Clinical trial NCT02862535
Conditions: Gastric Adenocarcinoma
Sponsor: Gilead Sciences
Start date: 2016-09-20; Completion date: 2019-10-25
Enrollment: 36 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to characterize the safety and tolerability of andecaliximab as monotherapy and in combination with anti-cancer agents in Japanese participants with inoperable advanced or recurrent gastric or recurrent gastroesophageal junction (GEJ) adenocarcinoma.

Detailed description:

Arms: arm 1: Participants will receive andecaliximab (ADX) 800 mg every 2 weeks on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. arm 2: Participants will receive ADX 800 mg every 2 weeks on Days 1 and 15 of each 28-day treatment cycle in combination with S-1 orally twice daily plus cisplatin chemotherapy (dosage and regimen will be based on participant condition, investigator discretion, institutional practice, and/or the in-country label) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. arm 3: Participants will receive ADX 1200 mg every 3 weeks on Day 1 of each 21-day treatment cycle in combination with chemotherapy (S-1 80 mg/day to 120 mg/day according to the body surface area orally twice daily for first 14 days of 21 day cycle plus oxaliplatin 100 mg/m\^2) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study. arm 4: Participants will receive ADX 800 mg every 2 weeks followed by chemotherapy (nivolumab 3 mg/kg) on Days 1 and 15 of each 28-day treatment cycle 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: S-1 intervention 3: Cisplatin intervention 4: Oxaliplatin intervention 5: Nivolumab
Intervention descriptions: intervention 1: Administered via intravenous (IV) infusion (approximately 30 minutes) intervention 2: Administered orally intervention 3: Administered via IV infusion on Day 8 of every 5 weeks intervention 4: Administered via IV infusion for over 2 hours on Day 1 of each 21-day cycle intervention 5: Administered via IV infusion (approximately 60 minutes) every 2 weeks

Protocol documents:
Prot_000.pdf: 
(rJ GILEAU 
CLINICAL STUDY PROTOCOL 
Study Title: 
A Phase 1 b Study to Evaluate the Safety and Tolerability of 
Andecaliximab (GS-5745) as Monotherapy and in 
Combination with Anti-Cancer Agents in Japanese Subjects 
with Gastric or Gastroesophageal Junction Adenocarcinoma 
Sponsor: 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
Clinical Trials.gov Identifier: 
02862535 
Indication: 
Gastric Adenocarcinoma 
Protocol ID: 
GS-US-296-1884 
Gilead Clinical Program 
Manager: 
Gilead Medical Monitor: 
Protocol Version/Date: 
Name: 
Telephone: 
Email: 
Name: 
Telephone: 
Email: 
Original: 
Amendment 1: 
Amendment 2: 
Amendment 3: 
PD 
PD 
PD 
PD 
PD 
PU 
5 Febrnaiy 2016 
13 May2016 
15 November 2016 
14 July2017 
CONFIDENTIALITY STATEMENT 
The info1mation contained in this document, paii iculai·ly unpublished data, is the prope1iy 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 infonnation is only to be used by you in 
connection with authorized clinical studies of the investigational drng described in the protocol. 
You will not disclose any of the infonnation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessa1y to obtain infonned consent from those 
persons to whom the drng may be administered. 


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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....................................................................21
1.
INTRODUCTION ..............................................................................................................................................25
1.1.
Background ............................................................................................................................................25
1.1.1.
Gastric Adenocarcinoma ......................................................................................................27
1.1.2.
MMP9 Expression in Oncology...........................................................................................28
1.2.
Andecaliximab .......................................................................................................................................29
1.2.1.
General Information .............................................................................................................29
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................29
1.2.3.
Clinical Trials of Andecaliximab .........................................................................................32
1.3.
Rationale for This Study ........................................................................................................................33
1.4.
Risk/Benefit Assessment for the Study..................................................................................................36
1.5.
Compliance ............................................................................................................................................36
2.
OBJECTIVES.....................................................................................................................................................37
3.
STUDY DESIGN................................................................................................................................................38
3.1.
Endpoints ...............................................................................................................................................38
3.2.
Study Design..........................................................................................................................................38
3.3.
Study Treatments ...................................................................................................................................42
3.4.
Duration of Treatment............................................................................................................................42
3.5.
Discontinuation Criteria from Study Treatment.....................................................................................42
3.6.
Premature Discontinuation from Study Treatment.................................................................................43
3.7.
Discontinuation Criteria from Study ......................................................................................................43
3.8.
End of Study...........................................................................................................................................44
3.9.
Long-Term Follow-Up for Overall Survival..........................................................................................44
3.10.
Source Data............................................................................................................................................44
3.11.
Biomarker Testing..................................................................................................................................45
3.11.1.
Biomarker Samples to Address the Study Objectives ..........................................................45
3.11.2.
Biomarker Samples for Optional Future Research...............................................................49
4.
SUBJECT POPULATION..................................................................................................................................50
4.1.
Number of Subjects and Subject Selection ............................................................................................50
4.2.
Inclusion Criteria....................................................................................................................................50
4.3.
Exclusion Criteria...................................................................................................................................52
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................55
5.1.
Enrollment..............................................................................................................................................55
5.2.
Description and Handling of Study Treatments .....................................................................................55
5.2.1.
Formulation..........................................................................................................................55
5.2.2.
Packaging and Labeling .......................................................................................................56
5.2.3.
Storage and Handling...........................................................................................................56
5.3.
Dosage and Administration of Andecaliximab, S-1, Cisplatin, Oxaliplatin, and Nivolumab ................56
5.3.1.
Dose Interruption and Reduction..........................................................................................57
5.4.
Prior and Concomitant Medications.......................................................................................................59
5.5.
Accountability for Andecaliximab and Andecaliximab/Nivolumab ......................................................59


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5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................60
6.
STUDY PROCEDURES ....................................................................................................................................61
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................61
6.2.
Pretreatment Assessments......................................................................................................................61
6.2.1.
Screening Visit .....................................................................................................................61
6.3.
Treatment Assessments – Cohort 1 (Andecaliximab Monotherapy)......................................................62
6.3.1.
Day 1 of Each 28-Day Cycle................................................................................................62
6.3.2.
Cycle 1 Day 2 and Cycle 1 Day 4 ........................................................................................63
6.3.3.
Cycle 1 Day 8.......................................................................................................................64
6.3.4.
Day 15 of Each 28-Day Cycle..............................................................................................64
6.3.5.
Cycle 1 Day 29/Cycle 2 Day 1.............................................................................................65
6.4.
Treatment Assessments – Cohorts 2, 3 and 4 (Combination Therapy Cohorts).....................................65
6.4.1.
Day 1 of Each 28-Day Cycle for Cohort 2 (Combination Therapy 
Andecaliximab and SP) and Cohort 4 (Combination Therapy 
Andecaliximab and Nivolumab) ..........................................................................................66
6.4.2.
Day 1 of Each 21-Day Cycle for Cohort 3 (Combination Therapy 
Andecaliximab and SOX) ....................................................................................................67
6.4.3.
Cycle 1 Day 8 for Cohort 4 (Combination Therapy Andecaliximab and 
Nivolumab) ..........................................................................................................................69
6.4.4.
Day 15 of Each 28-Day Cycle for Cohort 2 (Combination Therapy 
Andecaliximab and SP) and Cohort 4 (Combination Therapy 
Andecaliximab and Nivolumab) ..........................................................................................69
6.5.
Continuation of Treatment .....................................................................................................................70
6.5.1.
Every 8 Weeks for Cohorts 1, 2 and 4  Every 9 Weeks for Cohort 3...................................71
6.6.
Assessments for Premature Discontinuation from Study.......................................................................71
6.7.
Criteria for Discontinuation of Study Treatment....................................................................................71
6.8.
End of Treatment....................................................................................................................................71
6.9.
End of Study Visit..................................................................................................................................72
6.10.
Follow-up Visits.....................................................................................................................................73
6.10.1.
30-Day Safety Follow-Up ....................................................................................................73
6.10.2.
Cohort 4 (Combination Therapy Andecaliximab and Nivolumab) Only: 
5-Month Safety Follow-Up ..................................................................................................74
6.10.3.
Long Term Follow-Up .........................................................................................................74
6.11.
Replacement of Subjects........................................................................................................................75
6.12.
Description of Study Procedures............................................................................................................75
6.12.1.
Informed Consent.................................................................................................................75
6.12.2.
Re-Screening Criteria...........................................................................................................75
6.12.3.
Medical & Medication History.............................................................................................75
6.12.4.
Physical Examination...........................................................................................................76
6.12.5.
Vital Signs............................................................................................................................76
6.12.6.
Electrocardiogram Assessment ............................................................................................76
6.12.7.
Performance Status...............................................................................................................76
6.12.8.
Laboratory Assessments.......................................................................................................77
6.12.9.
Tumor Response Assessment...............................................................................................81
6.12.10.
Study Drug and Anti-Cancer Agent Administration ............................................................84
6.12.11.
Adverse Events.....................................................................................................................85
6.12.12.
Unscheduled Visits...............................................................................................................85
6.12.13.
Protocol Deviations..............................................................................................................85
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................86
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................86
7.1.1.
Adverse Events.....................................................................................................................86
7.1.2.
Serious Adverse Events........................................................................................................86


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7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................87
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................88
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................88
7.2.2.
Assessment of Severity ........................................................................................................88
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................89
7.3.1.
Adverse Events.....................................................................................................................89
7.3.2.
Serious Adverse Events........................................................................................................89
7.4.
Gilead Reporting Requirements.............................................................................................................92
7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or 
Serious Adverse Events..........................................................................................................................92
7.6.
Toxicity Management ............................................................................................................................93
7.7.
Special Situations Reports......................................................................................................................93
7.7.1.
Definitions of Special Situations..........................................................................................93
7.7.2.
Instructions for Reporting Special Situations.......................................................................94
8.
STATISTICAL CONSIDERATIONS................................................................................................................96
8.1.
Analysis Objectives and Endpoints........................................................................................................96
8.1.1.
Analysis Objectives..............................................................................................................96
8.1.2.
Primary Endpoint .................................................................................................................96
8.1.3.
Secondary Endpoint .............................................................................................................96
8.1.4.
Other Endpoints of Interest ..................................................................................................96
8.2.
Analysis Conventions.............................................................................................................................97
8.2.1.
Analysis Sets ........................................................................................................................97
8.3.
Data Handling Conventions ...................................................................................................................97
8.4.
Demographic Data and Baseline Characteristics ...................................................................................98
8.5.
Efficacy Analysis ...................................................................................................................................98
8.5.1.
Categorical Endpoints ..........................................................................................................99
8.5.2.
Time-to-Event Endpoints .....................................................................................................99
8.5.3.
Continuous Endpoints ..........................................................................................................99
8.6.
Safety Analysis.......................................................................................................................................99
8.6.1.
Extent of Exposure...............................................................................................................99
8.6.2.
Adverse Events.....................................................................................................................99
8.6.3.
Laboratory Evaluations ......................................................................................................100
8.6.4.
Other Safety Evaluations....................................................................................................100
8.7.
Pharmacokinetic Analysis....................................................................................................................100
8.8.
Biomarker Analysis..............................................................................................................................100
8.8.1.
Pharmacodynamic Analysis ...............................................................................................100
8.8.2.
Exploratory Biomarker Analysis........................................................................................101
8.9.
Sample Size..........................................................................................................................................101
9.
RESPONSIBILITIES........................................................................................................................................102
9.1.
Investigator Responsibilities ................................................................................................................102
9.1.1.
Good Clinical Practice........................................................................................................102
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval.........................................................................................................102
9.1.3.
Informed Consent...............................................................................................................102
9.1.4.
Confidentiality....................................................................................................................103
9.1.5.
Study Files and Retention of Records ................................................................................103
9.1.6.
Case Report Forms.............................................................................................................104
9.1.7.
Investigational Medicinal Product Accountability and Return...........................................105
9.1.8.
Inspections..........................................................................................................................105
9.1.9.
Protocol Compliance..........................................................................................................105


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9.2.
Sponsor Responsibilities ......................................................................................................................106
9.2.1.
Protocol Modifications.......................................................................................................106
9.2.2.
Study Report and Publications ...........................................................................................106
9.3.
Joint Investigator/Sponsor Responsibilities .........................................................................................106
9.3.1.
Payment Reporting.............................................................................................................106
9.3.2.
Access to Information for Monitoring................................................................................107
9.3.3.
Access to Information for Auditing or Inspections ............................................................107
9.3.4.
Study Discontinuation........................................................................................................107
10.
REFERENCES .................................................................................................................................................108
11.
APPENDICES ..................................................................................................................................................115
Appendix 1.
Investigator Signature Page..................................................................................................116
Appendix 2.
Study Procedures Table – Cohort 1 (Andecaliximab Monotherapy)....................................117
Appendix 3.
Study Procedures Table – Cohort 2: Combination Therapy Andecaliximab and SP............120
Appendix 4.
Study Procedures Table – Cohort 3: Combination Therapy Andecaliximab and SOX........123
Appendix 5.
Study Procedures Table – Cohort 4: Combination Therapy Andecaliximab and 
Nivolumab............................................................................................................................126
Appendix 6.
Proposed Regimen for Combination Therapy Andecaliximab and SP.................................129
Appendix 7.
Regimen for Combination Therapy Andecaliximab and SOX.............................................130
Appendix 8.
Regimen for Combination Therapy Andecaliximab and Nivolumab ...................................131
Appendix 9.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................132
Appendix 10.
Revised RECIST Guideline (Version 1.1)............................................................................135
LIST OF IN-TEXT TABLES
Table 3-1.
Cohort Dose Levels................................................................................................................42
Table 3-2.
Biomarker Objectives and Testing .........................................................................................46
Table 6-1.
Analytes..................................................................................................................................78
Table 6-2.
Imaging and Treatment after First Radiologic Evidence of Progressive Disease...................84
LIST OF IN-TEXT FIGURES
Figure 1-1.
Inhibition of MMP9 in the NeuT Model of Breast Cancer.....................................................31
Figure 1-2.
Combination Therapy of Anti-MMP9 and Anti-PDL1 Promotes an Increase in T 
Cells, Helper T cells, and Cytotoxic T Lymphocytes (CTL) in Tumors ................................31
Figure 1-3.
Hypothesis for synergy between andecaliximab and nivolumab............................................35
Figure 3-1.
Cohort 2 (Combination Therapy Andecaliximab and SP) Proposed Regimen.......................40
Figure 3-2.
Cohort 3 (Combination Therapy Andecaliximab and SOX) Regimen...................................41
Figure 3-3.
Cohort 4 (Combination Therapy Andecaliximab and Nivolumab) Regimen.........................41


Andecaliximab 
Protocol GS-US-296-1884 
Gilead Sciences, Inc. 
Study Title: 
Clinical Trials.gov 
Identifier: 
Study Centers 
Planned: 
Objectives: 
Study Design: 
CONFIDENTIAL 
PROTOCOL SYNOPSIS 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
Final 
Amendment3 
A Phase 1 b Study to Evaluate the Safety and Tolerability of 
Andecaliximab (GS-5745) as Monotherapy and in Combination with 
Anti-Cancer Agents in Japanese Subjects with Gastric or 
Gastrnesophageal Junction Adenocarcinoma 
02862535 
Approximately 4 centers in Japan 
The primaiy objective of this study is: 
• 
To characterize the safety and tolerability of andecaliximab as 
monotherapy and in combination with anti-cancer agents in 
Japanese subjects with inoperable advanced or recmTent gastric or 
gastroesophageal junction ( GEJ) adenocarcinoma 
The secondaiy objectives of this study ai·e: 
• 
To characterize the phaimacokinetics (PK) of andecaliximab 
• 
To evaluate the fo1mation of anti-andecaliximab antibodies 
The explorato1y objectives of this study ai·e: 
I 
I 
I 
This is a Phase l b, open-label, multicenter study to evaluate the safety 
and tolerability of andecaliximab as monotherapy and in combination 
with anti-cancer agents in Japanese subjects with inoperable advanced 
or recunent gastric or GEJ adenocarcinoma. 
Page6 
14 July 2017 


Andecalix
Protocol G
Gilead Sci
CONFID
 
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GS-US-296-18
ences, Inc.  
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84 
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Andecaliximab 
Protocol GS-US-296-1884 
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 Grade 4 neutropenia (absolute neutrophil count [ANC] < 500/µL) 
for > 7 days, or febrile neutropenia (per the National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events 
(CTCAE) Version 4.03 definition) regardless of duration.  
 Primary prophylaxis with granulocyte-colony stimulating factor 
(G-CSF) is not permitted during the first cycle of study treatment. 
G-CSF may be used at any time at the discretion of the investigator 
in response to treatment emergent neutropenia. Subjects who 
develop Grade 4 neutropenia related to andecaliximab will be 
considered a DLT (subjects may receive G-CSF at the discretion of 
the investigator in response to treatment emergent neutropenia).  
 Grade 4 thrombocytopenia, Grade 3 thrombocytopenia associated 
with bleeding, or Grade 3 or 4 thrombocytopenia requiring platelet 
transfusion 
 Grade 3 or 4 non-hematologic toxicity (excluding rash, nausea, 
diarrhea, and vomiting if controlled with standard supportive care) 
 Non-hematologic toxicity of ≥ Grade 2 (at any time during 
treatment) that, in the judgment of the investigator and the medical 
monitor, is dose-limiting 
 Treatment delay of > 14 days due to unresolved toxicity 
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 adverse 
event (AE) should be assessed as a DLT necessitating dose reduction. 
After all 6 subjects in Cohort 1 have completed the 28-day DLT 
assessment window and 0 or 1 out of 6 subjects experienced DLTs, an 
internal safety review team (SRT) will conduct a review of the safety 
and PK data from all subjects prior to proceeding with the combination 
therapy cohorts to evaluate andecaliximab with other anti-cancer 
agents.  
The SRT completed their review of all available clinical safety and PK 
data for 6 DLT-evaluable subjects in Cohort 1 on 11 May 2017 and 
determined the dose for the combination therapy cohorts (Cohorts 2 and 
4) to be 800 mg andecaliximab Q2W. See Section 1.3 for rationale of 
dose selection for Cohort 3 (1200 mg andecaliximab Q3W). The 
internal SRT consisted of Gilead study team members including the 
Medical Monitor, representatives from Clinical Operations, Drug 
Safety and Public Heath (DSPH), and Biostatistics.   


Andecaliximab 
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Cohorts 2, 3, and 4: Andecaliximab Combination Therapy Cohorts  
Japanese subjects with inoperable advanced or recurrent gastric or GEJ 
tumors will be enrolled in each combination therapy cohort to receive 
andecaliximab in combination with anti-cancer agents. Dosage and 
frequency of treatment in these cohorts will be as follows:  
 Cohort 2: Combination therapy andecaliximab and SP  
 Andecaliximab 800 mg via IV infusion over approximately 
30 (± 5) minutes Q2W until disease progression. The dose is 
based on safety data from Cohort 1. Andecaliximab treatment 
will be administered in 28-day cycles. 
 S-1 administered orally twice daily: dosage and regimen will be 
based on subject condition, investigator discretion, institutional 
practice and/or the in-country label 
 Cisplatin administered by IV infusion on Day 8 of every 
5 weeks: dosage and regimen will be based on subject 
condition, investigator discretion, institutional practice and/or 
the in-country label 
 Up to 6 subjects will be enrolled in this cohort 
 Cohort 3: Combination therapy andecaliximab and SOX  
 Andecaliximab 1200 mg via IV infusion over approximately 
30 (± 5) minutes every 3 weeks (Q3W) until disease 
progression. The dose is based on safety data from Cohort 1 and 
other ongoing phase 1 studies of andecaliximab. Andecaliximab 
treatment will be administered in 21-day cycles. 
 S-1 administered orally twice daily at 80 mg/day for body 
surface area (BSA) < 1.25m2, 100 mg/day for BSA ≥ 1.25 to 
< 1.5m2, and 120 mg/day for BSA ≥ 1.5m2 for the first 14 days 
of the 21-day cycle 
 Oxaliplatin administered by IV infusion at 100 mg/m2 over 
2 hours on Day 1 of each 21-day cycle 
 Up  to 10 subjects will be enrolled in this cohort 
 Cohort 4: Combination therapy andecaliximab and nivolumab 
 Andecaliximab 800 mg via IV infusion over approximately 
30 (± 5) minutes Q2W until disease progression. The dose is 
based on safety data from Cohort 1. Andecaliximab treatment 
will be administered in 28-day cycles. 


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 Nivolumab 3 mg/kg Q2W via IV infusion over 60 (± 5) minutes 
following the completion of andecaliximab administration. 
Dose is adjusted if the weight changes more than 10% from the 
baseline dosing weight. 
 Up to 10 subjects will be enrolled in this cohort 
For Cohorts 1, 2, and 4, computed tomography (CT) or magnetic 
resonance imaging (MRI) scans will be performed every 8 weeks to 
evaluate response to treatment by RECIST v1.1. For Cohort 4, response 
to treatment will also be evaluated using immune related response 
criteria recommendations {Wolchok 2009}. 
For Cohort 3, CT or MRI scans will be performed every 9 weeks to 
evaluate response to treatment by RECIST v1.1. 
The cohort dose levels for andecaliximab and associated combination 
anti-cancer agents are summarized below:  
Cohort  
Number 
of 
Subjects 
Andecaliximab 
Dose 
Andecaliximab 
Dosing Interval 
Combination 
Anti-Cancer 
Agent(s) 
1 
6 to 12 
800 mg or 600 
mg 
Q2W 
N/A 
2 
Up to 6 
800 mg  
Q2W 
SP 
3 
Up to 10 
1200 mg  
Q3W 
SOX 
4 
Up to 10 
800 mg  
Q2W 
Nivolumab 
Abbreviations: SOX = S-1 and oxaliplatin; SP = S-1 and cisplatin; Q2W = every 2 weeks; 
Q3W = every 3 weeks 
Number of 
Subjects Planned: 
Up to 38 subjects  
Target Population: 
Japanese subjects  20 years of age with histologically confirmed 
inoperable advanced or recurrent gastric or GEJ adenocarcinoma 
Duration of 
Treatment: 
For Cohorts 1, 2, and 4, each cycle will be 28 days and will continue in 
the absence of disease progression, unacceptable toxicity, withdrawal 
of consent, or other reasons specified in Section 3.5.  
For Cohort 3, each cycle will be 21 days, to align with the SOX dosing 
schedule, and will continue in the absence of disease progression, 
unacceptable toxicity, withdrawal of consent, or other reasons specified 
in Section 3.5. 


