Clinical trial NCT02301143
Conditions: Pancreatic Neoplasms
Keywords: Pancreatic Neoplasms Pancreatic Cancer Locally advanced pacriatic cancer nab-Paclitaxel Abraxane Gemcitabine ABI-007
Sponsor: Celgene
Start date: 2015-04-21; Completion date: 2018-04-26
Enrollment: 107 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This clinical study is in subjects who are 18 years old or older with locally advanced pancreatic cancer who have not received prior treatment for their pancreatic cancer. The study treats all subjects with nab-Paclitaxel plus gemcitabine for approximately 6 months of treatment. Subjects who complete the treatment will choose, with their treating physicians, what additional treatment should be given: more nab-Paclitaxel plus gemcitabine, Chemoradiation therapy, or surgery to treat the locally advanced pancreatic cancer.

Detailed description:
This is an international, non-randomized, open-label, multi-center, Phase 2 study in subjects who are 18 years old or older with locally advanced pancreatic cancer who have not received prior treatment for their pancreatic cancer. All subjects will be treated with nab-paclitaxel plus gemcitabine for 6 cycles followed by an Investigator's Choice of continuation of treatment with nab-paclitaxel plus gemcitabine, chemoradiation therapy, or surgery.

Safety assessments by laboratory testing and physical exams will be conducted through-out the study.

Efficacy assessments by physical exam will be preformed through-out the study and tumor imaging will be conducted approximately every 2 months.

Subjects will be considered active study participants from enrollment up to, but not including, survival follow-up period.

Arms: arm 1: nab-Paclitaxel 125 mg/m2 intravenous (IV) infusion over approximately 30 to 45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m2 IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle Subjects who complete 6 cycles of nab-paclitaxel and gemcitabine without disease progression or unacceptable toxicities, the Investigator will then determine the best option for the subject.

* Continuation of nab-paclitaxel and gemcitabine therapy to disease progression or unacceptable toxicity OR
* Chemoradiation therapy consisting of the concurrent use of capecitabine or gemcitabine with radiation according to institutional practice OR
* Surgical intervention
Interventions: intervention 1: nab-Paclitaxel intervention 2: Gemcitabine intervention 3: Chemoradiation intervention 4: Capecitabine intervention 5: Surgery
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: Surgical intervention

Protocol documents:
Prot_001.pdf: 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
1
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
TITLE PAGE
NAB-PACLITAXEL (ABRAXANE®) PLUS 
GEMCITABINE IN SUBJECTS WITH LOCALLY 
ADVANCED PANCREATIC CANCER (LAPC): AN 
INTERNATIONAL, OPEN-LABEL, MULTI-CENTER, 
PHASE 2 STUDY (LAPACT)
INVESTIGATIONAL PRODUCT (IP):
nab-Paclitaxel (ABI-007)
PROTOCOL NUMBER:
ABI-007-PANC-007
DATE FINAL:
27 Aug 2014
DATE AMENDMENT 1.0 FINAL
06 Feb 2018
EudraCT NUMBER:
2014-001408-23
IND NUMBER:
115027
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-PANC-007
Celgene Corporation
Confidential and Proprietary
2
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
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-PANC-007
Celgene Corporation
Confidential and Proprietary
3
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
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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-PANC-007
Celgene Corporation
Confidential and Proprietary
4
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
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-PANC-007
Celgene Corporation
Confidential and Proprietary
5
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
PROTOCOL SUMMARY
Study Title
nab®1-paclitaxel (Abraxane®) plus gemcitabine in subjects with locally advanced pancreatic 
cancer (LAPC): An international, open-label, multi-center, Phase 2 study (LAPACT).
Indication
Locally advanced pancreatic cancer.
Objectives
Primary
!
To evaluate the time to treatment failure (TTF) in LAPC subjects treated with 
nab-paclitaxel plus gemcitabine as induction therapy followed by Investigator’s 
Choice of treatment
Secondary 
!
To evaluate the disease control rate (DCR) after the first 6 cycles of nab-paclitaxel 
plus gemcitabine
!
To evaluate the overall response rate (ORR)
!
To evaluate the overall progression-free survival (PFS) and overall survival (OS)
!
To assess the overall safety profile
!
To evaluate the subject’s health-related quality of life (QoL)
 
 
Study Design
This is an international, non-randomized, open-label, multi-center, Phase 2 study in subjects with 
LAPC treated with nab-paclitaxel plus gemcitabine for 6 cycles followed by an Investigator’s 
Choice of continuation of treatment with nab-paclitaxel plus gemcitabine, chemoradiation 
therapy, or surgery.
Approximately 110 subjects with LAPC will be enrolled in the study. Subjects will be followed 
until documented progression of disease, withdrawal of consent, lost to follow-up, or death.
Study Population
Subjects with LAPC with no prior anticancer therapy for pancreatic cancer and ≥ 18 years old 
will be eligible for this study.
                                               
1 nab® is a registered trademark of Celgene Corporation.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
6
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Length of Study
Enrollment in the study is expected to take approximately 24 months. The total length of this 
study with treatment and follow-up for OS is estimated to last approximately 3.5 years or until 
up to 95% of survival data have been collected, whichever comes first.
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 
 analysis, as pre-specified in the protocol and/or the 
Statistical Analysis Plan (SAP), whichever is the later date.
Study Treatments
nab-Paclitaxel plus Gemcitabine for 6 Cycles
Approximately 110 subjects eligible for treatment with nab-paclitaxel plus gemcitabine for 
6 cycles will be enrolled, provided all inclusion/exclusion criteria are met within a 14-day 
screening period prior to Cycle 1 Day 1.
Treatment will commence on Day 1 for each of 6 cycles:
!
nab-Paclitaxel 125 mg/m2 intravenous (IV) infusion over approximately 30 to 45 
minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m2 IV infusion over 
approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle
Up to 2 dose reductions to 100 mg/m2 and 75 mg/m2 for nab-paclitaxel and 800 mg/m2 and 
600 mg/m2 for gemcitabine are allowed (see Section 8.2.1.2).
Once 6 cycles have been completed, subjects without disease progression or unacceptable 
toxicity will continue on to the Investigator’s Choice part of the study (see Investigator’s Choice 
below). 
At any time during the study, subjects with disease progression or unacceptable toxicity will be 
discontinued from the study treatment.
Investigator’s Choice
For subjects who complete 6 cycles of nab-paclitaxel plus gemcitabine without disease 
progression or unacceptable toxicities, the investigator will determine which of the following 
options are best for the subject:
!
Continuation of nab-paclitaxel plus gemcitabine therapy
OR
!
Chemoradiation therapy consisting of the concurrent use of capecitabine or 
gemcitabine with radiation according to institutional practice 
OR
!
Surgical intervention
If the Investigator’s Choice is to continue treatment with nab-paclitaxel plus gemcitabine, 
treatment should continue on schedule as per prior cycles of therapy until disease progression or 
unacceptable toxicity.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
7
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
If the Investigator’s Choice is chemoradiation therapy, a minimum of 3 weeks must have elapsed 
between the last chemotherapy infusion and the initiation of chemoradiotherapy. 
If tumor response allows a surgical intervention, the subject will be eligible for that treatment as 
deemed appropriate by the investigator. Surgical intervention may occur prior to completing the 
planned 6 cycles of nab-paclitaxel plus gemcitabine if subjects demonstrate a major response to 
therapy. In case of surgery, the delay may vary depending upon the surgery planning; however, 
the chemotherapy-induced neutropenia nadir should be avoided.
Statistical Summary
This is an international, non-randomized, open-label, multi-center, Phase 2 study which is 
designed in order to examine and better understand the place for nab-paclitaxel plus gemcitabine 
within the current treatment paradigms in LAPC. The use of data from this Phase 2 study will be 
utilized in planning the study design for the Phase 3 program.
An interim analysis of DCR will be conducted approximately after all subjects have completed 6 
cycles of nab-paclitaxel plus gemcitabine, discontinued therapy due to disease progression, died 
(death by any cause), or started on a new non-protocol-defined anticancer therapy prior to 
completing 6 cycles of therapy.
Statistical analyses for the primary and key secondary endpoints of the study are described 
below. Additional detail on the analyses of these endpoints will be described in the SAP.
The SAP supersedes the analyses described in the protocol should there be differences between 
the two. Further details related to the statistical analyses and sample size determination can be 
found in Section 10 of this protocol. 
Overview of Efficacy Assessments
Time-to-treatment failure is the primary endpoint for this study and is defined as the time after 
the first dose of study therapy to discontinuation of study therapy due to disease progression, 
death (by any cause), or the start of a non-protocol-defined anticancer therapy. If a subject does 
not progress, die, or start a non-protocol-defined anticancer therapy, or if a subject discontinued 
study therapy, then the subject will be censored as of the last tumor assessment date. Although 
the sample size for the study was estimated to detect a 30% increase in the median TTF observed 
in the randomized international Phase 3 study in the metastatic population (MPACT, CA046, 
NCT00394251), no formal statistical testing will be done with this endpoint. The TTF will be 
summarized using standard Kaplan-Meier methods. Median TTF and 2-sided 90% confidence 
interval (CI) will be reported with the accompanying Kaplan-Meier curve. 
The secondary efficacy endpoints are DCR at 6 months, ORR, PFS and OS. Details pertaining to 
the analyses of these endpoints are presented in Section 10.6.2 of this protocol.
Overview of Safety Assessments
All subjects who receive at least 1 dose of nab-paclitaxel plus gemcitabine will be evaluated for 
safety. The number and percent of subjects reporting adverse events (AEs, including treatment-
emergent laboratory abnormalities) will be summarized by system organ class and preferred 
term. All serious adverse events (SAEs) will be tabulated separately as well as included with all 
reported AEs.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
8
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Sample Size
The sample size estimation of 100 subjects provides a sufficient sample in the Intent-to-treat 
(ITT) population having 80% power to detect a 30% increase in the median TTF of 5.1 to 6.6 
months. The null (Ho) and alternative (Ha) hypotheses for this endpoint is as follows, where M is 
the median TTF and 5.1 is the median TTF observed in the CA046 study:
Ho:  M ≤ 5.1
Ha:  M > 5.1
The sample size is calculated assuming a one-sided alpha of 0.05, that subjects will be enrolling 
for 24 months and that each subject will be followed for a minimum of 1 year. One hundred ten 
subjects will be enrolled assuming a 10% drop out rate.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
9
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................5
1.
INTRODUCTION..................................................................................................16
1.1.
Pancreatic Cancer ...................................................................................................16
1.2.
Locally Advanced Pancreatic Cancer......................................................................16
1.3.
nab-Paclitaxel (Abraxane) ......................................................................................17
1.3.1.
Preclinical and Clinical Experience with nab-Paclitaxel Plus Gemcitabine in 
Pancreatic Cancer ...................................................................................................17
1.4.
Study Rationale ......................................................................................................19
2.
STUDY OBJECTIVES...........................................................................................20
2.1.
Primary Objective...................................................................................................20
2.2.
Secondary Objectives .............................................................................................20
3.
STUDY ENDPOINTS............................................................................................21
3.1.
Primary Endpoint....................................................................................................21
3.2.
Secondary Endpoints ..............................................................................................21
3.2.1.
Efficacy Endpoints .................................................................................................21
3.2.2.
Safety Endpoints.....................................................................................................21
4.
OVERALL STUDY DESIGN ................................................................................22
4.1.
Study Design ..........................................................................................................22
4.1.1.
nab-Paclitaxel plus Gemcitabine for 6 Cycles.........................................................22
4.1.2.
Investigator’s Choice..............................................................................................22
4.1.3.
Follow-up Period....................................................................................................23
4.2.
Study Design Rationale ..........................................................................................24
4.3.
Study Duration .......................................................................................................25
4.4.
End of Trial ............................................................................................................25
5.
TABLE OF EVENTS.............................................................................................26
6.
PROCEDURES......................................................................................................32
6.1.
Medical History......................................................................................................32
6.2.
Demographics.........................................................................................................32
6.3.
Physical Examinations............................................................................................32
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
10
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
6.4.
Vital Signs..............................................................................................................32
6.5.
Prior Medications/Procedures of Special Interest ....................................................32
6.6.
Pregnancy Testing ..................................................................................................33
6.7.
Computed Tomography or Magnetic Resonance Imaging Scan...............................33
6.8.
Weight and Height..................................................................................................33
6.9.
Eastern Cooperative Oncology Group (ECOG) Performance Score ........................33
6.10.
Concomitant Medications/Procedures of Special Interest........................................34
6.11.
Peripheral Neuropathy Assessment.........................................................................34
6.12.
Adverse Event Reporting........................................................................................34
6.13.
Quality of Life Questionnaires................................................................................34
6.14.
Laboratory Assessments .........................................................................................34
 
6.16.
Survival..................................................................................................................36
7.
STUDY POPULATION.........................................................................................37
7.1.
Number of Subjects and Sites .................................................................................37
7.2.
Inclusion Criteria....................................................................................................37
7.3.
Exclusion Criteria...................................................................................................38
8.
DESCRIPTION OF STUDY TREATMENTS........................................................40
8.1.
Description of Investigational Products...................................................................40
8.1.1.
Abraxane (nab-Paclitaxel) ......................................................................................40
8.1.2.
Gemcitabine ...........................................................................................................40
8.2.
Treatment Administration and Schedule .................................................................40
8.2.1.
Dose Modifications.................................................................................................41
8.2.1.1.
Rules for Dose Omissions and Modified Schedules ................................................41
8.2.1.2.
Dose Modification Tables.......................................................................................42
8.2.1.3.
Administration of Investigational Product to Subjects with Abnormal 
Hepatic Function ....................................................................................................44
8.2.1.4.
Pulmonary Embolism and Deep Vein Thrombosis..................................................44
8.2.1.5.
Interstitial Pneumonitis...........................................................................................44
8.2.1.6.
Prophylaxis Against Sepsis.....................................................................................45
8.2.1.7.
Hypersensitivity Reactions .....................................................................................45
8.2.2.
Overdose ................................................................................................................45
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8.3.
Method of Treatment Assignment...........................................................................46
8.4.
Packaging and Labeling..........................................................................................46
8.5.
Investigational Product Accountability and Disposal ..............................................46
8.6.
Investigational Product Compliance........................................................................47
9.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................48
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.
Overview................................................................................................................49
10.2.
Study Population Definitions ..................................................................................49
10.3.
Sample Size and Power Considerations...................................................................50
10.4.
Background and Demographic Characteristics........................................................50
10.5.
Subject Disposition.................................................................................................51
10.6.
Efficacy Analysis....................................................................................................51
10.6.1.
Primary Efficacy Analysis ......................................................................................51
10.6.2.
Secondary Efficacy Analyses..................................................................................51
10.6.2.1.
Disease Control Rate at 6 Months...........................................................................51
10.6.2.2.
Overall Response Rate............................................................................................52
10.6.2.3.
Progression-free Survival........................................................................................52
10.6.2.4.
Evaluation of Overall Survival................................................................................52
10.6.2.5.
Evaluation of Health-related Quality of Life ...........................................................52
10.7.
Safety Analysis.......................................................................................................52
10.8.
Interim Analysis .....................................................................................................53
10.9.
Other Topics...........................................................................................................53
11.
ADVERSE EVENTS..............................................................................................54
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................54
11.2.
Evaluation of Adverse Events.................................................................................55
11.2.1.
Seriousness.............................................................................................................55
11.2.2.
Severity / Intensity..................................................................................................56
11.2.3.
Causality ................................................................................................................57
11.2.4.
Duration .................................................................................................................57
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( 35


