Clinical trial NCT01803282
Conditions: Pancreatic Cancer Non-small Cell Lung Cancer Esophagogastric Cancer Colorectal Cancer Breast Cancer
Keywords: Solid Tumor
Sponsor: Gilead Sciences
Start date: 2013-03-29; Completion date: 2019-04-23
Enrollment: 236 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The primary objective of the study is to determine the maximum tolerated dose of andecaliximab monotherapy and to evaluate the safety and tolerability of andecaliximab (formerly GS-5745) alone and in combination with chemotherapy.

The study consists of 2 parts (Parts A and B). Participants can only qualify for and participate in 1 part.

Part A is a sequential dose escalation to determine the maximum tolerated dose of andecaliximab in participants with advanced solid tumors that are refractory to or intolerant to standard therapy or for which no standard therapy exists. In Part A, participants will receive andecaliximab only.

Part B is a dose expansion to obtain additional safety and tolerability data for andecaliximab in participants with advanced pancreatic adenocarcinoma, lung adenocarcinoma, lung squamous cell carcinoma, esophagogastric adenocarcinoma, colorectal cancer, or breast cancer. In Part B, participants will receive andecaliximab in combination with standard-of-care chemotherapy.

Detailed description:

Arms: arm 1: Participants with advanced solid tumors who fail or are intolerant to standard therapy or for whom no standard therapy exists, will receive 200 mg ADX as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. arm 2: Participants with advanced solid tumors who fail or are intolerant to standard therapy or for whom no standard therapy exists, will receive 600 mg ADX as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. arm 3: Participants with advanced solid tumors who fail or are intolerant to standard therapy or for whom no standard therapy exists, will receive 1800 mg ADX as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug arm 4: Participants with PAC will receive ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (gemcitabine and nab paclitaxel, on Days 1, 8, and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. arm 5: Participants with lung adenocarcinoma (LAC) will receive ADX 1200 mg every 3 weeks via IV infusion in addition to the 21-day cycle chemotherapy (carboplatin and pemetrexed, on Day 1) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. arm 6: Participants with lung squamous cell carcinoma (LSC) will receive ADX 1200 mg every 3 weeks via IV infusion in addition to the 21-day cycle chemotherapy (carboplatin and paclitaxel, on Day 1) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. arm 7: Participants with esophagogastric adenocarcinoma (EGC) will receive ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (leucovorin+oxaliplatin+5-fluorouracil {5-FU} \[mFOLFOX6\], on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. arm 8: Participants with colorectal cancer (CRC) will receive first-line (FL) treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (mFOLFOX6 and bevacizumab 5 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. arm 9: Participants with CRC will receive FL treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (mFOLFOX6 and bevacizumab 10 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. arm 10: Participants with CRC will receive second-line (SL) treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (leucovorin+irinotecan+5-FU \[FOLFIRI\] and bevacizumab 5 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. arm 11: Participants with CRC will receive SL treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (FOLFIRI and bevacizumab 10 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. arm 12: Participants with breast cancer (BRCA) will receive ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (paclitaxel, on Days 1, 8, and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Interventions: intervention 1: Andecaliximab intervention 2: Gemcitabine intervention 3: Nab-paclitaxel intervention 4: Carboplatin intervention 5: Pemetrexed intervention 6: Leucovorin intervention 7: Oxaliplatin intervention 8: 5-FU intervention 9: Bevacizumab intervention 10: Irinotecan intervention 11: Paclitaxel
Intervention descriptions: intervention 1: Administered intravenous infusion intervention 2: Administered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle intervention 3: Administered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle intervention 4: Administered intravenously on Day 1 of each 21-day treatment cycle intervention 5: Administered intravenously on Day 1 of each 21-day treatment cycle intervention 6: Administered intravenously on Days 1 and 15 of each 28-day treatment cycle intervention 7: Administered intravenously on Days 1 and 15 of each 28-day treatment cycle intervention 8: Administered intravenously on Days 1 and 15 of each 28-day treatment cycle intervention 9: Administered intravenously on Days 1 and 15 of each 28-day treatment cycle intervention 10: Administered intravenously on Days 1 and 15 of each 28-day treatment cycle intervention 11: Administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle (Breast cancer) or on Day 1 of each 21-day treatment cycle (NSCLC)

Protocol documents:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL
Study Title:
A Phase 1 Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics, and Pharmacodynamics of GS-5745 as 
Monotherapy and in Combination with Chemotherapy in Subjects 
with Advanced Solid Tumors
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND No.:
EudraCT Number:
116561
Not Applicable
Indication:
Solid Tumors
Protocol ID:
GS-US-296-0101
Gilead Sciences 
Medical Monitor:
Name:
Telephone:
Fax:
Protocol Version/Date:
Original:
17 December 2012
Amendment 1:
07 February 2013
Amendment 2:
27 March 2013
Amendment 3:
27 May 2014
Amendment 4:
04 September 2015
Amendment 5:
16 May 2016
Amendment 6:
01 August 2016
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable 
Institutional Review Board or Independent Ethics Committee. The information is only to be used 
by you in connection with authorized clinical studies of the investigational drug described in the 
protocol. You will not disclose any of the information to others without written authorization 
from Gilead Sciences, Inc., except to the extent necessary to obtain informed consent from those 
persons to whom the drug may be administered.
PPD
PPD
PPD
(r) GILEAU 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................5
LIST OF IN-TEXT FIGURES ......................................................................................................................................5
PROTOCOL SYNOPSIS ..............................................................................................................................................6
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS....................................................................18
1.
INTRODUCTION ..............................................................................................................................................22
1.1.
Background ............................................................................................................................................22
1.1.1.
MMP9 Expression in Oncology...........................................................................................22
1.2.
General Information...............................................................................................................................23
1.2.1.
Preclinical Pharmacology and Toxicology...........................................................................23
1.2.2.
Summary of Phase 1 Study of GS-5745 as Monotherapy and in 
Combination with Chemotherapy in Subjects with Advanced Solid 
Tumors (Study GS-US-296-0101) .......................................................................................24
1.2.3.
Rationale for Dose Selection................................................................................................28
1.2.4.
Clinical Trials of GS-5745 ...................................................................................................29
1.3.
Rationale for Evaluating GS-5745 in Select Solid Tumors....................................................................29
1.4.
Rationale for Chemotherapy Regimens in Part B ..................................................................................30
1.4.1.
Pancreatic Adenocarcinoma.................................................................................................30
1.4.2.
Non-Small Cell Lung Cancer...............................................................................................30
1.4.3.
Esophagogastric Adenocarcinoma .......................................................................................30
1.4.4.
Colorectal Cancer.................................................................................................................31
1.4.5.
Breast Cancer .......................................................................................................................32
2.
OBJECTIVES.....................................................................................................................................................33
3.
STUDY DESIGN................................................................................................................................................34
3.1.
Overview................................................................................................................................................34
3.1.1.
Part A ...................................................................................................................................34
3.1.2.
Part B....................................................................................................................................35
3.2.
Treatment Plan and Regimen .................................................................................................................36
3.2.1.
Part A ...................................................................................................................................36
3.2.2.
Part B....................................................................................................................................36
4.
SUBJECT POPULATION..................................................................................................................................38
4.1.
Number of Subjects and Subject Selection ............................................................................................38
4.2.
Inclusion Criteria....................................................................................................................................38
4.3.
Exclusion Criteria...................................................................................................................................40
4.4.
Excluded Medication .............................................................................................................................41
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................42
5.1.
Enrollment..............................................................................................................................................42
5.2.
Description and Handling of GS-5745...................................................................................................42
5.2.1.
Formulation..........................................................................................................................42
5.2.2.
Packaging, Labeling, Storage, and Handling .......................................................................42
5.3.
Dosage and Administration of GS-5745 ................................................................................................42
5.4.
Dosage and Administration of Chemotherapy .......................................................................................43
5.4.1.
Study Drug Accountability...................................................................................................44
5.4.2.
Study Drug Return or Disposal ............................................................................................44


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6.
STUDY PROCEDURES ....................................................................................................................................45
6.1.
Subject Enrollment and Treatment Assignment – Part A.......................................................................45
6.1.1.
Screening Visit .....................................................................................................................45
6.1.2.
Treatment Assessments ........................................................................................................46
6.1.3.
Continuation of Treatment ...................................................................................................50
6.1.4.
End-of-Study Visit ...............................................................................................................51
6.1.5.
Follow-up Visits...................................................................................................................52
6.2.
Subject Enrollment and Treatment Assignment – Part B.......................................................................52
6.2.1.
Screening Visit .....................................................................................................................52
6.2.2.
Cycle-Based Assessments ....................................................................................................53
6.2.3.
Continuation of Treatment ...................................................................................................55
6.2.4.
End-of-Study Visit ...............................................................................................................56
6.2.5.
Follow-up Visits...................................................................................................................56
6.3.
Assessments for Premature Discontinuation of Study Drug ..................................................................57
6.4.
Criteria for Discontinuation of Study Drug............................................................................................57
6.5.
Criteria for Removal from Study............................................................................................................58
6.6.
Replacement of Subjects........................................................................................................................58
6.7.
Dose Interruption and Reduction ...........................................................................................................58
6.7.1.
GS-5745 ...............................................................................................................................59
6.7.2.
Gemcitabine and Nab-Paclitaxel..........................................................................................59
6.7.3.
Carboplatin...........................................................................................................................60
6.7.4.
Paclitaxel..............................................................................................................................60
6.7.5.
Pemetrexed...........................................................................................................................61
6.7.6.
mFOLFOX6 .........................................................................................................................61
6.7.7.
FOLFIRI...............................................................................................................................62
6.8.
Description of Study Procedures............................................................................................................63
6.8.1.
Medical History....................................................................................................................63
6.8.2.
Physical Examination...........................................................................................................63
6.8.3.
Vital Signs............................................................................................................................63
6.8.4.
Electrocardiogram................................................................................................................63
6.8.5.
ECOG Performance Status...................................................................................................63
6.8.6.
Prior and Concomitant Medications.....................................................................................64
6.8.7.
Adverse Events.....................................................................................................................64
6.8.8.
CT or MRI............................................................................................................................64
6.8.9.
Independent Radiology Review ...........................................................................................65
6.8.10.
Blood and Urine Samples.....................................................................................................65
6.8.11.
Pregnancy Test for Females of Childbearing Potential ........................................................66
6.8.12.
Biomarkers ...........................................................................................................................66
6.8.15.
Unscheduled Procedures ......................................................................................................69
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................70
7.1.
Adverse Events.......................................................................................................................................70
7.2.
Serious Adverse Events..........................................................................................................................71
7.3.
Describing Adverse Event Relationship to Study Drug and Study Procedures......................................72
7.4.
Dose Escalation and Stopping Rules for Part A.....................................................................................73
7.5.
Adverse Drug Reactions.........................................................................................................................74
7.6.
Unexpected Adverse Event ....................................................................................................................74
7.7.
Grading of the Severity of an Adverse Event.........................................................................................75
7.8.
Special Situations Reports......................................................................................................................75
7.8.1.
Definition of Special Situations............................................................................................75
7.9.
Reporting Requirements.........................................................................................................................76
CCI


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7.9.1.
Site Reporting Requirements for Adverse Events................................................................76
7.9.2.
Special Situation Reporting Instructions..............................................................................77
7.9.3.
Gilead Sciences Reporting Requirements for Adverse Events.............................................77
7.9.4.
Post-Study Reporting Requirements ....................................................................................78
7.10.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or 
Serious Adverse Events..........................................................................................................................78
7.11.
Toxicity Management ............................................................................................................................78
7.12.
Contraception Requirements..................................................................................................................79
7.13.
Procedures to be Followed in the Event of Pregnancy...........................................................................81
8.
STATISTICAL CONSIDERATIONS................................................................................................................83
8.1.
Analysis Objectives and Endpoints........................................................................................................83
8.1.1.
Objectives.............................................................................................................................83
8.1.2.
Primary Endpoint .................................................................................................................83
8.1.3.
Exploratory Endpoints..........................................................................................................83
8.2.
Analysis Conventions.............................................................................................................................84
8.2.1.
Analysis Sets ........................................................................................................................84
8.2.2.
Subject Groups.....................................................................................................................84
8.2.3.
Data Handling Conventions .................................................................................................84
8.3.
Demographic Data and Baseline Characteristics ...................................................................................85
8.4.
Safety Analysis.......................................................................................................................................85
8.4.1.
Extent of Exposure...............................................................................................................85
8.4.2.
Adverse Events.....................................................................................................................85
8.4.3.
Laboratory Evaluations ........................................................................................................86
8.5.
Exploratory Analysis..............................................................................................................................86
8.5.1.
Exploratory Biomarker Analysis..........................................................................................87
8.6.
Pharmacokinetics Analysis ....................................................................................................................87
8.7.
Sample Size............................................................................................................................................87
9.
RESPONSIBILITIES..........................................................................................................................................89
9.1.
Investigator Responsibilities ..................................................................................................................89
9.1.1.
Good Clinical Practice..........................................................................................................89
9.1.2.
Institutional Review Board (IRB) Approval ........................................................................89
9.1.3.
Informed Consent.................................................................................................................89
9.1.4.
Confidentiality......................................................................................................................89
9.1.5.
Study Files and Retention of Records ..................................................................................90
9.1.6.
Electronic Case Report Forms..............................................................................................91
9.1.7.
Study Drug Accountability and Return ................................................................................91
9.1.8.
Inspections............................................................................................................................92
9.1.9.
Protocol Compliance............................................................................................................92
9.2.
Sponsor Responsibilities ........................................................................................................................92
9.2.1.
Protocol Modifications.........................................................................................................92
9.2.2.
Study Report and Publications .............................................................................................92
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................93
9.3.1.
Payment Reporting...............................................................................................................93
9.3.2.
Access to Information for Monitoring..................................................................................93
9.3.3.
Access to Information for Auditing or Inspections ..............................................................93
9.3.4.
Study Discontinuation..........................................................................................................93
10.
REFERENCES ...................................................................................................................................................94
11.
APPENDICES ....................................................................................................................................................98


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Appendix 1.
Investigator Signature Page....................................................................................................99
Appendix 2.
Study Procedures Table (Part A)..........................................................................................100
Appendix 3.
Study Procedures Table (Part B – Pancreatic Adenocarcinoma)..........................................102
Appendix 4.
Study Procedures Table (Part B – Esophagogastric Adenocarcinoma)................................104
Appendix 5.
Study Procedures Table (Part B – NSCLC) .........................................................................106
Appendix 6.
Study Procedures Table (Part B – CRC, First-Line) ............................................................108
Appendix 7.
Study Procedures Table (Part B – CRC, Second-Line)........................................................111
Appendix 8.
Study Procedures Table (Part B – Breast Cancer)................................................................114
Appendix 9.
Dose Modification Tables for Gemcitabine and Nab-Paclitaxel ..........................................117
Appendix 10.
Dose Modification Tables for mFOLFOX6 .........................................................................120
LIST OF IN-TEXT TABLES
Table 1-1.
GS-US-296-0101: Treatment-Emergent Adverse Events Occurring in > 15% of 
Monotherapy Subjects Overall by Dose Cohort.....................................................................26
Table 1-2.
GS-US-296-0101: Treatment-Emergent Adverse Events Occurring in > 15% of 
Combination Therapy Subjects Overall by Dose Cohort .......................................................27
Table 1-3.
Estimated Safety Margins for GS-5745 Based on Human Equivalent Dose and 
Projected Exposure at the Highest Proposed Human Dose ....................................................28
Table 1-4.
Estimated Exposure Margins for Intravenous GS-5745 800 mg, Every Other Week ............29
Table 3-1.
Dose and Regimen for GS-5745 in Parts A and B .................................................................35
Table 3-2.
Dose and Regimen of GS-5745 for Part B Based on the MTD Determined in Part A...........36
Table 6-1.
Dose Reduction Levelsa for Gemcitabine and Nab-Paclitaxel ...............................................59
Table 6-2.
Dose Reduction for Pemetrexed – Hematologic Toxicities....................................................61
Table 6-3.
Dose Reduction for Pemetrexed – Non-Hematologic Toxicitiesa ..........................................61
Table 6-4.
Dose Reduction Levelsa for mFOLFOX6...............................................................................62
Table 6-5.
Starting Dose and Modified Dose Levels (mg/m2).................................................................62
Table 6-6.
ECOG Performance Status.....................................................................................................64
Table 6-7.
Blood and Urine Samples Collected During the Course of the Study....................................65
Table 6-8.
Biomarker Objectives and Testing, CRC and Breast Cancer Subjects...................................68
Table 7-1.
Site Reporting Requirements for Adverse Events ..................................................................76
Table 7-2.
Contact Information for Reporting Serious Adverse Events ..................................................77
Table 7-3.
Protocol-Recommended Contraceptive Methods ...................................................................80
LIST OF IN-TEXT FIGURES
Figure 3-1.
Study Schema.........................................................................................................................37


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 1 Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics, and Pharmacodynamics of GS-5745 as 
Monotherapy and in Combination with Chemotherapy in Subjects 
with Advanced Solid Tumors
IND Number:
EudraCT Number:
116561
Not Applicable
Study Centers Planned:
Approximately 25 centers in the United States (US)
Primary Objectives:

To determine the maximum tolerated dose (MTD) of GS-5745 
monotherapy in subjects with advanced solid tumors

To characterize the safety and tolerability of GS-5745 as 
monotherapy and in combination with various chemotherapy
regimens in subjects with select tumor types
Secondary Objectives:

To characterize the pharmacokinetics (PK) of GS-5745

To evaluate the formation of anti-GS-5745 antibodies
 
 
Exploratory Objective:
 
 
Study Design:
This is an open-label, multicenter, sequential dose-escalation, and 
expansion study to evaluate the safety, tolerability, PK, and 
pharmacodynamics of GS-5745 alone and in combination with 
chemotherapy. The study will be conducted in 2 parts
(Part A and Part B).
CCI
CCI
I 
I 
I 


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Part A:
Cohorts of subjects with advanced solid tumors who have failed or 
are intolerant to standard therapy or for whom no standard therapy 
exists will be sequentially enrolled at progressively higher dose 
levels to receive GS-5745 as monotherapy via intravenous (IV) 
infusion every 2 weeks (Q2W). Dose escalation [3 + 3] will be 
performed with cohort sizes of 3 to 6 subjects. A single subject
will initially be enrolled into the first dosing cohort to evaluate any 
unexpected adverse effects. Provided that there are no significant 
safety signals up to 24 hours postdose, the remaining 2 subjects
will be dosed. The starting dose will be 200 mg. Subsequent doses 
of 600 and 1800 mg are planned. The safety and tolerability of 
each dose level will be assessed after all subjects in the cohort have 
been followed for at least 28 days after the first infusion of 
GS-5745. Cohort dose escalation will occur if no subjects 
experience dose limiting toxicities (DLTs) during the first 28 days 
of study drug dosing. If one subject within the initial cohort of 
3 subjects experiences a DLT during the first 28 days of study drug 
dosing, an additional 3 subjects will be enrolled at the same dose 
level. If no DLTs are observed in the additional 3 subjects, dose 
escalation will occur. If 2 or more subjects experience DLTs 
within the first 28 days, dose de-escalation to an intermediate dose 
will occur. Specifically, if 2 or more subjects experience DLTs at 
1800 mg, then 1200 mg will be explored, and if 2 or more subjects 
experience DLTs at 600 mg, then 400 mg will be explored. The 
maximum tolerated dose (MTD) is the highest dose level with a 
subject incidence of DLTs during the first 28 days of study drug 
dosing of 0 or 1 out of 6.
After determination of MTD, Part B will commence. During the 
conduct of Part B, up to 3 additional cohorts consisting of no more 
than 10 subjects each may be studied with GS-5745 at 
monotherapy doses up to MTD given every 2 weeks to obtain 
additional information on PK and pharmacodynamics.
A DLT is a toxicity defined below considered possibly related to 
GS-5745 occurring during the DLT assessment window 
(Day 1 through Day 29) in each dose escalation cohort.

Grade 4 neutropenia (absolute neutrophil count [ANC] 
< 500/μL) for > 7 days, or febrile neutropenia (ANC < 1000/μL 
with fever > 101 °F [38.5 °C])

Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia 
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
Grade 3 or 4 non-hematologic toxicity (excluding rash, nausea, 
diarrhea, and vomiting if controlled with standard 
supportive care)

Treatment delay of ≥14 days due to unresolved toxicity

Non-hematologic toxicity of ≥Grade 2 (at any time 
during treatment) that, in the judgment of the investigators and 
the Medical Monitor, is dose-limiting

For certain toxicities, such as laboratory assessments without a 
clear clinical correlate, a discussion between the investigator, 
Medical Monitor, and the Sponsor may take place to determine 
whether this adverse event (AE) should be assessed as a DLT 
necessitating dose reduction.
Part B:
The dose expansion will begin once all subjects in the dose 
escalation portion of Part A have completed the 28-day DLT 
period. Between 115 to 295 subjects with advanced pancreatic 
adenocarcinoma (Cohort 4), lung adenocarcinoma (Cohort 5), 
lung squamous cell carcinoma (Cohort 6), esophagogastric 
adenocarcinoma (Cohort 7), colorectal cancer (CRC) in the 
first-line setting (Cohort 8), CRC in the second-line setting 
(Cohort 9), or breast cancer (Cohort 10) will be enrolled to receive 
GS-5745 via IV every 2 to 3 weeks in combination with 
chemotherapy. Thirty-five subjects will be enrolled in Cohort 4, 
10 subjects each in Cohorts 5 and 6, and 15 subjects each in 
Cohorts 7 through 10. During the conduct of Part B, a maximum of 
25 additional subjects in each cohort may be enrolled to obtain 
information on safety, PK, pharmacodynamics, and tumor 
response.
The cohort dose levels for GS-5745 in Part B are presented below 
and will be based on the MTD determined in Part A.
MTD from Part A (mg)
Doses to be Used in Part B (mg)
Q2W
Q3W
200
133
200
400
267
400
600
400
600
1200
800
1200
1800
800
1200
Q2W = every 2 weeks; Q3W = every 3 weeks


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The planned number of subjects and dosing intervals for 
Parts A and B are presented below.
Cohort
No. Subjects
GS-5745 Dose (mg)
Dosing Interval
Part A: Dose Escalation
1
3 to 6
200
Q2W
2
3 to 6
600
Q2W
3
6
1800
Q2W
Part B: Dose Expansion
4
35
Based on MTD from 
Part A
(see table above)
Q2W
5
10 to 35
Q3W
6
10 to 35
Q3W
7
15 to 40
Q2W
8
15 to 55*
Q2W
9
15 to 55**
Q2W
10
15 to 40
Q2W
Q2W = every 2 weeks; Q3W = every 3 weeks
*
For Cohort 8 (first-line CRC), the sample size of 40 subjects was initially planned.
In amendment 5, the dose of bevacizumab is corrected to be 5 mg/kg Q2W. Up to 
15 subjects who previously started bevacizumab treatment at other dose levels will 
be replaced. Therefore, a total of up to 55 subjects may be enrolled in Cohort 8.
**
For Cohort 9 (second-line CRC), the sample size of 40 subjects was initially 
planned. In amendment 5, the dose of bevacizumab is corrected to be 5 mg/kg Q2W. 
Up to 15 subjects who previously started bevacizumab treatment at other dose levels 
will be replaced. Therefore, a total of up to 55 subjects may be enrolled in Cohort 9.
Number of Subjects 
Planned:
Up to 343 subjects will be enrolled. Part A will comprise between 
12 to 48 subjects; Part B will comprise between 115 to 295 subjects.
Target Population:
Part A: Adult subjects with a histologically or cytologically 
confirmed advanced malignant solid tumor that is refractory to or 
intolerant of standard therapy or for which no standard therapy is 
available
Part B: Adult subjects with histologically or cytologically 
confirmed advanced pancreatic adenocarcinoma, non-small cell 
lung cancer (NSCLC), esophagogastric adenocarcinoma, CRC, or 
breast cancer who are candidates for chemotherapy treatment
Duration of Treatment:
Until disease progression, unacceptable toxicity, withdrawal of 
consent, or other reasons specified in Section 6.4
Diagnosis and 
Eligibility Criteria:
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be 
eligible for participation in this study:


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1) Male or female ≥18 years of age
2) Part A: Histologically or cytologically confirmed advanced 
malignant solid tumor that is refractory to or intolerant of 
standard therapy or for which no standard therapy is available
3) Part B: Pancreatic Adenocarcinoma (Cohort 4)
a) Presence of histologically confirmed inoperable locally 
advanced or metastatic pancreatic adenocarcinoma
4) Part B: NSCLC (Cohorts 5 and 6)
a) Stage IIIB with malignant pleural effusion/pleural seeding 
or stage IV histologically confirmed NSCLC
b) Absence of known epidermal growth factor receptor (EGFR) 
mutation
c) Absence of known translocation or inversion events 
involving the ALK gene locus (resulting in 
EML4-ALK fusion)
5) Part B: Esophagogastric Adenocarcinoma (Cohort 7)
a) Histologically confirmed inoperable advanced gastric 
adenocarcinoma (including adenocarcinoma of the 
gastroesophageal junction) or relapsed gastric 
adenocarcinoma
b) Human epidermal growth factor receptor 2 (HER2)-negative 
tumor (primary tumor or metastatic lesion)
6) Part B: Colorectal Cancer (Cohort 8)
a) Histologically confirmed inoperable advanced 
adenocarcinoma of the colon or rectum
b) Radiographically measureable disease
c) No prior cytotoxic chemotherapy to treat their 
metastatic disease 
7) Part B: Colorectal Cancer (Cohort 9)
a) Histologically confirmed inoperable advanced 
adenocarcinoma of the colon or rectum
b) Radiographically measureable disease
c) Received first-line combination therapy containing 
oxaliplatin and fluoropyrimidine with or without 
bevacizumab for metastatic disease with documented 
evidence of disease progression during or after treatment 
completion


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8) Part B: Breast Cancer (Cohort 10)
a) Histologically or cytologically confirmed metastatic 
breast cancer
b) Radiographically measureable disease (bone-only, 
central nervous system [CNS], lymphangitic pulmonary 
metastases, and previously irradiated tumors without 
subsequent progression are considered nonmeasurable for 
the purposes of this study)
c) Previous hormonal therapy for metastatic breast cancer or 
cytotoxic adjuvant chemotherapy is allowed
d) Subjects who have received taxane-based adjuvant therapy 
are required to have had a disease-free interval of at least 
12 months after completion of taxane therapy
e) Treatment with weekly single-agent paclitaxel is 
appropriate in the opinion of the treating physician 
(eg, hormone-receptor negative disease, hormone therapy 
unresponsive)
f)
HER-2 negative tumor (primary tumor or metastatic lesion)
9) All acute toxic effects of any prior antitumor therapy resolved 
to Grade ≤1 before the start of study drug dosing (with the 
exception of alopecia [Grade 1 or 2 permitted] and 
neurotoxicity [Grade 1 or 2 permitted]).
10) Eastern Cooperative Oncology Group (ECOG) performance 
status of ≤1
11) Life expectancy of > 3 months in the opinion of the 
investigator
12) Adequate organ function defined as follows:
a) Hematologic: platelets ≥100 × 109/L; hemoglobin 
≥9.0 g/dL; ANC ≥1.5 × 109/L
b) Hepatic: aspartate aminotransferase (AST) / alanine 
aminotransferase (ALT) ≤2.5 × upper limit of normal 
(ULN) (if liver metastases are present, ≤5 × ULN); total or 
conjugated bilirubin ≤1.5 × ULN
c) Renal: serum creatinine ≤1.5 × ULN


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13) Coagulation: international normalized ratio (INR) ≤1.6 
(unless receiving anticoagulation therapy). Subjects on 
full-dose oral anticoagulation must be on a stable dose 
(minimum duration 14 days). If receiving warfarin, the subject 
must have an INR ≤3.0 and no active bleeding (ie, no bleeding 
within 14 days prior to first dose of study drug). Subjects on 
low molecular weight heparin will be allowed.
14) For female subjects of childbearing potential, willingness to 
use a protocol-recommended method of contraception (see 
Section 7.12) from the screening visit throughout the study 
treatment period and for 30 days following the last dose of 
GS-5745. Note: a female subject is considered to be of 
childbearing potential unless she has had a hysterectomy, 
bilateral tubal ligation, or bilateral oophorectomy; has 
medically documented ovarian failure (with serum estradiol 
and follicle-stimulating hormone [FSH] levels within the 
institutional postmenopausal range and a negative serum or 
urine -HCG), or is menopausal (age ≥55 years with 
amenorrhea for ≥6 months).
15) For male subjects of childbearing potential having intercourse 
with females of childbearing potential, willingness to use a 
protocol-recommended method of contraception from the start 
of study drug, throughout the study treatment period, and for 
90 days following the last dose of GS-5745, and to refrain from 
sperm donation from the start of study drug, throughout the 
study treatment period, and for 90 days following the last dose 
of GS-5745. Note: A male subject is considered able to father 
a child unless he has had a bilateral vasectomy with 
documented aspermia or a bilateral orchiectomy, or has 
ongoing testicular suppression with a depot luteinizing 
hormone-releasing hormone (LH-RH) agonist 
(eg, goserelin acetate [Zoladex®]), leuprolide acetate 
[Lupron®]), or triptorelin pamoate [Trelstar®]).
16) Willingness to comply with scheduled visits, drug 
administration plan, imaging studies, laboratory tests, other 
study procedures, and study restrictions
17) Evidence of a signed informed consent form


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Exclusion Criteria
Subjects who meet any of the following exclusion criteria will not 
be enrolled in this study:
1) History or evidence of clinically significant disorder, condition, 
or disease that, in the opinion of the investigator and 
Medical Monitor would pose a risk to subject safety or 
interfere with the study evaluations, procedures, or completion
2) Pregnant or lactating
3) Subject with known CNS metastases, unless metastases are 
treated and stable and the subject does not require systemic 
steroids
4) Part B: Small cell lung cancer
5) Part B: Diagnosis of pancreatic islet cell neoplasm
6) Part B: With the exception of Cohort 9, subjects who have 
received prior cytotoxic chemotherapy to treat their 
metastatic disease
7) Myocardial infarction, symptomatic congestive heart failure 
(New York Heart Association Classification > Class II), 
unstable angina, or serious uncontrolled cardiac arrhythmia 
within the last 6 months of study Day 1
8) History of major surgery within 28 days prior to enrollment
9) Serious systemic fungal, bacterial, viral, or other infection that 
is not controlled or requires IV antibiotics
10) Anti-tumor therapy (chemotherapy, antibody therapy, 
molecular targeted therapy) within 28 days or 5 half-lives, 
whichever is shorter, of study drug dosing (6 weeks for 
nitrosoureas, mitomycin C, or molecular agents with 
t1/2 > 10 days); concurrent use of hormone therapy for breast or 
prostate cancer is permitted
11) Clinically significant bleeding within 28 days of Day 1
12) Subjects known to be positive for human immunodeficiency 
virus (HIV), hepatitis C, or hepatitis B


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Study Procedures/
Frequency:
Screening
Screening (for Parts A and B) will commence with obtaining the 
subject’s signed informed consent and will occur up to 28 days 
prior to the first dosing of study drug on Day 1. Screening 
procedures will include the following: medical history review;
physical examination; vital signs; 12-lead electrocardiogram 
(ECG); ECOG performance status; prior/concomitant medication 
review; blood collection for pregnancy test (females), chemistry,
hematology, and coagulation; AE assessment, and computed 
tomography (CT) or magnetic resonance imaging (MRI)
(scans obtained as part of standard medical practice up to 28 days 
prior to Day 1 of Cycle 1 are acceptable). Baseline tumor lesions 
will be measured and characterized prior to Cycle 1 Day 1 to 
assess the subject disease status prior to beginning treatment.
Treatment
Part A
Subjects meeting eligibility will receive GS-5745 by IV infusion 
over approximately 30 minutes every 2 weeks. Safety and efficacy 
assessments will occur on an outpatient basis including assessment 
of tumor response, physical examination, vital signs, ECG, 
collection of blood samples (for routine safety laboratory 
assessments, GS-5745 PK, anti-GS-5745 antibody, tumor markers, 
and biomarkers at applicable visits), urine pregnancy (prior to each 
infusion of GS-5745 in women of childbearing potential), and 
assessment of AEs. In addition, subjects will undergo CT or MRI 
scans every 8 weeks.
A subject who does not show evidence of disease progression by 
clinical assessment or by CT or MRI may continue receiving 
GS-5745 every 2 weeks until disease progression 
(clinical or radiographic), unacceptable toxicity, withdrawal of 
consent, or other reasons specified in Section 6.4.
Part B
Subjects with pancreatic adenocarcinoma, esophagogastric
adenocarcinoma, CRC, or breast cancer will receive GS-5745 by 
IV infusion over approximately 30 minutes every 2 weeks in
addition to the 28-day cycle chemotherapy (gemcitabine and 
nab-paclitaxel for pancreatic; mFOLFOX6 for esophagogastric; 
mFOLFOX6 and bevacizumab for first-line CRC; FOLFIRI and 
bevacizumab for second-line CRC; paclitaxel for breast) as 
described in the Reference Therapy Section below.


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Subjects with NSCLC will receive GS-5745 by IV infusion over 
approximately 30 minutes every 3 weeks (Q3W) in addition to the 
21-day cycle chemotherapy (carboplatin and pemetrexed in 
subjects with lung adenocarcinoma; carboplatin and paclitaxel in 
subjects with lung squamous cell carcinoma) as described in the 
Reference Therapy Section below. 
Safety and efficacy assessments will occur on an outpatient basis 
including assessment of tumor response, physical examination, 
vital signs, ECG, collection of blood samples (for routine safety 
laboratory assessments, GS-5745 PK, anti-GS-5745 antibody,
tumor markers, and biomarkers at applicable visits), urine 
pregnancy (prior to each infusion of GS-5745 in women of 
childbearing potential), and assessment of AEs. A CT or MRI scan 
will be performed during the last week of even-numbered cycles 
(ie, Cycles 2, 4, 6, etc.) for subjects with pancreatic
adenocarcinoma, esophagogastric adenocarcinoma, CRC, and 
breast cancer and during the last week of every third cycle 
(ie, Cycles 3, 6, 9, etc.) for subjects with NSCLC.
Continuation of Treatment
In Parts A and B, study drug dosing will continue in the absence of 
disease progression or toxicity warranting discontinuation of 
therapy.
Test Product, Dose, and 
Mode of Administration:
GS-5745 is formulated as a sterile, aqueous buffered solution and 
is stored at 2 to 8 °C in single-use 10 mL vials.  Prior to 
administration, single and/or multiple vials of GS-5745 will be 
diluted into a sterile IV bag / solution.  Subjects will be 
administered GS-5745 IV over approximately 30 minutes.
Part A: subjects will be administered GS-5745 IV every 2 weeks.
Part B: subjects will be administered GS-5745 IV every 
2 weeks (pancreatic, esophagogastric, CRC, and breast) or every 
3 weeks (lung).


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Reference Therapy, 
Dose, and Mode of 
Administration:
Part B Only
Pancreatic Adenocarcinoma: Gemcitabine 1000 mg/m2 IV on 
Days 1, 8, and 15 of a 28-day treatment cycle and nab-paclitaxel 
125 mg/m2 IV on Days 1, 8, and 15 of a 28-day treatment cycle.
NSCLC: Carboplatin IV dosed to an area under the 
concentration-time curve of 6 mg/mL•min (AUC 6) on Day 1 of 
each 21-day treatment cycle and pemetrexed 500 mg/m2 IV on 
Day 1 of each 21-day treatment cycle in subjects with lung 
adenocarcinoma. Chemotherapy will consist of carboplatin IV 
dosed to an area under the concentration-time curve of 
6 mg/mL•min (AUC 6) on Day 1 of each 21-day treatment cycle 
and paclitaxel 200 mg/m2 IV on Day 1 of each 21-day treatment 
cycle in subjects with lung squamous cell carcinoma. Subjects who 
have not had disease progression after 4 cycles of treatment may 
have some of their treatment reduced based upon the investigator’s 
assessment of what is in the subject’s best interests. However, 
dosing with GS-5745 should be continued per protocol.
Esophagogastric Adenocarcinoma: mFOLFOX6 on 
Days 1 and 15 of each 28-day treatment cycle. The mFOLFOX6 
dosing regimen will consist of l-leucovorin (LV) 200 mg/m2 or 
dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 
5-FU 400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2. 
Administration of mFOLFOX6 will immediately follow 
administration of GS-5745 on Day 1 of each cycle.
First-Line CRC: mFOLFOX6 on Days 1 and 15 of each 28-day 
treatment cycle and bevacizumab 5 mg/kg IV on Days 1 and 15 of 
each 28-day treatment cycle; mFOLFOX6 dosing described above.
Second-Line CRC: FOLFIRI on Days 1 and 15 of each 28-day 
treatment cycle and bevacizumab 5 mg/kg IV on Days 1 and 15 of 
each 28-day treatment cycle. The FOLFIRI dosing regimen will 
consist of l-LV 200 mg/m2 or dl-LV 400 mg/m2 as a 2-hour 
infusion, and irinotecan 180 mg/m2 given as a 90-minute infusion 
in 500 mL dextrose 5% via a Y-connector, followed by bolus 5-FU 
400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2.
Breast Cancer: Paclitaxel 80 mg/m2 IV over 1 hour on 
Days 1, 8, and 15 of each 28-day treatment cycle.
Criteria for Evaluation:
Safety:
Safety will be evaluated by assessment of clinical laboratory tests,
physical examinations, 12-lead ECGs, vital sign measurements, 
and by the documentation of AEs.
PK:
The PK parameters calculated will include: Cmax, AUC, CL, and t1/2.