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Gilead Sciences, Inc.  
Amendment 3 
CONFIDENTIAL 
Page 11 
14 July 2017 
Diagnosis and 
Main Eligibility 
Criteria: 
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible 
for participation in this study: 
1) Male or female  20 years of age 
2) Subjects must have been born in Japan and must not have lived 
outside of Japan for a period >1 year in the 5 years prior to Day 1 
3) Subjects must be able to trace their maternal and paternal ancestry 
of parents and grandparents as ethnically Japanese 
4) Histologically confirmed inoperable advanced gastric 
adenocarcinoma (including adenocarcinoma of the GEJ) or relapsed 
gastric adenocarcinoma 
5) Cohorts 1 (andecaliximab monotherapy), 2 (combination therapy 
andecaliximab and SP) and 3 (combination therapy andecaliximab 
and SOX): Human Epidermal Growth Factor Receptor 2 
(HER2)-negative tumor (primary tumor or metastatic lesion). 
Enrollment in Cohort 4 (combination therapy andecaliximab and 
nivolumab) is not restricted by HER2 status (subjects with 
HER2-positive, HER2-negative, or unknown HER2 status are 
eligible). 
6) Cohort 1 (andecaliximab monotherapy): Prior antitumor therapy or 
cytotoxic chemotherapy is acceptable. Subjects who are not eligible 
to receive standard treatments should enroll on the study. All acute 
toxic effects of any prior antitumor therapy must be resolved to 
Grade ≤ 1 (or baseline) before the start of andecaliximab dosing 
(with the exception of alopecia [Grade 1 or 2 permitted] and 
neurotoxicity [Grade 1 or 2 permitted]). 
7) Cohorts 2 (combination therapy andecaliximab and SP) and 3 
(combination therapy andecaliximab and SOX): Prior antitumor 
therapy or cytotoxic chemotherapy for metastatic disease is not 
acceptable. Subjects must be chemo-naive in the metastatic setting. 
Subjects who relapse during adjuvant chemotherapy or within 
180 days after adjuvant chemotherapy for their gastric cancer 
should not be enrolled.  
8) Eastern Cooperative Oncology Group (ECOG) Performance Status 
of ≤ 1 
9) Life expectancy of > 3 months in the opinion of the investigator 


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Gilead Sciences, Inc.  
Amendment 3 
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10) Adequate baseline organ function (within 28 days prior to Day 1) as 
shown in the following table:  
Organ System 
Parameter 
Required Value 
Hematopoietic 
ANC 
≥ 1.5 x 109/L 
Platelets 
≥ 100 x 109/L 
Hemoglobin 
Cohorts 1-3: ≥ 8.0 g/dL (not RBC transfusion 
dependent) 
Hepatic 
Serum total or 
conjugated bilirubin 
≤ 1.5 x ULN 
Serum AST and ALT 
≤ 2.5 x ULN (if liver metastases are present, 
≤ 5 x ULN) 
Renal 
Serum Creatinine 
Cohort 1: ≤ 1.5 x ULN 
Cohorts 2 and 3: ≤ 1.0 x ULN 
Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; 
AST = aspartate aminotransferase; RBC =  red blood cell; ULN = upper limit of normal 
11) Coagulation: International Normalized Ratio (INR) ≤ 1.5 (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. 
12) For female subjects of childbearing potential, willingness to use a 
protocol-recommended method of contraception from the screening 
visit throughout the study treatment period and defined periods 
following the last dose of andecaliximab and/or anti-cancer agent(s) 
(See Appendix 9) 
13) 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 
andecaliximab, throughout the study treatment period, and defined 
periods following the last dose of andecaliximab and/or anti-cancer 
agent(s), and to refrain from sperm donation from the start of 
andecaliximab, throughout the study treatment period, and defined 
periods following the last dose of andecaliximab and/or anti-cancer 
agent(s) (See Appendix 9)  
14) Willingness to comply with scheduled visits, drug administration 
plan, imaging studies, laboratory tests, other study procedures, and 
study restrictions 
15) Evidence of a personally signed informed consent form 


Andecaliximab 
Protocol GS-US-296-1884 
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Gilead Sciences, Inc.  
Amendment 3 
CONFIDENTIAL 
Page 13 
14 July 2017 
16) In addition to the applicable criteria above, subjects in Cohort 4 
(combination therapy andecaliximab and nivolumab) must meet all 
of the following inclusion criteria to be eligible for participation in 
this study: 
a) Measureable gastric or GEJ adenocarcinoma according to 
RECIST v1.1 
b) Subject must have progressed on at least 1 prior systemic 
therapy or line of treatment for unresectable/metastatic disease. 
All toxicities attributed to prior anti-cancer therapy other than 
alopecia or fatigue must have resolved to Grade ≤ 1 
(NCI CTCAE Version 4) or baseline 
c) Adequate baseline organ function (within 28 days prior to 
Day 1) as shown in the following table:  
Organ System 
Parameter 
Required Value 
Hematopoietic 
ANC 
≥ 1.5 x 109/L 
Platelets 
≥ 100 x 109/L 
Hemoglobin 
≥ 9.0 g/dL 
Hepatic 
Serum total or 
conjugated bilirubin 
≤ 1.5 x ULN 
Serum AST and ALT 
≤ 2.5 x ULN (if liver metastases are present, 
≤ 5 x ULN) 
Renal 
Creatinine Clearance 
 Creatinine clearance (CLcr) ≥ 60 mL/min, 
estimated based on the Cockroft-Gault 
formula or measured based on 24 hour urine 
collection or other reliable method 
Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; 
AST = aspartate aminotransferase; CLcr = creatinine clearance; RBC =  red blood cell; 
ULN = upper limit of normal 
d) Subjects not receiving anticoagulant medication must have an 
activated partial thromboplastin (aPTT) ≤ 1.5 x ULN. The use 
of full-dose oral or parenteral anticoagulants is permitted as 
long as the aPTT is within therapeutic limits (according to the 
medical standard in the institution) and the subject has been on 
stable dose of anticoagulants for at least 1 week at the time of 
enrollment  
e) Thyroid function tests (thyroid-stimulating hormone (TSH), T3, 
free T4) should be within normal limits. Subjects with 
underlying thyroid disease are eligible if they are receiving 
appropriate medication and are clinically stable. 


Andecaliximab 
Protocol GS-US-296-1884 
Final 
Gilead Sciences, Inc.  
Amendment 3 
CONFIDENTIAL 
Page 14 
14 July 2017 
 
Exclusion Criteria 
Subjects who meet any of the following exclusion criteria will not be 
enrolled in this study: 
1) History or evidence of a 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. Enrollment of lactating females after 
discontinuation of breastfeeding is not acceptable. 
3) Subjects with known central nervous system (CNS) metastases, 
unless metastases are treated and stable and the subject does not 
require systemic steroids 
4) Radiotherapy within 28 days of Day 1; subjects given palliative 
radiotherapy to peripheral sites (eg, bone metastasis) may enter the 
study before 28 days have elapsed if subject has recovered from any 
acute reversible effects 
5) 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 Day 1 
6) History of major surgery within 28 days of Day 1  
7) Serious systemic fungal, bacterial, viral, or other infection that is 
not controlled or requires IV antibiotics 
8) Cohort 1 (andecaliximab monotherapy): Anti-tumor therapy 
(chemotherapy, antibody therapy, molecular targeted therapy) 
within 28 days or 5 half-lives, whichever is shorter, of Day 1 
(6 weeks for nitrosoureas, mitomycin C, or molecular agents with 
t½ > 10 days) 
9) Clinically significant bleeding within 28 days of Day 1 
10) Subjects known to be positive for human immunodeficiency virus 
(HIV), hepatitis C infection (per local standard diagnostic criteria), 
or acute or chronic hepatitis B infection (per local standard 
diagnostic criteria) 
11) Known hypersensitivity to any of the study drugs or components or 
to Chinese hamster ovary cell products or to recombinant human or 
humanized antibodies 


Andecaliximab 
Protocol GS-US-296-1884 
Final 
Gilead Sciences, Inc.  
Amendment 3 
CONFIDENTIAL 
Page 15 
14 July 2017 
 
12) History of a concurrent or second malignancy except for adequately 
treated local basal cell or squamous cell carcinoma of the skin; 
cervical carcinoma in situ; superficial bladder cancer; asymptomatic 
prostate cancer without known metastatic disease, with no 
requirement for therapy or requiring only hormonal therapy, and 
with normal prostate-specific antigen for ≥ 1 year prior to Day 1; 
adequately treated Stage 1 or 2 cancer currently in complete 
remission; or any other cancer that has been in complete remission 
for ≥ 5 years 
13) Known alcohol or drug abuse or any other medical or psychiatric 
condition which contraindicates participation in the study  
14) Subject is expected to require any form of systemic or localized 
antineoplastic therapy while on study 
15) In addition to the applicable criteria above, subjects in Cohort 4 
(combination therapy andecaliximab and nivolumab) who meet any 
of the following exclusion criteria will not be enrolled in this study: 
a) Subjects who have received only neoadjuvant or adjuvant 
therapy for gastric adenocarcinoma 
b) Chronic daily treatment with oral corticosteroids (dose of 
> 10 mg/day prednisone equivalent) or other 
immunosuppressive medications within 14 days of Day 1. 
Inhaled steroids and short courses of oral steroids for 
anti-emesis or as an appetite stimulant are allowed.  
c) Anti-tumor therapy (chemotherapy, antibody therapy, molecular 
targeted therapy) within 28 days or 5 half-lives, whichever is 
shorter, of Day 1 (6 weeks for nitrosoureas, mitomycin C, or 
molecular agents with t½ > 10 days) 
d) Prior treatment with anti-CTLA-4 agents (eg, ipilimumab), 
anti-PD-1 or anti-PD-L1 agents (eg, pembrolizumab, 
nivolumab, atezolizumab), anti-PD-L2 agents, anti-MMP 
agents, or other immunomodulatory therapies 
e) Prior therapy with anti-tumor vaccines or other immuno-
modulatory antitumor agents  
f) Current or history of pneumonitis or interstitial lung disease 
g) Active known or suspected autoimmune disease. Subjects with 
vitiligo, type I diabetes mellitus, residual hypothyroidism 
requiring hormone replacement, or conditions not expected to 
recur in the absence of an external trigger are permitted to enroll 
h) History of bone marrow, stem cell, or allogeneic organ 
transplantation 


Andecaliximab 
Protocol GS-US-296-1884 
Final 
Gilead Sciences, Inc.  
Amendment 3 
CONFIDENTIAL 
Page 16 
14 July 2017 
Study Procedures: 
Screening: 
Screening will commence with obtaining the subject’s signed informed 
consent, and will occur up to 28 days prior to the first dosing of 
andecaliximab on Day 1. Screening procedures will include the 
following: medical history review, physical exam (PE), vital signs, 
12-lead electrocardiogram (ECG), ECOG Performance Status, 
prior/concomitant medication review, blood collection for pregnancy 
test (females), urinalysis, chemistry, hematology, coagulation, thyroid 
function tests (for Cohort 4 only: combination therapy andecaliximab 
and nivolumab), biomarkers, AE assessment, pre-treatment fresh 
biopsy collection, and CT or MRI (scans obtained as part of standard 
medical practice up to 28 days prior to Day 1 are acceptable). Baseline 
tumor lesions will be measured and characterized prior to Day 1 to 
assess subject disease status prior to beginning treatment. 
Treatment: Cohort 1: Andecaliximab Monotherapy 
Treatment will occur over cycles comprised of 28 days. Subjects who 
meet eligibility will undergo CT or MRI scans every 8 weeks. 
Beginning with Day 1 of Cycle 1, subjects will receive andecaliximab 
800 mg by IV infusion over approximately 30 minutes Q2W for a total 
of 2 infusions per cycle (Day 1 and Day 15 of each 28-day cycle). 
Safety and efficacy assessments will occur on an outpatient basis 
including assessment of tumor response, physical exam, vitals, ECG, 
collection of blood samples, urine pregnancy, urinalysis, and 
assessment of AEs at the protocol specified time points.  
The DLT assessment window is 28 days. The safety and tolerability of 
the 800 mg dose will be assessed after all 6 subjects have been 
followed for at least 28 days after the first infusion of andecaliximab. If 
2 or more subjects within the cohort of 6 subjects experience DLTs 
during the first 28 days of andecaliximab dosing, 6 additional subjects 
will be enrolled at a reduced dose of 600 mg Q2W. If 2 additional 
DLTs occur at 600 mg, andecaliximab will be considered unsafe and 
will be discontinued. Therefore, a total of up to 12 subjects may be 
enrolled in Cohort 1.  
Once all subjects in Cohort 1 have completed the 28-day DLT 
assessment window and 1 or 0 out of 6 subjects experienced DLTs, an 
internal SRT will conduct a review of the safety and PK data from all 
subjects prior to proceeding with the combination therapy cohorts to 
evaluate andecaliximab with other anti-cancer agents. 
The SRT completed their review of all available clinical safety and PK 
data for 6 DLT-evaluable subjects in Cohort 1 on 11 May 2017 and 
determined the dose for the combination therapy cohorts (Cohorts 2 and 
4) to be 800 mg andecaliximab Q2W. See Section 1.3 for rationale of 


Andecalix
Protocol G
Gilead Sci
CONFID
imab 
GS-US-296-18
ences, Inc.  
ENTIAL 
84 
dose se
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Page 17
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14 July
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Andecalix
Protocol G
Gilead Sci
CONFID
imab 
GS-US-296-18
ences, Inc.  
ENTIAL 
84 
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Safety a
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Page 18
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14 July
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Andecaliximab 
Protocol GS-US-296-1884 
Gilead Sciences, Inc. 
Test Product, Dose, 
and Mode of 
Administration: 
Criteria for 
Evaluation: 
Safety 
Final 
Amendment3 
CT or MRI for assessment of tumor status will be conducted eve1y 
8 weeks for Coho1is 1, 2, and 4, and eve1y 9 weeks for Coho1i 3. 
However, tumor response may be assessed prior to the specified eve1y 
8- or 9-week time point if clinically indicated. 
Andecaliximab is formulated as a sterile, aqueous buffered solution and 
is stored at 2 to 8° C in single-use 10 ml vials containing 400 mg 
andecaliximab at a concentration of 40 mg/ml. 
Subjects will be administered 800 mg or 600 mg andecaliximab via IV 
infusion over approximately 30 minutes Q2W or 1200 mg 
andecaliximab via IV infusion over approximately 30 minutes Q3W. 
All subjects who meet eligibility criteria, have signed a consent fonn, 
and have begun treatment, will be evaluated for response. 
Safety will be evaluated by assessment of clinical laborato1y tests, 
physical examination, 12-lead ECG, vital sign measmements, and by 
the incidence of AEs. 
Phannacokinetics/ 
concentrations 
Phannacodynamics -
will be analyzed. 
Efficacy 
CONFIDENTIAL 
The explorato1y efficacy endpoints will include: 
I 
I 
I 
I 
I 
I 
I 
Page 19 
14 July 2017 


Andecaliximab 
Protocol GS-US-296-1884 
Final 
Gilead Sciences, Inc.  
Amendment 3 
CONFIDENTIAL 
Page 20 
14 July 2017 
Statistical Methods: 
Appropriate data analysis sets will be defined.  
The Safety Analysis Set is defined as all subjects who receive at least 
1 infusion at any dose of andecaliximab.  
The Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set is 
defined as all subjects in the Safety Analysis Set who have the 
necessary baseline and on-study measurements to provide interpretable 
results for specific parameters of interest. 
 
Subject characteristics and study results will be described and 
summarized by treatment dose level/cohort for the relevant analysis 
sets. Descriptive statistics including sample size, mean, median, 
standard deviation, and ranges will be summarized for continuous 
variables, and categorical variables will be summarized using 
frequency counts and percentages. 
The Safety Analysis Set will be used for both the safety and efficacy 
analyses. Andecaliximab plasma concentrations and parameters will be 
described and summarized using the PK Analysis Set. 
Sample size 
The sample size of 6 subjects in Cohort 1 (andecaliximab monotherapy) 
allows a relatively high probability (> 65%) to observe 2 or more 
subjects with DLT when the true underlying probability of DLT is 
greater than 33.3% at current dose level.  
Up to 6 subjects will be enrolled in Cohort 1 to receive 800 mg 
andecaliximab Q2W, and based on safety assessments, an additional 
6 subjects may be enrolled in Cohort 1 to receive 600mg andecaliximab 
Q2W prior to proceeding with the combination therapy cohorts. Based 
on the dose level selected by Cohort 1, up to 6 subjects will be enrolled 
in Cohort 2 (combination therapy andecaliximab and SP), and up to 
10 subjects will be enrolled in Cohorts 3 (combination therapy 
andecaliximab and SOX) and 4 (combination therapy andecaliximab 
and nivolumab), respectively.  
Therefore, up to 38 subjects will be enrolled in the study. 
 
 
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents. 


Andecaliximab
Protocol GS-US-296-1884
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 21
14 July 2017
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
AB0041
murine anti-human MMP9 monoclonal antibody
AB0046
murine anti-human MMP9 monoclonal antibody
ADR
adverse drug reaction
AE
adverse event
AFP
alpha-fetoprotein
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
BSA
body surface area
BUN
blood urea nitrogen
CA 19-9
carbohydrate antigen 19-9
CEA
carcinoembryonic antigen
CDDP
cisplatin
CDHP
5 chloro-2,4-dihydroxyphridine
CFR
Code of Federal Regulations
CI
confidence interval
CL
clearance
CLcr
creatinine clearance
Clast
last observed quantifiable drug concentration 
Cmax
the maximum observed drug concentration
CNS
central nervous system
ConMed
concomitant medication
CR
complete response
CRO
contract research organization
CSR
clinical study report
CT
computed tomography scan
CTCAE
Common Terminology Criteria for Adverse Events
CTL
cytotoxic T lymphocytes
DCR
disease control rate
dL
deciliter
DLT
dose limiting toxicity
DNA
deoxyribonucleic acid
DOR
duration of response
DPD
dihyropyrimidine dehydrogenase
DSPH
Drug Safety and Public Health


Andecaliximab
Protocol GS-US-296-1884
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 22
14 July 2017
ECG
electrocardiogram
ECM
extracellular matrix
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form(s)
EDC
electronic data capture
ELISA
enzyme-linked immunosorbent assay
EOI
end of infusion
EOS
end-of-study
EOT
end of treatment
eSAE
electronic serious adverse event reporting system
EU
European Union
EudraCT
European clinical trials database
FDA
(United States) Food and Drug Administration
FFPE
formalin-fixed paraffin-embedded 
FSH
follicle-stimulating hormone
g
gram
GCP
Good Clinical Practice (Guidelines)
G-CSF
granulocyte-colony stimulating factor
GEJ
gastroesophageal junction
-HCG
beta human chorionic gonadotropin
HCl
hydrochloric acid
HER2
Human Epidermal Growth Factor Receptor 2
HIV
Human Immunodeficiency Virus
HLGT
high-level group term
HLT
high-level term
HR
hazard ratio
hsCRP
high sensitivity c-reactive protein
IB
investigator’s brochure
ICF
informed consent form
ICH
International Conference on Harmonisation
ID
identification
IEC
independent ethics committee
IFNγ
interferon gamma
IHC
immunohistochemistry
IL1β
interleukin-1β
IL-8
interleukin-8
IMP
investigational medicinal product
INR
international normalized ratio
IRB
institutional review board
irRECIST
immune-related response evaluation criteria in solid tumors


Andecaliximab
Protocol GS-US-296-1884
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 23
14 July 2017
ISH
in-situ hybridization
ITT
intention to treat
IUD
intrauterine device
IV
intravenous
IWRS
interactive web response system
JCOG
Japanese Clinical Oncology Group
Kg
kilogram
KM
Kaplan-Meier methods
L
liter
LAM
lactational amenorrhea method
LLT
lower-level term
LTFU
long term follow-up
MDSC
myeloid-derived suppressor cells
MedDRA
Medical Dictionary for Regulatory Activities
mFOLFOX6
5-FU, leucovorin, and oxaliplatin
mg
milligram
min
minute
mL
millileter
mm
millimeter
MMP
matrix metalloproteinase
MRI
magnetic resonance imaging
MSS
musculoskeletal syndrome
NCCN
National Comprehensive Cancer Network
NCI
National Cancer Institute
NK
natural killer cell
NOAEL
no-observed adverse effect levels
NN
non-CR/non-PD
NSCLC
non-small cell lung cancer
ORR
objective response rate
OS
overall survival
PD
progressive disease
PD1
programmed cell death protein 1
PD-L1
programmed death-ligand 1
PE
physical examination
PFS
progression-free survival
PK
pharmacokinetic
PK/PD
pharmacokinetic/pharmacodynamic
PR
partial response
PT
prothrombin time
PTT
partial thromboplastin time


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Q2W
every two weeks
Q3W
every three weeks
QA
quality assurance
RBC
red blood cell 
RECIST
Response Evaluation Criteria in Solid Tumors
RNA
ribonucleic acid
SADR
serious adverse drug reaction
SAE
serious adverse event
SC
subcutaneous
SD
stable disease
SmPC
summary of product characteristics
SOC
system organ class
SOP
standard operating procedure
SOX
S-1 plus oxaliplatin
SP
S-1 plus cisplatin
SPIRITS
S-1 plus cisplatin vs S-1 in first line treatment of advanced gastric cancer trial
SRT
safety review team
SUSAR
suspected unexpected serious adverse reaction
t½
half life 
TAN
tumor-associated neutrophils
TAM
tumor-associated macrophages
TIMP
tissue inhibitors of metalloproteinases
Tlast
time (observed time point) of Clast
Tmax
time (observed time point) of Cmax
TSH
thyroid-stimulating hormone
TTR
time to response
ULN
upper limit of the normal range
US
United States
V
distribution volume
VEGF
vasoactive endothelial growth factor
WBC
white blood cell count
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 MMP, a 
group of cell surface tethered proteases {Hu 2007, Mott 2004}. The gelatinases comprise of
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 {Chen 2002, Kridel 
2001}. 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, as compared to disease-induced and pathology-associated expression and 
activity of MMP9 {Agrawal 2006, Castaneda 2005, Dubois 1999, Garg 2009, Hu 2007, Itoh 
2002, Li 2009, Miyazaki 2011, Naito 2005, Santana 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 
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 1995, Olson 1997, Vempati 2007}. 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 {Dubois 1999, Hu 2007, Itoh 2002, Itoh 1999, Opdenakker 
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 2007}. The disease-associated
induction and functions of MMP9 render it an attractive therapeutic target. MMP9 expression is 
elevated in a wide array of tumor types and high MMP9 levels are correlated with poor prognosis 
in many cancers including gastric cancer {Egeblad 2002, Roy 2009}. MMP9, which is produced 
by tumor cells as well as by stromal inflammatory cells such as tumor-associated neutrophils 
(TANs) and macrophages (TAMs) and myeloid-derived suppressor cells (MDSC), has roles in 
primary tumor growth, metastasis, angiogenesis and tumor-associated immune suppression 
{Condeelis 2006}. MMP9 expression by these cell types in the context of the tumor 
microenvironment is also associated with local protumorigenic immune dysregulation. 


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MMP9-mediated cleavage potentiates the activity of various cytokines such as IL-8 and IL1β 
and these liberated or activated signaling molecules are then able to promote primary tumor cell 
growth both directly and indirectly, in addition to promoting ongoing recruitment of suppressive 
myeloid infiltrating cells {Kessenbrock 2010, Perng 2011, Van den Steen 2000}. The activation 
of TGFβ from its latent complex by MMP9 could promote further immune suppression and 
polarization {Dayer 2015, Ge 2006, Jenkins 2008, Wang 2011, Yu 2000}}. Similarly, the 
cleavage of MICA and ULBPs, ligands for natural killer (NK) cell recognition of tumor cells via 
NKG2D, can blunt local anti-tumor innate immune responses {Baragano Raneros 2014, Fiore 
2002, Peng 2014, Shiraishi 2016, Sun 2011}. MMP9 degrades CXCL9, CXCL10 and CXCL11, 
3 ligands for CXCR3 {Cox 2008, Liao 1995, Van den Steen 2003}. This chemokine plays a 
critical role in the trafficking of Th1 and CD8+ T cells to peripheral sites of Th1-type 
inflammation and the establishment on Th1 amplification loop mediated by IFNγ and the 
IFNγ-inducible CXCR3 ligands{Chheda 2016, Mikucki 2015}. MMP9 activity in the tumor 
microenvironment could thus result in ineffective trafficking of these tumoricidal effector 
T cells.
Consistent with these published studies, independent analyses at Gilead indicate that MMP9 
expression is highly prevalent in gastric cancer, with widespread heterogeneous positivity 
observed for inflammatory infiltrate and tumor epithelia, as well as subpopulations of other cell 
types. While MMP9 expression in rodent tumor models is more limited than observed in the 
human disease, inhibition of tumor growth is observed using murine surrogate antibodies of 
andecaliximab (GS-5745). In an orthotopic xenograft model or colorectal cancer, treatment of 
established tumors with anti-MMP9 antibodies targeting the tumor epithelial (human) or stromal 
(murine) compartments resulted in consistent and significant inhibition of tumor growth across 
different studies, indicating that both tumor- and stroma-derived MMP9 contributed to tumor 
growth. Inhibition of tumor growth in this model was associated with reductions in metastasis, 
vascular endothelial growth factor (VEGF) levels, and tumor-associated fibrillar collagen. 
Additional studies in an established orthotopic, syngeneic model of lung tumorigenesis (using 
Lewis lung carcinoma lines) demonstrated benefit with murine surrogate AB0046 with respect to 
survival, tumor volume, and altered inflammatory infiltrate. In a rodent NeuT (ERBB2)-driven 
orthotopic model of breast cancer, which is resistant to programmed cell death protein 1/ 
programmed death ligand 1 (PD1/PDL1) checkpoint blockade, MMP9 expression was observed 
in infiltrating myeloid cells. Treatment of established tumors resulted in significant efficacy with 
respect to tumor volume and transcript and pathway analysis indicated favorable changes in the 
tumor inflammatory profile, with activation of cytotoxic anti-tumor T-cell activity. Inhibition of 
MMP9 resulted in reductions in regulatory T cells and M2-polarized, immune suppressive 
macrophages in the tumor microenvironment. Immunophenotyping of tumor-associated T cells 
by flow cytometry showed that anti-MMP9 and anti-PDL1 co-treatment increased total T cells 
(CD3), CD8, and CD4 T cells, and activated effector T cells. T cell checkpoint inhibitors, such 
as antibodies targeting PD1 and PDL1, have demonstrated substantial and sustained anti-tumor 
responses consistent with the restoration of anti-tumor T-cell responses, however, their activity is 
limited to a subset of patients in many tumor types, and a desmoplastic tumor microenvironment, 
immune suppression by infiltrating myeloid cells, and deficient trafficking of effector T cells 
have all been suggested as contributing factors {Gajewski 2010, Gajewski 2013, Hegde 2016}. 