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11.2.5.
Action Taken..........................................................................................................57
11.2.6.
Outcome.................................................................................................................57
11.3.
Abnormal Laboratory Values..................................................................................57
11.4.
Pregnancy...............................................................................................................58
11.4.1.
Females of Childbearing Potential: .........................................................................58
11.4.2.
Male Subjects.........................................................................................................58
11.5.
Reporting of Serious Adverse Events......................................................................58
11.5.1.
Safety Queries ........................................................................................................59
11.6.
Expedited Reporting of Adverse Events..................................................................59
12.
DISCONTINUATIONS .........................................................................................61
12.1.
Study Treatment Discontinuation............................................................................61
12.2.
Study Discontinuation ............................................................................................61
12.3.
Subject Replacement ..............................................................................................62
13.
EMERGENCY PROCEDURES.............................................................................63
13.1.
Emergency Contact.................................................................................................63
13.2.
Emergency Identification of Investigational Products .............................................63
14.
REGULATORY CONSIDERATIONS...................................................................64
14.1.
Good Clinical Practice............................................................................................64
14.2.
Investigator Responsibilities ...................................................................................64
14.3.
Subject Information and Informed Consent.............................................................64
14.4.
Confidentiality........................................................................................................65
14.5.
Protocol Amendments.............................................................................................65
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................65
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................66
14.8.
Closure of the Study ...............................................................................................66
15.
DATA HANDLING AND RECORDKEEPING.....................................................67
15.1.
Data/Documents.....................................................................................................67
15.2.
Data Management...................................................................................................67
15.3.
Record Retention....................................................................................................67
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................69
16.1.
Study Monitoring and Source Data Verification......................................................69
16.2.
Audits and Inspections............................................................................................69
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17.
PUBLICATIONS ...................................................................................................70
18.
REFERENCES.......................................................................................................71
19.
APPENDICES........................................................................................................73
19.1.
ECOG Performance Status Score............................................................................73
19.2.
List of Concomitant Medications or Procedures of Special Interest.........................73
19.3.
List of Laboratory Values of Special Interest ..........................................................73
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ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
LIST OF TABLES
Table 1:
Table of Events – Induction: nab-Paclitaxel Plus Gemcitabine................................26
Table 2:
Table of Events – Investigator’s Choice: Continuing with nab-Paclitaxel 
Plus Gemcitabine....................................................................................................28
Table 3:
Table of Events – Investigator’s Choice: Chemoradiation as per Institutional 
Standard of Care.....................................................................................................30
Table 4:
Table of Events – Investigator’s Choice: Surgery as per Institutional 
Standard of Care.....................................................................................................31
Table 5:
Dose Modifications.................................................................................................42
Table 6:
Dose Recommendation and Modifications for Neutropenia and/or 
Thrombocytopenia at the Start of a Cycle or Within a Cycle...................................43
Table 7:
Dose Modifications for Other Adverse Drug Reactions...........................................44
Table 8:
Power Calculation for Median Time to Treatment Failure and Sample Size ............50
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EDMS Doc. Number:
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ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................25
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EDMS Doc. Number:
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1.
INTRODUCTION
1.1.
Pancreatic Cancer
Worldwide, pancreatic cancer is the thirteenth most common cancer, with 278,684 new cases 
diagnosed in 2008. The prognosis is poor, and as a result, pancreatic cancer is the eighth leading 
cause of cancer-related death worldwide, with an estimated 266,669 deaths in 2008 
(CancerStats, 2011). Pancreatic cancer is the fourth leading cause of cancer-related death in the 
United States (US), with an estimated 39,590 deaths from the disease and an estimated 
46,420 new cases expected in 2014 (Siegel, 2014). The incidence of pancreatic cancer is higher 
in men than women and increases with age, with 90% of pancreatic cancer presenting in subjects 
over the age of 55 years and more than 70% presenting over the age of 65 years 
(Howlader, 2013). In Europe, pancreatic cancer is the fourth leading cause of cancer-related 
death with 80,266 deaths predicted in 2013 (Malvezzi, 2013). Forecasts from the United Nations, 
World Population Prospects, GLOBOCAN 2012 data for cancer incidence and mortality 
predicted that the incidence of new cases of pancreatic cancer in the European Union (EU) to be 
83,262 cases by 2015 (Ferlay, 2010). As in the US, the pancreatic cancer incidence in the EU is 
higher in men than women (Seufferlein, 2012), and incidence also increases with age.
The pancreas is composed of 2 main cell types: exocrine (cells that produce digestive enzymes) 
and endocrine (cells of the islets of Langerhans, that produce among others the hormones insulin 
and glucagon). Exocrine tumors are by far the most common type of pancreatic cancer, with 
adenocarcinoma accounting for about 95% of cancers of the exocrine pancreas (ACS, 2013). The 
focus of the proposed study is pancreatic adenocarcinoma.
The prognosis of subjects with adenocarcinoma is very poor with an overall median survival of 
5 to 8 months and fewer than 5% of long-term survival for more than 5 years (Werner, 2013).
Surgical resection of the pancreatic cancer and subsequent adjuvant chemotherapy is the main 
treatment option required to achieve long-term survival. It can be achieved in about 15% to 20% 
of subjects (Werner, 2013). For the vast majority of the subjects, the treatment will be palliative 
in nature consisting of chemotherapy alone or best supportive care for metastatic patients and 
chemotherapy with or without radiation for locally advanced disease.
1.2.
Locally Advanced Pancreatic Cancer
Locally advanced pancreatic cancer (LAPC) is typically too advanced to be removed surgically 
but still has no distant metastasis. The tumor of the pancreas head or body grow near the 
mesenteric vessels and the celiac trunk. It is defined anatomically by superior mesenteric artery 
encasement, aortic invasion, portal vein occlusion, and superior mesenteric vein involvement if 
not amenable to reconstruction.
At diagnosis, 30% to 35% of patients with pancreatic cancer have a locally advanced 
unresectable disease. There is currently no consensus on the accepted standard of care for the 
treatment of LAPC, although chemotherapy alone is considered the preferred treatment option by 
some oncologists, and chemotherapy followed by chemoradiation or upfront chemoradiation the 
preferred option by other oncologists. Historically, small randomized trials using chemotherapy 
and older radiation techniques did not result in better systemic control of the disease and were 
unable to establish role of chemoradiation (Philip, 2011). 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
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The last generation of clinical trials using gemcitabine as the backbone of chemotherapy or 
radiation showed a median survival between 11 and 16 months in patients with LAPC (Hammel, 
2013; Loehrer, 2011; Philip, 2011). Two new regimens, FOLFIRINOX and 
nab-paclitaxel/gemcitabine, demonstrated a superior efficacy compared to gemcitabine alone in 
metastatic pancreatic adenocarcinoma (Conroy, 2011; Von Hoff, 2013). In the same period of 
time, radiation techniques have considerably improved, and biomarkers are being tested to better 
identify the right populations to be treated. The coming generation of clinical trials are using new 
effective regimens and techniques in selected patients, and are expected to improve the efficacy 
of the treatment for LAPC.
1.3.
nab-Paclitaxel (Abraxane)
nab-Paclitaxel is a proprietary solvent-free, protein-stabilized formulation of paclitaxel 
comprised of paclitaxel and human albumin in a noncrystalline amorphous state, with a mean 
particle size of approximately 130 nanometers. nab-Paclitaxel was designed to improve the 
chemotherapeutic effects of paclitaxel by exploiting endogenous transport pathways to deliver 
higher doses of paclitaxel to the tumor and to reduce the solvent-related hypersensitivity and 
other toxicities associated with Taxol® (paclitaxel) injections, the solvent Cremophor EL, and 
ethanol vehicle. nab-Paclitaxel provides unique tumor selective localization through enhanced 
transport across endothelial cell monolayers, increased drug accumulation in tumors (potentially 
through macropinocytosis (Commisso, 2013), and overall improved pharmacokinetics compared 
with solvent-based paclitaxel. Furthermore, nab-paclitaxel synergizes with gemcitabine in 
preclinical models. The Cremophor EL-free medium enables nab-paclitaxel to be given at a 
higher dose and in a shorter duration without the need for premedication to prevent solvent-
related hypersensitivity reactions (Desai, 2006).
As of August 2014, nab-paclitaxel is approved under the trade name of Abraxane in over 
50 countries/regions, including the US, Canada, India, EU/European Economic Area (EEA), 
South Korea, China, Australia, United Arab Emirates, Nepal, New Zealand, Japan, Russia, Sri 
Lanka, Argentina, Hong Kong, Lebanon, Ecuador, India, Singapore and Chile, for the treatment 
of patients with metastatic breast cancer. Abraxane is also approved for the first-line treatment of 
locally advanced or metastatic non-small cell lung cancer (NSCLC) in the US, Japan, Argentina, 
Australia, New Zealand, Ecuador and Chile for the treatment of advanced gastric cancer in 
Japan, and for the first-line treatment of metastatic adenocarcinoma of the pancreas in the US,
EU/EEA, Australia, New Zealand, Argentina, Lebanon, Ecuador and Canada. nab-Paclitaxel 
alone and in combination is being evaluated as a chemotherapeutic agent for the treatment of 
patients with various solid tumor malignancies.
Please refer to the Investigator’s Brochure for more detail on and concerning the available 
preclinical, pharmacology, toxicology, drug metabolism, clinical study data, and AE profile of 
nab-paclitaxel.
1.3.1.
Preclinical and Clinical Experience with nab-Paclitaxel Plus Gemcitabine in 
Pancreatic Cancer
Preclinical studies have demonstrated that nab-paclitaxel may play a role in sensitizing the tumor 
to chemotherapeutic agents and specifically increases the antitumor efficacy when combined 
with gemcitabine. While the mechanism of action for the synergy is unclear, preclinical studies 
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.3


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
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have generated hypothetical models. One hypothesis is a remodeling and weakening of the 
stroma barrier, allowing the chemotherapeutic agents to have better access to the tumor cells. 
Weakening the tumor-stroma barrier is particularly important in cancer that is characterized by 
dense stroma, such as pancreatic cancer. In mice with primary patient-derived pancreatic tumor 
xenografts, nab-paclitaxel plus gemcitabine versus gemcitabine alone resulted in increased tumor 
regression and depleted the desmoplastic stroma as demonstrated by the disorganized collagen 
type 1 fibers of reduced density after 4 weeks of treatment (Von Hoff, 2011). In this study, the 
intratumoral concentration of gemcitabine was increased by 2.8-fold after 5 days of treatment 
when nab-paclitaxel was added to gemcitabine. It was hypothesized that nab-paclitaxel plays a 
role in reducing the dense stroma to facilitate increased intratumoral gemcitabine uptake. In 
additional preclinical studies in genetically engineered mouse models of pancreatic 
adenocarcinoma, the coadministration of nab-paclitaxel and gemcitabine also demonstrated 
tumor regression and increased intratumoral gemcitabine levels after 8 days of treatment. 
Apoptosis of tumor epithelial cells were observed; however, there were no changes in stromal 
components or collagen density in this treatment model (Frese, 2012). The increased 
intratumoral gemcitabine levels were attributed to a marked decrease in the primary gemcitabine 
metabolizing enzyme, cytidine deaminase. Finally, a recent clinical study in subjects with 
resectable pancreatic cancer treated with neoadjuvant nab-paclitaxel plus gemcitabine showed 
reduction in fibrotic collagenous stroma, further supporting a stroma active mechanism for nab-
paclitaxel (Alvarez, 2013).
In a clinical Phase 1/2 dose-ranging study (CA040, NCT003980860), nab-paclitaxel plus 
gemcitabine antitumor activity and tolerability were established in patients who had no prior 
treatment for metastatic pancreatic cancer (Von Hoff, 2011). The maximum tolerated dose and 
recommended dose for further studies was determined to be 125 mg/m2 nab-paclitaxel in 
combination with 1000 mg/m2 gemcitabine.
In the subsequent randomized international Phase 3 study (MPACT, CA046, NCT00394251) 
that enrolled 861 patients with metastatic pancreatic cancer, nab-paclitaxel in combination with 
gemcitabine exhibited a clinically meaningful, statistically significant improvement in overall 
survival (OS) and progression-free survival (PFS). The median OS (primary endpoint) in the ITT 
population was 8.5 months (95% CI = 7.89-9.53) with nab-paclitaxel/gemcitabine compared 
with 6.7 months (95% CI = 6.01-7.23) with gemcitabine, p < 0.0001, hazard ratio (HR) = 0.72 
(95% CI = 0.617-0.835). Long-term survival was improved in the nab-paclitaxel/gemcitabine 
arm versus gemcitabine alone, with a 59% increase at 1 year (35% versus 22%) and doubling at 
2 years (9% versus 4%). The secondary (PFS, overall response rate [ORR]) and most of all other 
efficacy endpoints showed consistent, statistically significant improvements with nab-paclitaxel 
plus gemcitabine, supporting the results from the primary analysis of OS. Specifically, PFS (by 
independent review) was 5.5 months (95% CI = 4.47-5.95) versus 3.7 months (95% CI = 3.61-
4.04) in the nab-paclitaxel/gemcitabine arm versus gemcitabine alone arms, respectively p < 
0.0001; HR = 0.69; 95% CI = 0.581-0.821). The improvement in PFS corresponded to a 31% 
reduction in the risk of progression or death with nab-paclitaxel plus gemcitabine. The estimated 
median time to treatment failure (TTF) was 5.1 months in the nab-paclitaxel plus gemcitabine 
arm and 3.6 months in the gemcitabine arm (HR = 0.70; 95% CI = 0.604-0.803). Furthermore, in 
this study of metastatic unresectable adenocarcinoma of the pancreas, subjects in the 
combination arm were on therapy longer than those receiving single agent gemcitabine, 
indicating disease improvement and tolerable treatment (Von Hoff, 2013). The suitability of the 
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dosing regimen was confirmed by the observation that the majority of patients did not require a 
dose reduction, and that 71% of nab-paclitaxel doses were delivered at the starting dose of 
125 mg/m2. The safety profile for both regimens was consistent with previous reports. Serious 
life-threatening toxicities were not increased; adverse events (AEs) were acceptable and 
manageable. The most notable differences in toxicity between the 2 treatment arms was 
peripheral neuropathy, which was cumulative and rapidly reversible with dose delay and 
reduction, and neutropenia, which was also manageable with dose delays and dose reductions. 
The incremental risks of sepsis and pneumonitis were managed by protocol amendments to 
increase awareness, and for early diagnosis and treatment to reduce the risk of fatal outcomes.
As a result of the clinically meaningful benefit observed in the MPACT trial, the 2013 National 
Comprehensive Cancer Network (NCCN) guidelines were updated to include nab-paclitaxel plus 
gemcitabine as a Category 1 treatment option for patients with metastatic pancreatic 
adenocarcinoma (NCCN, 2013), and the 2014 NCCN guidelines recommend nab-paclitaxel plus 
gemcitabine in patients with LAPC “based on extrapolation from randomized trials in patients in 
metastatic disease” (NCCN, 2014).
1.4.
Study Rationale
Single agent gemcitabine has been the standard of chemotherapy of pancreatic adenocarcinoma 
since its approval with a median survival of approximately 6 months and a response rate below 
10% (Burris, 1997). In metastatic disease, nab-paclitaxel in combination with gemcitabine has 
demonstrated improved median survival of 8.5 month compared with 6.7 months with 
gemcitabine alone (HR = 0.72, CI = 0.617-0.835) and a response rate of 23% by independent 
review and 29% by investigator assessment. The estimated median TTF was 5.1 months in the 
nab-paclitaxel plus gemcitabine arm and 3.6 months in the gemcitabine arm (HR = 0.70; 95% 
CI = 0.604-0.803) (Study CA046). This positive outcome is very encouraging and needs to be 
further explored in the locally advanced setting where the chance of improving the patient’s 
clinical benefit are higher, and there remains an unmet medical need. More effective 
chemotherapy during a sufficient period of time may increase the systemic effect of 
nab-paclitaxel and its benefit in this patient population.
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EDMS Doc. Number:
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ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
2.
STUDY OBJECTIVES
2.1.
Primary Objective
The primary objective of the study is:
!
To evaluate the TTF in LAPC subjects treated with nab-paclitaxel plus gemcitabine 
as induction therapy followed by Investigator’s Choice of treatment
2.2.
Secondary Objectives
The secondary objectives of the study are:
!
To evaluate the disease control rate (DCR) after the first 6 cycles of nab-paclitaxel 
plus gemcitabine
!
To evaluate the ORR
!
To evaluate the overall PFS and OS
!
To assess the overall safety profile
!
To evaluate the subject’s health-related QoL
 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
21
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
3.
STUDY ENDPOINTS
All primary, secondary 
 analyses will be based on the ITT population unless 
otherwise specified. Safety analyses will be performed on the Treated population, which consists 
of all subjects who take at least 1 dose of IP (referring to both nab-paclitaxel and gemcitabine).
All applicable efficacy endpoints will be evaluated by the Investigator using Response 
Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1 (Eisenhauer, 2009).
3.1.
Primary Endpoint
The primary endpoint is TTF, measured as the time after the first dose of study therapy to 
treatment failure. Treatment failure is defined as discontinuation of study therapy due to disease 
progression, death (by any cause), or the start of a non-protocol-defined anticancer therapy. 
3.2.
Secondary Endpoints
3.2.1.
Efficacy Endpoints
The secondary efficacy endpoints are:
!
The DCR after 6 cycles of nab-paclitaxel plus gemcitabine, defined as the combined 
incidence of complete response (CR), partial response (PR) and stable disease (SD) 
measured at the End of Treatment visit
!
The ORR, defined as the combined incidence of CR and PR
!
The PFS defined as the time after the first dose of study therapy to disease 
progression or death (by any cause)
!
The OS defined as the time after the first dose of study therapy to death (by any 
cause)
!
Differences in outcomes from baseline, during treatment, and after treatment with 
nab-paclitaxel plus gemcitabine for the European Organization for Research and 
Treatment of Cancer (EORTC) quality of life questionnaires (QLQ), EORTC QLQ-
C30 and QLQ-PAN26
3.2.2.
Safety Endpoints
!
The incidence of treatment-emergent AEs, serious AEs (SAEs), laboratory 
abnormalities and other safety parameters
 
