.
te.
i
areness
areness. Ac
A
The
The Diag
iag
ma
maint
intenanc
nan
2):1827
2):1827-18
18
testing pro
testing p
mey, DC,
mey, DC, e
oup.
up. Am J C
Am J 
s F, Dediu M
s F, Dediu 
sus placebo
s placebo
advanced 
advanced 
phase 3, ra
hase 3, r
, Ri
Riely GJ, 
ly GJ,
n-bound pa
bound pa
erer. J Clin O
J Clin O
Schell MJ,
Schell MJ,
continu
ontinu


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
77
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 2014
Socinski M, Manikhas GM, Stroyakovsky DL, 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):852-861.
Stinchcombe TE, Socinski MA. Current treatments for advanced stage non-small cell lung 
cancer. Proc Am Thorac Soc. 2009;6(2):233-241.
Weiss RB, Donehower RC, Wiernik PH, et al. Hypersensitivity reactions from Taxol. J Clin 
Oncol. 1990;8(7):1263-1268.
&(/*(1(35235,(7$5<,1)250$7,21


('06'RF1XPEHU
nab-paclitaxel
Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
78
ABI-007-NSCL-003 Amendment 1 Final: 28 Oct 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-003
Celgene Corporation
Confidential and Proprietary
1
STATISTICAL ANALYSIS PLAN
A PHASE III, RANDOMIZED, OPEN-LABEL, MULTI-CENTER, SAFETY AND 
EFFICACY STUDY TO EVALUATE NAB-PACLITAXEL (ABRAXANE®) AS 
MAINTENANCE TREATMENT AFTER INDUCTION WITH NAB-PACLITAXEL PLUS 
CARBOPLATIN IN SUBJECTS WITH SQUAMOUS CELL NON-SMALL CELL LUNG 
CANCER (NSCLC)
STUDY DRUG:
nab-Paclitaxel (Abraxane®)
PROTOCOL NUMBER:
ABI-007-NSCL-003
DATE FINAL:
19MAY-2017
Prepared by:
on behalf of
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
CONFIDENTIAL
The information contained in this document is regarded as confidential 
and, except to the extent necessary to obtain informed consent, may not be 
disclosed to another party unless such disclosure is required by law or 
regulations.  Persons to whom the information is disclosed must be 
informed that the information is confidential and may not be further 
disclosed by them.
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35


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
2
TABLE OF CONTENTS
SIGNATURE PAGE...................................................................................................................6
1.
LIST OF ABBREVIATIONS...................................................................................8
2.
INTRODUCTION..................................................................................................11
3.
STUDY OBJECTIVES...........................................................................................12
3.1.
Primary Objective...................................................................................................12
3.2.
Secondary Objectives .............................................................................................12
3.3.
Exploratory Objectives ...........................................................................................12
4.
INVESTIGATIONAL PLAN .................................................................................13
4.1.
Overall Study Design and Plan ...............................................................................13
4.2.
Study Endpoints .....................................................................................................13
4.2.1.
Primary Endpoint....................................................................................................13
4.2.2.
Secondary Efficacy Endpoints ................................................................................13
4.2.3.
Secondary Safety Endpoints ...................................................................................14
4.2.4.
Exploratory Endpoint(s)..........................................................................................14
4.3.
Stratification, Randomization, and Blinding............................................................14
4.3.1.
Induction Part.........................................................................................................14
4.3.2.
Randomization and Maintenance Part.....................................................................15
4.3.3.
Follow-up Period....................................................................................................15
4.4.
Sample Size Determination.....................................................................................15
5.
GENERAL STATISTICAL CONSIDERATIONS .................................................17
5.1.
Reporting Conventions ...........................................................................................17
6.
PROTOCOL DEVIATIONS/VIOLATIONS ..........................................................18
7.
STATISTICAL ANALYSIS...................................................................................19
7.1.
Subject Disposition.................................................................................................19
7.2.
Induction Part.........................................................................................................20
7.2.1.
Study Population Definitions ..................................................................................20
7.2.2.
Baseline values.......................................................................................................20
7.2.3.
Demographics.........................................................................................................20
7.2.4.
Baseline Characteristics..........................................................................................21
7.2.5.
Lung Cancer History...............................................................................................21
7.2.6.
Medical History......................................................................................................21
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2 4


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7.2.7.
Prior and Concomitant Anti-Cancer Therapy ..........................................................21
7.2.8.
Prior and Concomitant Medications........................................................................22
7.2.9.
Study Treatments and Extent of Exposure...............................................................22
7.2.10.
Efficacy Analysis....................................................................................................27
7.2.11.
Safety Analyses ......................................................................................................29
7.2.12.
Quality of Life Analysis..........................................................................................32
7.3.
Maintenance Part....................................................................................................34
7.3.1.
Study Population Definitions ..................................................................................34
7.3.2.
Demographics.........................................................................................................35
7.3.3.
Baseline Characteristics..........................................................................................35
7.3.4.
Lung Cancer History...............................................................................................35
7.3.5.
Medical History......................................................................................................36
7.3.6.
Prior and Concomitant Anti-Cancer Therapy ..........................................................36
7.3.7.
Prior Medications ...................................................................................................36
7.3.8.
Concomitant Medications .......................................................................................36
7.3.9.
Concurrent Radiation and Surgeries........................................................................36
7.3.10.
Study Treatments and Extent of Exposure...............................................................37
7.3.11.
Efficacy Analysis....................................................................................................41
7.3.12.
Subgroup Analyses.................................................................................................49
7.3.13.
Analyses of Exploratory Efficacy Endpoints...........................................................50
7.3.14.
Safety Analysis.......................................................................................................51
7.3.15.
Quality of Life Analysis..........................................................................................54
7.4.
Follow-up...............................................................................................................55
8.
INTERIM ANALYSIS...........................................................................................56
8.1.
General Information................................................................................................56
8.2.
Statistical Approaches for Control of Alpha............................................................56
8.3.
Probability of Clinically Meaningful PFS Effects Given the Interim Data...............57
8.4.
Conditional Power at the Interim Analysis for PFS .................................................57
8.5.
Conditional Power at the Interim Analysis for OS...................................................59
9.
CHANGES TO THE STATISTICAL ANALYSES SECTION OF THE
PROTOCOL...........................................................................................................61
10.
REFERENCES.......................................................................................................62
11.
APPENDICES........................................................................................................63
2
.......34
3
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9


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11.1.
Study schematic......................................................................................................63
11.2.
Handling of Dates...................................................................................................63
11.2.1.
Calculation Using Dates .........................................................................................64
11.3.
Date Imputation Guideline......................................................................................65
11.3.1.
Impute Missing Dates for Adverse Events/ Prior or Concomitant 
Medications............................................................................................................65
11.3.2.
Impute Missing Dates for Medical History..............................................................66
11.4.
Tumor Response Windows .....................................................................................66
11.5.
MedDRA Versions and Dates.................................................................................67
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66
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.......66
66
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nab-Paclitaxel (Abraxane®)
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LIST OF TABLES
Table 1:
Abbreviations and Specialist Terms..........................................................................8
Table 2:
Calculation of Induction Dosing Period for Each Study Drug Based on Cycle 
Day Number of Last Dose of the Study Drug..........................................................24
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Signature
{See appended electronic signature page}
Printed Name
Date
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1.
LIST OF ABBREVIATIONS
Table 1:
Abbreviations and Specialist Terms
Abbreviation
Meaning
ADT
Analysis date
AE
Adverse event
AESI
Adverse event of special interest
ALT
Alanine aminotransferase (SGPT)
ANC
Absolute neutrophil count
ANOVA
Analysis of variance
AST
Aspartate aminotransferase (SGOT)
AUC
Area under the curve
BMI
Body mass index
BSA
Body surface area
BSC
Best supportive care
CI
Confidence interval
CMH
Cochran-Mantel-Haenszel
CR
Complete response
CRF
Case report form
CT
Computerized tomography
CTCAE
Common Terminology Criteria for Adverse Events
DCR
Disease control rate
DMC
Data Monitoring Committee
ECOG
Eastern Cooperative Oncology Group
EOS
End of study
EQ-5D-5L
EuroQol 5-dimensional quality of life instrument
FNC
Fine cell cytology
Hgb
Hemoglobin
HR
Hazard ratio
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5L
FNC
NC


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Abbreviation
Meaning
IP
Investigational product
ITT
Intent-to-treat
IV
Intravenous
IVRS
Interactive voice response system
LCSS
Lung cancer symptom scale
MedDRA
Medical dictionary for regulatory activities
MRI
Magnetic resonance imaging
NA
Not applicable
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
RE
Response evaluable
RECIST
Response evaluation criteria in solid tumors
SAE
Serious adverse event
SAP
Statistical analysis plan
SD
Stable disease
SE
Standard error 
SGOT
Serum glutamic oxaloacetic transaminase (AST)
SGPT
Serum glutamic pyruvic transaminase (ALT)
SMQ
Standardized MedDRA query
SOC
System organ class
STDEV
Standard deviation
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Abbreviation
Meaning
TEAE
Treatment emergent adverse event
TTP
Time to progression
ULN
Upper limit of normal
UE
Unevaluable
US
United States
VAS
Visual analog scale
WBC
White blood cell
WHO 
World Health Organization 
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2.
INTRODUCTION
This statistical analysis plan (SAP) describes the analyses and data presentations for Celgene’s 
protocol ABI-007-NSCL-003 “A PHASE III, RANDOMIZED, OPEN-LABEL, MULTI-
CENTER, SAFETY AND EFFICACY STUDY TO EVALUATE NAB-PACLITAXEL 
(ABRAXANE®) AS MAINTENANCE TREATMENT AFTER INDUCTION WITH NAB-
PACLITAXEL PLUS CARBOPLATIN IN SUBJECTS WITH SQUAMOUS CELL NON-
SMALL CELL LUNG CANCER (NSCLC)” which was issued on 27SEP2013 and amended on 
28OCT2014, 07MAY2015 and 13MAR2017. It contains definitions of analysis populations, 
derived variables and statistical methods for the analysis of efficacy and safety.
These analyses include all the dry runs described in the Scope of Work, the non-inferential and 
non-binding interim analyses described in the protocol, and the final analysis for the clinical 
study report. The interim analyses will be performed by a different vendor. Throughout this SAP, 
for the Induction Part, the treatment arm will be referred to as the nab-Paclitaxel/carboplatin 
treatment, while in the Maintenance Part, the treatment arms will be referred to as the nab-
Paclitaxel+BSC (referring to nab-paclitaxel plus best supportive care) and BSC (referring to best 
supportive care) arms. 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 inferential interim analysis. This SAP is developed after the 
finalization of the protocol and will be finalized and signed 4 weeks prior to the clinical database 
lock for the first inferential interim analysis. All statistical analyses detailed in this SAP will be 
conducted using SAS® Version 9.2 or higher. The clinical cutoff date will be determined based 
on the occurrence of approximately 91 progression-free survival (PFS) events for the first non-
binding interim analysis and approximately 136 PFS events for the final PFS analysis and 
interim overall survival (OS) analysis. The clinical cutoff for the final OS analysis will occur at 
147 deaths, which is approximately 1.5 years after the final PFS analysis.
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3.
STUDY OBJECTIVES
3.1.
Primary Objective
The primary objective of the study is to evaluate progression-free survival (PFS) with nab-
paclitaxel as Maintenance treatment after response or stable disease (SD) with nab-paclitaxel 
plus carboplatin in subjects with squamous cell non small-cell lung cancer (NSCLC).
3.2.
Secondary Objectives
The secondary objectives of the study are:
!
To evaluate the safety and tolerability of nab-paclitaxel as Maintenance treatment after 
response or SD with nab-paclitaxel plus carboplatin in subjects with squamous cell 
NSCLC.
!
To further assess the efficacy with nab-paclitaxel as Maintenance treatment after 
response or SD with nab-paclitaxel plus carboplatin in subjects with squamous cell 
NSCLC, as measured by secondary efficacy endpoints.
3.3.
Exploratory Objectives
The exploratory objectives of the study are:
!
To determine baseline tumor characteristics which predict response and resistance to nab-
paclitaxel/carboplatin during the Induction Part of the study.
!
To determine what changes in peripheral tumor characteristics during treatment are 
associated with acquisition of resistance in the subjects who had initial clinical benefit.
!
To assess healthcare resource utilization during the Maintenance Part of the study.
!
To assess the Lung Cancer Symptom Scale (LCSS) and EuroQol Group 5-Dimension 
Self-Report Questionnaire score (EQ-5D-5L).
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nab-Paclitaxel (Abraxane®)
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4.
INVESTIGATIONAL PLAN
4.1.
Overall Study Design and Plan
This is a Phase 3, randomized, open-label, multi-center study of nab-paclitaxel plus best
supportive care (BSC) or BSC alone as Maintenance treatment after response or SD with nab-
paclitaxel plus carboplatin as Induction in subjects with squamous cell NSCLC. Approximately 
450 subjects with Stage IIIB/IV squamous cell NSCLC eligible to receive standard treatment of 
nab-paclitaxel plus carboplatin for 4 cycles will be enrolled in the Induction Part of the study. If 
after the 4 cycles, the subject has a radiologically assessed complete response (CR), partial 
response (PR), or SD without clinical progression, they will be randomized (2:1) in the 
Maintenance Part of the study to receive nab-paclitaxel plus BSC or BSC alone. BSC is defined 
as the best palliative care per investigator (including but not limited to: antibiotics, analgesics, 
antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and/or focal 
external-beam radiation for control of pain, cough, dyspnea, or hemoptysis) excluding 
antineoplastic agents. Approximately 216 subjects will be evaluable for the primary endpoint of 
PFS in Maintenance. 
The study schematic is presented in Section 11.1.
4.2.
Study Endpoints
4.2.1.
Primary Endpoint
The primary endpoint is PFS in months from randomization into the Maintenance Part of the 
study to the start of disease progression based on investigator assessment using RECIST 1.1 
guidelines or death.
4.2.2.
Secondary Efficacy Endpoints
4.2.2.1.
Secondary Efficacy Endpoints
Secondary efficacy endpoints specified in the protocol include the following:
!
Overall survival (OS) from randomization into the Maintenance Part of the study
!
Overall response rate (ORR) during the Induction and Maintenance Parts of the study
based on investigator assessment according to RECIST 1.1 guidelines
4.2.2.2.
Other Secondary Efficacy Endpoints
!
PFS from Day 1 Cycle 1
!
OS from Day 1 Cycle 1
!
ORR in Maintenance Part beyond response in Induction Part
!
Disease control rate (DCR) during the Induction Part and over the entire study
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PFS f
PFS 
!
O