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Inhibition of MMP9 thus offers the potential, in combination, for enhancement of anti-tumor 
activity.
1.1.1.
Gastric Adenocarcinoma
Adenocarcinoma of the stomach is the most common gastrointestinal cancer in the world and the 
third leading cause of cancer death worldwide {Ferlay 2013}. While the incidence of gastric 
adenocarcinoma has declined in the United States, gastric cancer remains quite frequent in 
certain minority populations and it is still the second most common cause of cancer death 
worldwide. Additionally, the disease continues to be common in Asian countries where nearly 
60% of new cases occur {Crew 2006}. Many important differences have been observed in 
gastric cancer presentation and anatomic location and patient receipt of multi-modality therapy 
and surgery between Asian countries and the West. When considering disease presentation and 
location (proximal, body, antrum, pylorus), for example, Asian patients are more likely to be 
younger at initial diagnosis and have a higher proportion of distal gastric cancers {Gill 2003, 
Theuer 2000}. Furthermore, Asians were more likely to have localized disease and undergo 
curative surgery {Kim 2010}. Asians are less likely to have inadequate lymphadenectomy 
compared to whites {Al-Refaie 2010}. There have been some additional factors such as 
differences in tumor biology {Theuer 2006, Theuer 2002, Theuer 2000}, and infectious 
etiologies such as Helicobacter pylori (H.pylori) {Fock 2010} that may influence some of these 
disparities to variable extents. 
McCulloch et al {McCulloch 1997, McCulloch 1995} showed that the oncogenes c-erbB2 and 
TP53 were expressed in similar ways in gastric cancer from Japanese and British patients. 
However, Theuer et al {Theuer 2002} showed a higher frequency of microsatellite stability in 
gastric cancer from Japanese compared to American patients. Theuer et al also showed that 
normal E-cadherin expression was more common in Japanese intestinal type gastric cancer 
whereas c-erbB2 expression was higher in American gastric cancer patients. This may be 
important because abnormal E-cadherin expression is associated with adverse features in gastric 
cancer such as loss of cell–cell adhesion {Becker 1994, Wang 2014b}, and increased c-erbB2 
expression may be associated with depth of invasion and metastasis {Mizutani 1993}.
H. pylori infection affects 50% of the world wide population {Marshall 1984}. It has been 
implicated in the role of chronic gastritis and peptic ulcer disease {Plummer 2004, Wang 
2014a}, and the association between H. pylori and gastric cancer is also well accepted 
{American Cancer Society 2005, National Comprehensive Cancer Network (NCCN) 2015, 
Wang 2014a}. Epidemiologic studies estimate that the risk of gastric cancer in H. pylori infected 
individuals is increased by 20 fold {Brenner 2004}. In general, H. pylori seroprevalence is 
higher in Asians {Fock 2010}. The higher rates of gastric cancer in Asia may occur from a 
complex interaction between many host factors, environmental factors, and H. pylori infection 
{Fock 2010}. 
Surgically curable early gastric cancers are usually asymptomatic and only infrequently detected 
outside the realm of a screening program (in countries which have a very high incidence of 
gastric cancer, such as Japan, Venezuela, and Chile). The common presenting symptoms and 
diagnostic approaches to gastric cancer include weight loss (usually results from insufficient 


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caloric intake rather than increased catabolism) and may be attributable to anorexia, nausea, 
abdominal pain, early satiety, and/or dysphagia. Abdominal pain is often present which tends to 
be epigastric, vague and mild early in the disease but more severe and constant as the disease 
progresses. Dysphagia is a common presenting symptom in patients with cancers arising in the 
proximal stomach or at the esophagogastric junction. Patients may also present with nausea or 
early satiety from the tumor mass or in cases of an aggressive form of diffuse-type gastric cancer 
called linitis plastica, from poor distensibility of the stomach. They may also present with a 
gastric outlet obstruction from an advanced distal tumor.
The platinum-fluoropyrimidine doublet is the major back bone of most regimens in Western 
countries and in East Asia. S-1 is an oral fluoropyrimidine combining tegafur – a prodrug of 
5-FU, 5 chloro-2, 4-dihydroxypyridine (CDHP) a reversible inhibitor of dihyropyrimidine 
dehydrogenase (DPD), and potassium oxonate, an antidiarrheal agent protective against 5-FU 
gastrointestinal toxicity in a molar ratio of 1:0.4:1. In a landmark Japanese study done by the 
Japanese Clinical Oncology Group (JCOG) 9912, S-1 was found to be non-inferior to 5-FU 
alone and irinotecan/cisplatin {Boku 2009}. Given the ease of oral dosing, without compromise 
in efficacy or excessive toxicity, S-1 was adopted as the standard treatment for metastatic gastric 
cancer in Japan. 
The SPIRITS (S-1 plus cisplatin (SP) vs S-1 in first line treatment of advanced gastric cancer) 
trial showed that SP resulted in a significantly longer median survival and progression free 
survival (PFS) compared to S-1 alone {Koizumi 2008}. Both regimens were well tolerated 
although patients assigned to combination treatment experienced increased Grade 3 and 4 events 
including neutropenia (40% vs 11%), anemia (26% vs 4), nausea (11% VS 1%) and anorexia 
(30% vs 6%) {Koizumi 2008}. Based on the SPIRITS trial, the SP doublet remains the standard 
chemotherapy regimen for advanced gastric cancer in Japan, replacing 5-FU/cisplatin. 
{Yamada 2015} compared SP and S-1 plus oxaliplatin (SOX) as first line therapy for advanced 
gastric cancer.  The PFS of SOX was non-inferior to SP in PFS [median, 5.5 versus 5.4 months; 
hazard ratio (HR) 1.004, 95% confidence interval (CI) 0.840–1.199] while the median overall 
survival (OS) was 14.1 and 13.1 months, respectively (HR 0.958 with 95% CI 0.803–1.142). In 
the intention to treat (ITT) population, the HRs in PFS and OS were 0.979 (95% CI 0.821–1.167) 
and 0.934 (95% CI 0.786–1.108), respectively. Additionally, SOX demonstrated a more 
favorable safety profile.  
Finally, {Kang 2017} demonstrated improved efficacy of nivolumab monotherapy compared to 
placebo as salvage treatment for patients who have received at least 2 lines of treatment for 
advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. The median OS was 
5.32 months in the nivolumab arm versus 4.14 months in the placebo arm  (HR, 0.63; 95%, CI, 
0.50-0.78; p,0.0001) while the median PFS was 1.61 months versus 1.45 months for the 
nivolumab and placebo arms, respectively (HR, 0.60; 95% CI, 0.49-0.75; p,0.0001).
1.1.2.
MMP9 Expression in Oncology
MMP9 is expressed heterogeneously by tumor epithelia as well as infiltrating myeloid cells 
including myeloid suppressor cells and tumor-associated macrophages and neutrophils, as well 
as components of fibroblastic stroma, and tumor-associated endothelial cells. Expression of 


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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 a temporal 
response to either changes in local tumor environment, or during processes such as invasion and 
proliferation. MMP9 expression by tumor-associated macrophages, neutrophils, myeloid-derived 
suppressor cells and other cell types in the tumor microenvironment is also associated with local 
pro-tumorigenic immunomodulation and angiogenesis {Farina 2014}. In gastric tumors, MMP9 
expression is consistently observed, often in several compartments including tumor epithelia, 
inflammatory infiltrate and stromal compartments.
1.2.
Andecaliximab
1.2.1.
General Information
Andecaliximab is a recombinant chimeric IgG4 monoclonal antibody {Marshall 2015}. It has 
been engineered to remove T-cell epitopes in an effort to reduce the risk of immunogenicity 
{Baker 2010, Perry 2008}. Andecaliximab binds with high affinity to human MMP9, but not to 
other human MMPs. Andecaliximab was derived from the murine anti-human MMP9 
monoclonal antibody, AB0041, and shares the same binding characteristics. Andecaliximab 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 andecaliximab and AB0041 on human MMP9.
For further information on andecaliximab, refer to the current investigator’s brochure (IB) for 
andecaliximab.
1.2.2.
Preclinical Pharmacology and Toxicology
1.2.2.1.
Pharmacology
The therapeutic potential of inhibitory antibodies targeting MMP9 was evaluated in orthotopic 
xenograft and syngeneic models of tumorigenesis. Treatment of established tumors generated 
orthotopically using the HCT116 colorectal cell line with anti-MMP9 antibodies targeting the 
tumor epithelial (human) or stromal (murine) compartments resulted in consistent and significant 
inhibition of tumor growth across different studies, indicating that both tumor- and 
stroma-derived MMP9 contributed to tumor growth. Inhibition of tumor growth in this model 
was associated with reductions in metastasis, vascular endothelial growth factor (VEGF) levels, 
and tumor-associated fibrillar collagen. In an aggressive, disseminated, xenograft pancreatic 
cancer model (AsPC-1), selective inhibition of MMP9 prolonged survival in combination with 
either gemcitabine/abraxane or 5-fluorouracil. Additional studies in an established orthotopic, 
syngeneic model of lung tumorigenesis (using Lewis lung carcinoma lines) demonstrated benefit 
with murine surrogate AB0046 with respect to survival, tumor volume, and altered inflammatory 
infiltrate. In a rodent NeuT (ERBB2)-driven orthotopic model of breast cancer (adapted 
genetically engineered model implanted in the mammary fat pad), MMP9 expression was 
observed in infiltrating myeloid cells only. As shown below, this model is refractory to 
PD1/PDL1 checkpoint blockade. Inhibition of MMP9 using AB0046 resulted in significant 


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efficacy with respect to tumor volume (Figure 1-1), and transcript and pathway analysis 
indicated favorable changes in the tumor inflammatory profile, toward a Th1 response, consistent 
with activation of cytotoxic anti-tumor T-cell activity {Juric 2017}. The NeuT model was 
utilized as a PD1 axis checkpoint-resistant model to explore the effect on combination with anti-
MMP9. Pharmacodynamic analyses were performed after 7 days of treatment of established 
tumors to ensure that tumors matched in mean volume across all groups.  Immunophenotyping of 
tumor-associated T cells by flow cytometry showed that anti-MMP9 and anti-PDL1 co-treatment 
increased total T cells (CD3), CD8 and CD4 T cells, and activated effector T cells, while
inhibition of MMP9 resulted in a decrease in regulatory T cells (Treg, with the effect maintained 
in combination) (Figure 1-2). In a separate study, inhibition of MMP9 resulted in significant 
decreases in both recruited and resident M2 polarized, immune-suppressive macrophages. These 
observations are consistent with the reported role of MMP9 activity in the tumor 
microenvironment in promoting immune-suppression via recruitment and activation of 
infiltrating myeloid cells, M2 macrophages, N2 neutrophils, and regulatory T cells, which both 
promote tumor growth and suppress anti-tumor T cells. In addition, studies in vitro revealed that 
cleavage of CXCR3 effector T-cell ligands CXCL9, 10 and 11 using activated MMP9 resulted in 
reduced migration of activated human primary T cells in chemotaxis assays, in a dose-dependent 
manner, for all 3 chemokines. These data suggest that inhibition of MMP9 could promote 
improved trafficking of effector T cells into the tumor microenvironment. 
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 
Lewis rat MSS model.
Further details on non-clinical pharmacology are available in the andecaliximab IB.


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Figure 1-1.
Inhibition of MMP9 in the NeuT Model of Breast Cancer
Inhibition of MMP9 in the NeuT model of breast cancer results in significant inhibition of tumor growth, whereas an anti-PDL1 
antibody is ineffective, presumably due to the immunosuppressive effects of infiltrating myeloid cells in this model. 
Figure 1-2.
Combination Therapy of Anti-MMP9 and Anti-PDL1 Promotes an 
Increase in T Cells, Helper T cells, and Cytotoxic T Lymphocytes 
(CTL) in Tumors
Immunophenotyping of whole tumors from 7 day pharmacodynamics study in NeuT model from animals treated with control 
IgG, anti-MMP9, anti-PDL1, or a combination of anti-MMP9 and anti-PDL1 (“combo”). CTL: cytotoxic T lymphocytes.
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


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1.2.2.2.
Toxicology
The toxicological profile of andecaliximab has been evaluated in a human tissue cross-reactivity 
study, 4-week repeat dose intravenous (IV) toxicity studies with 4-week recovery in rat and 
monkey, and 26-week repeat-dose toxicity studies with 12-week recovery in rats and monkeys. 
Reproductive toxicity has been assessed following IV administration in rat and rabbit embryo 
fetal developmental toxicity studies and a rat fertility study.
There was no specific andecaliximab staining observed in normal human tissues. Findings 
associated with andecaliximab IV treatment in the 4-week repeat-dose toxicity studies were 
limited to nonadverse reversible physeal hypertrophy in rats and reversible increased adrenal 
gland weight in female monkeys at all doses, which was associated with slight hypertrophy of 
the zona fasciculata in a single 100-mg/kg/dose female monkey. Physeal hypertrophy findings 
associated with andecaliximab in the 4-week rat study are likely directly attributable to inhibition 
of MMP9, as similar findings were observed in MMP9 null mice {Vu 1998} and in children with 
mutations in MMP9 and MMP13 {Lausch 2009}. In MMP9 null mice, the hypertrophic cartilage 
zone was lengthened with ectopic ossification that resolved with subsequent remodeling 
producing normal-appearing bone by 8 weeks of age. In children, mutations in MMP9 and 
MMP13 are associated with metaphyseal anadysplasia syndrome {Lausch 2009}. Mutations in 
MMP9 result in a milder form of skeletal dysplasia characterized by transient bowing of the legs 
early in childhood due to metaphyseal irregularities that spontaneously regresses in late 
childhood. In the 26-week studies, there were no findings of toxicological concern in rats or 
cynomolgus monkeys following weekly IV or subcutaneous (SC) administration of 
andecaliximab at doses up to 100 mg/kg/dose and 150 mg/kg/dose, respectively. The lack of 
physeal hypertrophy observed in the rat 26-week study is presumably due to the reversible nature 
of this finding as longitudinal bone growth and growth plate closure slows/completes. There 
were no adverse injection site reactions observed in the 26-week studies, and no adverse findings 
in the local tolerability study. The no observed adverse effect level (NOAEL) in the rat and 
monkey 26-week studies was 100 mg/kg/dose (IV) and 150 mg/kg/dose (SC), the highest doses 
evaluated by each route of administration in each study. At doses of andecaliximab up to 
100 mg/kg/dose IV, data indicate no test article-related maternal or fetal effects in rats and 
rabbits, and no test article-related effects on male or female fertility in rats.
Further details on toxicology are available in the andecaliximab IB.
1.2.3.
Clinical Trials of Andecaliximab
Andecaliximab is currently being developed for the treatment of various solid tumors. Details of
the clinical studies in these diseases can be found in the IB. 
Study GS US-296-0101 is a Phase 1, open-label, sequential dose-escalation, and expansion study 
to evaluate safety, pharmacokinetics (PK), and pharmacodynamics of andecaliximab following 
multiple IV administrations of andecaliximab alone (at 200, 600, and 1800 mg every 2 weeks
(Q2W)) or in combination with chemotherapy (at 800 mg Q2W or 1200 mg every 3 weeks
(Q3W)) in subjects with advanced solid tumors.  The study is active at centers in the 
United States.


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Study GS-US-296-2013 is a phase 2, open-label, randomized study evaluating the efficacy, 
safety, PK, and pharmacodynamics of andecaliximab (800 mg every two weeks (Q2W)) and 
nivolumab (3 mg/kg Q2W) or nivolumab (3 mg/kg Q2W) alone in patients with unresectable or 
recurrent gastric or GEJ adenocarcinoma.  The study is active at centers in the United States, 
Europe, and Australia.
Study GS-US-296-1080 is a Phase 3, randomized, double-blind, placebo-controlled study to 
evaluate the efficacy and safety of andecaliximab in combination with mFOLFOX6 as first line 
treatment in subjects with advanced gastric or GEJ adenocarcinoma. Andecaliximab 800 mg
Q2W in combination with mFOLFOX6 is being evaluated globally at centers in the United 
States, Europe, Latin America, and Australia. 
As of 31 August 2016, efficacy data is available from 40 subjects with advanced gastric/GEJ 
adenocarcinoma enrolled on Study GS-US-296-0101 treated with andecaliximab 800 mg IV
Q2W and mFOLFOX6. The investigator assessed objective response rate (ORR) for all 
40 subjects was 47.5% (90% CI, 33.8-61.5) with 3 (7.5%) CRs and 16 (40%) PRs. The duration 
of response was 8.4 months for all patients and 9.5 months for treatment-naïve patients. PFS was 
7.8 (90% CI, 5.5-13) months in all patients and 10.7 (90% CI, 5.5-18) months in treatment-naïve 
patients {Shah 2017}.
1.3.
Rationale for This Study
Andecaliximab was first evaluated in subjects with cancer in the Phase 1 Study GS-US-
296-0101. That study was divided into 2 parts: a monotherapy dose finding stage enrolling 
subjects with advanced solid tumors who had failed or were intolerant to standard therapy or for 
whom no standard therapy was available and a combination stage evaluating the safety and 
efficacy of andecaliximab at the dose determined from the monotherapy stage with available 
chemotherapies in subjects with advanced pancreatic, non-small cell lung cancer (NSCLC), 
human epidermal growth factor 2 (HER2) negative gastric/GEJ adenocarcinoma, colorectal, and 
breast cancer.
Results from non-Japanese subjects with HER2 negative advanced gastric/GEJ adenocarcinoma 
treated with andecaliximab 800 mg IV Q2W and mFOLFOX6 in the Phase 1 Study GS-US-
296-0101 demonstrated anti-tumor efficacy with an acceptable toxicity profile {Shah 2017}. 
To enable clinical investigation of andecaliximab in Japan, Gilead is evaluating the safety and 
PK profile of andecaliximab as monotherapy and in combination with anti-cancer agents in 
Japanese subjects with advanced gastric/GEJ adenocarcinoma.
Rationale for Andecaliximab Dose Levels in Japanese Subjects
The first dose level of andecaliximab monotherapy in this study will be 800 mg IV Q2W.  This 
dose was selected based on data from the dose-finding phase of the GS-US-296-0101 study.  No 
DLTs were observed at andecaliximab doses up to 1800 mg IV Q2W.  Based on safety and PK 
data from the dose finding phase of Study GS-US-296-0101, andecaliximab 800 mg IV Q2W 
was selected for the combination phase of the study for subjects with advanced gastric/GEJ 


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adenocarcinoma, pancreatic adenocarcinoma, colorectal adenocarcinoma and breast cancer.  
Data from these cohorts suggested andecaliximab 800 mg IV Q2W in combination with other 
anti-cancer agents was well tolerated and no new safety signal was identified compared to 
historic data from similar populations. Clinically relevant differences in andecaliximab PK 
between Japanese and Western subjects are not expected and it is anticipated that andecaliximab 
800 mg IV Q2W monotherapy will be well tolerated in Japanese subjects.
Subjects enrolled in the monotherapy cohort(s) of this study will be evaluated in a 28-day DLT 
window. Safety and tolerability will be assessed after all subjects have been followed for at least 
28 days after the first infusion of andecaliximab. If 2 or more subjects within the cohort of 
6 subjects experience DLTs during the first 28 days of andecaliximab dosing, 6 additional 
subjects will be enrolled at a reduced dose of 600 mg Q2W. If 2 additional DLTs are reported at 
the 600 mg Q2W dose level, andecaliximab will be considered unsafe and will be discontinued. 
Once all subjects in Cohort 1 have completed the 28-day DLT assessment period, an internal 
safety review team (SRT) will conduct a review of the safety and PK data from all subjects prior 
to opening the combination therapy cohorts.
In Study GS-US-296-0101, andecaliximab was administered at 1200 mg IV Q3W in 
combination with chemotherapy for subjects with advanced NSCLC (carboplatin plus 
pemetrexed for adenocarcinoma (n = 10) and carboplatin plus paclitaxel for squamous histology
(n = 10)).  Data from these cohorts suggested Q3W dosing of andecaliximab was well tolerated 
and no new safety signal was identified compared to historic data of carboplatin, paclitaxel, and 
pemetrexed in a similar population.  
Finally, PK data from Study GS-US-296-0101 demonstrated similar trough plasma 
concentrations of andecaliximab in subjects with advanced pancreatic, gastric/GEJ 
adenocarcinoma and NSCLC following 800 mg IV Q2W or 1200 mg IV Q3W dosing
irrespective of tumor histology or chemotherapy combination. These data support the use of 
these two alternate doses and schedules to facilitate co-administration with chemotherapies using 
either Q2W or Q3W dosing.
The SRT completed their review of all available clinical safety and PK data for 6 DLT-evaluable 
subjects in Cohort 1 on 11 May 2017 and determined the dose for the combination therapy 
cohorts (Cohorts 2 and 4) to be 800 mg andecaliximab Q2W, and Cohort 3 to be 1200 mg Q3W. 
Rationale for Combination Therapy Cohorts in Japanese Subjects:
The combination therapy cohorts (Cohorts 2-4) will evaluate the safety and tolerability of
andecaliximab in combination with the following anti-cancer regimens:

Andecaliximab and SP in subjects with treatment-naïve advanced gastric/GEJ 
adenocarcinoma (Cohort 2)

Andecaliximab and SOX in subjects with treatment-naïve advanced gastric/GEJ 
adenocarcinoma (Cohort 3)


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
Andecaliximab and nivolumab in subjects with advanced gastric/GEJ adenocarcinoma who 
have progressed on an least 1 prior systemic therapy or line of treatment for 
unresectable/metastatic disease (Cohort 4)
The SP and SOX regimen were selected for evaluation based on Phase 3 studies of Japanese 
patients with advanced gastric/GEJ adenocarcinoma and national guidelines {Koizumi 2008}.  
The safety profile of andecaliximab and a fluoropyrimidine and platinum based regimen has 
previously been characterized {Shah 2017}.
Nivolumab is a human monoclonal antibody directed against PD-1 that blocks the interaction of 
PD-1 with PD-L1 and PD-L2 which has demonstrated activity in previously treated advanced 
gastric cancer {Kang 2017, Le 2015}. Preclinical data suggesting that inhibition of MMP9 
activity within tumors may re-balance a myeloid-rich tumor-associated cellular milieu to one that 
is less repressive to cytotoxic T-cell entry and activity.  Additionally, the presence of myeloid 
suppressor cells may confer resistance to immune checkpoint directed therapy.  An anti-MMP9 
directed murine surrogate of andecaliximab has shown significant anti-tumor activity in models 
in which MMP9 is produced by infiltrating myeloid cells. Its anti-tumor activity is associated 
with reduction of tumor-associated fibrillar collagen and alterations in the immune cell transcript 
profile in the treated tumors. Inhibition of PD-1 on T cells in the presence of andecaliximab may 
allow for greater infiltration of activated lymphocytes into the tumor and augment the anti-tumor 
effect offered by a PD-1 inhibitor alone.  This potential synergy provides rationale for combining
andecaliximab and nivolumab in subjects with advanced gastric/GEJ adenocarcinoma (see 
Figure 1-3).
Figure 1-3.
Hypothesis for synergy between andecaliximab and nivolumab
Hypothesis for the combination of andecaliximab with nivolumab (figure adapted from Gajewski et al Nature Immunology, 
{Gajewski 2013}). Treatment with andecaliximab could convert “type b” tumors with dense fibrotic stroma, high myeloid 
suppressor cell contact, and deficiency of T-cell infiltration into “type a” tumors in which T-cell entry is enabled via remodeling 
of the microenvironment and re-balancing of suppressive myeloid-derived cytokines and chemokines. T cells in “type a” tumors 
are susceptible to checkpoint inhibition, which is overcome by treatment with nivolumab.