 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
22
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is an international, non-randomized, open-label, multi-center, Phase 2 study in subjects with 
LAPC treated with nab-paclitaxel plus gemcitabine for 6 cycles followed by an Investigator’s 
Choice of continuation of treatment with nab-paclitaxel plus gemcitabine, chemoradiation 
therapy, or surgery.
Subjects will be considered active study participants from enrollment up to, but not including, 
survival follow-up period. 
4.1.1.
nab-Paclitaxel plus Gemcitabine for 6 Cycles
Approximately 110 subjects eligible for treatment with nab-paclitaxel plus gemcitabine for 
6 cycles will be enrolled, provided all inclusion/exclusion criteria are met within a 14-day 
screening period prior to Cycle 1 Day 1.
Treatment will commence on Day 1 for 6 cycles: 
!
nab-Paclitaxel 125 mg/m2 intravenous (IV) infusion over approximately 30 to 45 
minutes on Days 1, 8, and 15, followed by gemcitabine 1000 mg/m2 IV infusion over 
approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle
Once 6 cycles have been completed, subjects without disease progression or unacceptable 
toxicity will continue on to the Investigator’s Choice part of the study (Section 4.1.2).
At any time during the study, subjects with disease progression or unacceptable toxicity will be 
discontinued from the study treatment.
4.1.2.
Investigator’s Choice
For those subjects who complete 6 cycles of nab-paclitaxel and gemcitabine without disease 
progression or unacceptable toxicities, the Investigator will then determine which of the 
following options are best for the subject:
!
Continuation of nab-paclitaxel and gemcitabine therapy
OR
!
Chemoradiation therapy consisting of the concurrent use of capecitabine or 
gemcitabine with radiation according to institutional practice
OR
!
Surgical intervention
If the Investigator’s Choice is to continue treatment with nab-paclitaxel plus gemcitabine, 
treatment should continue on schedule as per prior cycles of therapy until disease progression or 
unacceptable toxicity.
If the Investigator’s Choice is chemoradiation therapy, a minimum of 3 weeks must have elapsed 
between the last chemotherapy infusion and the initiation of the chemoradiotherapy.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
23
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
If tumor response allows a surgical intervention, the subject will be eligible for that treatment as 
deemed appropriate by the investigator. Surgical intervention may occur prior to completing the 
planned 6 cycles of nab-paclitaxel plus gemcitabine if subjects demonstrate a major response to 
therapy. In case of surgery, the delay may vary depending upon the surgery planning; however, 
the chemotherapy-induced neutropenia nadir should be avoided.
No additional non-protocol-defined anticancer agents are allowed during study treatment.
Protocol defined anticancer agents are:
!
nab-paclitaxel plus gemcitabine used during the induction phase, or 
!
Investigator’s Choice of continuing chemotherapy with:
∀
nab-paclitaxel plus gemcitabine
∀
chemoradiation consisting of the concurrent use of capecitabine or gemcitabine 
with radiation according to institutional standard, or
∀
surgery
All supportive care (including but not limited to growth factors, antiemetics, analgesics) is 
permitted as per the Investigator’s discretion and should be administered according to local 
institutional practice. 
During the study, subjects will have computed tomography (CT) or magnetic resonance imaging 
(MRI) scans every 56 days (-3/+7 days) until documented progression of disease, withdrawal of 
consent from active participation in the study, lost to follow-up, or death. Tumor evaluations will 
be assessed by the investigative sites and response will be determined according to RECIST v1.1 
guidelines.
All scheduled laboratory samples will be performed locally. Local laboratory values that are 
considered abnormal and clinically significant will be recorded as an AE or SAE and also 
recorded on the laboratory electronic case report form (eCRF). 
Safety data will be reviewed on an ongoing basis throughout the study by the study Medical 
Monitor and drug safety physician.
4.1.3.
Follow-up Period
Safety Follow-up
Subjects who discontinue treatment with nab-paclitaxel plus gemcitabine for any reason will 
have a safety follow-up visit 28 days after treatment discontinuation.
Subjects who are planned to undergo chemoradiation or surgery will have safety visit pre-
treatment (with chemoradiation or surgery), at 28 days after discontinuation with 
chemoradiation, or 28 days post surgery.
Efficacy Follow-up
Subjects who discontinue treatment without disease progression will continue to have CT/MRI 
scans every 56 days (-3/+7 days) until documented disease progression, withdrawal of consent,
lost to follow-up, or death (by any cause), whichever is earliest.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
24
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Additionally, subjects will be followed for OS and post-study anticancer therapies approximately 
every 90 days by phone or review of medical records until death, withdrawal of consent, or lost 
to follow-up. 
4.2.
Study Design Rationale
Despite the development of new systemic therapies for metastatic pancreatic cancer, there is no 
established combination chemotherapy regimen for LAPC.
The study design of this trial (Figure 1) is meant to reproduce the current predominant clinical 
practice with chemotherapy being prescribed upfront, followed by the options of chemoradiation 
therapy or, in rare cases, surgery. The combination of nab-paclitaxel plus gemcitabine as the 
upfront chemotherapy is expected to bring a more effective systemic control of the disease and 
may become the therapy backbone for the treatment of LAPC and testing of targeted agents in 
the future. In addition, with better systemic therapies, the role of chemoradiation therapy may be 
better studied. The purpose of this study, however, is not to prospectively test the role of 
chemoradiotherapy in LAPC.
The promising activity with nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer 
underscore the hypothesis for this study in subjects with LAPC. The nab-paclitaxel plus 
gemcitabine regimen used for this study will be in accordance with Food and Drug 
Administration (FDA) and European Commission (EC) approved label for metastatic pancreatic 
cancer: nab-paclitaxel 125 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15, followed by 
gemcitabine 1000 mg/m2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 28-day cycle. 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
25
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Figure 1:
Overall Study Design
CR = complete response; IV = intravenously; PD = progressive disease; PR = partial response; SD = stable disease.
4.3.
Study Duration
The enrollment period will last approximately 24 months. The total length of this study with 
enrollment into the nab-paclitaxel plus gemcitabine for 6 cycles, Investigator’s Choice, and 
follow-up is estimated to be approximately 3.5 years or until up to 95% of survival data have 
been collected, whichever comes first. 
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 
 analysis, as pre-specified in the protocol and/or the 
Statistical Analysis Plan, whichever is the later date.
Screening for Eligibility
(N = 110)
Follow-up Period
Continue nab-Paclitaxel 
+ Gemcitabine
until PD or toxicity
Chemoradiotherapy 
nab-Paclitaxel 125 mg/m2 IV over approximately 30 to 45 minutes on Days 1, 8, and 
15, followed by gemcitabine 1000 mg/m2 IV infusion over approximately 30 minutes 
on Days 1, 8, and 15 of each 28-day cycle for 6 cycles
If CR, PR, or SD
Investigator’s Choice
Surgical Intervention
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
26
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
5.
TABLE OF EVENTS
Table 1:
Table of Events – Induction: nab-Paclitaxel Plus Gemcitabine
Screenin
g/
Baseline
Treatment Period
Every 28-day Cycle
Follow-Up Period
a
Assessment
Reference 
to Protocol 
Section
Day -14 
to
Day -1
Day 1
( ±2 
days)
Day 8
(±1 
days)
Day 15
(±1 
days)
Every 56 
days 
(-3/+7 
days)
(starting 
C1D1)
28-day 
Follow-up 
Visit (after 
last dose of 
IP)
Survival 
Follow-Up
Every 90 
Days (± 14 
Days)
Informed Consent
Section 6
X
-
-
-
-
-
-
Medical History, Prior Medication and 
Procedures of Special Interest
Sections 6.1,
6.5
X
-
-
-
-
-
-
Demographics
Section 6.2
X
-
-
-
-
-
-
nab-PaclitaxelAdministration/Accountability
Section 4.1.1
-
X
X
X
-
-
-
Gemcitabine Administration/Accountability
Section 4.1.1
-
X
X
X
-
-
-
Physical Examination
Section 6.3
Will be done as per standard of care during the study and as clinically indicated
Vital Signs
Section 6.4
Pregnancy Test (Serum)
Section 6.6
X
-
-
-
-
-
-
Pregnancy Test (Urine)
Section 6.6
X
CT Scan and Any Other Studies Required for 
Tumor Imaging
Section 6.7
X
-
-
-
X
X
-
Height
Section 6.8
X
-
-
-
-
-
-
Weight
Section 6.8
X
X
-
-
-
-
-
ECOG Performance Status
Section 6.9
X
X
-
-
-
X
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
27
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Table 1:
Table of Events – Induction: nab-Paclitaxel Plus Gemcitabine (Continued)
Screening/
Baseline
Treatment Period
Every 28-day Cycle
Follow-Up Period
Assessment
Reference 
to Protocol 
Section
Day -14 to
Day -1
Day 1
( ±2 
days)
Day 8
(±1 
days)
Day 15
(±1 
days)
Every 56 
days 
(-3/+7 
days)
(starting 
C1D1)
28-day 
Follow-up 
Visit (after 
last dose of 
IP)
Survival 
Follow-Up
Every 90 
Days (± 14 
Days)
Concomitant Medications/Procedures of 
Special Interest
Section 6.10
X
X
-
-
-
X
-
Peripheral Neuropathy Assessment
Section 6.11
X
X
-
-
-
X
-
Adverse Event Evaluation
Section 6.12
After signing ICF and until 28 days after the last dose of IP or at the 28-day Follow-up Visit, 
whichever occurs later. Not during survival unless it is a suspected SAE (See Section 11.5)
EORTC QLQ-C30 and QLQ-PAN26
Section 6.13
X
X
-
-
-
X
-
Complete and Differential Blood Count
Section 6.14
X
X
X
X
-
X
-
Serum Chemistry
Section 6.14
X
X
-
-
-
X
-
Serum CA19-9
Section 6.14
X
-
-
-
X
X
-
Survival Status
Section 6.16
-
-
-
-
-
-
X
AE = adverse event; β-hCG = beta human chorionic gonadotropin; C = cycle; CT = computed tomography; D = day; ECOG = Eastern Cooperative Oncology Group; eCRF = 
electronic case report form; EORTC - European Organization for Research and Treatment of Cancer; FCBP = females of childbearing potential;  ICF = informed consent form; 
IP = investigational product; IV = intravenous; MRI = magnetic resonance imaging; QLQ = quality of life questionnaire; RECIST = Response Evaluation Criteria in Solid 
Tumors; SAE = serious adverse event; US = United States.
a Refer to Table 2, Table 3 or Table 4 if continuing to Investigator's Choice.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
28
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Table 2:
Table of Events – Investigator’s Choice: Continuing with nab-Paclitaxel Plus Gemcitabine
Treatment Period
Every 28-day Cycle
Follow-Up Period
Assessment
Reference to 
Protocol 
Section
Day 1
( ±2 days)
Day 8
(±1 
days)
Day 15
(±1 
days)
Every 56 
Days
(-3/+7 Days)
(Starting 
C1D1)
28-day 
Follow-up 
Visit (after 
last dose of 
IP)
Survival 
Follow-Up
Every 90 Days 
(± 14 Days)
nab-Paclitaxel Administration/Accountability
Section 4.1.1
X
X
X
-
-
-
Gemcitabine Administration/Accountability
Section 4.1.1
X
X
X
-
-
-
Physical Examination
Section 6.3
Will be done as per standard of care during the study and as clinically indicated
Vital Signs
Section 6.4
Pregnancy Test(Urine)
Section 6.6
-
-
-
-
X
-
CT Scan and Any Other Studies Required for Tumor 
Imaging
Section 6.7
X
-
-
X
X
-
Weight
Section 6.8
X
-
-
-
-
-
ECOG Performance Status
Section 6.9
X
-
-
-
X
-
Concomitant Medications/Procedures of Special Interest
Section 6.10
X
-
-
-
X
-
Peripheral Neuropathy Assessment
Section 6.11
X
-
-
-
X
-
Adverse Event Evaluation
Section 6.12
After signing ICF and until 28 days after the last dose of IP or 28-day Follow-up 
Visit, whichever occurs later. Not during survival unless it is a suspected SAE (See 
Section 11.5)
EORTC QLQ-C30 and QLQ-PAN26
Section 6.13
X
-
-
-
X
-
Complete and Differential Blood Count
Section 6.14
X
X
X
-
X
-
Serum Chemistry
Section 6.14
X
-
-
-
X
-
Serum CA19-9
Section 6.14
X
-
-
X
X
-
Survival Status
Section 6.16
-
-
-
-
-
X
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
29
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
AE = adverse event; β-hCG = beta human chorionic gonadotropin; C = cycle; CT = computed tomography; D = day; ECOG = Eastern Cooperative Oncology Group; eCRF = 
electronic case report form; EORTC - European Organization for Research and Treatment of Cancer; ICF = informed consent form; IP = investigational product; IV = 
intravenous; MRI = magnetic resonance imaging; QLQ = quality of life questionnaire; SAE = serious adverse event; US = United States.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
30
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Table 3:
Table of Events – Investigator’s Choice: Chemoradiation as per Institutional Standard of Care
Prior to 
Chemoradiation
Treatment Period
(Chemoradiation)
Follow-Up Period
Assessment
Reference to 
Protocol 
Section
28-day Follow-
up Visit After 
Last Dose of IP
Weekly 
During 
Chemo-
radiation
Every 56 
Days
(-3/+7 Days)
(From C1D1)
28-day 
Follow-
up Visit
Survival Follow-
Up
Every 90 Days
(± 14 Days)
Chemoradiation as per Institutional Standard of 
Care
Section 4.1.2
-
X
-
-
-
Physical Examination
Section 6.3
Will be done as per standard of care during the study and as clinically indicated
Vital Signs
Section 6.4
Pregnancy Test (Urine)
Section 6.6
X
-
-
-
-
CT Scan and any other studies required for tumor 
imaging
Section 6.7
X
-
X
X
-
ECOG Performance Status
Section 6.9
X
-
-
-
-
Concomitant Medications/Procedures of Special 
Interest
Section 6.10
X
X
-
-
X
Peripheral Neuropathy Assessment
Section 6.11
X
-
-
-
-
Adverse Events Evaluations
Section 6.12
After signing ICF and until 28 days after the last dose of chemoradiation or the 28-
day Follow-up Visit, whichever is later. Not during survival unless it is a suspected 
SAE (See Section 11.5)
EORTC QLQ-C30 and QLQ-PAN26
Section 6.13
X
-
-
-
-
Complete and Differential Blood Count
Section 6.14
X
X
-
X
-
Serum Chemistry
Section 6.14
X
X
-
X
-
Serum CA19-9
Section 6.14
X
-
X
X
-
Survival Status
Section 6.16
-
-
-
-
X
C = cycle; CT = computed tomography; D = day; ECOG = Eastern Cooperative Oncology Group; ICF = informed consent form; IP = investigational product; QLQ = quality of 
life questionnaire; RECIST = Response Evaluation Criteria in Solid Tumors; US = United States.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
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ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Table 4:
Table of Events – Investigator’s Choice: Surgery as per Institutional Standard of Care
Prior to Surgery Treatment Period (Surgery)
Follow-Up Period
Assessment
Reference 
to Protocol 
Section
28-day Follow-
up Visit After 
Last Dose of IP
Day of 
Surgery
Every 56 Days
(-3/+7 Days)
(Starting 
C1D1)
28-day Follow-
up Period
Survival Follow-
Up
Every 90 Days
(± 14 Days)
Surgery as per Institutional Standard of Care
Section 4.1.2
-
X
-
-
-
Physical Examination
Section 6.3
Will be done as per standard of care during the study and as clinically indicated
Vital Signs
Section 6.4
Pregnancy Test (Urine)
Section 6.6
X
-
-
-
-
CT Scan and any other studies required for tumor 
imaging
Section 6.7
X
-
X
X
-
ECOG Performance Status
Section 6.9
X
-
-
-
-
Concomitant Medications/Procedures of Special 
Interest
Section 6.10
X
X
-
X
X
Peripheral Neuropathy Assessment
Section 6.11
X
-
-
-
-
Adverse Events Assessment
Section 6.12
After signing ICF and until 28-days post surgery or the 28-day surgery Follow-up Visit, 
whichever is later. Not during survival unless it is a suspected SAE (See Section 11.5)
EORTC QLQ-C30 and QLQ-PAN26
Section 6.13
X
-
-
-
-
Complete and Differential Blood Count
Section 6.14
X
-
-
X
-
Serum Chemistry
Section 6.14
X
-
-
X
-
Serum CA-19-9
Section 6.14
X
-
X
X
-
FFPE Tumor Tissue From Surgical Resection
Section 6.15
-
X
-
-
-
Survival Status
Section 6.16
-
-
-
-
X
C = cycle; CT = computed tomography; D = day; ECOG = Eastern Cooperative Oncology Group; FFPE = formalin-fixed, paraffin-embedded; ICF = informed consent form; IP = 
investigational product; QLQ = quality of life questionnaire.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
32
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
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 
Randomization Technology (IRT) 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 for enrollment. 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 repeating screening procedures (some 
procedures may not need to be repeated if previously completed within 14 days prior to 
Screening).
Investigators will be asked at subject enrollment what their preferred treatment would be at the 
conclusion of the 6 cycles of therapy. The intended treatment will then be compared to the actual 
treatment given at the conclusion of the 6 cycles of therapy.
6.1.
Medical History
An abbreviated medical history for pancreatic cancer will be collected. All pancreatic cancer-
related medical history should be recorded regardless of time.
6.2.
Demographics
Gender, race and other categorical variables will be captured if allowed by local regulations.
6.3.
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 an AE or SAE).
6.4.
Vital Signs
Vital signs (temperature, systolic and diastolic blood pressure and pulse) 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 an AE or SAE). 
6.5.
Prior Medications/Procedures of Special Interest
Prior medications and procedures of special interest (Section 19.2) within 14 days of time of 
signature on the ICF should be recorded. All pancreatic cancer-related prior 
medications/procedures should be recorded regardless of time.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
33
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
6.6.
Pregnancy Testing
A serum pregnancy test with sensitivity of at least 25 mIU/mL is to be obtained in females of 
childbearing potential (FCBP) at Screening. A serum pregnancy test must be done within 
72 hours prior to Cycle 1 Day 1 of starting study therapy. The subject may not receive treatment 
until the Investigator has verified that the result of the pregnancy test is negative.
A urine pregnancy test must be performed at the 28-day Follow-up Visit after the subject’s last 
dose of IP. See inclusion criteria for pregnancy testing requirements. Any pregnancies that occur 
in women who have received investigational product (IP) during the study or within 28 days 
after the last dose of IP, or in the partner of the male subject during the study or within 6 months 
after the last dose of IP must be immediately reported to Celgene Drug Safety.
6.7.
Computed Tomography or Magnetic Resonance Imaging Scan
During the induction period, a CT/MRI scan with and without contrast of the chest, abdomen and 
pelvis and any other studies required for tumor imaging will be done at Screening, every 56 days 
(-3/+7 days) (schedule for scans will be based on calendar, not start of cycle), and at the 28-day 
Follow-up Visit (after the last dose of IP).
During the Investigator’s Choice part of the study, scans will be done every 56 days (-3/+7 days) 
(schedule for scans will be based on calendar, not start of cycle) and at the 28-day Follow-up 
Visit (after the last dose of IP and chemoradiation), and post surgery (28 days post surgery). 
All subjects should have CT/MRI until disease progression, withdrawal of consent from active 
participation in the study, lost to follow-up, death (by any cause), or the start of a non-protocol-
defined anticancer therapy, whichever is the earliest.
Additional CTs may be done at any time during the study if clinically indicated. A baseline MRI 
scan with contrast may replace a CT scan for tumor assessment based on the decision of the 
treating oncologist (eg, intolerance to IV contrast dye for CT). In those situations, follow-up 
scans for tumor assessment must be by MRI.
Screening CT or MRI scans will be de-identified and collected for potential central analysis of 
eligibility.
6.8.
Weight and Height
Weight will be obtained at Screening and at every Day 1 of every cycle during the Treatment 
Period before the administration of IP. Additional weight measurements may be collected per 
local standards at any time during the study as needed. Height will only be collected at 
Screening. All weight and height data will be recorded on eCRFs.
6.9.
Eastern Cooperative Oncology Group (ECOG) Performance Score
The ECOG performance score (Section 19.1) will be collected at Screening, Day 1 of every 
cycle, and at the 28-day Follow-up Visit (after last dose of IP). Additional ECOG performance 
scores may be collected at any time during the study as needed.
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cle, a


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
34
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
6.10.
Concomitant Medications/Procedures of Special Interest
All subjects will have concomitant medications and procedures of special interest (Section 19.2) 
recorded at the beginning of each cycle from the time of signature on the ICF until the 28-day 
Follow-up Visit. All pancreatic cancer-related concomitant medications will also be collected 
during the Survival Follow-Up. For SAEs, all concomitant medications will be collected
(Section 9.1).
6.11.
Peripheral Neuropathy Assessment
Peripheral neuropathy assessment will be assessed from the time of signature on the ICF and 
Day 1 of each cycle until the 28-day Follow-up Visit. The occurrence of peripheral neuropathy 
will be reported by the Investigator per protocol as an AE or SAE. Additional peripheral 
neuropathy assessments may be done at any time during the study as needed. Subjects with 
Grade 4 peripheral neuropathy will be discontinued from study treatment.
6.12.
Adverse Event Reporting
All subjects will have AEs recorded at each visit from time of signature on the ICF until 28 days 
after the last dose of IP, or at the 28-day Follow-up Visit, including any unscheduled visits, 
whichever occurs later. 
For subjects who undergo chemoradiation, AEs will be assessed until 28 days after the last dose 
of chemoradiation or the 28-day chemoradiation Follow-up Visit, whichever is later.
For subjects who undergo surgery, AEs will be assessed until 28 days post surgery or the 28-day 
surgery Follow-up Visit, whichever is later.
6.13.
Quality of Life Questionnaires 
The EORTC QLQ-C30 and QLQ-PAN26 questionnaires will be completed at Screening, Day 1 
of every cycle and at the 28-day Follow-up Visit during the nab-paclitaxel plus gemcitabine 
induction phase and for subjects continuing nab-paclitaxel plus gemcitabine as an Investigator’s 
Choice. Subjects who discontinue the nab-paclitaxel plus gemcitabine regimen before 
completing the treatment cycles should have 1 final quality of life (QoL) data collection at their 
28-day Follow-up Visit after the treatment discontinuation and no further QoL data collection is 
needed. The QoL data generated from these questionnaires will be analyzed per the description 
in the SAP.
6.14.
Laboratory Assessments
All scheduled laboratory samples will be analyzed locally. Laboratory values of special interest 
(Section 19.3) and laboratory values that are considered abnormal and clinically significant will 
be recorded as an AE/SAE and also recorded on the laboratory eCRF.
Laboratory assessments to include:
!
Clinical chemistry panel (including but not limited to sodium, potassium, chloride, 
glucose, blood urea nitrogen (BUN), alkaline phosphatase, aspartate 
aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
35
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
aminotransferase/ serum glutamic-pyruvic transaminase (ALT/SGPT), serum 
albumin, total bilirubin and creatinine) will be collected:
∀
at Screening, Day 1 of each dosing cycle of nab-paclitaxel plus gemcitabine, and 
at the 28-day Follow-up Visit
∀
weekly during treatment and at follow-up if continuing on chemoradiation
∀
28 days post surgery 
!
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∀
at Screening, Day 1, 8, and 15 of each dosing cycle of nab-paclitaxel plus 
gemcitabine, and at the 28-day Follow-up Visit 
∀
weekly during treatment and at follow-up if continuing on chemoradiation
∀
28 days post surgery 
!
Serum carbohydrate antigen 19-9 (CA19-9) levels will be collected at the time of 
every CT/MRI scan assessment
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
36
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.16.
Survival
Survival follow-up will be by phone or review of medical records approximately every 90 days 
until withdrawal of consent, lost to follow-up, or death (by any cause). Post-study anticancer 
therapies as well as their efficacy and tolerability will be recorded in the eCRF for further 
analysis. 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
37
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
Subjects with LAPC who are ≥ 18 years old will be eligible for this study. Approximately 
110 subjects will be enrolled. The study will be conducted in US, Canada, and the EU.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1. ≥ 18 years of age at the time of signing the ICF.
2. Histologically or cytologically confirmed adenocarcinoma of the pancreas.
3. Unresectable pancreatic cancer according to radiographic criteria (CT or MRI scans) or 
exploration:
a.
Superior mesenteric vein and portal vein: occlusion, thrombosis, or encasement 
extending several centimeters
b. Superior mesenteric artery: tumor abutment > 180 degrees or thrombosis of artery
c.
Celiac axis: abutment or encasement of the celiac axis
d. Lymph nodes: involvement
4. Without distant metastasis as defined by CT or MRI scan of the chest, abdomen and
pelvis.
5. ECOG performance status of 0 or 1.
6. Acceptable hematology parameters:
a.
Absolute neutrophil count (ANC) ≥ 1500 cell/mm3
b. Platelet count ≥ 100,000/mm3
c.
Hemoglobin (Hgb) ≥ 9 g/dL
7. Acceptable blood chemistry levels:
a.
AST/ SGOT and ALT/ SGPT ≤ 2.5 x upper limit of normal range (ULN)
b. Total bilirubin ≤ 1.5 ULN 
c.
Alkaline phosphatase ≤ 2.5 x ULN
d. Serum albumin > 3 g/dL
e.
Serum creatinine ≤ 1.5 ULN 
8. Female of childbearing potential (FCBP) (defined as a sexually mature woman who 
(1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral 
oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
38
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
postmenopausal for at least 24 consecutive months [ie, has had menses at any time during 
the preceding 24 consecutive months]) must:
a.
Either commit to true abstinence* or agree to the use of 2 physician-approved 
contraceptive methods (oral, injectable, or implantable hormonal contraceptive; 
tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or 
vasectomized partner) while on IP; and for 3 months following the last dose of IP; 
and
b. Has a negative serum pregnancy test (β-hCG) result at screening
9. Male subjects must practice true abstinence# or agree to use a condom during sexual 
contact with a pregnant female or a female of childbearing potential while participating in 
the study, during dose interruptions, and for 6 months following IP discontinuation, even 
if he has undergone a successful vasectomy.
10. Understand and voluntarily sign an informed consent document prior to any study related 
assessments/procedures are conducted.
11. Able to adhere to the study visit schedule and other protocol requirements.
7.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. Pancreatic tumors of endocrine or mixed origin.
2. Prior anticancer therapy for pancreatic carcinoma.
3. Presence of or history of metastatic pancreatic adenocarcinoma.
4. Any other malignancy within 5 years prior to enrollment, with the exception of 
adequately treated in-situ carcinoma of the prostate (Gleason score ≤ 7), cervix, uteri, or 
nonmelanomatous skin cancer (all treatment of which should have been completed 6 
months prior to enrollment).
5. Active bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as 
ongoing signs/symptoms related to the infection without improvement despite 
appropriate antibiotics, antiviral therapy, and/or other treatment.
6. Known infection with hepatitis B or C, or history of human immunodeficiency virus 
(HIV) infection, or subject receiving immunosuppressive or myelosuppressive 
medications that would, in the opinion of the Investigator, increase the risk of serious 
neutropenic complications.
7. History of allergy or hypersensitivity to nab-paclitaxel or gemcitabine or any of their 
excipients.
8. Peripheral sensory neuropathy Grade > 1.
                                               