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Celgene Corporation
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!
Time to response during the Induction Part and over the entire study, with and without 
the requirement of confirmation of response
!
Duration of response over the entire study, with and without the requirement of 
confirmation of response
4.2.3.
Secondary Safety Endpoints
Safety parameters such as AE and SAEs.
4.2.4.
Exploratory Endpoint(s)
!
Healthcare resource utilization during the Maintenance Part of the study using a 
questionnaire including hospitalizations, emergency room visits, doctor or nurse visits, 
procedures, and/or additional medication. 
!
Change in the LCSS and EQ-5D-5L.
The following exploratory endpoints will be described in a separate SAP:
!
The correlation between pretreatment tumor characteristics and response and resistance to 
the study treatment determined using next-generation sequencing methods, 
immunohistochemistry, or other analysis methods. 
!
The association between the changes in tumor characteristics and the acquisition of 
resistance to therapy from plasma samples taken at treatment failure during Maintenance. 
!
The association between DNA nucleotide polymorphisms in subject’s germ line DNA 
and association with treatment efficacy and toxicity. 
4.3.
Stratification, Randomization, and Blinding
4.3.1.
Induction Part
The Induction Part of the study is a one-arm, open label run-in period of nab-paclitaxel plus 
carboplatin that runs for four cycles (approximately 21 days per cycle). The main purpose of the 
Induction Part is to identify those subjects who are eligible for randomization in the Maintenance 
Part of the study. Approximately 450 subjects eligible for standard treatment with nab-paclitaxel 
plus carboplatin for 4 cycles will be enrolled, provided if all inclusion/exclusion criteria are met 
within a 28-day screening period prior to Cycle 1 Day 1.
Induction treatment will commence on Cycle 1 Day 1:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 
21-day cycle
!
Carboplatin AUC = 6 mg*min/mL IV on Day 1 of each 21-day cycle after completion 
of nab-paclitaxel infusion
If the subject has radiological or clinical PD, they will be discontinued from the study and their 
death dates will be provided if possible.
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!


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4.3.2.
Randomization and Maintenance Part
Once 4 cycles have been completed for Induction, if the subject has a radiologically assessed 
CR, PR, or SD without clinical progression, he/she will be evaluated for eligibility for the 
Maintenance Part. Subjects (approximately 216) who satisfy all inclusion/exclusion criteria will 
be randomized 2:1 to receive either:
!
nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-
day cycle plus BSC until disease progression (for guidelines on starting dose for 
Maintenance Part of the study if the subject had dose reduced during the Induction 
Part of the study see Section 8.3 of protocol ABI-007-NSCL-003 dated DD Feb 2017)
OR
!
BSC until disease progression 
Maintenance therapy should start at the time of randomization. If this is not possible, a maximum 
of 7 days will be allowed from the date of randomization to the start date of Maintenance
therapy. Subjects must start Maintenance therapy no earlier than 21 days and no later than 35 
days from Day 1 of the fourth cycle of Induction therapy. 
Randomization will be stratified by disease stage (IIIB vs IV), response in Induction (CR/PR vs 
SD), and Eastern Oncology Cooperative Group (ECOG) performance status (0 vs 1). 
In cases where there is a stratification error at randomization, then the actual stratum from the 
CRF will be used for the final analysis. 
A pooling algorithm will be employed to eliminate small stratums. Please refer to Pooling 
Algorithm for Eliminating Small Stratums in Section 7.3.11.2.   
4.3.3.
Follow-up Period
All subjects who discontinue from the Maintenance Part of the study for any reason other than 
withdrawal of consent, lost to follow-up, or death, will enter the Follow-up period that will have 
a visit 28 days after progression or discontinuation. Those subjects entering the follow up period 
without documented progression will continue to have CT scans in accordance with standard of 
care until documented progression of disease. Additionally, subjects will be followed for OS by 
phone approximately every 90 days for up to 1.5 year after final analysis of approximately 136
PFS events in which a total of 147 deaths is expected to be observed for the final OS analysis.
4.4.
Sample Size Determination
Sample sizes for this part of the study are based on the pragmatic requirements for achieving the 
necessary PFS events in the Maintenance part of the study.
The Maintenance part of the study is designed to detect a hazard ratio (HR) of 0.60 for PFS 
improvement with the nab-paclitaxel plus BSC regimen over the BSC alone regimen. There is an 
80% power to detect a hazard ratio of 0.60 using a two-sided test conducted at the 5% level of 
significance. This hazard ratio of 0.60 assumes an underlying exponential distribution for both 
treatment groups with a median time to PFS of 2 months for the BSC alone group and a median 
time to PFS of 3.33 months for the nab-paclitaxel plus BSC group. Hence, the final analysis will 
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nab-Paclitaxel (Abraxane®)
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be conducted after 136 PFS events (ie, events of disease progression or deaths from any cause) 
have occurred.
The final analysis of the primary endpoint will be performed when approximately 136 PFS 
events have been observed. A total of approximately 216 subjects will need to be randomized 
assuming an approximate 36 months accrual period and an approximate 2 months follow-up and 
an approximate 9% per month dropout rate.
The required number of PFS events and power calculation were obtained from 
 
Approximately up to 450 subjects will be enrolled in the Induction part of the study. This sample 
size would provide approximately 216 subjects eligible for randomization in the Maintenance 
part.   
In the nab-Paclitaxel Phase 3 NSCLC development study (Protocol CA031), 42% (13/31) and 
63% (125/198) of the squamous subjects from the North American and ex-North American sites, 
respectively, were progression free after 4 cycles of treatment and remained in the study in Cycle 
5 and beyond. It is assumed that approximately 50% (225/450) of the subjects in the Induction 
part of this study will meet the radiologic and clinical progression free criteria at the end of 
Cycle 4. Furthermore, it is expected that approximately 4% of these 225 subjects will not meet 
the other inclusion/exclusion criteria for the Maintenance part, yielding a total of approximately 
216 subjects entering the Maintenance part of the study.
The actual number of subjects enrolling into the Induction part, and then being randomized in the 
Maintenance part of the study will be monitored on an ongoing basis and adjusted accordingly to 
ensure that the targeted number of required PFS events for the Maintenance part is attained. 
Enrollment of the Induction part, therefore, could be discontinued early or extended beyond the 
planned number of 450 subjects.  
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5.
GENERAL STATISTICAL CONSIDERATIONS
Programming, statistical analysis, and reporting will be conducted according to 
 standard 
operating procedures.
5.1.
Reporting Conventions
The following reporting conventions apply generally to tables, listings, and figures:
!
The study part will be included as a column in the listings where applicable.
!
Data from all study centers will be combined for analysis;
!
All stratified efficacy analyses will use the stratification factors for randomization
(disease stage (IIIB vs IV), response in Induction (CR/PR vs SD), and ECOG 
performance status at randomization (0 vs 1));
!
All statistical tests of the treatment effect will be interpreted based on the stopping 
boundaries at each pre-specified interim analyses; 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, 
median, standard deviation, minimum, and maximum for continuous variables;
!
All mean and median values will be formatted to one more decimal place than the 
measured value. Standard deviation values will be formatted to two more decimal 
places than the measured value. Minimum and maximum will be formatted to the 
same decimal place as the measured value.
!
All percentages will be rounded to one decimal place. The number and percentage of 
responses will be presented in the form XX (XX.X%), where the percentage is in the 
parentheses;
!
All listings will be sorted for presentation in order of randomized treatment arm, 
study center, subject, and date of procedure or event. Subjects who are not 
randomized will be listed as a non-randomized group before randomized subjects;
!
All analysis and summary tables will have the analysis population sample size (i.e., 
number of subjects)
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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6.
PROTOCOL DEVIATIONS/VIOLATIONS
The protocol deviations/violations will be identified and assessed by clinical research physician 
or designee following company standard operational procedure. Protocol deviations and 
violations will be reviewed before database lock to determine the per protocol population 
(defined in Section 7.3.1.3 for the Maintenance Part of the study). Events that could trigger 
exclusion from the per protocol population include inclusion/exclusion criteria violations, failure 
to take any study drug as assigned, randomization errors, and prohibited concomitant 
medications and procedures.
The protocol deviations/violations will be summarized separately by treatment arm for the ITT 
population. A by-subject listing of subjects with protocol violations in the ITT population will be 
provided.
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the ITT
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ulatioion will 
n wil


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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7.
STATISTICAL ANALYSIS
Statistical analyses are presented below for Induction and Maintenance Parts separately. 
Analyses such as demography are similar for the two parts of the study, but are repeated to make 
each analysis description self-contained.
7.1.
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 of subjects in Induction ITT and Safety populations will be presented with 
percentages based on the number of subjects in the ITT population. 
The number of subjects who are randomized to the Maintenance Part as well as the number who 
are not randomized to the Maintenance Part will be presented. Of those who are not randomized, 
the number of subjects who do not screen fail but never receive treatment, along with the number 
of treated subjects discontinue treatment during the Induction Part and reasons for treatment 
discontinuation will be summarized for all subjects who are deemed eligible for the study 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 for all subjects who sign informed consent 
and discontinue study during the Induction Part with the following categories:
!
Screen failure
!
Death
!
Adverse event
!
Withdrawal by subject
!
Lost to follow up
!
Protocol violation
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-003
Celgene Corporation
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20
!
Other 
The size of following analysis populations for the Maintenance Part will be summarized based 
on number of subjects randomized in the Maintenance Part:
!
ITT Population
!
Response Evaluable Population
!
Safety Population
!
PP Population
Subjects discontinuing the Maintenance treatment will be summarized as well as reasons for 
treatment discontinuation. Subjects who discontinue from the study during the Maintenance Part
will be summarized as well as reasons for study discontinuation. 
Finally, the number of subjects who discontinue Maintenance and enter into the follow up part of 
the study will be summarized by counts and percentage based on those who are randomized in 
the Maintenance Part.
Listings will be provided for discontinued subjects with reason for treatment and study 
discontinuation.
7.2.
Induction Part
7.2.1.
Study Population Definitions
7.2.1.1.
Intent-to-Treat Population
The efficacy analysis will be performed on the ITT population, which includes all enrolled 
subjects who received at least 1 dose of study treatment regardless of whether the subject has any 
efficacy assessments collected.
7.2.1.2.
Safety Population
The safety population will be the analysis population for all safety/ tolerability analyses. The 
safety population includes all subjects enrolled who received at least 1 dose of study treatment. 
Only subjects with clear documentation that no study treatment was administered will be 
excluded from the safety population.
7.2.2.
Baseline values
For the Induction Part of the study, baseline is defined as the last non-missing value on or before
the first dose of administration of nab-paclitaxel or carboplatin. If multiple values are present for 
the same date, the average of these values will be used as the baseline.
7.2.3.
Demographics
Demographics will be summarized for the ITT population. Age (years) and weight (kg) at 
baseline will be summarized descriptively. Age category (<65 versus ≥65 years, <70 versus ≥70 
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.2.3.
.2.3.


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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years, and < 75 versus ≥ 75 years), sex, race, and ethnicity will be summarized by frequency 
counts.
Age will be calculated as follows: age = greatest integer ∀[(date of informed consent – date of 
birth + 1) / 365.25]. 
7.2.4.
Baseline Characteristics
Baseline characteristics, the latest collected on or before the first date of dosing, will be 
presented for the Induction Part of the study:
!
ECOG performance status at baseline (0 or 1)
!
Physician assessment of peripheral neuropathy (PN) at baseline
!
Assessment of diabetes in medical history, which will support subgroup analyses of 
diabetic subjects
7.2.5.
Lung Cancer History
The following items will be summarized for lung cancer history:
!
Disease stage before administration of Induction therapy (IIIB or IV)
!
Method of specimen collection (biopsy, surgical specimen, FNC, other)
!
Confirmation of squamous cell histology and type (papillary, clear cell, basaloid, and 
other)
!
Time from latest systemic anti-cancer therapy to first dose date in months
!
Time from latest cancer therapy (last to occur of systemic anti-cancer therapy, 
radiation, or cancer surgery) to first dose date in months.
Subject listings will be provided for all of the above, as well as date of specimen collection.
7.2.6.
Medical History
A summary of medical and surgical history will be presented by MedDRA 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.
7.2.7.
Prior and Concomitant Anti-Cancer Therapy
7.2.7.1.
Prior Systemic Anti-Cancer Therapy
Prior systemic therapies (e.g. chemotherapy) will be summarized by therapeutic drug classes and 
generic drug names using the World Health Organization (WHO) drug dictionary. The duration, 
whether the number of cycles is known, the number of cycles (if known), and the best response 
will be presented in a listing.
7.2.7.2.
Prior and Concomitant Radiation Therapy
The number and percentage of subjects who had any prior or concomitant radiation therapy will 
be presented. For subjects with prior and concomitant radiation therapy, the number and 
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will be p
will be p


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
22
percentage of subjects with each treatment site of radiation therapy will be presented. Duration, 
dose, fraction (where known), 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.
7.2.7.3.
Prior and Concomitant Non-small Cell Lung Cancer Surgeries
The number and percentage of subjects who had any prior or concomitant non-small cell lung 
cancer surgery will be presented by system organ class and preferred term. Prior and 
concomitant surgeries will be listed.
7.2.8.
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 2013. 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. 
7.2.8.1.
Prior Medications
Prior medications are defined as all medications that were started before Day 1 of treatment for 
the Induction Part. 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.
7.2.8.2.
Concomitant Medications
Concomitant medications for the Induction Part are defined as any non-study medications that 
were taken on/after the date of the first dose of study drug and within 28 days after the date of 
treatment discontinuation if the subject discontinues without being randomized, or taken on/after 
the date of the first dose of study drug and before the randomization date if the subject is 
randomized into the Maintenance Part.
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.
7.2.9.
Study Treatments and Extent of Exposure
All study treatment and extent of exposure summaries will be provided based on the safety 
population. Descriptive statistics will be provided for treatment duration, number of cycles, 
cumulative dose, dose intensity, and percentage of protocol dose. 
7.2.9.1.
Treatment and Cycle Start and End Dates
Induction treatment will commence on Day 1 Cycle 1, and planned cycle lengths are 21 days. 
Day 1 of treatment for the Induction Part is defined as the first day of any study drug.
Cycle Start and End Dates of Induction Part
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7.2.9.1.
7.2.9.1.
duct
duct


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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Cycle start dates in the Induction Part are the first day of any Day 1 carboplatin administration 
(as recorded on the eCRF). Cycle end dates in the Induction Part are defined as the day before 
Day 1 of the following cycle. The treatment end date defined below is the Cycle 4 end date.
Treatment End Date of Induction Part
Treatment end date for the Induction Part, and the end date of the last cycle in the Induction Part, 
will be calculated as follows:
!
For subjects who are not randomized, the maximum of date of last nab-paclitaxel 
dose + 6 and date of last carboplatin dose + 20 will be used as the treatment end 
date.
!
For subjects who are randomized: 
o
If the last dose is Day 1 of Cycle 4, then the minimum of Day 1 plus 20 days 
and the day before randomization date will be used for the treatment end date 
for the Induction Part.
o
If the last dose is Day 8 of Cycle 4, then the minimum of Day 8 plus 13 days 
and the day before randomization date will be used for the treatment end date 
for the Induction Part.
o
If the last dose is Day 15 of Cycle 4, then the minimum of Day 15 plus 6 days 
and the day before randomization date will be used for the treatment end date 
for the Induction Part.