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1.4.
Risk/Benefit Assessment for the Study
In Western subjects with advanced solid tumors, there were no DLTs observed with 
andecaliximab monotherapy doses of up to 1800 mg Q2W. Additionally, combining 
andecaliximab 800 mg IV Q2W or 1200 mg Q3W with available chemotherapy regimens in 
non-Japanese subjects with advanced solid tumors enrolled in Study GS-US-296-0101 appeared
safe and well-tolerated.  
The safety and efficacy profile of SP and SOX in Japanese subjects with advanced gastric/GEJ 
adenocarcinoma has been established {Koizumi 2008, Yamada 2015}.  Phase 1 data combining 
andecaliximab and mFOLFOX6 in advanced gastric/GEJ adenocarcinoma suggests clinical 
activity with an acceptable safety profile {Shah 2017}.  These data support combining 
andecaliximab with fluoropyrimidine and platinum doublets commonly used in Japanese subjects 
with gastric/GEJ adenocarcinoma. 
Phase 3 data demonstrating activity and safety of nivolumab monotherapy in Asian subjects with 
previously treated advanced gastric/GEJ adenocarcinoma {Kang 2017}, preclinical data 
suggesting potential synergy between andecaliximab and nivolumab, and safety data from the 
ongoing Phase 2 Study GS-US-296-2013 combining nivolumab and andecaliximab in a similar 
non-Japanese population (subjects with inoperable locally advanced or metastatic gastric/GEJ 
adenocarcinoma who have progressed on at least 1 prior systemic therapy or line of treatment for 
unresectable/metastatic disease) support evaluating the combination in a Japanese population. 
Thus, the favorable nonclinical and clinical data outweigh the risks associated with 
administration of andecaliximab and hence support the evaluation of andecaliximab as 
monotherapy or in combination with anti-cancer agents in Japanese subjects with advanced 
gastric/GEJ adenocarcinoma.
1.5.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2. 
OBJECTIVES 
The primary objective of this study is: 
Final 
Arnendment3 
• 
To characterize the safety and tolerability of andecaliximab as monotherapy and in 
combination with anti-cancer agents in Japanese subjects with inoperable advanced or 
recunent gastric or GEJ adenocarcinoma 
The secondaiy objectives of this study ai·e: 
• 
To chai·acterize the PK of andecaliximab 
• 
To evaluate the fo1mation of anti-andecaliximab antibodies 
The explorato1y objectives of this study ai·e: 
I 
I 
I 
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3.
STUDY DESIGN
3.1.
Endpoints
The endpoints for this study are described in Sections 8.1.2, 8.1.3, and 8.1.4.
3.2.
Study Design
This is a Phase 1b, open-label, multicenter study to evaluate the safety and tolerability of
andecaliximab as monotherapy and in combination with anti-cancer agents in Japanese subjects 
with inoperable advanced or recurrent gastric or GEJ adenocarcinoma. The study will comprise 
4 cohorts, 1 monotherapy cohort, and 3 combination therapy cohorts. 
Cohort 1 is andecaliximab monotherapy. Cohort 2 is combination therapy of andecaliximab with 
SP. Cohort 3 is combination therapy of andecaliximab with SOX. Cohort 4 is combination 
therapy of andecaliximab and nivolumab. Up to 38 subjects are expected to be enrolled in the 
study.
For Cohorts 1, 2, and 4, computed tomography (CT) or magnetic resonance imaging (MRI) scans 
will be performed every 8 weeks to evaluate response to treatment by RECIST v1.1. For 
Cohort 4, response to treatment will also be evaluated using immune-related response criteria 
recommendations {Wolchok 2009}.
For Cohort 3, CT or MRI scans will be performed every 9 weeks to evaluate response to 
treatment by RECIST v1.1.
Cohort 1: Andecaliximab Monotherapy 
Up to 6 Japanese subjects with inoperable advanced or recurrent gastric or GEJ tumors will be 
enrolled to receive andecaliximab 800 mg via IV infusion over approximately 30 (± 5) minutes
Q2W until disease progression.
The DLT assessment window is 28 days. The safety and tolerability of the 800 mg dose will be 
assessed after all 6 subjects have been followed for at least 28 days after the first infusion of 
andecaliximab. If 2 or more subjects within the cohort of 6 subjects experience DLTs during the 
first 28 days of andecaliximab dosing, up to 6 additional subjects will be enrolled at a reduced 
dose of 600 mg Q2W. If 2 additional DLTs occur at 600 mg, andecaliximab will be considered 
unsafe and will be discontinued. Therefore, a total of up to 12 subjects may be enrolled in
Cohort 1.
A DLT is a toxicity defined below, considered possibly related to andecaliximab occurring 
during the DLT assessment window (Day 1 through Day 28).

Grade 4 neutropenia (absolute neutrophil count [ANC] < 500/µL) for > 7 days, or febrile 
neutropenia (per the National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE) Version 4.03 definition) regardless of duration


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
Primary prophylaxis with granulocyte-colony stimulating factor (G-CSF) is not permitted 
during the first cycle of study treatment.  G-CSF may be used at any time at the discretion of 
the investigator in response to treatment emergent neutropenia.  Subjects who develop 
Grade 4 neutropenia related to andecaliximab will be considered a DLT (subjects may 
receive G-CSF at the discretion of the investigator in response to treatment emergent 
neutropenia).

Grade 4 thrombocytopenia, Grade 3 thrombocytopenia associated with bleeding, or Grade 3 
or 4 thrombocytopenia requiring platelet transfusion

Grade 3 or 4 non-hematologic toxicity (excluding rash, nausea, diarrhea, and vomiting if 
controlled with standard supportive care)

Non-hematologic toxicity of ≥ Grade 2 (at any time during treatment) that, in the judgment of 
the investigator and the medical monitor, is dose-limiting

Treatment delay of > 14 days due to unresolved toxicity

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 adverse event (AE) should be assessed as a DLT necessitating dose 
reduction
After all 6 subjects in Cohort 1 have completed the 28-day DLT assessment window and 1 or 
0 out of 6 subjects experienced DLTs, an internal SRT will conduct a review of the safety and 
PK data from all subjects prior to proceeding with the combination therapy cohorts to evaluate 
andecaliximab with other anti-cancer agents.
The SRT completed their review of all available clinical safety and PK data for 6 DLT-evaluable 
subjects in Cohort 1 on 11 May 2017 and determined the dose for the combination therapy 
cohorts (Cohorts 2 and 4) to be 800 mg andecaliximab Q2W. See Section 1.3 for rationale of 
dose selection for Cohort 3 (1200 mg andecaliximab Q3W). The internal SRT consisted of 
Gilead study team members including the Medical Monitor, representatives from Clinical 
Operations, Drug Safety and Public Heath (DSPH), and Biostatistics. 
Cohorts 2, 3 and 4: Andecaliximab Combination Therapy Cohorts
Japanese subjects with inoperable advanced or recurrent gastric or GEJ tumors will be enrolled 
in each combination therapy cohort to receive andecaliximab in combination with anti-cancer 
agents. Dosage and frequency of treatment in these cohorts will be as follows: 

Cohort 2: combination therapy andecaliximab and SP
Andecaliximab 800 mg via IV infusion over approximately 30 (± 5) minutes Q2W until 
disease progression. The dose is based on the safety data from Cohort 1. Andecaliximab
treatment will be administered in 28-day cycles.  


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S-1 administered orally twice daily: dosage and regimen will be based on subject
condition, investigator discretion, institutional practice and/or the in-country label (see 
Figure 3-1)
Cisplatin administered by IV infusion on Day 8 of every 5 weeks: dosage and regimen 
will be based on subject condition, investigator discretion, institutional practice and/or
the in-country label (see Figure 3-1)
Up to 6 subjects will be enrolled in this cohort
Figure 3-1.
Cohort 2 (Combination Therapy Andecaliximab and SP) Proposed 
Regimen

Cohort 3: combination therapy andecaliximab and SOX
Andecaliximab 1200 mg via IV infusion over approximately 30 (± 5) minutes Q3W until 
disease progression. The dose is based on safety data from Cohort 1 and other ongoing 
Phase 1 studies of andecaliximab. Andecaliximab treatment will be administered in 
21-day cycles.  
S-1 administered orally twice daily at 80 mg/day for body surface area (BSA) < 1.25m2, 
100 mg/day for BSA ≥1.25 to < 1.5m2, and 120 mg/day for BSA ≥ 1.5m2 for the first 
14 days of the 21-day cycle (See Figure 3-2)
Oxaliplatin administered by IV infusion at 100 mg/m2 over 2 hours on Day 1 of each 
21-day cycle (See Figure 3-2)
Up to 10 subjects will be enrolled in this cohort
  
 
  
  


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Figure 3-2.
Cohort 3 (Combination Therapy Andecaliximab and SOX) Regimen

Cohort 4: combination therapy andecaliximab and nivolumab
Andecaliximab 800 mg via IV infusion over approximately 30 (± 5) minutes Q2W until 
disease progression. The dose is based on safety data from Cohort 1. Andecaliximab
treatment will be administered over in 28-day cycles.
Nivolumab 3mg/kg Q2W via IV infusion over 60 (± 5) minutes following the completion 
of andecaliximab administration (See Figure 3-3). Dose is adjusted if the weight changes 
more than 10% from the baseline dosing weight.
Up to 10 subjects will be enrolled in this cohort 
Figure 3-3.
Cohort 4 (Combination Therapy Andecaliximab and Nivolumab) 
Regimen
The cohort dose levels for andecaliximab and associated combination anti-cancer agents are 
summarized below in Table 3-1: 
  
  
  
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 3-1.
Cohort Dose Levels 
Cohort 
Number of 
Subjects
Andecaliximab Dose
Andecaliximab 
Dosing Interval
Combination 
Anti-Cancer Agent(s)
1
6 to 12
800 mg or 600 mg
Q2W
N/A
2
Up to 6
800 mg 
Q2W
SP
3
Up to 10
1200 mg
Q3W
SOX
4
Up to 10
800 mg
Q2W
Nivolumab
Abbreviations: SOX = S-1 and oxaliplatin; SP = S-1 and cisplatin; Q2W = every 2 weeks; Q3W = every 3 weeks
3.3.
Study Treatments
Subjects meeting eligibility will receive andecaliximab by IV infusion over approximately 
30 (± 5) minutes. Administration of SP, SOX and nivolumab for the combination therapy cohorts
are described in Section 3.2.
Safety and efficacy assessments will occur on an outpatient basis, and will include the following: 
assessment of tumor response, physical examinations (PEs), vital signs, electrocardiograms
(ECGs), collection of blood samples (for routine safety laboratory analyses, andecaliximab PK, 
anti-andecaliximab antibodies, tumor markers, thyroid function tests (for Cohort 4 only: 
combination therapy andecaliximab and nivolumab), and biomarkers at applicable visits), urine 
pregnancy, urinalysis, and assessment of AEs at the protocol specified time points.
In the combination therapy cohorts, tolerability will be determined by assessing the frequency of 
andecaliximab interruptions and dose modifications.
3.4.
Duration of Treatment
The screening period will be up to 28 days. For Cohorts 1, 2, and 4, each cycle will be 28 days
and for Cohort 3, each cycle will be 21 days.
A subject who does not show evidence of disease progression by clinical assessment or by CT or 
MRI may continue receiving andecaliximab until disease progression (clinical or radiographic), 
unacceptable toxicity, withdrawal of consent, or other reasons specified in Section 3.5. CT or 
MRI for assessment of tumor status will be conducted every 8 weeks for Cohorts 1, 2, and 4, and 
every 9 weeks for Cohort 3. However, tumor response may be assessed prior to the specified 
every 8- or 9-week time point if clinically indicated. 
3.5.
Discontinuation Criteria from Study Treatment
Andecaliximab, S-1, cisplatin, oxaliplatin, and nivolumab can be discontinued for any of the 
following reasons: 

Adverse events 

Pregnancy


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
Investigator decision to remove the subject from the study treatment, in consultation with 
Gilead medical monitor

Disease progression

Intercurrent illness, that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree

Initiation of non-study specific anti-neoplastic therapy in the absence of progression

Subject request to discontinue treatment 

Withdrawal of consent 
A subject may withdraw consent solely from active participation in the study but still 
participate in follow up for disease progression and survival  

Death

Discontinuation of the study at the request of Gilead, a regulatory agency, or an institutional 
review board or independent ethics committee (IRB/IEC)

Loss to follow-up 

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

In addition to the drug discontinuation criteria above, nivolumab may be discontinued for any 
reason specified in the prescribing information. 
3.6.
Premature Discontinuation from Study Treatment
If a subject has discontinued all study treatments prior to definitive disease progression, the 
subject shall remain on study until at least 1 of the criteria for discontinuation from study is met 
(Section 3.7). Every attempt should be made to keep the subject in the study and continue to 
perform tumor evaluation by CT or MRI every 8 weeks (Cohorts 1, 2, and 4) or every 9 weeks 
(Cohort 3) until disease progression. If this is not possible or acceptable to the subject or 
investigator, the subject may be withdrawn from the study. It is recommended that the 
investigator consults with the medical monitor prior to removing the subject from study for any 
reason except subject withdrawal of consent.
3.7.
Discontinuation Criteria from Study
Subject study participation may be ended due to any of the following reasons: 

Initiation of non-study specific anti-neoplastic therapy in the absence of progression

Disease progression


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
Intercurrent illness, that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree

Withdrawal of consent 
A subject may withdraw consent solely from active participation in the study but 
participate in follow up for survival. 

Non-compliance with study treatments or protocol violation

Investigator decision to remove the subject from the study treatment, in consultation with 
Gilead medical monitor

Death

Discontinuation of the study at the request of Gilead, a regulatory agency, or an IRB/IEC

Loss to follow up 
3.8.
End of Study
End of study (EOS) assessments will be completed when the subject meets at least 1 of the 
criteria for study discontinuation in Section 3.7.
3.9.
Long-Term Follow-Up for Overall Survival
After EOS, long-term follow up (LTFU) will be initiated for subjects who discontinue from 
study due to reasons other than death. The subject shall remain on LTFU for OS until:

Death

Withdrawal of consent to participate in LTFU

Lost to follow up

End of LTFU period
Every attempt should be made to keep the subject in the LTFU for OS. See Section 6.10.2 for 
additional information. 
The end of the trial will be defined as when all subjects have completed LTFU or discontinued 
their participation the study due to death, withdrawal of consent or lost to follow up. 
3.10.
Source Data
The subject identification number assigned by the interactive web response system (IWRS) is 
considered source data. 


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3.11. 
3.11.1. 
Bio marker Testing 
Biomarker Samples to Address the Study Objectives 
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The following biological specimens will be collected in this study and will be used to investigate 
andecaliximab accumulation in tumor tissue and to understand the andecaliximab mechanism of 
action. Additionally, biomarkers in tumor tissue may be coITelated with circulating biomarkers. 
The specific analyses will include, but will not be limited to, the biomarkers and assays listed in 
Table 3-2 below. Because biomarker science is a rapidly evolving area of investigation, it is not 
possible to specify prospectively all tests that will be done on the specimens provided. The 
testing outlined below is based upon the cuITent state of scientific knowledge. It may be modified 
during or after the end of the study to remove tests no longer indicated and/or to add new tests 
based upon the growing state of aii knowledge. Any future testing must be approved by local 
authorities as applicable according to specific local regulations. 
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Table 3-2. 
Biomarker Objectives and Testing 
COHORTS 1 (Andecaliximab Monotherapy) AND 4 (Combination Therapy Andecaliximab and Nivolumab) 
Sample Type 
Tumor Tissue Biopsies 
• 
PRIOR TO FIRST 
DOSE Required 
• 
6WEEKS(±l 
WEEK) (Cohort 4) or 
6 WEEKS(+ 5 DAYS) 
(Cohort 1) Required 
(from same anatomical 
location as 1
st biopsy) 
I 
Endoscopic gastric samples 
(minimum 4, but 6-8 
encouraged) per time-point; 
metastasis to liver or lymph 
nodes acceptable as multiple 
pass 18g needle biopsy as 
described in the laboratory 
manual 
Non-Diseased Gastric tissue 
biopsy 
• 
PRIOR TO FIRST 
DOSE Required 
Endoscopic samples 
(minimum 4, but 6-8 
encouraged) to be processed 
as described in the laboratory 
manual; DO NOT collect if 
stomach is free of tumor 
Tumor Tissue - Archival 
CONFIDENTIAL 
Objective 
To provide a baseline for 
phannacodynamic and resistance 
biomarkers and investigate biomarkers 
at baseline that associate with 
response to andecaliximab plus 
nivolumab in Cohort 4 
To evaluate phrumacodynarnics and 
mechanism of action of andecaliximab 
in tumor tissue 
Required to provide a normal 
comparison for tumor tests, including 
somatic tumor mutations 
To evaluate biomarkers in primary 
disease in comparison to metastatic 
disease 
Page46 
Test 
Tests listed below may be used for all or 
some of the tumor tissue biopsies: 
MMP9, PD-Ll, other MMPs, Immune 
Cells and proteins by IHC and other 
methods 
Activity ofMMP9 
Gene expression patterns (RNA) for 
tumor subtyping and microenvironment 
characterization, such as IFNy and 
immune cell signatures 
Somatic tumor mutations 
MMP9, other MMPs, Immune Cells and 
proteins by IHC and other methods 
Activity ofMMP9 
Gene expression patterns for tumor 
subtyping and microenvironment 
characterization 
MMP9, PD-Ll, other MMPs and Immune 
Cells by IHC and other methods 
Gene expression patterns for 
microenvironment chru·acterization 
Somatic tumor mutations 
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COHORTS 1 (Andecaliximab Monotherapy) AND 4 (Combination Therapy Andecaliximab and Nivolumab) 
Sample Type 
Objective 
Test 
Endoscopic evaluation 
To evaluate new instances of or 
• 
PRIOR TO FIRST 
progression of existing gastritis and 
DOSE Required 
dysplasia before biopsies 
• 
At time of on-
treatment biopsy 
Required 
DO NOT perfo1m if stomach 
is free of tumor 
Blood 
To evaluate phaimacodynamics of 
MMP9 cleavage products such as ClM 
andecaliximab 
Circulating MMP9 protein 
To evaluate immune cell activation 
Circulating cytokines and inflanunat01y 
markers 
To evaluate circulating immune cells 
lllllllune monitoring assay by flow 
cytometty 
To evaluate other biomai·kers of 
Circulating growth factors such as VEGF 
andecaliximab activity 
To evaluate less-invasive methods for 
Circulating tumor DNA 
monitoring response and resistance 
Circulating RNA species 
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COHORTS 2 (Combination Therapy Andecaliximab and SP) AND 
3 (Combination Therapy Andecaliximab and SOX) 
Sample Type 
Tumor Tissue Biopsies 
• 
PRIOR TO FIRST 
DOSE Required 
• 
AT EOSwith 
documented disease 
progression Required 
Endoscopic gastric samples 
(minimum 4, but 6-8 
encouraged) per time-point; 
metastasis to liver or lymph 
nodes acceptable as multiple 
pass 18g needle biopsy as 
described in the laboratory 
manual 
Non-Diseased Gastric tissue 
biopsy 
• 
PRIOR TO FIRST 
DOSE Required 
Endoscopic samples 
(minimum 4, but 6-8 
encouraged) to be processed 
as described in the laboratory 
manual; DO NOT collect if 
stomach is free of tumor 
Tumor Tissue - Archival 
Endoscopic evaluation 
• 
PRIOR TO FIRST 
DOSE Required 
DO NOT perform if stomach 
is free of tumor 
CONFIDENTIAL 
Objective 
To provide a baseline for 
phannacodynamic and resistance 
biomarkers 
Required to provide a no1mal 
comparison for tumor tests, including 
somatic tumor mutations 
To evaluate biomarkers in primary 
disease in comparison to metastatic 
disease 
To evaluate gastritis and dysplasia 
before biopsies 
Page48 
Test 
Tests listed below may be used for all or 
some of the tumor tissue biopsies: 
MMP9, other MMPs, Immune Cells and 
proteins by IHC and other methods 
Activity ofMMP9 
Gene expression pattems for tumor 
subtyping and microenvirorunent 
characterization, such as IFNy and 
immune cell signatures 
Somatic tumor mutations 
MMP9, other MMPs, Immune Cells and 
proteins by IHC and other methods 
Activity ofMMP9 
Gene expression pattems for tumor 
subtyping and microenvirorunent 
characterization 
MMP9, other MMPs and Immune Cells 
by IHC and other methods 
Gene expression pattems for 
microenvirorunent characterization 
Somatic tumor mutations 
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COHORTS 2 (Combination Therapy Andecaliximab and SP) AND 
3 (Combination Therapy Andecaliximab and SOX) 
Sample Type 
Objective 
Test 
Blood 
To evaluate phrumacodynamics of 
MMP9 cleavage products such as ClM 
andecaliximab 
Circulating MMP9 protein 
To evaluate immune cell activation 
Circulating cytokines and inflrunmat01y 
markers 
To evaluate circulating immune cells 
lllllllune monitoring assay by flow 
cytometiy 
To evaluate other biomarkers of 
Circulating growth factors such as VEGF 
andecaliximab activity 
To evaluate less invasive methods for 
Circulating tumor DNA isolation and 
monitoring response and resistance 
sequencing 
Circulating RNA species 
Abbl'eviations: DNA = deoxyribonucleic acid; ELISA = enzyme-linked inununosorbent assay; EOT = end of treatment; 
IFNy = interferon gamma; IHC = inununohistochem.istiy; MMP = man-ix metalloproteinase; PD-Ll = progralllllled death-ligand 
1; RNA = ribonucleic acid; VEGF = vascular endothelial growih factor 
3.11.2. 
Biomarker Samples for Optional Future Research 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Up to 38 subjects will be enrolled. The target population is Japanese subjects 20 years of age
with histologically confirmed inoperable advanced or recurrent gastric or GEJ adenocarcinoma. 
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 20 years of age
2) Subjects must have been born in Japan and must not have lived outside of Japan for a period 
>1 year in the 5 years prior to Day 1
3) Subjects must be able to trace their maternal and paternal ancestry of parents and 
grandparents as ethnically Japanese
4) Histologically confirmed inoperable advanced gastric adenocarcinoma (including 
adenocarcinoma of the GEJ) or relapsed gastric adenocarcinoma
5) Cohorts 1 (andecaliximab monotherapy), 2 (combination therapy andecaliximab and SP) and 
3 (combination therapy andecaliximab and SOX): Human Epidermal Growth Factor 
Receptor 2 (HER2)-negative tumor (primary tumor or metastatic lesion). Enrollment in 
Cohort 4 (combination therapy andecaliximab and nivolumab) is not restricted by HER2 
status (subjects with HER2-positive, HER2-negative, or unknown HER2 status are eligible).
6) Cohort 1 (andecaliximab monotherapy): Prior antitumor therapy or cytotoxic chemotherapy 
is acceptable. Subjects who are not eligible to receive standard treatments should enroll on 
the study. All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 (or 
baseline) before the start of andecaliximab dosing (with the exception of alopecia [Grade 1 or 
2 permitted] and neurotoxicity [Grade 1 or 2 permitted])
7) Cohorts 2 (combination therapy andecaliximab and SP) and 3 (combination therapy 
andecaliximab and SOX): Prior antitumor therapy or cytotoxic chemotherapy for metastatic 
disease is not acceptable. Subjects must be chemo-naive in the metastatic setting. Subjects 
who relapse during adjuvant chemotherapy or within 180 days after adjuvant chemotherapy 
for their gastric cancer should not be enrolled. 
8) Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
9) Life expectancy of > 3 months in the opinion of the investigator


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10) Adequate baseline organ function (within 28 days prior to Day 1) as shown in the following 
able: 
Organ System
Parameter
Required Value
Hematopoietic
ANC
≥ 1.5 x 109/L
Platelets
≥ 100 x 109/L
Hemoglobin
Cohorts 1-3: ≥8.0 g/dL (not RBC transfusion dependent)
Hepatic
Serum total or conjugated 
bilirubin
≤1.5 x ULN
Serum AST and ALT
≤ 2.5 x ULN (if liver metastases are present, ≤ 5 x ULN)
Renal
Serum Creatinine
Cohort 1: ≤ 1.5 x ULN
Cohorts 2 and 3: ≤ 1.0 x ULN
Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase;
RBC = red blood cell; ULN = upper limit of normal
11) Coagulation: International Normalized Ratio (INR) ≤1.5 (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 andecaliximab). Subjects on 
low molecular weight heparin will be allowed
12) For female subjects of childbearing potential, willingness to use a protocol-recommended 
method of contraception from the screening visit throughout the study treatment period and 
defined periods following the last dose of andecaliximab and/or anti-cancer agent(s) (See
Appendix 9)
13) 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 andecaliximab, throughout the study treatment period, and defined periods following the 
last dose of andecaliximab and/or anti-cancer agent(s), and to refrain from sperm donation 
from the start of andecaliximab, throughout the study treatment period, and defined periods 
following the last dose of andecaliximab and/or anti-cancer agent(s) (See Appendix 9)
14) Willingness to comply with scheduled visits, drug administration plan, imaging studies, 
laboratory tests, other study procedures, and study restrictions
15) Evidence of a personally signed informed consent form
16) In addition to the applicable criteria above, subjects in Cohort 4 (combination therapy 
andecaliximab and nivolumab) must meet all of the following inclusion criteria to be eligible 
for participation in this study:
a) Measureable gastric or GEJ adenocarcinoma according to RECIST v1.1