# True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. (Periodic 
abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable 
methods of contraception).
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
39
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
9. Clinically significant ascites.
10. Plastic biliary stent. Metal biliary stent is allowed.
11. Serious medical risk factors involving any of the major organ systems, or serious 
psychiatric disorders, which could compromise the subject's safety or the integrity of the 
study data. These include, but are not limited to:
a.
History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa) 
b. History of interstitial lung disease, slowly progressive dyspnea and unproductive 
cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary 
hypersensitivity pneumonitis, or multiple allergies 
c.
History of the following within 6 months prior to Cycle 1 Day 1: a myocardial 
infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass 
graft, New York Heart Association (NYHA) Class III-IV heart failure, 
uncontrolled hypertension, clinically significant cardiac dysrhythmia or 
electrocardiogram (ECG) abnormality, cerebrovascular accident, transient 
ischemic attack, or seizure disorder 
12. Enrollment in any other clinical protocol or investigational study with an interventional 
agent or assessments that may interfere with study procedures.
13. Any significant medical condition, laboratory abnormality, or psychiatric illness that 
would prevent the subject from participating in the study.
14. Any condition including the presence of laboratory abnormalities, which places the 
subject at unacceptable risk if he/she were to participate in the study.
15. Any condition that confounds the ability to interpret data from the study.
16. Unwillingness or inability to comply with study procedures.
17. Pregnant or breast feeding.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
40
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Investigational Products
nab-Paclitaxel will be supplied by the sponsor and labeled appropriately as investigational 
material for this study. Labels will bear Celgene’s name and address, the protocol number, 
EudraCT number (if applicable), product name, dosage form and strength, medication 
identification/kit number, lot number, expiry date, dosing instructions, storage conditions, 
quantity of IP contained, and required caution statements and/or regulatory statements as 
applicable. 
Gemcitabine will be supplied or obtained according to local clinical study agreement and in 
accordance with local guidelines.
Additional information may be included on the label as needed or applicable. Label(s) for IP 
supplied to sites outside the US will contain information as required per local health authority.
The IP supply will be managed by IRT. All IP must be stored in accordance with the product 
label in a secure area to prevent unauthorized access.
IP refers to both nab-paclitaxel and gemcitabine.
8.1.1.
Abraxane (nab-Paclitaxel)
nab-Paclitaxel will be supplied by the sponsor, Celgene Corporation, in single-use vials in 
single-count cartons. Each single-use 50 mL vial will contain paclitaxel (100 mg) and human 
albumin as a stabilizer.
See local prescribing information for Abraxane for detailed instructions on the reconstitution, 
storage conditions, and IV administration of nab-paclitaxel.
Temperature records for nab-paclitaxel must be made available to Celgene or other sponsor-
nominated monitoring teams for verification of proper IP storage. 
8.1.2.
Gemcitabine
Gemcitabine is a nucleoside metabolic inhibitor.
Gemcitabine will be supplied or obtained according to local clinical study agreement and in 
accordance with local guidelines. 
See gemcitabine prescribing information for more details on available formulations, preparation, 
storage conditions, approved indications, known precautions, warnings, and adverse reactions of 
gemcitabine (see current Prescribing Information).
8.2.
Treatment Administration and Schedule
nab-Paclitaxel plus Gemcitabine for 6 Cycles
Approximately 110 subjects eligible for treatment with nab-paclitaxel plus gemcitabine for 
6 cycles will be enrolled, provided all inclusion/exclusion criteria are met within a 14-day 
screening period prior to Cycle 1 Day 1.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
41
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Treatment will commence on Day 1 for 6 cycles: 
!
nab-Paclitaxel 125 mg/m2 IV infusion over approximately 30 to 45 minutes on Days 
1, 8, and 15, followed by gemcitabine 1000 mg/m2 IV infusion over approximately
30 minutes on Days 1, 8, and 15 of each 28-day cycle
Once 6 cycles have been completed, subjects without disease progression or unacceptable 
toxicity will continue on to the Investigator’s Choice part of the study. 
At any time during the study, subjects with disease progression or unacceptable toxicity will be 
discontinued from the study treatment.
Investigator’s Choice
For subjects who complete 6 cycles of nab-paclitaxel and gemcitabine without disease 
progression or unacceptable toxicities, the Investigator will then determine which of the 
following options are best for the subject:
!
Continuation of nab-paclitaxel and gemcitabine therapy to disease progression or 
unacceptable toxicity
OR
!
Chemoradiation therapy consisting of the concurrent use of capecitabine or 
gemcitabine with radiation according to institutional practice
OR
!
Surgical intervention
Surgical intervention may occur prior to completing the planned 6 cycles of nab-paclitaxel plus 
gemcitabine if subjects demonstrate a major response to therapy. 
All IP will be administered by the clinical site, and administration will be documented in the
study source record. 
8.2.1.
Dose Modifications
8.2.1.1.
Rules for Dose Omissions and Modified Schedules
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered ≤ 2 days from the scheduled date. Study treatments days must be 7 or more days 
apart for each other.
Day 1 Dose Missed
If the dose held or missed was to be given on Day 1 of the next cycle, that next cycle will not be 
considered to start until the day the first dose is actually administered to the subject (ie, 
1-2-3-Rest, X-1-2-3-Rest, etc).
Day 8 Dose Is Missed
If the dose held or missed was to be given on Day 8 of the next cycle, that next cycle continues 
per protocol, with 1 dose not given (ie, 1-2-3-Rest, 1-X-3-Rest, 1-2-3-Rest, etc). Day 8 is 
administered as per cycle calendar if complete blood counts and chemistries permit.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
42
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Day 15 Dose Missed
If the dose held or missed was to be given on Day 15 of the next cycle, that week becomes the 
week of rest. Next dose (if counts and chemistries permit) becomes Day 1 of a new cycle, and 
the subject is considered to have had a x2Q3W (21-day) cycle (ie, 1-2-3-Rest, 1-2-X, 1-2-3-Rest, 
etc).
The maximum delay between a missed scheduled dose and the next one (whichever dose was 
missed) should not be longer than 21 days (except for peripheral neuropathy; see Table 7). 
8.2.1.2.
Dose Modification Tables
Doses will be reduced for hematologic and other toxicities. Dose adjustments are to be made 
according to the system showing the greatest degree of toxicity. Toxicities will be graded using 
the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 
v4.0. 
Two levels of dose modifications for Abraxane and/or gemcitabine are permitted according to 
the criteria below. If a toxicity requiring dose modification occurs following the second dose 
reduction of either IP, further treatment should be discontinued. Dose escalations are prohibited.
Table 5:
Dose Modifications
Dose Level
nab-Paclitaxel Dose (mg/m2)
a
Gemcitabine (mg/m2)a
Study Dose
125
1000
-1
100
800
-2
b
75
600
a Dose reductions may or may not be concomitant, refer to Table 6. If the dose is withheld due to hematologic toxicity on Day 
15, resume at the next lower dose level when the subject has adequate absolute neutrophil and platelet counts to begin Day 1 of 
the next cycle. Refer to Table 6 for specific recommendations regarding dose modifications for Day 1. 
b A maximum of 2 dose level reductions are allowed. 
Subjects experiencing IP-related toxicities that require a delay in scheduled nab-paclitaxel or 
gemcitabine dosing for ∃21 days will be discontinued from further treatment in this study 
(except for peripheral neuropathy; see Table 7). 
In the event dose modifications are required at the start of a cycle or within a cycle due to 
hematologic toxicities of neutropenia and/or thrombocytopenia, doses of nab-paclitaxel and 
gemcitabine may be adjusted as detailed in Table 6. The WBC growth factor may be given 
according to institutional guidelines for the treatment of neutropenic fever or infections 
associated with neutropenia and for the prevention of febrile neutropenia in subjects with an 
ANC < 500 cells/mm3. Subjects not experiencing resolution of neutropenia within 21 days, 
despite uninterrupted WBC growth factor treatment, will discontinue study treatment. In 
addition, WBC growth factors may be administered as supportive therapy to recover ANC 
adequately such that dosing levels may be maintained. If a dose reduction was required due to 
neutropenia, a dose re-escalation may be considered with continued growth factor support. If 
hematologic toxicity is restricted to platelet counts alone, dose modification of only gemcitabine 
could be considered after discussion with the sponsor.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
43
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Table 6:
Dose Recommendation and Modifications for Neutropenia and/or 
Thrombocytopenia at the Start of a Cycle or Within a Cycle
Cycle 
Day
ANC 
(cells/mm3)
Platelet count 
(cells/mm3)
nab-Paclitaxel Dose
Gemcitabine Dose
Day 1
≥ 1500 
AND
≥ 100,000
Treat on time at current dose levels
< 1500 
OR
< 100,000
Delay doses until recovery
Day 8
≥ 1000 
AND
≥ 75,000 
Treat on time at current dose levels
≥ 500 but 
< 1000
OR
≥ 50,000 but 
< 75,000
Reduce 1 dose level
< 500
OR
< 50,000
Withhold doses 
Day 15:  IF Day 8 doses were given without modification:
Day 15
≥ 1000 
AND
≥ 75,000 
Treat on time at current dose levels
≥ 500 but 
< 1000
OR
≥ 50,000 but 
< 75,000
Reduce 1 dose level from Day 8; consider following 
with WBC growth factors for support
a
< 500
OR
< 50,000
Withhold doses
Day 15:  IF Day 8 doses were reduced:
Day 15
≥ 1000 
AND
≥ 75,000 
Treat with same doses as Day 8; consider following 
with WBC growth factors for support
a
≥ 500 but 
< 1000
OR
≥ 50,000 but 
< 75,000
Reduce 1 dose level from Day 8; consider following 
with WBC growth factors for support
a
< 500
OR
< 50,000
Withhold doses
Day 15:  IF Day 8 doses were withheld:
Day 15
≥ 1000 
AND
≥ 75,000 
Option A: Maintain dose level from Day 1 and 
follow with WBC growth factors for support
a
OR
Option B: Reduce 1 dose levels from Day 1 
≥ 500 but 
< 1000
OR
≥ 50,000 but 
< 75,000
Option A: Reduce 1 dose level from Day 1 and 
follow with WBC growth factors for support
a
OR
Option B: Reduce 2 dose levels from Day 1 
< 500
OR
< 50,000
Withhold doses
ANC = absolute neutrophil count; WBC = white blood cell.
a The use of WBC growth factors is only applicable if the dose-limiting hematologic toxicity was limited to 
neutropenia or febrile neutropenia.
Dose modifications for other adverse drug reactions are provided in Table 7. 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
44
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Table 7:
Dose Modifications for Other Adverse Drug Reactions
Adverse Drug Reaction
nab-Paclitaxel Dose
Gemcitabine Dose
Febrile Neutropeniaa:
Grade 3 or 4
Withhold doses until fever resolves and ANC is ≥ 1500; resume at 
next lower dose levelb
Peripheral Neuropathy:
Grade 3
Withhold dose until improvement 
to ≤Grade 1;
resume at next lower dose levelb
Treat with same dose
Peripheral Neuropathy:
Grade 4
Discontinued from study treatment
Cutaneous Toxicity:
Grade 2 or 3
Withhold dose until improvement to ≤Grade 1;
resume at next lower dose levelb
Discontinue treatment if AE persists
For all other nonhematologic 
toxicities (except nausea, 
vomiting, alopecia and 
pulmonary embolism) of 
> Grade 3
Withhold doses until improvement to ≤Grade 1;
resume at next lower dose levelb
ADR = adverse drug reaction; ANC = absolute neutrophil count.
a White blood cell growth factor may be given according to institutional guidelines for the treatment of neutropenic 
fever or infections associated with neutropenia and for the prevention of febrile neutropenia in subjects with an 
ANC of < 500 cells/mm3
b See Table 5 for dose level reductions. 
8.2.1.3.
Administration of Investigational Product to Subjects with Abnormal Hepatic 
Function
The IP should only be administered if hepatic function is within the parameters established in the 
eligibility criteria. Hepatic toxicity may occur but it is uncommon. Therefore, hepatic 
dysfunction that occurs while the subject is on study should prompt an evaluation to determine 
the cause, including the possibility of metastatic disease and hepatotoxicity from concurrent 
medications, alcohol use, or other factors.
8.2.1.4.
Pulmonary Embolism and Deep Vein Thrombosis
To resume IP administration in the event of a pulmonary embolism or deep vein thrombosis, 
subjects must be started on low molecular weight heparin or similar anticoagulation therapy. 
Grade 4 events must be resolved to Grade ≤ 3 within 21 days to continue IP.
8.2.1.5.
Interstitial Pneumonitis
While participating in this study, subjects should be carefully monitored to prevent or minimize 
the occurrence of interstitial pneumonitis. Careful prestudy screening with continuous on-study 
monitoring for signs and symptoms is required. Should a subject develop symptoms of 
pneumonitis during this study, the timely initiation of appropriate management is required. 
Recommended guidelines are as follows:
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
45
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
1. Before enrollment, evaluate candidate subjects for familial, environmental, or 
occupational exposure to opportunistic pathogens, and do not enroll those with a history 
of slowly progressive dyspnea and unproductive cough, or of conditions such as 
sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity 
pneumonitis, or multiple allergies.
2. During study treatment, provide close attention to episodes of transient or repeated 
dyspnea with unproductive persistent cough or fever. Radiographic evaluation with chest 
x-rays and CT scans (normal or high resolution) may be indicated to evaluate for 
infiltrates, ground-glass opacities, or honeycombing patterns. Pulse oximetry and 
pulmonary function tests can show respiratory and ventilation compromise. 
3. Infections should be ruled out with routine immunological/microbiological methods. A 
transbronchial lung biopsy is not recommended, given its limited value and risk of 
pneumothorax and hemorrhage, and should be reserved for cases with unclear etiology. 
4. Administration of IP should be interrupted upon diagnosis of interstitial pneumonitis and 
subjects permanently discontinued from further IP treatment. After ruling out an 
infectious etiology, IV high-dose corticosteroid therapy should be instituted without 
delay, with appropriate premedication and secondary pathogen coverage. Subjects with 
an added immunological agent may also require immune modulation with azathioprine or 
cyclophosphamide. Appropriate ventilation and oxygen support should be used when 
required. 
8.2.1.6.
Prophylaxis Against Sepsis
In the metastatic pancreatic cancer Phase 3 study (CA046), an increase in cases of non-
neutropenic sepsis was observed with the combination of nab-paclitaxel and gemcitabine. An 
exploratory analysis suggested that the presence of biliary stents may have increased the risk of 
sepsis in that population. Investigators were to provide oral broad spectrum antibiotics to 
subjects who were then to initiate these antibiotics at the first occurrence of fever. Subjects 
enrolled in this clinical trial may not have the same risk of sepsis as metastatic pancreatic cancer 
patients. Subjects should be advised that there could be an increased risk of serious infection and 
they should contact their physician for evaluation when they develop a fever. Fever or similar 
symptoms should be fully evaluated as an early sign of a serious infection (see Section 9.1).
8.2.1.7.
Hypersensitivity Reactions
Hypersensitivity reactions are infrequent with nab-paclitaxel. If they do occur, minor symptoms 
such as flushing, skin reactions, dyspnea, hypotension, or tachycardia may require temporary 
interruption of the infusion. However, severe reactions, such as hypotension requiring treatment, 
dyspnea requiring bronchodilators, angioedema, or generalized urticaria, require immediate 
discontinuation of IP administration and aggressive symptomatic therapy.
Subjects who develop a severe hypersensitivity reaction to nab-paclitaxel should not be 
rechallenged.
8.2.2.
Overdose
Overdose, as defined for this protocol, refers to nab-paclitaxel or gemcitabine dosing only. 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
46
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of 
nab-paclitaxel or gemcitabine to a given subject, regardless of any associated AEs 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 eCRF. See Section 11.1 for the 
reporting of AEs associated with overdose. 
8.3.
Method of Treatment Assignment
Subjects who enter screening will be assigned the next available subject number. All eligible 
subjects will be enrolled to receive nab-paclitaxel in combination with gemcitabine. 
8.4.
Packaging and Labeling
The label(s) for IP will include sponsor name, address and telephone number, the protocol 
number, IP name, dosage form and strength (where applicable), amount of IP per container, lot 
number, expiry date (where applicable), medication identification/kit number, dosing 
instructions, storage conditions, and required caution statements and/or regulatory statements as 
applicable. Additional information may be included on the label as applicable per local 
regulations.
8.5.
Investigational Product Accountability and Disposal 
Celgene (or its designee) will review with the Investigator and relevant site personnel the process 
for IP return, disposal, and/or destruction, including the responsibilities for the site versus 
Celgene (or designee).
The IP refers to both nab-paclitaxel and gemcitabine.
Investigational product vials should be disposed of in accordance with institutional/regional 
requirements, unless otherwise agreed with Celgene. Disposition should be recorded on the 
Investigational Drug Accountability Record Form.
The Investigator, or designee, shall record the dispensing of IP to subjects in the 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 
its 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 study agreement and 
local guidelines permit.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
47
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
8.6.
Investigational Product Compliance
Accurate recording of all IP administration will be made in the appropriate section of the 
subject’s eCRF and source documents. The Investigator or designee is responsible for the 
accountability for all study-specific IP either administered or in their custody during the course 
of the study.
CCI
&(/*(1(35235,(7$5<,1)250$7,21