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Statistical Methods:
Descriptive statistics, including means, medians, standard 
deviations, and ranges will be calculated for continuous variables, 
and categorical data will be summarized using frequency counts 
and percentages.
Sample Size
Parts A and B: Part A will comprise 12 to 48 subjects and Part B 
will comprise 115 to 295 subjects (including up to 15 replacement 
subjects for Cohort 8 and Cohort 9, respectively). The sample size 
is based on practical considerations and is consistent with this type 
of study.
Ten subjects each will be enrolled in Cohorts 5 and 6, and 
15 subjects each in Cohorts 7, 8, 9 and 10. A maximum of 
25 additional subjects in each cohort may be enrolled to obtain 
information on safety, PK, pharmacodynamics, and tumor 
response.
Cohort 4 (Pancreatic Adenocarcinoma): With the assumption of 
an overall response rate of 40%, the 90% confidence interval (CI) 
would be 19% to 64% with a sample size of 15, and 26% to 55% 
with a sample size of 35. A total of 35 subjects will be enrolled in 
Cohort 4.
Cohort 8 (First-Line CRC): With the assumption of an ORR of 
60%, the 90% CI would be 36% to 81% with sample size of 15,
and 46% to 73% with a sample size of 40.
Cohort 9 (Second-Line CRC): With the assumption of an ORR
of 25%, the 90% CI would be 10% to 51% with sample size of 15,
and 14% to 39% with a sample size of 40.
Cohort 10 (Breast Cancer): With the assumption of an ORR of 
40%, the 90% CI would be 19% to 64% with sample size of 15,
and 27% to 54% with a sample size of 40.
This study will be conducted in accordance with the guidelines of Good Clinical Practices (GCPs) 
including archiving of essential documents.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
5-FU
5-fluorouracil
AB0041
murine anti-human MMP9 monoclonal antibody
AB0046
murine anti-human MMP9 monoclonal antibody
ADL
activities of daily living
ADR
adverse drug reaction
AE
adverse event
ALK
anaplastic lymphoma kinase
ALT
alanine aminotransferase
ANC
absolute neutrophil count
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
AUCinf
area under the concentration versus time curve extrapolated to infinite time, calculated as 
AUC0-last + (Clast/λz)
AUClast
area under the concentration versus time curve to the last measurable concentration
AUCtau
area under the concentration versus time curve over the dosing interval
BUN
blood urea nitrogen
CA-125
cancer antigen-125
CA 19-9
carbohydrate antigen 19-9
CBC
complete blood count
CEA
carcinoembryonic antigen
CFR
Code of Federal Regulations
cGMP
current Good Manufacturing Practices
CI
confidence interval
CL
clearance
Clast
last observed quantifiable drug concentration 
Cmax
the maximum observed drug concentration
CNS
central nervous system
ConMed
concomitant medication
CR
complete response
CRC
colorectal cancer
CRO
contract research organization
CT
computed tomography scan
Ctau
observed drug concentration at the end of the dosing interval
CTCAE
Common Terminology Criteria for Adverse Events
Da
dalton
dL
deciliter
DSPH
Drug Safety and Public Health
ECG
electrocardiogram
ECM
extracellular matrix


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ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form(s)
EGF
epidermal growth factor
EGFR
epidermal growth factor receptor
EML4
echinoderm microtubule associated protein like 4
EOI
end of infusion
EOS
end-of-study
EudraCT
European clinical trials database
FDA
(United States) Food and Drug Administration
FDP
fibrin degradation products
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice (Guidelines)
Gilead
Gilead Sciences, Inc.
β-HCG
beta human chorionic gonadotropin
HED
human equivalent dose
HER2
human epidermal growth factor receptor 2
HLGT
high-level group term
HLT
high-level term
hr
hour
HSP
hysterosalpingogram
HUS
hemolytic uremic syndrome
ICF
informed consent form
ICH
International Conference on Harmonisation
IHC
immunohistochemistry
IMP
investigational medicinal product
IND
Investigational New Drug (Application)
INR
international normalized ratio
IRB
institutional review board
ISH
in situ hybridization
IUD
intrauterine device
IV
intravenous
IxRS
interactive voice/web response system
Kg
kilogram
LLT
lower-level term
LV
leucovorin
m
meter
MedDRA
Medical Dictionary for Regulatory Activities
mFOLFOX6
5-FU, leucovorin, and oxaliplatin
mg
milligram
mL
milliliter


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mm
millimeter
MMP
matrix metalloproteinase
MRI
magnetic resonance image
MSS
musculoskeletal syndrome
MTD
maximum tolerated dose
MW
molecular weight
NCCN
National Comprehensive Cancer Network
NCI
National Cancer Institute
NGAL
neutrophil gelatinase-associated lipocalin
NOAEL
no-observed adverse effect levels
NSCLC
non-small cell lung cancer
ORR
objective response rate
OS
overall survival
PE
physical examination
PFS
progression-free survival
PK
pharmacokinetic
PLT
platelet(s)
PR
partial response
PSA
prostate-specific antigen
PT
prothrombin time
PTT
partial thrombin time
Q2W
every two weeks
Q3W
every three weeks
QRS
electrocardiographic deflection between the beginning of the Q wave and termination of the 
S wave representing time for ventricular depolarization
QT
electrocardiographic interval between the beginning of the Q wave and termination of the 
T wave representing the time for both ventricular depolarization and repolarization to occur
QTc
QT interval corrected for heart rate
RECIST
Response Evaluation Criteria in Solid Tumors
SADR
serious adverse drug reaction
SAE
serious adverse event
SD
standard deviation
SOC
system organ class
SOP
standard operating procedure
SUSAR
suspected unexpected serious adverse reaction
TIMP
tissue inhibitors of metalloproteinases
Tlast
time (observed time point) of Clast
Tmax
time (observed time point) of Cmax
T1/2
estimate of the terminal elimination half-life of the drug, calculated by dividing the natural 
log of 2 by the terminal elimination rate constant (λz)
UC
ulcerative colitis


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ULN
upper limit of the normal range
US
United States
USP
United States Pharmacopoeia
VEGF
vasoactive endothelial growth factor
WBC
white blood cell count
wks
weeks
Zn
zinc
λz
terminal elimination rate constant; estimated by linear regression of the terminal elimination 
phase of the log concentration versus time curve of the drug


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1.
INTRODUCTION
1.1.
Background
Matrix metalloproteinases (MMPs) comprise a family of at least 23 Zn2+-dependent proteases 
which are primarily involved in the degradation and remodeling of the extracellular matrix 
(ECM) and basement membranes in many normal as well as pathologic biological processes. 
They are typically grouped based on their structure or their primary substrates and include the 
gelatinases, collagenases, stromelysins, matrilysins, an elastase, and membrane-type MMPs, a 
group of cell surface tethered proteases {Hu et al 2007}, {Mott et al 2004}. The gelatinases 
comprise MMP2 and MMP9, sometimes referred to as type IV collagenases, which are named 
for their ability to degrade type IV collagen and gelatin, a denatured form of collagen {Kridel et 
al 2001}, {Chen et al 2002}. The contrasting roles of MMP9 and MMP2 have been revealed in a 
variety of studies which support a more ubiquitous expression pattern and associated role for 
MMP2 in normal tissue homeostasis, compared with disease-induced and pathology-associated 
expression and activity of MMP9 {Hu et al 2007}, {Garg et al 2009}, {Itoh et al 2002}, 
{Agrawal et al 2006}, {Dubois et al 1999}, {Li et al 2009}, {Miyazaki et al 2011}, {Castaneda 
et al 2005}, {Naito et al 2005}, {Santana et al 2006}. Additional substrates have been identified
for MMP9, and the active enzyme can release cytokines, growth factors, and bioactive 
fragments, which in turn modulate inflammation, neovascularization, and matrix remodeling
{Hijova 2005}. MMP9 is an inducible MMP that is secreted as a zymogen and activated in a 
“cysteine switch” mechanism by the cleavage of the peptidoglycan binding domain {Van Wart et 
al 1990}. While activation of MMP9 appears to be carried out by other MMPs, the protease’s 
activity is also regulated by the binding of tissue inhibitors of metalloproteinases (TIMPs), 
primarily by TIMP1 {Imai et al 1995}, {Vempati et al 2007}, {Olson et al 1997}. Elevated 
MMP9 expression in diseased tissue and plasma is associated with several human diseases. The 
health and largely normal development of the MMP9 knockout mouse has enabled evaluation in 
a variety of disease models, and these data support a significant role for MMP9 in a variety of 
inflammatory, fibrotic, and oncologic processes {Hu et al 2007}, {Itoh et al 2002}, {Dubois et al 
1999}, {Itoh et al 1999}, {Opdenakker et al 2003}.
More recent studies in the MMP field have revealed diversity in the functional roles of MMPs in 
disease and normal homeostasis, suggesting a therapeutic opportunity for selective inhibitors. 
Despite their structural similarities, expression analysis in human disease and data from 
knockout mice reveal contrasting roles for MMP9 and MMP2 regulation and activity in normal 
homeostasis and in disease. MMP9 expression is restricted to limited cell types in healthy tissues
whereas MMP2 is found to be more constitutively expressed {Hu et al 2007}. The disease-
associated induction and functions of MMP9 render it an attractive therapeutic target.
1.1.1.
MMP9 Expression in Oncology
Matrix metalloproteinase 9 is expressed by tumor epithelia as well as infiltrating macrophages,
other inflammatory cells, fibroblastic stroma, and tumor-associated endothelial cells. Expression 
of MMP9 by tumor epithelia in particular has been implicated in many pro-tumorigenic 
processes and is associated either with loss of tumor suppressor or gain of oncogenic activity, as 


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a temporal response to either changes in local tumor environment, or during processes such as 
invasion and proliferation. A selection bias was applied for tumors in which MMP9 expression 
by tumor cells was consistently evident. Immunohistochemical and transcript analysis across 
multiple tumor types demonstrate heterogeneous MMP9 expression across samples, and within 
different regions or sections of the same case. MMP2 expression was also assessed in a subset of 
tumors (lung, gastric, colorectal). While expression of MMP2 was observed, MMP9 showed a 
more consistent pattern of upregulation in tumor tissues compared with healthy tissues.
1.2.
General Information
GS-5745 is a humanized high-affinity monoclonal antibody selective for MMP9. GS-5745 was 
derived from the murine anti-human MMP9 monoclonal antibody, AB0041, and shares the same 
binding characteristics. GS-5745 and AB0041 cross-react with and inhibit rat and cynomolgus 
monkey MMP9, but not murine MMP9. AB0046, which cross-reacts with and inhibits murine 
MMP9, was generated via immunization in MMP9 knockout mice. Epitope mapping analysis 
revealed that AB0046 binds a similar region in murine MMP9 to that bound by GS-5745 and 
AB0041 in human MMP9.
1.2.1.
Preclinical Pharmacology and Toxicology
Pharmacology
The therapeutic potential of inhibitory antibodies targeting human MMP9 (AB0041) and mouse 
MMP9 (AB0046) was evaluated in a surgical orthotopic xenograft mouse model of colorectal 
carcinoma in which tumors were derived from the human tumor cell line HCT116. In this 
treatment model, selective inhibition of MMP9 using a cocktail of anti-human MMP9 and 
anti-mouse MMP9 antibodies significantly reduced growth of the primary tumor and reduced the 
incidence of metastases in 4 independent studies. Treatment with anti-human-MMP9 antibody 
alone yielded tumor growth reduction similar to treatment with both anti-human-MMP9 and 
anti-mouse-MMP9 antibodies, suggesting an important role for tumor epithelial-derived MMP9 
in primary tumor outgrowth. However, targeting of stromal MMP9 was necessary for maximum 
efficacy with respect to incidence of metastases, highlighting the disease-associated role of other 
cellular sources of MMP9 in tumorigenesis.
The major dose limiting toxicity (DLT) observed in clinical studies with pan-MMP inhibitors, 
such as marimastat, was musculoskeletal syndrome (MSS) consisting of tendonitis manifested by 
joint stiffness, edema, reduced mobility, and skin discoloration. A study to evaluate the potential 
of an anti-MMP9 antibody to induce MSS was conducted in Lewis rats. Unlike the pan-MMP 
inhibitor, Marimastat, AB0041 did not induce any evidence of MSS or other toxicities in this
MSS model.
Further details on non-clinical pharmacology are available in the GS-5745 Investigator’s Brochure.


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Toxicology
The toxicology program consists of a human-tissue cross-reactivity study, 4-week repeat-dose IV 
toxicity studies with 4-week recovery in both rats and monkeys, and 26-week toxicity studies in 
both rats and monkeys that included both IV and subcutaneous (SC) routes. Rat and rabbit 
embryo fetal development studies and a rat fertility study have been also concluded.
In the human-tissue cross-reactivity study, no specific GS-5745 staining was observed in normal 
human tissues. In the 4-week repeat-dose toxicity studies, findings associated with GS-5745 
were limited to non-adverse reversible physeal hypertrophy in rats and reversible increased 
adrenal gland weight in female monkeys at all doses. The increased adrenal weight was
associated with slight hypertrophy of the zona fasciculata in a single female monkey dosed at 
100 mg/kg. The physeal hypertrophy in rats is likely directly attributable to inhibition of MMP9,
as similar findings were observed in MMP9 null mice {Vu et al 1998} and in children with 
mutations in MMP9 and MMP13 {Lausch et al 2009}. In both mice and children, this is a 
transient finding that spontaneously regresses as the bone matures. The physeal hypertrophy 
noted in rats is not considered relevant to adult humans because the growth plates are closed and 
longitudinal bone growth is no longer ongoing in adults. In the 26-week studies, there were no 
findings of toxicological concern in rats or cynomolgus monkeys following weekly IV or SC 
administration at the highest tested doses of 100 mg/kg/dose (IV) and 150 mg/kg/dose (SC). 
These doses represent the no-observed-adverse-effect-level (NOAEL) in the rat and monkey in 
these chronic studies. At doses of GS-5745 up to 100 mg/kg IV, no test article-related maternal 
or fetal effects were observed in rats and rabbits, and no test article-related effects were observed 
on male or female fertility in rats.
Further details on the toxicology program are available in the GS-5745 Investigator’s Brochure.
1.2.2.
Summary of Phase 1 Study of GS-5745 as Monotherapy and in Combination 
with Chemotherapy in Subjects with Advanced Solid Tumors
(Study GS-US-296-0101)
As of 16 April 2015, 100 subjects had received up to 30 infusions of GS-5745 at the following 
strengths: 200 mg (n = 4), 600 mg (n = 3), 800 mg (n = 67), 1200 mg (n = 20), and 1800 mg 
(n = 6) as monotherapy or in combination with chemotherapy (800 and 1200 mg). Preliminary 
safety data for this ongoing study are provided herein. Table 1-1 and Table 1-2 summarize the 
treatment-emergent adverse events (AEs) reported by > 15% of subjects overall in Parts A and B 
of the study, respectively. The most common treatment-emergent AEs after monotherapy 
treatment were nausea, dyspnea, and fatigue. The most common treatment-emergent AEs after 
combination treatment of GS-5745 and chemotherapy were fatigue, nausea, and diarrhoea. There 
is currently no evidence of musculoskeletal symptoms associated with GS-5745 treatment.
A total of 106 serious adverse events (SAEs) involving 40 subjects were reported. The most 
common SAEs were pyrexia (n =5), dyspnea (n = 4), vomiting (n = 4), anemia (n = 3), atrial 
fibrillation (n = 3), deep vein thrombosis (n = 3), diarrhoea (n = 3), hypokalemia (n = 3), nausea 
(n = 3), and pneumonia (n = 3). Three SAEs were reported with a fatal outcome: duodenal 
perforation in a subject with pancreatic adenocarcinoma, which was considered by the 
investigator to be unrelated to GS-5745, gemcitabine, or paclitaxel; neutropenia in a subject with 


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lung adenocarcinoma, which was considered by the investigators to be related to carboplatin and 
unrelated to GS-5745 or pemetrexed; and septic shock in a subject with esophagogastric 
adenocarcinoma, which was considered by the investigators to be unrelated to GS-5745, 
oxaliplatin, leucovorin, or 5-FU. Overall, GS-5745 appears to be safe and well-tolerated at 
multiple doses up to 1800 mg every 2 weeks (Q2W) in subjects with advanced solid tumors.
In the pancreatic adenocarcinoma cohort, 33 subjects treated with GS-5745, gemcitabine, and 
nab-paclitaxel have had baseline and post-treatment scans. The best overall responses based on 
investigator assessment were, partial response (PR) in 14 subjects, stable disease (SD) in 
13 subjects, and progressive disease (PD) in 6 subjects, resulting in a response rate of 42% and 
disease stabilization rate of 82%. 36.1% of these subjects remain on study and continue to 
receive treatment with GS-5745, gemcitabine, and nab-paclitaxel.
In the esophagogastric adenocarcinoma cohort, 19 subjects treated with GS-5745 and 
mFOLFOX6 have had baseline and post-treatment scans. The best overall responses based on 
investigator assessment were complete response (CR) in 1 subject, PR in 10 subjects, SD in 
7 subjects, and PD in 1 subject resulting in a response rate of 58% and disease stabilization rate 
of 95%. A majority of these subjects remain on study and continue to receive treatment with 
GS-5745 and mFOLFOX6. 
Preliminary evaluation of serum markers of MMP9 enzymatic activity, including neo-epitope 
products of collagen cleavage by MMP9, demonstrate a decrease in several of the markers 
between Cycle 1 Day 1 predose and Cycle 2 Day 1 in a majority of subjects. These markers 
include the breakdown products of C1M, C3M, C4M2, and laminin.
Additional safety and efficacy data regarding GS-5745 is available in the Investigator's 
Brochure.


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Table 1-1.
GS-US-296-0101: Treatment-Emergent Adverse Events Occurring in 
> 15% of Monotherapy Subjects Overall by Dose Cohort
Adverse Events by SOC and PT
Cohort 1
200 mg
N = 4
n (%)
Cohort 2
600 mg
N = 3
n (%)
Cohort 3
1800 mg
N = 6
n (%)
Total
N = 13
n (%)
Gastrointestinal Disorders
2 (50.0)
2 (66.7)
2 (33.3)
6 (46.2)
Nausea
1 (25.0)
2 (66.7)
2 (33.3)
5 (38.5)
Vomiting
1 (25.0)
0
2 (33.3)
3 (23.1)
Diarrhoea
2 (50.0)
0
0
2 (15.4)
General Disorders and Administration Site Conditions
2 (50.0)
2 (66.7)
1 (16.7)
5 (38.5)
Fatigue
2 (50.0)
2 (66.7)
0
4 (30.8)
Asthenia
1 (25.0)
1 (33.3)
0
2 (15.4)
Chest Discomfort
1 (25.0)
0
1 (16.7)
2 (15.4)
Musculoskeletal and Connective Tissue Disorders
1 (25.0)
1 (33.3)
3 (50.0)
5 (38.4)
Arthralgia
0
1 (33.3)
1 (16.7)
2 (15.4)
Nervous System Disorders
1 (25.0)
1 (33.3)
2 (33.3)
4 (30.8)
Dizziness
1 (25.0)
1 (33.3)
1 (16.7)
3 (23.1)
Respiratory, Thoracic, and Mediastinal Disorders
1 (25.0)
0
3 (50.0)
4 (30.8)
Dyspnoea
1 (25.0)
0
3 (50.0)
4 (30.8)
Cough
1 (25.0)
0
2 (33.3)
3 (23.1)
PT = preferred term; SOC = system organ class
Adverse events were mapped according to MedDRA 17.0. Subjects were counted only once for each PT. Subjects with multiple 
PTs within an SOC were counted only once for that SOC.


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Table 1-2.
GS-US-296-0101: Treatment-Emergent Adverse Events Occurring in 
> 15% of Combination Therapy Subjects Overall by Dose Cohort
Adverse Events by SOC and PT
Cohort 4
800 mg
N = 36
n (%)
Cohort 5
1200 mg
N = 10
n (%)
Cohort 6
1200 mg
N = 10
n (%)
Cohort 7
800 mg
N = 31
n (%)
Total
N = 87
n (%)
Blood and Lymphatic System Disorders
20 (55.6)
10 (100)
5 (50.0)
16 (51.6)
51 (58.6)
Neutropenia
11 (30.6)
4 ( 40.0)
2 (20.0)
10 (32.3)
27 (31.0)
Anaemia
8 (22.2)
8 ( 80.0)
3 (30.0)
6 (19.4)
25 (28.7)
Thrombocytopenia
9 ( 25.0)
2 (20.0)
1 (10.0)
6 (19.4)
18 (20.7)
Gastrointestinal Disorders
30 (83.3)
7 (70.0)
9 (90.0)
21 (67.7)
67 (77.0)
Nausea
15 (41.7)
3 (30.0)
5 (50.0)
15 (48.4)
38 (43.7)
Diarrhoea
15 (41.7)
4 (40.0)
3 (30.0)
11 (35.5)
33 (37.9)
Constipation
9 (25.0)
1 (10.0)
4 (40.0)
8 (25.8)
22 (25.3)
Vomiting
10 (27.8)
1 (10.0)
3 (30.0)
4 (12.9)
18 (20.7)
General Disorders and Administration Site Conditions
34 (94.4)
7 (70.0)
8 (80.0)
16 (51.6)
65 (74.7)
Fatigue
26 (72.2)
5 (50.0)
7 (70.0)
11 (35.5)
49 (56.3)
Oedema Peripheral
18 (50.0)
2 (20.0)
0
5 (16.1)
25 (28.7)
Pyrexia
10 (27.8)
1 (10.0)
1 (10.0)
3 (9.7)
15 (17.2)
Metabolism and Nutrition Disorders
21 (58.3)
3 (30.0)
5 (50.0)
13 (41.9)
42 (48.3)
Decreased Appetite
11 (30.6)
1 (10.0)
2 (20.0)
4 (12.9)
18 (20.7)
Nervous System Disorders
24 (66.7)
3 (30.0)
6 (60.0)
15 (48.4)
48 (55.2)
Neuropathy Peripheral
10 (27.8)
0
4 (40.0)
9 (29.0)
23 (26.4)
Dysgeusia
10 (27.8)
1 (10.0)
1 (10.0)
5 (16.1)
17 (19.5)
Respiratory, Thoracic and Mediastinal Disorders
19 (52.8)
6 (60.0)
10 (100)
13 (41.9)
48 (55.2)
Dyspnoea
5 (13.9)
3 (30.0)
3 (30.0)
5 (16.1)
16 (18.4)
Cough
10 (27.8)
1 (10.0)
2 (20.0)
2 (6.5)
15 (17.2)
Skin and Subcutaneous Tissue Disorders
28 (77.8)
5 (50.0)
6 (60.0)
10 (32.3)
49 (56.3)
Alopecia
20 (55.6)
2 (20.0)
5 (50.0)
2 (6.5)
29 (33.3)
Rash
8 (22.2)
2 (20.0)
1 (10.0)
4 (12.9)
15 (17.2)
PT = preferred term; SOC = system organ class
Adverse were mapped according to MedDRA 17.1. Subjects were counted only once for each PT. Subjects with multiple PTs 
within an SOC were counted only once for that SOC.


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1.2.3.
Rationale for Dose Selection
Estimated safety margins for GS-5745 based on the NOAELs determined in the repeat-dose 
toxicity studies are presented in Table 1-3. The proposed human starting dose is 200 mg every 
2 weeks. Given the large safety margins (~33-fold) based on dose, the nonclinical toxicology 
studies are considered adequate for supporting the proposed study in oncology subjects. In 
addition, the observed exposures (AUC) at the NOAELs in the 4-week repeat dose rat and 
monkey studies are expected to be 18- and 44-fold higher, respectively, than the predicted human 
exposure at the starting dose of 200 mg Q2W in oncology subjects. The observed exposures 
(AUC) at the NOAELs in the 26-week IV repeat dose rat and monkey studies are expected to be 
8- and 24-fold higher, respectively, than the predicted human exposure at a dose of 800 mg Q2W
in oncology subjects (Table 1-4). Exposure margins at 1200 mg every 3 weeks (Q3W) are 
expected to be similar.
The doses for evaluation are expected to provide a wide range of exposures over a 9-fold dose 
range, using planned 3-fold (0.5 log) dose increments conventionally used in first-in-human 
studies and supported by overall nonclinical safety data. The GS-5745 doses of 800 mg Q2W or 
1200 mg Q3W are expected to reach pharmacokinetic (PK) linearity (or target saturation) at 
trough concentrations.
Table 1-3.
Estimated Safety Margins for GS-5745 Based on Human Equivalent 
Dose and Projected Exposure at the Highest Proposed Human Dose
Species
NOAEL
(mg/kg/dose)
HEDa
(mg/kg/dose)
Day 21 AUC0-336hr
b
(μg•hr/mL)
Safety/Exposure Margins
HEDc
AUCd
Rat
100
100
438,000
33
18
Monkey
100
100
1,062,000
33
44
HED = human equivalent dose
a
Because GS-5745 is a biologic with a MW of ~144,000 Da, the HED is normalized based on mg/kg rather than body surface area 
(FDA Guidance, 2005 Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers).
b
Mean combined male and female AUC0-168hr(7 days) × 2 to estimate AUC0-336hr(14 days) to allow comparison with projected 
human efficacious steady state AUC0-336hr(14 days).
c
Based on a starting dose of 200 mg (~3 mg/kg in a 66-kg patient) Q2W.
d
Based on a starting dose of 200 mg (~3 mg/kg in a 66-kg patient) Q2W with a projected steady state AUC0-336hr(14 days) of 
24,200 μg•hr/mL.


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Table 1-4.
Estimated Exposure Margins for Intravenous GS-5745 800 mg, 
Every Other Week
Species
Duration of Dosing
Route
NOAEL
(mg/kg/week)
GS-5745 AUC(0-336h)
(μg•h/mL)
Predicted 
Exposure Marginc
Rat
26 weeks
IV
100
538,000a
8.5
Monkey
26 weeks
IV
100
1,531,000b
24.3
Rat
26 weeks
SC
150
202,000a
3.2
Monkey
26 weeks
SC
150
1,438,000b
22.8
h = hour(s); IV = intravenous; SC = subcutaneous
a
PK data are from Week 24 of the 26-week repeat-dose rat study (AUC(0-336h) = AUC(0-168h) × 2).
b
PK data are from Week 25 of the 26-week repeat dose monkey study (AUC(0-336h) = AUC(0-168h) × 2).
c
Based on an estimated human AUCinf of 63040 μg•h/mL following every-other-week administration of GS-5745 800 mg. 
Value extrapolated using AUCinf at 1800 mg assuming dose proportionality (Study GS-US-296-0101).
Further details on the non-clinical toxicology and PK of GS-5745 are available in the 
Investigator’s Brochure.
1.2.4.
Clinical Trials of GS-5745
In addition to the clinical development program in solid tumors, GS-5745 is being developed for
the treatment of inflammatory bowel disease, rheumatoid arthritis, cystic fibrosis, and chronic
obstructive pulmonary disease. Details of the clinical studies of these diseases is available in the 
appropriate sections of the Investigator's Brochure.
1.3.
Rationale for Evaluating GS-5745 in Select Solid Tumors
Expression patterns of MMP9, previous clinical experience with a pan-MMP inhibitor, and data 
on correlation of MMP9 expression and survival are the basis for evaluating GS-5745 in 
combination with chemotherapy in pancreatic adenocarcinoma, non-small cell lung cancer 
(NSCLC), and esophagogastric adenocarcinoma. The expression of MMP9 in tumor epithelia as 
assessed by in situ hybridization (ISH, RNA) and immunohistochemistry (IHC, protein) is 
evident in a majority of patients with these tumor types. Elevated MMP9 levels (protein or RNA) 
have been significantly correlated with worse overall survival (OS). In addition, elevated 
expression of MMP9 has been directly implicated as a pathologic consequence of function of 
tumor suppressors such as KISS1, RUNX3, RECK, NDRG2, and KAI1/CD82; the loss of these 
tumor suppressors is associated with these tumor types.
Although Phase 3 clinical trials of previous MMP inhibitors have failed to meet their primary 
endpoints in advanced cancer, one trial highlighted the potential benefit of MMP inhibition in 
cancer. In a randomized trial of 369 subjects with gastric cancer, marimastat-treated subjects
trended toward better survival (p = 0.07) with a statistically significant benefit in favor of 
marimastat for progression-free survival (PFS, p = 0.009). A significant survival benefit was 
identified at study completion in the pre-defined subgroup of 123 subjects who had received 
prior chemotherapy (p = 0.043) {Bramhall et al 2002}.


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1.4.
Rationale for Chemotherapy Regimens in Part B
Following the conduct of this study, the next studies of GS-5745 will be randomized, 
placebo-controlled Phase 2 trials or randomized, placebo-controlled Phase 3 registration trials in 
combination with chemotherapy. The purpose of Part B is to obtain safety data with GS-5745 
when combined with commonly used, standard chemotherapy regimens for diseases in which 
GS-5745 is most likely to be efficacious: pancreatic adenocarcinoma, NSCLC, colorectal cancer 
(CRC), breast cancer, and esophagogastric adenocarcinoma.
The GS-5745 infusion schedules (Q2W in pancreatic adenocarcinoma, esophagogastric
adenocarcinoma, CRC, and breast cancer, and Q3W in NSCLC) have been proposed to align 
with the standard of care chemotherapy schedules.
1.4.1.
Pancreatic Adenocarcinoma
Gemcitabine is still commonly used as first-line therapy in pancreatic adenocarcinoma.
The combination chemotherapy regimen of FOLFIRINOX demonstrated improved survival 
compared with gemcitabine but was much more toxic and its use is restricted to patients with 
excellent performance status {Conroy et al 2011}. A study evaluating the addition of 
nab-paclitaxel to gemcitabine reported increased median OS of 1.8 months relative to 
gemcitabine alone. We anticipate that randomized Phase 2 trials of GS-5745 in pancreatic 
adenocarcinoma will use gemcitabine in combination with nab-paclitaxel. Given the tolerability 
issues and limited applicability of the FOLFIRINOX regimen, it will not be studied in 
combination with GS-5745 in Part B.
1.4.2.
Non-Small Cell Lung Cancer
Platinum agents (cisplatin and carboplatin) are the backbone of therapy for metastatic NSCLC 
that is epidermal growth factor (EGFR) mutation negative and EML4-ALK mutation negative. 
First-line cytotoxic combination chemotherapy includes a platinum agent with paclitaxel, 
gemcitabine, docetaxel, vinorelbine, irinotecan, or pemetrexed. In the United States (US), the
standard regimen is carboplatin and paclitaxel in patients with squamous cell carcinoma. 
Carboplatin and pemetrexed is commonly used in first-line lung adenocarcinoma patients not 
eligible for bevacizumab. In Part B, GS-5745 will be combined with carboplatin and paclitaxel 
(squamous) or carboplatin and pemetrexed (adenocarcinoma) to cover the 2 populations that may 
be evaluated in Phase 2 randomized studies in NSCLC.
1.4.3.
Esophagogastric Adenocarcinoma
Treatment of metastatic human epidermal growth factor receptor 2 (HER2) negative 
esophagogastric adenocarcinoma consists of combination chemotherapy with a triplet or doublet 
cytotoxic regimen. The triplet regimen of docetaxel/cisplatin/5-FU is the only approved 
combination in the US. Because of significant toxicity, this combination is reserved for patients who 
are medically fit and have good performance status. The National Comprehensive Cancer Network 
(NCCN) guidelines for the treatment of metastatic disease in the first-line setting recommend a 
2-drug regimen. A common regimen includes a fluoropyrimidine (5-FU or capecitabine) and 


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platinum agent (cisplatin or oxaliplatin). There are no definitive studies demonstrating the 
superiority of either fluoropyrimine or platinum over the other. An mFOLFOX6 regimen is 
commonly used and generally acceptable in the first-line setting to treat advanced esophagogastric 
adenocarcinoma and will be evaluated in Part B in combination with GS-5745.
1.4.4.
Colorectal Cancer
The current management of metastatic CRC in the first- and second-line settings involves 
combination chemotherapy with active agents including 5-FU/LV, oxaliplatin, irinotecan, and 
bevacizumab, among others. Although the NCCN guidelines for the treatment of CRC divide 
treatment regimens into discrete lines of therapy (initial therapy, therapy after first progression, 
etc.), current management of the disease considers the active treatment regimens as a continuum 
of care and it is recommended that patients receive all active agents at some point during their 
treatment course.
The FOLFOX regimen is a well-studied and commonly used initial treatment regimen for 
patients with metastatic CRC since multiple studies demonstrated superiority of FOLFOX over 
LV/FU and LV/FU bolus plus irinotecan {Goldberg et al 2004}, {de Gramont et al 2000}. The 
addition of the anti- vasoactive endothelial growth factor (VEGF) monoclonal antibody,
bevacizumab, to oxaliplatin-based combination chemotherapy resulted in a statistically 
significant improvement in PFS (9.4 months vs. 8 months for placebo) {Saltz et al 2008}, and 
the addition of bevacizumab to FOLFOX has become established as a first-line therapy for 
metastatic CRC. The occurrence of sensory neuropathy is one of the limiting toxicities of 
oxaliplatin-based combination chemotherapy, and is significant because it may cause patients 
who are continuing to respond to treatment to discontinue therapy. One potential approach to 
avoiding the problem of oxaliplatin neurotoxicity is to limit oxaliplatin administration to 6 to 
8 cycles, while continuing 5-FU/LV (and bevacizumab, if used), with the possibility of 
reintroducing oxaliplatin again (if it was discontinued due to neurotoxicity and not disease 
progression). This “stop-and-go” approach was found to be equivalent to continued therapy in 
the OPTIMOX1 trial {Tournigand et al 2006}, and is recommended in the most current NCCN 
guidelines.
For patients receiving oxaliplatin-based chemotherapy (eg, FOLFOX) in the first-line setting, the 
use of irinotecan-based combination therapy such as FOLFIRI is recommended at the time of 
initial progression. The FOLFIRI regimen has been shown in multiple Phase 3 trials to be an 
effective treatment in both the first- and second-line settings {Fuchs et al 2007}. While the order 
in which patients receive oxaliplatin-based therapy and irinotecan-based therapy has been shown 
to be unimportant, exposure to both FOLFOX and FOLFIRI regimens during the treatment 
course for metastatic CRC patients has led to median OS exceeding 20 months for this disease
{Tournigand et al 2004}. In addition, the continuation of bevacizumab treatment after initial 
progression on combination chemotherapy + bevacizumab shows continued benefit in the setting 
of progressive disease {Grothey et al 2008}.


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1.4.5.
Breast Cancer
Chemotherapy for patients with metastatic breast cancer is used for patients who are not 
candidates for hormone therapy (eg, hormone receptor negative disease) or in those with disease 
that is no longer responsive to hormone therapy. Taxanes are among the most active agents for
the treatment of metastatic breast cancer, and have been extensively studied in multiple clinical 
trials. The Cancer and Leukemia Group B (CALGB) performed a randomized comparison of 
weekly vs. Q3W paclitaxel which demonstrated that weekly paclitaxel is more effective than 
Q3W administration for the treatment of metastatic breast cancer. Weekly paclitaxel showed 
superior response rate (RR; 42% vs. 29%, unadjusted odds ratio [OR] 1.75; p = 0.0004), time to 
progression (TTP; median, 9 vs. 5 months; adjusted HR 1.43; p < 0.0001), and survival 
(median, 24 vs. 12 months; adjusted HR 1.28; p = 0.0092) {Seidman et al 2008}. However, 
Grade 3 neuropathy was more common with weekly dosing (24% vs. 12%; p = 0.0003). The 
superiority of weekly paclitaxel was corroborated by the results of a 2010 meta-analysis, which 
showed that compared with Q3W treatment, weekly administration of paclitaxel resulted in an 
improvement in OS (HR 0.78, 95% CI: 0.67, 0.89) {Mauri et al 2010}.


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2.
OBJECTIVES
The primary objectives of this study are:

To determine the maximum tolerated dose (MTD) of GS-5745 monotherapy in subjects with 
advanced solid tumors

To characterize the safety and tolerability of GS-5745 as monotherapy and in combination 
with various chemotherapy regimens in subjects with select tumor types
The secondary objectives of this study are:

To characterize the PK of GS-5745

To evaluate the formation of anti-GS-5745 antibodies
 
The exploratory objective of this study is:
 
 
CCI
CCI
I 
I 
I 


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3.
STUDY DESIGN
3.1.
Overview
This is an open-label, multicenter, sequential dose-escalation and expansion study to evaluate the 
safety, tolerability, PK, and pharmacodynamics of GS-5745 alone and in combination with 
chemotherapy. The study will be conducted in 2 parts (Parts A and B).
3.1.1.
Part A
Cohorts of subjects with advanced solid tumors who have failed or are intolerant to standard 
therapy or for whom no standard therapy exists will be sequentially enrolled at progressively 
higher dose levels to receive GS-5745 as monotherapy via intravenous (IV) infusion Q2W. Dose 
escalation [3 + 3] will be performed with cohort sizes of 3 to 6 subjects. A single subject will 
initially be enrolled into the first dosing cohort to evaluate any unexpected adverse effects. 
Provided that there are no significant safety signals up to 24 hours postdose, the remaining 
2 subjects will be dosed. The starting dose will be 200 mg. Subsequent doses of 600 mg and 
1800 mg are planned. The safety and tolerability of each dose level will be assessed after all 
subjects in the cohort have been followed for at least 28 days after the first infusion of GS-5745. 
Cohort dose escalation will occur if no subjects experience a DLT during the first 28 days of 
study drug dosing. If 1 subject within the initial cohort of 3 subjects experiences a DLT during 
the first 28 days of study drug dosing, an additional 3 subjects will be enrolled at the same dose 
level. If no DLTs are observed in the additional 3 subjects, dose escalation will occur. If 2 or 
more subjects experience DLTs within the first 28 days, dose de-escalation to an intermediate 
dose will occur. Specifically, if 2 or more subjects experience DLTs at 1800 mg, then 1200 mg 
will be explored. If 2 or more subjects experience DLTs at 600 mg, then 400 mg will be 
explored. The MTD is the highest dose level with a subject incidence of DLTs during the first 
28 days of study drug dosing of 0 or 1 out of 6.
After determination of MTD, Part B will commence. During the conduct of Part B, up to 
3 additional cohorts consisting of no more than 10 subjects each may be studied with GS-5745 at 
monotherapy doses up to the MTD given Q2W to obtain additional information on PK and 
pharmacodynamics.
A DLT is a toxicity defined below considered possibly related to GS-5745 occurring during the 
DLT assessment window (Day 1 through Day 29) in each dose escalation cohort.

Grade 4 neutropenia (absolute neutrophil count [ANC] < 500/μL) for > 7 days, or febrile 
neutropenia (ANC < 1000/μL with fever > 101 °F [38.5 °C])

Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia associated with bleeding

Grade 3 or 4 non-hematologic toxicity (excluding rash, nausea, diarrhea, and vomiting if 
controlled with standard supportive care)


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
Treatment delay of ≥14 days due to unresolved toxicity

Non-hematologic toxicity of ≥Grade 2 (at any time during treatment) that, in the judgment of 
the investigators and the Medical Monitor, is dose-limiting.