In the event that the last dose is administered on the same day as 
randomization, then the treatment end date will be the randomization 
date.
The cycle number for each date of interest, e.g., AE start date, will be calculated based on the 
cycle window set by the start and end dates of the study medication. 
7.2.9.2.
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. 
Conceptually, the dosing period for a study drug is the time period starting at the first dose of the 
study drug and ending a protocol- and subject-specific number of days after the last dose, 
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. To 
avoid such overestimation, additional days of dosing period beyond the date of the last dose 
allow for the calculated dose intensity to reflect the degree to which the subject’s dosing 
schedule aligned with the protocol-specified dose intensity. A subject’s dosing period never 
extends beyond the date of death, but it can extend beyond the treatment discontinuation date in 
some circumstances.
For subjects who participate in the Maintenance Part, nab-paclitaxel dosing periods in the 
Induction Part are equal to treatment duration for the Induction Part. See Sections 7.2.9.1 and 
7.2.9.3. For subjects who participate in the Maintenance Part, carboplatin dosing period is the 
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-003
Celgene Corporation
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minimum of the study day of the Cycle 4 Day 1 dose of carboplatin plus 20 and the day number 
of the day before randomization.
For subjects who are still on treatment in the Induction Part at the time of clinical cutoff and 
subjects who discontinue during the Induction Part prior to the clinical cutoff date, the specific 
calculations of the Induction Part dosing period for each study drug and arm are given in Table 2
below:
Table 2:
Calculation of Induction Dosing Period for Each Study Drug Based on Cycle 
Day Number of Last Dose of the Study Drug
(For subjects who are still on treatment in the Induction Part at the time of clinical cutoff and 
subjects who discontinue during the Induction Part prior to the clinical cutoff date)
nab-Paclitaxel
Carboplatin
Last dose record is D1, D8, or D15
Last dose record is D1
min{study day of death date (if it exists), study day of 
date of last dose of nab-paclitaxel + 6}
min{study day of death date (if it 
exists), study day of date of last 
dose of carboplatin +20}
where the last dose is the latest exposure record of the respective treatment regardless of the 
actual dose or whether the dose was administered.
7.2.9.3.
Treatment Duration
Treatment duration (in weeks) is defined as: 
[(Treatment end date for the Induction Part) – (Day 1 of treatment for the Induction Part) + 
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 Induction cycle, the end date is the treatment end date for the 
Induction Part as defined in Section 7.2.9.1.
Descriptive statistics will be provided for treatment duration and total number of cycles for both 
carboplatin and nab-paclitaxel. Number of subjects will also be tabulated by total number of 
cycles received for both carboplatin and nab-paclitaxel.
7.2.9.4.
Cumulative Dose 
Cumulative dose is defined as the sum of the values entered on the dose assigned field on the 
exposure eCRF, taken across the Induction Part 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 safety population.
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atisti


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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7.2.9.5.
Dose Intensity
Dose intensity for a study drug 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 drug for the Induction Part of the study for the safety
population.
7.2.9.6.
Exposure, Dose Reduction/Delay, and Doses Not Administered
7.2.9.6.1. Dose Reduction 
A dose reduction is defined as a dose administered after the Cycle 1 Day 1 dose which is at a 
lower dose level than the dose the subject received at the previous dosing visit.   
7.2.9.6.2. Dose Not Administered
A dose not administered is any scheduled dose that is not administrated.
7.2.9.6.3. Dose Delay
A dose is considered delayed if the dose was administered later than the expected date prescribed 
by the protocol in the Tables of Events, given the consideration that an administrative window of 
± 2 days is permitted for all visits except C1D1.    
Subjects are to be dosed with either nab-paclitaxel on Day 1, 8, and 15 and with carboplatin on 
D1 in each of the 4 cycles in the Induction Part.  
7.2.9.6.3.1. Definitions of actual dose date, reference date, and expected dose date
Assuming all the dose and visit dates are available and entered in the database as described in the 
CRF completion guidelines, then the definitions below provide the precise method for the 
determination of a dose delay. If any of the dates required for the determination of a dose delay 
is missing, then the imputation rules in the next section (Section 7.2.9.6.3.2) will be applied to 
facilitate the calculations. 
The actual dose date is defined as the date when at least one of the IPs was administered, or 
when all the planned IPs were not administered as entered by the site in the Exposure CRF page
and the visits module.  
!
If more than one IP was to be administered at a dose visit, but the IPs were given at 
different dates, then the latest dose dates among the IPs will be taken as the actual dose 
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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date for that visit.  Similarly, if an IP is given more than one time for a visit, then the 
latest of the dose dates will be taken as the actual dose date for that visit.
!
For the calculation of dose delay parameters, if none of the planned IPs was administered 
at a dose visit, then that dose visit will be considered for “dose not administered” 
calculations only, but not for “dose delay” calculations.  
The reference date is defined as the previous visit at which the patient was to be dosed with any 
of the IPs. For example, the reference date for Day 8 is D1.    
The expected dose date for the current visit is defined as 7+2 days after the reference date for 
nab-paclitaxel and carboplatin.     
A dose delay is declared if the actual dose visit date is later than the expected dose visit date. 
7.2.9.6.3.2. Imputation Rules for the Reference Date
For the determination of the actual dose date, the current dose date of the visit of concern 
should be utilized.  If the dose date is not available, then the dose is considered “not 
administered”.  No further consideration should be given regarding dose delay for that visit. 
For the determination of the reference date, use the previous dose date if available, or the 
previous visit date if the previous dose date is missing.  If both are missing, then use the dose 
date from two visits prior to the current dose visit, or the corresponding visit date if the former is 
missing.  If both are missing, then use the dose date from three visits prior to the current dose 
visit, or the corresponding visit date if the dose date is missing. This logic can be extended 
accordingly until a dose date or visit date can be identified for the calculation of the reference 
date for the current dose visit of concern.  
It should be noted that there are two scenarios for which the dose date could be missing:  
1. The patient was physically present at the clinic and some measurements were taken, but 
the IPs were not administered as prescribed by the protocol, then the dose date in the 
Exposure database will be missing while the visit date would have been entered and is 
available in the Visit module database. 
2. If the patient was not physical present at the clinic, then both the dose date in the 
Exposure database and the visit date in the Visit module database will be missing.
Each dosing record of the IPs will be listed. If any overdose occurred and reported on the 
Investigational Drug Overdose CRF page, then it will be summarized (e.g., number of subjects 
with overdose on each IP, difference in planned duration of infusion and actual duration of 
infusion, difference in planned dose and actual dose, whether the overdose result in any adverse 
event), and will also be displayed in a listing. 
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nab-Paclitaxel (Abraxane®)
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Treatment exposure and dose reductions, 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. If the reason for dose not administered is not 
given, it will be categorized as “Data Not Available” in summary tables.
7.2.9.7.
Percentage of Protocol Dose
Percentage of protocol dose is the dose intensity divided by the protocol weekly dose, expressed 
as a percentage.
!
Percentage of protocol dose = (dose intensity / protocol weekly dose) * 100%
The protocol weekly doses are as follows:
!
nab-Paclitaxel: 100 mg/m2/wk (total of 12 doses – 1 each for days 1, 8, and 15 for 
each cycle * 4 cycles / 12 weeks in duration)
!
Carboplatin: 2 mg*min/mL/wk (6 mg*min/mL * total of 4 doses – 1 on day 1 of each 
of 4 cycles / 12 weeks in duration)
Percentage of protocol dose for carboplatin and nab-paclitaxel will be categorized into <20%,
≥20% to < 30%, ≥30% to < 40%, ≥40% to < 50%, ≥50% to < 60%, ≥60% to < 70%, ≥70% to < 
80%, and ≥80 to <90% and ≥90%, and frequency counts will be provided for the safety 
population.
7.2.10.
Efficacy Analysis
All efficacy evaluations will be conducted using the ITT population. Any presentation of 
response for the Induction Part of the study will be for descriptive or estimation purposes only. 
The percent change from nadir during the Induction Part in sum of total length is required to 
assess target lesions for tumor progression. This is calculated as follows:
Percent change from nadir at a given visit= (total length – nadir in total length) / (nadir in total 
length) x 100%, where nadir is calculated using all measurements before the visit in question, 
including baseline.
Listings will be provided for all endpoints. To support RECIST 1.1 assessments, the following 
information will be presented in listings:
!
Per subject visit:
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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28
o
Date of assessment
o
Number of target lesions
o
Total length of target lesions
o
Percent change from nadir of sum of total length (derived as above to review 
assessment of progressive disease)
o
Percent change from baseline of sum of total length to review assessment of 
response
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Assessment of target lesions
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Presence of symptomatic deterioration
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Best overall response
!
Per lesion at each subject visit:
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Location
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Method of assessment
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Tumor length (target lesions only)
!
Overall per subject
o
The best response over the Induction Part
7.2.10.1.
Tumor Response and Overall Response Rate
The primary purpose of the Induction Part is to identify subjects who achieve a radiologically 
assessed tumor response of SD, PR, or CR without clinical progression according to RECIST 1.1 
criteria at the end of Cycle 4 and are therefore eligible for randomization into the Maintenance 
Part of the study.
The number and percentage of those with a tumor response of SD, PR, or CR will be presented, 
as well as the number and percentage with each of PD, SD, PR, CR, and unevaluable (UE). The 
denominator for the percentage will include all Induction Part ITT subjects, regardless of 
whether they had a tumor assessment. Subjects with no tumor assessments will be considered 
UE. This analysis will be presented for each protocol-specified CT scan (Week 6 for the end of 
Cycle 2, and Week 12 for the end of Cycle 4). 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 11.4.
The overall response rate is the percentage of subjects who achieved best response of confirmed
PR or CR compared with baseline, where baseline is the last CT-scan obtained prior to or on Day 
1 of treatment for the Induction Part. In this study, the best response of PR or CR has to be 
confirmed by repeated assessment no less than 28 days after the response criteria are met. The 
ORR along with 95% Clopper-Pearson confidence interval will be presented. The following 
rules will be observed for response rate in the Induction Part:
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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29
!
For subjects who participate in the Maintenance Part, use best response among any 
tumor assessments on or before the day of randomization.  The first radiographical 
evaluation performed within 91 days after randomization can be utilized as the 
confirmation scan, if necessary.
!
For subjects discontinued prior to the Maintenance Part, use best response on or up 
until the patient receives a subsequent anti-cancer therapy
!
All Induction Part ITT subjects will be included for this analysis.
!
Confirmation of CR/PR will be programmed according to the standard guidance 
document created by the Biostatistics department.
7.2.10.2.
Disease Control Rate
Disease Control rate is defined as the percent of subjects who have a radiologic complete 
response, partial response, or stable disease according to RECIST 1.1 guidelines, as determined 
by the investigator. Disease Control rate over the Induction Part along with associated Clopper-
Pearson 95% CI will be presented for the Induction ITT population.
7.2.10.3.
Time to Response
Time to response is defined as the time from the first dose of study drug to the first occurrence of 
confirmed response (CR or PR). Time to response will be summarized with descriptive statistics.
Only subjects with a CR or PR as a best overall confirmed response during Induction will be 
included in this analysis.
7.2.11.
Safety Analyses
The purpose of this section is to describe the safety analyses for the Induction Part of the study. 
Adverse events and laboratories will be analyzed based on the safety population.
7.2.11.1.
Adverse events
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA)
Version 17.0 or above. Appendix 11.5 gives the dates of application of new versions of 
MedDRA.
Adverse events will be analyzed in terms of treatment emergent adverse events (TEAEs), defined 
as any AEs that began or worsened in grade on or after Day 1 of treatment for the Induction Part
and on or before the date of randomization for those who enter in the Maintenance Part, or 
through treatment discontinuation date plus 28 days for those who do not enter in the 
Maintenance Part. In addition, any SAE deemed by the investigator to be related to study drug is 
a TEAE, even if beyond the 28-day window.
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 
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com