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
48
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
9.
CONCOMITANT MEDICATIONS AND PROCEDURES
9.1.
Permitted Concomitant Medications and Procedures
All supportive care is permitted.
Ciprofloxacin (or the alternative broad spectrum antibiotic) must be distributed to subject with 
instructions to begin treatment if they experience a febrile episode (temperature of 
38.5°C/101.3°F). Administration of long-term prophylactic ciprofloxacin (or the alternative 
antibiotic) to prevent recurrences in subjects already having experienced a first febrile episode 
will be at the discretion of the treating physician.
Over the course of this study, additional medications may be required to manage aspects of the 
disease state of the subjects, including side effects from study treatments or disease recurrence. 
Supportive care, including but not limited to antiemetic medications, may be administered at the 
discretion of the Investigator.
WBC growth factors may be administered at the discretion of the Investigator, consistent with 
institutional guidelines and with the Prescribing Information for such growth factors. WBC 
growth factors should be used only in patients who have demonstrated prior events of 
neutropenia; primary prophylaxis with WBC growth factors is not permitted.
Erythropoietin may be administered at the discretion of the Investigator, consistent with 
institutional guidelines.
For information regarding other drugs that may interact with either nab-paclitaxel or gemcitabine 
and affect their metabolism, pharmacokinetics, or excretion, see the nab-paclitaxel and 
gemcitabine package inserts (refer to Prescribing Information).
All concomitant treatments of special interest, including blood and blood products for the 
treatment of SAEs (Section 19.2), must be reported on the eCRF.
9.2.
Prohibited Concomitant Medications and Procedures
Other antineoplastic agents or investigational drugs other than what is specified in the protocol 
(as defined in Section 4.1.1 and Section 4.1.2) are prohibited.
9.3.
Required Concomitant Medications and Procedures
Not applicable.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
49
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
10.
STATISTICAL ANALYSES
Statistical analyses for the primary and key secondary endpoints of the study are described 
below. Additional detail on the analyses of these endpoints as well as subgroup analyses will be 
described in the SAP.
The SAP supersedes the analyses described in the protocol should there be differences between 
the two.
10.1.
Overview
This is an international, non-randomized, open-label, multi-center, Phase 2 study of 
nab-paclitaxel plus gemcitabine in subjects with LAPC. This study includes an Investigator’s 
Choice component in order to examine and better understand the place for nab-paclitaxel plus 
gemcitabine within the current treatment paradigms in LAPC. The use of data from this Phase 2 
study will be utilized in planning the study design for the Phase 3 program.
This study consists of 2 parts: a fixed treatment part that consists of a single arm where subjects 
receive nab-paclitaxel plus gemcitabine on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. 
Once 6 cycles have been completed, subjects without disease progression or unacceptable 
toxicity will continue on to the Investigator’s Choice of continuation of treatment with 
nab-paclitaxel plus gemcitabine, chemoradiation therapy, or surgery. If tumor response allows a 
surgical intervention, the subject will be eligible for that treatment as deemed appropriate by the 
investigator. Surgical intervention may occur prior to completing the planned 6 cycles of nab-
paclitaxel plus gemcitabine if subjects demonstrate a major response to therapy.
A consort diagram will be presented showing the relative proportions of subjects going onto 
nab-paclitaxel plus gemcitabine therapy, chemoradiation therapy, or surgical intervention. A data 
listing will also be provided.
At any time during the study, subjects with disease progression or unacceptable toxicity will be 
discontinued from the study treatment. During the study, subjects will have CT/MRI scans every 
56 days (-3/+7 days) until documented progression of disease, withdrawal of consent from active 
participation in the study, lost to follow-up, or death. Tumor evaluations will be assessed by the 
Investigators and response will be determined according to RECIST v1.1 guidelines. Subjects 
who discontinue treatment without disease progression will continue to have CT/MRI scans 
every 56 days (-3/+7 days) until disease progression, withdrawal of consent, lost to follow-up, or 
death. Subjects will then continue to be followed for OS approximately every 90 days by phone
or review of medical records.
10.2.
Study Population Definitions
The population for this study will consist of all subjects enrolled in the study who were 
diagnosed with LAPC. The following study populations will be examined:
!
Intent-to-treat (ITT) population: The ITT population is defined as all subjects enrolled 
in the study who receive at least 1 dose of IP
!
Per-protocol (PP) population: The PP population is defined as all subjects enrolled in 
the study who receive at least 1 dose of IP and fulfill the study enrollment criteria. 
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!


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
50
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
The PP population may be used for additional analyses which will be described in the 
SAP
!
Treated population: The Treated population consists of all subjects who receive at 
least 1 dose of nab-paclitaxel plus gemcitabine
The primary efficacy analysis will be performed on the ITT population. The secondary efficacy 
analyses will be performed on the PP population, and the safety analyses will be performed on 
the Treated population.
10.3.
Sample Size and Power Considerations
The primary endpoint for this study is median TTF. The null (Ho) and alternative (Ha) 
hypotheses for this endpoint is as follows, where M is the median TTF and 5.1 months is the 
median TTF observed in the CA046 study:
Ho:  M ≤ 5.1
Ha:  M > 5.1
A total sample size of 100 subjects will have 80% power to detect a 30% increase in the median 
TTF of 5.1 to 6.6 months (Table 8). The sample size is calculated assuming a one-sided alpha of 
0.05, that subjects will be enrolling for 24 months and that each subject will be followed for a 
minimum of 1 year. One hundred ten subjects will be enrolled assuming a 10% drop out rate.
Table 8:
Power Calculation for Median Time to Treatment Failure and Sample Size
Percent 
Increase in 
Median TTF
Median TTF for the 
Alternative-Hypothesis 
(Months)
Accrual Duration 
(Months)
N
Power
20%
6.1
24
100
0.54
30
100
0.55
30%
6.6
24
100
0.80
30
100
0.81
50%
7.7
24
100
0.99
30
100
0.99
TTF = time to treatment failure.
10.4.
Background and Demographic Characteristics
Subjects’ 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.
Subject characteristics including demographics, disease duration, and relevant medical history at 
baseline will be summarized for the purpose of characterizing the locally advanced subject 
population.
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bjej


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
51
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Prior medications or procedures of special interest (Section 19.2) taken within 30 days of first 
drug administration and all concomitant medications for the treatment of SAEs will be coded to 
therapeutic drug classes and generic drug names using the World Health Organization (WHO) 
Drug Classification. The incidence of prior and concomitant medication usage will be 
summarized. 
Investigator’s Choice
Investigators will be asked at subject enrollment what their preferred treatment would be at the 
conclusion of the 6 cycles of therapy. The intended treatment will then be compared to the actual 
treatment given at the conclusion of the 6 cycles of therapy. A change in the Investigator’s 
preferred treatment will not be considered a treatment failure.
10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent for both treatment 
and follow-up phases. A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
Subject disposition including the number of subjects enrolled, treated, and each reason for 
discontinuation of therapy will be summarized for each part of the study.
10.6.
Efficacy Analysis
All primary and secondary efficacy analyses will be conducted on the ITT population.
10.6.1.
Primary Efficacy Analysis
Time to treatment failure is the primary endpoint for this study and is defined as the time after
the first dose of study therapy to discontinuation of study therapy due to disease progression, 
death (by any cause), or the start of a new non-protocol-defined anticancer therapy. If a subject 
does not progress, die or start a new non-protocol-defined anticancer therapy, or if a subject 
discontinued study therapy, then the subject will be censored on the last tumor assessment date. 
Although the sample size for the study was estimated to detect a 30% increase in the median 
TTF observed in the CA046 study, no formal statistical testing will be done with this endpoint. 
The TTF will be summarized using standard Kaplan-Meier methods. Median TTF and a 2-sided 
90% CI will be reported with the accompanying Kaplan-Meier curve.
10.6.2.
Secondary Efficacy Analyses
Because of the exploratory nature of this study and the lack of statistical testing, no adjustment 
for multiplicity of endpoints is required.
10.6.2.1.
Disease Control Rate at 6 Months
The secondary efficacy endpoint of DCR is calculated by defining responders as the summation 
of all subjects with CR + PR + SD. To quality for DCR calculation, SD must last for ≥ 16 weeks.
This endpoint will be summarized and presented with the 2-sided 90% CI. All subjects 
discontinued from study due to disease progression, death (by any cause), or the start of a new 
non-protocol-defined anticancer therapy will be considered non-responders.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
52
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
10.6.2.2.
Overall Response Rate
Overall response rate will be summarized. Subjects with Investigator-determined CR or PR will 
be considered responders and the ORR will be presented with 90% CIs around the proportion. 
All subjects discontinued from study due to disease progression, death (by any cause), or the 
start of a new non-protocol-defined anticancer therapy will be considered non-responders.
10.6.2.3.
Progression-free Survival
Progression-free survival is defined as the time after the first dose of study therapy to the start of 
disease progression or death (by 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 was 
progression-free. If a subject begins a new anticancer therapy or has palliative radiotherapy or 
surgery at a lesion site prior to documented progression or death then the subject will be 
censored at the last assessment where the subject was documented as progression-free prior to 
intervention. Subjects with 2 or more consecutive missing response prior to a visit with 
documented progression or death will be censored at the last date that the subject was 
documented to be progression-free.
Progression-free survival will be summarized using standard Kaplan-Meier methods. Median 
PFS and the 90% CI will be reported with the accompanying Kaplan-Meier curve.
10.6.2.4.
Evaluation of Overall Survival
Overall survival is defined as the time after the first dose of study therapy to the date of death (by 
any cause). Subjects who are alive will be censored at the last known time that the subject was 
alive.
Overall survival of nab-paclitaxel plus gemcitabine will be summarized by median survival time 
with 90% CI and the accompanying Kaplan-Meier curve.
10.6.2.5.
Evaluation of Health-related Quality of Life
Differences in outcomes from baseline, during treatment, and after treatment for the EORTC 
QLQs, EORTC QLQ-C30 and QLQ-PAN26 will be will be described in an analysis plan 
separate from the SAP. 
 
10.7.
Safety Analysis
All subjects who receive at least 1 dose of nab-paclitaxel plus gemcitabine (ie, Treated 
population; see Section 10.2) will be evaluated for safety. The number and percent of subjects 
reporting AEs (including treatment-emergent laboratory abnormalities) will be summarized by
system organ class, and preferred term. All SAEs will be tabulated separately as well as included 
with all reported AEs.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
53
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
10.8.
Interim Analysis
An interim analysis of the DCR will be conducted after all subjects have completed 6 cycles of 
nab-paclitaxel plus gemcitabine, discontinued therapy due to disease progression, died from any 
cause, or started a new non-protocol-defined anticancer therapy prior to completing 6 cycles of 
therapy. The results of this analysis will be provided in the final clinical study report following 
study completion.
10.9.
Other Topics
No other topic will be studied.
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&(/*(1(35235,(7$5<,1)250$7,21


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
54
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An 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, PD assessed using the RECIST v1.1 guidelines of LAPC will not 
require reporting as an AE.
Abuse, withdrawal, sensitivity or toxicity to an investigational product should be reported as an 
AE. Overdose, accidental or intentional, whether or not it is associated with an AE should be 
reported on the overdose CRF. (See Section 8.2.2 for the definition of overdose.) Any sequela 
of an accidental or intentional overdose of an investigational product should be reported as an 
AE on the AE CRF. If the sequela of an overdose is an SAE, then the sequela must be reported 
on an SAE report form and on the AE CRF. The overdose resulting in the SAE should be 
identified as the cause of the event on the SAE report form and CRF but should not be reported 
as an SAE itself.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for nab-paclitaxel, or 
gemcitabine 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 and those SAEs made known to the Investigator at any time 
thereafter that are suspected of being related to IP. Adverse events and SAEs will be recorded on 
the AE page of the eCRF and in the subject’s source documents. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form or approved equivalent form.
Safety Follow-up
Subjects who discontinue treatment with nab-paclitaxel plus gemcitabine for any reason will 
have a Safety Follow-up Visit 28 days or End of Treatment Visit, whichever occurs later).
Subjects who discontinue treatment with nab-paclitaxel plus gemcitabine and are planned to 
undergo chemoradiation or surgery therapy will have the safety visit before that treatment.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
55
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
For subjects who undergo chemo radiation, AEs will be assessed until 28 days after the last dose 
of chemoradiation or the 28-day chemoradiation.
For subjects who undergo surgery, AEs will be assessed until 28 days after the surgery.
11.2.
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to: 
11.2.1.
Seriousness 
An 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.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
56
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
!
A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the eCRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE.
!
An elective treatment of a pre-existing condition unrelated to the studied indication. 
!
Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to IP, action taken regarding IP, and outcome.
11.2.2.
Severity / Intensity
For both AEs and SAEs, the Investigator must assess the severity/intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current active minor version of National Cancer Institute (NCI) Common Terminology Criteria 
for Adverse Events (CTCAE v4.0) 
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.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
57
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
11.2.3.
Causality 
The Investigator must determine the relationship between the administration of IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
Means the causal relationship of the adverse event to IP 
administration is unlikely or remote, or other medications, 
therapeutic interventions, or underlying conditions provide a 
sufficient explanation for the observed event.
Suspected:
Means there is a reasonable possibility that the administration 
of IP caused the adverse event.  ‘Reasonable possibility’ means 
there is evidence to suggest a causal relationship between the IP 
and the adverse event.
Causality should be assessed and provided for every AE/SAE based on currently available 
information. Causality is to be reassessed and provided as additional information becomes 
available.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP 
that has not been manufactured or provided by 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, interruption, 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.
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!


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
58
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a SAE. 
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF. If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE. 
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
11.4.
Pregnancy
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 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 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
59
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
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) and 
those made known to the Investigator at anytime thereafter that are suspected of being related to 
IP. SAEs occurring prior to treatment (after signing the ICF) will be captured.
The SAE report should provide a detailed description of the SAE and include a concise summary 
of hospital records and other relevant documents. If a subject died and an autopsy has been 
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available. Any follow-up data should be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety. 
Where required by local legislation, the Investigator is responsible for informing the IRB/EC of 
the SAE and providing them with all relevant initial and follow-up information about the event. 
The Investigator must keep copies of all SAE information on file including correspondence with 
Celgene and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than five (5) business 
days. Urgent queries (eg, missing causality assessment) may be handled by phone.
11.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to nab-paclitaxel based on the Investigator’s Brochure. 
In the United States, all suspected unexpected serious adverse reactions (SUSARs) will be 
reported in an expedited manner in accordance with 21 CFR 312.32.
For countries within the 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.
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, gemcitabine, based on the 
United Kingdom Summary of Product Characteristics (SmPC). 
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);
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EDMS Doc. Number:
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Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
60
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
!
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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Report 
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
61
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
12.
DISCONTINUATIONS
The reason for study 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 with the decision to 
discontinued/withdraw a subject due to an AE (any unacceptable toxicity) and forward 
appropriate supporting documents for review and discussion.
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 LAPC treatment/therapy, unless the subject has specifically withdrawn 
consent from further follow-up. The Investigator should make every effort to obtain minimal 
information regarding the subject’s survival status before determining the subject is lost to 
follow-up.
12.1.
Study Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the IP:
!
Adverse event(s)
!
Disease progression 
!
Investigator’s decision
!
Withdrawal of consent 
!
Death
!
Lost to follow-up
!
Protocol violation
All subjects discontinued from nab-paclitaxel plus gemcitabine for any reason will have a 
treatment discontinuation visit at the time of nab-paclitaxel plus gemcitabine discontinuation and 
should undergo early termination procedures.
All subjects discontinued from nab-paclitaxel plus gemcitabine 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.
12.2.
Study Discontinuation
The following are considered sufficient reasons for discontinuing a subject from the study:
!
Withdrawal of consent (decision from the subject not to provide follow-up 
information)
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12.2
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
62
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
!
Investigator’s decision
!
Death
!
Lost to follow-up
The following may be considered a sufficient reason for discontinuing a subject from the study:
!
Protocol violation
!
AE or unacceptable toxicity
12.3.
Subject Replacement
Subjects who discontinue will not be replaced.
CCI
&(/*(1(35235,(7$5<,1)250$7,21


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
63
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research 
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page).This global Emergency 
Call Center is available 24 hours a day and 7 days a week. The representatives are responsible 
for obtaining your call-back information and contacting the on call Celgene/Contract Research 
Organization (CRO) Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls.
13.2.
Emergency Identification of Investigational Products
This is an open-label study; therefore, IP will be identified on the package labeling.
CCI
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the pack


EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
64
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, 
and Investigator abide by Good Clinical Practice (GCP), as described in International 
Conference on Harmonization (ICH) Guideline E6 and in accordance with the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
IRB/EC prior to commencement. The Investigator will conduct all aspects of this study in 
accordance with applicable national, state, and local laws of the pertinent regulatory authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. Celgene staff or an authorized representative will evaluate and approve all 
Investigators who in turn will select their staff.
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions. 
The Investigator should maintain a list of Sub-investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The Investigator is responsible for keeping a record of all subjects who sign an ICF and are 
screened for entry into the study. Subjects who fail screening must have the reason(s) recorded in 
the subject’s source documents.
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The Investigator must ensure timely and accurate completion of eCRFs and queries.
14.3.
Subject Information and Informed Consent
The Investigator must obtain informed consent of a legal representative prior to any study related 
procedures.
Documentation that informed consent occurred prior to the subject’s entry into the study and of 
the informed consent process should be recorded in the subject’s source documents including the 
date. The original ICF signed and dated by the subject and by the person consenting the subject 
prior to the subject’s entry into the study, must be maintained in the Investigator’s study files and 
a copy given to the subject. In addition, if a protocol is amended and it impacts the content of the 
informed consent, the ICF must be revised. Subjects participating in the study when the amended 
protocol is implemented must be re-consented with the revised version of the ICF. The revised 
ICF signed and dated by the subject and by the person consenting the subject must be maintained 
in the Investigator’s study files and a copy given to the subject.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
65
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
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.
Investigational Product can only be supplied to an Investigator by Celgene or its authorized 
representative after documentation on all ethical and legal requirements for starting the study has 
been received by Celgene or its authorized representative. This documentation must also include 
a list of the members of the IRB/EC and their occupation and qualifications. If the IRB/EC will 
not disclose the names, occupations and qualifications of the committee members, it should be 
asked to issue a statement confirming that the composition of the committee is in accordance 
with GCP. For example, the IRB General Assurance Number may be accepted as a substitute for 
this list. Formal approval by the IRB/EC should mention the protocol title, number, amendment 
number (if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
66
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
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 AEs 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-PANC-007
Celgene Corporation
Confidential and Proprietary
67
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
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;
!
Investigational Product 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-PANC-007
Celgene Corporation
Confidential and Proprietary
68
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
!
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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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
69
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
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 SOPs.
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-PANC-007
Celgene Corporation
Confidential and Proprietary
70
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
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.
CCI
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
71
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
18.
REFERENCES
American Cancer Society. Pancreatic Cancer 2013.
Alvarez R, Musteanu M, Garcia-Garcia E, et al. Stromal disrupting effects of nab-paclitaxel in 
pancreatic cancer. Br J Cancer. 2013:109:926-933.
Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early- and late-
stage human malignancies. Science Translational Med. 2014;6(224):1-11.
Burris HA III, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with
gemcitabine as first-line therapy for patients with advanced pancreas cancer:  a randomized trial.  
J Clin Oncol. 1997;15:2403-2413.
Cancer Research UK. CancerStats: Cancer Worldwide. Sep 2011.
Commisso C, Davidson SM, Soydaner-Azeloglu RG, et al. Macropinocytosis of proteins is an 
amino acid supply route in Ras-transformed cells. Nature. 2013;497:633-637.
Conroy T, Desseigne F, Ychou M, et al.  FOLFIRINOX versus gemcitabine for metastatic 
pancreatic cancer. N Engl J Med. 2011;364:1817-1825.
Desai N, Trieu V, Yao Z, et al. Increased antitumor activity, intratumor paclitaxel 
concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-
007, compared with cremophor-based paclitaxel. Clin Cancer Res. 2006;12(4):1317-24.
Diaz LA Jr, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 
2014:32(6):579-586.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: 
revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. 
Ferlay J, Shin HR, Bray F, et al. GLOBOCAN 2008 v2.0, Cancer incidence and mortality 
worldwide: IARC Cancer Base No. 10 [Internet].Lyon, France: International Agency for 
Research on Cancer; 2010. Available from: http://globocan.iarc.fr.
Frese KK, Neesse A, Cook N, et al. nab-Paclitaxel potentiates gemcitabine activity by reducing 
cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer Dis. 2012;2(3):260-
269.
Hammel P, Huguet F, Van Laethem J-L, et al. Comparison of chemoradiotherapy (CRT) and 
chemotherapy (CT) in patients with locally advanced pancreatic cancer (LAPC) controlled after 
4 months of gemcitabine with or without erlotinib: Final results of the international phase III 
LAP 07 study. J Clin Oncol. 2013;31(suppl; abstr #LBA4003).
Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2010, 
National Cancer Institute. 2013. Available at: http://seer.cancer.gov/csr/1975_2011/. Accessed 
09 May 2014.
Loehrer PJ Sr, Feng Y, Cardenes H, et al. Gemcitabine alone versus gemcitabine plus 
radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative 
Oncology Group trial. J Clin Oncol. 2011;29(31):4105-4112.
Malvezzi M, Bertuccio P, Levi F, La Vecchia C, Negri E. European cancer mortality predictions 
for the year 2013. Ann Oncol. 2013;24:792-800.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
72
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
Misale S, Arena S, Lamba S, et al. Blockade of EGFR and MEK intercepts heterogeneous 
mechanisms of acquired resistance to anti-EGFR therapies in colorectal cancer.  Science 
Translational Med. 2014;6(224):1-10.
National Comprehensive Cancer Network (NCCN) v1.2013. NCCN Clinical Practice Guidelines 
in Oncology: pancreatic adenocarcinoma. Available at: 
http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed 15 Apr 2013.
National Comprehensive Cancer Network (NCCN) v1.2014. NCCN Clinical Practice Guidelines 
in Oncology: pancreatic adenocarcinoma. Available at: 
http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed 24 Apr 2014.
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655.
Philip PA. Locally advanced pancreatic cancer: where should we go from here? J Clin Oncol.
2011 Nov 1;29(31):4066-8. DOI: 10.1200/JCO.2011.37.2532; published online ahead of print at 
www.jco.org on October 3, 2011.
Seufferlein T, Bachet JB, Van Cutsem E, Rougier P. Pancreatic adenocarcinoma: ESMO-ESDO 
Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 
2012;23(Suppl 7):vii33-vii40.
Siegel R, Ma J, Zou A, Jemal A, et al. Cancer Statistics, 2014. CA Cancer J Clin. 2014,64:9-29.
Von Hoff DD, Ramanathan RK, Borad MJ, et al. Gemcitabine plus nab-paclitaxel is an active 
regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol.
2011;29(34):4548-4554.
Von Hoff DD, Ervin T, Arena FP, et al. Randomized Phase III study of weekly nab-paclitaxel 
plus gemcitabine vs gemcitabine alone in patients with metastatic adenocarcinoma of the 
pancreas (MPACT).  Poster presented at the 2013 Gastrointestinal Cancers Symposium in San 
Francisco, California, January 24-26, 2013.
Werner J, Combs SE, Springfeld C, et al. Advanced-stage pancreatic cancer: therapy options. 
Nat Rev Clin Oncol. 2013;10:323-333.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
73
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
19.
APPENDICES
19.1.
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
Source: Oken, 1982.
19.2.
List of Concomitant Medications or Procedures of Special Interest
!
Anti-infectives
!
Steroids
!
Narcotics
!
IV fluids
!
For blood support (eg, transfusions, growth factors)
!
For cardiac events (eg, myocardial infarction, angina pectoris, heart failure, 
uncontrolled hypertension, clinically significant cardiac dysrhythmia or 
electrocardiogram (ECG) abnormality)
!
For cerebrovascular accident, transient ischemic attack, or seizure
!
For peripheral sensory neuropathy
!
For ascites
!
For lung disease
!
For prevention or therapy of nausea/vomiting 
19.3.
List of Laboratory Values of Special Interest
!
Liver functions
!
Renal functions
!
Albumin levels
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EDMS Doc. Number:
Celgene Signing Page
This is a representation of an electronic record that was signed electronically in Livelink.
This page is the manifestation of the electronic signature(s) used in compliance with
the organizations electronic signature policies and procedures.
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EDMS Doc. Number:
nab-paclitaxel
Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
3
ABI-007-PANC-007 Amendment 1.0 Final: 06 Feb 2018
1.
JUSTIFICATION FOR AMENDMENT
Significant changes included in this amendment are summarized below:
!
Administrative Amendment to update details of Medical Monitor and Therapy Area 
Head. Updated details found in the MEDICAL MONITOR / EMERGENCY CONTACT 
INFORMATION and CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE 
sections.
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nab-paclitaxel
Statistical Analysis Plan. Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
1
STATISTICAL ANALYSIS PLAN
nab-Paclitaxel (Abraxane®) plus Gemcitabine in Subjects with Locally Advanced Pancreatic
Cancer (LAPC): An International, Open-label, Multi-center, Phase 2 Study (LAPACT)
STUDY DRUG:
nab®1-PACLITAXEL 
PROTOCOL NUMBER:
ABI-007-PANC-007
DATE FINAL:
13 Nov 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.
1 nab® is a registered trademark of Celgene Corporation
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nab-paclitaxel
Statistical Analysis Plan. Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
2
Table of Contents
SIGNATURE PAGE.................................................................................................................................... 5
1.
LIST OF ABBREVIATIONS...................................................................................................... 7
2.
INTRODUCTION................................................................................................................... 9
3.
STUDY OBJECTIVES ............................................................................................................ 10
3.1.
Primary Objective.............................................................................................................. 10
3.2.
Secondary Objectives ........................................................................................................ 10
4.
INVESTIGATIONAL PLAN.................................................................................................... 11
4.1.
Overall Study Design and Plan ........................................................................................... 11
4.2.
Study Endpoints ................................................................................................................ 13
4.2.1.
Primary Endpoint .............................................................................................................. 13
4.2.2.
Secondary Endpoints......................................................................................................... 13
4.3.
Stratification, Randomization and Blinding ........................................................................ 14
4.4.
Sample Size Determination................................................................................................ 14
5.
GENERAL STATISTICAL CONSIDERATIONS .......................................................................... 15
5.1.
Reporting Conventions...................................................................................................... 15
5.2.
Analysis Populations.......................................................................................................... 16
5.2.1.
Intent-to-treat (ITT) Population ......................................................................................... 16
5.2.2.
Per Protocol (PP) Population ............................................................................................. 16
5.2.3.
Treated Population............................................................................................................ 16
6.
SUBJECT DISPOSITION ....................................................................................................... 17
7.
PROTOCOL VIOLATIONS .................................................................................................... 18
8.
DEMOGRAPHICS AND BASELINE CHARACTERISTICS........................................................... 19
8.1.
Demographics ................................................................................................................... 19
8.2.
Baseline Lesion Status ....................................................................................................... 19
8.3.
Medical History ................................................................................................................. 19
8.4.
Prior Therapy .................................................................................................................... 20
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nab-paclitaxel
Statistical Analysis Plan. Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
3
8.5.
Prior and Concomitant Medications .................................................................................. 20
8.5.1.
Prior Medications.............................................................................................................. 20
8.5.2.
Concomitant Medications.................................................................................................. 20
8.6.
Concomitant Procedures/Surgeries ................................................................................... 20
9.
STUDY TREATMENTS AND EXTENT OF EXPOSURE .............................................................. 22
9.1.
Treatment Duration........................................................................................................... 22
9.2.
Cumulative Dose ............................................................................................................... 22
9.3.
Dose Intensity ................................................................................................................... 22
9.4.
Relative Dose Intensity...................................................................................................... 22
9.5.
Dose Reduction/Delay/Omission ....................................................................................... 23
9.6.
Overdose........................................................................................................................... 23
10.
EFFICACY ANALYSIS ........................................................................................................... 25
10.1.
Multiplicity........................................................................................................................ 25
10.2.
Analysis of Primary Efficacy Endpoint ................................................................................ 25
10.3.
Analysis of Secondary Efficacy Endpoints........................................................................... 25
10.3.1.
Disease Control Rate ......................................................................................................... 25
10.3.2.
Overall Response Rate....................................................................................................... 26
10.3.3.
Progression-free Survival................................................................................................... 26
10.3.4.
Overall Survival ................................................................................................................. 28
10.3.5.
Tumor Response................................................................................................................ 28
10.3.6.
Subsequent Anti-cancer Therapy....................................................................................... 28
10.3.7.
Health-related Quality of Life ............................................................................................ 29
10.5.
Other Efficacy Analyses ..................................................................................................... 29
11.
SAFETY ANALYSIS............................................................................................................... 30
11.1.
Adverse Events.................................................................................................................. 30
11.2.
Adverse Events of Special Interest..................................................................................... 31
11.2.1.
AE of Special Interest......................................................................................................... 31
11.2.2.
Peripheral Neuropathy...................................................................................................... 33
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nab-paclitaxel
Statistical Analysis Plan. Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
4
11.3.
Clinical Laboratory Evaluations.......................................................................................... 33
11.3.1.
Clinical Chemistry.............................................................................................................. 33
11.3.2.
Hematology....................................................................................................................... 33
11.3.3.
Serum Carbohydrate Antigen 19-9 (CA19-9) ...................................................................... 33
11.4.
Vital Sign Measurements................................................................................................... 33
11.5.
Physical Examination......................................................................................................... 34
11.6.
ECOG Performance Score .................................................................................................. 34
11.7.
Other Safety Analysis......................................................................................................... 34
12.
INTERIM ANALYSIS ............................................................................................................ 35
12.1.
Analysis Methods .............................................................................................................. 35
13.
CHANGES TO THE STATISTICAL ANALYSES SECTION OF THE PROTOCOL ............................. 36
14.
REFERENCES...................................................................................................................... 37
15.
APPENDICES...................................................................................................................... 38
15.1.
Handling of Dates.............................................................................................................. 38
15.2.
Date Imputation Guideline ................................................................................................ 38
15.2.1.
Impute Missing Adverse Events/ Prior or Concomitant Medications/Procedures............... 38
LIST OF TABLES
Table 1:
Abbreviations and Specialist Terms..........................................................................7
Table 2:
Power Calculation for Median Time to Treatment Failure and Sample Size ............14
Table 3:
Censoring Rules for Progression-free Survival........................................................27
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nab-paclitaxel
Statistical Analysis Plan. Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
7
1.
LIST OF ABBREVIATIONS
Table 1:
Abbreviations and Specialist Terms
AE
Adverse event
ALT
Alanine aminotransferase (SGPT)
AST
Aspartate aminotransferase (SGOT)
BMI
Body mass index
BSA
Body surface area
CA19-9
Carbohydrate antigen 19-9
CBC
Complete blood cell
CI
Confidence interval
CRF
Case report form
CT
Computerized tomography
CTCAE
Common Terminology Criteria for Adverse Events
DCR
Disease control rate
ECOG
Eastern Cooperative Oncology Group
EORTC
European Organization for Research and Treatment of Cancer
EOT
End of trial
Hgb
Hemoglobin
IC
Investigator’s choice
IP
Investigational product
IV
Intravenous
LAPC
Locally advanced pancreatic cancer
MedDRA
Medical Dictionary for Regulatory Activities
MRI
Magnetic resonance imaging
NA
Not applicable
NCI
National Cancer Institute
ND
Not done
NQ
Not quantifiable 
ORR
Overall Response Rate
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nab-paclitaxel
Statistical Analysis Plan. Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
8
OS
Overall survival
PFS
Progression-free survival
PT
Preferred term
QoL
Quality of life
RECIST
Response Evaluation Criteria in Solid Tumors
RNL
Ratio of lymphocytes to neutrophils
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SAS
Statistical Analysis Software
SGOT
Serum glutamic oxaloacetic transaminase (AST)
SGPT
Serum glutamic pyruvic transaminase (ALT)
SI
Standard international
SOC
System organ class
STDEV
Standard deviation
TEAE
Treatment-emergent adverse event
TTF
Time to treatment failure
ULN
Upper limit of normal
WBC
White blood cell
WHO
World Health Organization
WNL
Within normal limit
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nab-paclitaxel
Statistical Analysis Plan. Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
9
2.
INTRODUCTION
This statistical analysis plan (SAP) describes the analyses and data presentations for Celgene’s 
protocol ABI-007-PANC-007 “nab-Paclitaxel (Abraxane®) plus Gemcitabine in Subjects with 
Locally Advanced Pancreatic Cancer (LAPC): An International, Open-label, Multi-center, Phase 
2 Study (LAPACT)” which was issued on 27 Aug 2014. It contains definitions of analysis 
populations, derived variables and statistical methods for the analysis of efficacy and safety.
These analyses include one interim analysis and one final analysis. Throughout this SAP, the 
treatment arm will be referred to as nab-paclitaxel and gemcitabine. The purpose of the SAP is to 
ensure the credibility of the study findings by pre-specifying the statistical approaches to any 
data analysis prior to database lock. This SAP will be finalized and signed prior to the clinical 
database lock for the interim analysis. Significant changes after interim analysis and prior to final 
database lock will be documented in Final SAP Amendment. All statistical analyses detailed in 
this SAP will be conducted using SAS® version 9.2 or higher. 
The SAP supersedes the analyses described in the protocol should there be differences between 
the two.
P is to 
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3.
STUDY OBJECTIVES
3.1.
Primary Objective
The primary objective of this study is to evaluate the time to treatment failure (TTF) in LAPC 
subjects treated with nab-paclitaxel plus gemcitabine as induction therapy followed by 
Investigator’s Choice of treatment.  
3.2.
Secondary Objectives
The secondary objectives are:
!
To evaluate the disease control rate (DCR) after the first 6 cycles of nab-paclitaxel 
and gemcitabine;
!
To evaluate the overall response rate (ORR);
!
To evaluate progression-free survival (PFS) and overall survival (OS);
!
To evaluate the overall safety profile;
!
To evaluate the subject’s health-related QoL (will be described in an analysis plan 
separate from this SAP).
 
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nab-paclitaxel
Statistical Analysis Plan. Protocol ABI-007-PANC-007
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4.
INVESTIGATIONAL PLAN
4.1.
Overall Study Design and Plan
This is an international, non-randomized, open-label, multi-center, Phase 2 study in subjects with 
LAPC treated with nab-paclitaxel and gemcitabine for 6 cycles followed by an Investigator’s 
Choice of continuation of treatment with nab-paclitaxel and gemcitabine, chemoradiation 
therapy, or surgery. 
This study consists of 2 parts (see Figure 1): 
1) A treatment induction phase that consists of a single arm where subjects receive nab-
paclitaxel and gemcitabine on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. 
2) Investigator’s Choice phase: once 6 cycles of study drug have been completed, subjects 
without disease progression or unacceptable toxicity may continue on to the Investigator’s 
Choice of either: continuation of treatment with nab-paclitaxel and gemcitabine, chemoradiation
therapy, or surgery. If tumor response allows for surgical intervention, the subject will be eligible 
for that treatment as deemed appropriate by the investigator. Surgical intervention may occur 
prior to completing the planned 6 cycles of nab-paclitaxel and gemcitabine if subjects 
demonstrate a major response to therapy.
Subjects who discontinue treatment with nab-paclitaxel and gemcitabine, chemoradiation, or 
surgery for any reason will have a safety follow-up visit 28 days after treatment discontinuation 
and will be followed for disease progression approximately every 56 days. All subjects will be 
followed for overall survival (OS) and post-study anticancer therapies approximately every 90 
days by phone or review of medical records until death, withdrawal of consent, or lost to follow-
up. At any time during the study, subjects with disease progression or unacceptable toxicity will 
be discontinued from the study treatment. During the study, subjects, including those who 
discontinue treatment without disease progression, will have CT/MRI scans every 56 days (-3/+7 
days) until documented progression of disease, withdrawal of consent from active participation 
in the study, lost to follow-up, or death, whichever is earliest. Tumor evaluations will be assessed 
by the Investigators and response will be determined according to RECIST v1.1 guidelines.
The study will consist of the following visits: 
Screening/re-screening Assessments: to be obtained ≤ 14 days prior to study drug 
administration. 
Treatment: Treatment will commence on Day 1 for 6 cycles:

nab-Paclitaxel 125 mg/m2 IV infusion over approximately 30 to 45 minutes on Days 1, 
8, and 15, followed by gemcitabine 1000 mg/m2 IV infusion over approximately 30 
minutes on Days 1, 8, and 15 of each 28-day cycle.
Once 6 cycles have been completed, subjects without disease progression or unacceptable 
toxicity will continue on to the Investigator’s Choice treatment. See description in study parts
(see Figure 1).
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nab-paclitaxel
Statistical Analysis Plan. Protocol ABI-007-PANC-007
Celgene Corporation
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Safety Follow-up: Subjects who discontinue treatment with nab-paclitaxel and gemcitabine for 
any reason will have a safety follow-up visit 28 days after treatment discontinuation. Subjects 
who are planned to undergo chemoradiation or surgery will have a safety visit pretreatment (with 
chemoradiation or surgery), and at 28 days after discontinuation with chemoradiation, or 28 days
post surgery.
Efficacy Follow-up: Subjects who discontinue treatment without disease progression will 
continue to have CT/MRI scans every 56 days (-3/+7 days) until documented disease 
progression, withdrawal of consent, lost to follow-up, or death (by any cause), whichever is 
earliest.
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 
 analysis, whichever is the later date.
Figure 1:
Overall Study Design
CR = complete response; IV = intravenously; PD = progressive disease; PR = partial response; SD = stable disease.
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nab-paclitaxel
Statistical Analysis Plan. Protocol ABI-007-PANC-007
Celgene Corporation
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4.2.
Study Endpoints
4.2.1.
Primary Endpoint
The primary endpoint of the study is TTF, measured as the time from the first dose of study 
therapy to treatment failure. Treatment failure is defined as discontinuation of study therapy due 
to disease progression, death (by any cause), or the start of a non-protocol-defined anticancer 
therapy.
4.2.2.
Secondary Endpoints
4.2.2.1.
Secondary Efficacy Endpoints
The secondary efficacy endpoints included in this SAP are:
!
The disease control rate (DCR) after 6 cycles of nab-paclitaxel and gemcitabine, 
defined as the combined incidence of complete response (CR), partial response (PR) 
and stable disease (SD);  
!
Overall response rate(ORR), defined as the combined incidence of CR and PR;
!
Progression-free survival (PFS) defined as the time from the first dose of study 
therapy to disease progression or death (by any cause);
!
Overall survival (OS) defined as the time from the first dose of study therapy to death 
(by any cause);
!
Differences in outcomes from baseline, during treatment, and after treatment with 
nab-paclitaxel and gemcitabine for the European Organization for Research and 
Treatment of Cancer (EORTC) quality of life questionnaires (QLQ), EORTC 
QLQC30 and QLQ-PAN26 (will be described in an analysis plan separate from this 
SAP).
4.2.2.2.
Secondary Safety Endpoints
The safety endpoints are:
!
Treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse 
events (SAEs);
!
Laboratory results (chemistries and blood counts) analyzed using NCI CTCAE V4.0;
!
Other safety parameters including incidence of dose reductions, delays and omissions. 
 