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b) Subject must have progressed on at least 1 prior systemic therapy or line of treatment for 
unresectable/metastatic disease. All toxicities attributed to prior anti-cancer therapy other 
than alopecia or fatigue must have resolved to Grade ≤1 (NCI CTCAE Version 4) or 
baseline
c) Adequate baseline organ function (within 28 days prior to Day 1) as shown in the 
following table: 
Organ System
Parameter
Required Value
Hematopoietic
ANC
≥ 1.5 x 109/L
Platelets
≥ 100 x 109/L
Hemoglobin
≥9.0 g/dL
Hepatic
Serum total or conjugated 
bilirubin
≤1.5 x ULN
Serum AST and ALT
≤ 2.5 x ULN (if liver metastases are present, ≤ 5 x ULN)
Renal
Creatinine Clearance
Creatinine clearance (CLcr) ≥60 mL/min, estimated based on the 
Cockroft-Gault formula or measured based on 24 hour urine 
collection or other reliable method
Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; 
CLcr = creatinine clearance; RBC = red blood cell; ULN = upper limit of normal
d) Subjects not receiving anticoagulant medication must have an activated partial 
thromboplastin (aPTT) ≤ 1.5 x ULN. The use of full-dose oral or parenteral 
anticoagulants is permitted as long as the aPTT is within therapeutic limits (according to 
the medical standard in the institution) and the subject has been on stable dose of 
anticoagulants for at least 1 week at the time of enrollment 
e) Thyroid function tests (thyroid-stimulating hormone (TSH), T3, free T4) should be 
within normal limits. Subjects with underlying thyroid disease are eligible if they are 
receiving appropriate medication and are clinically stable.
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 a 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. Enrollment of lactating females after discontinuation of breastfeeding 
is not acceptable.
3) Subjects with known central nervous system (CNS) metastases, unless metastases are treated 
and stable and the subject does not require systemic steroids
4) Radiotherapy within 28 days of Day 1; subjects given palliative radiotherapy to peripheral 
sites (eg, bone metastasis) may enter the study before 28 days have elapsed if subject has
recovered from any acute, reversible effects


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5) 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 Day 1
6) History of major surgery within 28 days prior to Day 1
7) Serious systemic fungal, bacterial, viral, or other infection that is not controlled or requires 
IV antibiotics
8) Cohort 1 (andecaliximab monotherapy): Anti-tumor therapy (chemotherapy, antibody 
therapy, molecular targeted therapy) within 28 days or 5 half-lives, whichever is shorter, of 
Day 1 (6 weeks for nitrosoureas, mitomycin C, or molecular agents with t½ > 10 days)
9) Clinically significant bleeding within 28 days of Day 1
10) Subjects known to be positive for human immunodeficiency virus (HIV), hepatitis C
infection (per local standard diagnostic criteria), or acute or chronic hepatitis B infection 
(per local standard diagnostic criteria) 
11) Known hypersensitivity to any of the study drugs or components or to Chinese hamster ovary 
cell products or to recombinant human or humanized antibodies
12) History of a concurrent or second malignancy except for adequately treated local basal cell or 
squamous cell carcinoma of the skin; cervical carcinoma in situ; superficial bladder cancer; 
asymptomatic prostate cancer without known metastatic disease, with no requirement for 
therapy or requiring only hormonal therapy, and with normal prostate-specific antigen for 
≥1 year prior to Day 1; adequately treated Stage 1 or 2 cancer currently in complete 
remission; or any other cancer that has been in complete remission for ≥ 5 years
13) Known alcohol or drug abuse or any other medical or psychiatric condition which 
contraindicates participation in the study 
14) Subject is expected to require any form of systemic or localized antineoplastic therapy while 
on study
15) In addition to the applicable criteria above, subjects in Cohort 4 (combination therapy 
andecaliximab and nivolumab) who meet any of the following exclusion criteria will not be 
enrolled in this study:
a) Subjects who have received only neoadjuvant or adjuvant therapy for gastric 
adenocarcinoma
b) Chronic daily treatment with oral corticosteroids (dose of > 10 mg/day prednisone 
equivalent) or other immunosuppressive medications within 14 days of Day 1. Inhaled 
steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are 
allowed   


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c) Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy) within 
28 days or 5 half-lives, whichever is shorter, of Day 1 (6 weeks for nitrosoureas, 
mitomycin C, or molecular agents with t½ > 10 days)
d) Prior treatment with anti-CTLA-4 agents (eg, ipilimumab), anti-PD-1 or anti-PD-L1 
agents (eg, pembrolizumab, nivolumab, atezolizumab), anti-PD-L2 agents, anti-MMP 
agents, or other immunomodulatory therapies
e) Prior therapy with anti-tumor vaccines or other immuno-modulatory antitumor agents 
f)
Current or history of pneumonitis or interstitial lung disease
g) Active known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes 
mellitus, residual hypothyroidism requiring hormone replacement, or conditions not 
expected to recur in the absence of an external trigger are permitted to enroll
h) History of bone marrow, stem cell, or allogeneic organ transplantation


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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 via an interactive web response 
system (IWRS). Once eligibility is confirmed subjects will be assigned a unique subject number
via IWRS. The IWRS will be used to maintain a central log documenting screening, to 
implement enrollment, to assess current inventories of andecaliximab and nivolumab, to initiate 
necessary resupply of drug and to document discontinuation of drug. 
This is an open-label study.
The IWRS will assign kit numbers and provide instructions for dispensing of andecaliximab 
(Cohorts 1-3) or andecaliximab and nivolumab (Cohort 4). It is anticipated that subjects will 
usually begin treatment immediately after enrollment in IWRS. 
All baseline tests and procedures must be completed prior to the administration of the first dose
of andecaliximab 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 Study Treatments
5.2.1.
Formulation
5.2.1.1.
Andecaliximab
Andecaliximab is formulated as a sterile, aqueous buffered solution containing acetate at pH 5.0, 
with sucrose and polysorbate 20 added for stabilization. Each 10 mL vial contains 400 mg 
andecaliximab at a concentration of 40 mg/mL.
5.2.1.2.
S-1
S-1 is commercially sourced. Additional information regarding the formulation can be found in 
the current prescribing information. 
5.2.1.3.
Cisplatin
Cisplatin is commercially sourced. Additional information regarding the formulation can be 
found in the current prescribing information. 
5.2.1.4.
Oxaliplatin
Oxaliplatin is commercially sourced. Additional information regarding the formulation can be 
found in the current prescribing information. 


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5.2.1.5.
Nivolumab
Nivolumab is commercially sourced. Additional information regarding the formulation can be 
found in the current prescribing information. 
5.2.2.
Packaging and Labeling
Andecaliximab (labeled as GS-5745) will be supplied in 10 mL glass vials with coated 
elastomeric stoppers and aluminum crimp overseals with a flip-off cap.
Andecaliximab to be distributed to centers in Japan shall be labeled to meet applicable 
requirements of the local regulations as applicable. 
S-1, cisplatin, and oxaliplatin to be used in this study will be obtained from available commercial 
supplies at each study site. 
Commercially available nivolumab will be used for this study and provided by Gilead. 
Nivolumab to be distributed to centers in Japan shall be labeled to meet applicable requirements 
of the local regulations.
5.2.3.
Storage and Handling
Andecaliximab should be stored at 2°C - 8 ºC. Storage conditions are specified on the 
andecaliximab label. Until dispensed to subjects, all drug should be stored in a securely locked 
area, accessible only to authorized site personnel. To ensure stability and proper identification, 
the drug should be stored in the containers and packaging in which it was supplied until
administration to the subjects.
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure when handling.
Commercial product of S-1, cisplatin oxaliplatin, and nivolumab will be used for the study. 
Further information regarding storage, handling, and preparation are available in the prescribing 
information for commercial products.
Information regarding preparing andecaliximab IV infusions can be found in the pharmacy 
manual. 
5.3.
Dosage and Administration of Andecaliximab, S-1, Cisplatin, Oxaliplatin,
and Nivolumab
The target dose of andecaliximab will be administered by preparing a sterile IV solution. The 
target dose of 600 mg or 15 mL of andecaliximab 40 mg/mL will be prepared from two 10 mL 
vials. The target dose of 800 mg or 20 mL of andecaliximab 40 mg/mL will be prepared from 
two 10 mL vials. The target dose of 1200 mg or 30 mL of andecaliximab 40 mg/mL will be 
prepared from three 10 mL vials. Andecaliximab will be administered via IV infusion over 
approximately 30 (± 5) minutes at the research clinic by a qualified staff member. 


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For Cohort 2, combination therapy andecaliximab and SP: Andecaliximab 800 mg will be 
administered via IV infusion over approximately 30 (± 5) minutes on Days 1 and 15 of each 
28-day cycle. S-1 will be administered orally twice daily with the dosage and regimen based on 
subject condition, investigator discretion, institutional practice and/or the in-country label. 
Cisplatin will be administered by IV infusion on Day 8 of every 5 weeks with the dosage and
regimen based on subject condition, investigator discretion, institutional practice and/or the 
in-country label. 
For Cohort 3, combination therapy andecaliximab and SOX: Andecaliximab 1200 mg will be 
administered via IV infusion over approximately 30 (± 5) minutes on Days 1 of each 21-day 
cycle. S-1 will be administered orally twice daily at 80 mg/day for BSA < 1.25m2, 100 mg/day 
for BSA ≥1.25 to < 1.5m2, and 120 mg/day for BSA ≥ 1.5m2 for the first 14 days of the 21-day 
cycle. Oxaliplatin will be administered by IV infusion at 100 mg/m2 over 2 hours on Day 1 of 
each 21-day cycle. 
For Cohort 4, combination therapy andecaliximab and nivolumab: Andecaliximab 800 mg will 
be administered via IV infusion over approximately 30 (± 5) minutes on Days 1 and 15 of each 
28-day cycle. Following administration of andecaliximab, nivolumab will be administered via IV 
infusion over approximately 60 (± 5) minutes on Day 1 and 15 of each 28 day cycle. Dose is 
adjusted if the weight changes more than 10% from the baseline dosing weight.
Documentation of andecaliximab, S-1, cisplatin, oxaliplatin, and nivolumab administration will 
be noted on the electronic case report form (eCRF) and in the source documentation.
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.
Details of preparing and administering andecaliximab and nivolumab are included in the 
Pharmacy Binder provided by Gilead.
5.3.1.
Dose Interruption and Reduction
If an AE is attributed to only 1 drug (ie, study drug or other anti-cancer agent), the investigator’s 
discretion will be used to determine if 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. 
5.3.1.1.
Andecaliximab
In Cohort 1 (andecaliximab monotherapy), if a subject experiences a DLT (see Section 3.2 for 
the definition of a DLT), andecaliximab 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 andecaliximab at 50% of the originally assigned dose level. If the subject 
experiences a recurrence of the toxicity meeting criteria for DLT after restarting andecaliximab 


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or if the toxicity does not resolve within 28 days, treatment with andecaliximab will be 
discontinued. Alternatively, if there is no recurrence of the toxicity, the dose of andecaliximab
may be increased to 100% of the originally assigned level after discussion with the medical 
monitor.
Dose modification or delay of andecaliximab following adverse events that do not meet the 
criteria for a DLT (either during the DLT window or afterwards for subjects in Cohort 1) may be 
permitted at the discretion of the Investigator after discussion with the medical monitor.
For subjects enrolled in the combination therapy cohorts (Cohorts 2-4), dose delay of 
andecaliximab following adverse events may be permitted at the discretion of the Investigator 
after discussion with the medical monitor. Dose modification of andecaliximab is not permitted 
in the combination therapy cohorts without prior discussion with the medical monitor. 
Additionally, in the combination therapy cohorts, subjects in whom anti-cancer agent (SP, SOX, 
or nivolumab) administration must be delayed may continue to receive andecaliximab while 
anti-cancer agent(s) are held, in the absence of disease progression. If anti-cancer agent treatment 
(SP, SOX, or nivolumab) is permanently discontinued, andecaliximab treatment must be 
permanently discontinued. Subjects enrolled in Cohorts 2 and 3 may permanently discontinue 1 
of the 2 anti-cancer agents (ie, cisplatin or oxaliplatin) for reasons other than disease progression, 
and still continue treatment with S-1 and andecaliximab until they meet 1 of the discontinuation 
criteria in Protocol Section 3.5 or 3.7. 
Subjects who discontinue andecaliximab for reasons other than disease progression may continue 
to receive anti-cancer agent treatment (SP, SOX, or nivolumab) until disease progression. 
If the subject was not receiving andecaliximab at the time disease progression was documented
(eg, due to reversible toxicity), after discussion with the medical monitor, andecaliximab may be 
re-started if the criteria for resuming treatment as described in Section 5.3.1.1 are met and the 
investigator feels it is in the subject’s best interest to do so.
Dose delay of andecaliximab due to holidays, site closures and subject availability may be 
permitted after discussion with the medical monitor. The reason for interruption or delay should 
be documented in the subject's study record.
5.3.1.2.
S-1 and Cisplatin
Administration of S-1 and cisplatin, along with anti-emetic administration and pre and post 
anti-cancer agent hydration must follow the institutional practice for these agents and the 
in-country label. Dose reductions of the drugs must also agree with their clinical practice and the 
country-specific label. Sites may also follow their institutional practice and the country specific 
label for dose reductions. 


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5.3.1.3.
S-1 and Oxaliplatin
Administration of S-1 and oxaliplatin must follow the institutional practice for these agents and 
the in-country label. Dose reductions of the drugs must also agree with their clinical practice and 
the country-specific label. Sites may also follow their institutional practice and the country 
specific label for dose reductions. 
5.3.1.4.
Nivolumab
Administration of nivolumab must follow the institutional practice for these agents and the 
in-country label. Dose reductions of the drugs must also agree with their clinical practice and the 
country-specific label/prescribing information. Sites may also follow their institutional practice 
and the country specific label for dose reductions. 
5.4.
Prior and Concomitant Medications
At Screening, all medication taken up to 28 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. 
During the course of the clinical trial, subjects are anticipated to continue the use of prescribed 
medications identified during screening procedures, consistent with the study inclusion and 
exclusion criteria. 
Non-study anticancer chemotherapy or immunotherapy (approved or investigational) is not 
permitted during the trial. If administered, the subject may be removed from the trial. 
Inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are 
allowed; however, chronic daily treatment with oral corticosteroids (dose of ˃ 10 mg/day 
prednisone equivalent) are not allowed.
5.5.
Accountability for Andecaliximab and Andecaliximab/Nivolumab
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 andecaliximab and nivolumab (quantity and 
condition) and tracking of vials assigned/utilized for subject dosing. 
Andecaliximab and andecaliximab/nivolumab accountability records will be provided to each 
study site to:

Record the date received and quantity of andecaliximab and nivolumab vials


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
Record the date, subject number, subject initials, the vial number(s) dispensed

Record the date, quantity of used and unused andecaliximab and nivolumab vials returned, 
along with the initials of the person recording the information.
Dispensing records will include the initials of the person dispensing the andecaliximab or 
nivolumab or supplies.
5.5.1.
Investigational Medicinal Product Return or Disposal
Andecaliximab, S-1, cisplatin, oxaliplatin, and nivolumab 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 presented in 
tabular form in Appendix 2-Appendix 5 and described in the text that follows. 
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
Safety and tolerability assessments will include regular monitoring of AEs, changes from
baseline in laboratory variables, PEs, vital signs, and special safety assessments like ECGs.
6.1.
Subject Enrollment and Treatment Assignment
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 28 days before Day 1 to determine eligibility for participation in 
the study. 
Subject eligibility will be established at the conclusion of the screening evaluations. Subjects will 
be assigned a unique screening number at the time of consent. Subject eligibility must be 
determined by results received from the central lab with exceptions made for re-screening and 
HER2 testing as described in Sections 6.12.2 and 6.12.8.2. It is the responsibility of the 
investigator to ensure that each subject is eligible for the study before enrollment.
Once eligibility is confirmed subjects will be assigned a unique subject number. 
The following will be performed and documented at screening:

Obtain written informed consent

Obtain medical history (including review of disease under study, prior surgeries, and prior 
anti-cancer therapies)

Review of prior/concomitant medication(s)

Complete PE including, body weight, and height

Vital signs including blood pressure, respiratory rate, pulse, and temperature

12-lead ECG

ECOG Performance Status


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
Obtain blood and/or urine samples for: 
Chemistry (See Section 6.12.8)
Hematology (See Section 6.12.8)
Coagulation (See Section 6.12.8)
Serum pregnancy test for females of childbearing potential (See Section 6.12.8)
Blood biomarkers (See Section 3.11)
Urinalysis
For Cohort 4 (combination therapy andecaliximab and nivolumab): Thyroid function tests 
(See Section 6.12.8)

CT or MRI (scans taken as part of standard medical practice within 28 days of Day 1 are 
acceptable)

Record any serious adverse events (SAEs) and all AEs related to protocol mandated 
procedures occurring after signing of the consent form.
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic on Day 1 (within 28 days after screening) for enrollment into the study.
6.3.
Treatment Assessments – Cohort 1 (Andecaliximab Monotherapy)
6.3.1.
Day 1 of Each 28-Day Cycle
The following will be performed and documented on Day 1.
Pre Dose: 

Modified PE 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 6.12.8)
Hematology (See Section 6.12.8)


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Coagulation (See Section 6.12.8)
Andecaliximab concentration (Cycles 2, 3, 5, 7 and every 3 cycles thereafter) 
(See Section 6.12.8)
Anti-andecaliximab antibodies (Cycles 1, 2, 3, 5, 7 and every 3 cycles thereafter)
(See Section 6.12.8)
Blood biomarkers (See Section 3.11)
Urine pregnancy test for females of childbearing potential (Day 1 of Cycle 1 only) 
(See Section 6.12.8)
Urinalysis (See Section 6.12.8)

Obtain tumor tissue biopsy (Day 1 of Cycle 1 Pre Dose) and perform endoscopic evaluation 
noting extent and grade of disease and new instances of, or progression of, existing gastritis 
and dysplasia before biopsies

Obtain normal gastric tissue biopsy (Day 1 of Cycle 1 Pre Dose)

Collection of archival tumor tissue specimen as applicable: efforts to acquire a tissue sample 
should begin on Day 1

Review of concomitant medication(s)

Record any SAEs and all AEs related to protocol mandated procedures 
Dosing: 

Administer andecaliximab via IV infusion over approximately 30 (± 5) minutes
Post Dose: End of Infusion (EOI)

Obtain blood samples for:
Andecaliximab concentration (30 ± 15 minutes for Cycles 1, 2, 3, 5, 7, and every 3 cycles 
thereafter) (See Section 6.12.8)

Record any SAEs and all AEs related to protocol mandated procedures 
6.3.2.
Cycle 1 Day 2 and Cycle 1 Day 4
The following will be performed and documented Cycle 1 Day 2 and Cycle 1 Day 4 (± 1 day): 

Vital signs including blood pressure, respiratory rate, pulse, and temperature

ECOG Performance Status


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
Obtain blood samples for: 
Andecaliximab concentration (See Section 6.12.8)
Blood biomarkers (See Section 3.11)

Review of concomitant medication(s)

Record any SAEs and all AEs related to protocol mandated procedures 
6.3.3.
Cycle 1 Day 8
The following will be performed and documented on Day 8 (± 1 day): 

Vital signs including blood pressure, respiratory rate, pulse, and temperature

ECOG Performance Status

Obtain blood samples for: 
Chemistry (See Section 6.12.8)
Hematology(See Section 6.12.8)
Andecaliximab concentration (See Section 6.12.8)
Blood biomarkers (See Section 3.11)

Review of concomitant medication(s)

Record any SAEs and all AEs related to protocol mandated procedures 
6.3.4.
Day 15 of Each 28-Day Cycle
The following will be performed and documented on Day 15 (± 1 day):
Pre Dose:

Modified PE 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 6.12.8)


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Hematology (See Section 6.12.8)
Coagulation (See Section 6.12.8)
Andecaliximab concentration (Day 15 of Cycle 1 only) (See Section 6.12.8)
Blood biomarkers (See Section 3.11)
Obtain tumor tissue biopsy (Day 15 of Cycle 2 (+5d) only) and perform endoscopic 
evaluation noting extent and grade of disease and new instances of, or progression of, 
existing gastritis and dysplasia before biopsies
Urinalysis (See Section 6.12.8)

Review of concomitant medication(s)

Record any SAEs and all AEs related to protocol mandated procedures 
Dosing: 

Administer andecaliximab via IV infusion over approximately 30 (± 5) minutes
Post Dose: End of Infusion (EOI)

Obtain blood samples for:
Andecaliximab concentration (30 ± 15 minutes, Day 15 of Cycle 1 only) (See 
Section 6.12.8)

Record any SAEs and all AEs related to protocol mandated procedures 
6.3.5.
Cycle 1 Day 29/Cycle 2 Day 1 
The Cycle 1 Day 29 visit, which overlaps with the Cycle 2 Day 1 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 dose of andecaliximab, completed all safety procedures through 
Day 28, or have experienced a DLT prior to Day 28. Assessments should be performed as listed 
in Section 6.3.1 for Day 1 of each 28-day cycle. Additionally, see Section 6.5 for Continuation of 
Treatment Assessments. 
6.4.
Treatment Assessments – Cohorts 2, 3 and 4 (Combination Therapy 
Cohorts)
The below assessments outline study procedures to occur at each visit with andecaliximab dosing 
(Days 1 and 15 of each 28-day cycle for Cohorts 2 and 4; Day 1 of each 21-day cycle for 
Cohort 3). 


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6.4.1.
Day 1 of Each 28-Day Cycle for Cohort 2 (Combination Therapy 
Andecaliximab and SP) and Cohort 4 (Combination Therapy Andecaliximab
and Nivolumab)
The following will be performed and documented on Day 1 (± 1 day). C1D1 must occur within 
3 days following enrollment in IWRS.
Pre Dose: 

Modified PE 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 6.12.8)
Hematology (See Section 6.12.8)
Coagulation (See Section 6.12.8)
Andecaliximab concentration (Cycles 2, 3, 5, 7, and every 3 cycles thereafter) 
(See Section 6.12.8
Anti-andecaliximab antibodies (Cycles 1, 2, 3, 5, 7, and every 3 cycles thereafter) 
(See Section 6.12.8)
Blood biomarkers (See Section 3.11)
Urine pregnancy test for females of childbearing potential (See Section 6.12.8)
Urinalysis (See Section 6.12.8)

Obtain tumor tissue biopsy (within 28 days prior to or on Day 1 of Cycle 1 Pre Dose only)
and perform endoscopic evaluation noting extent and grade of disease and new instances of, 
or progression of, existing gastritis and dysplasia before biopsies

Obtain normal gastric tissue biopsy (within 28 days prior to or on Day 1 of Cycle 1 Pre Dose
only)

Collection of archival tumor tissue specimen as applicable: efforts to acquire a tissue sample 
should begin on Day 1


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
Review of concomitant medication(s)

Record any SAEs and all AEs related to protocol mandated procedures 
Dosing: 

Administer andecaliximab via IV infusion over approximately 30 (± 5) minutes 

For Cohort 2 (combination therapy andecaliximab and SP): S-1 and cisplatin chemotherapy 
administration will follow dosage and regimen based on subject condition, investigator 
discretion, institutional practice and/or the in-country label. Due to expected variation in 
administration schedules, chemotherapy dosing may or may not take place on Days 1 and 15 
of each 28-day cycle. 