For certain toxicities such as laboratory assessments without a clear clinical correlate,
a discussion between the investigator, Medical Monitor, and the Sponsor may take place to 
determine if this AE should be assessed as a DLT necessitating dose reduction.
3.1.2.
Part B
The dose expansion will begin once all subjects in the dose escalation portion of Part A have 
completed the 28-day DLT period. Approximately 115 to 295 subjects with advanced pancreatic 
adenocarcinoma (Cohort 4), lung adenocarcinoma (Cohort 5), lung squamous cell carcinoma 
(Cohort 6), and esophagogastric adenocarcinoma (Cohort 7), CRC in the first-line (Cohort 8), 
CRC in the second-line (Cohort 9), or breast cancer (Cohort 10) will be enrolled to receive 
GS-5745 IV every 2 to 3 weeks in combination with chemotherapy. Thirty-five subjects will be 
enrolled in Cohort 4; ten subjects each in Cohorts 5 and 6, and 15 subjects each in 
Cohorts 7 through 10. During the conduct of Part B, up to a maximum of 25 additional subjects 
in each cohort may be enrolled to obtain information on safety, PK, pharmacodynamics, and 
tumor response.
Table 3-1.
Dose and Regimen for GS-5745 in Parts A and B
Cohort
Number of Subjects
GS-5745 Dose (mg)
Dosing Interval (Wks)
Part A: Dose Escalation
1
3 to 6
200
Q2W
2
3 to 6
600
Q2W
3
6
1800
Q2W
Part B: Dose Expansion
4
35
Based on MTD from Part A 
(see Table 3-2)
Q2W
5
10 to 35
Q3W
6
10 to 35
Q3W
7
15 to 40
Q2W
8
15 to 55*
Q2W
9
15 to 55 **
Q2W
10
15 to 40
Q2W
*
For Cohort 8 (first-line CRC), the sample size of 40 subjects was initially planned. In amendment 5, the dose of 
bevacizumab is corrected to be 5 mg/kg Q2W. Up to 15 subjects who previously started bevacizumab treatment at other 
dose levels will be replaced. Therefore, a total of up to 55 subjects may be enrolled in Cohort 8.
**
For Cohort 9 (second-line CRC), the sample size of 40 subjects was initially planned. In amendment 5, the dose of 
bevacizumab is corrected to be 5 mg/kg Q2W. Up to 15 subjects who previously started bevacizumab treatment at other 
dose levels will be replaced. Therefore, a total of up to 55 subjects may be enrolled in Cohort 9.


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As described in Table 3-2, the cohort dose levels for GS-5745 in Part B will be based on the 
MTD determined in Part A. Dose reduction of GS-5745 is not permitted for subjects enrolled in 
Part B.
Table 3-2.
Dose and Regimen of GS-5745 for Part B Based on the MTD 
Determined in Part A
MTD from Part A (mg)
Doses to be Used in Part B (mg)
Q2W
Q3W
200
133
200
400
267
400
600
400
600
1200
800
1200
1800
800
1200
3.2.
Treatment Plan and Regimen
3.2.1.
Part A
Subjects meeting eligibility will receive GS-5745 by IV infusion over approximately 30 minutes 
Q2W. Safety and efficacy assessments will occur on an outpatient basis, and will include the 
following: assessment of tumor response, physical examinations, vital signs, electrocardiograms 
(ECGs), collection of blood samples (for routine safety laboratory analyses, GS-5745 PK, 
anti-GS-5745 antibody, tumor markers, and biomarkers at applicable visits), urine pregnancy 
(prior to each infusion of GS-5745 in women of childbearing potential), and assessment of AEs.
In addition, subjects will undergo computed tomography (CT) or magnetic resonance imaging 
(MRI) scans every 8 weeks.
A subject who does not show evidence of disease progression by clinical assessment or by CT or 
MRI may continue receiving GS-5745 Q2W until disease progression (clinical or radiographic), 
unacceptable toxicity, withdrawal of consent, or other reasons specified in Section 6.4.
3.2.2.
Part B
Subjects with pancreatic adenocarcinoma, esophagogastric adenocarcinoma, CRC, or breast 
cancer will receive GS-5745 by IV infusion over approximately 30 minutes Q2W in addition to
the 28-day cycle chemotherapy (gemcitabine and nab-paclitaxel for pancreatic adenocarcinoma; 
mFOLFOX6 for esophagogastric adenocarcinoma; mFOLFOX6 and bevacizumab for first-line 
CRC; FOLFIRI and bevacizumab for second-line CRC; and paclitaxel for breast cancer). 
Subjects with NSCLC will receive GS-5745 by IV infusion over approximately 30 minutes Q3W
in addition to the 21-day cycle chemotherapy (carboplatin and pemetrexed in subjects with lung 
adenocarcinoma; carboplatin and paclitaxel in subjects with lung squamous cell carcinoma). 
Safety and efficacy assessments will occur on an outpatient basis and will include the following:


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assessment of tumor response, physical examinations, vital signs, ECGs, collection of blood 
samples (for routine safety laboratory assessments, GS-5745 PK, anti-GS-5745 antibody, tumor 
markers, and biomarkers at applicable visits), urine pregnancy (prior to each infusion of 
GS-5745 in women of childbearing potential), and assessment of AEs. A CT or MRI scan will be
performed during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) for subjects 
with pancreatic adenocarcinoma, esophagogastric adenocarcinoma, CRC, and breast cancer, and 
during the last week of every third cycle (ie, Cycles 3, 6, 9, etc.) for subjects with NSCLC.
Study drug dosing will continue in the absence of disease progression or toxicity warranting 
discontinuation of therapy.
Dose reduction of GS-5745 is not permitted for subjects enrolled in Part B.
Figure 3-1.
Study Schema
Dose Escalation 
3 3 
200 mi Q2 
600 mi Q2 
-+ 
1800 me Q2 
p 
,. 
Dose Expo nsion 
H• f0-40/cohort 


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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Up to 343 subjects who meet the eligibility criteria will be enrolled. Part A will comprise
approximately 12 to 48 subjects, and Part B will comprise between 115 to 295 subjects.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) Male or female ≥18 years of age
2) Part A: histologically or cytologically confirmed advanced malignant solid tumor that is 
refractory to or intolerant of standard therapy or for which no standard therapy is available
3) Part B: Pancreatic Adenocarcinoma
a) Presence of histologically confirmed inoperable locally advanced or metastatic pancreatic 
adenocarcinoma
4) Part B: NSCLC
a) Stage IIIB with malignant pleural effusion/pleural seeding or stage IV histologically 
confirmed NSCLC
b) Absence of known Epidermal Growth Factor Receptor (EGFR) mutation
c) Absence of known translocation or inversion events involving the ALK gene locus 
(resulting in EML4-ALK fusion)
5) Part B: Esophagogastric Adenocarcinoma
a) Histologically confirmed inoperable advanced gastric adenocarcinoma 
(including adenocarcinoma of the gastroesophageal junction) or relapsed
gastric adenocarcinoma
b) Human Epidermal Growth Factor Receptor 2 (HER2)-negative tumor (primary tumor or 
metastatic lesion)
6) Part B: CRC (Cohort 8)
a) Histologically confirmed inoperable advanced adenocarcinoma of the colon or rectum
b) Radiographically measureable disease
c) No prior cytotoxic chemotherapy to treat their metastatic disease


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7) Part B: CRC (Cohort 9)
a) Histologically confirmed inoperable advanced adenocarcinoma of the colon or rectum
b) Radiographically measureable disease
c) Received first-line combination therapy containing oxaliplatin and fluoropyrimidine with 
or without bevacizumab for metastatic disease with documented evidence of disease 
progression during or after treatment completion
8) Part B: Breast Cancer (Cohort 10)
a) Histologically or cytologically confirmed metastatic breast cancer
b) Radiographically measureable disease (bone-only, central nervous system [CNS], 
lymphangitic pulmonary metastases, and previously irradiated tumors without subsequent 
progression are considered nonmeasurable for the purposes of this study)
c) Previous hormonal therapy for metastatic breast cancer or cytotoxic adjuvant 
chemotherapy is allowed
d) Patients who have received taxane-based adjuvant therapy are required to have had a 
disease-free interval of at least 12 months after completion of taxane therapy
e) Patients for whom treatment with weekly single-agent paclitaxel is appropriate in the 
opinion of the treating physician (eg, hormone-receptor negative disease, hormone 
therapy unresponsive)
f)
HER-2 negative tumor (primary tumor or metastatic lesion)
9) All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 before the start of 
study drug dosing (with the exception of alopecia [Grade 1 or 2 permitted] and neurotoxicity 
[Grade 1 or 2 permitted]).
10) Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1
11) Life expectancy of > 3 months in the opinion of the investigator
12) Adequate organ function defined as follows:
a) Hematologic: platelets ≥100 × 109/L; hemoglobin ≥9.0 g/dL; ANC ≥1.5 × 109/L
b) Hepatic: aspartate aminotransferase (AST) / alanine aminotransferase (ALT)
≤2.5 × upper limit of normal (ULN) (if liver metastases are present, ≤5 × ULN); 
total or conjugated bilirubin ≤1.5 × ULN
c) Renal: Serum Creatinine ≤1.5 × ULN


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13) Coagulation: International Normalized Ratio (INR) ≤1.6 (unless receiving anticoagulation 
therapy). Subjects on full-dose oral anticoagulation must be on a stable dose 
(minimum duration 14 days). If receiving warfarin, the subject must have an INR ≤3.0 and 
no active bleeding (ie, no bleeding within 14 days prior to first dose of study drug).
Subjects on low molecular weight heparin will be allowed.
14) For female subjects of childbearing potential, willingness to use a protocol-recommended 
method of contraception (see Section 7.12) from the screening visit throughout the study 
treatment period and for 30 days following the last dose of GS-5745. Note: A female subject 
is considered to be of childbearing potential unless she has had a hysterectomy, bilateral 
tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with 
serum estradiol and follicle-stimulating hormone [FSH] levels within the institutional 
postmenopausal range and a negative serum or urine β-HCG), or is menopausal 
(age ≥55 years with amenorrhea for ≥6 months).
15) For male subjects of childbearing potential having intercourse with females of childbearing 
potential, willingness to use a protocol-recommended method of contraception from the start 
of study drug, throughout the study treatment period, and for 90 days following the last dose 
of GS-5745, and to refrain from sperm donation from the start of study drug, throughout the 
study treatment period, and for 90 days following the last dose of GS-5745. Note: A male 
subject is considered able to father a child unless he has had a bilateral vasectomy with 
documented aspermia or a bilateral orchiectomy, or has ongoing testicular suppression 
with a depot luteinizing hormone-releasing hormone (LH-RH) agonist (eg, goserelin 
acetate [Zoladex®]), leuprolide acetate [Lupron®]), or triptorelin pamoate [Trelstar®]).
16) Willingness to comply with scheduled visits, drug administration plan, imaging studies, 
laboratory tests, other study procedures, and study restrictions
17) Evidence of a signed informed consent form
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) History or evidence of clinically significant disorder, condition, or disease that, in the opinion 
of the investigator and Medical Monitor would pose a risk to subject safety or interfere with 
the study evaluations, procedures, or completion
2) Pregnant or lactating
3) Subject with known CNS metastases, unless metastases are treated and stable and the subject 
does not require systemic steroids
4) For Part B, small cell lung cancer
5) For Part B, diagnosis of pancreatic islet cell neoplasm


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6) For Part B, with the exception of Cohort 9, subjects who have received prior cytotoxic 
chemotherapy to treat their metastatic disease
7) Myocardial infarction, symptomatic congestive heart failure (New York Heart Association 
Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within 
the last 6 months of study Day 1
8) History of major surgery within 28 days prior to enrollment
9) Serious systemic fungal, bacterial, viral, or other infection that is not controlled or requires 
IV antibiotics
10) Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy) within 
28 days or 5 half-lives, whichever is shorter, of study drug dosing (6 weeks for nitrosoureas, 
mitomycin C, or molecular agents with t1/2 > 10 days); concurrent use of hormone therapy for 
breast or prostate cancer is permitted
11) Clinically significant bleeding within 28 days of Day 1
12) Subjects known to be positive for human immunodeficiency virus (HIV), hepatitis C, or 
hepatitis B
4.4.
Excluded Medication
During the course of the clinical trial, study subjects are anticipated to continue the use of 
prescribed medications identified during the screening procedures, consistent with study 
inclusion and exclusion criteria. 
Non-study anticancer chemotherapy, radiation therapy or immunotherapy (approved or 
investigational) are not permitted during the trial. If administered, the subject may be removed 
from the trial.
Concurrent use of hormone therapy for breast or prostate cancer is permitted.


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Enrollment
It is the responsibility of the investigator to ensure that subjects are eligible for the study prior to 
enrollment. Subjects will be assigned a unique screening number at the time of consent.
Once eligibility is confirmed subjects will be assigned a unique subject number. This is an 
open-label study.
All baseline tests and procedures must be completed prior to the administration of the first dose 
of study drug on Day 1. Once a subject number is assigned to a subject, it will not be reassigned 
to another subject.
5.2.
Description and Handling of GS-5745
5.2.1.
Formulation
GS-5745 is formulated as a sterile, aqueous buffered solution and is stored at 2 to 8 °C in 
single-use 10 mL vials.
5.2.2.
Packaging, Labeling, Storage, and Handling
GS-5745 solution will be supplied in 10-mL glass vials with elastomeric stoppers and aluminum 
overseals with flip-off caps. GS-5745 drug product is shipped and stored at 2 °C to 8 °C.
All labels for study drug vials to be distributed to centers in the US will meet all applicable 
requirements of the US Food and Drug Administration (FDA) and other local regulations as 
applicable.
Gilead or designated distribution depots will distribute study drug vials to sites as per current 
Good Manufacturing Practices (cGMP) requirements.
5.3.
Dosage and Administration of GS-5745
The target dose of GS-5745 will be prepared by diluting a single and/or multiple vials of 
GS-5745 into a sterile IV bag / solution.
Study drug will be administered via IV infusion over approximately 30 (± 5) minutes at the 
research clinic by a qualified staff member. The investigator or a qualified designee must be 
present during administration. Subjects should be observed following end of infusion and 
discharged at the discretion of the investigator or qualified designee.
Dose reduction of GS-5745 is not permitted for subjects enrolled in Part B.
Documentation of the GS-5745 administration will be noted on the electronic case report form 
(eCRF) and in the source documentation.


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Details of preparing and administering study drug are included in the Pharmacy Binder provided 
by Gilead.
5.4.
Dosage and Administration of Chemotherapy
Chemotherapy will be administered after study drug dosing according to the following dose and 
schedule:
Pancreatic Adenocarcinoma: gemcitabine 1000 mg/m2 IV on Days 1, 8, and 15 of a 28-day 
treatment cycle and nab-paclitaxel 125 mg/m2 IV on Days 1, 8, and 15 of a 28-day treatment 
cycle. Administration of gemcitabine and nab-paclitaxel will immediately follow administration 
of GS-5745 on Days 1 and 15 of each cycle.
NSCLC: carboplatin IV dosed to an area under the concentration-time curve of 6 mg/mL•min
(AUC 6) on Day 1 of each 21-day treatment cycle, and pemetrexed 500 mg/m2 IV on Day 1 of 
each 21-day treatment cycle in subjects with lung adenocarcinoma. Chemotherapy will consist of 
carboplatin IV dosed to AUC 6 on Day 1 of each 21-day treatment cycle and paclitaxel 
200 mg/m2 IV on Day 1 of each 21-day treatment cycle in subjects with lung squamous cell 
carcinoma. Administration of chemotherapies will immediately follow administration of 
GS-5745 on Day 1 of each cycle. Subjects who have not had disease progression after 4 cycles of 
treatment may have some of their treatment reduced based upon the investigator’s assessment of 
what is in the subject’s best interests. However, dosing with GS-5745 should be continued per 
protocol.
Esophagogastric Adenocarcinoma: mFOLFOX6 on Days 1 and 15 of each 28-day treatment 
cycle. The mFOLFOX6 dosing regimen will consist of l-leucovorin (LV) 200 mg/m2 or dl-LV 
400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5-FU 400 mg/m2 and a 46-hour infusion 
of 5-FU 2400 mg/m2. Administration of mFOLFOX6 will immediately follow administration of 
GS-5745 on Day 1 of each cycle. Administration of mFOLFOX6 will immediately follow 
administration of GS-5745 on Day 1 of each cycle. Administration of mFOLFOX6 will 
immediately follow administration of GS-5745 on Day 1 of each cycle.
First-Line CRC: mFOLFOX6 on Days 1 and 15 of each 28-day treatment cycle and 
bevacizumab at 5 mg/kg IV on Days 1 and 15 of each 28-day treatment cycle. The mFOLFOX6 
dosing is described above.
Second-Line CRC: FOLFIRI on Days 1 and 15 of each 28-day treatment cycle and 
bevacizumab at 5 mg/kg IV on Days 1 and 15 of each 28-day treatment cycle. The FOLFIRI 
dosing regimen will consist of l-LV 200 mg/m2 or dl-LV 400 mg/m2 as a 2-hour infusion, and 
irinotecan 180 mg/m2 given as a 90-minute infusion in 500 mL dextrose 5% via a Y-connector, 
followed by bolus 5-FU 400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2.
Breast Cancer: Paclitaxel 80 mg/m2 IV over 1 hour on Days 1, 8, and 15 of each 28-day 
treatment cycle.


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Dose reductions or discontinuation may be required based on emerging toxicities and should 
follow guidelines specified in the package insert and in Section 6.7. Dosing of gemcitabine, 
nab-paclitaxel, carboplatin, paclitaxel, pemetrexed, 5-FU, leucovorin, and oxaliplatin will be 
documented on the eCRF (and/or the interactive voice/web response system [IxRS] as applicable).
Patients with weight changes +/- 10% compared to screening weight may have their BSA 
recalculated and the dose of drugs (other than GS-5745) modified to reflect weight changes 
according to local practice.
Documentation of chemotherapy administration will be noted on the eCRF and in the source 
documentation.
Please refer to the product package inserts for additional information.
5.4.1.
Study Drug Accountability
The investigator or designee (eg, pharmacist) is responsible for ensuring adequate accountability 
of all used and unused investigational medicinal product during the study. This includes 
acknowledgement of receipt of each shipment of study drug (quantity and condition) and 
tracking of vials assigned/utilized for subject dosing.
Investigational Drug Accountability records will be provided to each study site to:

Record the date of receipt and quantity of study drug.

Record the date of dispensation, subject identifier, and study drug vial number(s) dispensed
(if applicable).
Dispensing records will include the initials of the person dispensing the study drug or supplies.
5.4.2.
Study Drug Return or Disposal
The study drug should be disposed of at the site as per local standard operating procedures. 
Please see Section 9.1.7 for additional instructions.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are described herein 
and presented in tabular form in Appendix 2 to Appendix 8. Any deviation from protocol 
procedures should be noted in the source documents and the Sponsor or 
Contract Research Organization (CRO) should be notified.
Subjects who fail to meet eligibility or complete the initial Screening will be permitted to 
rescreen provided that the reason for screen failure has been resolved and no new exclusions 
have been identified. If the subject is rescreened > 30 days from their original screening date 
(date of informed consent), all screening activities, including informed consent, need to be 
repeated.
6.1.
Subject Enrollment and Treatment Assignment – Part A
6.1.1.
Screening Visit
Subjects will be screened within 28 days before enrollment to determine eligibility for 
participation in the study.
The following procedures will be conducted at Screening:

Obtain written informed consent

Medical history (including review of disease under study, prior surgeries, and prior 
anti-cancer therapies)

Review prior/concomitant medication

Complete physical examination including height and weight

Vital signs including blood pressure, respiratory rate, pulse, and temperature

12-lead ECG

ECOG Performance Status

Obtain blood and/or urine samples for:
Chemistry (see Section 6.8.10)
Hematology (see Section 6.8.10)
Coagulation (see Section 6.8.10)
Serum pregnancy test (females of childbearing potential)


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Serum and plasma biomarkers (see Section 6.8.12.2)
Urinalysis

CT or MRI (scans taken as part of standard medical practice within 4 weeks of Day 1 
are acceptable)

Record any AEs occurring after signing of the consent form

Register subject visit in IxRS
6.1.2.
Treatment Assessments
6.1.2.1.
Day 1
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic on Day 1 to conduct study-required procedures prior to dosing.
The following procedures will be conducted on Day 1:
Pre-dose:

Modified physical examination capturing changes from prior examinations, and weight

Vital signs, including blood pressure, respiratory rate, pulse, and temperature

12-lead ECG

ECOG Performance Status

Obtain blood and/or urine samples for:
Chemistry (see Section 6.8.10)
Hematology (see Section 6.8.10)
Coagulation (see Section 6.8.10)
GS-5745 concentration
Anti-GS-5745 antibody
Serum and plasma biomarkers (see Section 6.8.12.2)
Urine pregnancy test (females of childbearing potential)
Urinalysis


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
Collect archival tumor tissue specimen as applicable; efforts to acquire a tissue sample 
should begin on Day 1

Review of AEs and concomitant medications

Register subject visit in IxRS
Dosing:

Administer GS-5745 via IV infusion over approximately 30 (± 5) minutes
Post-dose: End of Infusion (EOI):

Vital signs including blood pressure, respiratory rate, pulse, and temperature

12-lead ECG

Obtain blood samples for GS-5745 concentration (± 10 minutes)

Review of AEs
Post-dose: Approximately 6 Hours (± 10 minutes) After EOI:

Vital signs including blood pressure, respiratory rate, pulse, and temperature

12-lead ECG

Obtain blood samples for GS-5745 concentration (± 10 minutes)

Review of AEs
6.1.2.2.
Day 2 (24 Hours After EOI ± 2 Hours), Day 3 (48 Hours After EOI ± 4 Hours), 
and Day 5 (96 Hours After EOI ± 4 Hours)
The following procedures will be conducted on Days 2, 3, and 5:

Vital signs including blood pressure, respiratory rate, pulse, and temperature

ECOG Performance Status

Obtain blood samples for GS-5745 concentration

Review of AEs and concomitant medications


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6.1.2.3.
Day 8 (168 Hours After EOI ± 4 Hours)
The following procedures will be conducted on Day 8:

Modified physical examination capturing changes from prior examinations, and weight

Vital signs including blood pressure, respiratory rate, pulse, and temperature

ECOG Performance Status

Obtain blood samples for:
Chemistry (see Section 6.8.10)
Hematology (see Section 6.8.10)
GS-5745 concentration

Review of AEs and concomitant medications
6.1.2.4.
Day 15, Day 29, and Day 43
The following procedures will be conducted on Days 15 (± 1 day), 29 (± 1 day), and 43 (± 2 days):
Pre-dose:

Modified physical examination capturing changes from prior examinations, and weight

Vital signs including blood pressure, respiratory rate, pulse, and temperature

12-lead ECG

ECOG Performance Status

Obtain blood and/or urine samples for:
Chemistry (see Section 6.8.10)
Hematology (see Section 6.8.10)
Coagulation (see Section 6.8.10)
GS-5745 concentration
Anti-GS-5745 antibody (Day 43 only)
Serum and plasma biomarkers (Days 15 and 43 only) (see Section 6.8.12.2)


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Urine pregnancy test (females of childbearing potential)
Urinalysis

Review of AEs and concomitant medications

Register subject visit in IxRS
Dosing:

Administer GS-5745 via IV infusion over approximately 30 (± 5) minutes
Post-dose: EOI:

Vital signs including blood pressure, respiratory rate, pulse, and temperature

12-lead ECG (Day 43 only)

Obtain blood samples for GS-5745 concentration (± 10 minutes)

Review of AEs
For all subjects in Part A, the Day 29 visit is the end of the DLT assessment window. In order for 
a subject to be evaluable for the DLT observation, the subject must have received the first 
2 doses of GS-5745, completed all safety procedures through Day 29, or have experienced a 
DLT prior to Day 29.
6.1.2.5.
Day 57
The following procedures will be conducted on Day 57 (± 2 days):
Pre-dose:

Modified physical examination capturing changes from prior examinations, and weight

Vital signs including blood pressure, respiratory rate, pulse, and temperature

12-lead ECG

ECOG Performance Status

CT or MRI

Obtain blood and/or urine samples for:
Chemistry (see Section 6.8.10)
Hematology (see Section 6.8.10)
Coagulation (see Section 6.8.10)
GS-5745 concentration


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Serum and plasma biomarkers (see Section 6.8.12.2)
Urine pregnancy test (females of childbearing potential)
Urinalysis

Review of AEs and concomitant medications

Register subject visit in IxRS
Dosing:

Administer GS-5745 via IV infusion over approximately 30 (± 5) minutes
6.1.3.
Continuation of Treatment
A subject who does not show evidence of disease progression by clinical assessment or by CT or 
MRI may continue receiving GS-5745 Q2W until disease progression (clinical or radiographic), 
unacceptable toxicity, withdrawal of consent, or other reasons specified in Section 6.4.
6.1.3.1.
Every 2 Weeks (from Day 57)
For subjects continuing treatment, the following procedures will be conducted Q2W (± 2 days) 
from the Day 57 visit:
Pre-dose:

Vital signs including blood pressure, respiratory rate, pulse, and temperature

ECOG Performance Status

Obtain blood and/or urine samples for:
Chemistry (see Section 6.8.10)
Hematology (see Section 6.8.10)
Coagulation (see Section 6.8.10)
Urine pregnancy test (females of childbearing potential)
Urinalysis

Review of AEs and concomitant medications

Register subject visit in IxRS
Dosing:

Administer GS-5745 via IV infusion over approximately 30 (± 5) minutes


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6.1.3.2.
Every 8 Weeks (from Day 57): Assessment of Tumor Response
For subjects continuing treatment, the following procedures will be conducted every 
8 weeks (± 5 days) from the Day 57 visit:

CT or MRI

Obtain blood and/or urine samples for:
Chemistry (see Section 6.8.10)
Hematology (see Section 6.8.10)
Coagulation (see Section 6.8.10)
GS-5745 concentration
Anti-GS-5745 antibody
Serum and plasma biomarkers (see Section 6.8.12.2)

Review of AEs and concomitant medications
6.1.4.
End-of-Study Visit
The following procedures will be conducted at the End-of-Study visit:

Modified physical examination capturing changes from prior examinations, and weight

Vital signs including blood pressure, respiratory rate, pulse, and temperature

12-lead ECG

ECOG Performance Status

Obtain blood and/or urine samples for:
Chemistry (see Section 6.8.10)
Hematology (see Section 6.8.10)
Coagulation (see Section 6.8.10)
GS-5745 concentration
Anti-GS-5745 antibody
Serum and plasma biomarkers (see Section 6.8.12.2)


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Urine pregnancy test (females of childbearing potential)
Urinalysis

CT or MRI (if not conducted within the previous 4 weeks)

Review of AEs and concomitant medications

Register subject visit in IxRS
6.1.5.
Follow-up Visits
6.1.5.1.
Post-Study Telephone Call
Subjects will be contacted by telephone 30 days (± 2 days) after the last dose of GS-5745 to 
assess AEs. For subjects who come off study for reasons other than disease progression, the site 
should also obtain information on post-study anti-cancer therapies, surgeries, and date of 
definitive disease progression (if known).
6.2.
Subject Enrollment and Treatment Assignment – Part B
6.2.1.
Screening Visit
Subjects will be screened within 28 days before enrollment to determine eligibility for 
participation in the study.
The following procedures will be conducted at Screening:

Obtain written informed consent

Medical history (including review of disease under study, prior surgeries, and prior 
anti-cancer therapies)

Review prior/concomitant medication

Complete physical examination including height and weight

Vital signs including blood pressure, respiratory rate, pulse, and temperature

12-lead ECG

ECOG Performance Status

Obtain blood and/or urine samples for:
Chemistry (see Section 6.8.10)
Hematology (see Section 6.8.10)


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Coagulation (see Section 6.8.10)
Serum pregnancy test (females of childbearing potential)
Urinalysis

Obtain stool sample (can be collected any time prior to first dose, CRC cohort only, 
see Section 6.8.12.3)

CT or MRI (scans taken as part of standard medical practice within 4 weeks of Day 1 
are acceptable)

Record any AEs occurring after signing of the consent form

Register subject visit in IxRS
6.2.2.
Cycle-Based Assessments
6.2.2.1.
Day 1 of Each 28-Day Cycle (for Pancreatic Adenocarcinoma, Esophagogastric
Adenocarcinoma, CRC, and Breast Cancer) or Day 1 of Each 21-Day Cycle 
(for NSCLC)
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic on Day 1 to conduct study-required procedures prior to dosing.
The following procedures will be conducted on Day 1 of each cycle:
Pre-dose:

Modified physical examination capturing changes from prior examinations, and weight

Vital signs including blood pressure, respiratory rate, pulse, and temperature

12-lead ECG

ECOG Performance Status

Obtain blood and/or urine samples for:
Chemistry (see Section 6.8.10)
Hematology (see Section 6.8.10)
Coagulation (see Section 6.8.10)
CCI


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GS-5745 concentration
Anti-GS-5745 antibody
Serum and plasma biomarkers (Day 1 of cycles as specified in the laboratory manual; 
see Section 6.8.12.2)
Urine pregnancy test (females of childbearing potential)
Urinalysis

Collect archival tumor tissue specimen as applicable; efforts to acquire a tissue sample 
should begin on Day 1 of Cycle 1

Review of AEs and concomitant medications

Register subject visit in IxRS
Dosing:

Administer GS-5745 via IV infusion over approximately 30 (± 5) minutes followed by 
chemotherapy (see Section 5.4)

Obtain blood samples for:
GS-5745 concentration (at the end of GS-5745 infusion for Cycle 1 and Cycle 3 only)
6.2.2.2.
Day 8 of Each 28-Day Cycle (for Pancreatic Adenocarcinoma and 
Breast Cancer Only)
For subjects who continue to receive gemcitabine ± nab-paclitaxel (Pancreatic Adenocarcinoma) 
and Paclitaxel (Breast Cancer) in subsequent cycles, the following procedures will be conducted 
on Day 8 (± 2 days) of each cycle:

Vital signs including blood pressure, respiratory rate, pulse, and temperature

Obtain blood samples for hematology (see Section 6.8.10)

Review of AEs and concomitant medications
Dosing:

Administer chemotherapy (see Section 5.4).


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6.2.2.3.
Day 15 of Each 28-Day Cycle (for Pancreatic Adenocarcinoma, Esophagogastric
Adenocarcinoma, CRC, and Breast Cancer)
The following procedures will be conducted on Day 15 (± 2 days) of each cycle:

Vital signs including blood pressure, respiratory rate, pulse, and temperature

ECOG Performance Status

Obtain blood and/or urine samples for:
Chemistry (see Section 6.8.10)
Hematology (see Section 6.8.10)
GS-5745 concentration
Serum and plasma biomarkers (Cycle 1 Day 15 only; see Section 6.8.12.2)
Urine pregnancy test (females of childbearing potential)

Review of AEs and concomitant medications

Register subject visit in IxRS
Dosing:

Administer GS-5745 via IV infusion over approximately 30 minutes (± 5 minutes) followed 
by chemotherapy (see Section 5.4).
6.2.2.4.
Cycle 2 Day 15 (+ 14 Days / - 7 Days)

Obtain tumor tissue biopsy (from subjects with breast cancer only)

Obtain stool sample (from subjects with CRC only)
6.2.2.5.
Assessment of Tumor Response
Assessment of tumor response by CT scan or MRI will be performed during the last week of 
even-numbered cycles (ie, Cycles 2, 4, 6, etc.) for subjects with pancreatic adenocarcinoma, 
esophagogastric adenocarcinoma, CRC, and breast cancer, and during the last week of every 
third cycle (ie, Cycles 3, 6, 9, etc.) for subjects with NSCLC.
6.2.3.
Continuation of Treatment
Study drug dosing will continue in the absence of disease progression or toxicity warranting 
discontinuation of therapy.


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6.2.4.
End-of-Study Visit
The following procedures will be conducted at the End-of-Study visit:

Modified physical examination capturing changes from prior examinations, and weight

Vital signs including blood pressure, respiratory rate, pulse, and temperature

ECOG Performance Status

Obtain blood and/or urine samples for:
Chemistry (see Section 6.8.10)
Hematology (see Section 6.8.10)
Coagulation (see Section 6.8.8)
GS-5745 concentration
Anti-GS-5745 antibody
Serum and plasma biomarkers (see Section 6.8.12.2)
Urine pregnancy test (females of childbearing potential)
Urinalysis

CT or MRI (if not conducted within the previous 4 weeks)

Review of AEs and concomitant medications

Register subject visit in IxRS
6.2.5.
Follow-up Visits
6.2.5.1.
Post-Study Phone Call
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess 
AEs. For subjects who come off study for reasons other than disease progression, the site should 
also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive 
disease progression (if known).
CCII 


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6.2.5.2.
Long-term Follow-up
Long-term follow-up (LTFU) begins after the EOS visit, or the last visit on study if EOS does 
not occur. Subjects will be contacted via phone call every 3 months for determination survival 
status and record of any other anti-cancer therapy or cancer related surgery for up to 5 years after
the EOS visit. 
Subjects who are not deceased by the time the Sponsor has made the determination the study will 
end will receive a final follow-up phone call to assess survival status and to communicate the 
Sponsor’s decision to end the study. 
The investigator will make every effort to contact the subject or a close relative or caretaker by 
phone to collect survival information. The investigator should show due diligence by 
documenting in the source documents steps taken to contact the subject (ie, dates of phone calls, 
registered letters, etc).
6.3.
Assessments for Premature Discontinuation of Study Drug
In order to assess PFS, if a subject discontinues study drug (for example, as a result of an AE), 
every attempt should be made to keep the subject in the study to collect tumor assessments 
(CT/MRI), chemistry, and hematology until disease progression and according to the following 
schedule: every 8 weeks for Part A, during the last week of even-numbered cycles 
(ie, Cycles 2, 4, 6, etc.) for Part B subjects with pancreatic adenocarcinoma, esophagogastric
adenocarcinoma, CRC, and breast cancer, and during the last week of every third cycle 
(ie, Cycles 3, 6, 9, etc.) for Part B subjects with NSCLC.
If this is not possible or acceptable to the subject or investigator, the subject may be withdrawn 
from the study.
6.4.
Criteria for Discontinuation of Study Drug
Study medication may be discontinued in the following instances:

Documented progression of malignant disease

Pregnancy

Investigator discretion (the reason for investigator decision to discontinue study drug must be 
recorded on the eCRF)

Non-compliance with study drug

Protocol violation

Withdrawal of consent (the reason for withdrawal of consent, if known, must be recorded on 
the eCRF)


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
Lost to follow-up

Study termination by the Sponsor

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree

Unacceptable toxicity, as defined in the toxicity management section of the protocol, or 
toxicity that, in the judgment of the investigator, compromises the ability to continue 
study-specific procedures or is considered to not be in the subject’s best interest; if toxicity is 
related to chemotherapy, the subject may continue GS-5745 alone.
6.5.
Criteria for Removal from Study
Subjects may be removed from the study for the following reasons:

Documented progression of malignant disease

Death

Pregnancy

Investigator discretion (if progression of disease has not been documented, the reason for 
removal from study must be recorded on the eCRF)

Non-compliance with study drug

Subject never dosed with study drug

Protocol violation

Withdrawal of consent (if progression of disease has not been documented, the reason for 
withdrawal of consent, if provided by the subject, must be recorded on the eCRF)

Lost to follow-up

Study termination by the Sponsor
6.6.
Replacement of Subjects
In Part A, if a subject is withdrawn from the study for any reason other than a DLT prior to 
completion of the DLT assessment window, a replacement subject will be enrolled at the same 
dose level as the replaced subject. To be evaluable for the DLT observation, a subject in Part A 
must receive the first 2 doses of GS-5745, complete all safety procedures through Day 29, or 
experience a DLT prior to Day 29.
6.7.
Dose Interruption and Reduction
If an AE is attributed to only 1 drug (ie, study drug or chemotherapy), the investigator’s 
discretion will be used to determine whether the drug not attributed to the AE will be withheld
based on the investigator’s assessment of risk-benefit of withholding 1 or both drugs.


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6.7.1.
GS-5745
If a subject experiences a DLT (see Section 7.4 for the definition of a DLT), GS-5745 treatment 
will be postponed until the toxicity is resolved to Grade 0 or 1 (as defined by the Common 
Terminology Criteria for Adverse Events [CTCAE], version 4.03) or returns to the subject’s 
baseline value. If the toxicity is resolved to Grade 0 or 1, or returns to the subject’s baseline 
value within 28 days from the start of the event, the subject may resume GS-5745 at 
50% of the originally assigned dose level. If the subject experiences a recurrence of the toxicity
meeting criteria for DLT after restarting study drug or if the toxicity does not resolve within 
28 days, treatment with GS-5745 will be discontinued. Alternatively, if there is no recurrence of 
the toxicity, the dose of GS-5745 may be increased to 100% of the originally assigned level after 
discussion with the Medical Monitor.
In Part B, subjects in whom chemotherapy administration must be delayed > 3 weeks or 
permanently discontinued may continue to receive GS-5745 every 2 to 3 weeks in the absence of 
disease progression.
If the subject was not receiving GS-5745 at the time disease progression was documented 
(eg, due to reversible toxicity), after discussion with the Medical Monitor, GS-5745 may be 
re-started if the criteria for resuming treatment as described in Section 6.7.1 are met and the 
investigator feels it is in the subject’s best interest to do so.
6.7.2.
Gemcitabine and Nab-Paclitaxel
Dose reduction for gemcitabine and nab-paclitaxel should be made according to the system 
showing the greatest degree of toxicity. Toxicities will be graded using the NCI CTCAE 
(version 4.03). Two dose levels are permitted according to the criteria in Appendix 9. If a 
toxicity requiring dose modification occurs following the second dose reduction of either 
chemotherapy, further treatment should be discontinued. Any further dose modification requires 
prior Gilead approval.
Table 6-1.
Dose Reduction Levelsa for Gemcitabine and Nab-Paclitaxel
Drug
Dose Level
Starting Dose
-1
-2b
Gemcitabine
1000 mg/m2
800 mg/m2
600 mg/m2
Nab-Paclitaxel
125 mg/m2
100 mg/m2
75 mg/m2
a
Dose reductions may or may not be concomitant. Please refer to Appendix 9 (Appendix Table 1 and Appendix Table 2) for 
specific recommendations regarding dose modifications for Day 1 of each cycle for hematologic and non-hematologic
toxicity, respectively. Please refer to Appendix 9 (Appendix Table 3 and Appendix Table 4) for specific recommendations 
regarding dose modifications within a cycle for hematologic and non-hematologic toxicities, respectively.
b
A maximum of 2 dose level reductions are allowed.