 
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4.3.
Stratification, Randomization and Blinding
Not applicable for this study.
4.4.
Sample Size Determination
The primary endpoint for this study is median TTF. The null (H0) and alternative (Ha) 
hypotheses for this endpoint are as follows, where M is the median TTF and 5.1 months is the 
median TTF observed in the CA046 study:
H0:  M ≤5.1
Ha:  M > 5.1
A total sample size of 100 subjects will have 80% power to detect a 30% increase in the median 
TTF of 5.1 to 6.6 months (Table 2). The sample size is calculated assuming a one-sided alpha of 
0.05, that subjects will be enrolling for 24 months and that each subject will be followed for a 
minimum of 1 year. One hundred ten subjects will be enrolled assuming a 10% drop out rate.
Table 2:
Power Calculation for Median Time to Treatment Failure and Sample Size
Percent increase in 
median TTF
Median TTF for the
Alternative-Hypothesis
(Months)
Accrual 
Duration
(Months)
N
Power
20%
6.1
24
100
0.54
30
100
0.55
30%
6.6
24
100
0.80
30
100
0.81
50% 
7.7
24
100
0.99
30
100
0.99
TTF = time to treatment failure.
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5.
GENERAL STATISTICAL CONSIDERATIONS
5.1.
Reporting Conventions
!
For the purposes of data analysis, two analysis phases for post-baseline data are 
defined: the induction chemotherapy phase and the Investigator’s Choice phase.
!
Data from all study sites will be combined for analysis;
!
P-values will be rounded to 4 decimal places. P-values that round to 0.0000 will be 
presented as ‘<0.0001’ and p-values that round to 1.000 will be presented as 
‘>0.9999’; 
!
Confidence intervals (CIs) will be presented as 2-sided 90% CIs unless specified 
differently in specific 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 (STDEV), Q1 and Q3, 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;
!
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 study site, subject ID and date 
of procedure or event;
!
All analysis and summary tables will have the analysis population sample size (i.e., 
number of subjects) in the column heading;
!
The day of the first dose of any study drug will be defined as Day 1; 
!
Each cycle starts with the date of the first dose date of the cycle, and the last day of 
the cycle is the day before the first dose date of the subsequent cycle; 
!
For the last cycle, the last day of the cycle is the treatment completion or 
discontinuation date on the case report form (CRF). For subjects who are still on 
treatment at the time of the clinical cutoff, a nominal 28 days will be used as the last 
cycle duration. 
!
In by cycle analyses, assessments taken pre-dose on Day 1 of a given cycle (e.g. 
laboratory measures) will be grouped with the previous cycle;
!
Baseline value will be defined as the last non-missing value on or before the date that 
the first dose of study drug is administered; if multiple values are present for the same 
date, the average of these values will be used as the baseline. For subjects who were 
not treated, the baseline will be the assessment value taken on the visit of Cycle 1 
Day 1 if available; otherwise, the value on or prior to first dose date will be used; 
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!
Partial dates will be imputed based on the rules specified in Section 15.2;
!
All laboratory data will be reported using standard international (SI) units; 
!
Summaries of the most severe toxicity grade in clinical laboratory in each treatment 
cycle and most severe grade post-baseline overall and shifts from baseline to most 
severe toxicity grade post-baseline overall will include all scheduled and unscheduled 
assessments;
!
SAS∀Version 9.2 (or higher) will be the statistical software package used to produce 
all data summaries, listings, graphs, and statistical analyses.
5.2.
Analysis Populations
The population for this study will consist of all subjects enrolled in the study who were 
diagnosed with LAPC. 
All statistical analyses including but not limited to tables, listings and graphs will be based on the 
definitions of analysis populations in this SAP.  If there are any discrepancies between SAP and 
protocol, the definitions in SAP overwrite those in the protocol.
5.2.1.
Intent-to-treat (ITT) Population
The ITT population is defined as all subjects enrolled in the study.
5.2.2.
Per Protocol (PP) Population
The PP population is defined as all subjects enrolled in the study who receive at least 1 dose of 
investigational product (nab-paclitaxel and gemcitabine) and fulfill the study enrollment criteria. 
5.2.3.
Treated Population 
The Treated population consists of all subjects who receive at least 1 dose of nab-paclitaxel or 
gemcitabine.  Treated population is used for all safety analyses.
A summary of analysis populations will be presented.
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6.
SUBJECT DISPOSITION
The number of subjects with screen failure will be summarized. The subjects with the violated 
eligibility criteria will be included in the summary. A summary of subject disposition will be 
presented for the ITT population. The number of subjects treated and reasons for treatment 
discontinuation for both induction phase and Investigator’s choice phase will be presented. 
Reasons for discontinuation of the study (i.e., no more follow up visit and no longer participating
the study) will be summarized per CRF for all treated subjects.
The enrollment will also be summarized by study site. 
Listings of subject eligibility and listings for subject disposition and study disposition will also be 
provided. 
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7.
PROTOCOL VIOLATIONS
The protocol deviations/violations will be identified and assessed by clinical research physician 
or designee following institution standard operational procedures. The protocol violations will be 
summarized for the ITT population. 
A listing of subjects with protocol violations in the ITT population will be provided. 


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8.
DEMOGRAPHICS AND BASELINE CHARACTERISTICS
The demographics and baseline characteristics will be summarized. No inferential statistics will 
be presented. Individual subject listings will be provided to support the summary tables.
8.1.
Demographics
The following characteristics will be summarized and listed:
!
Age (years)
!
Age category (<65 years , 65 - 75 years, and > 75 years)
!
Sex
!
Primary race
!
Ethnicity
!
Height (cm) and weight (kg)
!
Body mass index 
!
Baseline ECOG performance status
!
Physician assessment of peripheral neuropathy (PN) at baseline
!
Time from primary diagnosis to first dose (days)
Age will be calculated as follows: Age = maximum integer # ([Date of Informed Consent – Date 
of Birth +1] / 365.25). 
The demographics and baseline characteristics will be summarized for ITT population. 
The baseline albumin, serum CA 19-9 level and specified categories for serum CA 19-9 level
will be summarized descriptively for ITT population.
8.2.
Baseline Lesion Status
For lesions identified at baseline, descriptive statistics will be provided for the following 
variables based on ITT population. 
!
Number of target lesions
!
Sum of longest lesion diameters (mm) of target lesions
8.3.
Medical History
A frequency summary of relevant medical history will be presented by system organ class (SOC) 
and preferred term for the ITT population according to Medical Dictionary for Regulatory
Activities (MedDRA version 20.0).
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frequency
and prefe
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ctivi
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8.4.
Prior Therapy
Subjects who had prior anticancer therapy for pancreatic carcinoma will be excluded from this 
study. Prior anticancer surgeries will be coded using MedDRA version 20.0. The number and 
percentage of subjects who had any prior cancer surgery for this disease by system organ class 
and preferred term will be presented for the ITT population. The prior anticancer surgery data 
will be presented in a listing. 
8.5.
Prior and Concomitant Medications
Medications reported on the Prior and Concomitant Medications CRF will be coded using WHO 
Drug Enhanced March, 2017 and will be summarized by Anatomical Therapeutic Chemical 
(ATC) classification level 1 and preferred drug name for the ITT population. Concomitant 
medications and procedures of special interest as listed in Protocol section 19.2 will be 
summarized separately. 
8.5.1.
Prior Medications
A prior medication will be any medication stopped prior to the date of the first dose of study 
drug. A summary will be presented showing the number and percentage of subjects who took 
prior medications by therapeutic drug class and preferred drug name, as well as the number and 
percentage of subjects that took any prior medication.
8.5.2.
Concomitant Medications
Concomitant medication is defined as the medication that was either initiated 14 day before the 
first dose of study drug and continued during the study treatment, or initiated on/after the date of 
the first dose of study drug but continued on or before 28 days after the last dose of study drug. 
A summary will be presented for ITT population showing the number and percentage of subjects 
who took concomitant medications by therapeutic drug class and preferred drug name, as well as 
the number and percentage of subjects who took any concomitant medications. 
Separate summaries of concomitant medication of interest focusing on subjects receiving 
concomitant white blood cell (WBC) growth factors, transfusions with blood and blood-derived 
products, erythropoietins, antiemetic medications and systemic anti-infective will be provided.
Separate summary of concomitant medications of special interest as listed in Protocol section 
19.2 will be provided.
Listing of prior and concomitant medications by subject will be provided. Concomitant 
medications of special interest will be indicated in a flag column of the listing.
8.6.
Concomitant Procedures/Surgeries
A concomitant procedure/surgery is defined in a manner similar to the concomitant medication 
(Section 8.5.2). Procedures/Surgeries will be coded using MedDRA version 20.0.
A frequency table will be presented showing the number and percentage of subjects who had 
concomitant procedures/surgeries by system organ class and preferred term, as well as the 
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number and percentage of subjects who had any concomitant procedures/surgeries. Separate 
summary of concomitant procedures/surgeries of special interest as listed in Protocol section 
19.2 will be provided.
Listing of concomitant procedures/surgeries by subject will be provided. Concomitant 
procedures/surgeries of special interest will be indicated in a flag column of the listing.


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9.
STUDY TREATMENTS AND EXTENT OF EXPOSURE
Study treatment with nab-paclitaxel or gemcitabine and extent of exposure summaries will be 
provided based on the treated population. Summaries will be provided for subjects that have nab-
paclitaxel or gemcitabine treatment during the induction phase. In addition, treatment exposure 
data will also be summarized for subjects continuing with treatment of any nab-paclitaxel or 
gemcitabine per Investigator’s Choice after 6-cycles of study drug.
9.1.
Treatment Duration
The treatment start date is the date of the first dose of study drug. For subjects who are 
discontinued early from study treatment, the treatment end date is the date of last dose recorded 
on the CRF treatment disposition page plus drug holidays. The number of drug holidays to be 
added is 6 days for Day 1 dose as the last dose administration, 6 days for Day 8 dose 
administration and 13 days for Day 15 dose administration. For subjects who are still on 
treatment at the time of study closure or clinical cutoff, the treatment end date will be the last 
date of the planned cycle (27 days after first dose of the last cycle). If the treatment end date as 
defined is beyond the clinical cutoff date, the cutoff date is used as the treatment end date.
Treatment duration (in weeks) is calculated as (treatment end date – the date of the first dose of 
study drug + 1) / 7 and rounded to one decimal place. Summary statistics for treatment duration 
(in weeks) as well as a frequency summary of treatment duration categories (<2 weeks, ≥ 2 to < 
4 weeks, ≥ 4 to < 8 weeks, ≥ 8 to < 12 weeks, and every 4 week intervals so forth) will be 
provided. 
Descriptive statistics for the total number of treatment cycles subjects received and the number 
of doses administered for each study drug will be provided. A summary of the frequency of 
subjects dosed at each cycle and number of cycles administered per subject will also be provided.
9.2.
Cumulative Dose
Cumulative dose is defined as the sum of all administered doses in mg/m2. Descriptive statistics 
for the cumulative dose (mg/m2) separately for nab-paclitaxel and gemcitabine by induction 
phase and Investigator’s Choice phase will be provided. 
9.3.
Dose Intensity
Dose intensity (DI) will be calculated as the cumulative dose divided by the total treatment 
weeks. Descriptive statistics for the dose intensity (mg/m2/week) for induction phase and 
Investigator’s Choice phase will be provided. 
9.4.
Relative Dose Intensity
Relative Dose Intensity (RDI) will be defined as follows.
RDI = 100 x (cumulative dose through treatment completion/discontinuation) / (expected amount 
of dose given through treatment completion/discontinuation per schedule).
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DI =
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The expected amount of dose assumes no modification of dose or schedule. The cumulative dose 
as defined in Section 9.2 includes dose modification. Both of these measures are measured in 
mg/m2 unit.
9.5.
Dose Reduction/Delay/Omission
If, for administrative reasons, treatment cannot be administered on the planned visit date, IP may 
be administered up to 2 days from the scheduled date. Study treatments must be 7 or more days 
apart from each other. A dose reduction is defined as the planned dose reduced to the next lower 
dose level compared to the planned previous dose due to toxicities. Up to 2 dose reductions to 
100 mg/m2 and 75 mg/m2 for nab-paclitaxel and 800 mg/m2 and 600 mg/m2 for gemcitabine are 
allowed (See Table 5 in section 8.2.1.2 of protocol). 
Dose delay is defined as the scheduled dose administered >= 3 days after the scheduled dosing 
date. 
Dose omission is defined as the scheduled dose not given for the scheduled visit which does not 
include dose delay.
Dose reduction/delay/omission will be summarized as follows:  
!
Separately for nab-paclitaxel and gemcitabine, the number and percentage of subjects 
with at least 1 dose reduction, reasons for reduction, number of dose reductions, and 
dose reduction for each treatment cycle;
!
Separately for nab-paclitaxel and gemcitabine, the number and percentage of subjects 
with at least 1 dose delay, number of dose delays, dose delay for each treatment 
cycle;
!
Separately for nab-paclitaxel and gemcitabine, the number and percentage of subjects 
with at least 1 dose omitted, reasons for omission, number of doses omitted, and dose 
omission for each treatment cycle.
A listing of investigational product administration will be provided. 
9.6.
Overdose 
Overdose, as defined in this study, refers to dosing for nab-paclitaxel or gemcitabine only.
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
paclitaxel or gemcitabine to a given subject, regardless of any associated adverse events (AEs) 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.
Drug overdose will be summarized as follows: 
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and gem
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!
Separately for nab-paclitaxel and gemcitabine for induction phase and Investigator’s 
Choice phase, respectively, the number and percentage of subjects with at least 1 
drug overdose, overdose frequency as defined by overdose definition for each  
category (on per dose basis, on schedule or frequency basis, and on infusion rate 
basis) and for each treatment cycle.
A listing of investigational drug overdose will be provided.
&(/*(1(35235,(7$5<,1)250$7,21


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10.
EFFICACY ANALYSIS
The primary analyses will be performed on the ITT and PP population. The secondary efficacy 
analysis will be performed on the ITT population.
Summaries of efficacy endpoints will be provided at the end of study. Disease control rate will 
be analyzed only for induction phase.
10.1.
Multiplicity
There is no adjustment for multiplicity of endpoints because of the exploratory nature of this 
study and the lack of statistical testing. 
10.2.
Analysis of Primary Efficacy Endpoint
Time to treatment failure is defined as the time after the first dose of study therapy to 
discontinuation of study therapy due to disease progression, death (by any cause), or the start of a 
new non-protocol-defined anticancer therapy. If a subject does not progress, die or start a new 
non-protocol-defined anticancer therapy, then the subject will be censored on the last tumor 
assessment date. Therapies serving as maintenance or standard of care after surgery or 
chemoradiation are not considered as part of non-protocol-defined anticancer therapies.  A listing 
of these subsequent anticancer therapies (section 10.3.5) is provided for clinical review to 
determine the nature of the anticancer therapy. The TTF will be summarized using standard 
Kaplan-Meier methods. Median TTF and a 2-sided 90% CI using the method of Brookmeyer and 
Crowley will be reported. 
Summaries will be provided at the end of study for both ITT population and PP population.
A Kaplan-Meier plot will also be produced.
No formal statistical testing will be done with this endpoint.
10.3.
Analysis of Secondary Efficacy Endpoints
10.3.1.
Disease Control Rate 
Disease control rate is defined as the percentage of responders, defined as subjects with CR, PR
or SD. In order to qualify for DCR calculation, SD must last for >= 16 weeks from the date of 
first treatment. The tumor response is assessed by investigators according to RECIST 1.1 
guidelines. Disease control rate after 6 cycles of nab-paclitaxel and gemcitabine and 90% CI 
using Wilson score method [1] will be provided during induction phase.
The summaries will be repeated for the following endpoints.
!
DCR during induction phase with SD >=16 weeks excluding tumor assessments 
after non-protocol-defined anticancer therapy/surgery
!
DCR during induction phase with SD >=24 weeks
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thihis s
therapy
therapy toto
ny cause), o
cause
y
ogress, die 
ogress, die 
ensored on
ensored o
of care afte
of care afte
fined
fined antntici
s s provi
provided
ded
F will be su
F will be s
90% CI usi
90% CI u
dy
dy fo
for both
r both
ced.
ced.
done with 
done with
econdary
econdary
ntrol Rate
ntrol Rate
e is defined
e is defined
o qualify f
o qualify f
nt. The tum
t. The tum
. Dis
D ease c
ease c
Wilson sco
Wilson sco
he s
he summar
ummar


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!
DCR during induction phase with SD >=24 weeks excluding tumor assessments 
after non-protocol-defined anticancer therapy/surgery
!
DCR at month 6
!
DCR at month 6 excluding tumor assessments after non-protocol-defined anticancer 
therapy/surgery
10.3.2.
Overall Response Rate 
Subjects with Investigator-determined CR or PR according to RECIST 1.1 guidelines will be 
considered as responders. The ORR will be presented with 2- sided 90% CI using Wilson score 
method. Summaries will be provided at the end of study. 
10.3.3.
Progression-free Survival
Progression-free survival is defined as the time from the first dose of study therapy to the start of 
disease progression or death (by any cause), whichever occurs first. Subjects who do not have 
disease progression or have not died will be censored to last tumor assessment date with 
progression-free. 
The following sensitivity analysis of progression-free survival will also be conducted: if a 
subject had disease progression or died right after missing 2 or more consecutive scheduled 
tumor assessment, the subject will be censored on the previous tumor assessment date with 
progression-free; if a subject received a new non-protocol-defined anti-cancer therapy/surgery 
prior to documented disease progression or death, the subject will be censored on the last tumor 
assessment date with progression-free prior to the initiation of this new therapy/surgery.
The censoring rule is illustrated in Table 3.
&(/*(1(35235,(7$5<,1)250$7,21
be
n score 
score
therapy
therapy to 
to
y
jects who d
cts wh
sessment d
sessment 
l will also 
l will also
2 or more 
2 or more
previous tum
previous tu
otocol
otocol-defi
de
h, the subje
the subje
o th
o the init
e initiat
iat
3.