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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30
related. AEs with a missing relationship will be presented in the summary table as a relationship 
category of “treatment-related”.
The incidence of TEAEs/treatment related TEAEs will be summarized by MedDRA system 
organ class (SOC) and preferred term (PT) in a decreasing frequency order for SOC or PT. If a 
subject experiences multiple AEs under the same preferred term (system organ class), then the 
subject will be counted only once for that preferred term (system organ class). The intensity of 
AEs will be graded 1 to 5 according to the National Cancer Institute Common Terminology 
Criteria for Adverse Events (CTCAE) Version 4.0. For all other AEs not described in the 
CTCAE criteria, the intensity will be assessed by the investigator as mild (grade 1), moderate 
(grade 2), severe (grade 3), life-threatening (grade 4) or death (grade 5). If a subject experiences 
the same AE more than once with different toxicity grade, then the event with the highest grade 
will be tabulated in “by grade” tables. In addition, AEs with a missing intensity will be presented 
in the summary table as an intensity category of “Missing.”
Tables summarizing the incidence of TEAEs will be generated for each of the following:
!
Overall summary of TEAEs;
!
TEAEs presented by MedDRA system organ class, preferred term, and worst CTCAE 
grade
!
Treatment-related TEAEs by grade category (grade 1-2 vs. grade 3-4 vs. grade 5; 
overall and by cycle);
!
Serious TEAE by worst CTCAE grade;
!
Treatment-related serious TEAE by worst CTCAE grade;
!
TEAEs with action of study drug withdrawn;
!
Treatment-related TEAEs with action of study drug withdrawn;
!
TEAEs with action of study drug dose reduced or interrupted;
!
Treatment-related TEAEs with action of study drug dose reduced or interrupted;
!
TEAEs with fatal outcome;
!
Treatment-related TEAEs with fatal outcome;
!
All deaths within 28 days of treatment discontinuation date with cause of death;
!
Most frequent TEAEs (≥5%; sorted by Preferred Term, without SOC);
!
TEAEs for the following baseline subgroups (provided the number of subjects are 
sufficient):
#
Age (<65 years versus 65 to ≤ 74 years versus ≥ 75 years)
#
Sex (male versus female)
For TEAEs that are summarized by cycle, the following rules will be used:
!
TEAEs which occur on Day 1 Cycle 1 belong to Cycle 1.
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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!
After cycle 1, TEAEs will be categorized by the “throw-back rule”, that is, TEAEs 
that occur on Day 1 of a cycle will be allocated to the previous cycle.
!
All TEAEs which occur after Day 1 of last cycle will be included in the last cycle.
For subjects who are randomized, all TEAEs which occur after Day 1 of Cycle 4 and
on or before the randomization date will be included in Cycle 4.
Data listings will be presented for all TEAEs. A listing for non-treatment-emergent AEs will also 
be provided. 
7.2.11.2.
Peripheral Neuropathy
Peripheral neuropathy events will be collected on the Physician Assessment of Peripheral 
Neuropathy eCRF and reported as AEs and will be included in analyses described in 
Section 7.2.11.1. A summary of PN grade by Induction cycle will be provided based on the 
eCRF data.
For subjects who were treated in the Induction Part only (i.e., subjects who discontinued 
treatment without being randomized), additional summaries of peripheral neuropathy events will 
be presented using both the AE data and the PN eCRF data. Adverse events will be considered 
PN events if they are TEAEs and are identified as peripheral neuropathy based on the 
Standardized MedDRA Queries (SMQs). The following will be summarized:
!
Number and percentage of subjects who develop grade 3 or higher peripheral 
neuropathy;
!
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; 
and
!
Time to improvement of grade 3 or higher peripheral neuropathy to grade 0 or grade 
1. 
Due to the small number of events expected, time to first onset will be summarized with 
descriptive statistics for only those subjects who experienced peripheral neuropathy of the 
relevant grade. There will be no censoring. 
Time to improvement of the grade ≥3 PN events listed above will be summarized for subjects 
who have a grade ≥3 PN event using the Kaplan-Meier methods. Subjects who do not achieve 
the relevant improvement by the time of the last evaluation of adverse events will be censored at 
the last time the subject is evaluated for adverse events. 
7.2.11.3.
Adverse Events of Special Interest
The following summaries will be provided for TEAEs included in the above-mentioned AEs of 
interest: 
1. TEAEs by maximum CTCAE grade; 
2. Serious TEAEs; 
3. TEAEs with action of drug withdrawn;
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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32
4. TEAEs with action of dose reduced or interrupted;
5. TEAEs with fatal outcome;
TEAEs of special interest will be listed.
7.2.11.4.
Clinical Laboratory Evaluations
Listings will be provided for the local laboratory data. 
7.2.11.4.1. Hematology
All hematology data will be listed. 
7.2.11.4.2. Clinical Chemistry
All clinical chemistry data will be listed.
7.2.11.5.
Concurrent Radiation and Surgeries
The number of subjects having concomitant radiation or surgeries and procedures performed will 
be summarized.
Concomitant radiation or surgeries will be listed.
7.2.12.
Quality of Life Analysis
The Lung Cancer Symptom Scale (Pol) 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, and at Early 
Treatment Discontinuation/End of Cycle 4 during the Induction Part of the study. 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.
For administrative purposes (e.g., planning of new studies, publication of data) the LCSS and 
EQ-5D measurements collected during the Induction Part will be summarized overall and by 
subgroup using descriptive statistics as needed when approximately 50, 100, 200, 400, and all 
subjects, respectively, have either discontinued during or completed the Induction Part of the 
study. Subgroups may include but are not limited to radiological response and baseline symptom 
status.
7.2.12.1.
LCSS
The LCSS is designed to measure quality of life specifically affected by lung cancer and its 
symptoms. It evaluates burden due to six major symptoms:
!
Appetite
!
Fatigue
!
Coughing
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symptom
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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33
!
Shortness of breath
!
Blood in sputum
!
Pain
In addition, it measures how bad a subject’s symptoms are, how much lung cancer has affected 
normal activities, and global 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 general health scale.
Summary statistics of the individual LCSS items and summary scale scores, the change from 
baseline, and percent change from baseline will be summarized for the ITT population at every 
time point at which the instrument is given, and at end of Induction (i.e., last assessment during 
Induction or Cycle 5 Day 1, whichever is latest). In addition, the change from baseline to the 
LCSS score during the Induction Part, defined as the difference between the last reported LCSS 
score during the Induction Part, either the end of 4 cycles or early discontinuation visit or the last 
reported LCSS score before clinical cutoff for subjects who have not reached that point at an 
interim analysis, will be presented.
7.2.12.2.
EQ-5D-5L
The EQ-5D-5L has been designed as an international, standardized, generic instrument for 
describing and valuing health-related quality of life. It contains only the domains common to 
generic health status measures, contains the minimum number of questions for each domain, was 
designed for ease of self-administration, and produces a single index for analysis. 
Five dimensions are covered by the EQ-5D-5L:
!
Mobility
!
Self-care
!
Usual Activities
!
Pain/Discomfort
!
Anxiety/Depression
The 5 dimensions are scored on a 5-point Likert scale. In addition, there is a question covering 
perceived change in health status over the previous 12 months measured on a 20 cm vertical 
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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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. The overall utility score, change from baseline, and percent 
change from baseline in the overall utility score will be summarized for every time point at 
which the instrument is given for the ITT population. 
Shifts from baseline to each time point at which the instrument is given will be presented for 
each dimension for the ITT population. 
Summaries of the VAS results and the change and percent change from baseline will be 
presented for every time point at which the instrument is given.
7.3.
Maintenance Part
7.3.1.
Study Population Definitions
7.3.1.1.
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 regimen or has any 
efficacy assessments collected. In all ITT analyses, subjects are analyzed according to their 
randomized treatment, regardless of what treatment they may receive at any time after 
randomization.
7.3.1.2.
Response Evaluable Population
Response evaluable (RE) population includes all randomized subjects who meet eligibility 
criteria, take at least one dose of study drug or are on BSC and have at least one baseline and one 
post-randomization efficacy assessment. The response evaluable population will be used in a 
replication of the primary and major secondary efficacy analyses to assess the effect of subjects 
who were randomized but not treated or assessed on the efficacy analysis.
7.3.1.3.
Per-Protocol Population
The per-protocol (PP) population, which will include all subjects randomized in the Maintenance 
part who receive at least one dose of the study therapy or on BSC arm and do not have any 
known major protocol deviations and fulfill the study enrollment criteria. The PP population will 
be used in a replication of the primary and major secondary efficacy analyses to assess the effect 
of major protocol deviations on efficacy. Protocol deviations and their handling for analysis 
purposes, are discussed in more detail in Section 6.
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7.3.1.4.
Safety Population
The safety population includes all randomized subjects. The safety population will be the basis
of all safety analyses. Subjects who receive nab-paclitaxel in error will be analyzed by actual 
treatment received.
7.3.2.
Demographics
Demographics will be summarized for the ITT population. Age (years) and weight (kg) at 
baseline will be summarized descriptively. Age category (<65 versus > 65 years, <70 versus ≥70 
years, and < 75 versus ≥ 75 years), sex, race, and ethnicity will be summarized by frequency 
counts.
Age will be calculated as follows: age = Integer ∀[(Date of informed consent – Date of Birth + 
1) / 365.25]. 
7.3.3.
Baseline Characteristics
The following characteristics collected before the beginning of the Induction Part will also be 
presented for the subjects in the Maintenance Part of the study by treatment arm for the ITT 
population:
!
Assessment of diabetes in medical history, which will support subgroup analyses of 
diabetic subjects
In addition, the following measures collected before the Maintenance Part of the study will be 
summarized. The last non-missing measure before randomization be considered baseline for 
these measures:
!
ECOG performance status at end of Induction (0 or 1)
!
Physician assessment of peripheral neuropathy (PN)
!
The tumor response (CR, PR, and SD) achieved in the Induction Part
7.3.4.
Lung Cancer History
The following items will be summarized by treatment arm for lung cancer history:
!
Disease stage before administration of Induction therapy (IIIB or IV)
!
The time from the first diagnosed date of lung cancer (specimen collection date if the 
diagnosed date is unknown) to Day 1 of treatment for the Induction Part in months, 
defined as (Day 1 of treatment for the Induction Part – the first diagnosed date (or 
specimen collection date if the diagnosed date is unknown) + 1)/30.4375
!
Method of specimen collection (biopsy, surgical specimen, fine needle cytology 
(FNC), other)
!
Confirmation of squamous cell histology and type (papillary, clear cell, basaloid, and 
other)
Subject listings will be provided for all of the above, as well as date of specimen collection.
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7.3.5.
Medical History
A summary of medical and surgical history will be presented by MedDRA system and organ 
class (SOC) and preferred term (PT). A similar summary will be generated for the currently 
active abnormalities only at randomization, by SOC and PT.
7.3.6.
Prior and Concomitant Anti-Cancer Therapy
Subject listings described in the Induction Part of this SAP will include a column for treatment 
group, if applicable.
7.3.6.1.
Prior Systemic Anti-Cancer Therapy
The number and percentage of subjects with any prior systemic anti-cancer therapy will be 
presented by treatment group for the ITT population.
7.3.6.2.
Prior and Concomitant Radiation Therapy
The number and percentage of subjects who had any prior or concomitant radiation therapy will 
be presented by treatment group for the ITT population. For subjects with prior and concomitant 
radiation therapy, the number and percentage of subjects with each site of radiation therapy will 
be presented.
7.3.6.3.
Prior and Concomitant Non-small Cell Lung Cancer Surgeries
The number and percentage of subjects with any prior or concomitant cancer surgery will be 
presented by treatment group, system organ class and preferred term for the ITT population. The 
time from the last prior non-small cell lung cancer surgery to date of first dose will be 
summarized.
7.3.7.
Prior Medications
Prior medications are defined as in the Induction Part. A summary showing the number and 
percentage of subjects randomized to the Maintenance Part 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.
7.3.8.
Concomitant Medications
Concomitant medications for the Maintenance Part are defined as non-study medications that 
were taken on/before the randomization and within 28 days of the treatment discontinuation date. 
Summaries showing the number and percentage of subjects who took concomitant medications 
by WHO therapeutic drug class and generic drug name will be presented for the ITT population.
7.3.9.
Concurrent Radiation and Surgeries
The number of subjects having concomitant surgeries and procedures performed will be 
summarized.
Concomitant surgeries will be listed.
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s
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will
will b
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The num
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mm


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
37
7.3.10.
Study Treatments and Extent of Exposure
All study treatment and extent of exposure summaries will be provided based on the safety 
population. Descriptive statistics will be provided for treatment duration, number of cycles, 
cumulative dose, dose intensity, and percentage of protocol dose by treatment arm. 
7.3.10.1.
Treatment and Cycle Start and End Dates
Maintenance treatment will commence on Day 1 Cycle 5, and planned cycle lengths are 21 days. 
Day 1 of treatment for the Maintenance Part is defined as the date when the Day 1 Cycle 5 nab-
paclitaxel dose was administered for the nap-paclitaxel arm, and the first visit date of any Day1 
Cycle 5 assessments for the BSC arm.    
Cycle Start and End Dates of Maintenance Part
For subjects randomized to nab-paclitaxel + BSC, Day 1 of Cycle 5 is defined as the date when 
the Day 1 Cycle 5 nab-paclitaxel dose was administered and Day 1 of any cycle beyond Cycle 5 
is the date of Day 1 nab-paclitaxel administration in a cycle. For subjects randomized to BSC 
alone, Day 1 of Cycle 5 is defined as the first visit date of any Day1 Cycle 5 assessments and 
Day 1 of any cycles beyond Cycle 5 is the first visit date of any Day 1 assessments for that cycle. 
Cycle end dates are the day before Day 1 of the following cycle. The treatment end date 
described in the section below is the end date for the last cycle.
Cycle duration is defined as the time period from Day 1 of each cycle to one day prior to the Day 
1 of subsequent cycle (see details in Section 5.2.2).
Treatment End Date of Maintenance Part
Treatment end date for the Maintenance Part, is defined as the date before the next planned 
cycle.
The cycle number for each date of interest, e.g., AE start date, will be calculated based on the 
cycle window set by their start and end dates.
7.3.10.2.
Dosing Period for nab-Paclitaxel
The Maintenance Part dosing period will be defined for nab-paclitaxel and will be used as the 
denominator for the calculation of dose intensity. 
Conceptually, the dosing period for a study drug is the time period starting at the first dose of a 
study drug and ending at subject-specific number of days after the last dose, 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 as the exposure to the 
study drug extends beyond the dosing date. 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 for a study drug never extends beyond the date of death, but 
it can extend beyond the treatment discontinuation date in some circumstances. The specific 
calculations of the Maintenance Part dosing period are given in Table 4 below:
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-
Day1 
y1 
s s th
the date w
date w
cle bey
cle b
on
ond
ando
ndomized
mized
ycle 5 asses
cle 5 asse
1 assessm
 assessm
The treatm
he treatm
each cycle
each cycl
defined as
defined a
est,
est, e.g.
e.g., AE
A
nd dates.
nd dates
ab
ab-Paclita
Paclita
ng period 
g period w
ulat
ula ion of
o d
f
osing period
ing perio
nding a
nding at sub
sub
le for the tr
e for the 
dose woul
dose would
ug extends 
extends
g period be
g period be
e degree to 
degree to 
intntensi
ensity
ty
i . A
. A
t can ex
can e