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Subjects experiencing study drug-related toxicities that require a delay in scheduled gemcitabine 
or nab-paclitaxel dosing for ≥21 days will be discontinued from further chemotherapy treatment 
in this study (except for peripheral neuropathy). When a dose reduction is required, no dose 
re-escalation will be permitted for the duration of study treatment.
Dose Modifications at Day 1
In the event dose modifications are required at the beginning of a cycle due to AEs or 
hematologic toxicities, doses of gemcitabine and nab-paclitaxel may be adjusted as detailed in 
Appendix 9, Appendix Table 1 and Appendix Table 2.
Dose Adjustments Within a Treatment Cycle
In the event that a subject must have treatment delayed within a treatment cycle due to toxicities, 
those doses held during a cycle will not be made up. Dose modifications due to AEs or 
hematologic toxicities as represented by the blood counts and toxicities within a treatment cycle 
should be adjusted as outlined in Appendix 9, Appendix Table 3 and Appendix Table 4.
Peripheral Neuropathy
Nab-paclitaxel treatment should be withheld in subjects who experience ≥Grade 3 peripheral
neuropathy. Gemcitabine administration can continue during this period. Nab-paclitaxel 
treatment may be resumed at the next lower dose level in subsequent cycles after the peripheral 
neuropathy improves to ≤Grade 1. Subjects experiencing peripheral neuropathy that requires a 
delay in scheduled nab-paclitaxel dosing for ≥21 days will discontinue nab-paclitaxel treatment. 
The time to resolution to Grade ≤1 should be the AE duration used for AE reporting.
For more information, please refer to the prescribing information. Local practices and guidelines 
may be followed.
6.7.3.
Carboplatin
Dose reduction for carboplatin is frequently required for hematologic toxicities. As per the 
prescribing information, carboplatin dose should be reduced 75% in subjects with platelets 
< 50 × 109/L and neutrophil count < 0.5 × 109/L.
For more information, please refer to the prescribing information. Local practices and guidelines 
may be followed.
6.7.4.
Paclitaxel
Dose reduction for paclitaxel is frequently required for hematologic toxicities. As per the 
prescribing information, the following dosage reduction guidelines are recommended. Paclitaxel 
therapy should not be administered to subjects with baseline neutrophil counts < 1.5 × 109/L. 
Subjects should not be re-treated with subsequent cycles of paclitaxel until neutrophils recover to 
a level > 1.5 × 109/L and platelets recover to a level > 100 × 109/L. In the case of severe 
neutropenia (< 0.5 × 109/L for 7 days or more) during a course of paclitaxel therapy, the dose 
should be reduced 20% for subsequent courses of therapy.


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For more information, please refer to the prescribing information. Local practices and guidelines 
may be followed.
6.7.5.
Pemetrexed
Per the prescribing information, dose adjustments at the start of a subsequent cycle should be 
based on nadir hematologic counts or maximum non-hematologic toxicity from the preceding 
cycle of therapy. Treatment may be delayed to allow sufficient time for recovery. Upon 
recovery, subjects should be retreated using the guidelines in Table 6-2 and Table 6-3.
Table 6-2.
Dose Reduction for Pemetrexed – Hematologic Toxicities
Nadir ANC < 500/mm3 and nadir platelets ≥50,000/mm3
75% of previous dose
Nadir platelets < 50,000/mm3 without bleeding regardless of nadir ANC
75% of previous dose
Nadir platelets < 50,000/mm3 with bleeding, regardless of nadir ANC
50% of previous dose
If a subject develops non-hematologic toxicities (excluding neurotoxicity) ≥Grade 3, treatment 
should be withheld until resolution to less than or equal to the subject’s pre-therapy value. 
Treatment should be resumed according to guidelines in Table 6-3.
Table 6-3.
Dose Reduction for Pemetrexed – Non-Hematologic Toxicitiesa
Dose of Pemetrexed (mg/m2)
Any Grade 3 or 4 Toxicities Except Mucositis
75% of previous dose
Any Diarrhea Requiring Hospitalization (Irrespective of Grade) or 
Grade 3 or 4 Diarrhea
75% of previous dose
Grade 3 or 4 Mucositis
50% of previous dose
a
NCI CTCAE version 4.03
Pemetrexed therapy should be discontinued if a subject experiences any hematologic or 
non-hematologic Grade 3 or 4 toxicity after 2 dose reductions, or immediately if Grade 3 or 4 
neurotoxicity is observed.
For more information, please refer to the prescribing information. Local practices and guidelines 
may be followed.
6.7.6.
mFOLFOX6
Recommended dose reduction for the components of mFOLFOX6 is described in Table 6-4 and 
is based on the AE table described in Appendix 10. Sites may also follow their institutional 
practice for dose reductions. Leucovorin doses may be adjusted per institutional guidelines in the 
event of a supply shortage.


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Table 6-4.
Dose Reduction Levelsa for mFOLFOX6
Drug
Dose Level
Starting Dose
-1
-2a
Oxaliplatin
85 mg/m2
65 mg/m2
50 mg/m2
5-FU Bolus
400 mg/m2
OMIT
OMIT
5-FU Continuous Infusion over 46 to 48 Hours
2400 mg/m2
1900 mg/m2
1500 mg/m2
dl-Leucovorin/l-Leucovorinc
400/200 mg/m2
100%
100%
a
If an AE is believed likely to be due to 1 drug, it is permissible to decrease dose of that drug.
Further dose levels (−3, −4, etc.) will be 20% dose reductions from the previous level for oxaliplatin and 5-FU continuous 
infusion. In addition, the bolus dose of 5-FU will continue to be omitted, and the leucovorin dose will remain unadjusted (100%).
Dosing of leucovorin will remain fixed at 100% of recommended dose.
6.7.6.1.
Modifications for the First 2 Cycles
Follow the modifications in Appendix 10 for the first 2 cycles, until individual treatment 
tolerance can be ascertained. Thereafter, these modifications should be regarded as guidelines to 
prevent side effects from exceeding a mild-to-moderate level, and minimize the incidence and 
duration of debilitating side effects.
If multiple AEs are seen, administer dose based on greatest reduction required for any single AE
observed.
Subjects should be assessed clinically for AEs prior to, during, and after each infusion.
6.7.6.2.
Implications of Dose Reductions for Subsequent Cycles
If the subject experiences a significant AE requiring a dose reduction at the start of the next 
cycle, then the dose will remain lowered for all subsequent cycles.
For more information, please refer to the prescribing information. Local practices and guidelines 
may be followed.
6.7.7.
FOLFIRI
FOLFIRI consists of 5-FU, leucovorin, and irinotecan. Dose reductions for neutropenia, diarrhea, 
or thrombocytopenia are frequently required. Appendix 10, Appendix Table 7 provides the 
starting dose and modified dose levels for the individual components of FOLFIRI.
Table 6-5.
Starting Dose and Modified Dose Levels (mg/m2)
Drug
Dose Level
Starting Dose
-1
-2
Irinotecan
180
150
120
l-LV/dl-LV
200/400
200/400
200/400
5-FU Bolus
400
320
240
5-FU Infusion 
2400
2000
1500


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6.8.
Description of Study Procedures
6.8.1.
Medical History
A complete medical history will be obtained by the investigator or designee. Medical history will 
include information on the subject’s significant past medical events (eg, prior hospitalizations 
or surgeries), a review of the disease under study, prior anti-cancer therapies, and any concurrent 
medical illnesses.
6.8.2.
Physical Examination
The investigator or qualified designee will perform a physical examination at screening and time
points outlined in the Study Procedures Tables (Appendix 2 to Appendix 8). Pre-dose abnormal 
findings will be reported on the medical history page of the eCRF. Any changes from the 
pre-dose baseline physical examination which represent a clinically significant deterioration will 
be documented on the AE page of the eCRF.
Weight (without shoes) should be measured with each physical examination and reported in 
kilograms.
Height (without shoes) should be measured at Screening only and reported in centimeters.
6.8.3.
Vital Signs
Vital signs, including blood pressure, respiratory rate, pulse, and temperature will be measured at 
the time points listed in the Study Procedures Tables in Appendix 2 to Appendix 8. All 
measurements will be recorded on the appropriate eCRF page with appropriate source 
documentation. Any abnormal measurements may be repeated and reported as AEs if appropriate. 
All measures of blood pressure will be performed using standard sphygmomanometry. 
Measurements of blood pressure should be taken per institutional guidelines.
6.8.4.
Electrocardiogram
Twelve (12)-lead ECGs reporting ventricular rate, PR, QRS, QT, and QTc intervals will be 
obtained at the time points outlined in the Study Procedures Tables (Appendix 2 to Appendix 8).
The investigator or qualified designee will review all ECGs. The ECG tracings will be maintained 
in the source documentation of each subject and the appropriate data reported on the eCRF.
6.8.5.
ECOG Performance Status
The ECOG Performance Status will be performed at the time points listed in the 
Study Procedures Tables in Appendix 2 to Appendix 8 and in accordance with Table 6-6.


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Table 6-6.
ECOG Performance Status
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 self-care but unable to carry out any work activities. 
Up and about more than 50% of waking hours
3
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5
Dead
Source: {Oken et al 1982}
6.8.6.
Prior and Concomitant Medications
At screening, all medication taken up to 30 days prior to the screening visit will be recorded on 
the eCRF. At each study visit, the site will capture any and all medications taken by the subject 
since the last visit or during the visit (as applicable). Concomitant medications include 
prescription and non-prescription medications, pre-infusion medications (eg, anti-emetics), and 
vitamins and minerals.
In addition, supportive therapies given during the course of the study (eg, blood transfusion, 
growth factor) should be collected and recorded on the eCRF.
6.8.7.
Adverse Events
Subjects will be assessed for AEs per guidelines in the CTCAE (version 4.03) at the time points 
outlined in the Study Procedures Tables (Appendix 2 to Appendix 8). Any AEs reported after 
informed consent is obtained and throughout the study will be recorded on the eCRF with 
appropriate source documentation. The site will contact the study subject by phone 30 days after 
the last dose of study drug to assess AEs.
Please refer to Section 7 for additional information on AE reporting.
6.8.8.
CT or MRI
Computed tomography scans will be obtained to document metastatic disease, identify target 
lesions as described in RECIST (version 1.1), and to assess response and disease progression. In 
subjects who cannot tolerate iodinated contrast, a CT of the lung without contrast and MRI of the 
abdomen should be performed. Imaging by CT scan (with contrast) or MRI will be performed at 
Screening (within 4 weeks before Day 1 if the scan was performed as part of standard 
medical practice) and at the time points outlined in the Study Procedures Tables
(Appendix 2 to Appendix 8).
The same radiographic procedure and specification (eg, the same contrast agent, slice thickness, 
etc.) used to define measurable lesions must be used throughout the study for each subject. Any 
subject with symptoms suggestive of disease progression should be evaluated for tumor response 


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at the time the symptoms occur. Tumor burden will be characterized at baseline and subsequent 
response assessments will be carried out according to the RECIST (version 1.1) criteria.
6.8.9.
Independent Radiology Review
An independent radiology review (IRR) committee will be established to provide a blinded 
review of radiographic data in order to provide independent interpretation of changes in tumor 
status. The IRR will include board-certified radiologist(s) and will be managed by a contract 
research organization (CRO) selected by Gilead. The review of radiographic data by the IRR will 
be performed on an ongoing basis. The specifics of the IRR’s processes and reading methods 
will be described in an independent review charter developed by the contracted imaging facility 
in conjunction with Gilead.
6.8.10.
Blood and Urine Samples
Blood and urine (for pregnancy and urinalysis) for laboratory safety tests will be collected 
according to the Study Procedures Tables (Appendix 2 to Appendix 8). The date and time of 
blood and urine collection will be recorded in the subject’s source documentation. The tests will 
be analyzed using standard procedures. White blood cell differentials will be reported as absolute 
counts. All laboratory tests must be reviewed for clinical significance by the investigator or 
qualified designee.
Day 1 pre-dose samples may be drawn up to 2 days prior to the Day 1 visit.
The analytes listed in Table 6-7 will be tested.
Table 6-7.
Blood and Urine Samples Collected During the Course of the Study
Serum Chemistry
Hematology
Other
Sodium
Potassium
Chloride
Glucose
BUN
Creatinine
ALT
AST
Alkaline phosphatase
Total bilirubin
Total protein
Albumin
Calcium
Magnesium
Phosphate
Creatinine 
White Blood Cell (WBC) Count
Hemoglobin
Hematocrit
Platelet Count
ANC
Neutrophils
Lymphocytes
Monocytes
GS-5745 concentration
Anti-GS-5745 antibody
Serum and Plasma Biomarkers
Coagulation
PT/INR
aPTT
Pregnancy Testing
Urine
Serum Qualitative -HCG (females)
Urine Pregnancy (females)
Urinalysis


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6.8.11.
Pregnancy Test for Females of Childbearing Potential
All female subjects of childbearing potential (as defined in Section 4.2) will have a serum 
pregnancy test at Screening and a urine pregnancy test prior to each dose of GS-5745 and at the 
End-of-Study visit. The results must be confirmed as negative prior to administration of study 
drug on the respective days the test is performed.
6.8.12.
Biomarkers
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI
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Table 6-8.
Biomarker Objectives and Testing, CRC and Breast Cancer Subjects
Sample Type
Objective
Tests Outlined Below May Include, 
but Are Not Limited to, the Following:
Blood
To evaluate pharmacodynamics of 
GS-5745
MMP9 cleavage products (eg, C1M)
To evaluate the effect of GS-5745 and 
other study drugs on circulating 
markers correlated with immune 
activation, MMP9 substrates and 
MMP family members
Circulating chemokines and inflammatory cytokines 
(eg, interleukin 6 [IL-6], interferon gamma [IFN-], 
CXCL10, VEGF, MMP2)
To evaluate disease burden and 
investigate mutations and patterns of 
gene expression
Quantification and sequencing of blood-based tumor 
DNA, RNA or other descriptive analyses 
(circulating tumor cells or cell-free fraction)
Stool
To evaluate the gut microbiome and 
other markers
Microbiome complexity may be determined through 
16s rRNA sequencing and other MMP9-related 
biomarkers may be evaluated for CRC subjects only
Tissue Biopsy: 
Archival Tissue
To evaluate baseline biomarkers that 
associate with GS-5745 plus 
combination therapy activity
MMP9 and other relevant proteins by IHC 
(eg PDL1, infiltrating immune cells), gene 
expression patterns (RNA), DNA somatic mutations
MSI, MSS and CIMP status to be determined for 
CRC subjects only
Tissue Biopsy Week 6 
(C2D15)
To evaluate biomarkers for which 
change from baseline associates with 
GS-5745 plus combination 
therapy activity
MMP9 and other relevant markers by IHC 
(eg, PDL1, immune cells), gene expression patterns 
(RNA) for breast cancer subjects only
 
 
 
 
 
 
 
 
 
 
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6.8.14.
Biologic Samples for Optional Future Research
 
 
 
 
 
 
 
 
 
 
6.8.15.
Unscheduled Procedures
Unscheduled procedures, including, but not limited to, vital signs, 12-lead ECG, and CT or MRI, 
will be recorded on the applicable eCRFs.
CCI


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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Adverse Events
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
medicinal product and which does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product.
AEs also include the following:

All AEs that occur from the study screening visit onwards and throughout the duration of the 
study, including the follow-up off study medication period should be recorded as an AE

Pre- or post-treatment complications that occur as a result of protocol-mandated procedure
(eg, such as venipuncture or biopsy) during or after screening (before the administration of 
study investigational medicinal product)

Any pre-existing condition that increases in severity, or changes in nature during or as a 
consequence of the study investigational medicinal product phase of a human clinical trial, 
will also be considered an AE

Complications and termination of pregnancy (see Section 7.13 for additional information)
An AE does not include the following:

Medical or surgical procedures (eg, surgery, endoscopy, tooth extraction, transfusion)
performed; the condition that leads to the procedure is an AE

Pre-existing diseases or conditions or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae 

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history eCRF.

Uncomplicated pregnancy

An induced elective abortion to terminate a pregnancy without medical reason


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7.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as follows:
Any adverse drug experience occurring at any dose that results in any of the following outcomes:

Death

Life-threatening situation (subject is at immediate risk of death)

In-patient hospitalization or prolongation of existing hospitalization (excluding those for 
study therapy or placement of an indwelling catheter, unless associated with other SAEs)

Persistent or significant disability/incapacity

Congenital anomaly/birth defect in the offspring of a subject who received investigational 
medicinal product

Other: medically significant events that may not be immediately life-threatening or result in 
death or hospitalization, but based upon appropriate medical and scientific judgment, may 
jeopardize the subject or may require medical or surgical intervention to prevent one of the 
outcomes listed above
Examples of such events are as follows:
Intensive treatment in an emergency room or at home for allergic bronchospasm
Blood dyscrasias or convulsions that do not result in hospitalization
Development of drug dependency or drug abuse
Clarification of Serious Adverse Events

Death is an outcome of an AE, and not an AE in itself.

An SAE may occur even if the subject was not on investigational medicinal product at the 
time of occurrence of the event. Dosing may have been given as treatment cycles or 
interrupted temporarily before the onset of the SAE.

“Life-threatening” means that the subject was at immediate risk of death from the event as it 
occurred. This does not include an event that might have led to death if it had occurred with 
greater severity.

Complications that occur during hospitalizations are AEs. If a complication prolongs the 
hospitalization, it is a SAE.


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
“In-patient hospitalization” means the subject is formally admitted to a hospital for medical 
reasons, for any length of time. This may or may not be overnight. It does not include 
presentation and care within an emergency department.

The investigator should attempt to establish a diagnosis of the event on the basis of signs, 
symptoms and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE and/or SAE and not the individual signs/symptoms.
Disease Progression and Death Related to Disease Progression

To maintain the integrity of the study, disease progression and death from disease 
progression should be reported as SAEs by the investigator only if it is assessed that the 
study drugs caused or contributed to the disease progression (ie, by a means other than lack 
of effect). Unrelated disease progression should be captured on the eCRF.

In addition, events that are indicative of the following disease- related SAEs that are assessed 
as unrelated to study drugs, will not be reported as expedited reports by Gilead during the 
study:
Progression of malignancy being studied
Death related to disease progression
These events will be exempt from global expedited reporting requirements for the duration of the 
study as they are the primary endpoints of this study. They will be reported as appropriate in the 
final clinical study report as well as any relevant aggregate safety report.
7.3.
Describing Adverse Event Relationship to Study Drug and Study Procedures
The relationship of an AE or SAE to investigational medicinal product should be assessed using 
clinical judgment, describing the event as either unrelated (No) or related (Yes) consistent with 
the following definitions:

No: Evidence exists that the AE has an etiology other than the investigational medicinal 
product. For SAEs, an alternative causality must be provided (eg, pre-existing condition, 
underlying disease, intercurrent illness, or concomitant medication).

Yes: A temporal relationship exists between the AE onset and administration of the 
investigational medicinal product that cannot be readily explained by the subject’s clinical 
state or concomitant therapies. Furthermore, the AE appears with some degree of certainty to 
be related, based on the known therapeutic and pharmacologic actions or AE profile of the 
investigational medicinal product. In case of cessation or reduction of the dose the AE may 
abate or resolve and it may reappear upon re-challenge.
It should be emphasized that ineffective treatment should not be considered as causally related in 
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The relationship of an AE or SAE to study procedures (eg, invasive procedures such as 
venipuncture or biopsy) should be assessed using clinical judgment, describing the event as 
either unrelated (No) or related (Yes) consistent with the following definitions:

No: Evidence exists that the AE has an etiology other than the study procedure.

Yes: A temporal relationship exists between the AE onset and a protocol-mandated 
procedure that cannot be readily explained by the subject’s clinical state or concomitant 
therapies. Furthermore, the AE appears with some degree of certainty to be related to the 
study procedure based on the known potential complications of that procedure.
7.4.
Dose Escalation and Stopping Rules for Part A
In the dose escalation phase of the study (Part A), subjects will be assigned sequentially to
cohorts of up to 6 subjects each. Three subjects will initially be enrolled in each cohort for DLT 
observation. Three additional subjects will be enrolled in each cohort in the event that a DLT is 
observed and/or additional safety, PK, or pharmacodynamic data are needed. The DLT 
observation period ends on Day 29 for all subjects in Part A. In order for a subject to be 
evaluable for the DLT observation, the subject must have received the first 2 doses of GS-5745, 
completed all safety procedures through Day 29, or have experienced a DLT prior to Day 29.
The starting dose of GS-5745 in Part A is 200 mg. A single subject will initially be enrolled into 
the first dosing cohort to evaluate any unexpected adverse effects. Provided that there are no 
significant safety signals up to 24 hours post-dose, the remaining 2 subjects will be dosed.
The safety data will be reviewed once all 3 subjects in a given cohort complete study Day 29. 
The decision to proceed to the next dose level will be made by the Investigators in conjunction 
with the Gilead study team after careful consideration and review of all available safety and 
laboratory findings. Dose escalation decisions will be made in accordance with a standard 
3 + 3 design using the following rules:
1) If no DLT is observed within the first 28 days in the initial 3 subjects of a cohort, then dose
escalation to the next higher dose level cohort will occur.
2) If one DLT is observed within the first 28 days in the initial 3 subjects of a cohort, then 
3 additional subjects will be enrolled in that cohort. If no further DLT(s) are observed in the 
6 subjects, then dose escalation to the next higher dose level cohort will occur. If DLTs are 
experienced by 2 or more study subjects in a cohort during the defined DLT period, dose 
de-escalation will occur to an intermediate dose (1200 mg and 400 mg as described in 
Section 3.1).
The MTD is defined as the highest dose level with a subject incidence of DLTs during the 
first 28 days of study drug dosing of 0 or 1 out of 6.
The assessment of a DLT will follow the guidelines provided in the CTCAE (version 4.03). 
These criteria are available online at:
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf


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If an AE is not specified in the CTCAE, the severity grading of the AE should be recorded and 
graded as follows:

Mild (Grade 1): Awareness of signs or symptoms, but easily tolerated;

Moderate (Grade 2): Discomfort sufficient to cause interference with usual activities;

Severe (Grade 3 or 4): Incapacitation with inability to work or perform usual activities.
Grade 5 (death) is an outcome and will not be recorded as a severity.
A DLT is a toxicity defined below considered possibly related to GS-5745 occurring during the 
DLT assessment window (Day 1 through Day 29) in each dose escalation cohort.

Grade 4 neutropenia (ANC < 500/µL) for > 7 days, or febrile neutropenia (ANC < 1000/µL 
with fever > 101 °F [38.5 °C])

Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia associated with bleeding

Grade 3 or 4 non-hematologic toxicity (excluding rash, nausea, diarrhea, and vomiting if 
controlled with standard supportive care)

Treatment delay of ≥14 days due to unresolved toxicity

Non-hematologic toxicity of ≥ Grade 2 (at any time during treatment) that, in the judgment of 
the investigators and the Medical Monitor, is dose-limiting.

For certain toxicities such as laboratory assessments without a clear clinical correlate, a 
discussion between the Investigator, Medical Monitor, and the Sponsor may take place to 
determine if this AE should be assessed as a DLT necessitating dose reduction.
7.5.
Adverse Drug Reactions
An adverse drug reaction (ADR) is defined as an AE that is considered causally related to an 
investigational medicinal product. A serious ADR (SADR) is an ADR which meets the 
seriousness criteria.
7.6.
Unexpected Adverse Event
An unexpected AE is defined as an event that has a nature or severity, or specificity that is not 
consistent with the applicable Investigator’s Brochure or that is symptomatically and 
pathophysiologically related to a known toxicity but differs because of greater severity or 
specificity. For example, under this definition, hepatic necrosis would be unexpected 
(by virtue of greater severity) if the Investigator’s Brochure only referred to elevated hepatic 
enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral vasculitis would be 
unexpected (by virtue of greater specificity) if the Investigator’s Brochure only listed 


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cerebral vascular accidents. “Unexpected,” as used in this definition, refers to an adverse drug 
experience that has not been previously observed and reported rather than an experience that has 
not been anticipated based on the pharmacological properties of the study drug.
7.7.
Grading of the Severity of an Adverse Event
The severity grading of AEs will be assessed as Grade 1, 2, 3, 4 or 5 using the CTCAE 
(version 4.03). For AEs associated with laboratory abnormalities, the event should be graded on 
the basis of the clinical severity in the context of the underlying conditions; this may or may not 
be in agreement with the grading of the laboratory abnormality.
The distinction between the seriousness and the severity of an AE should be noted. Severe is a 
measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For example, a 
headache may be severe in intensity, but would not be classified as serious unless it met one of 
the criteria for serious events listed above.
7.8.
Special Situations Reports
7.8.1.
Definition of Special Situations
Special situation reports include pregnancy reports, reports of medication error, abuse, misuse, or 
overdose, and reports of adverse reactions associated with product complaints. 
A pregnancy report is used to report pregnancies following maternal or paternal exposure to the 
product. 
Medication error is any preventable event that can cause or lead to inappropriate medication use 
or patient harm while the medication is in the control of a healthcare professional, patient or 
consumer. 
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
patient accompanied by harmful, physical, and/or psychological effects.
Misuse is defined as any use of a medicinal product in a way that the product is intentionally and 
inappropriately used not in accordance with the protocol instructions or the local prescribing 
information.
An overdose is defined as a dose taken (accidentally or intentionally) exceeding the dose as 
prescribed by the protocol or the maximal recommended daily dose as stated in the 
Product Labeling (as it applies to the daily dose for the subject/patient in question). 
In cases of a discrepancy in drug accountability, overdose will be established only when it is 
clear that the subject has taken the excess dose(s) or the investigator has reason to suspect that 
the subject has taken the additional dose(s). 
Product complaint is defined as any written or verbal report arising from potential deviations in 
the manufacture, packaging or distribution of the product.
Instructions for reporting Special Situation Reports are described in Section 7.9.2.


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7.9.
Reporting Requirements
7.9.1.
Site Reporting Requirements for Adverse Events
Classification of an event as serious or non-serious (see Sections 7.1 and 7.2) determines the 
reporting procedures to be followed by the site.
Site reporting requirements for AEs are summarized in Table 7-1.
Table 7-1.
Site Reporting Requirements for Adverse Events
Classification
Reporting Time
Reporting Action
Serious
Within 24 hours
Fax report on designated SAE Report Form to Gilead DSPH, 
and to the site IRB, as per local IRB requirements; include 
copies of relevant source documents (eg, progress notes, 
autopsy reports, laboratory and diagnostic test results, 
discharge summaries) in communication to Gilead DSPH.
Per eCRF submission procedure
Record and submit information on appropriate eCRFs
Non-serious
Per eCRF submission procedure
Record and submit information on appropriate eCRFs
For SAEs, in addition to completing the AE portion of the eCRF, the SAE Report Form must 
also be completed. The information in the AE portion of the eCRF page and the SAE Report 
Form(s) must match or be reconciled. Where the same data are collected, the forms must be 
completed in a consistent manner. For example, the same AE term should be used on both forms.
Particularly for fatal or life-threatening events, copies of progress notes, autopsy reports, 
laboratory and diagnostic test results, discharge summaries, and other relevant documents should 
be e-mailed or faxed when requested and applicable. Follow-up information to the SAE should 
be clearly documented as “follow up” in the SAE Report Form and must be faxed to these same 
parties. Gilead or the CRO may request additional information from the investigator to ensure 
the timely completion of accurate safety reports. 
The subject’s name, address, and other personal identity information should be obscured on any 
source documents (eg, progress notes, nurses’ notes, laboratory and diagnostic test results, 
discharge summaries). Only the subject’s study number, initials, or date of birth are to be 
provided.
The SAE Report Form must be communicated to the Gilead Drug Safety and Public Health 
(DSPH) and to the site IRB (if required by local regulations) within 24 hours. In the rare event 
that the investigator does not become aware of the occurrence of a SAE immediately 
(for example, if a subject initially seeks treatment elsewhere), the investigator is to report the 
event within 24 hours after learning of it and to document his/her first awareness of the AE.


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Follow-up of AEs will continue through the last day on study or until the investigator and 
Gilead Sciences, or its designee, determine that the subject’s condition is stable. Gilead Sciences 
may request that certain AEs be followed until resolution.
Contact information for reporting SAEs to Gilead is provided in Table 7-2:
Table 7-2.
Contact Information for Reporting Serious Adverse Events
Gilead Drug Safety and Public Health (DSPH):
Fax:
E-mail:
7.9.2.
Special Situation Reporting Instructions
Instructions for Reporting Pregnancies:

The Investigator should report all pregnancies to Gilead DSPH using the Pregnancy Report 
form within 24 hours of becoming aware of the pregnancy as outlined in Section 7.13.
Contact information for reporting pregnancies is provided in Table 7-2.
Instructions for Reporting Other Special Situations:

All other Special Situation reports must be reported on the Special Situation Report Form and 
forwarded to Gilead DSPH within 24 hours using the contact information provided in 
Table 7-2.

All clinical sequelae in relation to Special Situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms 
and signs, clinical management and outcome will be reported, when available
7.9.3.
Gilead Sciences Reporting Requirements for Adverse Events
Depending on relevant legislation or regulations in different regions and countries, 
Gilead Sciences may be required to expedite reports to regulatory authorities for the following 
types of AEs: SAEs including events related to study procedures; SADRs; and suspected, 
unexpected, serious adverse reactions (SUSARs).
Each SAE report received from the investigator will be evaluated by Gilead Sciences DSPH who 
will assess the seriousness of the event (see Section 7.2), the relationship to participation in the 
study (Section 7.3), and the expectedness of the event (see Section 7.6). For regulatory reporting 
purposes, expectedness will be determined by Gilead Sciences DSPH using reference safety 
information specified in the Investigator’s Brochure.
Gilead Sciences or its designee will also provide all investigators and the Data Monitoring 
Committee (if applicable) a safety letter e-mail, fax, or overnight mail notifying them of a 
SUSAR. Investigators will be requested to provide written notification of the SUSAR to the IRB 
as soon as is practical, consistent with local regulatory requirements and local institutional 
policy.
PPD
PPD


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7.9.4.
Post-Study Reporting Requirements
All AEs and SAEs including deaths, regardless of cause or relationship, must be reported for 
subjects on study through the last study visit and the 30-day follow-up phone call.
Any SAEs and deaths that occur after the End of Study visit but within 30 days of the last dose 
of investigational medicinal product, regardless of causality, should also be reported.
Investigators are not obligated to actively seek SAEs after the 30 day time period. However, if 
the investigator learns of any SAEs that occur after study participation and the event is deemed 
relevant to the use of investigational medicinal products, he/she should promptly document and 
report the event to Gilead Sciences DSPH.
7.10.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities are usually not recorded as AEs or SAEs. However, laboratory 
abnormalities (eg, clinical chemistry, hematology, and urinalysis) that require medical or surgical 
intervention or lead to investigational medicinal product interruption or discontinuation must be 
recorded as an AE, as well as an SAE, if applicable. In addition, laboratory or other abnormal 
assessments (eg, electrocardiogram, X-rays, vital signs) that are associated with signs and/or 
symptoms must be recorded as an AE or SAE if they meet the definition of an AE or SAE as 
described in Sections 7.1 and 7.2, respectively. If the laboratory abnormality is part of a 
syndrome, record the syndrome or diagnosis (ie, anemia) not the laboratory result 
(ie, decreased hemoglobin).
Severity should be recorded and graded according to the CTCAE (version 4.03).
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the 
clinical severity in the context of the underlying conditions; this may or may not be in agreement 
with the grading of the laboratory abnormality.
7.11.
Toxicity Management
Treatment-emergent toxicities will be noted by the Investigator and brought to the attention of 
the Gilead Sciences Medical Monitor or designee. Whether or not considered treatment-related, 
all subjects experiencing AEs must be monitored periodically until symptoms subside, any 
abnormal laboratory values have resolved or returned to baseline levels or they are considered 
irreversible, or until there is a satisfactory explanation for the changes observed.
Grade 3 or 4 clinically significant laboratory abnormalities should be confirmed by repeat testing 
as soon as practical to do so, and preferably within 3 calendar days after receipt of the original 
test results.
Any questions regarding toxicity management should be directed to the Gilead Medical Monitor 
or designee.


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7.12.
Contraception Requirements
Although there are no adequate and well-controlled studies of gemcitabine, nab-paclitaxel, 
paclitaxel, carboplatin, pemetrexed, oxaliplatin, or fluorouracil in pregnant women, based on 
animal studies these drugs can cause fetal harm when administered to a pregnant woman.
There are no adequate and well-controlled clinical studies of leucovorin in pregnant women, and 
formal animal reproductive toxicity studies have not been conducted.
The risks of treatment with GS-5745 during pregnancy have not been evaluated in humans. The
potential for genotoxicity is not expected, given that GS-5745 is a monoclonal antibody. In both
the rat and rabbit definitive embryo-fetal developmental toxicity studies, there were no GS-5745-
related effects on embryo-fetal survival and growth and no fetal anomalies. In a fertility study in 
male and female rats, no test article-related effects on reproductive performance and intrauterine 
survival were observed at any dosage level. In addition, male and female reproductive organ 
weights were unaffected by GS-5745 at all dose levels. There were no test article-related effects 
on spermatogenic endpoints at any dose level. The animal peri/post-natal study is ongoing.
Women of childbearing potential should be informed of the potential risk and use highly
effective methods of birth control during treatment with GS-5745 from screening until 30 days
after the end of relevant systemic exposure. A clinically relevant interaction between GS-5745
and contraceptive steroids is not expected because of their distinct metabolic pathways and
therefore, hormonal contraception may be used as part of the birth control methods. If females 
are using hormonal agents for contraception, the safety and/or efficacy may be affected by 
possible drug-drug interaction. However, it is recommended that the subject continue the 
hormonal agent and that a non-hormonal method (or methods) be used concurrently. If females 
utilize hormonal agents as one of their contraceptive methods, the same hormonal method must 
have been used for at least 3 months before study dosing.
Women of childbearing potential must have a negative serum pregnancy test at screening and a
negative urine pregnancy test at the Baseline/Day 1 visit prior to drug administration. At 
minimum, a pregnancy test will be performed at the end of relevant systemic exposure. In the 
event of a delayed menstrual period (over 1 month between menstruations), a pregnancy test 
must be performed to rule out pregnancy. This is true even for women of childbearing potential 
with infrequent or irregular periods.
It is theoretically possible that a relevant systemic concentration may be achieved in a female
partner from exposure of the male subject’s seminal fluid. Therefore, male subjects with female
partners of childbearing potential must use condoms during treatment until the end of relevant
systemic exposure.
Please refer to the latest version of the GS-5745 Investigator’s Brochure for additional 
information, as well as the prescribing information for gemcitabine, nab-paclitaxel, paclitaxel, 
carboplatin, pemetrexed, oxaliplatin, leucovorin, and fluorouracil.


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In the context of this protocol, a female subject is considered to be of childbearing potential 
unless she has had a hysterectomy, a bilateral tubal ligation, or a bilateral oophorectomy; has 
medically documented ovarian failure (with serum estradiol and FSH levels within the 
institutional postmenopausal range and a negative serum or urine β-HCG); or is menopausal 
(age ≥55 years with amenorrhea for ≥6 months).
Sexually active females of childbearing potential must agree to use a protocol-recommended 
method of contraception during heterosexual intercourse from screening until 30 days following 
discontinuation of GS-5745. In addition, please refer to the latest prescribing information for 
contraception requirements concerning gemcitabine, nab-paclitaxel, paclitaxel, carboplatin, 
pemetrexed, oxaliplatin, leucovorin, and fluorouracil.
Protocol-recommended contraceptive methods are described in Table 7-3. If tubal sterilization is 
via the Essure procedure, verification of tubal blockage by hysterosalpingogram (HSP) must be 
performed approximately 3 months after micro-insertion. Prior to verification, Essure is not 
considered a reliable form of contraception and the contraception methods described below must 
be used.
Lactating females must discontinue nursing before investigational medicinal product administration.
Male subjects who are sexually active are required to use barrier contraception 
(condom with spermicide) during heterosexual intercourse from screening through to study 
completion and for 90 days from the last dose of GS-5745. In addition, please refer to the latest 
prescribing information for contraception requirements concerning gemcitabine, nab-paclitaxel, 
paclitaxel, carboplatin, pemetrexed, oxaliplatin , leucovorin, and fluorouracil..
Males must also refrain from sperm donation from the start of study drugs, throughout the study 
treatment period, and for 90 days following the last dose of GS-5745. In addition, please refer to 
the latest prescribing information for contraception requirements concerning gemcitabine, 
nab-paclitaxel, paclitaxel, carboplatin, pemetrexed, oxaliplatin , leucovorin, and fluorouracil..
Table 7-3.
Protocol-Recommended Contraceptive Methods
Single Methods
Combination Methods
Intra-Uterine Devices (IUDs)
Tubal Sterilization
Vasectomy
Estrogen and Progesterone

Oral contraceptives plus condom/spermicide

Transdermal patch plus condom/spermicide

Vaginal ring plus condom/spermicide
Progesterone + Barrier

Injection plus condom/spermicide

Implant plus condom/spermicide
Two Barrier Methods

Female barrier/spermicide (ie, Diaphragm or other cervical caps) 
plus male condom


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The Gilead Medical Monitor or designee should be consulted regarding any questions relating to 
childbearing status or contraception.
7.13.
Procedures to be Followed in the Event of Pregnancy
Each female subject should be instructed to discontinue further study therapy and inform the 
investigator immediately if she becomes pregnant at any time between the initiation of study 
drug until 30 days (or 90 days for the partner of male subjects) after last receiving study drugs.
The investigator must report any pregnancy to Gilead DSPH within 24 hours of the time the 
investigator becomes aware of the pregnancy.
The investigator should counsel the subject regarding the possible effects of investigational 
medicinal product exposure on the fetus and the need to inform the study site of the outcome of 
the pregnancy.
All pregnancies of study subjects and female partners of male subjects that occur during the 
study and follow-up period should be reported using the Pregnancy Report eCRF. Monitoring of 
the pregnancy in both female study subjects and female partner of male study subjects should 
continue until the conclusion of the pregnancy. The outcome of the pregnancy should be reported 
on the Pregnancy Outcome Report eCRF within 5 days of the conclusion of the pregnancy. If the 
end of the pregnancy occurs after the study is completed, the outcome should be reported directly 
to Gilead DSPH (facsimile: 
 e-mail: 
Neither the pregnancy itself nor an induced elective abortion to terminate the pregnancy without 
medical reasons is considered an AE; such occurrences should be reported on the appropriate 
pregnancy report forms. However, if the outcome of the pregnancy meets the criteria for 
classification as an SAE (ie, spontaneous abortion, induced abortion due to complications, 
stillbirth, neonatal death, or congenital anomaly [including that in an aborted fetus]), the 
investigator should follow the procedures for reporting SAEs, ie, report the event to 
Gilead DSPH by telephone and follow up by submission of the appropriate AE eCRFs.
Pregnancy outcomes that are classified as SAEs include:

Any spontaneous abortion, including miscarriage and missed abortion.

An induced therapeutic abortion to terminate any pregnancy due to complications or other 
medical reasons. The underlying medical reason for this procedure should be recorded as the 
AE term.