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Table 3:
Censoring Rules for Progression-free Survival
Value of Progression-free 
Survival/Censor Date 
Censored 
Derivation
Analysis Date = minimum 
(death date, disease 
progression date) 
No
If a subject died or had disease progression. 
Analysis Date = the last 
progression-free assessment 
date/ first dose date
Yes*
If a subject had disease progression or died right 
after missing 2 or more consecutive scheduled 
tumor assessments (as defined by the time interval 
between the death date/progression date and the 
previous tumor assessment date with progression-
free response or the first dose date is greater than 
120 days).
Analysis Date = the last tumor 
assessment date/first dose date 
Yes
If a subject did not die or have progression. 
If there was no post-baseline tumor assessment, 
then ADT = the first dose date.
Analysis Date = last tumor 
assessment date with 
progression-free prior to the 
initiation of this new 
therapy/surgery
Yes*
If a subject received a new non-protocol-defined 
anti-cancer therapy/surgery prior to documented 
disease progression or death.
Note: Progression-free response refers to a response that was neither progressive disease (PD) nor 
un-evaluable (UE). * This rule applies to sensitivity analysis.
The survival distribution of PFS will be estimated using the Kaplan-Meier method, the median 
and associated 2-sided 90% CIs calculated using the method of Brookmeyer and Crowley will be 
provided. The PFS rates will be provided for different time points.
Summaries will be provided at the end of study.
A Kaplan-Meier plot will also be produced for both PFS and sensitivity PFS endpoints.
&(/*(1(35235,(7$5<,1)250$7,21
$7
ion or died 
on or died
ecutive sche
ecutive sche
fined by 
ned by the
/progression
/progression
ssment date
ssment da
the first dos
the first dos
50
subject did 
subject di
If there wa
If there w
then AD
then AD
$5
5
e
Yes
Yes*
35
35
5
on-free resp
free resp
(UE).
(UE). * Th
T
(
(
al distribut
l distribut
ociated 2
ted 2-sis
ded. 
ded. The P
The 
Summaries 
Summaries
A Kapl
Kapl


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10.3.4.
Overall Survival 
The overall survival is defined as the time from the date of first dose of study therapy to the date 
of death (by any cause). Subjects who are alive at the end of study or clinical data cut will be 
censored on the last known time that the subject was alive or the clinical cutoff date, whichever 
is earlier. 
The survival distribution of OS will be estimated using the Kaplan-Meier method, the median 
including 2-sided 90% CI calculated using the method of Brookmeyer and Crowley will be 
provided. The survival rates will be provided for different time points.
Summaries will be provided at the end of study.
A Kaplan-Meier plot will also be produced.
10.3.5.
Tumor Response
Tumor evaluations are assessed by the Investigators and response (complete response (CR), 
partial response (PR), stable disease (SD), progressive disease (PD), unevaluable (UE)) is
determined according to RECIST v1.1 guidelines.
Data listings for tumor response will be provided:
!
Overall best response for subject
!
Per subject visit:
o
Date of assessment
o
Assessment of target lesions
o
Assessment of non-target lesions
o
Presence of symptomatic deterioration
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)
A waterfall plot will be provided for best percent change from baseline in sum of longest 
diameter (SLD) of target lesions.
10.3.6.
Subsequent Anti-cancer Therapy
The subsequent anti-cancer therapies will be summarized. Listings will be provided. 
&(/*(1(35235,(7$5<,1)250$7,21
te response
e response
evaluable (
evaluable
ns
get l
get lesi
esions
ons
omatic dete
omatic d
response as
response 
ll response
ll response
each subjec
ach sub
cati
cation
on
Method o
Method o
o
Tum
Tum
fall plot wil
plot w
eter 
ter (SLD) 
(SLD
10.3.6.
0.3.6.
he su
he su


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10.3.7.
Health-related Quality of Life
Differences in outcomes from baseline, during treatment, and after treatment for the EORTC 
QLQs, EORTC QLQ-C30 and QLQ-PAN26 will be described in an analysis plan separate from 
this SAP.
 
10.5.
Other Efficacy Analyses 
For subjects with surgical intervention during the study per Investigator’s Choice, the number 
and percentage of subjects will be summarized with respect to surgery type, pancreas position, 
nodal status, resection status, and histology details.
CCI
the numbe
he numb
ncreas posi
ncreas po


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11.
SAFETY ANALYSIS
All safety analyses will be conducted based on the treated population. Whenever possible,
combine induction phase and investigator’s choice phase into one summary table. Summaries 
will be provided for data collected during chemotherapy induction phase, chemotherapy 
including both phases, chemoradiation therapy for IC phase, and surgery for IC phase.  The 
columns in the headers of summary tables are (1) Induction Phase nab-Paclitaxel/Gemcitabine, 
(2) Overall nab-Paclitaxel/Gemcitabine, (3) Chemoradiation, (4) Surgical Intervention.
11.1.
Adverse Events
Adverse events (AEs) will be analyzed in terms of TEAEs of a study phase which are defined as 
any AEs that begin or worsen on or after the start of study drug or procedure of the phase. (1) 
TEAE  in the induction phase is an AE onset on or after the first dose of chemotherapy up to 
cycle 7 day 1 if the subject enters IC with chemotherapy, or to 28 days after last dose of nab-
Paclitaxel and Gemcitabine if the subject discontinues the study during induction phase, or to the 
date of chemoradiation or surgery.  (2) TEAE in chemotherapy overall is an AE that has to start 
on or after the first dose of chemotherapy up to 28 days after last dose of chemotherapy. (3) 
TEAE in Chemoradiation is an AE onset on or after first chemoradiation up to 28 days after last 
dose of chemoradiation. (4) TEAE in Surgical Intervention is an AE onset on or after the surgery 
up to 28 days after the surgery. All AEs will be coded using the MedDRA Version 20.0. 
A treatment-related TEAE is defined as TEAE which was considered to be related to one or both 
of the study drugs and reported as “Suspected” on the CRF. AEs with a missing relationship will 
be treated as “treatment-related” in summary and presented as missing in subject data listings. 
The incidence of TEAE will be summarized by MedDRA system organ class (SOC) and 
preferred terms (PTs). 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 will be generated for each of the 
following:
!
All TEAEs;
!
Treatment-related TEAEs;
!
TEAEs by maximum grade;
!
Treatment-related grade 3 or higher TEAEs;
!
Serious TEAEs;
!
Serious TEAEs by maximum grade;
!
Treatment-related Serious TEAEs;
!
Serious TEAEs by SAE criteria;
!
TEAEs with action of study drug withdrawn;
&(/*(1(35235,(7$5<,1)250$7,21
defined as
defined as
phase. (1) 
phase. (1)
herapy up t
herapy up t
ast dose of 
ast dose of
uction pha
uction pha
s an AE tha
an AE
e of chemo
 of chem
diata ion up t
n up 
n AE onset
n AE o
the
the MedDR
MedD
as conside
as conside
he CRF. AE
e CRF. A
presented 
presented
by
by MedDR
MedDR
Es will
Es will b
l e g
e g
y Cri
y Criteri
ter
i
a f
a f
TCAE crit
TCAE cri
oderate (gr
oderate (gr
arizing the 
arizing the
-related TE
related TE
Es s by 
by maxim
maxi
reatment
atment-r
Seri
Serious 
ous
!
Ser
Ser
!


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!
TEAEs with action of study drug dose reduced;
!
TEAEs with action of study drug dose interrupted;
!
TEAEs with outcome of death;
!
All deaths within 28 days of last dose with cause of death.
If a subject experiences the same AE more than once with a different toxicity grade, then the 
event with the maximum grade will be tabulated in “by grade” tables. If a subject experiences 
multiple AEs under the same system organ class/preferred term, then the subject will be counted 
only once for that system organ class/preferred term In addition, AEs with a missing 
severity/intensity will be presented in the summary table as an intensity category of “Missing”.
Listings will be prepared that include the verbatim term, PT, and SOC as well as full details of 
all AEs for subjects in the treated population. 
Separate listings will also be prepared for grade 3 and higher TEAEs, serious TEAEs, TEAEs 
leading to death (either outcome of death or SAE due to death), and TEAEs resulting in 
discontinuation of IP. All deaths will be listed with the cause of death collected on the Death 
CRF page.
Treatment-related TEAE, TEAE (and treatment-related TEAE) with action of drug withdrawn, 
dose reduction or dose interruption will not be summarized for surgery group and 
chemoradiation group at investigator’s choice phase.
11.2.
Adverse Events of Special Interest
11.2.1.
AE of Special Interest
Adverse events of special interest of nab-paclitaxel and gemcitabine combination identified in 
previous trials in a similar population will be summarized. TEAEs of special interest are as 
follows:
!
Myelosuppression (to include Anaemia, Neutropenia, and Thrombocytopenia);
!
Peripheral Neuropathy;
!
Gastrointestinal events;
!
Myalgia and arthralgia;
!
Hypersensitivity;
!
Cranial nerve paralysis;
!
Cardiotoxicity including Congestive Heart Failure/Left Ventricular Dysfunction;
!
Stevens-Johnson Syndrome/toxic epidermal necrolysis;
!
Pneumonitis;
!
Infusion site reactions/extravasation;
&(/*(1(35235,(7$5<,1)250$7,21
es 
counted 
ounted 
“Missing”
Missing”
as full detai
s full det
rious TEAE
ous TE
TEAEs resu
EAEs resu
ath collect
ath collec
AE) with a
AE) with a
zed for surg
d for su
nterest
terest
nab
nab-paclita
pac
ion will be
ion will be
on (to inclu
(to inc
n
Neuropathy
Neuropathy
ntestinal ev
ntestinal ev
yalgia and a
algia and
Hy
H persen
persen
y
!
Cran
Cran
!
C


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!
Cystoid macular edema; 
!
Hepatotoxicity; 
!
Acute renal failure and Hemolytic uremic syndrome; 
!
Clinically severe infections; sepsis
!
Posterior reversible encephalopathy syndrome (PRES);
!
Capillary leak syndrome (CLS).
The following summaries will be provided for TEAEs included in the above-mentioned AEs of 
interest: 
!
All TEAEs; 
!
Grade 3 or higher TEAEs; 
!
Serious TEAEs; 
!
TEAEs leading to death.
TEAE of special interest leading to action of drug withdrawn, dose reduction or dose interruption 
will not be summarized for surgery group and chemoradiation group at investigator’s choice 
phase.
In addition, sub-risks of AE of special interest as defined in subjects older than 75 years are to be 
analyzed by age group < 65 years, 65-74 years and ≥ 75 years for the TEAEs of special interest 
in this population as specified below:
!
Myelosuppression (anemia, neutropenia, febrile neutropenia, thrombocytopenia);
!
Peripheral neuropathy;
!
Clinically severe infections – pneumonia;
!
Clinically severe infections – sepsis;
!
Clinically severe infections – pneumonia and sepsis;
!
Dehydration;
!
Decreased appetite;
!
Diarrhea;
!
Epistaxis;
!
Fatigue;
!
Peripheral edema.
&(/*(1(35235,(7$5<,1)250$7,21
Es of 
of 
se reductio
reductio
group at in
group at
efined
efined in su
in s
and 
and ≥ 75 y
≥ 75 ye
ropenia, feb
openia, feb
ns
ns – pneu
pneu
ect
ectioions
ns – s
e infect
e infe ioion
n;
sed appet
ed appetit
arrhea;
rhea;
Epistaxis;
Epistaxis;
!
Fat
Fatigig
!
P


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11.2.2.
Peripheral Neuropathy
Peripheral neuropathy (PN) will be assessed by physician using the NCI CTCAE Version 4.0 of 
“Neuropathy – Sensory”. An overview of peripheral neuropathy will be summarized. The 
frequency of physician assessment of PN grade (0 – 5) will be presented by phase and cycle. The 
frequency of worst PN grade during treatment will also be presented. Additionally, PN events 
will be reported as part of the AEs and will be analyzed as outlined in Section 11.1. 
11.3.
Clinical Laboratory Evaluations
All scheduled laboratory samples will be performed locally. The laboratory values will be graded 
using NCI CTCAE V4.0. For hematologic and chemistry laboratory values that fall outside of 
the grade criteria of NCI CTCAE V4.0, the grade of 0 will be assigned. Listings will be provided 
for all clinical lab evaluations with normal ranges included.
11.3.1.
Clinical Chemistry
The NCI CTCAE grade for chemistry panel tests will be summarized by the most severe grade 
during treatment of chemotherapy in induction phase, of chemotherapy overall, of 
chemoradiation, and of surgery.   
11.3.2.
Hematology
The NCI CTCAE grade for hematology panel tests will be summarized by the most severe grade 
during treatment of chemotherapy in induction phase, of chemotherapy overall, of 
chemoradiation, and of surgery.
11.3.3.
Serum Carbohydrate Antigen 19-9 (CA19-9)
Serum CA19-9 levels will be collected at the time of every CT/MRI scan assessment. Absolute 
CA19-9 levels and change from baseline will be summarized by cycle during induction 
chemotherapy phase and Investigator’s Choice phase. The maximum change of CA19-9 from 
baseline is defined as the percentage change at the nadir from the baseline value and will be 
summarized descriptively. For subjects with both baseline and post baseline assessments, the 
percent of subjects with a maximum drop in CA19-9 of at least 20%, 50%, 70% and 90% will be 
calculated. The maximum change in CA19-9 from baseline for each subject will be produced in a 
waterfall plot. 
11.4.
Vital Sign Measurements
For vital signs, results will not be collected in the eCRF, and 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 an AE or SAE. 
Therefore, there will be no separate analysis for vital sign.
&(/*(1(35235,(7$5<,1)250$7,21
ll be graded
be grade
 outside o
outside of
 will be pro
will be pro
ed by
ed by the m
the
y
herapy
hera
ove
ve
y
will be sum
will be su
hase, of che
ase, of ch
en 19
en 19-9 (C
9 (C
ed at the tim
ed at the 
aseline wil
aseline w
tigator
gator’s Ch
C
rcentage ch
rcentage 
y. For subje
y. For su
th a maxim
th a maxim
ximum
mum cha
cha
m
Vital S
Vital S
ital
tal
i
signs, r
signs,
l
inically sign
nically sig
abnorm
bnormalal
heref
heref


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11.5.
Physical Examination
Any results from physical examination will not be collected in the eCRF, and 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 an AE or 
SAE. Therefore, there will be no separate analysis for physical examination.
11.6.
ECOG Performance Score
The worst ECOG performance status during treatment will be summarized for the induction 
phase, chemoradiation therapy for IC phase and overall.
11.7.
Other Safety Analysis
A descriptive summary table for the treated population will be provided with respect to 
neutrophils, lymphocytes and ratio of neutrophils to lymphocytes (NLR), as well as a frequency 
summary of NLR categories (NLR ≤ 5 vs. NLR > 5).
&(/*(1(35235,(7$5<,1)250$7,21
ith respect 
th respect 
R), 
), as well a
as wel


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12.
INTERIM ANALYSIS
12.1.
Analysis Methods
An interim analysis will be conducted when all subjects completed 6 cycles of nab-paclitaxel and
gemcitabine in the induction phase or discontinued early from the study. The DCR analysis 
proposed in this SAP and analyses listed below that are deemed necessary for the induction 
phase will be performed for the interim analysis. The same analysis methods will be used as full 
analysis described in previous sections of this SAP. 
In addition to DCR, interim analysis also includes:
!
Subjects who discontinued from study therapy in induction phase, subjects who 
completed induction phase and subjects who entered Investigator’s Choice phase will 
be summarized. Reasons for discontinuation from induction phase will be 
summarized;
!
The demographics, baseline characteristics, and medical history will be summarized 
in the same way as full analysis;
!
Summary of concomitant medications, treatment exposure and dose modification for 
the induction phase;
!
Overall summary of TEAE for the induction phase; 
!
Summary of treatment-related TEAE by system organ class and preferred term for the 
induction phase;
!
Analysis of other efficacy endpoints including TTF, PFS and OS.
&(/*(1(35235,(7$5<,1)250$7,21
s who 
who 
oicice phase
e phase
ill
ill b
l e
ory will be 
will
osure and d
ure and 
hase;
hase;
ystem
yste
orga
orga
m
ts including
ts including


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13.
CHANGES TO THE STATISTICAL ANALYSES SECTION OF 
THE PROTOCOL
Section 10.3.3 of this SAP: progression-free survival analysis will be conducted by two 
approaches. The different censoring rules are used to examine the sensitivity of PFS analysis.
&(/*(1(35235,(7$5<,1)250$7,21


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14.
REFERENCES
[1] Robert G. Newcombe, Two-Sided Confidence Intervals for the Single Proportion: 
Comparison of Seven Methods. Statistics in Medicine 1998;17:857-872
[2] Eisenhauer EA, et al. New response evaluation criteria in solid tumours: revised RECIST 
guideline (version 1.1). Eur J Cancer. 2009 Jan; 45 (2): 228-47.
&(/*(1(35235,(7$5<,1)250$7,21


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15.
APPENDICES 
15.1.
Handling of Dates 
Dates will be stored as numeric variables in the SAS analysis files and reported in 
DDMMMYYYY format (ie, the Date9. datetime format in SAS).  Dates in the clinical database 
are classified into the categories of procedure dates, log dates, milestone dates, outcome dates, 
and special dates.
!
Procedure Dates are the dates on which given protocol-specified procedure are 
performed.  They include the dates of laboratory testing, physical examinations, 
tumor scans, etc.  They should be present whenever data for a protocol-specified 
procedure are present and should only be missing when a procedure are marked as 
NOT DONE in the database.  Procedure dates will not be imputed.
!
Log Dates are dates recorded in CRF data logs. Specifically, they are the start and 
end dates for adverse events and concomitant medications/procedures.  They should 
not be missing unless an event or medication is marked as ongoing in the database.  
Otherwise, incomplete log dates will be imputed according to the rules in Appendix 
16.2 (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 and
disease recurrence.  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 disease 
recurrence date is derived from the date of the tumor scan that was used to determine 
disease recurrence).  They may be subject to endpoint-specific censoring rules if the 
outcome did not occur or disease recurrence or death following more than 1 missing 
tumor assessment, 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. 
Dates recorded in comment fields will not be imputed or reported in any specific format.
15.2.
Date Imputation Guideline
15.2.1.
Impute Missing Adverse Events/ Prior or Concomitant Medications/Procedures 
Incomplete Start 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 doing date will be assigned to the missing fields.
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nab-paclitaxel
Statistical Analysis Plan. Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
39
!
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.
!
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, month, and year
!
No imputation is needed, the corresponding AE will be included as TEAE. 
Incomplete Stop Date: If the imputed stop date is before the start date, then the imputed stop 
date will be equal to the start date.
Missing day and month
!
If the year of the incomplete stop date is the same as the year of the last dosing date, 
then the day and month of the last dosing date will be assigned to the missing fields. 
!
If the year of the incomplete stop date is prior to the year of the last dosing date or 
prior to the year of the first dosing date, then December 31 will be assigned to the 
missing fields. 
!
If the year of the incomplete stop date is prior to the year of the last dosing date but 
is the same as the year of the first dosing date, then the first dosing date will be 
assigned to the missing date. 
!
If the year of the incomplete stop date is after the year of the last dosing date, then 
January 1 will be assigned to the missing fields.
Missing day only 
!
If the month and year of the incomplete stop date are the same as the month and year 
of the last dosing date, then the day of the last dosing date will be assigned to the 
missing day. 
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the
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is before t
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th of the las
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If the ye
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Janua
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Missing day 
Missing day


nab-paclitaxel
Statistical Analysis Plan. Protocol ABI-007-PANC-007
Celgene Corporation
Confidential and Proprietary
40
!
If either the year of the partial date is not equal to the year of the last dosing date or 
the years of the partial date and the last dosing date are the same but the month of 
partial date is not equal to the month of the last dosing date, then the last day of the 
month will be assigned to the missing day.  
&(/*(1(35235,(7$5<,1)250$7,21