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
38
Table 4:
Calculation of Maintenance nab-Paclitaxel Dosing Period Based on Cycle 
Day of Last Dose
Last dose record is D1
Last dose record is D8
min{study day of death date (if it exists), study 
day of date of last dose of nab-paclitaxel + 9.5}
min{study day of death date (if it exists), 
study day of date of last dose of nab-
paclitaxel + 13}
where the last dose is the latest exposure record of nab-paclitaxel regardless of the actual dose or 
whether the dose was administered.
7.3.10.3.
Treatment Duration
Treatment start date for the Maintenance Part is defined as the date when the Day 1 Cycle 5 nab-
paclitaxel dose was administered for the nap-paclitaxel arm, and the first visit date of any Day1 
Cycle 5 assessments for the BSC arm.  For the BSC arm, treatment duration is an indicator for 
the duration the subject participated in the Maintenance period prior to discontinuation due to 
death, adverse event, progressive disease, symptomatic deterioration, withdrawal by subject, lost 
to follow up, protocol violation, or other reason, although no study regimen was administered.
Treatment duration (in weeks) is defined as: 
[(Treatment end date for the Maintenance Part) – (Treatment start date for the Maintenance Part) 
+ 1]/7.    
Descriptive statistics will be provided for treatment duration and total number of cycles for the 
nab-paclitaxel+BSC arm, both for the Maintenance Part and for the entire study. Number of 
subjects will also be tabulated by total number of cycles received in the Maintenance Part and in 
the entire study.
7.3.10.4.
Cumulative Dose
Cumulative dose is defined as the sum of the values entered on the dose assigned field on the 
exposure eCRF, taken across the study period in mg/m2 for nab-paclitaxel. Only doses that were 
actually administered will be included in the sum. 
As subjects who entered the Maintenance Part might have a different dose intensity profile than 
subjects who did not, descriptive statistics will be presented for cumulative dose over the 
Induction Part (by Maintenance treatment arm) and Maintenance Part for the nab-
paclitaxel+BSC arm for the safety population (subjects treated) in the Maintenance Part. In 
addition, cumulative dose for carboplatin from the Induction Part, calculated as described in 
Section 7.2.9.4, will be summarized by Maintenance treatment arm for the same safety 
population in the Maintenance Part. 
7.3.10.5.
Dose Intensity
Dose intensity of nab-paclitaxel during the Maintenance Part or entire study is defined as the 
cumulative dose divided by the dosing period for the Maintenance Part or the entire study, 
respectively.  Dose intensity of carboplatin will be calculated for the Induction Part only.  
&(/*(1(35235,(7$5<,1)250$7,21
$7
ose or 
se or 
$7
$7
50$7
Day 1 Cyc
Day 1 Cyc
visit date of
visit date of
ation is an 
ation is a
to discont
o disconti
ion, withdr
n, withdr
tudy regim
tudy reg
atment star
atment sta
ment durati
ent durat
enance Par
enance Pa
umber of cy
mber of cy
s the sum o
s the sum o
oss the
s the stu
will be inclu
will be incl
ntered the
ntered the M
d not, d
d not, desc
rt (by
(by Main
ain
+BSC
BSC arm
arm
n, cum
n, cumulat
ulat
m
ion
on 7.2.9.4
7.2.9.4
opul
opulatatioion i
3.10
3 10


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
39
Dose intensities will be calculated as follows:
!
Dose intensity for nab-paclitaxel = [cumulative dose for nab-paclitaxel in mg/m2]/[dosing 
period in weeks].
Dose intensity for nab-paclitaxel will be presented for the safety subjects in nab-paclitaxel+BSC.
In addition, dose intensity from the Induction Part, described in Section 7.2.9.5, will be 
summarized by Maintenance treatment arm including only Maintenance safety subjects.
7.3.10.6.
Exposure, Dose Reduction/ Delay, and Doses Not Administered
7.3.10.6.1. Dose Reduction 
A dose reduction is defined as a dose administered after the Cycle 5 Day 1 dose which is at a 
lower dose level than the dose the subject actually received at the previous dosing visit for the 
nab-paclitaxel + BSC arm.   
7.3.10.6.2. Dose Not Administered
A dose not administered is any scheduled dose that is not administrated. 
7.3.10.6.3. Dose Delay
A dose is considered delayed if the dose was administered later than the expected date prescribed 
by the protocol in the Tables of Events, given the consideration that an administrative window of 
± 2 days is permitted for all visits except C5D1.    
Subjects are to be dosed with nab-paclitaxel on Day 1 and 8 in the Maintenance Part.
7.3.10.6.3.1.Definitions of actual dose date, reference date, and expected dose date
Assuming all the dose and visit dates are available and entered in the database as described in the 
CRF completion guidelines, then the definitions below provide the precise method for the 
determination of a dose delay. If any of the dates required for the determination of a dose delay 
is missing, then the imputation rules in the next section (Section 7.2.9.6.3.2) will be applied to 
facilitate the calculations. 
The actual dose date is defined as the date when nab-paclitaxel was administered, or when the 
planned dose was not administered as entered by the site in the Exposure CRF page and the visits 
module.  
!
If nab-paclitaxel is given more than one time for a visit, then the latest of the dose dates 
will be taken as the actual dose date for that visit.
!
For the calculation of dose delay parameters, if nab-paclitaxel was not administered at a 
dose visit, then that dose visit will be considered for “dose not administered” calculations 
only, but not for “dose delay” calculations.  
The reference date is defined as the previous visit at which the patient was to be dosed with 
nab-paclitaxel. For example, the reference date for Day 8 is D1 and the reference date for Day 1 
of a cycle is D8 of the previous cycle.   
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ch is at a
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or th
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ater than th
ater than th
eration that
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ay
ay 1
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and
and 8
e, referenc
, referenc
are availabl
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definitioio
any of the 
any of the
n rul
rules in th
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is define
not adminis
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ab-pacli
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will be tak
will be tak
!
For th
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do
do


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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The expected dose date for the current visit is defined as 7+2 days after Day 1 and 14+ 2 days 
after Day 8.       
A dose delay is declared if the actual dose visit date is > the expected dose visit date. 
7.3.10.6.3.2.Imputation Rules for the Reference Date
For the determination of the actual dose date, the dose date of the visit of concern should be 
utilized.  If the dose date is not available, then the dose is considered “not administered”.  No 
further consideration should be given regarding dose delay for that visit. 
For the determination of the reference date, use the previous dose date if available, or the 
previous visit date if the previous dose date is missing.  If both are missing, then use the dose 
date from two visits prior to the current dose visit, or the corresponding visit date if the dose date
is missing.  If both are missing, then use the dose date from three visits prior to the current dose 
visit, or the corresponding visit date if the dose date is missing. This logic can be extended 
accordingly until a dose date or visit date can be identified for the calculation of the reference 
date for the current dose visit of concern.  
It should be noted that there are two scenarios for which the dose date could be missing:  
1. The patient was physically present at the clinic and some measurements were taken, but 
nab-paclitaxel was not administered as prescribed by the protocol, then the dose date in 
the Exposure database will be missing while the visit date would have been entered and 
is available in the Visit module database. 
2. If the patient was not physical present at the clinic, then both the dose date in the 
Exposure database and the visit date in the Visit module database will be missing.
Each dosing record of nab-paclitaxel will be listed. If any overdose occurred and reported on the 
Investigational Drug Overdose CRF page, then it will be summarized (e.g., number of subjects 
with overdose on nab-paclitaxel, difference in planned duration and actual duration, difference in 
planned dose and actual dose, whether the overdose result in any adverse event), and will also be 
displayed in a listing.
7.3.10.7.
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%
For subjects who start Maintenance therapy with an assigned dose of 100 mg/m2, the protocol 
weekly dose for nab-paclitaxel during the Maintenance Part is 66.7 mg/m2/week (the subject will 
receive two 100 mg/m2 doses of nab-paclitaxel on Days 1 and 8 of the 21-day cycle).
r the
the
e the dose
e the dose
e if the
e if the dos
dos
to the curre
to the curre
can be exte
an be exte
latioion of th
n of
se date cou
e date
some meas
ome me
ed by the
ed by the pr
the visit da
the visit
nt at the cli
nt at the cli
date in the 
date in th
axel
axel will
will be
b
l
e CRF pag
e CRF pag
taxel
axel, diffe
, diff
dose, whe
dose, wh
centage of 
centage of 
of protocol
of protoco
entage.
age.
Percent
Percent
For subject
For subject
weekly 
weekly
eiv


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
Confidential and Proprietary
41
While it is possible that a starting dose for the Maintenance Part of 75 mg/m2 may be given for 
subjects who had two dose reductions during Induction, the protocol weekly dose is 66.7 
mg/m2/week for all subjects randomized to nab-paclitaxel + BSC.
Percentage of protocol dose for nab-paclitaxel will be categorized into 10% intervals, and 
frequency counts will be provided for the safety population.
Treatment exposure and dose reductions, delays, and interruptions will be summarized for the 
nab-paclitaxel+BSC arm 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 (Per Protocol, 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. If the reason for dose not administered is not 
given, it will be categorized as “Data Not Available” in summary tables.
7.3.11.
Efficacy Analysis
All efficacy evaluations will be conducted using the ITT population. Supportive analysis of the 
primary and key secondary efficacy endpoints using the PP and RE population will be conducted 
for the final analysis. Statistical comparisons will be made between BSC and nab-
paclitaxel+BSC arms for the Maintenance Part only. Efficacy results that will be considered 
statistically significant after consideration of the strategy for controlling the Type 1 error rate are 
described in Section 7.3.11.1. All statistical tests will be two-sided at the significance level of α 
= 0.05, and the corresponding p-values and two-sided confidence intervals (CIs) for intended 
point estimates will be reported.
Listings will be provided for all endpoints. To support review of tumor response data, the 
following information will be presented in listings:
!
Per subject visit:
o
Date of assessment
o
Number of target lesions
o
Total length of target lesions
o
Percent change from nadir of sum of total length (derived as in Section 
7.3.11.2 to review assessment of progressive disease)
o
Percent change from baseline of sum of total length to review assessment of 
response
o
Assessment of target lesions
o
Assessment of non-target lesions
o
Presence of symptomatic deterioration
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f dose
ose
on, by
on, by cycle
cycl
y
umber of do
umber of d
administer
administe
her) for do
her) for do
ose not adm
e not ad
e” in summ
e” in sum
ITT
ITT popul
popu
ing the PP
ng the PP
will be mad
ll be mad
art
art only
only. E
n of the str
n of the 
ststicicalal tests
tl
lues and 
es and tw
tw
r all endpo
r all endp
ill be prese
ill be pre
ct visit:
t visit
Date of a
Date of a
o
Numb
Num
o
To
T
o


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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42
o
Overall tumor response assessment
o
Best overall response
!
Per lesion at each subject visit:
o
Location
o
Method of assessment
o
Tumor length (target lesions only)
!
Overall per subject
o
The best response over the entire study
7.3.11.1.
Multiplicity
A step down procedure will be used to control the family-wise Type 1 error rate. Overall 
Survival will only be tested if PFS demonstrates superiority for nab-paclitaxel+BSC vs. BSC. 
Strategies to control alpha due to repeated testing are described in Section 8.2 .
7.3.11.2.
Analysis of Primary Efficacy Endpoint
The primary efficacy endpoint of 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 analysis, with 
the un-stratified analysis considered a supporting analysis.  The method for determining the 
strata is detailed below.
Progressive disease is measured using the percent change from nadir over all tumor assessments 
in sum of total length. This is calculated as follows:
Percent change from nadir at a given visit= (total length – nadir in total length) / (nadir in total 
length) x 100%, where nadir is calculated using all measurements before the visit in question, 
including baseline, Induction, and Maintenance scans.
Progression-free survival will be based on investigator assessment according to RECIST 1.1 
criteria. PFS is defined as the time in months from the date of randomization to the date of 
disease progression (documented by CT-scan result, not including symptomatic deterioration) or 
death (any cause) on or prior to the clinical cutoff date, whichever occurs earlier. RECIST 1.1 
criteria defines disease progression as the occurrence of any of the following circumstances:
!
Increase of 20% in the sum of diameters of the target tumors based on the smallest sum 
(nadir) over the study (for this study it is possible that the nadir occurs at baseline or 
during the Induction Part of the study even though those time points are before 
randomization), with a 5 mm minimum increase
!
Appearance of new lesions
!
Unequivocal progression of non-target tumors
Therefore, the calculation of PFS is a two-step process:
!
Determination of date of disease progression, which is the date of assessment 
corresponding to the first time that overall tumor response is “Progressive Disease” on 
the Overall Response eCRF
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Overall
verall
+BSC
BSC vs. B
vs.
8.2
8.2 .
p-value fro
value fro
idered the p
dered th
The metho
The metho
hange from 
hange from
s:s:
otal
otal ll ength
ength
using all m
using all m
tenance
tenance sc
s
sed
ed on inv
on inv
me
me inin mo
montnth
nted by
nted by CT
CT
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or to the cl
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progression
progressio
20% in the
% in the
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Uneq
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Therefor
Therefo


nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
43
!
Calculation of PFS as (date of disease progression, death, or censoring – date of 
randomization + 1)/30.4375 as described below
Subjects who do not have disease progression and have not died, regardless of whether they were 
discontinued from treatment or not, will be censored at the date of last tumor assessment, on or 
prior to the clinical cutoff date that the subject was progression-free. If a subject begins a 
subsequent anti-cancer chemotherapy prior to documented disease progression (or death), the 
subject will be censored at the date of last assessment when the subject was documented as 
progression-free prior to the intervention. In the event that curative radiotherapy or surgery at 
lesion sites occurs, the subject will be censored at the date of last assessment when the subject 
was documented as progression-free prior to the intervention. Subjects with a single missing 
radiologic assessment prior to a visit with documented disease progression (or death) will be 
analyzed as a PFS event at the time of the radiologic assessment that shows progression or death 
(whichever is earlier). Subjects with two or more consecutive missing radiologic assessments 
prior to an assessment with documented progression (or death) will be censored at the date of last 
assessment when the subject was documented as progression-free prior to the first of the two 
missing assessments. This is further illustrated in
. below.
Table 5:
Censoring Rules for PFS
Situation
Analysis Date 
Censored or 
Event
Disease progression, and time 
interval between progression date 
and previous tumor assessment date 
with progression-free response is 
less than or equal to 91 days
Earliest of:
!
Date of first tumor 
assessment showing new 
lesion
!
Date of 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,
or time interval between the 
progression date and the 
randomization date is greater than 
91 days if the PD occurred at the 
first post baseline tumor assessment
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 wi
Death with
th
i
radi
adiol
olo
intntere
ra
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Date
ate
< ,
<
ate of 
ate o fir
first
assessmen
assessme
lesi
esion
on
!
Dat
Dat
$5
$5
23
ession
ession
umor 
mor 
h progressio
progres
reater than
reater tha
betetween t
ween t
date and th
date and th
atioion date 
n date 
ys if the PD
if the PD
t post basel
post base
L
23
23
23
23
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&
1)250$7,21
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1)