All neonatal deaths that occur within 1 month of birth, regardless of causality. In addition, 
any infant death after 1 month that the investigator assesses as possibly related to the in utero 
exposure to the study drug should also be reported as a SAE.
In the case of a live birth, the “normality” of the newborn can be assessed at time of birth 
(ie, there is no required minimum follow-up of a presumably normal infant before the Pregnancy 
Outcome Report eCRF can be completed).
PPD
PPD


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The “normality” of an aborted fetus can be assessed by gross visual inspection unless there are 
pre-abortion laboratory findings suggestive of a congenital anomaly, in which case pathologic 
examination should be requested.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Objectives
The primary objectives of this study are:

To determine the MTD of GS-5745 monotherapy in subjects with advanced solid tumors

To characterize the safety and tolerability of GS-5745 as monotherapy and in combination 
with various chemotherapy regimens in subjects with select tumor types
The secondary objectives of this study are:

To characterize the PK of GS-5745

To evaluate the formation of anti-GS-5745 antibodies
The exploratory objective of this study is:
 
8.1.2.
Primary Endpoint
Safety will be evaluated by incidence of AEs, assessment of clinical laboratory test findings, 
physical examination, 12-lead ECG, and vital signs measurements.
8.1.3.
Exploratory Endpoints
 
 
 
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8.2.
Analysis Conventions
Descriptive statistics including means, medians, standard deviations, and ranges will be 
calculated for continuous variables, and categorical data will be summarized using frequency 
counts and percentages. 
8.2.1.
Analysis Sets
8.2.1.1.
Safety Analysis Set
The Safety Analysis Set includes all subjects who receive at least 1 infusion at any dose of 
GS-5745. This analysis set will be used for both the safety and efficacy analyses.
Determination of the MTD in Part A will be in DLT-evaluable subjects (ie, subjects in the 
Safety Analysis Set who received the first 2 doses of GS-5745, completed all safety procedures 
through Day 29, or experienced a DLT prior to Day 29).
For Cohort 8 (first-line CRC) and Cohort 9 (second-line CRC), subjects initially dosed with 
bevacizumab 10 mg/kg Q2W will be replaced. The safety and efficacy data of these subjects will 
be listed but will not be included in the summary of safety or efficacy evaluations.
8.2.1.2.
Pharmacokinetic/Pharmacodynamic Analysis Set
The Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set include subjects in the 
Safety Analysis Set who have the necessary baseline and on-study measurements to provide 
interpretable results for specific parameters of interest.
8.2.2.
Subject Groups
In Part A, 3 proposed dose level cohorts (200 mg, 600 mg, and 1800 mg) will be enrolled. 
In Part B, 7 cohorts (pancreatic adenocarcinoma, lung adenocarcinoma, lung squamous cell 
carcinoma, and esophagogastric adenocarcinoma, first-line CRC, second-line CRC, and breast 
cancer) will be enrolled. Intermediate dose cohorts (400 mg and 1200 mg) will be enrolled if 
≥2 DLTs are observed in the proposed dose level cohorts.
8.2.3.
Data Handling Conventions
In general, values for missing data will not be imputed. However, a missing pre-treatment 
laboratory result would be treated as normal (ie, no toxicity grade) for the laboratory abnormality 
summary.
All available data for subjects that do not complete the study will be included in data listings.


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8.3.
Demographic Data and Baseline Characteristics
Demographic and baseline measurements will be summarized for the safety analysis set by 
dose level (Part A) and tumor type (Part B) using standard descriptive summaries or categorical 
summaries, as appropriate.
8.4.
Safety Analysis
Safety will be evaluated for all subjects in the Safety Analysis Set through assessment of clinical 
laboratory test findings, physical examinations, 12-lead ECGs, vital sign measurements, and by 
the documentation of AEs.
Concomitant medication intake will also be recorded and coded to the corresponding WHO drug 
term and displayed in data listings.
Safety data will be listed by subject and summarized by dose level (Part A) and tumor type 
(Part B), and by frequency of treatment-emergent AEs and laboratory abnormalities.
All safety data collected on or after the date of the first dose of study drug through to completion 
of the follow-up evaluation will be summarized.
Data for the pre-treatment period will be included in data listings.
In Part B, safety data provided in the form of data listings will be reviewed by the 
Medical Monitor on an ongoing basis (at least monthly while subjects are actively enrolling). 
The Sponsor will organize regularly scheduled calls with the clinical sites to discuss study 
updates, safety data, and ongoing clinical experience with GS-5745.
8.4.1.
Extent of Exposure
Dosing information for individual subjects will be listed and summarized by dose level (Part A) 
and tumor type (Part B).
8.4.2.
Adverse Events
Adverse events will be classified using the Medical Dictionary for Regulatory Activities 
(MedDRA) (http://www.meddramsso.com) with descriptions by System Organ Class (SOC), 
High-Level Group Term (HLGT), High-Level Term (HLT), Preferred Term (PT), and 
Lower-Level Term (LLT). AEs will be summarized on the basis of the date of onset of the event. 
All AEs will be listed by subject.
A treatment-emergent AE will be defined as any AE that begins on or after the date of first study 
drug administration and within 30 days after last study drug administration.
Separate listings and summaries will be prepared for all subjects and by dose level (Part A) and 
tumor type (Part B) for the following types of treatment-emergent AEs:


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
Study-drug-related AEs

AEs that are Grade ≥3 in severity

AEs leading to study drug interruption and/or dose modification

AEs leading to study drug discontinuation

Serious AEs (with categorization of the primary reason that the AE is considered serious, 
eg, death, hospitalization, etc)
8.4.3.
Laboratory Evaluations
All laboratory data will be listed and summarized based on observed values. Reference ranges 
provided by the laboratory for each parameter will be used to evaluate the clinical significance of 
laboratory test results. Values falling outside of the relevant reference range will be flagged, as 
appropriate, in the data listings.
Selected laboratory data will be summarized (eg, n, mean, SD, median, Q1, Q3, minimum, and 
maximum) by dose level (Part A) and tumor type (Part B) at scheduled visits and for 
corresponding change from baseline.
Hematologic, serum biochemistry, and coagulation data will be programmatically graded 
according to CTCAE (version 4.03) severity grade, when applicable. For parameters for which a 
CTCAE (version 4.03) scale does not exist, reference ranges from the central laboratory will be 
used to determine programmatically if a laboratory parameter is below, within, or above the 
normal range for the subject’s age, sex, etc. Separate listings and summaries will be prepared for 
laboratory abnormalities that are Grade ≥3 in severity.
The incidence of treatment-emergent laboratory abnormalities, defined as values that increase at 
least 1 toxicity grade from baseline at any time post-baseline up to and including 30 days after 
the last dose of study drug administration, will be summarized by dose level (Part A) and tumor 
type (Part B). If baseline data are missing, then any graded abnormality (ie, at least Grade 1) will 
be considered treatment-emergent.
Laboratory abnormalities that occur before the first dose of study drug or after the subject has 
been discontinued from treatment for at least 30 days will be included in data listings.
8.5.
Exploratory Analysis
Objective response rate by tumor type (Part B) will be presented with corresponding two-sided 
 
CCI


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8.6.
Pharmacokinetics Analysis
Pharmacokinetic parameters will be listed and summarized for GS-5745 using descriptive 
statistics (eg, sample size, arithmetic mean, geometric mean, % coefficient of variation, standard 
deviation, median, Q1, Q3, minimum, and maximum). GS-5745 concentrations over time will be 
plotted in semi logarithmic and linear formats as mean ± standard deviation. Relevant PK 
parameters will be determined using standard non-compartmental methods with the linear up-log
down trapezoidal rule utilizing a PK data analysis program (eg, WinNonlin® or equivalent). The 
following PK parameters will be calculated for GS-5745, as applicable: Cmax, Clast, Tmax, Tlast, λz, 
AUClast, AUCinf, CL, V, and T1/2. The relationship between PK and pharmacodynamics may be 
explored as appropriate.
8.7.
Sample Size
The sample size of the study will depend on the number of dose levels evaluated and the
emerging GS-5745-related toxicities. Part A will comprise 12 to 48 subjects and Part B will 
comprise 115 to 295 subjects (35 subjects in Cohort 4 [pancreatic], 10 subjects each in Cohort 5 
[lung adenocarcinoma] and Cohort 6 [lung squamous cell carcinoma], and 15 subjects each in 
Cohort 7 [esophagogastric], Cohort 8 [first-line CRC], Cohort 9 [second-line CRC] and 
Cohort 10 [breast cancer]. Up to a maximum of 25 additional subjects in each cohort may be 
enrolled to obtain information on safety, PK, pharmacodynamics, and tumor response. For 
Cohort 4, with the assumption of an observed ORR of 40%, the 90% CI would be 19% to 64% 
with a sample size of 15, and 26% to 55% with a sample size of 35. This sample size also 
includes up to 15 replacement subjects for Cohort 8 and Cohort 9, respectively.
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For Cohort 8 (first-line CRC), with the assumption of an ORR of 60%, the 90% CI would be 
36% to 81% with sample size of 15, and 46% to73% with a sample size of 40.
For Cohort 9 (second-line CRC), with the assumption of an ORR of 25%, the 90% CI would be 
10% to 51% with sample size of 15, and 14% to 39% with a sample size of 40.
For Cohort 10 (breast cancer), with the assumption of an ORR of 40%, the 90% CI would be 
19% to 64% with sample size of 15, and 27% to 54% with a sample size of 40.The sample size is 
based on practical considerations and is consistent for this type of study.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
“Declaration of Helsinki” (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on Harmonisation (ICH) guidelines, or with the laws and 
regulations of the country in which the research is conducted, whichever affords the greater 
protection to the study subject. For studies conducted under a United States IND, the investigator 
will ensure that the basic principles of “Good Clinical Practice,” as outlined in 21 CFR 312, 
subpart D “Responsibilities of Sponsors and Investigators,” 21 CFR, part 50, 1998, and 21 CFR, 
part 56, 1998, are adhered to.
9.1.2.
Institutional Review Board (IRB) Approval
This protocol and any accompanying material to be provided to the subject (such as 
advertisements, subject information sheets, or descriptions of the study used to obtain informed 
consent) will be submitted by the investigator to an IRB. Approval from the IRB must be 
obtained before starting the study and should be documented in a letter to the investigator 
specifying the protocol number, protocol version, protocol date, documents reviewed, and date 
on which the committee met and granted the approval.
Any modifications made to the protocol after receipt of IRB approval must also be submitted to 
the IRB for approval before implementation.
9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 
investigator must utilize an IRB-approved consent form for documenting written informed 
consent. Each informed consent will be appropriately signed and dated by the subject or the 
subject’s legally authorized representative and the person obtaining consent.
9.1.4.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, date of birth, and an 
identification code (ie, not names) should be recorded on any form or biological sample 
submitted to the Sponsor, IRB, or laboratory. The investigator must keep a screening log 
showing codes, names, and addresses for all subjects screened and for all subjects enrolled in the 
trial.


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The investigator agrees that all information received from Gilead, including but not limited to the 
Investigator’s Brochure, this protocol, eCRFs, the investigational new drug, and any other study 
information, remain the sole and exclusive property of Gilead during the conduct of the study 
and thereafter. This information is not to be disclosed to any third party (except employees or 
agents directly involved in the conduct of the study or as required by law) without prior written 
consent from Gilead. The investigator further agrees to take all reasonable precautions to prevent 
the disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following 2 categories: (1) investigator’s study file, and (2) subject 
clinical source documents.
The investigator’s study file will contain the protocol/amendments, eCRF and query forms, IRB 
and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.
The required source data are listed in the Source Data Verification Plan, and should include 
sequential notes containing at least the following information for each subject:

subject identification (name, date of birth, gender)

documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria)

participation in trial (including trial number)

trial discussed and date of informed consent

dates of all visits

documentation that protocol specific procedures were performed

results of efficacy parameters, as required by the protocol

start and end date (including dose regimen) of trial medication (preferably drug dispensing 
and return should be documented as well)

record of all AEs and other safety parameters (start and end date, and preferably including 
causality and intensity)

concomitant medication (including start and end date, dose if relevant; dose changes should 
be motivated)

date of trial completion and reason for early discontinuation, if applicable


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All clinical study documents must be retained by the investigator until at least 2 years after the 
last approval of a marketing application in an ICH region (ie, United States, Europe, or Japan) 
and until there are no pending or contemplated marketing applications in an ICH region; or, if no 
application is filed or if the application is not approved for such indication, until 2 years after the 
investigation is discontinued and regulatory authorities have been notified. Investigators may be 
required to retain documents longer if required by applicable regulatory requirements, by local 
regulations, or by an agreement with Gilead. The investigator must notify Gilead before 
destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot guarantee this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these in sealed containers outside of the site so that they can be returned sealed to the 
investigator in case of a regulatory audit. When source documents are required for the continued 
care of the subject, appropriate copies should be made for storage outside of the site.
Please see Section 6.8.12 for information on storage of biological samples at the conclusion of 
the study.
9.1.6.
Electronic Case Report Forms
For each subject enrolled, an eCRF must be completed and signed by the principal investigator 
or sub-investigator (as appropriate) within a reasonable time period after data collection. If a 
subject withdraws from the study, the reason must be noted on the eCRF. If a subject is 
withdrawn from the study because of a treatment-limiting AE, thorough efforts should be made 
to clearly document the outcome.
9.1.7.
Study Drug Accountability and Return
Where possible, IMP should be destroyed at the site. At the start of the study, the study monitor 
will evaluate each study center’s IMP disposal procedures and provide appropriate instruction for 
disposal or return of unused IMP supplies. If the site has an appropriate standard operating 
procedure (SOP) for drug destruction as determined by Gilead, the site may destroy used 
(empty or partially empty) and unused IMP supplies as long as performed in accordance with the 
site’s SOP. This can occur only after the study monitor has performed drug accountability during 
an on-site monitoring visit.
A copy of the site’s IMP Disposal SOP or written procedure (signed and dated by the principal 
investigator or designee) will be obtained for Gilead site files. If the site does not have 
acceptable procedures in place, arrangements will be made between the site and Gilead 
(or Gilead’s representative) for return of unused study drug supplies.


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If IMP is destroyed on site, the investigator must maintain accurate records for all IMPs
destroyed. Upon study completion, copies of the IMP accountability records must be filed at the 
site. Another copy will be returned to Gilead.
The study monitor will review IMP supplies and associated records at periodic intervals
9.1.8.
Inspections
The investigator should understand that source documents for this trial should be made available 
to appropriately qualified personnel from Gilead or its representatives, to IRBs or to regulatory 
authority or health authority inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. All protocol modifications must be submitted to the IRB in accordance 
with local requirements. Approval must be obtained before changes can be implemented.
9.2.2.
Study Report and Publications
A clinical study report will be prepared and provided to the regulatory agency(ies). Gilead will 
ensure that the report meets the standards set out in the ICH Guideline for Structure and Content 
of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in certain 
cases.
After conclusion of the study and without prior written approval from Gilead, investigators in 
this study may communicate, orally present, or publish in scientific journals or other scholarly 
media only after the following conditions have been met:

the results of the study in their entirety have been publicly disclosed by or with the consent of 
Gilead in an abstract, manuscript, or presentation form; or

the study has been completed at all study sites for at least 2 years.
No such communication, presentation, or publication will include Gilead’ confidential 
information (see Section 9.1.4).
The investigator will submit any proposed publication or presentation along with the respective 
scientific journal or presentation forum at least 30 days before submission of the publication or 
presentation. The investigator will comply with Gilead’ request to delete references to its 


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confidential information (other than the study results) in any paper or presentation and agrees to 
withhold publication or presentation for an additional 60 days in order to obtain patent protection 
if deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, eg, attendance at Investigator’s Meetings. If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.
9.3.2.
Access to Information for Monitoring
In accordance with ICH GCP guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the data recorded on the eCRFs for 
consistency.
The monitor is responsible for routine review of the eCRFs at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered. The monitor should have access to any subject records needed to verify the 
entries on the eCRFs. The investigator agrees to cooperate with the monitor to ensure that any 
problems detected in the course of these monitoring visits are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead Medical Monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the Sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies) and IRB(s). In terminating the study, Gilead and the investigator will 
assure that adequate consideration is given to the protection of the subjects’ interests.


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10.
REFERENCES
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Bramhall SR, Hallissey MT, Whiting J, Scholefield J, Tierney G, Stuart RC, et al. Marimastat as 
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Br J Cancer 2002;86 (12):1864-70.
Castaneda FE, Walia B, Vijay-Kumar M, Patel NR, Roser S, Kolachala VL, et al. Targeted 
deletion of metalloproteinase 9 attenuates experimental colitis in mice: central 
role of epithelial-derived MMP. Gastroenterology 2005;129 (6):1991-2008.
Chen EI, Kridel SJ, Howard EW, Li W, Godzik A, Smith JW. A unique substrate recognition 
profile for matrix metalloproteinase-2. J Biol Chem 2002;277 (6):4485-91.
Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX 
versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364 
(19):1817-25.
de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, et al. Leucovorin and 
fluorouracil with or without oxaliplatin as first-line treatment in advanced 
colorectal cancer. J Clin Oncol 2000;18 (16):2938-47.
Dubois B, Masure S, Hurtenbach U, Paemen L, Heremans H, van den Oord J, et al. Resistance of 
young gelatinase B-deficient mice to experimental autoimmune encephalomyelitis 
and necrotizing tail lesions. J Clin Invest 1999;104 (11):1507-15.
Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, et al. Randomized, 
Controlled Trial of Irinotecan Plus Infusional, Bolus, or Oral Fluoropyrimidines 
in First-Line Treatment of Metastatic Colorectal Cancer: Results From the BICC-
C Study. J Clin Oncol 2007;25 (30):4779-86.
Garg P, Vijay-Kumar M, Wang L, Gewirtz AT, Merlin D, Sitaraman SV. Matrix 
metalloproteinase-9-mediated tissue injury overrides the protective effect of 
matrix metalloproteinase-2 during colitis. American journal of physiology. 
Gastrointestinal and liver physiology 2009;296 (2):G175-84.
Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, et al. A 
Randomized Controlled Trial of Fluorouracil Plus Leucovorin, Irinotecan, and 
Oxaliplatin Combinations in Patients With Previously Untreated Metastatic 
Colorectal Cancer. J Clin Oncol 2004;22 (1).


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 95
01 August  2016
Grothey A, Sugrue MM, Purdie DM, Dong W, Sargent D, Hedrick E, et al. Bevacizumab 
Beyond First Progression Is Associated With Prolonged Overall Survival in 
Metastatic Colorectal Cancer: Results From a Large Observational Cohort Study 
(BRiTE). J Clin Oncol 2008;26 (33):5326-34.
Hijova E. Matrix metalloproteinases: their biological functions and clinical implications. 
Bratislavske lekarske listy 2005;106 (3):127-32.
Hu J, Van den Steen PE, Sang QX, Opdenakker G. Matrix metalloproteinase inhibitors as 
therapy for inflammatory and vascular diseases. Nat Rev Drug Discov 2007;6 
(6):480-98.
Imai K, Yokohama Y, Nakanishi I, Ohuchi E, Fujii Y, Nakai N, et al. Matrix metalloproteinase 7 
(matrilysin) from human rectal carcinoma cells. Activation of the precursor, 
interaction with other matrix metalloproteinases and enzymic properties. J Biol 
Chem 1995;270 (12):6691-7.
Itoh T, Matsuda H, Tanioka M, Kuwabara K, Itohara S, Suzuki R. The role of matrix 
metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis. 
J Immunol 2002;169 (5):2643-7.
Itoh T, Tanioka M, Matsuda H, Nishimoto H, Yoshioka T, Suzuki R, et al. Experimental 
metastasis is suppressed in MMP-9-deficient mice. Clinical & experimental 
metastasis 1999;17 (2):177-81.
Kridel SJ, Chen E, Kotra LP, Howard EW, Mobashery S, Smith JW. Substrate hydrolysis by 
matrix metalloproteinase-9. J Biol Chem 2001;276 (23):20572-8.
Lausch E, Keppler R, Hilbert K, Cormier-Daire V, Nikkel S, Nishimura G, et al. Mutations in 
MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum 
of metaphyseal anadysplasia. American journal of human genetics 2009;85 
(2):168-78.
Li H, Mittal A, Makonchuk DY, Bhatnagar S, Kumar A. Matrix metalloproteinase-9 inhibition 
ameliorates pathogenesis and improves skeletal muscle regeneration in muscular 
dystrophy. Human molecular genetics 2009;18 (14):2584-98.
Mauri D, Kamposioras K, Tsali L, Bristianou M, Valachis A, Karathanasi I, et al. Overall 
survival benefit for weekly vs. three-weekly taxanes regimens in advanced breast 
cancer: A meta-analysis. Cancer treatment reviews 2010;36 (2010):69-74.
Miyazaki D, Nakamura A, Fukushima K, Yoshida K, Takeda S, Ikeda S. Matrix 
metalloproteinase-2 ablation in dystrophin-deficient mdx muscles reduces 
angiogenesis resulting in impaired growth of regenerated muscle fibers. Human 
molecular genetics 2011;20 (9):1787-99.


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 96
01 August  2016
Mott JD, Werb Z. Regulation of matrix biology by matrix metalloproteinases. Current opinion in 
cell biology 2004;16 (5):558-64.
Naito Y, Yoshikawa T. Role of matrix metalloproteinases in inflammatory bowel disease. 
Molecular aspects of medicine 2005;26 (4-5):379-90.
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and 
response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 
1982;5 (6):649-55.
Olson MW, Gervasi DC, Mobashery S, Fridman R. Kinetic analysis of the binding of human 
matrix metalloproteinase-2 and -9 to tissue inhibitor of metalloproteinase (TIMP)-
1 and TIMP-2. J Biol Chem 1997;272 (47):29975-83.
Opdenakker G, Nelissen I, Van Damme J. Functional roles and therapeutic targeting of 
gelatinase B and chemokines in multiple sclerosis. Lancet neurology 2003;2 
(12):747-56.
Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in 
Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in 
Metastatic Colorectal Cancer: A Randomized Phase III Study. J Clin Oncol 
2008;26 (12):2013-9.
Santana A, Medina C, Paz-Cabrera MC, Diaz-Gonzalez F, Farre E, Salas A, et al. Attenuation of 
dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient 
mice. World J Gastroenterol 2006;12 (40):6464-72.
Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, et al. Randomized Phase 
III Trial of Weekly Compared With Every-3-Weeks Paclitaxel for Metastatic 
Breast Cancer, With Trastuzumab for all HER-2 Overexpressors and Random 
Assignment to Trastuzumab or Not in HER-2 Nonoverexpressors: Final Results 
of Cancer and Leukemia Group B Protocol 9840. J Clin Oncol 2008;26 
(10):1642-9.
Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D, et al. FOLFIRI 
Followed by FOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer: 
A Randomized GERCOR Study. J Clin Oncol 2004;22 (2):229-37.
Tournigand C, Cervantes A, Figer A, Lledo G, Flesch M, Buyse M, et al. OPTIMOX1: A 
Randomized Study of FOLFOX4 or FOLFOX7 With Oxaliplatin in a Stop-and-
Go Fashion in Advanced Colorectal Cancer—A GERCOR Study. J Clin Oncol 
2006;24 (3):394-400.
Van Wart HE, Birkedal-Hansen H. The cysteine switch: a principle of regulation of 
metalloproteinase activity with potential applicability to the entire matrix 
metalloproteinase gene family. Proc Natl Acad Sci U S A 1990;87 (14):5578-82.


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 97
01 August  2016
Vempati P, Karagiannis ED, Popel AS. A biochemical model of matrix metalloproteinase 9 
activation and inhibition. J Biol Chem 2007;282 (52):37585-96.
Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA, Hanahan D, et al. MMP-9/gelatinase B is 
a key regulator of growth plate angiogenesis and apoptosis of hypertrophic 
chondrocytes. Cell 1998;93 (3):411-22.


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 98
01 August  2016
11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table (Part A)
Appendix 3.
Study Procedures Table (Part B – Pancreatic Adenocarcinoma)
Appendix 4.
Study Procedures Table (Part B – Esophagogastric Adenocarcinoma)
Appendix 5.
Study Procedures Table (Part B – NSCLC)
Appendix 6.
Study Procedures Table (Part B – CRC, First-Line)
Appendix 7.
Study Procedures Table (Part B – CRC, Second-Line)
Appendix 8.
Study Procedures Table (Part B – Breast Cancer)
Appendix 9.
Dose Modification Tables for Gemcitabine and Nab-Paclitaxel
Appendix 10.
Dose Modification Tables for mFOLFOX6


PPD
PPD
GS-5745 
Protocol GS-US-296-0101 
Final 
Gilead Sciences, Inc. 
Amendment 6 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase l Study to Evaluate the Safety, Tolerability, Phannacokinetics, and Pharmacodynamics 
ofGS-5745 as Monotherapy and in Combination with Chemotherapy in Subjects with 
Advanced Solid Tumors 
GS-US-296-0101, Amendment 6, 01 August 2016 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
N rune (Printed) 
Author 
Signature 
INVESTIGATOR STATE:MENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I wiJl discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 99 
01 August 2016 


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 100
01 August 2016
Appendix 2.
Study Procedures Table (Part A)
Week
1
2
3
5
7
9
Q2Wl
Q8Wm
EOSn
Day
-28 to -1
1
2
3
5
8
15
29
43
57
Window
± 1
± 1
± 2
± 2
± 2
± 5
Hours 
(Relative to Dosing)
Pre-
dose
EOI
6
24 ± 2
48 ± 4
96 ± 4
168 ± 4
Pre-
dose
EOI
Pre-
dose
EOI
Pre-
dose
EOI
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
X
X
X
X
X
Vital Signsc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-Lead ECG
X
X
X
X
X
X
X
X
X
X
ECOG Performance Status
X
X
X
X
X
X
X
X
X
X
X
X
Prior/Concomitant Medsd
X
X
X
X
X
X
X
X
X
X
X
X
X
AEse
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CT or MRIf
X
X
X
X
Collect Archival Tumor 
Tissue (if Available)g
X
Register Subject Visit in 
IxRS
X
X
X
X
X
X
X
X
Sample Collection
Chemistry
X
Xj
X
X
X
X
X
X
Xk
X
Hematology
X
Xj
X
X
X
X
X
X
Xk
X
Coagulation
X
Xj
X
X
X
X
X
X
Urinalysis
X
Xj
X
X
X
X
X
X
Pregnancy Testh
X
Xj
X
X
X
X
X
X
GS-5745 Concentrationi
Xj
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
I 
I 
I 


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 101
01 August 2016
Week
1
2
3
5
7
9
Q2Wl
Q8Wm
EOSn
Day
-28 to -1
1
2
3
5
8
15
29
43
57
Window
± 1
± 1
± 2
± 2
± 2
± 5
Hours 
(Relative to Dosing)
Pre-
dose
EOI
6
24 ± 2
48 ± 4
96 ± 4
168 ± 4
Pre-
dose
EOI
Pre-
dose
EOI
Pre-
dose
EOI
Anti-GS-5745 Antibody
Xj
X
X
X
Serum and Plasma 
Biomarkers
X
Xj
X
X
X
X
X
Study Drug Dosing
GS-5745 IV Dosing
X
X
X
X
X
X
EOI = end of infusion; EOS = End-of-Study (visit); PE = physical examination; Q2W = every 2 weeks; Q8W = every 8 weeks
a
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any 
concurrent medical illnesses.
b
A complete physical examination (PE) will be performed at Screening. A modified PE capturing changes from prior examinations will be performed at subsequent applicable 
visits. Weight (without shoes) should be measured at each PE and reported in kilograms. Height (without shoes) should be measured at Screening only and reported in
centimeters.
c
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken per institutional guidelines.
d
Prior/concomitant medications include all medication taken up to 30 days prior to Screening, any and all medications taken during the course of the study, and supportive 
therapies given during the course of the study (eg, blood transfusion, growth factor).
e
AEs will be assessed before and after GS-5745 dosing during applicable visits.
f
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and every 8 weeks thereafter. The same radiographic procedure used to define 
measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if not conducted within the previous 4 weeks. If a 
subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology every 8 weeks until disease progression.
g
Unstained slides (10 to 12) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1.
h
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the EOS visit.
i
Blood samples to measure GS-5745 concentration will be collected pre- and post-dose at each applicable visit.
j
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
k
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology every 8 weeks until disease progression.
l
A subject who does not show evidence of disease progression by clinical assessment or by CT or MRI may continue receiving GS-5745 Q2W until disease progression 
(clinical or radiographic), unacceptable toxicity, withdrawal of consent, or other reasons specified in Section 6.3. Q2W visits will occur every 2 weeks (± 2 days) from the 
Day 57 visit.
m
Q8W visits will occur every 8 weeks (± 5 days) from the Day 57 visit.
n
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than PD, the site 
should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive disease progression.


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 102
01 August 2016
Appendix 3.
Study Procedures Table (Part B – Pancreatic Adenocarcinoma)
Study Phase
Screening
Each Cycle 
(28 Days)
Every 2 Cycles
EOSl
LTFU
Every 3 months
Cycle Day
Screening
1
8
15
N/A
N/A
Window
−28
0m
± 2
± 2
N/A
N/A
Treatment Day
−28
1
8
15
N/A
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
Vital Signsc
X
X
X
X
X
12-Lead ECG
X
X
ECOG Performance Status
X
X
X
X
Prior/Concomitant Medsd
X
X
X
X
X
AEse
X
X
X
X
X
CT or MRIf
X
Xk
X
Collect Archival Tumor Tissue 
(if Available)g
X
Register Subject Visit in IxRS
X
X
X
X
Sample Collection
Chemistry
X
Xj
X
Xk
X
Hematology
X
Xj
X
X
Xk
X
Coagulation
X
Xj
X
Urinalysis
X
Xj
X
Pregnancy Testh
X
Xj
X
X
GS-5745 Concentrationi
X
X
X
Anti-GS-5745 Antibody
Xj
X


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 103
01 August 2016
Study Phase
Screening
Each Cycle 
(28 Days)
Every 2 Cycles
EOSl
LTFU
Every 3 months
Cycle Day
Screening
1
8
15
N/A
N/A
Window
−28
0m
± 2
± 2
N/A
N/A
Treatment Day
−28
1
8
15
N/A
N/A
Serum and Plasma Biomarkers
X
Xj
X
Overall Survival
X
Study Drug Dosing / Chemotherapy
GS-5745 IV Dosing
X
X
Gemcitabine Dosing
X
X
X
Nab-Paclitaxel Dosing
X
X
X
EOS = End-of-Study (visit); PE = physical examination
a
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any 
concurrent medical illnesses.
b
A complete PE will be performed at Screening. A modified PE capturing changes from prior exams will be performed at subsequent applicable visits. Weight (without shoes) 
should be measured at each PE and reported in kilograms. Height (without shoes) should be measured at Screening only and reported in centimeters.
c
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken per institutional guidelines.
d
Prior/concomitant medications include all medication taken up to 30 days prior to Screening, any and all medications taken during the course of the study, and supportive 
therapies given during the course of the study (eg, blood transfusion, growth factor).
e
AEs will be assessed before and after GS-5745 and gemcitabine dosing during applicable visits. The site will call subjects 30 days after the last dose of GS-5745 to assess 
AEs and SAEs.
f
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.). 
The same radiographic procedure used to define measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if 
not conducted within the previous 4 weeks. If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the 
study to collect tumor assessments (CT/MRI), chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
g
Unstained slides (10 to 12) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1 of Cycle 1 only.
h
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the EOS visit.
i
Blood samples to measure GS-5745 concentration will be collected pre-dose on Day 1 and Day 15 of each cycle.
j
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
k
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
l
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than disease 
progression, the site should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive disease progression.
m
A ± 2 day window applies to visits following Cycle 1 Day 1. There is no window for Cycle 1 Day 1.
I I I I 


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 104
01 August 2016
Appendix 4.
Study Procedures Table (Part B – Esophagogastric Adenocarcinoma)
Study Phase
Screening
Each Cycle 
(28 Days)
Every 2 Cycles
EOSm
LTFU
Every 3 months
Cycle Day
Screening
1
15
N/A
N/A
Window
−28
0n
± 2
N/A
N/A
Treatment Day
−28
1
15
N/A
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
Vital Signsc
X
X
X
X
12-Lead ECG
X
X
ECOG Performance Status
X
X
X
X
Prior/Concomitant Medsd
X
X
X
X
AEse
X
X
X
X
CT or MRIf
X
Xl
X
Collect Archival Tumor Tissue 
(if Available)g
X
Register Subject Visit in IxRS
X
X
X
X
Sample Collection
Chemistry
X
Xk
X
Xl
X
Hematology
X
Xk
X
Xl
X
Coagulation
X
Xk
X
Urinalysis
X
Xk
X
Pregnancy Testh
X
Xk
X
X
GS-5745 Concentrationi
X
X
X
Anti-GS-5745 Antibody
Xk
X


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 105
01 August 2016
Study Phase
Screening
Each Cycle 
(28 Days)
Every 2 Cycles
EOSm
LTFU
Every 3 months
Cycle Day
Screening
1
15
N/A
N/A
Window
−28
0n
± 2
N/A
N/A
Treatment Day
−28
1
15
N/A
N/A
Serum and Plasma Biomarkers
X
Xk
X
Overall Survival
X
Study Drug Dosing / Chemotherapy
GS-5745 IV Dosing
X
X
mFOLFOX6 Dosingj
X
X
EOS = End-of-Study (visit); PE = physical examination
a
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any
concurrent medical illnesses.
b
A complete PE will be performed at Screening. A modified PE capturing changes from prior exams will be performed at subsequent applicable visits. Weight (without shoes) 
should be measured at each PE and reported in kilograms. Height (without shoes) should be measured at Screening only and reported in centimeters.
c
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken per institutional guidelines.
d
Prior/concomitant medications include all medication taken up to 30 days prior to Screening, any and all medications taken during the course of the study, and supportive 
therapies given during the course of the study (eg, blood transfusion, growth factor).
e
AEs will be assessed before and after GS-5745 and mFOLFOX6 dosing during applicable visits. The site will call subjects 30 days after the last dose of GS-5745 to assess 
AEs and SAEs.
f
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.). 
The same radiographic procedure used to define measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if 
not conducted within the previous 4 weeks. If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the 
study to collect tumor assessments (CT/MRI), chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
g
Unstained slides (10 to 12) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1 of Cycle 1 only.
h
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the EOS visit.
i
Blood samples to measure GS-5745 concentration will be collected pre-dose on Day 1 and Day 15 of each cycle.
j
mFOLFOX6 dosing regimen will consist of l-LV 200 mg/m2 or dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5-FU 400 mg/m2 and a 46-hour infusion 5-FU 
2400 mg/m2.
k
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
l
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
m
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than disease 
progression, the site should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive disease progression
n
A ± 2 day window applies to visits following Cycle 1 Day 1. There is no window for Cycle 1 Day 1.


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 106
01 August 2016
Appendix 5.
Study Procedures Table (Part B – NSCLC)
Study Phase
Screening
Each Cycle 
(21 Days)
Every 3 Cycles
EOSl
LTFU
Every 3 Months
Cycle Day
Screening
1
N/A
N/A
Window
−28
± 2
N/A
N/A
Treatment Day
−28
1
N/A
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
Vital Signsc
X
X
X
12-Lead ECG
X
X
ECOG Performance Status
X
X
X
Prior/Concomitant Meds
X
X
X
AEsd
X
X
X
CT or MRIe
X
Xk
X
Collect Archival Tumor Tissue 
(if Available)f
X
Register Subject Visit in IxRS
X
X
X
Sample Collection
Chemistry
X
Xj
Xk
X
Hematology
X
Xj
Xk
X
Coagulation
X
Xj
X
Urinalysis
X
Xj
X
Pregnancy testg
X
Xj
X
GS-5745 Concentrationh
X
X
Anti-GS-5745 Antibody
Xj
X


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 107
01 August 2016
Study Phase
Screening
Each Cycle 
(21 Days)
Every 3 Cycles
EOSl
LTFU
Every 3 Months
Cycle Day
Screening
1
N/A
N/A
Window
−28
± 2
N/A
N/A
Treatment Day
−28
1
N/A
N/A
Serum and Plasma Biomarkers
X
Xj
X
Overall Survival
X
Study Drug Dosing / Chemotherapy
GS-5745 IV Dosing
X
Chemotherapy Dosingi
X
EOS = End-of-Study (visit); PE = physical examination
a
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any 
concurrent medical illnesses.
b
A complete PE will be performed at Screening. A modified PE capturing changes from prior exams will be performed at subsequent applicable visits. Weight (without shoes) 
should be measured at each PE and reported in kilograms. Height (without shoes) should be measured at Screening only and reported in centimeters.
c
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken per institutional guidelines.
d
AEs will be assessed before and after GS-5745 dosing during applicable visits. The site will call subjects 30 days after the last dose of GS-5745 to assess AEs and SAEs.
e
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and during the last week of every third cycle (ie, Cycles 3, 6, 9, etc.). The 
same radiographic procedure used to define measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if not 
conducted within the previous 4 weeks. If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study 
to collect tumor assessments (CT/MRI), chemistry, and hematology during the last week of every third cycle (ie, Cycles 3, 6, 9, etc.) until disease progression.
f
Unstained slides (10 to 12) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1 of Cycle 1 only.
g
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the EOS visit.
h
Blood samples to measure GS-5745 concentration will be collected pre-dose on Day 1 of each cycle.
i
NSCLC chemotherapy regimen: carboplatin IV dosed to AUC 6 on Day 1 of each 21-day treatment cycle and pemetrexed 500 mg/m2 IV on Day 1 of each 21-day treatment 
cycle in subjects with lung adenocarcinoma. Chemotherapy will consist of carboplatin IV dosed to AUC 6 on Day 1 of each 21-day treatment cycle and paclitaxel 200 mg/m2
IV on Day 1 of each 21-day treatment cycle in subjects with lung squamous cell carcinoma. Subjects who have not had disease progression after 4 cycles of treatment may 
have some of their treatment reduced based upon the investigator’s assessment of what is in the subject’s best interests. However, dosing with GS-5745 should be continued 
per protocol.
j
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
k
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology during the last week of every third cycle (ie, Cycles 3, 6, 9, etc.) until disease progression.
l
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than disease 
progression, the site should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive disease progression.