For Cohort 4 (combination therapy andecaliximab and nivolumab): Following administration 
of andecaliximab, administer nivolumab via IV infusion over approximately 60 (± 5) minutes 
Post Dose: End of Infusion (EOI)

Obtain blood samples for:
Andecaliximab concentration (30 ± 15 minutes for Cycles 1, 2, 3, 5, 7, and every 3 cycles 
thereafter) (See Section 6.12.8)

Record any SAEs and all AEs related to protocol mandated procedures 
6.4.2.
Day 1 of Each 21-Day Cycle for Cohort 3 (Combination Therapy 
Andecaliximab and SOX)
The following will be performed and documented on Day 1 (± 1 day). C1D1 must occur within 
3 days following enrollment in IWRS.
Pre Dose: 

Modified PE 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 6.12.8)
Hematology (See Section 6.12.8)


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Coagulation (See Section 6.12.8)
Andecaliximab concentration (Cycles 2, 3, 5, 7, and every 3 cycles thereafter) 
(See Section 6.12.8
Anti-andecaliximab antibodies (Cycles 1, 2, 3, 5, 7, and every 3 cycles thereafter) 
(See Section 6.12.8)
Blood biomarkers (See Section 3.11)
Urine pregnancy test for females of childbearing potential (See Section 6.12.8)
Urinalysis (See Section 6.12.8)

Obtain tumor tissue biopsy (within 28 days prior to or on Day 1 of Cycle 1 Pre Dose only)
and perform endoscopic evaluation noting extent and grade of disease and new instances of, 
or progression of, existing gastritis and dysplasia before biopsies

Obtain normal gastric tissue biopsy (within 28 days prior to or on Day 1 of Cycle 1 Pre Dose
only)

Collection of archival tumor tissue specimen as applicable: efforts to acquire a tissue sample 
should begin on Day 1

Review of concomitant medication(s)

Record any SAEs and all AEs related to protocol mandated procedures 
Dosing: 

Administer andecaliximab via IV infusion over approximately 30 (± 5) minutes 

S-1 to be administered orally twice daily for the first 14 days of the 21-day cycle

Administer Oxaliplatin by IV infusion over 2 hours 
Post Dose: End of Infusion (EOI)

Obtain blood samples for:
Andecaliximab concentration (30 ± 15 minutes for Cycles 1, 2, 3, 5, 7, and every 3 cycles 
thereafter) (See Section 6.12.8)

Record any SAEs and all AEs related to protocol mandated procedures 


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6.4.3.
Cycle 1 Day 8 for Cohort 4 (Combination Therapy Andecaliximab and 
Nivolumab)
The following will be performed and documented on Day 8 (± 1 day): 

Vital signs including blood pressure, respiratory rate, pulse, and temperature

ECOG Performance Status

Obtain blood samples for: 
Chemistry (See Section 6.12.8)
Hematology (See Section 6.12.8)
Andecaliximab concentration (See Section 6.12.8)
Blood biomarkers (See Section 3.11)

Review of concomitant medication(s)

Record any SAEs and all AEs related to protocol mandated procedures 
6.4.4.
Day 15 of Each 28-Day Cycle for Cohort 2 (Combination Therapy 
Andecaliximab and SP) and Cohort 4 (Combination Therapy Andecaliximab
and Nivolumab)
The following will be performed and documented on Day 15 (± 1 day):
Pre Dose: 

Modified PE 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 6.12.8)
Hematology (See Section 6.12.8)
Coagulation (See Section 6.12.8)
For Cohort 2 (combination therapy andecaliximab and SP): Andecaliximab concentration 
(Day 15 of Cycle 1 only) (See Section 6.12.8)


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For Cohort 4 (combination therapy andecaliximab and nivolumab): Andecaliximab
concentration (Day 15 of Cycles 1, 2, 3, 5, 7, and every 3 cycles thereafter) (See 
Section 6.12.8)
Blood biomarkers (Day 15 of Cycle 1 and Cycle 2 only) (See Section 3.11)
For Cohort 4 (combination therapy andecaliximab and nivolumab): Obtain tumor tissue 
biopsy (at 6 weeks (± 1 week) after the first dose of andecaliximab) and perform 
endoscopic evaluation noting extent and grade of disease and new instances of, or 
progression of, existing gastritis and dysplasia before biopsies
Urine pregnancy test (females of childbearing potential) (See Section 6.12.8)
Urinalysis (See Section 6.12.8)

Review of concomitant medication(s)

Record any SAEs and all AEs related to protocol mandated procedures 
Dosing: 

Administer andecaliximab via IV infusion over approximately 30 (± 5) minutes 

For Cohort 2 (combination therapy andecaliximab and SP): S-1 and cisplatin chemotherapy 
administration will follow dosage and regimen based on subject condition, investigator 
discretion, institutional practice and/or the in-country label. Due to expected variation in 
administration schedules, chemotherapy dosing may or may not take place on Days 1 and 15 
of each 28-day cycle. 

For Cohort 4 (combination therapy andecaliximab and nivolumab): Following administration 
of andecaliximab, administer nivolumab via IV infusion over approximately 60 (± 5) minutes 
Post Dose: End of Infusion (EOI)

Obtain blood samples for:
Andecaliximab concentration (30 ± 15 minutes for Cycles 1, 2, 3, 5, 7, and every 3 cycles 
thereafter for Cohort 4) (See Section 6.12.8)

Record any SAEs and all AEs related to protocol mandated procedures 
6.5.
Continuation of Treatment
Study drug dosing will continue in the absence of disease progression or toxicity warranting 
discontinuation therapy.


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6.5.1.
Every 8 Weeks for Cohorts 1, 2 and 4
Every 9 Weeks for Cohort 3
For subjects continuing treatment, or subjects who discontinue all treatment prior to disease 
progression but remain on study, the following will be performed and documented every 8 weeks 
(± 5 days) for subjects in Cohorts 1 (andecaliximab monotherapy), 2 (combination therapy 
andecaliximab and SP), and 4 (combination therapy andecaliximab and nivolumab), and every 
9 weeks (± 5 days) for subjects in Cohort 3 (combination therapy andecaliximab and SOX): 

Assessment of tumor response
CT or MRI

If not collected in the last 2 weeks, obtain blood samples for: 
Chemistry (See Section 6.12.8)
Hematology (See Section 6.12.8)
Coagulation (See Section 6.12.8)
Blood biomarkers (See Section 3.11)
For Cohort 4 (combination therapy andecaliximab and nivolumab): Thyroid function tests 
(See Section 6.12.8)

Review of concomitant medication(s)

Record any SAEs and all AEs related to protocol mandated procedures 
6.6.
Assessments for Premature Discontinuation from Study
If a subject discontinues study dosing (for example, as a result of an AE), every attempt should 
be made to keep the subject in the study and continue to perform the required study-related 
follow-up and procedures (see Section 3.6). If this is not possible or acceptable to the subject or 
investigator, the subject may be withdrawn from the study. It is recommended that the 
investigator consults with the medical monitor prior to removing the subject from study for any 
reason except subject withdrawal of consent.
6.7.
Criteria for Discontinuation of Study Treatment
See Sections 3.5 and 3.7 for discontinuation criteria.
6.8.
End of Treatment
EOT assessments will be requested from subjects in all cohorts who discontinue all treatment 
prior to disease progression. These assessments should be completed as soon as possible after the 
decision is made. Every attempt should be made to keep the subject in the study and continue to 
perform tumor evaluation by CT or MRI every 8 weeks (for Cohorts 1, 2, and 4) or every 
9 weeks (for Cohort 3) until disease progression.


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The following will be performed and documented at the EOT visit: 

Modified PE capturing changes from prior examinations and weight

Vital signs including blood pressure, respiratory rate, pulse, and temperature

ECOG Performance Status

If not conducted in the last 2 weeks, obtain blood samples for: 
Chemistry (See Section 6.12.8) 
Hematology (See Section 6.12.8)
Coagulation (See Section 6.12.8)
Andecaliximab concentration (See Section 6.12.8)
Anti-andecaliximab antibodies (See Section 6.12.8)
Blood biomarkers (See Section 3.11)
For Cohort 4 (combination therapy andecaliximab and nivolumab): Thyroid function tests 
(See Section 6.12.8)

Review of concomitant medication(s)

Record any SAEs and all AEs related to protocol mandated procedures 
6.9.
End of Study Visit
The following will be performed and documented at the EOS visit: 

Modified PE 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 6.12.8)
Hematology (See Section 6.12.8)
Coagulation (See Section 6.12.8)
Andecaliximab concentration (See Section 6.12.8)


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Anti-andecaliximab antibodies (See Section 6.12.8)
Blood biomarkers (See Section 3.11)
Urine pregnancy test for females of childbearing potential (See Section 6.12.8)
Urinalysis (See Section 6.12.8)
For Cohort 4 (combination therapy andecaliximab and nivolumab): Thyroid function tests 
(See Section 6.12.8)

CT or MRI (if not conducted within the previous 28 days)

Tumor tissue biopsy (at progression for Cohorts 2 and 3,
)

Review of concomitant medication(s)

Record any SAEs and all AEs related to protocol mandated procedures 
6.10.
Follow-up Visits
6.10.1.
30-Day Safety Follow-Up
A safety follow-up visit will be performed 30 days (± 7 days) after the last dose of 
andecaliximab. The 30-day safety follow-up visit may be substituted by a scheduled study visit if 
it occurs within the same window. The following will be performed and documented at the 
30-day follow-up visit: 

Modified PE 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 6.12.8)
Hematology (See Section 6.12.8)
Anti-andecaliximab antibodies (See Section 6.12.8)
Urine pregnancy test for females of childbearing potential (See Section 6.12.8)
Urinalysis (See Section 6.12.8)
For Cohort 4 (combination therapy andecaliximab and nivolumab): Thyroid function tests 
(See Section 6.12.8)
For Cohort 4 (combination therapy andecaliximab and nivolumab): Blood biomarkers 
(See Section 3.11)
CCI


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
Review of concomitant medication(s)

Record any SAEs and all 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).
6.10.2.
Cohort 4 (Combination Therapy Andecaliximab and Nivolumab) Only: 
5-Month Safety Follow-Up
A safety follow-up visit will be performed 5 months (± 7 days) following the last dose of 
nivolumab for subjects in Cohort 4 (combination therapy andecaliximab and nivolumab). The 
5-month follow-up visit may be substituted by a scheduled study visit if it occurs within the same 
window. The following will be performed and documented at the 5-month follow-up visit: 

Obtain blood and/or urine samples for: 
Chemistry (See Section 6.12.8)
Hematology (See Section 6.12.8)
Anti-andecaliximab antibodies (See Section 6.12.8)
Urine pregnancy test for females of childbearing potential (See Section 6.12.8)
Urinalysis (See Section 6.12.8)
Thyroid function tests (See Section 6.12.8)
Blood biomarkers (See Section 3.11)

Review of concomitant medication(s)

Record any SAEs and all AEs 
6.10.3.
Long Term Follow-Up
Long term follow-up (LTFU) for OS 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 of 
long term survival status and record of any other anti-cancer therapy, cancer-related surgery for 
up to 5 years after the EOS visit.
Subjects who are not deceased by the time Gilead has made the determination the study will be 
ended will receive a final follow-up phone call to assess survival status and communicate the 
sponsor’s decision.


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The investigator will make eve1y effo1i to contact the subject or a close relative or caretaker by 
phone to collect survival infonnation. 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). 
6.11. 
Replacement of Subjects 
In Coho1i 1 (andecaliximab monotherapy), 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 emolled. 
6.12. 
6.12.1. 
Description of Study Procedures 
Informed Consent 
All sub· ects must si n and date the most re 
6.12.2. 
Re-Screening Criteria 
Subjects who fail to meet eligibility or complete the initial screening will be pennitted to 
rescreen provided that the reason for screen failure has been resolved and no new exclusions 
have been identified. If the subject is rescreened > 28 days from their original screening date 
( date of info1med consent), all screening activities, including info1med consent, need to be 
repeated. 
Subject eligibility must be detennined by results received from the central lab. However, if there 
have been 2 failed attempts to obtain test results from the central lab, eligibility may be 
dete1mined using local lab results, with documentation of failed attempts, local lab results and 
sponsor approval. 
6.12.3. 
Medical & Medication History 
A complete medical and surgical histo1y will be obtained by the investigator or designee at 
screening, including disease histo1y, and recorded on the electronic case repo1i fo1m ( eCRF). 
All medications taken within 28 days prior to screening and during the screening period will be 
obtained prior to Day 1 and recorded on the eCRF. For all coho1is, 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, 
vitamins and minerals. 
In addition, suppo1iive therapies given during the course of the study ( eg, blood transfusion, 
growth factor) should be collected and recorded on the eCRF. 
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6.12.4.
Physical Examination
A complete PE will be performed for all cohorts at screening. This will include assessment of 
clinical signs and symptoms. The exam will be performed by a physician or designee qualified to 
perform assessments. Breast, genital, and rectal examinations are not required, unless warranted 
in opinion of the healthcare provider.
For Cohorts 1, 2, and 4, a modified physical exam capturing changes from prior exams will be 
performed on Day 1 and 15 of each 28-day cycle, at the EOT visit, at the EOS visit, and at the 
30-day safety follow-up visit. 
For Cohort 3, a modified physical exam capturing changes from prior exams will be performed 
on Day 1 of each 21-day cycle, at the EOT visit, at the EOS visit, and at the 30-day safety 
follow-up visit.
Weight (without shoes) should be measured with each PE (complete and modified) and reported 
in kilograms. Height (without shoes) should be measured at screening only and reported in 
centimeters. Weight will be collected any time a complete or modified PE is performed.
Pre dose abnormal findings will be reported on the medical history page of the eCRF. Any 
changes from pre dose baseline PE which represent a clinically significant deterioration will be 
documented on the AE page of the eCRF.
6.12.5.
Vital Signs 
Vital signs, including blood pressure, pulse, respiratory rate, and temperature, will be measured 
by the investigator or qualified designee as per standard institutional guidelines at each study 
visit as indicated in Appendix 2-Appendix 5. 
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.
6.12.6.
Electrocardiogram Assessment
For all cohorts, a single 12-lead ECG will be collected at screening, on Day 1 of each cycle, and 
at the EOS Visit, per standard practice. 
The investigator or qualified designee will review all ECGs and retain the tracing with the source 
documents. Appropriate data will be reported on the eCRF.
6.12.7.
Performance Status
Performance status will be scored using the ECOG performance status scale index at each study 
visit (for all cohorts) as indicated in Appendix 2-Appendix 5. ECOG used to determine eligibility 
must be the performance status during the screening period. 


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6.12.8.
Laboratory Assessments
The central laboratory will be responsible for chemistry, hematology, coagulation, urinalysis, 
and serum pregnancy testing (per Table 6-1) as well as processing and/or storage of other study 
samples. Specific instructions for processing, labeling, and shipping samples will be provided in 
a central laboratory manual. 
If central laboratory results are not available, local laboratories may be used for dosing decisions. 
Local laboratory assessments resulting in a dose change or as part of an adverse event 
assessment, which is not supported by central lab results, will be reported on the eCRF. 
Urine pregnancy test will be performed at the site.
The date and time of blood and/or urine sample collection will be recorded in the subject’s 
source documentation and reported to the central laboratory. Screening laboratory samples 
should be obtained within 28 days prior to enrollment. Specified Day 1 pre dose samples may be 
drawn up to 2 days prior to the Day 1 visit (see Appendix 2-Appendix 5). The tests will be 
analyzed using standard procedures. White blood cell differentials will be reported as absolute 
counts. 
Blood samples will be obtained for chemistry, hematology, coagulation, pregnancy testing for 
female subjects, andecaliximab concentration and anti-andecaliximab antibodies, and serum and 
plasma biomarkers as indicated in Appendix 2-Appendix 5. Urine samples will be obtained for 
urinalysis and pregnancy testing for female subjects as indicated in Appendix 2-Appendix 5.


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Table 6-1.
Analytes
Serum Chemistry
Urinalysis
Hematology
Other
Albumin
Alkaline phosphatase
ALT
AST
Bicarbonate
BUN
Calcium
Chloride
Creatininea
Glucose
Amylase
Lipase
Magnesium
Phosphorus
Potassium
Sodium
Total bilirubin
Direct bilirubin
Total protein
CA19-9
CEA
hsCRP
COHORTS 3 & 4 
ONLY: 
AFP
Color and appearance
Specific gravity
pH
Occult blood
Protein
Glucose
Bilirubin
Leukocyte esterase
Nitrite
Urobilinogen
Ketones
Microscopicb
WBC
Hemoglobin
Hematocrit
Platelet
ANC
Differential
Eosinophils
Lymphocytes
Monocytes
Neutrophils
Serum β-hCGc (females)
Urine pregnancy testc (females)
Andecaliximab concentration
Anti-andecaliximab antibodies
Serum and plasma biomarkers
COHORT 4 ONLY: Thyroid 
Function Tests: (TSH, T3, free 
T4)d
Coagulation
PT/INR
aPTT
Abbreviations: AFP = alpha-fetoprotein; ANC = absolute neutrophil count; ALT = alanine aminotransferase; aPTT = Activated 
Partial Thromboplastin Time; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CA19-9 = carbohydrate antigen 
19-9; CEA = carcinoembryonic antigen; β-hCG = betahuman chorionic gonadotropin; HER2 = human epidermal growth factor 
receptor 2; INR = International Normalized Ratio; hsCRP = High sensitivity C-Reactive protein; PT = Prothrombin Time; 
TSH = thyroid-stimulating hormone; WBC = white blood cell
a
Estimated creatinine clearance (CLcr)/glomerular filtration rate will be calculated based on the Cockroft-Gault formula 
using actual body weight: CLcr (mL/min) = (140 – age [years])* weight (kg) / (serum creatinine [mg/dL]*72). If the subject 
is female, multiply the quantity by 0.85.
b
Reflex testing based on other abnormalities
c
Females of child-bearing potential only. Serum pregnancy will be conducted at Screening. Urine pregnancy tests will be 
performed at the time points specified in Section 6.12.8.1 and Appendix 2-Appendix 5.
d
TSH, T3, free T4 will be test by the central laboratory at screening. At the every 8 week visit and beyond, T3 and T4 will be 
tested reflexively based on abnormal TSH results. 
At any time during the study, abnormal laboratory parameters that are clinically relevant
(eg, lead to clinical symptoms or signs, require therapeutic intervention), and constitute an AE
must be recorded in the eCRF. All laboratory tests must be reviewed for clinical significance by 
the investigator or qualified designee.


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6.12.8.1.
Pregnancy Test
All females of childbearing potential (see Appendix 9) will have a serum pregnancy test at 
screening. 
For female subjects in Cohort 1 (andecaliximab monotherapy), urine pregnancy tests will be 
performed on Cycle 1 Day 1 Pre Dose, at the EOS visit and at the 30-day safety follow-up visit.
For female subjects in Cohort 2 (combination therapy andecaliximab and SP), urine pregnancy 
tests will be performed Pre Dose on Days 1 and 15 of each 28-day cycle, at the EOS visit, and at 
the 30-day safety follow-up visit. 
For female subjects in Cohort 3 (combination therapy andecaliximab and SOX), urine pregnancy 
tests will be performed Pre Dose on Day 1 of each 21-day cycle, at the EOS visit, and at the 
30-day safety follow-up visit.
For female subjects in Cohort 4 (combination therapy andecaliximab and nivolumab), urine 
pregnancy tests will be performed Pre Dose on Days 1 and 15 of each 28-day cycle, at the EOS 
visit, and at the 30-day and 5-month safety follow-up visits.
The results must be confirmed as negative prior to administration of study drug on the respective 
days the test is performed. 
6.12.8.2.
HER2 Testing
Prior to enrollment in Cohorts 1 (andecaliximab monotherapy), 2 (combination therapy 
andecaliximab and SP), and 3 (combination therapy andecaliximab and SOX), the subject’s 
tumor should have been tested for HER2 status with approved IHC and in situ hybridization 
(ISH) kits. HER2 positivity is defined as IHC3+ or IHC2+/ISH+ (ISH positivity is defined as 
HER2:CEP17 ratio of ≥ 2.0). Results for HER2 status obtained prior to signing informed consent 
are acceptable if obtained with approved IHC and ISH kits. HER2 status may be determined 
during screening by testing the tumor at the central lab or a local lab with approved IHC and ISH 
kits.
6.12.8.3.
Andecaliximab Pharmacokinetics
For Cohort 1 (andecaliximab monotherapy), plasma samples for andecaliximab PK will be 
collected prior to andecaliximab dosing and 30 (15) minutes after the end of infusion on Day 1 
of Cycles 2, 3, 5, 7, and every 3 cycles thereafter and anytime at the EOT visit (if not conducted 
in the last 2 weeks), and EOS visit. Additionally, PK plasma samples will be collected at the 
following time points in Cycle 1 only: 30 (15) minutes after the end of infusion on Day 1;
anytime on Days 2, 4, and 8; prior to dosing and 30 (15) minutes after the end of infusion on 
Day 15.
For Cohort 2 (combination therapy andecaliximab and SP), plasma samples for andecaliximab
PK in Cycle 1 will be collected 30 (15) minutes after the end of andecaliximab infusion on 
Day 1 and prior to andecaliximab dosing on Day 15. Additionally, plasma samples for 


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andecaliximab PK will be collected prior to andecaliximab dosing and 30 (±15) minutes after the 
end of infusion on Day 1 of Cycles 2, 3, 5, 7, and eve1y 3 cycles thereafter, and anytime at the 
EOT visit (if not conducted in the last 2 weeks), and EOS visit. 
For Cohort 3 (combination therapy andecaliximab and SOX), plasma samples for andecaliximab 
PK in Cycle 1 will be collected 30 (±15) minutes after the end of andecaliximab infusion on 
Day 1. Additionally, plasma samples for andecaliximab PK will be collected prior to 
andecaliximab dosing and 30 (± 15) minutes after the end of infusion on Day 1 of Cycles 2, 3, 5, 
7, and eve1y 3 cycles thereafter, and anytime at the EOT visit (if not conducted in the last 
2 weeks), and EOS visit. 
For Coho1t 4 ( combination therapy andecaliximab and nivolumab ), plasma samples for 
andecaliximab PK in Cycle 1 will be collected 30 (± 15) minutes after the end of andecaliximab 
infusion on Day 1, anytime on Day 8, and prior to andecaliximab dosing and 30 (± 15) minutes 
after the end of infusion on Day 15. Additionally, plasma samples for andecaliximab PK will be 
collected prior to andecaliximab dosing and 30 (± 15) minutes after the end of infusion on Day 1 
and Day 15 of Cycles 2, 3, 5, 7, and eve1y 3 cycles thereafter, and anytime at the EOT visit (if 
not conducted in the last 2 weeks), and EOS visit. 
6.12.8.4. 
Anti-Andecaliximab Antibodies 
For all coho1ts, blood samples for anti-andecaliximab antibodies will be collected prior to dosing 
on Day 1 of Cycles 1, 2, 3, 5, 7, and eve1y 3 cycles thereafter, at the EOT visit (if not conducted 
in the last 2 weeks), at the EOS visit, and at the 30 day safety follow-up visit. 
For Coho1t 4 ( combination therapy andecaliximab and nivolumab ), blood samples for 
anti-andecaliximab antibodies will also be collected at the 5-month safety follow-up visit. 
6.12.8.5. 
Tumor Tissue Biopsy 
Coho1ts 1 (andecaliximab monotherapy) and 4 (combination therapy andecaliximab and 
nivolumab ): Tumor tissue biopsy will be collected within 28 days prior to the first dose of 
andecaliximab (Pre Dose, Cycle 1 Day 1) in both Coho1ts 1 and 4, on Cycle 2 Day 15 (+ 5 days) 
for Coho1t 1, and at 6 weeks(± 1 week) after the first dose of andecaliximab for Cohort 4. A 
n01mal gastric tissue biopsy will also be collected within 28 days prior to the first dose of 
andecaliximab Pre Dose, C cle 1 Da 1 in both Coho1ts 1 and 4. 
Coho1ts 2 ( combination therapy andecaliximab and SP) and 3 ( combination therapy 
andecaliximab and SOX): Tumor tissue biopsy will be collected within 28 days prior to the first 
dose of andecaliximab (Pre Dose, Cycle 1 Day 1) and at EOS with documented disease 
progression. A nonnal gastric tissue biopsy will also be collected within 28 days prior to the first 
dose of andecaliximab (Pre Dose, Cycle 1 Day 1). Endoscopic samples (minimum 4, but 6-8 
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encouraged) or 18 gauge needle biopsies (4 passes) of metastases to liver or lymph nodes are 
acceptable and are to be processed as described in the laboratory manual.
6.12.8.6.
Archival Tumor Tissue
Archival tumor tissue formalin-fixed paraffin embedded (FFPE) blocks will be collected from all 
subjects and shipped to the central laboratory for sectioning. If blocks are not available to be 
shipped, 15 x 5-micron slides and 5 x 10-micron slides prepared within 2 weeks from the 
archival tissue block are requested. Efforts to acquire the archival tissue should begin on Day 1 
of Cycle 1.
6.12.8.7.
Biomarkers
Samples for biomarker analysis will be obtained as indicated in Section 3.11.
6.12.9.
Tumor Response Assessment
6.12.9.1.
Tumor Imaging
Either contrast-enhanced CT or gadolinium-enhanced MRI of the chest, abdomen, and pelvis 
will be performed at screening (scans taken as part of medical practice within 28 days of Day 1 
are acceptable), every 8 weeks (for Cohorts 1, 2, and 4) or every 9 weeks (for Cohort 3), and at 
the EOS visit if one has not been performed within the previous 28 days. Tumor burden will be 
evaluated solely based on radiographic imaging per RECIST v1.1. Chest x-ray, ultrasound, 
endoscopy, laparoscopy, positron-emission tomography, radionuclide scans, or tumor markers 
will not be considered for response assessment.
For radiographic evaluations, the same method of assessment and the same technique (eg, scan 
type, scanner, subject position, dose of contrast, injection/scan interval) should be used to 
characterize each identified and reported lesion at baseline and during study treatment and 
follow-up.
Scans taken as part of standard medical practice up to 28 days prior to enrollment can be used for 
screening as long as they meet all study requirements. During the treatment phase, scans may be 
performed at time points other than every 8 or 9 weeks as clinically indicated to assess tumor 
progression.
If a subject has discontinued all study treatments prior to definitive disease progression, the 
subject shall remain on study until at least 1 of the criteria for discontinuation from study is met 
(Section 3.7). Every attempt should be made to keep the subject in the study and continue to 
perform tumor evaluation by CT or MRI every 8 weeks (for Cohorts 1, 2, and 4) or every 9 
weeks (for Cohort 3) until disease progression. If this is not possible or acceptable to the subject 
or investigator, the subject may be withdrawn from the study. It is recommended that the 
investigator consults with the medical monitor prior to removing the subject from study for any 
reason except subject withdrawal of consent.