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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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
Subsequent anti-cancer treatment 
(i.e., systemic anti-cancer therapy, 
anti-cancer surgery, curative 
radiotherapy) started prior to 
progression or death
Latest of 
!
the last progression-free 
assessment date prior to 
start of anti-cancer 
treatment
!
randomization date
Censored
Disease progression and the 
progression date is before the
randomization date
Randomization date
Censored
Note: Progression-free response refers to a response that was neither progressive disease 
(PD) nor un-evaluable (UE). 
A superiority test will be performed for the primary efficacy endpoint of PFS. The corresponding 
two-sided hypotheses are: 
H0: HR(nab-paclitaxel+BSC vs. BSC only) = 1
versus
H1: HR(nab-paclitaxel+BSC vs. BSC only) ≠1, 
&(/*(1(35235,(7$5<,1)250$7,21
0$
Censored
ensored
50
1)
progression
rogressio
sment date
ment dat
ndo
ndomizat
miza io
<
Latest of 
Latest of 
!
5,(
23
n and the
and the
is before t
s before 
n date
n date
3
ogression
ogression-f
nor un
r un-eval
eval
(1
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periority y tes
t
o-sided 
sided hy
hy
H0: H
: H


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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45
where HR(nab-paclitaxel+BSC vs. BSC only) is the hazard ratio between two treatment arms 
in the Maintenance Part of the study.
The final analysis for PFS will be conducted when a total of approximately 136 PFS events
occur. All disease progression and death events that have occurred on or prior to the clinical 
cutoff date will be included. The survival distribution of PFS will be estimated using the Kaplan-
Meier method. The median PFS, including the two-sided 95% confidence interval (CI) for each 
treatment arm, will be provided. The survival distributions for the two treatment arms will be 
compared using the stratified log-rank test, and the p-value will be provided (Klein, 2003). The 
stratification factors are disease stage at diagnosis (IIIB vs. IV), response in Induction (CR/PR 
vs. SD), and ECOG performance status (0 vs. 1) after Induction. Refer to the pooling of sparse 
stratums below for situations in which the full stratified analysis will be replaced by a pooled 
stratified analysis due to a lack of information which could adversely affect power and modeling 
estimation.
The PFS rates, including two-sided 95% confidence intervals, will be provided for every 2 
months relative to randomization (Greenwood’s formula, Klein, 2003). Kaplan-Meier curves will 
be provided by treatment arm. The associated HR and two-sided 95% confidence interval will be 
estimated by using a stratified Cox proportional hazard model, with the same stratification 
factors (Cox, 1972). Refer to the pooling of sparse stratums below for situations in which the full 
stratified analysis will be replaced by a pooled stratified analysis due to a lack of information 
which could adversely affect power and modeling estimation.
Pooling Algorithm for Eliminating Sparse Stratums
If there exists unacceptable sparseness in some stratum cells for the smallest treatment arm due 
to the 2:1 randomization ratio (i.e., a stratum cell that has fewer than 5 PFS events for the BSC
treatment arms in the ITT population of the Maintenance part), then an algorithm for eliminating 
some full strata will be employed until there are at least 5 events in any given revised stratum 
cell. The initial stratum cells for the combined treatment arms will start out as 8 cells that 
represents all possible permutations of the 3 strata (baseline Eastern Cooperative Oncology 
Group [ECOG] performance status at the end of the Induction part [0 vs. 1]; tumor response to 
induction chemotherapy [CR/PR vs. SD]; and disease stage before administration of induction 
therapy [IIIB vs. IV]). Hence, the 8 cells representing all possible permutations among the strata 
may be reduced down to either 4 cells (all possible permutations of just 2 relatively large strata), 
2 cells (just 1 large stratum); or no strata at all when implementing the algorithm. However, it is 
extremely unlikely that the algorithm will result in no stratum. Once the revised strata have been 
determined through this algorithm, then it will be used consistently for all endpoints and 
populations involving a pre-specified stratified analysis.
If a sparse strata cell exists, then first consider all 3 pooling possibilities to start off with and then 
select the pooled stratum that provides the largest number of events in the smallest stratum cell. 
For example, consider three candidate pooling sets (a, b), (a, c), and (b, c), where set (a, b) has 
event cell counts {(a1, b1), (a1, b2), (a2, b1), (a2, b2)}; set (a, c) has event counts {(a1, c1), (a1, 
c2), (a2, c1), (a2, c2)}; and set (b, c) has event counts {(b1, c1), (b1, c2), (b2, c1), (b2, c2)}. 
Now let (a, b)* = min { (ai, bj) } for i=1, 2 and j=1, 2; and (a, c)* = min { (ai, cj) } for i=1, 2 and 
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-003
Celgene Corporation
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46
j=1, 2; and (b, c)* = min { (bi, cj) } for i=1, 2 and j=1, 2. The newly pooled stratum would be a 
two strata combination of a, b, or c that is the maximum of set { (a, b)*, (a, c)*, (b, c)* } for i=1, 
2 and j=1, 2. In the case of tied cases (e.g., (a, c) and (b, c) are both suggested as the two strata to 
be used in the analysis), then priority will be based on what is clinically more relevant to keep.  
If a sparse strata cell still exists in the first round of pooling, then the above pooling process 
would start over again to form a single stratum. The pooled candidate stratums are now a, b, and
c with the final pooled strata being the max { a*, b*, c* } in which no sparse strata cell exists. In 
selecting the final pooled strata; a* = min{ ai } for i=1, 2; b* = min{ bi } for i=1,2; and c* = min 
{ci } for i=1, 2. Again, in the case of tied cases, (e.g., b and c are both suggested as the strata to 
be used in the analysis), then then priority will be based on what is clinically more relevant to 
keep.
If there still exists a sparse cell, then the primary analysis will default to an unstratified one.
For this particular application, 
a = baseline Eastern Cooperative Oncology Group [ECOG] performance status at the end of the 
Induction part [a1=0 vs. a2=1] strata; 
b = tumor response to induction chemotherapy [b1=CR/PR vs. b2=SD] strata;
c = disease stage before administration of induction therapy [c1=IIIB vs. c2=IV]) strata.
In case of ties, clinical priority will be given to stratums a) baseline ECOG at end of Induction 
part; b) tumor response to induction chemotherapy; and c) disease stage before administration of 
induction therapy in this order (i.e., strata a: baseline ECOG has the highest priority and strata c:
disease stage before administration of induction therapy has the lowest priority). 
Supportive and Sensitivity Analyses
The following analyses will be conducted as supporting or sensitivity analyses using the same 
methods (i.e. p-value from stratified log-rank test, HR and two-sided 95% confidence interval 
from the stratified Cox model):
!
PFS as calculated from Day 1 of treatment for the Induction Part. For this analysis, 
the stratification factors will be the same as those used in the primary efficacy 
analysis.
!
PFS where subsequent anti-cancer therapy is considered a PFSevent
!
To assess the impact on PFS of response assessments not occurring at the regularly 
scheduled assessment times, the frequency of these unscheduled/off-scheduled visits 
will be presented for each treatment arm. In addition, 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. The 
methods similar to the primary analysis will be used to estimate the median PFS 
along with HRs.
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minin
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!
To a
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sc


nab-Paclitaxel (Abraxane®)
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Celgene Corporation
Confidential and Proprietary
47
!
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.  
!
Sensitivity analyses to address the impact of measurability of endpoints and 
adherence to protocol will be done by performing the PFS analyses mentioned above 
on the response evaluable and per protocol populations.
7.3.11.3.
Analyses of Secondary Efficacy Endpoints
7.3.11.3.1. Overall Survival
Overall survival is defined as the duration in months between randomization and death from any 
cause:
Time to OS = (Day of death or censoring– Day of randomization + 1)/30.4375
Subjects who are still alive at the end of the study will be followed up for overall survival for 1.5 
years after final analysis of approximately 136 PFS events or approximately 147 deaths have 
occurred, whichever is earlier. Subjects who are still alive after this time will have their overall 
survival censored at the date of last contact or clinical cutoff, whichever is earlier. The last 
contact date is the last non-imputed date of any record in the database for that subject, or if the 
subject is dead, the last known date the subject was alive.
However in the interim analysis of PFS a different rule will be used for simplicity. All subjects 
who do not have a death record prior to or on the cutoff date will be censored at the ‘last date 
known alive’. For subjects who have withdrawn consent during the study, the last date known 
alive will be the date of consent withdrawal from the study. For all other subjects, the last date 
known alive will be the data cutoff date.
Analysis of OS will parallel the analysis of PFS described in Section 7.3.11.2. P-values 
generated from these analyses will only be interpreted if the primary analysis is significant. The 
p-value for the stratified log-rank test using the ITT population will be considered the main 
analysis for the secondary endpoint, with unstratified analyses and analyses based on per 
protocol and response evaluable populations considered supporting analyses.
Additional supporting and sensitivity analyses will be performed as follows:
!
Overall Survival calculated from Day 1 of treatment for the Induction Part (Time to OS = 
Day of death – Day 1 of treatment for the Induction Part + 1),
!
Overall survival using the additional censoring rule of Day 1 of treatment for the cross-
over part for subjects in BSC arm who crossed over to nab-paclitaxel before protocol 
amendment 2 was implemented.
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 
&(/*(1(35235,(7$5<,1)250$7,21
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above
atatioion and d
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or app
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Day
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!
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at the initiation date of the subsequent chemotherapy; a method similar to the primary analysis 
will be applied to estimate the medians of OS and compare the survival distributions between 
two treatment arms. 
7.3.11.3.2. Tumor Response and Overall Response Rate
Overall response over the entire study is defined as a complete or partial response (CR/PR) to 
BSC or nab-paclitaxel+BSC based on the baseline established within 28 days on or before the 
start of Induction therapy according to RECIST 1.1 criteria and confirmed in no less than 28 
days. Thus, a subject will be considered to have an overall response if there is any tumor 
assessment where the confirmed overall tumor response is “Complete Response” or “Partial 
Response.” The best response among any tumor assessments after Day 1 of treatment for the 
Induction treatment up until the subject receives a subsequent anti-cancer therapy will be used 
for this analysis. This will be calculated for randomized subjects only.
The ORR will be summarized by number and percent of randomized subjects with CR/PR and 
presented with 95% confidence intervals for the percent. The treatment effect size will be 
estimated by the response rate ratio (Pnab-P+BSC/P BSC). The ORR will be analyzed using the 
Cochran-Mantel-Haenszel (CMH) test with stratification factors:
!
Disease stage at diagnosis (IIIB vs. IV); 
!
Response in Induction (CR/PR vs. SD); 
!
ECOG performance status at end of Induction (0 vs. 1). 
If strata cell sizes are too small based on Mantel-Fleiss criterion, Pearson chi-square test will be 
used instead. This analysis based on the ITT population will be used as the main analysis of 
ORR.
As sensitivity analyses, a CMH (or Pearson chi-square) test with the above strata will be 
performed on the PP and response evaluable populations.
An additional analysis will be performed on the ITT population of ORR in which subjects with a 
best overall response of CR or PR with or without confirmation of response are considered 
responders.
The number and percentage of those with a best overall tumor response over the entire study of 
PD, SD, PR, CR, and unevaluable (UE) will be presented. The denominator for the percentage 
will include all ITT subjects (subjects who were randomized in the Maintenance Part), regardless 
of whether they had a tumor assessment. Subjects with no tumor assessments will be considered 
UE. This analysis will be presented for each protocol-specified CT scan. If there is more than 
one CT scan within a relative day range, the best response will be counted. Relative study day 
windows are presented in Section 11.4.
The best (i.e., smallest) percent change from baseline will be calculated for all subjects and will 
be presented by treatment arm in a waterfall plot.
ialal
or the
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be presen