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 108
01 August 2016
Appendix 6.
Study Procedures Table (Part B – CRC, First-Line)
Study Phase
Screening
Each Cycle (28 Days)
Cycle 2
Cycle 3
Every 2 Cycles
EOSm
LTFU
Every 3 
Months
Cycle Day
Screening
1
15
15
1
N/A
N/A
Window
−28
0r
± 2
+14 Days /
−7 Days
N/A
N/A
Treatment Day
−28
1
15
N/A
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
Vital Signsc
X
X
X
X
12-Lead ECG
X
X
ECOG Performance Status
X
X
X
X
Prior/Concomitant Medsd
X
X
X
X
AEse
X
X
X
X
CT or MRIf
X
Xl
X
Collect Archival Tumor Tissue 
(if Available)g
Xg
Register Subject Visit in IxRS
X
X
X
X
Sample Collection
Chemistry
X
Xk
X
Xl
X
Hematology
X
Xk
X
Xl
X
Coagulation
X
Xk
X
Urinalysis
X
Xk
X
Pregnancy Testh
X
Xk
X
X


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 109
01 August 2016
Study Phase
Screening
Each Cycle (28 Days)
Cycle 2
Cycle 3
Every 2 Cycles
EOSm
LTFU
Every 3 
Months
Cycle Day
Screening
1
15
15
1
N/A
N/A
Window
−28
0r
± 2
+14 Days /
−7 Days
N/A
N/A
Treatment Day
−28
1
15
N/A
N/A
GS-5745 Concentrationi
X
X
X
X
Anti-GS-5745 Antibody
Xk
X
Serum and Plasma Biomarkers
Xk,n
Xn
Xn
Stool Sample
Xo
Xo
Overall Survival
X
Study Drug Dosing / Chemotherapy
GS-5745 IV Dosing
X
X
mFOLFOX6/Bev Dosingj
X
X
EOS = End-of-Study (visit); PE = physical examination
a
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any 
concurrent medical illnesses.
b
A complete PE will be performed at Screening. A modified PE capturing changes from prior exams will be performed at subsequent applicable visits. Weight (without shoes) 
should be measured at each PE and reported in kilograms. Height (without shoes) should be measured at Screening only and reported in centimeters.
c
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken per institutional guidelines.
d
Prior/concomitant medications include all medication taken up to 30 days prior to Screening, any and all medications taken during the course of the study, and supportive 
therapies given during the course of the study (eg, blood transfusion, growth factor).
e
AEs will be assessed before and after GS-5745 and mFOLFOX6 dosing during applicable visits. The site will call subjects 30 days after the last dose of GS-5745 to assess 
AEs and SAEs.
f
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.). 
The same radiographic procedure used to define measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if 
not conducted within the previous 4 weeks. If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the 
study to collect tumor assessments (CT/MRI), chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
g
Unstained slides (5×10 micron and 10×5 micron) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1 of 
Cycle 1 only.
CCI
CCI


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 110
01 August 2016
h
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the EOS visit.
i
Blood samples to measure GS-5745 concentration will be collected pre-dose on Day 1 and Day 15 of each cycle, end of GS-5745 infusion on Day 1 of Cycle 1 and Cycle 3, 
and at the EOS visit.
j
mFOLFOX6 and bevacizumab dosing regimen on Days 1 and 15 of each 28-day treatment cycle will consist of:  bevacizumab at 5 mg/kg IV and mFOLFOX6 dosing regimen 
will consist of l-leucovorin (LV) 200 mg/m2 or dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5 FU 400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2
k
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
l
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
m
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than disease
progression, the site should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive disease progression.
n
Blood samples for biomarkers should be drawn pre-dose on all specified visits. Note that Day 15 is only required for Cycle 1 and that a blood sample at EOS is required if due 
to disease progression. The exact schedule of blood draws is outlined in the laboratory manual.
o
A stool sample is required at study start and can be collected any time within the screening window prior to first dose. An additional stool sample at Cycle 2 Day 15 
(+14 days/−7 days) is requested.
r
A ± 2 day window applies to visits following Cycle 1 Day 1. There is no window for Cycle 1 Day 1.
CCII 


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 111
01 August 2016
Appendix 7.
Study Procedures Table (Part B – CRC, Second-Line)
Study Phase
Screening
Each Cycle (28 Days)
Cycle 2
Cycle 3
Every 2 Cycles
EOSm
LTFU
Every 3 
Months
Cycle Day
Screening
1
15
15
1
N/A
N/A
Window
-28
0r
±2
+14 Days /
−7 Days
N/A
N/A
Treatment Day
-28
1
15
N/A
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
Vital Signsc
X
X
X
X
12-Lead ECG
X
X
ECOG Performance Status
X
X
X
X
Prior/Concomitant Medsd
X
X
X
X
AEse
X
X
X
X
CT or MRIf
X
Xl
X
Collect Archival Tumor Tissue 
(if Available)g
X
Register Subject Visit in IxRS
X
X
X
X
Sample Collection
Chemistry
X
Xk
X
Xl
X
Hematology
X
Xk
X
Xl
X
Coagulation
X
Xk
X
Urinalysis
X
Xk
X
Pregnancy Testh
X
Xk
X
X


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 112
01 August 2016
Study Phase
Screening
Each Cycle (28 Days)
Cycle 2
Cycle 3
Every 2 Cycles
EOSm
LTFU
Every 3 
Months
Cycle Day
Screening
1
15
15
1
N/A
N/A
Window
-28
0r
±2
+14 Days /
−7 Days
N/A
N/A
Treatment Day
-28
1
15
N/A
N/A
GS-5745 Concentrationi
X
X
X
X
Anti-GS-5745 Antibody
Xk
X
Serum and Plasma Biomarkers
Xk,n
Xn
Xn
Stool Sample
Xo
Xo
Overall Survival
X
Study Drug Dosing / Chemotherapy
GS-5745 IV Dosing
X
X
FOLFIRI/Bev Dosingj
X
X
EOS = End-of-Study (visit); PE = physical examination
a
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any 
concurrent medical illnesses.
b
A complete PE will be performed at Screening. A modified PE capturing changes from prior exams will be performed at subsequent applicable visits. Weight (without shoes) 
should be measured at each PE and reported in kilograms. Height (without shoes) should be measured at Screening only and reported in centimeters.
c
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken per institutional guidelines.
d
Prior/concomitant medications include all medication taken up to 30 days prior to Screening, any and all medications taken during the course of the study, and supportive 
therapies given during the course of the study (eg, blood transfusion, growth factor).
e
AEs will be assessed before and after GS-5745 and FOLFIRI dosing during applicable visits. The site will call subjects 30 days after the last dose of GS-5745 to assess AEs 
and SAEs.
f
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.). 
The same radiographic procedure used to define measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if 
not conducted within the previous 4 weeks. If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the 
study to collect tumor assessments (CT/MRI), chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
g
Unstained slides (10 to 12) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1 of Cycle 1 only.
CCI
CCI


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 113
01 August 2016
h
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the EOS visit.
i
Blood samples to measure GS-5745 concentration will be collected pre-dose on Day 1 and Day 15 of each cycle, end of GS-5745 infusion on Day 1 of Cycle 1 and Cycle 3, 
and at the EOS visit.
j
FOLFIRI and bevacizumab dosing regimen on Days 1 and 15 of each 28-day treatment cycle will consist of: bevacizumab at 5 mg/kg IV, and FOLFIRI at l-LV 200 mg/m2 or 
dl LV 400 mg/m2 as a 2-hour infusion, and irinotecan 180 mg/m2 given as a 90-minute infusion in 500 mL dextrose 5% via a Y-connector, followed by bolus 
5-FU 400 mg/m2 and a 46-hour infusion 5-FU 2400 mg/m2.     
k
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
l
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI),
chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression
m
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than disease 
progression, the site should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive disease progression.
n
Blood samples for biomarkers should be drawn pre-dose on all specified visits. Note that Day 15 is only required for Cycle 1 and that a blood sample at EOS is required if due 
to disease progression. The exact schedule of blood draws is outlined in the laboratory manual.
o
A stool sample is required at study start and can be collected any time within the screening window prior to first dose. An additional stool sample at Cycle 2 Day 15 
(+14 days/−7 days) is requested.
r
A ± 2 day window applies to visits following Cycle 1 Day 1. There is no window for Cycle 1 Day 1.
CCII 


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 114
01 August 2016
Appendix 8.
Study Procedures Table (Part B – Breast Cancer)
Study Phase
Screening
Each Cycle (28 Days)
Cycle 2
Cycle 3
Every 2 
Cycles
EOSm
LTFU
Cycle Day
Screening
1
8
15
15
1
N/A
N/A
Window
−28
0q
± 2
± 2
+14 Days /
−7 Days
N/A
N/A
Treatment Day
−28
1
8
15
N/A
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
Vital Signsc
X
X
X
X
X
12-Lead ECG
X
X
ECOG Performance Status
X
X
X
X
Prior/Concomitant Medsd
X
X
X
X
X
AEse
X
X
X
X
X
CT or MRIf
X
Xl
X
Collect Archival Tumor Tissue 
(if Available)g
X
Register Subject Visit in IxRS
X
X
X
X
Sample Collection
Chemistry
X
Xk
X
Xl
X
Hematology
X
Xk
X
X
Xl
X
Coagulation
X
Xk
X
Urinalysis
X
Xk
X


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 115
01 August 2016
Study Phase
Screening
Each Cycle (28 Days)
Cycle 2
Cycle 3
Every 2 
Cycles
EOSm
LTFU
Cycle Day
Screening
1
8
15
15
1
N/A
N/A
Window
−28
0q
± 2
± 2
+14 Days /
−7 Days
N/A
N/A
Treatment Day
−28
1
8
15
N/A
N/A
Pregnancy Testh
X
Xk
X
X
GS-5745 Concentrationi
X
X
X
X
Anti-GS-5745 Antibody
Xk
X
Serum and Plasma Biomarkers
Xk,n
Xn
Xn
Overall Survival
X
Study Drug Dosing / Chemotherapy
GS-5745 IV Dosing
X
X
Paclitaxelj
X
X
X
EOS = End-of-Study (visit); PE = physical examination
a
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any 
concurrent medical illnesses.
b
A complete PE will be performed at Screening. A modified PE capturing changes from prior exams will be performed at subsequent applicable visits. Weight (without shoes) 
should be measured at each PE and reported in kilograms. Height (without shoes) should be measured at Screening only and reported in centimeters.
c
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken per institutional guidelines.
d
Prior/concomitant medications include all medication taken up to 30 days prior to Screening, any and all medications taken during the course of the study, and supportive 
therapies given during the course of the study (eg, blood transfusion, growth factor).
e
AEs will be assessed before and after GS-5745 and Paclitaxel dosing during applicable visits. The site will call subjects 30 days after the last dose of GS-5745 to assess AEs 
and SAEs.
f
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.). 
The same radiographic procedure used to define measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if 
not conducted within the previous 4 weeks. If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the 
study to collect tumor assessments (CT/MRI), chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
g
Unstained slides (10 to 12) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1 of Cycle 1 only.
CCI


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 6
CONFIDENTIAL
Page 116
01 August 2016
h
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the EOS visit.
i
Blood samples to measure GS-5745 concentration will be collected pre-dose on Day 1 and Day 15 of each cycle, end of GS-5745 infusion on Day 1 of Cycle 1 and Cycle 3, 
and at the EOS visit.
j
Paclitaxel dosing regimen will consist of Paclitaxel 80 mg/m2 IV.
k
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
l
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
m
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than disease 
progression, the site should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive disease progression.
n
Blood samples for biomarkers should be drawn pre-dose on all specified visits. Note that Day 15 is only required for Cycle 1 and that a blood sample at EOS is required if due 
to disease progression. The exact schedule of blood draws is outlined in the laboratory manual.
 
q
A ± 2 day window applies to visits following Cycle 1 Day 1. There is no window for Cycle 1 Day 1.
CCII 


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
Page 117
16 May 2016
Appendix 9.
Dose Modification Tables for Gemcitabine and Nab-Paclitaxel
Appendix Table 1.
Dose Modifications for Day 1 of Each Cycle (Hematologic Toxicity)
Treatment Day Counts and Toxicity
ANC
Platelets
Timing
≥1.5 × 109/L
And
≥100 × 109/L
Treat on time
< 1.5 × 109/L
Or
< 100 × 109/L
Delay by 1 week intervals until recovery
Appendix Table 2.
Dose Modifications for Day 1 of Each Cycle (Non-Hematologic Toxicity)
Non-Hematologic Toxicity and/or Dose Hold with Previous Cycle
Toxicity/Dose Held
Gemcitabine/Gemcitabine + Nab-Paclitaxel Dose this Cycle
Grade 0, 1, or 2 Toxicity
Same as Day 1 of previous cycle (except for Grade 2 cutaneous 
toxicity where doses of gemcitabine and nab-paclitaxel should both 
be reduced to next lower dose level
Grade 3 Toxicitya
Decrease gemcitabine and nab-paclitaxel to next lower dose level
Grade 4 Toxicitya,b
Off chemotherapy treatment
Dose Held in 2 Previous Consecutive Cycles
Decrease gemcitabine to next lower dose level and continue 
throughout the rest of treatment
a
If the toxicity only affects neuropathy, then only nab-paclitaxel should be reduced.
b
Pulmonary embolism if mild or asymptomatic will be exempt from this requirement.
I 
I 


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
Page 118
16 May 2016
Appendix Table 3.
Dose Modifications for Hematologic Toxicity within a Cycle
Day 8 Blood Counts
Day 8 Nab-P
Day 8 Gem
Day 15 Blood Counts
Day 8 Nab-P
Day 8 Gem
Any Day Nab-P
Any Day Gem
ANC > 1000 and 
Platelets ≥75,000
100%
100%
ANC > 1000 and 
Platelets ≥75,000
100%
ANC 500-1000 or 
Platelets 50,000 -74,999
Full Dose (treat on time)
ANC < 500 or 
Platelets < 50,000
Hold
ANC 500-1000a or 
Platelets 50,000-74,999
Decrease dose by 1 level 
(treat on time)
ANC > 1000 and 
Platelets ≥75,000
Return to Previous Level 
(treat on time)
ANC 500-1000 or 
Platelets 50,000-74,999
Same Dose 
(as Day 8, treat on time)
ANC < 500 or 
Platelets < 50,000
Hold
ANC < 500b or 
Platelets < 50,000
Hold
Hold
ANC > 1000 and 
Platelets ≥75,000
Decrease Day 8 by 1 level 
(treat on time)
ANC 500-1000 or 
Platelets 50,000-74,999
Decrease Day 8 by 1 level 
(treat on time)
ANC < 500 or 
Platelets < 50,000
Hold
Febrile Neutropenia 
(Grade 3 or 4)d
Hold. Upon resuming dosing, decrease to next 
lower dose level and do not re-escalate 
throughout rest of treatment.
Recurrent Febrile 
Neutropenia
(Grade 3 or 4)a
Decrease to next lower 
dose level and do not 
re-escalate throughout 
the rest of treatment.
Decrease 2 dose levels 
(to 600 mg/m2) and do 
not re-escalate 
throughout the rest of 
treatment.
a
Gem = gemcitabine; Nab-P = nab-paclitaxel
b
If the subject does not experience resolution of neutropenia within 21 days, chemotherapy treatment will be discontinued.
c
Febrile subjects (regardless of neutrophil count) should have their chemotherapy treatment interrupted. Blood counts must have returned to baseline levels before resuming 
chemotherapy treatment. A full sepsis diagnostic work-up should be performed while continuing broad spectrum antibiotics. If cultures are positive, the antibiotic treatment 
may or may not be changed, depending on the sensitivity profile of the isolated organism. Subjects with persisting fever after 3 weeks, despite uninterrupted antibiotic 
treatment, will discontinue chemotherapy treatment. 
d
Pulmonary embolism if mild or asymptomatic, will be exempt from this requirement.
I 


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
Page 119
16 May 2016
Appendix Table 4.
Dose Modifications for Non-Hematologic Toxicity within a Cycle
CTCAE Grade
Percent of Day 1
Gemcitabine + Nab-Paclitaxel
Grade 0 to 2 (and Grade 3 Nausea/Vomiting)
100%
Grade 3 (Except Nausea/Vomiting)
Hold either one or both drugsa until resolution to ≤Grade 1, 
then resume treatment at the next lower dose level.
Grade 4
Hold
a
This decision as to which drug should be modified will depend upon the type of non-hematologic toxicity seen and which 
course is medically most sound in the judgment of the investigator.
Pulmonary embolism (a Grade 4 toxicity in the CTCAE tables) if mild or asymptomatic, will be exempt from this requirement.


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
Page 120
16 May 2016
Appendix 10.
Dose Modification Tables for mFOLFOX6
Appendix Table 5.
Recommended Dose Modifications for Oxaliplatin + 5-Fluorouracil/Leucovorina
CTCAE v. 4.03
System Organ Classa
Adverse Eventb
Dose Level for Subsequent Cycles
Based on Interval AEs
At Time of Retreatment
All Adverse Events < 1
Maintain dose level
Maintain dose level
Blood and Lymphatic System 
Disorders:
Hemolytic uremic syndrome (HUS)c
> Grade 3
Discontinue oxaliplatin
Discontinue oxaliplatin
Investigations:
Neutrophil count decreased
If ANC < 1500 at start of cycle, hold 
and check weekly then treat based on 
interval adverse event. If ANC < 1500 
after 4 weeks, discontinue therapy.
Grade 1 (ANC < LLN - 1500/mm3)
Maintain dose level
Grade 2 (ANC < 1500 - 1000/mm3)
Maintain dose level
Grade 3 (ANC < 1000 - 500/mm3)
Omit 5-FU bolus AND 1 oxaliplatin 
dose level
Grade 4 (ANC < 500/mm3)
Omit bolus 5-FU and both infusional 
5-FU and oxaliplatin 1 dose level
Platelet count decreased
If PLT < 75,000 at start of cycle, hold 
and check weekly then treat based on 
interval adverse event. If PLT < 75,000 
after 4 weeks, discontinue therapy.
Grade 1 (PLT < LLN - 75,000/mm3)
Maintain dose level
Grade 2 (PLT < 75,000 - 50,000/mm3)
Maintain dose level
Grade 3 (PLT < 50,000 - 25,000/mm3)
Omit 5-FU bolus AND 1 oxaliplatin 
dose level
Grade 4 (PLT < 25,000/mm3)
Omit 5-FU bolus AND 2 oxaliplatin 
dose levels
Gastrointestinal Disorders: 
Diarrhea
If Grade ≥2 at start of cycle, hold and 
check weekly then treat based on 
interval adverse event. If Grade ≥2 after 
4 weeks, discontinue therapy.
Grades 1, 2
Maintain dose level
Grade 3
One 5-FU dose level
Grade 4
Both 5-FU and oxaliplatin 1 dose level
Mucositis oral
Grades 1, 2
Maintain dose level
Grade 3
One 5-FU dose level
Grade 4
One 5-FU dose level


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Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
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CTCAE v. 4.03
System Organ Classa
Adverse Eventb
Dose Level for Subsequent Cycles
Based on Interval AEs
At Time of Retreatment
Vomiting
Grades 1, 2
Maintain dose level
Grade 3
1 oxaliplatin dose level
Grade 4
Both 5-FU and oxaliplatin 1 dose level
Metabolism and Nutrition 
Disorders:
Hypomagnesaemia
Dose reduction is not required for hypomagnesaemia unless symptoms are present. 
If Grade ≥2 after 4 weeks, discontinue therapy.
Neurology:
Do not use CTCAE.
See Appendix 10, Appendix Table 6 for AE scale and oxaliplatin dose modifications.
Respiratory, Thoracic, and 
Mediastinal Disorders:
Cough ≥Grade 3
Dyspnea ≥Grade 3
Hypoxia ≥Grade 3
Pneumonitis ≥Grade 3
Hold oxaliplatin until interstitial lung disease is ruled out. If interstitial lung 
disease, oxaliplatin should be permanently discontinued.
Other Non-Hematologic AEsd,e:
Grades 1, 2
Maintain dose level
Grades 3, 4
1 5-FU dose level
a
The dose of leucovorin will not be adjusted due to AEs. It should remain at 400 mg/m2 dl-leucovorin or 200 mg/m2 of l-leucovorin for all courses. Leucovorin will be given 
immediately prior to each 5-FU dose; thus, if 5-FU is delayed, leucovorin will be delayed. Leucovorin doses may be adjusted per institutional guidelines in the event of a 
supply shortage.
b
For ≤NCI CTCAE v. 4.03 Grade 2 toxicity not described, maintain dose level of agent.
c
Recommended evaluation of suspected HUS: Evaluation should include CBC differential, platelets, PT, PTT, fibrinogen, FDP, Anti thrombin III, Von Willebrand factor, 
anti-nuclear antibody, rheumatoid factor, Compliment Cascade C3, C4, and CH50, anti-platelet antibodies, platelet-associated IgG, and circulating immune complexes.  Renal 
evaluation should include creatinine, BUN, and urinalysis with microscopic examination. Other laboratory and hematologic evaluations as appropriate should also be 
obtained, including peripheral blood smear and free hemoglobin.
d
Exceptions:  fatigue, anorexia, nausea/vomiting if can be controlled by antiemetics, and viral infections.
e
Dose modifications for other non-hematologic adverse events at the start of subsequent courses of therapy, and at time of retreatment are also based on NCI CTCAE v. 4.03
criteria.


GS-5745
Protocol GS-US-296-0101
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
Page 122
16 May 2016
Appendix Table 6.
Oxaliplatina Dose Modifications for Non-CTCAE Neurologic 
Adverse Events
Adverse Events
Duration of Adverse Event
Persistentb Between 
Cycles
1 −7 Days
> 7 Days
Paresthesias/Dysesthesias
Paresthesias/dysesthesiasc of 
short duration that resolve and do 
not interfere with function 
(Grade 1)
No change
No change
No change
Paresthesias/dysesthesiasc
interfering with function, but not 
activities of daily living (ADL)
(Grade 2)
No change
No change
1 oxaliplatin dose level
Paresthesias/dysesthesiasc with 
pain or with functional 
impairment that also interfere 
with ADL (Grade 3)
First time:
1 oxaliplatin dose level
First time:
1 oxaliplatin dose level
Discontinue
Second time:
1 oxaliplatin dose level
Second time:
1 oxaliplatin dose level
Persistent paresthesias/dysesthesias 
that are disabling or 
life-threatening (Grade 4)
Discontinue
Discontinue
Discontinue
Laryngeal Dysesthesias (investigator discretion used for grading):
Grade 0 = none
Grade 1 = mild
No change
duration of infusion to 
6 hours
duration of infusion to 
6 hours
Grade 2 = moderate
Also recommended is 
administration of benzodiazepine 
and patient education. 
Management of patient if 
≥Grade 2 laryngeal dysesthesias 
occurs while treatment is being 
administered.
Stop oxaliplatin infusion.
Administer benzodiazepine and give patient reassurance.
At the discretion of the investigator, the infusion can be restarted at 
1/3 the original rate of infusion.
Grade 3 = severe
a
If oxaliplatin is discontinued, continue other study agents unless adverse events preclude their continuation.
b
Not resolved by the beginning of the next cycle.
c
May be cold-induced.
I 


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Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
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Each cycle consists of two 14-day courses of FOLFIRI plus study drug. A new course of therapy 
should not begin until the granulocyte count has recovered to ≥ 1500/mm3, the platelet count has 
recovered to ≥100,000/mm3, and treatment-related diarrhea is fully resolved. Subjects should 
return to pre-treatment bowel function without requiring antidiarrhea medications for at least 
24 hours before the next chemotherapy administration. Treatment should be delayed 1 week, and
if necessary 2 weeks, to allow for recovery from treatment related toxicities.
Dose modifications for subsequent courses of therapy will be carried out for Grade 3 and 4 
neutropenia/hematologic toxicity and Grade 2, 3 and 4 non-hematologic toxicities. Subjects who 
require persistent 1- or 2-week delays for the resolution of recurring Grade 1 toxicities, may have 
their dose reduced by 1 dose level to permit administration of FOLFIRI every 2 weeks, at the 
investigator’s discretion.
If the subject has not recovered after a 2-week delay or requires more than 2 dose reductions, 
consideration should be given to discontinuing FOLFIRI therapy and continuing treatment with 
GS-5745 alone.
Appendix Table 7.
Recommended Dose Modifications for FOLFIRI
Toxicity NCI CTCAE Gradea
(Value)
During a 2-Week Course of FOLFIRI Therapy or at the Time the 
Next Course of FOLFIRI is to Start
Neutropenia
1 (1500 to 1999/mm3)
Maintain dose level
2 (1000 to 1499/mm3)
Omit dose until resolved to ≤ Grade 1, maintain dose level
3 (500 to 999/mm3)
Omit dose until resolved to ≤ Grade 1, then ↓ 1 dose level
4 (< 500/mm3)
Omit dose until resolved to ≤ Grade 1, then ↓ 2 dose levels
Neutropenic Fever
Omit dose until resolved, then ↓ 2 dose levels
Other Hematologic Toxicities
Dose modifications for leukopenia or thrombocytopenia are also based on NCI 
CTCAE toxicity criteria and are the same as recommended for neutropenia above.
Diarrhea
1 (2-3 stools/day > pretxb)
Delay dose until resolved to baseline, then give same dose
2 (4-6 stools/day > pretx)
Omit dose until resolved to baseline, then ↓ 1 dose level
3 (7-9 stools/day > pretx)
Omit dose until resolved to baseline, then ↓ 1 dose level
4 (≥10 stools/day > pretx)
Omit dose until resolved to baseline, then ↓ 2 dose levels
Other Non-Hematologic 
Toxicitiesc
1
Maintain dose level
2
Omit dose until resolved to ≤ Grade 1, then ↓ 1 dose level
3
Omit dose until resolved to ≤ Grade 2, then ↓ 1 dose level
4
Omit dose until resolved to ≤ Grade 2, then ↓ 2 dose levels
For mucositis/stomatitis decrease only 5-FU, not irinotecan
a
National Cancer Institute’s Common Terminology Criteria for Adverse Events, v 4.03
b
Pre-treatment
c
Excludes alopecia, anorexia, asthenia

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 1 Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics, and Pharmacodynamics of GS-5745 as 
Monotherapy and in Combination with Chemotherapy in 
Subjects with Advanced Solid Tumors
Name of Test Drug:
Andecaliximab (GS-5745)
Study Number:
GS-US-296-0101
Protocol Version:
Amendment 6
Protocol Date:
01 August 2016
Analysis Type:
Final Analysis
Analysis Plan Version:
1.0
Analysis Plan Date:
24 July 2019
Analysis Plan Author:
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(r) GILEAU 


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TABLE OF CONTENTS
STATISTICAL ANALYSIS PLAN..............................................................................................................................1
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................4
LIST OF ABBREVIATIONS........................................................................................................................................5
PHARMACOKINETIC ABBREVIATIONS................................................................................................................7
1.
INTRODUCTION ................................................................................................................................................8
1.1.
Study Objectives ......................................................................................................................................8
1.2.
Study Design............................................................................................................................................8
1.3.
Sample Size and Power..........................................................................................................................10
2.
TYPE OF PLANNED ANALYSES ...................................................................................................................12
2.1.
Interim Analyses ....................................................................................................................................12
2.2.
Final Analysis ........................................................................................................................................12
2.3.
Follow-up Analysis ................................................................................................................................12
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSIS .............................................................................13
3.1.
Analysis Sets..........................................................................................................................................13
3.1.1.
All Enrolled Analysis Set.....................................................................................................13
3.1.2.
Safety Analysis Set...............................................................................................................13
3.1.3.
Full Analysis Set ..................................................................................................................13
3.1.4.
DLT Analysis Set.................................................................................................................14
3.1.5.
Pharmacokinetic (PK) Analysis Set .....................................................................................14
3.1.6.
Immunogenicity Analysis Set ..............................................................................................14
3.1.7.
Biomarker Analysis Sets ......................................................................................................14
3.2.
Subject Grouping ...................................................................................................................................14
3.3.
Strata and Covariates..............................................................................................................................15
3.4.
Examination of Subject Subsets.............................................................................................................15
3.5.
Multiple Comparisons............................................................................................................................15
3.6.
Missing Data and Outliers......................................................................................................................16
3.6.1.
Missing Data ........................................................................................................................16
3.6.2.
Outliers.................................................................................................................................16
3.7.
Data Handling Conventions and Transformations .................................................................................16
3.8.
Analysis Visit Windows.........................................................................................................................17
3.8.1.
Definition of Study Day .......................................................................................................17
3.8.2.
Analysis Visit Windows.......................................................................................................18
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis 
Window................................................................................................................................21
4.
SUBJECT DISPOSITION ..................................................................................................................................22
4.1.
Subject Enrollment and Disposition.......................................................................................................22
4.2.
Extent of Exposure.................................................................................................................................23
4.2.1.
Exposure to Study Drug (GS-5745) .....................................................................................23
4.2.2.
Exposure to Chemotherapy ..................................................................................................24
4.3.
Protocol Deviations................................................................................................................................24
5.
BASELINE CHARACTERISTICS....................................................................................................................25


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5.1.
Demographics and Baseline Characteristics ..........................................................................................25
5.2.
Medical History......................................................................................................................................25
5.3.
Prior Chemotherapy and Radiotherapy..................................................................................................26
5.4.
Concomitant Cancer Related Surgeries and Procedures ........................................................................26
6.
EFFICACY ANALYSES ...................................................................................................................................27
6.1.
Definition and Analysis of Efficacy Endpoints......................................................................................27
6.1.1.
Objective Response Rate......................................................................................................27
6.1.2.
Progression-Free Survival ....................................................................................................27
6.1.3.
Overall Survival ...................................................................................................................29
6.1.4.
Duration of Response...........................................................................................................29
6.1.5.
Time to Response.................................................................................................................29
6.1.6.
Change in Tumor Size..........................................................................................................30
6.1.7.
ECOG Performance Status...................................................................................................30
7.
SAFETY ANALYSES........................................................................................................................................31
7.1.
Adverse Events.......................................................................................................................................31
7.1.1.
Adverse Event Dictionary ....................................................................................................31
7.1.2.
Adverse Event Severity........................................................................................................31
7.1.3.
Relationship of Adverse Event to Study Treatment .............................................................31
7.1.4.
Serious Adverse Events........................................................................................................31
7.1.5.
Treatment-Emergent Adverse Events...................................................................................32
7.1.6.
Summaries of Adverse Events..............................................................................................32
7.1.7.
Additional Analyses of Adverse Events...............................................................................34
7.2.
Laboratory Evaluations ..........................................................................................................................34
7.2.1.
Graded Laboratory Values ...................................................................................................35
7.2.2.
Shifts Relative to the Baseline Value ...................................................................................35
7.2.3.
Summaries of Laboratory Results ........................................................................................36
7.3.
Vital Signs..............................................................................................................................................36
7.4.
Prior and Concomitant Medications.......................................................................................................36
7.4.1.
Prior Medications .................................................................................................................36
7.4.2.
Concomitant Medications.....................................................................................................37
7.5.
Electrocardiogram (ECG) Results..........................................................................................................37
7.5.1.
Investigator Electrocardiogram Assessment ........................................................................38
7.5.2.
Corrected QT Intervals.........................................................................................................38
7.5.3.
PR and QRS Intervals...........................................................................................................39
7.6.
Other Safety Measures ...........................................................................................................................39
7.7.
Changes From Protocol-Specified Safety Analyses...............................................................................39
8.
PHARMACOKINETIC ANALYSES ................................................................................................................40
8.1.
PK Sample Collection............................................................................................................................40
8.2.
Statistical Analysis Methods ..................................................................................................................40
8.2.1.
GS-5745 Plasma Concentration ...........................................................................................40
8.2.2.
GS-5745 PK Parameters.......................................................................................................40
9.
IMMUNOGENICITY ANALYSES...................................................................................................................42
9.1.
ADA Sample Collection.........................................................................................................................42
9.2.
Statistical Analyses Methods .................................................................................................................42
10.
BIOMARKER ANALYSES...............................................................................................................................43
10.1.
Statistical Analysis Methods ..................................................................................................................43
11.
REFERENCES ...................................................................................................................................................44


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12.
SOFTWARE.......................................................................................................................................................45
13.
APPENDICES ....................................................................................................................................................46
Appendix 1.
Study Procedures Table (Part A)............................................................................................47
Appendix 2.
Study Procedures Table (Part B – Pancreatic Adenocarcinoma)............................................49
Appendix 3.
Study Procedures Table (Part B – Esophagogastric Adenocarcinoma)..................................51
Appendix 4.
Study Procedures Table (Part B – NSCLC) ...........................................................................53
Appendix 5.
Study Procedures Table (Part B – First Line CRC)................................................................55
Appendix 6.
Study Procedures Table (Part B- Second Line CRC).............................................................58
Appendix 7.
Study Procedures Table (Part B – Breast Cancer)..................................................................61
Appendix 8.
List of Laboratory Tests for Safety Summary ........................................................................64
LIST OF IN-TEXT TABLES
Table 1.
Chemotherapy Treatments for Cohorts 4 through 10 .............................................................10
Table 2.
The number of subjects in each cohort for Part B ..................................................................11
Table 3.
Post Baseline Visit Windows for Central Lab (Cohorts 1, 2 & 3)..........................................18
Table 4.
Post Baseline Visit Windows for Central Lab, Vital Signs, ECG, Performance 
Status (Cohorts 4 and 10) .......................................................................................................18
Table 5.
Post Baseline Visit Windows for Central Lab, Vital Signs, ECG, Performance 
Status (Cohorts 5 and 6) .........................................................................................................19
Table 6.
Post Baseline Visit Windows for Central Lab, Vital Signs, ECG, Performance 
Status (Cohort 7, 8, 9).............................................................................................................19
Table 7.
Post Baseline Visit Windows for Tumor Assessment (Cohorts 4, 7, 8, 9, and 10) ................19
Table 8.
Post Baseline Visit Windows for Tumor Assessment (Cohorts 5 and 6) ...............................20
Table 9.
Post Baseline Visit Windows for Free and Total MMP9 (Cohorts 1, 2 and 3).......................20
Table 10.
Post Baseline Visit Windows for Free and Total MMP9 (Cohorts 4 and 7)...........................20
Table 11.
Post Baseline Visit Windows for Free and Total MMP9 (Cohorts 5 and 6)...........................20
Table 12.
PK parameters for GS-5745 ...................................................................................................41


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LIST OF ABBREVIATIONS
ADA
anti-drug antibody
AE
adverse event
ALT 
alanine aminotransferase 
ANC
absolute neutrophil count 
AST
aspartate aminotransferase
ATC
Anatomical Therapeutic Chemical
AUC
area under the drug concentration over time curve
BEV
bevacizumab
BLQ
below the limit of quantitation
CI
confidence interval
CSR
clinical study report
CR
complete response
CRC
colorectal cancer
CT
computerized tomography
CTCAE
Common Terminology Criteria for Adverse Events
DLT
dose limiting toxicity
DOR
duration of response
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form(s)
EOI
end of infusion
EOS
end of study
HLGT
high-level group term
HLT
high-level term
INR
international normalized ratio
LLT
lower-level term
MedDRA
Medical Dictionary for Regulatory Activities
MMP
matrix metalloproteinase
MRI
magnetic resonance imaging
MTD
maximum tolerated dose
NSCLC
non-small cell lung cancer
ORR
objective response rate
PE
physical exam
PFS
progression-free survival
PK
pharmacokinetics
PR
partial response
PT
preferred term
Q1
first quartile


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Q2W
once every two weeks
Q3
third quartile
Q3W
once every three weeks
QRS
electrocardiographic deflection between the beginning of the Q wave and termination of 
the S wave representing time for ventricular depolarization
QT
electrocardiographic interval between the beginning of the Q wave and termination of the 
T wave representing the time for both ventricular depolarization and repolarization to 
occur
QTc
corrected QT interval
QTcF
corrected QT interval based on Fridericia’s formula
RECIST
Response Evaluation Criteria in Solid Tumors
SAE
serious adverse event
SE
standard error
SOC
system organ class
StD
standard deviation
TEAE
treatment-emergent adverse event
ULN
upper limit of the normal range
VR
ventricular rate
WHO
World Health Organization


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PHARMACOKINETIC ABBREVIATIONS
AUClast
area under the concentration versus time curve from time zero to the last quantifiable concentration
AUCinf
area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast 
(Clast/z)
Ceoi
observed concentration of drug at the end of infusion
Clast
last observed quantifiable concentration of the drug 
Cmax
maximum observed concentration of drug 
CL
Systemic clearance of the drug after intravenous administration
t1/2
estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log of 2 
by the terminal elimination rate constant (z)
Tlast
time (observed time point) of Clast
Tmax
time (observed time point) of Cmax
z
terminal elimination rate constant, estimated by linear regression of the terminal elimination phase 
of the concentration of drug versus time curve
V
volume of distribution of the drug after intravenous administration


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the synoptic clinical study 
report (CSR) for Study GS-US-296-0101. This SAP is based on the study protocol amendment 6
dated 01 August 2016 and the electronic case report form (eCRF). The SAP will be finalized 
before database finalization. Any changes made after the finalization of the SAP will be 
documented in the CSR.
1.1.
Study Objectives
The primary objectives of this study are as follows:

To determine the maximum tolerated dose (MTD) of GS-5745 monotherapy in subjects with 
advanced solid tumors

To characterize the safety and tolerability of GS-5745 as monotherapy and in combination 
with various chemotherapy regimens in subjects with select tumor types.
The secondary objectives of this study are as follows:

To characterize the pharmacokinetics (PK) of GS-5745

To evaluate the formation of anti-GS-5745 antibodies 
 
 
The exploratory objective of the study is as follows:
 
1.2.
Study Design
This is an open-label, multicenter, sequential dose-escalation, and expansion study to evaluate 
the safety, tolerability, PK, and pharmacodynamics of GS-5745 alone and in combination with 
chemotherapy. The study will be conducted in 2 parts (Part A and Part B).
CCI
CCI
I 
I 
I 


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Dose Escalation – Part A:
Cohorts of subjects with advanced solid tumors who have failed or are intolerant to standard 
therapy or for whom no standard therapy exists will be sequentially enrolled at progressively 
higher dose levels to receive GS-5745 as monotherapy via intravenous (IV) infusion every 
2 weeks (Q2W). Dose escalation [3+3] will be performed with cohort sizes of 3 to 6 subjects. 
The starting dose for Cohort 1 will be 200 mg. Subsequent doses of 600 and 1800 mg are planned. 
The decision to escalate to the next higher dose cohort will be made by a Dose Escalation 
Committee consisting of site investigators and Gilead study team members. Specifically, if 2 or 
more subjects experience dose limiting toxicities (DLTs) at 1800 mg, then 1200 mg will be 
explored. If 2 or more subjects experience DLTs at 600 mg, then 400 mg will be explored. The 
maximum tolerated dose (MTD) is the highest dose level with a subject incidence of DLT during 
the first 28 days of study drug dosing of 0 or 1 out of 6. 
After determination of MTD, Part B will commence. During Part B of the study, up to 3 additional 
cohorts consisting of no more than 10 subjects each may be studied with GS-5745 at 
monotherapy doses up to MTD given every 2 weeks to obtain additional information on PK and 
pharmacodynamics.
Dose Expansion – Part B:
The dose expansion will begin once all subjects in the dose escalation portion of Part A have 
completed the 28-day DLT period. Subjects with advanced pancreatic adenocarcinoma 
(Cohort 4), lung adenocarcinoma (Cohort 5), lung squamous cell carcinoma (Cohort 6), 
esophagogastric adenocarcinoma (Cohort 7), colorectal cancer (CRC) in the first-line setting 
(Cohort 8), CRC in the second-line setting (Cohort 9), or breast cancer (Cohort 10) will be enrolled 
to receive GS-5745 via IV (Q2W for Cohorts 4, 7, 8, 9 and 10; Q3W for Cohorts 5 and 6) in 
combination with chemotherapy.
The cohort dose levels for GS-5745 in Part B are presented below and will be based on the MTD 
determined in Part A.
MTD from Part A (mg)
Q2W
Doses to be used in Part B (mg)
Q2W
Q3W
200
133
200
400
267
400
600
400
600
1200
800
1200
1800
800
1200
The chemotherapies for each cohort in Part B are outlined in Table 1.