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6.12.9.2.
Efficacy Measurements for Cohort 4 (Combination Therapy Andecaliximab and 
Nivolumab) ONLY
RECIST version 1.1 {Eisenhauer 2009} (Appendix 10) will be used for assessment of tumor
responses for the purposes of study evaluation, managing patients on protocol treatment, and
decision making for discontinuation of study therapy due to disease progression, with some
modifications to account for atypical responses which may occur with immune-based therapies
{Swaika 2015}. Given that anti PD-1 agents produce antitumor effects by potentiating
endogenous cancer-specific immune responses, the response patterns seen with these agents may
extend beyond the typical time course of responses seen with cytotoxic agents. In addition, anti-
PD-1 therapies can occasionally manifest a clinical response after an initial increase in tumor
burden or even the appearance of new lesions (“tumor flare” or “pseudoprogression”) {Topalian 
2014}. In these cases, standard RECIST may not provide an accurate response assessment of anti 
PD-1 agents.
Therefore, for subjects enrolled in Cohort 4, RECIST 1.1 will be used (Appendix 10) with the 
following adaptations:
If imaging shows a CR or PR, tumor imaging should be repeated at least 4 weeks (≥4 weeks)
later to confirm response, per RECIST 1.1 guidelines. Subjects will then return to regular
scheduled imaging every 8 weeks starting with the next protocol-specified imaging time-point
(every 8 weeks from Day 1).
Subjects who obtain a confirmatory scan do not need to undergo scheduled imaging assessment
≤2 weeks later (eg, if a subject obtains a scan at Week 22 to confirm a Week 16 response, they
will not also be required to complete the scheduled Week 24 scan).
If imaging shows progressive disease (PD), it is at the discretion of the investigator to keep the
subject on study treatment or to stop study treatment until imaging is repeated ≥4 weeks later in
order to confirm PD (adapted from the immune-related response criteria recommendations)
{Wolchok 2009}. Patients that are deemed clinically unstable or who have biopsy-proven new 
metastatic lesions are not required to have repeat imaging for confirmation. The decision to
continue a subject on study while awaiting PD confirmation will be based on clinical judgment
of a subject’s overall clinical condition, including performance status, clinical symptoms, and
laboratory data.
At a minimum, subjects must meet the following criteria for continued treatment on study after
disease progression is identified at a tumor assessment:

Absence of signs and symptoms (including worsening laboratory values) indicating disease 
progression

No decline in ECOG performance status

Absence of rapid progression of disease or of progressive disease at critical anatomical sites 
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Study treatment may continue under the following circumstances after repeat/confirmatory 
imaging (≥4 weeks after initial scan showing PD):

If repeat imaging shows < 20% tumor burden increase compared to nadir, stable or improved 
previous new lesion (if identified as cause for initial PD), and stable/improved non-target 
disease (if identified as cause for initial PD), treatment may be continued and/or resumed
(PD is not confirmed).  

If repeat imaging confirms PD due to any of the scenarios listed below, subjects will be 
discontinued from study therapy with the following exception: if the subject is achieving a 
clinically meaningful benefit, and there is no further increase in the tumor burden at the 
confirmatory tumor imaging compared to the initial PD assessment, an exception to continue 
treatment may be considered following consultation with the Sponsor. In this case, if 
treatment is continued, tumor imaging should continue to be performed at the protocol 
specified intervals.
In determining whether or not the tumor burden has increased or decreased, site study team 
should consider all target lesions as well as non-target lesions.
If repeat imaging shows an objective response or stable disease relative to nadir, treatment with
study medication may continue and subjects will return to regular scheduled imaging every
8 weeks starting with the next protocol-specified imaging time-point. Subjects who obtain a 
confirmatory scan do not need to undergo scheduled imaging assessment ≤2 weeks later (eg, if a
subject obtains a scan at Week 14 to confirm a Week 8 PD and progression is not confirmed,
they will not also be required to complete the scheduled Week 16 scan).
Progressive Disease is confirmed at repeat imaging if:

Tumor burden remains ≥ 20% (and at least 5 mm absolute increase) compared to nadir

Non-target disease resulting in initial PD is worse (qualitative)

New lesion(s) resulting in initial PD is worse (qualitative)

Additional new lesion(s) since last evaluation
If repeat imaging confirms PD, subjects will be discontinued from study therapy.


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Table 6-2.
Imaging and Treatment after First Radiologic Evidence of 
Progressive Disease 
Clinically Stable
Clinically Unstable
Imaging
Treatment
Imaging
Treatment
First radiologic 
evidence of PD 
by RECIST 1.1 
Repeat imaging at 
> 4 weeks at site 
to confirm PD
May continue study 
treatment at the local 
site Investigator’s 
discretion while 
awaiting 
confirmatory tumor 
imaging by site by 
irRECIST.
Repeat imaging at 
> 4 weeks to 
confirm PD per 
physician discretion 
only
Discontinue treatment
Repeat tumor 
imaging confirms 
PD by RECIST 
(see 
modifications in 
protocol)
No additional 
imaging required
Discontinue 
treatment (exception 
is possible upon 
consultation with 
sponsor)
No additional 
imaging required
N/A
Repeat tumor 
imaging shows 
SD, PR, or CR by 
RECIST (see 
protocol for 
details)
Continue 
regularly 
scheduled 
imaging 
assessments
Continue study 
treatment at the local 
site Investigator’s 
discretion
Continue regularly 
scheduled imaging 
assessments
May restart study 
treatment if condition has 
improved and/or clinically 
stable per Investigator’s 
discretion. Next tumor 
image should occur 
according to the every 
8 week imaging schedule
In subjects who discontinue study therapy early without documented disease progression, every 
effort should be made to continue monitoring their disease status by radiologic imaging 
following guidelines for end of study follow-up (Section 6.6).
When feasible, subjects should not be discontinued until progression is confirmed; investigators 
should discuss with the Gilead Medical Monitor prior to subject discontinuation.  
6.12.10.
Study Drug and Anti-Cancer Agent Administration
For Cohort 1, andecaliximab 800 mg (or 600 mg if applicable) will be administered via IV
infusion over approximately 30 (± 5) minutes on Days 1 and 15 of each 28-day cycle. For 
Cohorts 2, and 4, andecaliximab 800 mg will be administered via IV infusion over approximately 
30 (± 5) minutes on Days 1 and 15 of each 28-day cycle. For Cohort 3, andecaliximab 1200 mg 
will be administered via IV infusion over approximately 30 (± 5) minutes on Day1 of each 
21-day cycle. Study drug dosing must be documented on the eCRF.


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Subjects in Cohort 2 will also be administered S-1 orally twice daily, and cisplatin administered 
by IV infusion on Day 8 of every 5 weeks, with the dosage and regimen based on subject
condition, investigator discretion, institutional practice and/or the in-country label.
Chemotherapy dosing and regimen changes must be documented on the eCRF.
Subjects in Cohort 3 will also be administered S-1 orally twice daily at 80 mg/day for BSA 
< 1.25m2, 100 mg/day for BSA ≥1.25 to < 1.5m2, and 120 mg/day for BSA ≥ 1.5m2 for the 
first 14 days of the 21-day cycle. Oxaliplatin will be administered by IV infusion at 100 mg/m2
over 2 hours on Day 1 of each 21-day cycle. Chemotherapy dosing and regimen changes must be 
documented on the eCRF.
Subjects in Cohort 4 will also be administered nivolumab 3 mg/kg via IV infusion over 
approximately 60 (± 5) minutes following administration of andecaliximab.
6.12.11.
Adverse Events
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all SAEs, as well as any AEs related to protocol-mandated procedures 
on the adverse events eCRF.  All other untoward medical occurrences observed during the 
screening period, including exacerbation or changes in medical history are to be captured on the 
medical history eCRF.  See Section 7 Adverse Events and Toxicity Management for additional 
details.
6.12.12.
Unscheduled Visits
Unscheduled visits may occur at any time while the subject is enrolled on study. Unscheduled 
procedures, including, but not limited to, vital signs, 12-lead ECG, and CT or MRI may be 
conducted at these visits. Data generated during an unscheduled visit will be collected on the 
eCRF.
6.12.13.
Protocol Deviations
Gilead’s policy prohibits exemptions from protocol inclusion/exclusion criteria. In the event of a 
significant deviation related to gross non-compliance from the protocol or incidences that impose 
significant risk to subject safety, the investigator or designee must notify Gilead and/or its 
designee immediately. The site will be required to document deviations in accordance with 
Gilead’s procedures and in accordance with the site’s procedures and processes.


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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An AE is any untoward medical occurrence in a clinical study subject administered a medicinal 
product, which does not necessarily have a causal relationship with the treatment. An AE can 
therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated 
with the use of a medicinal product, whether or not considered related to the medicinal product.
AEs may also include pre or post treatment complications that occur as a result of protocol 
specified procedures, overdose, drug abuse/misuse reports, or occupational exposure. Preexisting 
events that increase in severity or change in nature during or as a consequence of participation in 
the clinical study will also be considered AEs.
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion.
The condition that led to the procedure may be an adverse event and must be reported.

Pre-existing diseases, 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 
chemotherapy infusion per institutional guidelines, elective surgery, social and/or 
convenience admissions)

Overdose without clinical sequelae (see Section 7.7)

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.
7.1.2.
Serious Adverse Events
An SAE is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)


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
In-patient hospitalization or prolongation of existing hospitalization (Note: Hospitalization 
for chemotherapy infusion or other ‘social hospitalization’ per institutional guidelines will 
not be considered an SAE)

Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately life-threatening
or result in death or hospitalization but may jeopardize the subject or may require 
intervention to prevent one of the other outcomes constituting SAEs. Medical and scientific 
judgment must be exercised to determine whether such an event is a reportable under 
expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.1.2.1.
Protocol-Specific Serious Adverse Event Instructions
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 gastric cancer

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.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to study drug interruption, modification, 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 


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definition of an AE or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (eg, decreased hemoglobin).
For specific information on handling of clinical laboratory abnormalities in this study, please 
refer to Section 7.5.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified sub-investigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified sub-investigator is responsible for assessing the relationship to 
study drug using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the IMP. For SAEs, an 
alternative causality must be provided (eg, preexisting condition, underlying disease, 
intercurrent illness, or concomitant medication)

Yes: There is reasonable possibility that the event may have been caused by the study drug
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting. 
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study procedure

Yes: The adverse event occurred as a result of protocol procedures, (eg, venipuncture)
7.2.2.
Assessment of Severity
The severity of AEs will be graded using the Common Terminology Criteria for Adverse Events
(CTCAE), Version 4.03 in the study manual.
If a CTCAE term is not available for the AE/SAE, the severity will be graded using Grade 1 
through Grade 5 as defined in the CTCAE definitions.
The distinction between the seriousness and the severity of an AE should be noted. Severe is a
measure of intensity; thus, a severe (Grade 3) reaction is not necessarily a serious reaction.


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7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the case report form (eCRF): 

All SAEs and adverse events related to protocol-mandated procedures.
7.3.1.
Adverse Events
Following initiation of study medication, all AEs, regardless of cause or relationship, until 
30 days after last administration of andecaliximab and 5 months post-treatment of nivolumab,
must be reported to the eCRF database as instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible.
Gilead Sciences may request that certain AEs be followed beyond the protocol defined follow-up 
period.
7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol required post treatment follow-up period, must be reported to the 
eCRF database and Gilead DSPH as instructed. This also includes any SAEs resulting from 
protocol associated procedures performed after informed consent is signed.
Any SAEs and deaths that occur after the post treatment follow-up visit but within 30 days of the 
last dose of andecaliximab and 5 months post-treatment of nivolumab, regardless of causality, 
should also be reported.
Investigators are not obligated to actively seek SAEs after the protocol defined follow up period, 
however, if the investigator learns of any SAEs that occur after study participation has concluded 
and the event is deemed relevant to the use of study drug, he/she should promptly document and 
report the event to Gilead DSPH.

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline

SAEs will be reported using an electronic SAE (eSAE) system


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• 
Site personnel record all SAE data in the eCRF database within 24 hours of the investigator's 
knowledge of the event. Immediately after SAE data are recorded in the database, Gilead 
DSPH and Gilead Japan DSPH are notified via email that new SAE data are available. 
Detailed instructions can be found in the eCRF completion guidelines. 
• If for any reason it is not possible to record the SAE infonnation electr·onically, ie, the eCRF 
database is not functioning, record the SAE on the paper serious adverse event repo1ting 
fo1m and subinit within 24 hours to: 
GileadDSPH 
Fax: 
Email: 
Gilead DSPH will immediately fo1ward the infonnation received to DSPH at Gilead Japan. 
• 
As soon as it is possible to do so, any SAE reported via paper must be tr·anscribed into the 
eCRF Database according to instructions in the eCRF completion guidelines 
• If an SAE has been repo1ted via a paper fonn because the eCRF database has been locked, no 
fuither action is necessa1y 
• 
For fatal or life-threatening events, copies of hospital case reports, autopsy repo1ts, and other 
documents are also to be subinitted by e-mail or fax when requested and applicable. 
Transinission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers. 
• 
Additional infonnation may be requested to ensure the timely completion of accurate safety 
repolis 
• 
Any medications necessaiy for tr·eatinent of the SAE must be recorded onto the concomitant 
medication section of the subject's eCRF and the event description section of the SAE fonn 
7.3.2.2. 
Communication of Study Safety Info1mation to Study Sites 
Gilead Japan will conduct weekly calls with study investigators in Japan. During these calls, 
reviews of safety events obse1ved in all subjects in the study will be reviewed. Additionally, 
safety data will be collected and distributed to sites per the appropriate Gilead Standard 
Operating Procedures and local GCP. In the event of major safety events, Gilead Japan will 
urgently contact investigators via email or phone. Study monitoring will be perfo1med by the 
local CRO, Gilead Japan, and Gilead USA (available by phone, email, or fax as described in the 
protocol). The following table outlines the methods for shai·ing emerging safety ale1t in Study 
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Major Safety Information
Other Safety Information
Urgent/emergent communication via email/phone with 
investigators within 24 hours of determining an urgent 
safety measure needs to be disseminated to investigators
Weekly investigator calls with minutes distributed to all 
participants
Weekly investigator calls with minutes distributed to all 
participants 
Updates to informed consent form (ICF)
Updates to ICF
Updates to Investigator Brochure if there is any safety 
signal identified and routine annual updates
Updates to Investigator Brochure if there is any safety 
signal identified
Expedited reporting
Investigator Safety Letter is required for all suspected 
unexpected serious adverse reactions (SUSARs)
occurring in any GSI sponsored conventional clinical 
trials and compassionate use trials.  Those safety letters 
will be distributed to all investigators accordingly. 
7.3.2.3.
Communication of Andecaliximab Safety Information from Other Studies
Safety information related to andecaliximab from other than the proposed study will be collected 
according to the same processes as for this study. For non-serious safety information, adverse 
events are collected through electronic data capture (EDC) system and databased in Gilead’s 
clinical database. Pre-clinical safety data that is non-urgent in nature will be presented to DSPH 
for inclusion in periodic aggregate reports. SAEs are collected/databased into both the Gilead 
safety (DSPH) database and clinical database according to the timelines specified in the clinical 
protocol or, in the event that a CRO is involved in safety reporting, per relevant Clinical Trial 
Safety Reporting Procedure. 
Urgent safety issues from any source are presented to Gilead clinical and safety representatives 
as urgently as possible for cross functional committee review. Safety data will be collected at 
night/after business hours/holidays via the eCRF system and will be assessed by Gilead 
immediately. If the eCRF database is not available, data should be collected via a paper reporting 
form, for SAEs this data should be recorded within 24 hours. Protocol Section 7.3 describes this 
process in more detail.
In the event of a major safety event, Gilead Japan will urgently contact investigators via email or 
phone within 24 hours of determining an urgent safety measure needs to be disseminated to 
investigators. Routine safety data from other studies will be shared in annual investigator 
brochure updates. The following table outlines the methods for sharing emerging safety 
information with Study GS-US-296-1884 investigators. 


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Major Safety Information
Other Safety Information
Urgent/emergent communication via email/phone with 
investigators within 24 hours of determining an urgent 
safety measure needs to be disseminated to investigators
Updates to ICF
Weekly investigator calls with minutes distributed to all 
participants 
Updates to Investigator Brochure if there is any safety 
signal identified and routine annual updates
Updates to ICF
Investigator Safety Letter is required for all SUSARs 
occurring in any GSI sponsored conventional clinical 
trials and compassionate use trials.  All investigators 
receive a copy of the investigator safety letters.
Updates to Investigator Brochure if there is any safety 
signal identified
7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the IB or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy.
7.5.
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 study drug interruption or discontinuation must be recorded as an AE, as 
well as an SAE, if applicable. In addition, laboratory or other abnormal assessments (eg, ECG, 
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 7.1.1 and 7.1.2, 
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).


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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.
7.6.
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. Laboratory abnormalities (eg, thiamine deficiency) identified at screening/baseline 
and during study participation should be treated at the investigators discretion.
Any questions regarding toxicity management should be directed to the Gilead Sciences medical 
monitor or designee.
7.7.
Special Situations Reports
7.7.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, and pregnancy reports regardless of an 
associated AE.  
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject 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). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.  


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7.7.2. 
7.7.2.1. 
Instructions for Reporting Special Situations 
Instiuctions for Repo1iing Pregnancies 
Final 
Arnendment3 
The investigator should repo1i pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study, including the post study drng follow-up 
period, to Gilead DSPH using the pregnancy repo1i fo1m within 24 hours of becoming aware of 
the pregnancy. 
Refer to the eCRF completion guidelines for full instiuctions on the mechanism of pregnancy 
repo1iing. 
The pregnancy itself is not considered an AE nor is an induced elective abortion to te1minate a 
pregnancy without medical reasons. 
Any premature te1mination of pregnancy ( eg, a spontaneous abo1iion, an induced therapeutic 
abo1iion due to complications or other medical reasons) must be repo1ied within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE te1m. 
A spontaneous abortion is always considered to be an SAE and will be repo1ied. Fmihe1more, 
any SAE occmTing as an adverse pregnancy outcome post study must be reported to Gilead 
DSPH. 
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be repo1ied to Gilead DSPH using the pregnancy outcome repo1i 
fo1m. If the end of the pregnancy occurs after the study has been completed, the outcome should 
be reported directly to Gilead DSPH. 
Pregnancies of female paiiners of male study subjects exposed to Gilead or other study diugs 
must also be repo1ied and relevant info1mation should be submitted to Gilead DSPH using the 
pregnancy and pregnancy outcome fo1ms within 24 hours. Monitoring of the subject should 
continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after the study 
has been completed, the outcome should be reported directly to Gilead DSPH. 
Gilead DSPH contact infonnation is as 
follows: 
Email: 
Fax: 
PD 
PD 
Refer to Appendix 9 for Pregnancy Precautions, Definition for Female of Childbeai·ing Potential, 
and Contl'aceptive Requirements. 
7.7.2.2. 
Repo1iing Other Special Situations 
All other special situation repo1is must be repo1ied on the special situations repo1i fonn and 
fo1wai·ded to Gilead DSPH within 24 hours of the investigator becoming aware of the situation. 
These repo1is must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead conc01nitant medications. 
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Special situations involving non-Gilead concomitant medications do not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form. 
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to the eCRF completion guidelines for full instructions on the mechanism of special 
situations reporting.
All clinical sequelae in relation to these 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.


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8. 
8.1. 
8.1.1. 
STATISTICAL CONSIDERATIONS 
Analysis Objectives and Endpoints 
Analysis Objectives 
The prima1y objective is: 
Final 
Arnendment3 
• 
To characterize the safety and tolerability of andecaliximab as monotherapy and in 
combination with anti-cancer agents in Japanese subjects with inoperable advanced or 
recunent gastric or GEJ adenocarcinoma 
The secondaiy objectives are: 
• 
To chai·acterize the PK of andecaliximab 
• 
To evaluate the fo1mation of anti-andecaliximab antibodies 
The explorato1y objectives ai·e: 
I 
I 
I 
8.1.2. 
Primary Endpoint 
The prima1y endpoint is safety, which will be evaluated by clinical laborato1y test findings, PEs, 
12-lead ECGs, vital signs measurements, and incidence of AEs in each treatment dose 
level/ coho1i . 
8.1.3. 
Secondary Endpoint 
Secondai·y endpoints ai·e: 
• 
Plasma concentrations and PK pai·ameters (e.g. Cmax, AUC) of andecaliximab 
• 
fucidence rate of positive anti-andecaliximab antibodies 
8.1.4. 
Other Endpoints of Interest 
Explorato1y endpoints of interest ai·e: 
I 
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I 
I 
I 
I 
I 
I 
I 
I 
8.2. 
8.2.1. 
8.2.1.1. 
Analysis Conventions 
Analysis Sets 
Safety Analysis Set 
Final 
Arnendment3 
The Safety Analysis Set is defined as all subjects who receive at least 1 infusion at any dose of 
andecaliximab. This analysis set will be used for both safety and efficacy analyses. 
8.2.1.2. 
Phaimacokinetic/Phaimacodynamic Analysis Set 
The PK/PD Analysis Set is defined as all subjects in the Safety Analysis Set who have the 
necessaiy baseline and on study measmements to provide interpretable results for specific 
pai·ameters of interest. 
8.2.1.3. 
Biomai·kers 
Refer to Section 8.8 for Biomai·ker Analysis. 
8.3. 
Data Handling Conventions 
By-subject listings will be created for important variables from each eCRF module. Summaiy 
tables for continuous vai·iables will contain the following statistics: N (number in population), 
n (number with data), mean, standard deviation, 90% confidence intervals (Cls) on the mean, 
median, minimum, and maximum. Summaiy tables for categorical vai·iables will include: N, n, 
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percentage, and 90% CIs on the percentage. Unless otherwise indicated, 90% CIs for binary 
variables will be calculated using the binomial distribution (exact method) and will be 2 sided. 
Data will be described and summarized by dose level/cohort, analysis set, and time point. 
As appropriate, changes from baseline to each subsequent time point will be described and 
summarized. Similarly, as appropriate, the best change from baseline during the study will also 
be described and summarized. Graphical techniques (eg, waterfall plots, Kaplan-Meier (KM)
curves, line plots) may be used when such methods are appropriate and informative. 
The baseline value used in each analysis will be the last (most recent) pretreatment value. 
Data from all sites will be pooled for all analyses. Analyses will be based upon the observed data 
unless methods for handling missing data are specified. If there is a significant degree of 
non-normality, analyses may be performed on log-transformed data or nonparametric tests may 
be applied, as appropriate. 
The following censoring conventions will be applied to tumor control endpoints:

PFS: Data from surviving, non-progressing subjects will be censored at the earliest of the 
time of initiation of antitumor treatment other than the study treatment or the last time that 
lack of definitive progression was objectively documented. Data from subjects who have 
disease progression or die after ≥ 2 consecutive missing tumor assessments will be censored 
at the last time prior to the missing assessments that lack of definitive disease progression 
was objectively documented.