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7.3.11.4.
Analyses of Other Secondary Endpoints
7.3.11.4.1. Disease Control Rate
Disease Control rate is defined as the percent of subjects who have a radiologic complete 
response, partial response, or stable disease according to RECIST 1.1 guidelines, as determined 
by the investigator. Disease Control rate over the entire study along with associated Clopper-
Pearson 95% CI will be presented for the Maintenance ITT population. The relative treatment 
effect will be summarized by the ratio of the disease control rate and the associated two-sided 
95% CI.
7.3.11.4.2. Time to Response
Time to confirmed response is defined as the time from the first day of Induction study drug to 
the first occurrence of confirmed response (CR or PR) over the entire study. The time to 
confirmed response will be presented by treatment arm using the summary statistics. Only 
subjects with a confirmed CR or PR as a best overall response will be included in this analysis.
The same analysis will be performed for time to response with or without confirmation of 
response.
7.3.11.4.3. Duration of Response
For subjects who had a confirmed CR or PR, the duration of overall response is measured from 
the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first 
date that recurrent or progressive disease is radiologically documented (taking as reference for 
progressive disease the smallest measurements recorded on study). 
Subjects who are non-responders (i.e., do not achieve at least a PR) will be excluded from this 
analysis. Subjects who do not have PD after the response will be censored on the date of last 
tumor assessment. If a subject died before PD, then the subject will be censored on the date of 
death. 
The duration of response 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 stratified Cox 
proportional hazard model (Cox, 1972). For this analysis, the stratification factors will be the 
same as those used in the primary efficacy analysis, if stratum sizes are sufficient. 
The same analysis will be performed for duration of response with or without confirmation of 
response.
7.3.12.
Subgroup Analyses
PFS, OS, and ORR will all be analyzed within the following subgroups (with subgroup data 
based on the clinical database rather than IVRS). Subgroup factors will not be used as regression 
adjustment covariates for relevant analyses, but otherwise these analyses will parallel the 
analyses for the endpoint performed on the whole population:
1. Age (< 65 years and ≥ 65 years, < 70 years and ≥ 70 years, < 75 years and ≥ 75 years); 
2. Race (white versus non-white)
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3. ECOG status (0 versus 1) at end of Induction;
4. Sex (male versus female); 
5. Region (North America versus Rest of the World)
6. Stage at diagnosis (IIIB versus IV); 
7. Response at the end of Induction (PR/CR versus SD);
8. Subjects with medical history that includes diabetes
If there are less than 5 PFS events per treatment per subgroup for the smaller treatment subgroup, 
we will drop the subgroup analysis for PFS, OS and ORR.
Forest plots will be provided displaying the HRs and corresponding 95% CIs for each subgroup
for PFS and OS. The overall HRs with 95% CIs will also be provided in forest plots.
7.3.13.
Analyses of Exploratory Efficacy Endpoints
7.3.13.1.
Overall Response Rate in Maintenance Part beyond Response in Induction
Overall response during the Maintenance Part beyond the response to Induction therapy is 
defined as a complete or partial response (CR/PR) based on RECIST 1.1, taking as reference the 
sum of the longest diameters of the target lesions measured at the last tumor assessment before 
randomization.  For example, if the sum of the longest diameters of the target lesions at the last 
CT-scan prior to randomization is 10 mm, then the subject will have to have a ≥3 mm reduction 
from the 10 mm during the Maintenance Part in order for the subject to be deemed having partial 
response, assuming the criteria for the non-target lesions and new lesions are satisfied also. 
Naturally, only subjects who have partial response or stable disease at the end of the Induction 
Part will be able to have further improvement during the Maintenance Part according to this 
definition.  
The target lesions identified prior to the start of Induction therapy will be retained as the target 
lesions for this exploratory analysis.  All subjects who enter the Maintenance Part in each 
treatment arm will be counted in the denominator of this analysis.    
The percentage of subjects achieving partial response, complete response, and either partial or 
complete response (ORR) as defined above will each be presented with the associated 95% 
confidence interval.
7.3.13.2.
Tumor Characteristics
The following analyses will be covered under a separate SAP:
!
The correlation between pretreatment tumor characteristics and response and 
resistance to the study treatment determined using next-generation sequencing 
methods, immunohistochemistry, or other analysis methods.
!
The association between the changes in tumor characteristics and the acquisition of 
resistance to therapy from plasma samples taken at treatment failure during 
Maintenance.
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CIST 1.1, t
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!
The relationships between variants in subject pharmacogenomics, such as 
polymorphisms in enzymes involved in drug metabolism, and treatment efficacy and 
toxicity.
7.3.13.3.
Healthcare Resource Utilization
Summary statistics 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 at each time 
point the utilization questionnaire is given (i.e. Day 1 of every cycle and Early Treatment 
Discontinuation/End of Cycle 4 during Induction, Day 1 of every cycle and disease progression 
during Maintenance Part of study).
7.3.14.
Safety Analysis
The purpose of this section is to define the safety parameters for the Maintenance Part. All 
summaries of safety data will be conducted using the safety population. 
7.3.14.1.
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 after the randomization date and through 28 days 
after the treatment discontinuation date. In addition, any SAE with an onset date more than 28 
days after treatment discontinuation date 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 17.0 or higher. The severity will be graded 
based on NCI CTCAE Version 4.0.
The following rules will be implemented for cycle calculations:
!
TEAEs which start after randomization date and on or before Cycle 6 Day 1 belong to 
only Cycle 5.
!
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 the 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 nab-paclitaxel. 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. AEs with a missing relationship will be presented in the summary table as a relationship 
category of “treatment-related”.
The summaries below will be presented for the Maintenance Part of the study and based on the 
safety population.
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 
time
tim
ogression 
gression 
enance Par
enance Par
ent adverse
ent advers
omization
mization d
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AE with
ti
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he s


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AEs under the same preferred term (system organ class), then the subject will be counted only 
once for that preferred term (system organ class). In addition, AEs with a missing intensity will 
be presented in the summary table as an intensity category of “Missing.” 
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 will be generated for each of the 
following:
!
Overall summary of TEAEs;
!
TEAEs presented by MedDRA system organ class, preferred term and worst CTCAE 
grade;
!
Treatment-related TEAEs by grade category (grade 1-2 vs. grade 3-4 vs. grade 5; 
overall and by cycle);
!
Serious TEAE by worst CTCAE grade;
!
Treatment-related serious TEAE by worst CTCAE grade;
!
TEAEs with action of study drug withdrawn;
!
Treatment-related TEAEs with action of study drug withdrawn;
!
TEAEs with action of study drug dose reduced or interrupted;
!
Treatment-related TEAEs with action of study drug dose reduced or interrupted;
!
TEAEs that lead to death;
!
Treatment-related TEAEs with fatal outcome;
!
All death within 28 days of treatment discontinuation date 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 (<65 versus 65 to ≤74 years versus ≥ 75 years)
#
Sex (Male versus Female)
All TEAEs will be listed. A listing for non-treatment-emergent AEs will also be provided. 
7.3.14.2.
Peripheral Neuropathy
Peripheral neuropathy events will be collected in the Physician Assessment of Peripheral 
Neuropathy eCRF and reported as AEs. PN AEs will be included in analyses described in 
Section 7.3.14.1. A summary of PN grade by treatment arm and cycle will be provided based on 
the eCRF data. In addition, time from first dose in Induction to the first occurrence or worsening 
5).
5).
f the
the
d worst CT
d worst CT
ade 3
de 3-4 vs. 
4
E grade;
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study
tudy d
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e reduced o
reduced o
tioion of stu
n of stu
s with 
with fat
fata
days o
days of f tre
tre
TEAEs (
EAEs ( ≥ 5
≥
he fo
he followi
w
t):
Age
Age (<65 v
(<65 v
Sex (
Sex (M
AEs will be
Es will b
3.14.2.
3.14.2.
P
Peri
Per pher
phe
i