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Table 1.
Chemotherapy Treatments for Cohorts 4 through 10
Cohort 
Chemotherapy Treatment(s)
Cohort 4 (pancreatic cancer)
gemcitabine
nab-paclitaxel
Cohort 5 (lung adenocarcinoma)
carboplatin
pemetrexed
Cohort 6 (lung squamous cell carcinoma)
carboplatin
paclitaxel
Cohort 7 (esophagogastric adenocarcinoma)
mFOLFOX6a
Cohort 8 (colorectal cancer in first-line setting)
mFOLFOX6
bevacizumab
Cohort 9 (colorectal cancer in second-line setting)
FOLFIRIb
bevacizumab
Cohort 10 (breast cancer)
paclitaxel
a
mFOLFOX6 regimen includes 5-FU, leucovorin, and oxaliplatin
b
FOLFIRI regimen includes 5-FU, leucovorin, and irinotecan
Subjects in both Part A and B will be treated until disease progression, unacceptable toxicity, 
withdrawal of consent, or other reasons specified in the study protocol Section 6.4.
For Part A tumor evaluation by computerized tomography (CT) or magnetic resonance imaging 
(MRI) will be performed during screening (within 4 weeks of Day 1) and every 8 weeks 
thereafter. CT or MRI should be conducted at the end of study (EOS) visit if not conducted 
within the previous 4 weeks.
For Part B tumor evaluation by CT or MRI scan will be performed during screening and during 
the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) for all cohorts except for Cohort 5 
and 6, in which a CT or MRI scan will be performed during the last week of every third cycle (ie, 
Cycles 3, 6, 9, etc.). CT or MRI should be conducted at the EOS visit if not conducted within the 
previous 4 weeks.
The schedule of assessments is located in Appendix 1 to Appendix 7 of the SAP.
1.3.
Sample Size and Power
The sample size of the study will be determined based on the number of dose levels evaluated 
and the emerging GS-5745-related toxicities. Part A will consist of 12 to 48 subjects, and Part B 
will consist of 115 to 295 subjects (35 subjects in Cohort 4, 10 subjects each in Cohort 5 and 
Cohort 6, and 15 subjects each in Cohort 7, Cohort 8, Cohort 9 and Cohort 10). Up to a 
maximum of 25 additional subjects may be enrolled in Cohorts 5-10 to obtain information on 
safety, PK, pharmacodynamics, and tumor response. This sample size also includes up to 
additional 15 replacement subjects for Cohort 8 and Cohort 9, respectively.


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Table 2 below summarizes the number of subjects in each cohort for Part B.
Table 2.
The number of subjects in each cohort for Part B
Part B: Dose Expansion
Cohort
Disease Subtype
No. Subjects
4
Pancreatic adenocarcinoma
35
5
Lung adenocarcinoma
10-35
6
Lung squamous cell carcinoma
10-35
7
Esophagogastric adenocarcinoma
15-40
8
First-line colorectal cancer
15-55*
9
Second-line colorectal cancer
15-55**
10
Breast cancer
15-40
*
For Cohort 8 (first-line CRC), the sample size of 40 subjects was initially planned. In protocol amendment 5, the dose of 
bevacizumab is corrected to be 5 mg/kg Q2W. Up to 15 subjects who previously started bevacizumab treatment at other 
dose levels will be replaced. Therefore, a total of up to 55 subjects may be enrolled in Cohort 8.
**
For Cohort 9 (second-line CRC), the sample size of 40 subjects was initially planned. In protocol amendment 5, the dose of 
bevacizumab is corrected to be 5 mg/kg Q2W. Up to 15 subjects who previously started bevacizumab treatment at other 
dose levels will be replaced. Therefore, a total of up to 55 subjects may be enrolled in Cohort 9.


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2.
TYPE OF PLANNED ANALYSES
2.1.
Interim Analyses
No formal interim efficacy analysis with the possibility of early termination for efficacy or 
futility is planned.
2.2.
Final Analysis
After all subjects have discontinued the study, outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned and finalized, the final analysis of 
the data will be performed.
2.3.
Follow-up Analysis
No follow-up analysis is planned for this study.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSIS
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each category will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (StD) or standard error (SE), median, first 
quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
By-subject listings will be presented for all subjects in the All Enrolled Analysis Set and sorted 
by subject ID number, visit date, and time (if applicable). Data collected on log forms, such as 
adverse events (AEs), will be presented in chronological order within the subject. The treatment 
group to which subjects were initially assigned will be used in the listings. Age, sex at birth, 
race, and ethnicity will be included in the listings, as space permits.
3.1.
Analysis Sets
Analysis sets define the subjects to be included in an analysis. Analysis sets and their definitions 
are provided in this section. The analysis set will be identified and included as a subtitle of each 
table, figure, and listing.
For each analysis set, the number and percentage of subjects included will be summarized. 
3.1.1.
All Enrolled Analysis Set
The All Enrolled Analysis Set includes all subjects who are assigned a study subject 
identification number in the study after screening.
The All Enrolled Analysis Set will be used for subject enrollment summary. 
3.1.2.
Safety Analysis Set
The Safety Analysis Set includes all subjects who received at least 1 infusion at any dose level of 
study drug GS-5745.
The Safety Analysis Set will be used for safety analyses. 
3.1.3.
Full Analysis Set
The Full Analysis Set includes all subjects in the Safety Analysis Set, except for those who were 
initially dosed with bevacizumab 10 mg/kg Q2W in Cohort 8 and Cohort 9. The Full Analysis 
Set will be used for efficacy analyses, unless otherwise specified.
The reason those subjects are excluded from efficacy analysis is that 10 mg/kg Q2W is not the 
intended bevacizumab dose (per protocol amendment 5) and it is not meaningful to summarize 
the efficacy under this treatment combination.


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3.1.4.
DLT Analysis Set
The DLT Analysis Set includes all subjects in the Safety Analysis Set who 

received 2 doses of GS-5745 prior to Day 29, or

experienced a DLT prior to Day 29.
The DLT Analysis Set will be used for analyses related to DLT in Part A.
3.1.5.
Pharmacokinetic (PK) Analysis Set
The Pharmacokinetic (PK) Analysis Set will include all subjects in the Safety Analysis Set who 
have at least 1 nonmissing post dose concentration value reported by the PK laboratory. It will be 
used for all PK analyses.
3.1.6.
Immunogenicity Analysis Set
The Immunogenicity Analysis Set will include all subjects in the Safety Analysis Set who have 
at least 1 nonmissing postdose antidrug antibody (ADA) status reported. This is the primary 
analysis set for all immunogenicity analyses.
3.1.7.
Biomarker Analysis Sets
The Biomarker Analysis Set will include subjects in the Safety Analysis Set who have at least 
1 evaluable biomarker measurement available.
3.2.
Subject Grouping
Unless otherwise specified, subjects will be analyzed by study part (A or B) and then by cohort. 
In Part A, the cohorts are by dose levels:

Cohort 1: 200 mg Q2W mono

Cohort 2: 600 mg Q2W mono

Cohort 3: 1800 mg Q2W mono
In Part B, the cohorts are disease types:

Cohort 4: Pancreatic adenocarcinoma 

Cohort 5: Lung adenocarcinoma

Cohort 6: Lung squamous cell carcinoma


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
Cohort 7: Esophagogastric adenocarcinoma 

Cohort 8 BEV 5 mg/kg: Colorectal cancer (CRC) in first-line setting with bevacizumab 
initially dosed at 5 mg/kg

Cohort 8 BEV 10 mg/kg: Colorectal cancer (CRC) in first-line setting with bevacizumab 
initially dosed at 10 mg/kg (not included in efficacy analysis)

Cohort 9 BEV 5 mg/kg: Colorectal cancer (CRC) in second line setting with bevacizumab 
initially dosed at 5 mg/kg.

Cohort 9 BEV 10 mg/kg: Colorectal cancer (CRC) in second line setting with bevacizumab 
initially dosed at 10 mg/kg. (not included in efficacy analysis)

Cohort 10: Breast cancer
3.3.
Strata and Covariates
This study does not use a stratified randomization schedule when enrolling subjects. No 
covariates will be included in efficacy and safety analyses.
3.4.
Examination of Subject Subsets
Overall summary of treatment-emergent adverse events will be examined in the following 
subgroups for cohorts in Part B:

Age group
< 65
≥ 65

Gender
Male
Female

Race
White
Non-White
3.5.
Multiple Comparisons
Adjustments for multiplicity will not be made, because no formal statistical testing will be 
performed in this study.


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3.6.
Missing Data and Outliers
3.6.1.
Missing Data
In general, values for missing data will not be imputed unless methods for handling missing data 
are specified.
For missing last dosing date of study drug, imputation rules are described in Section 4.2.1. The 
handling of missing or incomplete dates for the start date of new anti-cancer therapy is in 
Section 6.1.2, for date of death in Section 6.1.3, for AE onset in Section 7.1.5.2, and for prior and 
concomitant medications in Section 7.4.
3.6.2.
Outliers
Unless otherwise specified, outliers will not be excluded from the analysis in general.  
3.7.
Data Handling Conventions and Transformations
In general, age (in years) on the date of the first dose of study drug will be used for analyses and 
presentation in listings. If an enrolled subject was not dosed with any study drug, the enrollment
date will be used instead of the first dosing date of study drug. For screen failures, the date the 
informed consent was signed will be used for age calculation. If only the birth year is collected 
on the CRF, “01 July” will be used for the unknown birth day and month for the purpose of age 
calculation. If only birth year and month are collected, “01” will be used for the unknown birth 
day.
Non-PK data that are continuous in nature but are less than the lower limit of quantitation (LOQ)
or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used for calculation of descriptive statistics if 
the datum is reported in the form of “< x” (x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, then values of 49 and 4.9 will be used for calculation 
of summary statistics, respectively. An exception to this rule is any value reported as < 1 or 
< 0.1, etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be 
used to calculate summary statistics.

A value that is 1 unit above the LOQ will be used for calculation of descriptive statistics if 
the datum is reported in the form of “> x” (x is considered the LOQ). For example, if the 
values are reported as > 50 and > 5.0, then values of 51 and 5.1 will be used for calculation 
of summary statistics, respectively. Values with decimal points will follow the same logic as 
above.

The LOQ will be used for calculation of descriptive statistics if the data is reported in the 
form of “≤x” or “≥ x” (x is considered as the LOQ).


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If analyses based on the assumption that the data are normally distributed are not adequate, 
analyses may be performed on log-transformed data or nonparametric analysis methods may be 
used, as appropriate.
Natural logarithmic transformation will be used for plasma/blood concentrations and analysis of 
PK parameters. Plasma concentration values that are below the limit of quantitation (BLQ) will 
be presented as “BLQ” in the concentration data listing. Values that are BLQ will be treated as 
0 at predose time points, and one-half the value of the LOQ at postdose time points for 
determination of summary and order statistics. 
The following conventions will be used for the presentation of summary and order statistics: 

If at least 1 subject has a concentration value of BLQ for the time point, the minimum value 
will be displayed as “BLQ.”

If more than 25% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum and Q1 values will be displayed as “BLQ.” 

If more than 50% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, and median values will be displayed as “BLQ.” 

If more than 75% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, median, and Q3 values will be displayed as “BLQ.” 

If all subjects have concentration data values of BLQ for a given time point, all order 
statistics (minimum, Q1, median, Q3, and maximum) and summary statistics will be 
displayed as “BLQ.”
PK parameters that are BLQ will be imputed as one-half LOQ before log transformation or 
statistical model fitting.
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study day will be calculated from the date of first dose of study drug (GS-5745) administration 
and derived as follows:

For post-dose study days: Assessment Date – First Dosing Date + 1

For days prior to the first dose: Assessment Date – First Dosing Date
Therefore, study day 1 is the day of first dose of study drug administration.


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3.8.2.
Analysis Visit Windows
Subject visits might not occur on protocol-specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows.
Baseline is defined as the last observation prior to the first dose, unless otherwise specified.
The visit windows are specified in Table 3, Table 4, Table 5, Table 6, Table 7, and Table 8. The 
visit windows for biomarkers, matrix metalloproteinase 9 (MMP9), are specified in Table 9, 
Table 10, and Table 11. The lowest and highest study days are inclusive. 
Table 3.
Post Baseline Visit Windows for Central Lab (Cohorts 1, 2 & 3)
Analysis Visit
Relative Day
Lowest Relative Day 
(inclusive)
Highest Relative Day 
(inclusive)
Week 1
8
Day 1 Post First GS-5745 
Dose
11
Week 2
15
12
21
Week 4
29
22
35
Week 6
43
36
49
Week X=8, 10, …
7*x+1
7x-6
7*x + 7
Table 4.
Post Baseline Visit Windows for Central Lab, Vital Signs, ECG, 
Performance Status (Cohorts 4 and 10)
Analysis Visit
Relative Day
Lowest Relative Day 
(inclusive)
Highest Relative Day 
(inclusive)
Week 1
8
Day 1 Post First GS-5745 
Dose
11
Week 2
15
12
21
Week 4
29
22
32
Week X=4*k+1
28*k+8
28*k+5
28*k+11
Week X=4*k+2
28*k+15
28*k+12
28*k+21
Week X=4*k+4
28*k+29
28*k+22
28*k+32


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Table 5.
Post Baseline Visit Windows for Central Lab, Vital Signs, ECG, 
Performance Status (Cohorts 5 and 6)
Analysis Visit
Relative Day
Lowest Relative Day 
(inclusive)
Highest Relative Day 
(inclusive)
Week 3
22
Day 1 Post First GS-5745 
Dose
33
Week 6
43
34
54
Week 9
64
55
75
Week X=12, 15, …
7*x+1
7*x-8
7*x+12
Table 6.
Post Baseline Visit Windows for Central Lab, Vital Signs, ECG, 
Performance Status (Cohort 7, 8, 9)
Analysis Visit
Relative Day
Lowest Relative Day 
(inclusive)
Highest Relative Day 
(inclusive)
Week 2
15
Day 1 Post First GS-5745 
Dose
21
Week 4
29
22
35
Week 6
43
36
49
Week X=8, 10, …
7*x+1
7*x-6
7*x+7
Table 7.
Post Baseline Visit Windows for Tumor Assessment (Cohorts 4, 7, 8, 9, 
and 10)
Analysis Visit
Relative Day
Lowest Relative Day 
(inclusive)
Highest Relative Day 
(inclusive)
Week 8
57
Day 1 Post First GS-5745 
Dose
85
Week 16
113
86
141
Week 24
169
142
197
Week X=32, 40, …
7*x+1
7*x-27
7*x+28


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Table 8.
Post Baseline Visit Windows for Tumor Assessment (Cohorts 5 and 6)
Analysis Visit
Relative Day
Lowest Relative Day 
(inclusive)
Highest Relative Day 
(inclusive)
Week 9
64
Day 1 Post First GS-5745 
Dose
94
Week 18
127
95
157
Week 27
190
158
220
Week X=36, 45, …
7*x+1
7*x-31
7*x+31
Table 9.
Post Baseline Visit Windows for Free and Total MMP9 (Cohorts 1, 2 
and 3)
Analysis Visit
Relative Day
Lowest Relative Day 
(inclusive)
Highest Relative Day 
(inclusive)
Week 2
15
Day 1 Post First GS-5745 
Dose
29
Week 6
43
30
50
Week 8
57
51
85
Week X=16, 24, 32, …
7*x+1
7*x-26
7*x+29
Table 10.
Post Baseline Visit Windows for Free and Total MMP9 (Cohorts 4 
and 7)
Analysis Visit
Relative Day
Lowest Relative Day 
(inclusive)
Highest Relative Day 
(inclusive)
Week 4
29
Day 1 Post First GS-5745 
Dose
43
Week 8 
57
44
71
Week X=12, 16, 20, …
7*x+1
7*x - 12
7*x +15
Table 11.
Post Baseline Visit Windows for Free and Total MMP9 (Cohorts 5 
and 6)
Analysis Visit
Relative Day
Lowest Relative Day 
(inclusive)
Highest Relative Day 
(inclusive)
Week 3
22
Day 1 Post First GS-5745 
Dose
32
Week 6
43
33
53
Week X=9, 12, 15, …
7*x + 1
7*x - 9
7*x +11


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For Cohorts 1, 2 and 3, the analysis window will not be applied to vital signs, electrocardiogram 
(ECG) and Eastern Cooperative Oncology Group (ECOG) performance status. Nominal visit 
name will be used. Any data relating to unscheduled visits will not be assigned to a particular 
visit or time point. However, the following exceptions will be made:

An unscheduled visit prior to first dosing of study drug may be included in the calculation of 
the baseline value, if applicable.

Unscheduled visits after the first dosing of study drug will be included in determining the 
maximum postbaseline toxicity grade.

End of study visit data will be summarized as a separate visit, labeled as “End of Study”.
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Window
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time-to-event analysis would not require 1 value per analysis window.
If multiple, valid, non-missing values exist in an analysis window, records will be chosen based 
on the following rules if a single value is needed:

For baseline, the last nonmissing value on or prior to the first dosing date of study drug will 
be selected, unless specified differently. If there are multiple records with the same time or 
no time recorded on the same day, the baseline value will be the average of the measurements 
for continuous data, or the measurement with the lowest severity (eg, normal will be selected 
over abnormal for safety ECG findings) for categorical data.

For postbaseline values:
The record closest to the relative day for that visit will be selected.
If there are 2 records that are equidistant from the relative day, the later record will be 
selected.
If there is more than 1 record on the selected day, the last measurement will be used; if 
the measurement occur at the same time or time cannot be determined, the average will 
be taken for continuous data and the worse severity will be taken for categorical data, 
unless otherwise specified.


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
A summary of subject enrollment will be provided by study part and cohort for each investigator 
and overall. The summary will present the number and percentage of subjects enrolled. For each 
column, the denominator for the percentage calculation will be the total number of subjects 
analyzed for that column.
A summary of subject disposition will be provided by study part and cohort. This summary will 
present the number of subjects screened, the number of subjects enrolled, and the number of 
subjects in each of the categories listed below:

Treated with study drug (GS-5745) (applicable to part A and B)
Treatment discontinued 
■
Reasons for discontinuation

Treated with chemotherapy (applicable to part B)
Treatment discontinued 
■
Reasons for discontinuation

Discontinued study
Reasons for study discontinuation
For the discontinuation reasons of chemotherapy with more than 1 drug component category, the 
reason of the earliest discontinued drug will be used for summary table. If multiple drug 
discontinued on the same day with different reasons category is selected, the reason with the 
highest rank (Adverse Event > Progressive Disease > Others) will be selected. Discontinuation 
reasons for each drug components will be provided in the listing. 
For the status of study drug and study completion and reasons for premature discontinuation
categories, the number and percentage of subjects in each category will be provided. The 
denominator for the percentage calculation will be the total number of subjects in the Safety
Analysis Set corresponding to that column. In addition, a flowchart will be provided to depict the 
disposition.
A listing of subject enrollment will be provided to describe site, subject ID, informed consent 
date, and first screening date. Those enrolled but not treated will be flagged.
A separate listing of inclusion/exclusion findings for all screened subjects who did not meet all 
inclusion/exclusion criteria will also be provided.


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A listing of subject disposition will be provided, including site ID, subject ID, cohort, date of 
first and last dose of study drug (GS-5745), duration of study drug exposure, date of last dose of 
chemotherapy (if applicable), reason for discontinuing treatments (GS-5745, chemotherapy 
respectively) (if applicable), and reason for study discontinuation.
4.2.
Extent of Exposure
4.2.1.
Exposure to Study Drug (GS-5745)
Exposure to GS-5745 will be summarized by study part and cohort for the Safety Analysis Set.
Duration of Exposure
Duration of exposure to study drug will be defined as (last dose date – first dose date + 1),
regardless of temporary interruptions in study drug administration, and will be expressed in 
weeks using up to 1 decimal place (eg, 4.5 weeks).  If the last study drug dosing end date is 
missing, the last study drug start date will be used to impute the end date of the last study drug. 
Duration of exposure to study drug will be summarized using descriptive statistics (N, mean, 
standard deviation [StD], median, minimum and maximum). Summaries will be provided by 
study part and cohort for the Safety Analysis Set.
Number of Doses
The number and percentage of subjects receiving a given number of planned doses of GS-5745
will be presented. A subject is said to have received a dose of GS-5745 if he/she received any 
dose of GS-5745.
Actual Dose Amount
In addition, the total and average actual dose amount received for GS-5745 in mg will be 
summarized using descriptive statistics (N, mean, StD, median, Q1, Q3, minimum, and 
maximum). 
The average actual dose amount of GS-5745 is defined as (total actual dose amount received in 
mg) / (number of doses given), regardless of whether the doses were interrupted/completed or 
full/reduced. 
A by-subject listing of study drug (GS-5745) administration will be provided by subject ID 
number (in ascending order) and visit (in chronological order), including dosing date/time, 
planned dosage, actual dosage administered, infusion outcome and reason for dose reduction (if 
applicable).


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4.2.2.
Exposure to Chemotherapy
Exposure to chemotherapy will be listed and summarized for each drug component in a similar 
manner as for GS-5745. Chemotherapy received prior to study enrollment and after the start of 
other anti-cancer therapy will not be included in the summary.
4.3.
Protocol Deviations
Subjects who did not meet the eligibility criteria for study entry, but enrolled in the study, will be 
summarized regardless of whether they were exempted by the sponsor or not. The summary will 
present the number and percentage of subjects who did not meet at least 1 eligibility criterion and 
the number of subjects who did not meet specific criteria by study part and cohort based on the 
All Enrolled Analysis Set. A by-subject listing will be provided for those subjects who did not 
meet at least 1 eligibility (inclusion or exclusion) criterion. The listing will present the eligibility 
criterion (or criteria if more than 1 deviation) that subjects did not meet and related comments, if 
collected.
Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. The number and percentage of subjects with important protocol deviations by 
deviation reason (eg, nonadherence to study drug, violation of select inclusion/exclusion criteria) 
will be summarized by study part and cohort for the All Enrolled Analysis Set. A by-subject 
listing will be provided for those subjects with important protocol deviation.


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
The following demographic and baseline characteristics will be listed and summarized for the 
Safety Analysis Set:

Age

Sex

Race

Ethnicity

Weight (at baseline, overall and by sex)

Height (at baseline, overall and by sex)

Body Mass Index (at baseline, overall and by sex)

ECOG Status at Baseline
Demographic and baseline characteristics summaries will be presented by study part and cohort 
using descriptive statistics (N, mean, StD, median, Q1, Q3, minimum, and maximum) for 
continuous data and displaying the number and percent of subjects for categorical data. Age at 
baseline is calculated in years at the first dosing date of study drug.
A by-subject demographic listing will be provided by subject ID number in ascending order.
5.2.
Medical History
Medical history will be collected at screening for disease-specific and general conditions 
(ie, conditions not specific to the disease being studied).
Disease-specific medical history will be summarized by cohort and overall by the number and 
percentage of subjects with each prepopulated condition. The summary will be provided for the 
Safety Analysis Set. 
Variables to be summarized include:

Stage at Screening

Location of Tumor (applicable to esophagogastric cohort only)

Histology of cancer (applicable to Gastric cancer only)


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A by-subject listing of disease history will be provided by subject ID number in ascending order.
General medical history data will not be coded, but will be listed only. A by-subject listing of 
general medical history will be provided by subject ID number in ascending order.
5.3.
Prior Chemotherapy and Radiotherapy
Number of prior chemotherapy and radiotherapy will be summarized using descriptive statistics 
and by number of subjects in each category for the Safety Analysis Set. 
The details of prior chemotherapy will be listed including line of therapy, type of regimen, and 
regimen start/stop date.  
The details of prior radiotherapy will also be listed, including site irradiated and radiotherapy 
start/stop date.
5.4.
Concomitant Cancer Related Surgeries and Procedures
A listing of concomitant cancer related surgeries and procedures will be provided for the All 
Enrolled Analysis Set.


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6.
EFFICACY ANALYSES
Efficacy parameters will be listed for Parts A and B, and summarized for Part B only by cohort 
based on Full Analysis Set. The investigator assessments will be used for analyses of efficacy 
endpoints. 
6.1.
Definition and Analysis of Efficacy Endpoints
6.1.1.
Objective Response Rate
Objective response rate (ORR) is defined as the proportion of subjects with best overall response 
during GS-5745 therapy of complete response (CR) or partial response (PR) based on RECIST 1.1. 
Response assessments occurring after new anticancer therapy, the assessments after missing 
2 previous consecutive tumor scans, or the assessments after progressive disease (PD) will not be 
included for ORR analysis.
The following will be performed for the Full Analysis Set by cohort in Part B:

Best overall response will be summarized using the number and the percentage of subjects in 
each category (eg, Complete Response [CR], Partial Response [PR], Stable Disease [SD], 
Non-CR/Non-PD [NN], Progressive Disease [PD] or Not Evaluable [NE]). Subject 
discontinued study before post-baseline scans are performed (NA) will also be summarized. 

Objective response rates will be presented with corresponding 2-sided 90% exact confidence 
intervals (CIs) based on Clopper-Pearson method. Subjects who do not have sufficient 
baseline or on-study tumor assessments to characterize response will be counted as 
non-responders and included in the denominator only. 
The investigator assessment for tumor response will be listed in details including site of lesion, 
date and method of evaluation, longest diameters, sum of longest diameters of the measurable 
target lesions (SLD), and responses. 
6.1.2.
Progression-Free Survival
Progression-free survival (PFS) is defined as the time interval from the first dose of GS-5745 to 
the earlier of the first documentation of definitive disease progression or death from any cause. 
Definitive disease progression is determined based on RECIST 1.1. All scans, whether scheduled 
or unscheduled, will be considered. 
The date of definitive progression will be the time point at which progression is first identified 
by relevant radiographic imaging data. Clinical progression is not considered as PFS event. Data 
will be censored on the date of last adequate tumor assessment (including assessments with a not 
evaluable [NE] outcome) prior to anti-cancer therapy or prior to ≥2 consecutive missing 
assessments, whichever is earlier for subjects:


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
who do not have disease progression or die before study discontinuation, or 

who start new anticancer therapy prior to documented disease progression or death, or

who have ≥2 consecutive missing or inadequate tumor assessments before disease 
progression or death
If subjects don’t have an adequate baseline tumor assessment or any adequate post-baseline 
tumor assessments, they will be censored on the date of Study Day 1 unless they died before or 
on the 2nd scheduled post-baseline tumor assessment without receiving anti-cancer therapy. 
PFS in months = (date of event/censoring – date of first GS-5745 infusion + 1) / 30.4375.
When imaging examinations for one visit are conducted on various dates, the following rules 
apply for the calculation of the assessment date:

The response date will be the last date associated with that particular imaging time point.

The progression date will be the first date associated with that particular imaging time point.
Follow up time for PFS will be summarized as continuous variable with descriptive statistics by 
cohorts. 

For subject who is censored from PFS and has discontinued from study, duration of PFS 
follow up = Date of censoring – date of first GS-5745 infusion +1

For the remaining subjects (including subjects has PD based on RECIST 1.1), duration of 
PFS follow up = date of last tumor assessment in the database – date of first GS-5745 infusion 
+1
When the start date of new anti-cancer therapy is incomplete or missing, the following 
imputation rules will be applied. 

If day is missing but the month and year are available, then the imputed day will be the last 
day of the month;

If day and month are missing but year is available, then the imputed day and month will be 
01 January or the last day of the month for the last adequate disease assessment if they have 
the same year, whichever is later.
PFS rates at 3, 6, 9, 12, and 18 months and median PFS times with 90% CIs using log-log 
transformation will be derived using Kaplan-Meier methods, by cohort for Part B. Kaplan-Meier 
curves will also be provided. 
PFS derived from investigator assessment will be listed.


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6.1.3.
Overall Survival
Overall survival (OS) is defined as the time from the first dose of GS-5745 to death from any 
cause. Data from surviving subjects will be censored at the last time that subject was known to 
be alive.
Every attempt will be made to ensure that complete death dates are recorded. In those rare 
instances where complete death dates are not recorded, the following algorithm will be used:

If day is missing but the month and year are available, then the imputed day will be the 
midpoint of the month or the last known alive date + 1, whichever is later.

If day and month are missing but year is available, then the imputed day and month will be 
01 Jan of that year or the last day of the latest month that the subject was known to be alive if 
they have the same year, whichever is later.
OS in months = (date of event/censoring – date of first GS-5745 infusion + 1) / 30.4375.
OS rates at 3, 6, 9, 12, 18, and 24 months and median OS times with 90% CIs using log-log 
transformation will be derived using Kaplan-Meier methods, by cohort for Part B. Kaplan-Meier 
curves will also be provided. 
OS data will be analyzed for Cohort 8, 9, and 10. For the rest of cohorts, OS data will not be 
analyzed since the majority of discontinued subjects’ OS status cannot be collected.
6.1.4.
Duration of Response
Duration of response (DOR) is defined as the interval from the first time response (CR or PR) is 
achieved to the earlier of the first documentation of definitive disease progression or death from 
any cause. The analyses of DOR will be based on the subjects in the Full Analysis Set who 
achieve a CR or PR. The same censoring rules as for PFS will be applied to DOR.
DOR in months = (date of event/censoring – date of first response [CR or PR] + 1)/ 30.4375.
Median DOR and 90% CIs will be estimated using Kaplan-Meier methods, by cohort for Part B. 
Kaplan-Meier curves will also be provided.
DOR derived from investigator assessment will be listed.
6.1.5.
Time to Response
Time to response (TTR) is defined as the time interval from the first dose of GS-5745 to time 
response (CR or PR) is first achieved. The analyses of TTR will be based on the subjects in the 
Full Analysis Set who achieve a CR or PR. TTR will be summarized using descriptive summary 
statistics by cohort in Part B. 
TTR derived from investigator assessment will be listed.


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6.1.6.
Change in Tumor Size
The percent change from baseline in the sum of the diameters of target lesions as documented 
radiographically will be determined for each post-baseline assessment.  The best percent change 
from baseline in the sum of the diameters is defined as the largest decrease (or smallest increase) 
in tumor size among all post baseline target lesion assessments with target lesions present at 
baseline measured. Tumor assessment after new anticancer therapy or after ≥2 consecutive 
missing or inadequate tumor assessments will not be included in the analysis for change in tumor 
size. The baseline sum of the diameters will be the value of last target lesion assessment prior to 
the start of GS-5745 therapy.  
The best percent change in tumor size will be summarized by cohort for Part B for subjects in the 
Full Analysis Set with baseline and at least one post-baseline measurement available for tumor 
size.
Waterfall plots of the best percent change from baseline will be created.
Change in tumor size derived from investigator assessment by each visit will be listed.
6.1.7.
ECOG Performance Status
The ECOG performance status score has a range from 0 (Fully active; able to carry on all 
pre-disease performance without restriction) to 5 (Dead). The baseline status will be the last 
score prior to the start of GS-5745 therapy. The worst post-baseline performance status will be 
the highest score following the start of GS-5745 therapy.
Shift table will be provided showing the change of ECOG performance status from baseline to 
the worst post-baseline performance status by cohort for Part B for subjects in the Full Analysis 
Set. Subjects without baseline or post-baseline ECOG performance status will be considered as 
missing in the shift table. 


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7.
SAFETY ANALYSES
Safety will be evaluated for all subjects in the Safety Analysis Set through assessment of clinical 
laboratory tests, physical examination findings, 12-lead ECG abnormalities, vital signs 
measurements, and by the documentation of AEs. Concomitant medication intake will also be 
recorded, coded to the corresponding WHO drug term, and displayed in data listings.
All safety data collected at baseline and post-baseline through to the completion of the follow-up 
evaluation will be summarized. Data for the pre-treatment period will be included in data 
listings.
Safety analysis will be conducted by study part and cohort using Safety Analysis Set, unless 
otherwise specified. For Cohort 8 (first-line CRC) and Cohort 9 (second-line CRC), subjects 
initially dosed with bevacizumab 10 mg/kg Q2W will be summarized separately as grouped in 
Section 3.2.
7.1.
Adverse Events
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the current version of 
MedDRA. System organ class (SOC), high-level group term (HLGT), high-level term (HLT), 
preferred term (PT), and lower-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1, 2, 3, 4, or 5 according to Common 
Toxicity Criteria for Adverse Events (CTCAE) Version 4.03. The severity grade of events for 
which the investigator did not record severity will be categorized as “missing” for tabular 
summaries and data listings. The missing category will be listed last in data presentation.
7.1.3.
Relationship of Adverse Event to Study Treatment
Related AEs are those for which the investigator selected “Related” on the AE case report form 
(CRF) to the question of related to study treatment.  Relatedness will always default to the 
investigator’s choice, not that of the medical monitor. Events for which the investigator did not 
record relationships to study treatment will be considered related to study treatment for summary 
purposes. However, by-subject data listings will show the relationship as missing from that 
captured on the CRF.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definitions 
of SAE specified in the study protocol. Serious adverse events captured and stored in the clinical 
database will be reconciled with the SAE database from the Gilead Pharmacovigilance & 
Epidemiology before database finalization.


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7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent
Treatment-emergent AEs (TEAEs) are events in a given study period that meet 1 or both of the 
following criteria:

Any AEs with onset date of on or after the study drug start date and no later than 30 days 
after permanent discontinuation of study drugs or

AEs leading to premature discontinuation of study drug
7.1.5.2.
Incomplete Dates
All AEs with partial onset dates will be identified and the partial dates will be imputed for TEAE 
determination. The imputation rules are as follows:

If day and month are missing but year is available, then the imputed day and month will be 
01 Jan or the first dosing date of the study drug if they have the same year, whichever is later. 

If day is missing but the month and year are available, then the imputed day will be the first 
day of the month or the first dosing date if they have the same month and year, whichever is 
later. 

AE with completely missing onset dates and stop dates, or with the onset date missing and a 
stop date later than the first dosing date of study drug, will be considered to be treatment 
emergent. In addition, an AE with the onset date missing and an incomplete stop date with 
the same or later month and year (or year alone if month is not recorded) as the first dosing 
date of study drug will be considered treatment emergent.
7.1.6.
Summaries of Adverse Events
A brief summary of treatment-emergent AEs will show the number and percentage of subjects 
who had:

any TEAE; 

any TEAE related to GS-5745; 

any TEAE related to any chemotherapy; 

any Grade 3 or higher TEAE; 

any Grade 3 or higher TEAE related to GS-5745; 

any Grade 3 or higher TEAE related to any chemotherapy;


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
any TE SAE; 

any TE SAE related to GS-5745; 

any TE SAE related to any chemotherapy; 

any TEAE leading to GS-5745 dose modification or interruption; 

any TEAE leading to any chemotherapy dose modification or interruption; 

any TEAE leading to GS-5745 discontinuation; 

any TEAE leading to any chemotherapy discontinuation;

any TEAE leading to death
For each SOC and PT, the number and percentage of subjects reporting an event will be 
calculated. In summary tables, SOC will be presented alphabetically and events within SOC will 
be presented by decreasing frequency count based on the total number of events.
Summary tables (number and percentage of subjects) of treatment-emergent AEs (by SOC and 
PT) will be provided by study part and cohort as follows:

TEAEs

Grade 3 or higher TEAEs

TEAEs related to GS-5745

TEAEs related to any chemotherapy

Grade 3 or higher TEAEs related to GS-5745

Grade 3 or higher TEAEs related to any chemotherapy

TE SAEs 

TE SAEs related to GS-5745

TE SAEs related to any chemotherapy

TEAEs leading to GS-5745 interruption and/or dose modification

TEAEs leading to any chemotherapy interruption and/or dose modification

TEAEs leading to GS-5745 discontinuation


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
TEAEs leading to any chemotherapy discontinuation

TEAEs leading to deaths
All death will be summarized by whether it is considered as treatment emergent and the cause of 
the death (AE, PD, or other reasons). 
Data listings will be provided as follows:

AEs

AEs with Grade 3 or higher

SAEs

AEs related to GS-5745

AEs related to any chemotherapy

Grade 3 or higher AEs related to GS-5745

Grade 3 or higher AEs related to any chemotherapy

AEs leading to GS-5745 dose modification, drug interruption or discontinuation

AEs leading to any chemotherapy dose modification, drug interruption or discontinuation

AEs occurred during the infusion or within 24 hours of infusion

Deaths (if any)
7.1.7.
Additional Analyses of Adverse Events
7.1.7.1.
Dose Limiting Toxicity
A listing of the DLT AEs will be provided by cohort including cohort number with dose level, 
subject identification, actual dose amount prior to or on the start date of the AE, DLT term from 
investigator as well as CTCAE term and associated severity grade, if available.
A summary of DLT will be presented by SOC and decreasing frequency of preferred term within 
SOC using the DLT Analysis Set by cohort in Part A.
7.2.
Laboratory Evaluations
Laboratory data collected during the study, scheduled and unscheduled, will be analyzed and 
summarized using both quantitative and qualitative methods. Summaries of selected laboratory 
parameters listed in Appendix 8 will be provided for the Safety Analysis Set. Data collected up 


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to the last dose of study drug plus 30 days for subjects who have permanently discontinued study 
drug, or all available data for subjects who were ongoing at the time of the database cut-off, will 
be included in the analysis. Local lab results will not be summarized, and will only be included 
in listings.
The analysis will be based on values reported in conventional units. When values are below the 
LOQ, they will be listed as such, and the closest imputed value will be used for the purpose of 
calculating summary statistics as specified in Section 3.7.
A by-subject listing for laboratory test results will be provided by subject ID number and time 
point in chronological order for hematology, serum chemistry, and coagulation separately. 
Values falling outside of the relevant reference range and/or having a severity grade of 1 or 
higher on the CTCAE severity grade will be flagged in the data listings, as appropriate.
No inferential statistics will be generated.
7.2.1.
Graded Laboratory Values
CTCAE version 4.03 will be used for assigning toxicity grades (0 to 4) to laboratory results for 
analysis. Grade 0 includes all values that do not meet the criteria for an abnormality of at least 
Grade 1. Some laboratory tests have criteria for both increased and decreased levels; analyses for 
each direction (ie, increased, decreased) will be presented separately.
7.2.1.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any post-baseline time point, up to 30 days after the last dose of 
study drug for subjects who permanently discontinued study drug, or all available data in the 
database cut-off for subjects who were still on treatment at the time of analysis. If the relevant 
baseline laboratory value is missing, then any abnormality of at least Grade 1 observed within 
the time frame specified above will be considered treatment emergent.
7.2.1.2.
Summaries of Laboratory Abnormalities
The summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test for each cohort in Part A and Part B separately; 
subjects will be summarized by the most severe post-baseline abnormality grade for given lab 
tests.
7.2.2.
Shifts Relative to the Baseline Value
Shift tables will be presented by showing change in CTCAE grade from baseline to the worst 
post-baseline grade. 


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7.2.3.
Summaries of Laboratory Results 
If warranted, a summary of selected laboratory test results will be presented. Descriptive
statistics (N, mean, StD, median, Q1, Q3, minimum, and maximum) will be provided by study 
part and cohort for numerical laboratory test as follows:

Baseline values

Values at each post-baseline time point

Change from baseline at each post-baseline time point
Change from baseline to a post baseline visit will be defined as the visit value minus the baseline 
value. The mean, median, Q1, Q3, minimum, and maximum will be displayed to the reported 
number of digits; StD to the reported number of digits plus 1.
Categorical laboratory data will be summarized using the number and percentage of subjects 
with the given response at baseline and each post-baseline visit windows (as Section 3.8.2) by 
study part and cohort.
7.3.
Vital Signs
Summaries of vital sign and change from baseline data will include values from all scheduled 
and unscheduled visits. A baseline value is defined as the last available value prior to the first 
dose of study drug. Each vital signs measurement (including temperature, pulse, systolic blood 
pressure, diastolic blood pressure, and respiratory rate) will be summarized by study part and 
cohort using descriptive statistics (N, mean, StD, median, Q1, Q3, minimum, and maximum).
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.
A listing of all individual subject vital signs data will be provided.
7.4.
Prior and Concomitant Medications
7.4.1.
Prior Medications
Prior medications are defined as any medications begun before a subject took the first study 
drug.
For the purposes of analysis, any medication with a start date prior to the first dosing date of 
study drug will be considered as prior medication regardless of when the stop date is. If a partial 
start date is entered the medication will be considered prior unless the month and year (if day is 
missing) or year (if day and month are missing) of the start date are after the first dosing date. 
Medications with a completely missing start date will be considered as prior medication, unless 
otherwise specified.
A summary of prior medications will not be provided.


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7.4.2.
Concomitant Medications
Concomitant medications are defined as medications taken while a subject took study drug. 
Concomitant medications will be summarized by Anatomical Therapeutic Chemical (ATC) drug 
class Level 2 and preferred name using the number and percentage of subjects for each treatment 
group. A subject reporting the same medication more than once will be counted only once when 
calculating the number and percentage of subjects who received that medication. The summary 
will be ordered alphabetically by ATC medical class and then by preferred term in descending 
overall frequency within each ATC medical class. For drugs with the same frequency, sorting 
will be done alphabetically.
Concomitant medication is defined as any medications

started prior to or on the first dosing date of study drug and continued to take after the first 
dosing date, or 

started after the first dosing date but no later than last dosing date of study drug.
Medications started and stopped on the same day as the first dosing date or the last dosing date of 
study drug will also be considered concomitant. Medications with a stop date that is prior to the 
date of first dosing date of study drug or a start date that is after the last dosing date of study drug 
will be excluded from the concomitant medication summary.
If a partial stop date is entered, any medication with the month and year (if day is missing) or 
year (if day and month are missing) prior to the date of first study drug administration will be 
excluded from the concomitant medication summary. If a partial start date is entered, any 
medication with the month and year (if day is missing) or year (if day and month are missing) 
after the study drug stop date will be excluded from the concomitant medication summary. 
Medications with completely missing start and stop dates will be included in the concomitant 
medication summary.
Summaries of concomitant medications by study part and cohort will be provided for the Safety 
Analysis Set. A listing of prior and concomitant medications will also be provided.
7.5.
Electrocardiogram (ECG) Results
Electrocardiogram (ECG) analysis results are intended to identify meaningful changes in the QT 
interval. If potential abnormalities of interest are identified, further analyses may be conducted. 
Summaries of investigator assessment of ECG readings will be provided for the Safety Analysis 
Set from all scheduled and unscheduled visits. In the case of multiple values in an analysis 
window, data will be selected for analysis as described in Section 3.8.3. 


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7.5.1.
Investigator Electrocardiogram Assessment
The number and percentage of subjects in the Safety Analysis Set with an investigator’s ECG 
assessment of normal, abnormal and clinically significant, or abnormal but not clinically 
significant will be summarized for baseline and for each visit.
A shift table of the investigators’ assessment of ECG results at each visit compared with baseline 
values will be presented by study part and cohort using the following categories: normal; 
abnormal, not clinically significant; abnormal, clinically significant; or missing. The number and 
percentage of subjects in each cross-classification group of the shift table will be presented. 
A by-subject listing for ECG assessment results will be provided by subject ID number and time 
point in chronological order.
7.5.2.
Corrected QT Intervals
The QT interval (measured in millisecond [msec]) is a measure of the time between the start of 
the Q wave and the end of the T wave in the heart’s electrical cycle. The QT interval represents 
electrical depolarization and repolarization of the ventricles. The QT interval is affected by heart 
rate, and a number of methods have been proposed to correct QT for heart rate. 
Corrected QT (QTc) intervals will be derived using Fridericia’s correction (QTcF) as follows:
 = 
√


where QT is measured in msec; RR = 60/Heart Rate (beats per min [bpm]) and RR is measured 
in seconds. Per Gilead data collection standard, ventricular rate (VR) is taken as heart rate and 
will be used to derive RR. 
The maximum postdose QTcF interval values obtained during the study will be summarized 
within the following categories:

> 450 msec

> 480 msec

> 500 msec
The maximum postdose change in QTcF interval values obtained during the study will also be 
summarized within the following categories:

> 30 msec

> 60 msec
QTcF and uncorrected QT values at each visit and change from baseline at each visit will be 
summarized for the Safety Analysis Set by study part and cohort using descriptive statistics.


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7.5.3.
PR and QRS Intervals
The PR interval (measured in msec) is a measure of the time between the start of the P wave (the 
onset of atrial depolarization) and the beginning of the QRS complex (the onset of ventricular 
depolarization). The QRS interval measures the duration of the QRS complex. The maximum 
ventricular rate (VR) and PR and QRS intervals observed during the study will be categorized. 
The number and percentage of subjects having values in the following ranges will be presented 
by treatment group:

VR > 100 bpm

PR interval > 200 msec

QRS interval > 110 msec
In addition, VR, PR, RR, and QRS values at each visit and change from baseline at each visit 
will be summarized for the Safety Analysis Set by study part and cohort using descriptive 
statistics.
7.6.
Other Safety Measures
A data listing will be provided for the results of all pregnancy tests conducted in the study.
Post-treatment anti-cancer therapies will be listed for applicable subjects.
7.7.
Changes From Protocol-Specified Safety Analyses
There are no deviations from the protocol-specified safety analyses.


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8.
PHARMACOKINETIC ANALYSES
8.1.
PK Sample Collection
Plasma samples will be collected to measure concentrations of GS-5745 at protocol specified 
time points.
8.2.
Statistical Analysis Methods
8.2.1.
GS-5745 Plasma Concentration
GS-5745 plasma concentration data will be summarized using descriptive statistics for subjects 
in the PK Analysis Set in Part A by time point and visit. Subjects in different dose cohorts will 
be presented separately. The sample size for each time point will be based on the number of 
subjects with nonmissing concentration data at that time point. The number of subjects with 
concentration BLQ will be presented for each time point. For summary statistics, BLQ values 
will be treated as 0 at predose and one-half of the lower limit of quantitation (LLOQ) for 
postdose time points.
The following figures may be provided by dose level in Part A:

Mean (± StD) concentration data versus time (on linear and semilogarithmic scales)

Median (Q1, Q3) concentration data versus time (on linear and semilogarithmic scales) 
The following table will be provided by dose level in Part A:

Individual subject concentration data and summary statistics
GS-5745 plasma concentration data and PK sampling details will be listed for all subjects in the 
PK Analysis Set.
8.2.2.
GS-5745 PK Parameters
For subjects in Part A, relevant PK parameters will be determined using Phoenix WinNonlin®
software and utilizing standard noncompartmental methods. The linear/log trapezoidal rule will 
be applied in conjunction with the appropriate noncompartmental model, with input values for 
dose level, dosing time, plasma concentration, and corresponding real time values, based on drug 
dosing times whenever possible. Descriptive statistics will be presented for PK parameters of 
GS-5745 by dose cohort.
All predose sample times before time-zero will be converted to 0. For area under the curve 
(AUC), samples BLQ of the bioanalytical assays occurring prior to the achievement of the first 
quantifiable concentration will be assigned a concentration value of 0 to prevent overestimation 
of the initial AUC. Samples that are BLQ at all other time points will be treated as missing data 
in WinNonlin. The nominal time point for a key event or dosing interval (τ) may be used to 
permit direct calculation of AUC over specific time intervals. The appropriateness of this 
approach will be assessed by the PK scientist on a profile by profile basis.


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Pharmacokinetic parameters such as λz and t1/2 are dependent on an accurate estimation of the 
terminal elimination phase of drug. The appropriateness of calculating these parameters will be 
evaluated upon inspection of PK data on a profile-by-profile basis by the PK scientist.
The PK parameters for GS-5745 presented in Table 12 will be computed for all subjects in the 
PK Analysis Set in Part A, as applicable.
Table 12.
PK parameters for GS-5745
Analyte
PK Parameters
GS-5745
Ceoi, Cmax, Tmax, AUClast, AUC0-336h, C336h, Clast, Tlast, λz, 
T1/2
Individual PK parameter data listings and summaries will include all subjects for whom PK 
parameter(s) can be derived. The sample size for each PK parameter will be based on the number 
of subjects with nonmissing data for that PK parameter.
The following table will be provided by dose level:

Individual subject plasma PK parameters and summary statistics will be presented for PK 
parameters of GS-5745 by dose cohort.


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9.
IMMUNOGENICITY ANALYSES
9.1.
ADA Sample Collection
Serum samples will be collected to measure anti-GS-5745 antibody (ADA) at protocol specified 
time points.
9.2.
Statistical Analyses Methods
Immunogenicity data will be listed and summarized for all subjects in the Immunogenicity 
Analysis Set. Subjects in different dose cohorts (Part A) and different disease cohorts (Part B) 
will be presented separately. Immunogenicity of andecaliximab will be evaluated based upon the 
positive ADA rate. The number and percentage of subjects exhibiting positive ADA status, 
defined as ADA presence in serum confirmed in validated assay and reported by bioanalytical 
laboratory, will be summarized at each specified time point. The number and percentage of 
subjects exhibiting positive ADA status at any post-andecaliximab time point will also be 
summarized. 
A by-subject listing for ADA status at each time point and the titer for subjects with positive 
ADA status will be provided by subject ID number and time point in chronological order.


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Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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24 July 2019
10.
BIOMARKER ANALYSES
To evaluate GS-5745 coverage on MMP9 and to evaluate the pharmacodynamics effect of 
GS-5745, samples for assessment of drug activity are obtained at protocol-specified time points.
A comprehensive analysis may be documented separately.
Biomarker Analysis Set will be used for biomarker analysis. 
10.1.
Statistical Analysis Methods
All summaries will be presented in tabular or graphical form.  Descriptive statistics refers to 
number of subjects, mean, median, standard deviation (StD), 1st quartile (Q1), 3rd quartile (Q3), 
minimum, and maximum for continuous measurements and number and percentage of subjects 
in each level of a categorical measurement.
The following tables will be provided for each biomarker for Part A and Part B, separately:

Descriptive Statistics for Peripheral Free MMP9 at Time Points by Cohort 

Descriptive Statistics for Peripheral Total MMP9 at Time Points by Cohort 
The following figures will be provided for each biomarker for Part A and Part B, separately:

Mean (± SE) Plot for Peripheral Free and Total MMP9 Over Time by Cohort 

Median (Q1, Q3) Plot for Peripheral Free and Total MMP9 Over Time by Cohort
Listings of free and total MMP9 will be provided for Part A and Part B, separately.


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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11.
REFERENCES
Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03, U.S. Department of 
Health and Human Services, National Institutes of Health, National Cancer Institute, 14 June 2010.
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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12.
SOFTWARE
SAS® (SAS Institute Inc., Cary, NC) is to be used for all programming of tables, listings, and 
figures.
WinNonlin® (Pharsight Corporation, Mountain View, CA) is to be used for all PK analyses.


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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24 July 2019
13.
APPENDICES
Appendix 1.
Study Procedures Table (Part A)
Appendix 2.
Study Procedures Table (Part B – Pancreatic Adenocarcinoma)
Appendix 3.
Study Procedures Table (Part B – Esophagogastric Adenocarcinoma)
Appendix 4.
Study Procedures Table (Part B – NSCLC)
Appendix 5.
Study Procedures Table (Part B – First Line CRC)
Appendix 6.
Study Procedures Table (Part B- Second Line CRC)
Appendix 7.
Study Procedures Table (Part B – Breast Cancer)
Appendix 8.
List of Laboratory Tests for Safety Summary


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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24 July 2019
Appendix 1.
Study Procedures Table (Part A)
Weeks
1
2
3
5
7
9
Q2W 
(l)
Q8W 
(m)
EOS 
(n)
Days
-28 
to -1
1
2
3
5
8
15
29
43
57
Window
± 1
± 1
± 2
± 2
± 2
± 5
Hours (relative to dosing)
Pre-
dose
EOI
6
24
48
96
168
Pre-
dose
EOI
Pre-
dose EOI
Pre-
dose EOI
Study Assessments
Informed Consent
X
Medical History (a)
X
Physical Exam (b)
X
X 
X
X
X
X
X
X
Vital signs (c)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
X
X
X
X
X
ECOG Performance Status
X
X
X
X
X
X
X
X
X
X
X
X
Prior/Concomitant Meds (d)
X
X
X
X
X
X
X
X
X
X
X
X
X
AEs (e)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CT or MRI (f)
X
X
X
X
Collect Archival Tumor Tissue 
(if available) (g)
X
Register subject visit in IxRS
X
X
X
X
X
X
X
X
Sample Collection
Chemistry
X
X (j)
X
X
X
X
X
X
X (k)
X
Hematology
X
X (j)
X
X
X
X
X
X
X (k)
X
Coagulation
X
X (j)
X
X
X
X
X
X
Urinalysis
X
X (j)
X
X
X
X
X
X
Pregnancy test (h)
X
X (j)
X
X
X
X
X
X
GS-5745 Concentration (i)
X (j)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
Page 48
24 July 2019
Weeks
1
2
3
5
7
9
Q2W 
(l)
Q8W 
(m)
EOS 
(n)
Days
-28 
to -1
1
2
3
5
8
15
29
43
57
Window
± 1
± 1
± 2
± 2
± 2
± 5
Hours (relative to dosing)
Pre-
dose
EOI
6
24
48
96
168
Pre-
dose
EOI
Pre-
dose EOI
Pre-
dose EOI
Anti-GS-5745 Antibody
X (j)
X
X
X
Serum and plasma biomarkers
X
X (j)
X
X
X
X
X
Urine biomarkers
X
X (j)
X
X
X
X
X
Study Drug Dosing
GS-5745 IV Dosing
X
X
X
X
X
X
a.
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any 
concurrent medical illnesses.
b.
A complete PE will be performed at Screening. A modified PE capturing changes from prior exams will be performed at subsequent applicable visits. Weight (in kilograms 
and without shoes) should be measured at each PE. Height (in centimeters and without shoes) should be measured at Screening only.
c.
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken after the subject has been sitting for at least 5 minutes.
d.
Prior/concomitant medications include all medication taken up to 30 days prior to Screening, any and all medications taken during the course of the study, and supportive 
therapies given during the course of the study (eg, blood transfusion, growth factor).
e.
AEs will be assessed before and after GS-5745 dosing during applicable visits. 
f.
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and every 8 weeks thereafter. The same radiographic procedure used to define 
measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if not conducted within the previous 4 weeks. If a 
subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology every 8 weeks until disease progression.
g.
Unstained slides (10-12) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1.
h.
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the End-of-Study visit.
i.
Blood samples to measure GS-5745 concentration will be collected pre- and post-dose at each applicable visit.
j.
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
k.
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology every 8 weeks until disease progression.
l.
A subject who does not show evidence of disease progression by clinical assessment or by CT or MRI may continue receiving GS-5745 every 2 weeks until disease 
progression (clinical or radiographic), unacceptable toxicity, withdrawal of consent, or other reasons specified in Study Protocol. Q2W visits will occur every 2 weeks 
(± 2 days) from the Day 57 visit.
m.
Q8W visits will occur every 8 weeks (± 5 days) from the Day 57 visit.
n.
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than PD, the site 
should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive PD.


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
Page 49
24 July 2019
Appendix 2.
Study Procedures Table (Part B – Pancreatic Adenocarcinoma)
Study Phase
Screening
Each Cycle (28 days)
Every 2 Cycles
EOS (l)
Cycle Day
Screening
1
8
15
N/A
Window
-28
0
2
2
N/A
Treatment Day
-28
1
8
15
N/A
Study Assessments
Informed Consent
X
Medical History (a)
X
Physical Exam (b)
X
X 
X
Vital signs (c)
X
X
X
X
X
12-lead ECG
X
X
ECOG Performance Status
X
X
X
X
Prior/Concomitant Meds (d)
X
X
X
X
X
AEs (e)
X
X
X
X
X
CT or MRI (f)
X
X (k)
X
Collect Archival Tumor Tissue (if available) (g)
X
Register subject visit in IxRS
X
X
X
X
Sample Collection
Chemistry
X
X (j)
X
X (k)
X
Hematology
X
X (j)
X
X
X (k)
X
Coagulation
X
X (j)
X
Urinalysis
X
X (j)
X
Pregnancy test (h)
X
X (j)
X
X
GS-5745 Concentration (i)
X
X
X


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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Study Phase
Screening
Each Cycle (28 days)
Every 2 Cycles
EOS (l)
Cycle Day
Screening
1
8
15
N/A
Window
-28
0
2
2
N/A
Treatment Day
-28
1
8
15
N/A
Anti-GS-5745 Antibody
X (j)
X
Serum and plasma biomarkers
X
X (j)
X
Urine biomarkers
X
X (j)
X
Study Drug Dosing/Chemotherapy
GS-5745 IV Dosing
X
X
Gemcitabine Dosing
X
X
X
Nab-Paclitaxel Dosing
X
X
X
a.
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any 
concurrent medical illnesses.
b.
A complete PE will be performed at Screening. A modified PE capturing changes from prior exams will be performed at subsequent applicable visits. Weight (in kilograms 
and without shoes) should be measured at each PE.  Height (in centimeters and without shoes) should be measured at Screening only.
c.
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken after the subject has been sitting for at least 5 minutes.
d.
Prior/concomitant medications include all medication taken up to 30 days prior to Screening, any and all medications taken during the course of the study, and supportive 
therapies given during the course of the study (eg, blood transfusion, growth factor).
e.
AEs will be assessed before and after GS-5745 and gemcitabine dosing during applicable visits. The site will call subjects 30 days after the last dose of GS-5745 to assess 
AEs and SAEs.
f.
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.). 
The same radiographic procedure used to define measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if 
not conducted within the previous 4 weeks. If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the 
study to collect tumor assessments (CT/MRI), chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
g.
Unstained slides (10-12) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1 of Cycle 1 only.
h.
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the End-of-Study visit.
i.
Blood samples to measure GS-5745 concentration will be collected pre-dose on Day 1 and Day 15 of each cycle.
j.
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
k.
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
l.
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than PD, the site 
should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive PD. 


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
Page 51
24 July 2019
Appendix 3.
Study Procedures Table (Part B – Esophagogastric Adenocarcinoma)
Study Phase
Screening
Each Cycle (28 days)
Every 2 Cycles
EOS (l)
Cycle Day
Screening
1
15
N/A
Window
-28
0
2
N/A
Treatment Day
-28
1
15
N/A
Study Assessments
Informed Consent
X
Medical History (a)
X
Physical Exam (b)
X
X 
X
Vital signs (c)
X
X
X
X
12-lead ECG
X
X
ECOG Performance Status
X
X
X
X
Prior/Concomitant Meds (d)
X
X
X
X
AEs (e)
X
X
X
X
CT or MRI (f)
X
X (k)
X
Collect Archival Tumor Tissue (if available) (g)
X
Register subject visit in IxRS
X
X
X
X
Sample Collection
Chemistry
X
X (j)
X
X (k)
X
Hematology
X
X (j)
X
X (k)
X
Coagulation
X
X (j)
X
Urinalysis
X
X (j)
X
Pregnancy test (h)
X
X (j)
X
X
GS-5745 Concentration (i)
X
X
X
Anti-GS-5745 Antibody
X (j)
X


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
Page 52
24 July 2019
Study Phase
Screening
Each Cycle (28 days)
Every 2 Cycles
EOS (l)
Cycle Day
Screening
1
15
N/A
Window
-28
0
2
N/A
Treatment Day
-28
1
15
N/A
Serum and plasma biomarkers
X
X (j)
X
Urine biomarkers
X
X (j)
X
Study Drug Dosing/Chemotherapy
GS-5745 IV Dosing
X
X
mFOLFOX6 Dosing (m)
X
X
a.
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any 
concurrent medical illnesses.
b.
A complete PE will be performed at Screening. A modified PE capturing changes from prior exams will be performed at subsequent applicable visits. Weight (in kilograms 
and without shoes) should be measured at each PE.  Height (in centimeters and without shoes) should be measured at Screening only.
c.
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken after the subject has been sitting for at least 
5 minutes.
d.
Prior/concomitant medications include all medication taken up to 30 days prior to Screening, any and all medications taken during the course of the study, and supportive 
therapies given during the course of the study (eg, blood transfusion, growth factor).
e.
AEs will be assessed before and after GS-5745 and mFOLFOX6 dosing during applicable visits. The site will call subjects 30 days after the last dose of GS-5745 to assess 
AEs and SAEs.
f.
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.). 
The same radiographic procedure used to define measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if 
not conducted within the previous 4 weeks. If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the
study to collect tumor assessments (CT/MRI), chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
g.
Unstained slides (10-12) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1 of Cycle 1 only.
h.
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the End-of-Study visit.
i.
Blood samples to measure GS-5745 concentration will be collected pre-dose on Day 1 and Day 15 of each cycle.
j.
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
k.
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
l.
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than PD, the site 
should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive PD.  
m.
mFOLFOX6 dosing regimen will consist of l-LV 200 mg/m2 or dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5-FU 400 mg/m2 and a 46-hour infusion 5-FU 
2400 mg/m2.


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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24 July 2019
Appendix 4.
Study Procedures Table (Part B – NSCLC)
Study Phase
Screening
Each Cycle (21 days)
Every 3 Cycles
EOS (l)
Cycle Day
Screening
1
N/A
Window
-28
±2
N/A
Treatment Day
-28
1
N/A
Study Assessments
Informed Consent
X
Medical History (a)
X
Physical Exam (b)
X
X 
X
Vital signs (c)
X
X
X
12-lead ECG
X
X
ECOG Performance Status
X
X
X
Prior/Concomitant Meds
X
X
X
AEs (d)
X
X
X
CT or MRI (e)
X
X (k)
X
Collect Archival Tumor Tissue (if available) (f)
X
Register subject visit in IxRS
X
X
X
Sample Collection
Chemistry
X
X (j)
X (k)
X
Hematology
X
X (j)
X (k)
X
Coagulation
X
X (j)
X
Urinalysis
X
X (j)
X
Pregnancy test (g)
X
X (j)
X
GS-5745 Concentration (h)
X
X
Anti-GS-5745 Antibody
X (j)
X


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
Page 54
24 July 2019
Study Phase
Screening
Each Cycle (21 days)
Every 3 Cycles
EOS (l)
Cycle Day
Screening
1
N/A
Window
-28
±2
N/A
Treatment Day
-28
1
N/A
Serum and plasma biomarkers
X
X (j)
X
Urine biomarkers
X
X (j)
X
Study Drug Dosing/Chemotherapy
GS-5745 IV Dosing
X
Chemotherapy Dosing (i)
X
a.
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any 
concurrent medical illnesses.
b.
A complete PE will be performed at Screening. A modified PE capturing changes from prior exams will be performed at subsequent applicable visits. Weight (in kilograms 
and without shoes) should be measured at each PE.  Height (in centimeters and without shoes) should be measured at Screening only.
c.
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken after the subject has been sitting for at least 
5 minutes.
d.
AEs will be assessed before and after GS-5745 dosing during applicable visits. The site will call subjects 30 days after the last dose of GS-5745 to assess AEs and SAEs.
e.
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and during the last week of every third cycle (ie, Cycles 3, 6, 9, etc.). The 
same radiographic procedure used to define measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if not 
conducted within the previous 4 weeks. If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study 
to collect tumor assessments (CT/MRI), chemistry, and hematology during the last week of every third cycle (ie, Cycles 3, 6, 9, etc.) until disease progression.
f.
Unstained slides (10-12) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1 of Cycle 1 only.
g.
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the End-of-Study visit.
h.
Blood samples to measure GS-5745 concentration will be collected pre-dose on Day 1 of each cycle.
i.
NSCLC chemotherapy regimen: carboplatin IV dosed to AUC 6 on Day 1 of each 21-day treatment cycle and pemetrexed 500 mg/m2 IV on Day 1 of each 21-day treatment
cycle in subjects with lung adenocarcinoma.  Chemotherapy will consist of carboplatin IV dosed to AUC 6 on Day 1 of each 21-day treatment cycle and paclitaxel 200 mg/m2
IV on Day 1 of each 21-day treatment cycle in subjects with lung squamous cell carcinoma.  Subjects who have not had disease progression after 4 cycles of treatment may 
have some of their treatment reduced based upon the Investigator’s assessment of what is in the subject’s best interests. However, dosing with GS-5745 should be continued 
per protocol.
j.
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
k.
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology during the last week of every third cycle (ie, Cycles 3, 6, 9, etc.) until disease progression.
l.
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than PD, the site 
should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive PD.


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
Page 55
24 July 2019
Appendix 5.
Study Procedures Table (Part B – First Line CRC)
Study Phase
Screening
Each Cycle (28 Days)
Cycle 2
Cycle 3
Every 2 Cycles
EOSm
LTFU
Every 3 
Months
Cycle Day
Screening
1
15
15
1
N/A
N/A
Window
−28
0r
± 2
+14 Days / −7 
Days
N/A
N/A
Treatment Day
−28
1
15
N/A
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
Vital Signsc
X
X
X
X
12-Lead ECG
X
X
ECOG Performance Status
X
X
X
X
Prior/Concomitant Medsd
X
X
X
X
AEse
X
X
X
X
CT or MRIf
X
Xl
X
Collect Archival Tumor Tissue 
(if Available)g
Xg
Register Subject Visit in IxRS
X
X
X
X
Sample Collection
Chemistry
X
Xk
X
Xl
X
Hematology
X
Xk
X
Xl
X
Coagulation
X
Xk
X


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
Page 56
24 July 2019
Study Phase
Screening
Each Cycle (28 Days)
Cycle 2
Cycle 3
Every 2 Cycles
EOSm
LTFU
Every 3 
Months
Cycle Day
Screening
1
15
15
1
N/A
N/A
Window
−28
0r
± 2
+14 Days / −7 
Days
N/A
N/A
Treatment Day
−28
1
15
N/A
N/A
Urinalysis
X
Xk
X
Pregnancy Testh
X
Xk
X
X
GS-5745 Concentrationi
X
X
X
X
Anti-GS-5745 Antibody
Xk
X
Serum and Plasma Biomarkers
Xk,n
Xn
Xn
Stool Sample
Xo
Xo
Overall Survival
X
Study Drug Dosing / Chemotherapy
GS-5745 IV Dosing
X
X
mFOLFOX6/Bev Dosingj
X
X
EOS = End-of-Study (visit); PE = physical examination
a
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any 
concurrent medical illnesses.
b
A complete PE will be performed at Screening. A modified PE capturing changes from prior exams will be performed at subsequent applicable visits. Weight (without shoes) 
should be measured at each PE and reported in kilograms. Height (without shoes) should be measured at Screening only and reported in centimeters.
c
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken per institutional guidelines.
d
Prior/concomitant medications include all medication taken up to 30 days prior to Screening, any and all medications taken during the course of the study, and supportive 
therapies given during the course of the study (eg, blood transfusion, growth factor).
e
AEs will be assessed before and after GS-5745 and mFOLFOX6 dosing during applicable visits. The site will call subjects 30 days after the last dose of GS-5745 to assess 
AEs and SAEs.
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f
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.). 
The same radiographic procedure used to define measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if 
not conducted within the previous 4 weeks. If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the 
study to collect tumor assessments (CT/MRI), chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
g
Unstained slides (5×10 micron and 10×5 micron) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1 of 
Cycle 1 only.
h
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the EOS visit.
i
Blood samples to measure GS-5745 concentration will be collected pre-dose on Day 1 and Day 15 of each cycle, end of GS-5745 infusion on Day 1 of Cycle 1 and Cycle 3, 
and at the EOS visit.
j
mFOLFOX6 and bevacizumab dosing regimen on Days 1 and 15 of each 28-day treatment cycle will consist of:  bevacizumab at 5 mg/kg IV and mFOLFOX6 dosing regimen 
will consist of l-leucovorin (LV) 200 mg/m2 or dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5 FU 400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2
k
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
l
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
m
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than disease 
progression, the site should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive disease progression.
n
Blood samples for biomarkers should be drawn pre-dose on all specified visits. Note that Day 15 is only required for Cycle 1 and that a blood sample at EOS is required if due
to disease progression. The exact schedule of blood draws is outlined in the laboratory manual.
o
A stool sample is required at study start and can be collected any time within the screening window prior to first dose. An additional stool sample at Cycle 2 Day 15 
(+14 days/−7 days) is requested.
r
A ± 2 day window applies to visits following Cycle 1 Day 1. There is no window for Cycle 1 Day 1.
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Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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Appendix 6.
Study Procedures Table (Part B- Second Line CRC)
Study Phase
Screening
Each Cycle (28 Days)
Cycle 2
Cycle 3
Every 2 Cycles
EOSm
LTFU
Every 3 
Months
Cycle Day
Screening
1
15
15
1
N/A
N/A
Window
-28
0r
±2
+14 Days / −7 
Days
N/A
N/A
Treatment Day
-28
1
15
N/A
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
Vital Signsc
X
X
X
X
12-Lead ECG
X
X
ECOG Performance Status
X
X
X
X
Prior/Concomitant Medsd
X
X
X
X
AEse
X
X
X
X
CT or MRIf
X
Xl
X
Collect Archival Tumor Tissue 
(if Available)g
X
Register Subject Visit in IxRS
X
X
X
X
Sample Collection
Chemistry
X
Xk
X
Xl
X
Hematology
X
Xk
X
Xl
X
Coagulation
X
Xk
X


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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Study Phase
Screening
Each Cycle (28 Days)
Cycle 2
Cycle 3
Every 2 Cycles
EOSm
LTFU
Every 3 
Months
Cycle Day
Screening
1
15
15
1
N/A
N/A
Window
-28
0r
±2
+14 Days / −7 
Days
N/A
N/A
Treatment Day
-28
1
15
N/A
N/A
Urinalysis
X
Xk
X
Pregnancy Testh
X
Xk
X
X
GS-5745 Concentrationi
X
X
X
X
Anti-GS-5745 Antibody
Xk
X
Serum and Plasma Biomarkers
Xk,n
Xn
Xn
Stool Sample
Xo
Xo
Overall Survival
X
Study Drug Dosing / Chemotherapy
GS-5745 IV Dosing
X
X
FOLFIRI/Bev Dosingj
X
X
EOS = End-of-Study (visit); PE = physical examination
a
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any 
concurrent medical illnesses.
b
A complete PE will be performed at Screening. A modified PE capturing changes from prior exams will be performed at subsequent applicable visits. Weight (without shoes) 
should be measured at each PE and reported in kilograms. Height (without shoes) should be measured at Screening only and reported in centimeters.
c
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken per institutional guidelines.
d
Prior/concomitant medications include all medication taken up to 30 days prior to Screening, any and all medications taken during the course of the study, and supportive 
therapies given during the course of the study (eg, blood transfusion, growth factor).
e
AEs will be assessed before and after GS-5745 and FOLFIRI dosing during applicable visits. The site will call subjects 30 days after the last dose of GS-5745 to assess AEs 
and SAEs.
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Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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f
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.). 
The same radiographic procedure used to define measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if 
not conducted within the previous 4 weeks. If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the 
study to collect tumor assessments (CT/MRI), chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
g
Unstained slides (10 to 12) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1 of Cycle 1 only.
h
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the EOS visit.
i
Blood samples to measure GS-5745 concentration will be collected pre-dose on Day 1 and Day 15 of each cycle, end of GS-5745 infusion on Day 1 of Cycle 1 and Cycle 3, 
and at the EOS visit.
j
FOLFIRI and bevacizumab dosing regimen on Days 1 and 15 of each 28-day treatment cycle will consist of: bevacizumab at 5 mg/kg IV, and FOLFIRI at l-leucovorin 200 
mg/m2 or dl-leucovorin 400 mg/m2 as a 2-hour infusion, and irinotecan 180 mg/m2 given as a 90-minute infusion in 500 mL dextrose 5% via a Y-connector, followed by 
bolus 5-FU 400 mg/m2 and a 46-hour infusion 5-FU 2400 mg/m2.     
k
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
l
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression
m
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than disease 
progression, the site should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive disease progression.
n
Blood samples for biomarkers should be drawn pre-dose on all specified visits. Note that Day 15 is only required for Cycle 1 and that a blood sample at EOS is required if due 
to disease progression. The exact schedule of blood draws is outlined in the laboratory manual.
o
A stool sample is required at study start and can be collected any time within the screening window prior to first dose. An additional stool sample at Cycle 2 Day 15 
(+14 days/−7 days) is requested.
r
A ± 2 day window applies to visits following Cycle 1 Day 1. There is no window for Cycle 1 Day 1.
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Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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Appendix 7.
Study Procedures Table (Part B – Breast Cancer)
Study Phase
Screening
Each Cycle (28 Days)
Cycle 2
Cycle 3
Every 2 
Cycles
EOSm
LTFU
Cycle Day
Screening
1
8
15
15
1
N/A
N/A
Window
−28
0q
± 2
± 2
+14 Days / −7 
Days
N/A
N/A
Treatment Day
−28
1
8
15
N/A
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
Vital Signsc
X
X
X
X
X
12-Lead ECG
X
X
ECOG Performance Status
X
X
X
X
Prior/Concomitant Medsd
X
X
X
X
X
AEse
X
X
X
X
X
CT or MRIf
X
Xl
X
Collect Archival Tumor Tissue 
(if Available)g
X
Register Subject Visit in IxRS
X
X
X
X
Sample Collection
Chemistry
X
Xk
X
Xl
X
Hematology
X
Xk
X
X
Xl
X
Coagulation
X
Xk
X
Urinalysis
X
Xk
X


Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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24 July 2019
Study Phase
Screening
Each Cycle (28 Days)
Cycle 2
Cycle 3
Every 2 
Cycles
EOSm
LTFU
Cycle Day
Screening
1
8
15
15
1
N/A
N/A
Window
−28
0q
± 2
± 2
+14 Days / −7 
Days
N/A
N/A
Treatment Day
−28
1
8
15
N/A
N/A
Pregnancy Testh
X
Xk
X
X
GS-5745 Concentrationi
X
X
X
X
Anti-GS-5745 Antibody
Xk
X
Serum and Plasma Biomarkers
Xk,n
Xn
Xn
Overall Survival
X
Study Drug Dosing /
Chemotherapy
GS-5745 IV Dosing
X
X
Paclitaxelj
X
X
X
EOS = End-of-Study (visit); PE = physical examination
a.
Medical history includes significant past medical events (eg, prior hospitalizations or surgeries), a review of the disease under study, prior anti-cancer therapies, and any 
concurrent medical illnesses.
b.
A complete PE will be performed at Screening. A modified PE capturing changes from prior exams will be performed at subsequent applicable visits. Weight (without shoes) 
should be measured at each PE and reported in kilograms. Height (without shoes) should be measured at Screening only and reported in centimeters.
c.
Vital signs include blood pressure, respiratory rate, pulse, and temperature. Measurements of blood pressure should be taken per institutional guidelines.
d.
Prior/concomitant medications include all medication taken up to 30 days prior to Screening, any and all medications taken during the course of the study, and supportive 
therapies given during the course of the study (eg, blood transfusion, growth factor).
e.
AEs will be assessed before and after GS-5745 and Paclitaxel dosing during applicable visits. The site will call subjects 30 days after the last dose of GS-5745 to assess AEs 
and SAEs.
f.
Tumor evaluation by CT or MRI will be performed during screening (within 4 weeks of Day 1) and during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.). 
The same radiographic procedure used to define measurable lesions must be used throughout the study for each subject. CT or MRI should be conducted at the EOS visit if 
not conducted within the previous 4 weeks. If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the 
study to collect tumor assessments (CT/MRI), chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
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Andecaliximab (GS-5745)
Study GS-US-296-0101
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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g.
Unstained slides (10 to 12) from archival tumor tissues prepared within 2 weeks of shipment to Gilead or its designee will be requested after Day 1 of Cycle 1 only.
h.
For females of childbearing potential, a serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed prior to each dose of GS-5745 and 
at the EOS visit.
i.
Blood samples to measure GS-5745 concentration will be collected pre-dose on Day 1 and Day 15 of each cycle, end of GS-5745 infusion on Day 1 of Cycle 1 and Cycle 3, 
and at the EOS visit.
j.
Paclitaxel dosing regimen will consist of Paclitaxel 80 mg/m2 IV.
k.
Day 1 pre-dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit.
l.
If a subject discontinues study drug (for example, as a result of an AE), every attempt should be made to keep the subject in the study to collect tumor assessments (CT/MRI), 
chemistry, and hematology during the last week of even-numbered cycles (ie, Cycles 2, 4, 6, etc.) until disease progression.
m.
Subjects will be contacted by phone 30 days (± 2 days) after the last dose of GS-5745 to assess AEs. For subjects who come off study for reasons other than disease 
progression, the site should also obtain information on post-study anti-cancer therapies, surgeries, and date of definitive disease progression.
n.
Blood samples for biomarkers should be drawn pre-dose on all specified visits. Note that Day 15 is only required for Cycle 1 and that a blood sample at EOS is required if due
to disease progression. The exact schedule of blood draws is outlined in the laboratory manual.
 
q.
A ± 2 day window applies to visits following Cycle 1 Day 1. There is no window for Cycle 1 Day 1.
CCII 


Andecaliximab (GS-5745) 
Study GS-US-296-0101 
Statistical Analysis Plan - Final Analysis 
Appendix 8. 
List of Laboratory Tests for Safety Summary 
Se1·um Chemistry 
Hematology 
Sodium 
White Blood Cell Count 
Potassium 
Hemoglobin 
Chloride 
Hematocri.t 
Glucose 
Platelet Count 
BUN 
ANC 
Creatinine 
N eutrophils 
ALT 
Lymphocytes 
AST 
Monocytes 
Alkaline phosphatase 
Total bilirnbin 
Total protein 
Albumin 
Calcium 
Magnesium 
Phosphate 
CONFIDENTIAL 
Page 64 
Version 1.0 
Coagulation 
PT/INR 
aPIT 
24 July 2019