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of peripheral neuropathy and time from occurrence or worsening to improvement in peripheral 
neuropathy will be presented by treatment arm using both the AE data and the PN eCRF data 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; 
and
!
Time to improvement of grade 3 or higher peripheral neuropathy to grade 0 or grade 
1. 
Due to the small number of events expected, time to first onset will be summarized with
descriptive statistics for only those subjects who experienced peripheral neuropathy of the 
relevant grade. There will be no censoring. 
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.
7.3.14.3.
Adverse Events of Special Interest
The following summaries will be provided for TEAEs included in the above-mentioned AEs of 
interest: 
1. TEAEs by maximum CTCAE grade; 
2. Serious TEAEs; 
3. TEAEs with action of treatment discontinuation;
4. TEAEs with action of dose reduction or interruption;  
5. TEAEs with fatal outcome;
In addition, time from first dose in Induction to the first occurrence or worsening of 
Myelosuppression and Peripheral Neuropathy and time from occurrence or worsening to 
improvement in Myelosuppression and Peripheral Neuropathy will be presented by treatment 
arm as follows:
!
Time to first onset of grade 3 or AESI;
!
Time to improvement of grade 3 or AESI by at least 1 grade; and
!
Time to improvement of grade 3 or higher AESI to grade 0 or grade 1. 
Due to the small number of events expected, time to first onset will be summarized with 
descriptive statistics for only those subjects who experienced an AESI of the relevant grade. 
There will be no censoring. 
Time to improvement will include only subjects who experienced an AESI of the relevant 
grades. Subjects who do not experience improvement will be censored at the last time the subject 
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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is evaluated for adverse events. Kaplan Meier methods will be used to attain the median and 95% 
confidence interval.
AESIs will be listed.
7.3.14.4.
Clinical Laboratory Evaluations
7.3.14.4.1. Hematology
All hematology data will be listed.
7.3.14.4.2. Clinical Chemistry
All clinical chemistry data will be listed.
7.3.15.
Quality of Life Analysis
The LCSS and EQ-5D-5L, as described in Section 7.2.12 , will be administered in the 
Maintenance Part of the study as well. Baseline scores are defined as scores captured on Day 1 of 
Induction.
7.3.15.1.
LCSS
LCSS scores (overall constitutional score, symptom burden index, respiratory symptom scale, 3-
item scale) will be calculated in the same way as described in Section 7.2.12.1.
Summary statistics of the individual LCSS items and summary scale scores, the change from 
baseline, and percent change from baseline for these scores will be summarized by treatment arm 
for the ITT population at every Maintenance Part time point at which the instrument is given, i.e. 
Day 1 of every cycle. In addition, the change from baseline to the LCSS score during the 
Maintenance Part, defined as the difference between the last reported LCSS score during the 
Maintenance Part, last visit or early discontinuation visit or the last reported LCSS score before 
clinical cutoff for subjects who have not reached that point at an interim analysis, will be 
presented. 
Statistical comparisons will be made between the BSC and nab-paclitaxel+BSC groups in the 
Maintenance Part for change from baseline to last administration in Maintenance using analysis 
of covariance. Disease stage, ECOG status, and response during Induction will be the covariates.
7.3.15.2.
EQ-5D-5L
EQ-5D scores will be calculated in the same way as described for Baseline scores and are 
defined as the score captured on Day 1 of Induction, and missing baseline scores will not be 
imputed.
The utility score as well as the change from baseline and percent change from baseline in the 
utility score will be summarized for every time point at which the instrument is given for the ITT 
population. In addition, the change from baseline to the utility score during the Induction Part, 
defined as the difference between the last reported overall score during the Induction Part, early 
discontinuation or disease progression visit or the last reported overall score before clinical 
cutoff for subjects who have not reached that point at an interim analysis will be presented.
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nab-Paclitaxel (Abraxane®)
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Summaries of the VAS (with the exception of the missing values) results, the change from 
baseline, and percent change from baseline will be presented for every time point at which the 
instrument is given. In addition, the change from baseline to the last reported overall score 
during the Maintenance Part, either the disease progression or early discontinuation visit or the 
last reported overall score before clinical cutoff for subjects who have not reached that point at 
an interim analysis will be presented.
Shifts from baseline to each time point at which the instrument is given will be presented for 
each dimension of the EQ-5D-5L for the ITT population. 
For the utility score and the VAS, statistical comparisons will be made between the BSC and 
nab-paclitaxel+BSC groups in the Maintenance Part for change from baseline to last 
administration in Maintenance using analysis of covariance. Disease stage, ECOG status, and 
response during Induction will be the covariates. 
7.4.
Follow-up
First subsequent systemic anti-cancer regimens will be summarized by treatment arm. 
To assess how quickly the second line therapy will be initiated for the subjects who discontinued 
the study treatment, the time to first subsequent therapy, defined as the time interval from the 
date of treatment discontinuation to the start date of the first subsequent anti-cancer regimen. The 
start date of the first subsequent anti-cancer regimen is the earliest start date of any anti-cancer 
therapy taken in the follow-up/survival period. Subjects who don’t have a subsequent therapy 
and have not died as of the cutoff date for the statistical analysis will be censored at the last 
follow up date. Subjects who die before initiating a subsequent therapy will be censored at the 
date of death.
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 the Cox 
proportional hazard model (Cox, 1972).
In addition, first subsequent anti-cancer treatment regimens will be summarized by the number 
and percentage of subjects receiving each regimen category and regimen; the number of cycles
overall, and the number of cycles for each regimen category and regimen administered. The best 
response overall and for each regimen category and regimen administered will be summarized. 
Treatment duration, defined as (date of last dose of any treatment in a regimen - date of first dose 
of any treatment in the same regimen) + 1 will be summarized as well. Additional subsequent 
anti-cancer treatment regimens will be listed.
Anti-cancer surgeries during follow-up will be summarized by treatment group and by system 
organ class and preferred term Follow-up surgeries will be listed.
Radiation therapy during follow-up will be summarized by treatment arm and by category (prior, 
concomitant, follow up); type (External beam, radio-immuno therapy, brachytherapy, other);
location (if external beam); dose; fraction; intent (adjuvant, curative, palliative, unknown); and 
setting (stand alone radiation therapy, concurrent with other anti-cancer therapy, sequential to 
other anti-cancer therapy). Follow-up radiation therapy will be listed.
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nab-Paclitaxel (Abraxane®)
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8.
INTERIM ANALYSIS
8.1.
General Information
An independent DMC will be convened with experts not otherwise involved in the study as 
investigators. During the course of the study, the DMC will review the progression-free survival 
efficacy data once and overall survival data separately in accordance with the guidelines for the 
pre-planned interim analysis. The committee will also review safety data periodically. 
Operational details for the DMC and the algorithm and its validation by an expert panel will be 
detailed in the DMC charter.
The DMC is advisory in nature, and the decision to implement DMC recommendations will be 
made by the sponsor. Specifically, the futility analyses for PFS and OS are nonbinding.
For data cleaning purposes, a cut-off date of December 12, 2016 in conjunction with the cut-off 
date algorithm will be used to create the necessary analysis populations for the interim analysis.
The details of data cut-off algorithm for the interim analysis will be provided in a separate file. In 
order to effectively deal with a substantial number of over-runs expected to occur after this 
December 12th cut-off date, the most current PFS data will be analyzed again using the Cox 
regression model and a plot of Kaplan-Meier product limit estimates. All data for patients not 
experiencing a PFS event may not be totally clean as of the December 12th cut-off date.     
8.2.
Statistical Approaches for Control of Alpha
There will be one non-binding interim analysis for futility for the primary endpoint, PFS, when 
approximately 91 events (67% information) have been observed. Futility may be declared and 
the study discontinued if the conditional power at the interim analysis is < 10%. The final 
analysis of PFS will be performed when approximately 136 PFS events have been observed.
A Step-down procedure from PFS to OS will be used to control the family-wise two-sided Type-
I error rate to 5%. That is, OS will be tested only if the nab-paclitaxel plus BSC regimen 
demonstrates superiority over the BSC alone with PFS.
The marginal significance level for OS will be adjusted according to O'Brien-Fleming type of 
boundary. The nominal two-sided p-values for declaring superiority will be calculated using the 
statistical software 
 The analysis and boundaries will be adjusted 
based on the actual number of deaths observed. 
There will be two analyses for the secondary OS endpoint. The interim analysis of OS will be 
conducted based on the number of deaths observed up to the clinical cutoff date. Futility may be 
declared and the study discontinued if the conditional power at the interim analysis for OS is < 
10% or the nab-paclitaxel plus BSC regimen does not demonstrate superiority over the BSC 
alone with PFS. For efficacy, the two-sided nominal value p-value stopping boundary for OS 
interim analysis is 0.009. Efficacy will be declared and study discontinued if p-value crosses 
stopping boundary and the nab-paclitaxel plus BSC regimen demonstrates superiority over the 
BSC alone with PFS. If neither futility nor efficacy is declared at the interim analysis of OS, the 
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nab-Paclitaxel (Abraxane®)
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final OS analysis will be performed after approximately 147 deaths have been observed, if 
applicable. The final two-sided nominal p-value efficacy stopping boundary is 0.047.
8.3.
Probability of Clinically Meaningful PFS Effects Given the Interim 
Data
At the interim analysis, the probability of clinically meaning PFS effects given the interim data 
will be provided. Clinically meaningful PFS effects is defined as Hazard Ratio (HR) <0.85. 
In the stratified Cox proportional hazard model, denote the Log(Hazard Ratio) parameter as .
The estimated Log(HR) at the interim analysis approximately has a normal distribution
, where 
is the estimator for the hazard ratio (HR) on the natural log scale with mean 
and variance
. So the probability of clinically meaningful PFS effects is
,
where 
and is the estimated hazard ratio on the natural log scale 
with standard error 
. and 
are readily available on SAS Proc PHREG output. The 
hazard ratio of 0.85 is deemed to be the minimal clinically significant effect. Other probabilities 
of meaningful HRs that may represent stronger PFS effects will also be provided (e.g.,
))
60
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log(
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8.4.
Conditional Power at the Interim Analysis for PFS
The two-sided conditional power for PFS at the interim analysis is computed as 
(Jennison and Turnbull (2000) Page 205-208)
where
(the log hazard ratio under the alternative 
hypothesis);
: the unstratified log-rank test statistic computed from the observed data at the interim;
: the information level at the interim stage, 
;
: the number of PFS events at the interim stage;
: the proportion of the subjects randomized to nab+BSC arm;
: the information level at the end of the study, 
;
: the total number of events at the end of study (136);
: 1.96.
More details about sequential trial design can be found in Lan and DeMets 1983; Lan and Zucker 
1993; Jennison and Turnbull 2000.
Conditional Power depends on the observed test statistic
and the alternative hypothesis . The 
following graph shows the relationship between the observed hazard ratio and the conditional 
power at the interim analysis under different assumptions of alternative hypothesis.
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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58
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The plot above shows the relationship of the conditional power and the observed hazard ratio at 
the interim based upon the assumed unkown true hazard ratio. The light green hashed line is the 
assumed true hazard ratio of 0.60 which was used in determining the 136 PFS events required to 
provide 80% power under a two sided test at the nominal 5% level of significance). 
Operating charatceristics for stopping the study at the interim for futility under some various 
conditional power/ observed hazard ratios based upon 5,000 simulated trials under the protocol 
assumption of a true hazard ratio of 0.60 are provided in the tables below.
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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59
8.5.
Conditional Power at the Interim Analysis for OS
Interim Analysis for OS will be conducted when 136 PFS events are achieved and the 
nab-paclitaxel plus BSC regimen demonstrates superiority over the BSC alone with PFS.
Otherwise, OS will not be tested and therefore there will not be an interim analysis for OS.
The two-sided conditional power for OS at the interim analysis is computed as
(Jennison and Turnbull (2000) Page 205-208)
where
(the log hazard ratio under the alternative hypothesis
for OS);
: the unstratified log-rank test statistic of OS computed from the observed data at the interim;
: the information level at the interim stage, 
;
: the number of OS events at the interim stage;
: the proportion of the subjects randomized to nab+BSC arm;
: the information level at the end of the study, 
;
: the total number of OS events 1.5 years after final analysis of PFS (147);
: 1.96.
Conditional Power depends on the observed test statistic 
and the alternative hypothesis . The 
following graph shows the relationship between the observed hazard ratio and the conditional 
power at the interim analysis of OS under different assumptions of alternative hypothesis, in 
which the assumption is that the number of OS events in the interim analysis is 92.
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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60
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The plot above shows the relationship of the conditional power and the observed hazard ratio at 
the interim based upon the assumed unkown true hazard ratio. The purple hashed line is the 
assumed true hazard ratio of 0.70 which was used in determining the 147 OS events required to 
provide 53% power under a two sided test at the nominal 5% level of significance). 
Operating charatceristics for stopping the study at the interim for futility under some various 
conditional power/ observed hazard ratios based upon 5,000 simulated trials under the protocol 
assumption of a true hazard ratio of 0.70 are provided in the tables below.
Observed HR at Interim
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and the assumption that the true HR=0.7
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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61
9.
CHANGES TO THE STATISTICAL ANALYSES SECTION OF 
THE PROTOCOL
For the Induction Part, the following changes were made to the secondary efficacy endpoints:
!
Disease control rate: protocol originally stated DCR over the entire study, statistical 
analysis plan is adding text to clarify DCR will also be analyzed separately during 
Induction Part
For the Maintenance Part, the following changes were made to the secondary efficacy endpoints:
!
PFS from Day 1 Cycle 1, protocol originally stated PFS from randomization into the 
Maintenance Part of the study, statistical analysis plan is adding additional analyses to 
further characterize the PFS endpoint;
!
OS from Day 1 Cycle 1, protocol originally stated OS from randomization into the 
Maintenance Part of the study, statistical analysis plan is adding additional analyses to 
further characterize the PFS endpoint;
!
ORR without confirmation required for PR or CR: protocol originally stated ORR during 
Induction and Maintenance Parts, statistical analysis plan is adding additional analyses to 
further characterize the ORR endpoint.
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nab-Paclitaxel (Abraxane®)
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62
10.
REFERENCES
Cox, DR. Regression Models and Life-Tables. Journal of the Royal Statistical Society. Series B
(Methodological). 1972, 34 (2): 187–220.
Klein JP and Moeschberger ML. Survival Analysis: Techniques for Censored and Truncated
Data, 2nd ed. Springer, 2003.
Mantel N and Fleiss JL (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, 112: 129-134.
Lan and DeMets (1983). Discrete Sequential Boundaries for Clinical Trials. 
Biometrika (1983) 70 (3): 659-663.
Lan and Zucker (1993). Sequential Monitoring of Clinical Trials: The Role of Information and 
Brownian Motion. Statistics in Medicine 12(8):753 - 765
Jennison and Turnbull (2000). Group Sequential Methods with Applications to Clinical Trials. 
CRC/Chapman & Hall, U.K., 2000.
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11.
APPENDICES
11.1.
Study schematic
11.2.
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.  
f Dates
f Date
as numeric
s numeri
form
format (
at (i
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Otherwise, incomplete log dates will be imputed according to the rules in Appendix 
16.2 (eg, for duration or cycle assignment, etc). However, in listings, log dates will be 
shown as recorded without imputation.
!
Milestone Dates are dates of protocol milestones such as randomization, study drug 
start date, study drug termination date, study closure date, etc.  They should not be 
missing if the milestone occurs for a subject. They will not be imputed.
!
Outcome Dates are dates corresponding to study endpoints such as survival, 
progression, etc. In most cases they are derived either from a milestone (eg, the 
survival date is derived from the death date), or a procedure date (eg, the progression 
date is derived from the date of the tumor scan that was used to determine 
progression). They may be subject to endpoint-specific censoring rules if the outcome 
did not occur, but are not otherwise subject to imputation.
!
Special Dates cannot be classified in any of the above categories and they include the 
date of birth. They may be subject to variable-specific censoring and imputation rules. 
!
Last Contact Dates for the survival analysis are the maximum date collected in the 
database, if the imputed date used for response date or AE date, the last contact dates 
should be the latest date of those imputed date and maximum date in the database.
Dates recorded in comment fields will not be imputed or reported in any specific format. 
11.2.1.
Calculation Using Dates
Calculations using dates (e.g., subject’s age or relative day after the first dose of study drug) will 
adhere to the following conventions: 
!
Study days after the start day of study drug will be calculated as the difference 
between the date of interest and the first date of dosing of study drug plus 1 day. The 
generalized calculation algorithm for relative day is the following: 
#
If TARGET DATE >= DSTART then STUDY DAY = (TARGET DATE –
DSTART) + 1; 
#
Else use STUDY DAY = TARGET DATE – DSTART.
Note that Study Day 1 is the first day of treatment of study drug. Negative study days 
are reflective of observations obtained during the baseline/screening period. Note: 
Partial dates for the first study drug are not imputed in general. All effort should be 
made to avoid incomplete study drug start dates. 
!
Age (expressed in days) is calculated: AGE = CONSENT DATE – DATE of BIRTH 
+ 1.  In practice, age will be transformed to years by dividing the difference by 
365.25 days, then truncating.
#
Preference is for using calculated age from clinical database. When not available, 
calculated age from CRF or IVRS may be used
#
Partial birth date: impute missing day as 15th of the month; impute missing month 
as July; set missing age for missing year
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y n
g and impu
g and impu
mum date c
mum date c
AE date, the
AE date, t
aximum da
aximum da
ported in an
orted in an
ative day a
ative day 
study
study
f
drug
dru
y
and the fi
nd the firs
gorithm for
gorithm 
TE >= DST
TE >= DST
;
TUDY DA
TUDY 
Study
Study Day
Da
y
ect
ective of o
ive of o
ialal date
date
l
s fo
made
made to avo
to avo
Age (ex
Age (e
+ 1. 
+ 1
36
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nab-Paclitaxel (Abraxane®)
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Celgene Corporation
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65
!
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
11.3.
Date Imputation Guideline
11.3.1.
Impute Missing Dates for Adverse Events/ Prior or Concomitant Medications
Incomplete Start Date
!
If the stop date is not missing, and the imputed start date is after the stop date, the 
start date will be imputed by the stop date.
Missing day and month
!
If the year is the same as the year of the first dosing date, then the day and month of 
the first dosing date will be assigned to the missing fields.
!
If the year is prior to the year of first dosing date, then December 31 will be assigned 
to the missing fields.
!
If the year is after the year of first dosing, then January 1 will be assigned to the 
missing fields.
Missing day only 
!
If the month and year are the same as the year and month of first dosing date, then the 
first 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 
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.
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cations
cations
he stop date
he stop date
ate, then the
, then th
fields.
ields.
ate, then De
, then D
g, then Jan
, then Ja
same
same as t
as
signed to th
signed to
he parti
he partialal d
l
l date and t
l date and t
he mo
montn h
the missing
he missin
r the y
the year o
ear o
s o of th
the part
e par
te is 
is after
after
assigned t
assigned t
issing day, 
issing day, 
!
N
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-003
Celgene Corporation
Confidential and Proprietary
66
Missing day only 
!
The last day of the month will be assigned to the missing day. 
11.3.2.
Impute Missing Dates for Medical History
Partially missing medical history start dates will be imputed in the derived dataset for medical 
history. The 16th of the month will be used to impute a partially missing start date that has only 
the day missing, and July 1st will be used to impute a partially missing start date that has both the 
month and day missing.
11.4.
Tumor Response Windows
Relative Day Ranges for the CT-Scans
Study 
Week
Study Part
Relative Weeks 
in 
Study Part
Relative Days in 
Study Part
6
Induction
6
2 - 63
12
12
≥64 and before 
randomization
18
Maintenance
6
2 - 63
24
12
64 - 105
30
18
106 - 147
36
24
148 - 189
42
30
190 - 231
48
36
232 - 273
54
42
274 - 315
60
48
316 - 357
66
54
358 - 399
72
60
400 - 441
78
66
442 - 483
84
72
484 - 525
90
78
526 - 567
96
84
568 - 609
102
90
610 - 651
108
96
652 - 693
114
102
694 - 735
120
108
736 - 777
126
114
778 - 819
132
120
820 - 861
138
126
862 - 903
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he
he
e Days in
e Days in
udy Part
udy Part
25
2 - 6
2 - 6
1
≥64
≥64 an
an
ran
,1
5<
5<
5<
5<
6
$5
12
1
7$
18
18
(7$
2
(7
5,(
5
3
78
78
3
84
84
(
90
90
1(
(1
9
(1
(1
(1
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nab-Paclitaxel (Abraxane®)
Statistical Analysis Plan. Protocol ABI-007-NSCL-003
Celgene Corporation
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67
11.5.
MedDRA Versions and Dates
For reports dated: 
MedDRA version
05May2014 – 01Nov2014
17.0
02Nov2014 – 03May2015
17.1
04May2015 – 01Nov2015
18.0
02Nov2015 – present
18.1
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