OS: Data from surviving subjects will be censored at the last time that the subject was known 
to be alive.

DOR: Data from surviving, non-progressing subjects will be censored at the earliest of the 
time of initiation of antitumor treatment other than the study treatment or the last time that 
lack of definitive disease progression was objectively documented. Data from subjects who 
have disease progression or die after ≥ 2 consecutive missing tumor assessments will be 
censored at the last time prior to the missing assessments that lack of definitive disease 
progression was objectively documented.
8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline measurements will be summarized for the Safety Analysis Set by 
treatment dose level/cohort using standard descriptive methods 
Demographic summaries will include sex, race/ethnicity, and age.
Baseline data will include a summary of body weight, height and body mass index.
8.5.
Efficacy Analysis
The efficacy of andecaliximab when used as monotherapy or in combination with chemotherapy 
will be evaluated using the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1.


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8.5.1.
Categorical Endpoints
Categorical endpoints, such as ORR and DCR will be summarized. The corresponding 
90% exact CIs may be present if appropriate. 
8.5.2.
Time-to-Event Endpoints
Time-to-event endpoints, such as PFS, OS, and DOR, will be analyzed using KM methods.
The KM estimate of the survival function will be computed and the results will be presented 
using KM curves. The median will be provided along with the corresponding 90% CI. 
Additionally, the 25% and 75% percentiles for these endpoints will also be provided.
8.5.3.
Continuous Endpoints
Continuous endpoints, such as TTR and change in tumor size, will be summarized using 
descriptive statistics as standard. Waterfall plots may be used. 
8.6.
Safety Analysis
All safety data collected on or after the date that andecaliximab and if applicable, nivolumab was 
first administered up to 30 days after the last dose of andecaliximab or if applicable, 5 months 
post-treatment of nivolumab (whichever is later), will be summarized by treatment dose 
level/cohort. Data for the pre-treatment and post-treatment follow-up period will be included in 
data listings. 
For categorical safety data including incidence of adverse events and categorizations of 
laboratory data, count and percent of subjects will be summarized. For continuous safety data 
including laboratory data, sample size, mean, standard deviation, minimum, quartiles, median, 
and maximum will be summarized.
8.6.1.
Extent of Exposure
Data on a subject’s extent of exposure to study treatments (andecaliximab, S-1, cisplatin, 
oxaliplatin, and nivolumab) will be generated from the drug administration eCRF pages 
respectively. Exposure data will be summarized by treatment dose level/cohort.
8.6.2.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term, and Lower-Level Term (LLT) will be 
attached to the clinical database.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
adverse event will be defined as any adverse event that begins on or after the date of first dose of 
andecaliximab up to 30 days after the last dose of andecaliximab.


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Summaries (number and percentage of subjects) of treatment-emergent adverse events (by SOC, 
and PT) will be provided by treatment dose level/cohort.
8.6.3.
Laboratory Evaluations
Selected laboratory data (using conventional units) will be summarized using only observed data. 
Data and change from baseline at all scheduled time points will be summarized.
Graded laboratory abnormalities will be defined using the CTCAE Version 4.03. 
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time point post baseline will be summarized by treatment 
cohort. If baseline data are missing, then any graded abnormality (ie, at least a Grade 1) will be 
considered treatment-emergent.
Laboratory abnormalities that occur before the first dose of andecaliximab or after the subject 
has been discontinued from treatment for at least 30 days will be included in a data listing.
8.6.4.
Other Safety Evaluations
Similar general approaches to the AE and clinical laboratory data will be utilized to summarize 
other safety measures.
8.7.
Pharmacokinetic Analysis
The plasma concentration data of andecaliximab will be summarized by nominal sampling time 
using descriptive statistics (eg, sample size, arithmetic mean, geometric mean, % coefficient of 
variation, standard deviation, median, minimum, and maximum) by dose level/cohort. 
Pharmacokinetic parameters (Cmax, Clast, tmax, tlast, λz, AUClast, AUCinf, CL, V, and t½, as 
applicable) will be listed and summarized using descriptive statistics by dose level/cohort. 
Plasma concentrations of andecaliximab over time may be plotted in semi logarithmic and linear 
formats as mean standard deviation by dose level/cohort.
The number and percentage of positive or negative anti-andecaliximab antibody values at each 
specified timepoint will be summarized. The effect of anti-andecaliximab antibodies on 
andecaliximab PK, safety, and efficacy may be evaluated.
8.8.
Biomarker Analysis
8.8.1.
Pharmacodynamic Analysis
The pharmacodynamic biomarkers of interest are described in Section 3.11. The baseline level 
and change over time from baseline level will be evaluated. Descriptive statistics will be 
provided at each sampling time, by dose level.


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8.8.2. 
Exploratory Biomarker Analysis 
8.9. 
Sample Size 
Final 
Arnendment3 
The sample size of 6 subjects in Coho1i 1 allows a relatively high probability (> 65%) to observe 
2 or more subjects with DLT when the hue underlying probability of DLT is greater than 33.3% 
at cmTent dose level. 
Up to 6 subjects will be enrolled in Coho1i 1 to receive 800 mg andecaliximab Q2W, and based 
on safety assessments, an additional 6 subjects may be enrolled in Coho1i 1 to receive 600mg 
andecaliximab Q2W prior to proceeding with the combination therapy coho1is. Based on the 
dose level selected by Coho1i 1, up to 6 subjects will be enrolled in Coho1i 2 (combination 
therapy andecaliximab and SP), and up to 10 subjects will be enrolled in Coho1is 3 (combination 
therapy andecaliximab and SOX) and 4 (combination therapy andecaliximab and nivolumab), 
respectively. 
Therefore, up to 38 subjects will be enrolled in the 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. 
The investigator will ensure adherence to 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.
The investigator and all applicable subinvestigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, informed consent form, 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) to an IRB/IEC. The investigator will not begin any study subject activities 
until approval from the IRB/IEC has been documented and provided as a letter to the 
investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/IEC for any modifications made to the protocol or any accompanying material to be 
provided to the subject after initial approval, with the exception of those necessary to reduce 
immediate risk to study subjects.
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 use the most current IRB/IEC-approved consent form for documenting written 


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informed consent. Each informed consent (or assent as applicable) will be appropriately signed 
and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by IRB/IEC local 
requirements. The consent form will inform subjects about pharmacogenomic testing and sample 
retention, and their right to receive clinically relevant pharmacogenomic analysis results.
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, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form or biological sample submitted to the Sponsor, IRB/IEC, or laboratory. Laboratory 
specimens must be labeled in such a way as to protect subject identity while allowing the results 
to be recorded to the proper subject. Refer to specific laboratory instructions. NOTE:
The investigator must keep a screening log showing codes, names, and addresses for all subjects 
screened and for all subjects enrolled in the trial. Subject data will be processed in accordance 
with all applicable regulations. 
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator brochure, this protocol, eCRF, the IMP, 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 two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, CRF and query forms,
IRB/IEC 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 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, PE, and confirmation of 
diagnosis (to support inclusion and exclusion criteria);


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
Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);

Study 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 IMP, including dates of dispensing and return;

Record of all adverse events and other safety parameters (start and end date, and including 
causality and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, 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 planned 
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 
specified by 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 provide for 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 records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRFs should be 
completed on the day of the subject visit to enable the sponsor to perform central monitoring of 
safety data. The Eligibility Criteria eCRF should be completed only after all data related to 
eligibility have been received. Subsequent to data entry, a study monitor will perform source data 


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verification within the EDC system. Original entries as well as any changes to data fields will be 
stored in the audit trail of the system. Prior to database lock (or any interim time points as 
described in the clinical data management plan), the investigator will use his/her log in 
credentials to confirm that the forms have been reviewed, and that the entries accurately reflect 
the information in the source documents. The eCRF capture the data required per the protocol 
schedule of events and procedures. System-generated or manual queries will be issued to the 
investigative site staff as data discrepancies are identified by the monitor or internal Gilead staff, 
who routinely review the data for completeness, correctness, and consistency. The site 
coordinator is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry, and providing the reason 
for the update (e.g. data entry error). At the conclusion of the trial, Gilead will provide the site 
with a read-only archive copy of the data entered by that site. This archive must be stored in 
accordance with the records retention requirements outlined in Section 9.1.5.
9.1.7.
Investigational Medicinal Product Accountability and Return
Used and unused study drug supplies should be destroyed on site 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 study drug supplies in accordance with that 
site’s approved SOP. A copy of the site’s approved SOP will be obtained for central files.
The study monitor will evaluate each study center’s study drug disposal procedures and provide 
appropriate instruction for destruction of unused study drug supplies on site. The investigator 
must maintain accurate records for all study drug destroyed at the site. Records must show the 
identification and quantity of each unit destroyed, the method of destruction, and the person who 
disposed of the study drug. Upon study completion, copies of the study drug accountability 
records must be filed at the site. Another copy will be returned to Gilead.
If destruction of study drug on site is not possible, arrangements will be made between the site 
and Gilead Sciences (or Gilead Sciences’ representative) for return of unused study drug 
supplies. The monitor will provide further instructions for the return.
The study monitor will review IMP supplies and associated records at study monitoring visits. 
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRBs/IECs, 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.


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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. The investigator must submit all protocol modifications to the IRB/IEC in 
accordance with local requirements and receive documented IRB/IEC approval before 
modifications can be implemented.
9.2.2.
Study Report and Publications
A clinical study report (CSR) 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.
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

The investigator will submit to Gilead 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. 

No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.4).
The investigator will comply with Gilead’s request to delete references to its 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.


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9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
eCRF.
The monitor is responsible for routine review of the eCRF at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the eCRF. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected through any type of monitoring (central, on site) 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), IRBs, and IECs. 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.
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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table – Cohort 1 (Andecaliximab Monotherapy)
Appendix 3.
Study Procedures Table – Cohort 2: Combination Therapy Andecaliximab and SP
Appendix 4.
Study Procedures Table – Cohort 3: Combination Therapy Andecaliximab and SOX
Appendix 5.
Study Procedures Table – Cohort 4: Combination Therapy Andecaliximab and 
Nivolumab
Appendix 6.
Proposed Regimen for Combination Therapy Andecaliximab and SP
Appendix 7.
Regimen for Combination Therapy Andecaliximab and SOX
Appendix 8.
Regimen for Combination Therapy Andecaliximab and Nivolumab
Appendix 9.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 10.
Revised RECIST Guideline (Version 1.1)


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Amendment 3 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY CA 94404 
STIJDYACKNOWLEDGEMENT 
A Phase lb Study to Evaluate the Safety and Tolerability of Andecaliximab (GS-5745) as 
Monotherapy and in Combination with Chemotherapy in Japanese Subjects with Gastric or 
Gastroesophageal Junction Adenocarcinoma 
GS-US-296-1884, Amendment 3, 14 July 2017 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
PPn 
·ppo 
[PPD 
Medical Monitor 
Date 
INVESTIGATOR STATEMENT 
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 will 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 
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14 July 2017 


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Appendix 2.
Study Procedures Table – Cohort 1 (Andecaliximab Monotherapy)
Cohort 1 (Andecaliximab Monotherapy)
Study Phase
Screening
Each Cycle
(28 Days)
Cycle 1
Every 
8 Weeksk
EOTl
EOS
30-Day 
Safety 
Follow-
Upm
5-Year 
LTFUr
Cycle Day
Screening
1
15
2
4
8
29/Cycle 2 
Day 1q
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1
± 1
± 1
± 5
N/A
N/A
± 7
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
X
X
X
X
Vital Signsc
X
X
X
X
X
X
X
X
X
X
12-Lead ECG
X
X
X
X
ECOG Performance 
Status
X
X
X
X
X
X
X
X
X
X
Prior/Concomitant 
Meds
X
X
X
X
X
X
X
X
X
X
X
AEsd
X
X
X
X
X
X
X
X
X
X
X
CT or MRIe
X
X
X
Collect Archival 
Tumor Tissue 
(if Available)f
X
Sample Collection
Chemistry
X
Xh
X
X
X
X
X
X
X
Hematology
X
Xh
X
X
X
X
X
X
X
 
 


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Cohort 1 (Andecaliximab Monotherapy)
Study Phase
Screening
Each Cycle
(28 Days)
Cycle 1
Every 
8 Weeksk
EOTl
EOS
30-Day 
Safety 
Follow-
Upm
5-Year 
LTFUr
Cycle Day
Screening
1
15
2
4
8
29/Cycle 2 
Day 1q
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1
± 1
± 1
± 5
N/A
N/A
± 7
N/A
Coagulation
X
Xh
X
X
X
X
X
Urinalysis
X
Xh
X
X
X
X
Pregnancy testg
X
Xh
X
X
Andecaliximab 
Concentrationi
X
X
X
X
X
X
X
X
X
Anti-Andecaliximab 
Antibodiesj
X
X
X
X
Blood Biomarkersn
X
X
X
X
X
X
X
X
X
X
Tumor Tissue 
Biopsyo
X
X
Normal Gastric 
Tissue Biopsyp
X
Overall Survival 
and Other 
Antitumor Therapy
X (Every 
3 months)
Study Drug Dosing
Andecaliximab IV 
Dosing
X
X
X
EOS = End of Study (visit); EOT = End of treatment (visit); LTFU = Long Term Follow Up; PE = physical examination; PK: pharmacokinetics 
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.


Andecaliximab
Protocol GS-US-296-1884
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
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14 July 2017
b
A complete PE will be performed at screening. A modified PE capturing changes from prior exams will be performed on Day 1 and 15 of each 28-day cycle, and at the EOT 
visit, at the EOS visit, and at the 30-day safety follow-up visit. 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 andecaliximab dosing during applicable visits. 
e
Tumor evaluation by CT or MRI will be performed during screening (scans taken as part of standard medical practice within 28 days of Day 1 are acceptable), every 8 weeks, 
and at the EOS visit (if not conducted within the previous 28 days). The same radiographic procedure used to define measurable lesions must be used throughout the study for 
each subject. 
f
Archival tumor tissue FFPE blocks will be collected from all subjects. Efforts to acquire archival tissue block should begin on Cycle 1 Day 1.
g
For females of childbearing potential, a serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Cycle 1 Day 1 Pre Dose, at the 
EOS visit, and at the 30-day safety follow-up visit. 
h
Day 1 pre dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit. 
i
Plasma samples for andecaliximab PK will be collected prior to andecaliximab dosing and 30 (15) minutes after the end of infusion on Day 1 of Cycles 2, 3, 5, 7, and every 
3 cycles thereafter, at the EOT visit (if not conducted in the last 2 weeks), and EOS visit. Additionally, PK plasma samples will be collected at the following time points in 
Cycle 1 only: 30 (15) minutes after the end of infusion on Day 1; anytime on Days 2, 4, and 8; prior to dosing and 30 (15) minutes after the end of infusion on Day 15
j
Blood samples for anti-andecaliximab antibodies will be collected prior to dosing on Day 1 of Cycles 1, 2, 3, 5, 7, and every 3 cycles thereafter, at the EOT visit (if not 
conducted in the last 2 weeks), at the EOS visit, and at the 30-day safety follow-up visit. 
k
Every 8 Weeks (± 5 days) assessments will be performed for subjects continuing treatment, or subjects who discontinue all treatment prior to disease progression but remain 
on study. 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), and blood samples for chemistry, hematology, coagulation, and blood biomarkers (if not collected in the last 2 weeks) every 8 weeks until disease progression.
l
EOT assessments will be requested by subjects who discontinue all treatment prior to disease progression. These assessments should be completed as soon as possible after 
the decision is made. Every attempt should be made to keep the subject in the study and continue to perform tumor evaluation by CT or MRI every 8 weeks until disease 
progression. Blood samples for hematology, coagulation, chemistry, blood biomarkers, andecaliximab concentration and anti-andecaliximab antibodies should only be 
collected if not conducted in the last 2 weeks.
m
A safety follow-up visit will be performed 30 days (± 7 days) after the last dose of andecaliximab. The 30-day safety follow-up visit may be substituted by a scheduled study 
visit if it occurs within the same window. 
n
Blood samples for biomarkers will be collected Pre Dose on Day 1 of each cycle, Day 15 of Cycles 1 and 2, and every 8 weeks, at the EOT (if not conducted in the last 
2 weeks) visit, and EOS visit. Additionally, blood samples for biomarkers will be collected on Days 2, 4, and 8 of Cycle 1.
o
Tumor tissue biopsy must be collected within 28 days prior to first dose and on Cycle 2 Day 15 (+ 5 days). Endoscopic samples (minimum 4, but 6-8 encouraged) to be 
processed as described in the laboratory manual.
p
Normal gastric tissue biopsy must be collected within 28 days prior to first dose (Day 1 of Cycle 1 Pre Dose). Endoscopic samples (minimum 4, but 6-8 encouraged) to be 
processed as described in the laboratory manual.
q
The Cycle 1 Day 29 visit, which overlaps with the Cycle 2 Day 1 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 dose of GS-5745, completed all safety procedures through Day 28, or have experienced a DLT prior to Day 28.
Assessments should follow schedule for Day 1 of each 28-day cycle. 
r
LTFU for OS 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 of long 
term survival status and record of any other anti-cancer therapy, cancer-related surgery for up to 5 years after the EOS visit. 


Andecaliximab
Protocol GS-US-296-1884
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 120
14 July 2017
Appendix 3.
Study Procedures Table – Cohort 2: Combination Therapy Andecaliximab and SP
Cohort 2: Combination Therapy Andecaliximab and SP
Study Phase
Screening
Each Cycle 
(28 Days)
Every 
8 Weeksr
EOTs
EOSt
30-Day Safety 
Follow-Upu
5-Year 
LTFUv
Cycle Day
Screening
1
15
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1q
± 1
± 5
N/A
N/A
± 7
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
X
X
X
Vital Signsc
X
X
X
X
X
X
12-Lead ECG
X
X
X
ECOG Performance 
Status
X
X
X
X
X
X
Prior/Concomitant 
Meds
X
X
X
X
X
X
X
AEsd
X
X
X
X
X
X
X
CT or MRIe
X
X
X
Collect Archival 
Tumor Tissuef
X
Sample Collection
Chemistry
X
Xh
X
X
X
X
X
Hematology
X
Xh
X
X
X
X
X
Coagulation
X
Xh
X
X
X
X
Urinalysis
X
Xh
X
X
X


Andecaliximab
Protocol GS-US-296-1884
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 121
14 July 2017
Cohort 2: Combination Therapy Andecaliximab and SP
Study Phase
Screening
Each Cycle 
(28 Days)
Every 
8 Weeksr
EOTs
EOSt
30-Day Safety 
Follow-Upu
5-Year 
LTFUv
Cycle Day
Screening
1
15
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1q
± 1
± 5
N/A
N/A
± 7
N/A
Pregnancy testg
X
Xh
X
X
X
Andecaliximab 
Concentrationi
X
X
X
X
Anti-Andecaliximab 
Antibodiesj
X
X
X
X
Blood Biomarkersk
X
X
X
X
X
X
Tumor Tissue Biopsyl
X
X
Normal Gastric 
Tissue Biopsym
X
Endoscopic 
Evaluationn
X
Overall Survival and 
Other Antitumor 
Therapy
X (Every 
3 months)
Dosing
Andecaliximab IV 
Dosingo
X
X
S-1 Dosingp
Cisplatin Dosingp
EOS = End of Study (visit); EOT = End of treatment (visit); LTFU = Long Term Follow Up; PE = physical examination; PK = pharmacokinetics
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 on Day 1 and 15 of each 28-day cycle, at the EOT visit, 
at the EOS visit, and at the 30-day safety follow-up visit. 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.


Andecaliximab
Protocol GS-US-296-1884
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 122
14 July 2017
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 andecaliximab dosing during applicable visits. 
e
Tumor evaluation by CT or MRI will be performed during screening (scans taken as part of standard medical practice within 28 days of Day 1 are acceptable), every 8 weeks, 
and at the EOS visit (if not conducted within the previous 28 days). The same radiographic procedure used to define measurable lesions must be used throughout the study for 
each subject. 
f
Archival tumor tissue will be collected from all subjects with available tissue. Efforts to acquire archival tissue should begin on Cycle 1 Day 1.
g
For females of childbearing potential, a serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Pre Dose on Days 1 and 15 of 
each cycle, at the EOS visit, and at the 30-day safety follow-up visit
h
Day 1 pre dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit. 
i
Plasma samples for andecaliximab PK in Cycle 1 will be collected 30 (± 15) minutes after the end of infusion on Day 1 and prior to andecaliximab dosing on Day 15. 
Additionally, plasma samples for andecaliximab PK will be collected prior to andecaliximab dosing and 30 (± 15) minutes after the end of infusion on Day 1 of Cycles 2, 3, 5, 
7, and every 3 cycles thereafter and anytime at the EOT visit (if not conducted in the last 2 weeks), and EOS visit. 
j
Blood samples for anti-andecaliximab antibodies will be collected prior to dosing on Day 1 of Cycles 1, 2, 3, 5, 7, and every 3 cycles thereafter; at the EOT visit (if not 
conducted in the last 2 weeks), at the EOS visit, and at the 30-day safety follow-up visit.
k
Blood samples for biomarkers will be collected Pre Dose on Day 1 of every cycle, Day 15 of Cycles 1 and 2, and every 8 weeks; at the EOT visit (if not conducted in the last 
2 weeks), and at the EOS visit. 
l
Tumor tissue biopsy must be collected within 28 days prior to or on Day 1 of Cycle 1 Pre Dose and at EOS with documented disease progression. 
m
Normal gastric tissue biopsy must be collected within 28 days prior to or on Day 1 of Cycle 1 Pre Dose. Do not collect if stomach is free of tumor. 
n
An endoscopic evaluation must be performed alongside tissue biopsy collection 28 days prior to or on Day 1 of Cycle 1 Pre Dose. Do not perform if stomach is free of tumor. 
o
Andecaliximab to be administered by IV infusion over 30 (± 5) minutes 
p
The dosage and regimen of S-1 and cisplatin will be based on subject condition, investigator discretion, institutional practice and/or in the in country label. Due to expected 
variation in administration schedules, chemotherapy dosing may or may not take place on Days 1 and 15 of each 28-day cycle. See Appendix 6 for proposed regimen.
q
C1D1 must occur within 3 days following enrollment in IWRS. A ± 1 day window applies to visits following Cycle 1 Day 1. 
r
Every 8 Weeks (± 5 days) assessments will be performed for subjects continuing treatment, or subjects who discontinue all treatment prior to disease progression but remain 
on study. 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), and blood samples for chemistry, hematology, coagulation, and blood biomarkers (if not collected in the last 2 weeks) every 8 weeks until disease progression.
s
EOT assessments will be requested from subjects who discontinue all treatment prior to disease progression. These assessments should be completed as soon as possible after 
the decision is made. Every attempt should be made to keep the subject in the study and continue to perform tumor evaluation by CT or MRI every 8 weeks until disease 
progression. Blood samples for hematology, coagulation, chemistry, blood biomarkers, andecaliximab concentration and anti-andecaliximab antibodies should only be 
collected if not conducted in the last 2 weeks.
t
EOS assessments will be completed when the subject meets at least 1 criterion for study discontinuation in Section 3.7. 
u
A safety follow-up visit will be performed 30 days (± 7 days) after the last dose of andecaliximab. The 30-day safety follow-up visit may be substituted by a scheduled study
visit if it occurs within the same window.
v
LTFU for OS 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 of long 
term survival status and record of any other anti-cancer therapy, cancer-related surgery for up to 5 years after the EOS visit.


Andecaliximab
Protocol GS-US-296-1884
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 123
14 July 2017
Appendix 4.
Study Procedures Table – Cohort 3: Combination Therapy Andecaliximab and SOX
Cohort 3: Combination Therapy Andecaliximab and SOX
Study Phase
Screening
Each Cycle 
(21 Days)
Every 9 Weekss
EOTt
EOSu
30-Day Safety 
Follow-Up 
Visitv
5-Year LTFUw
Cycle Day
Screening
1
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1r
± 5
N/A
N/A
± 7
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
X
X
Vital Signsc
X
X
X
X
X
12-Lead ECG
X
X
X
ECOG Performance 
Status
X
X
X
X
X
Prior/Concomitant 
Meds
X
X
X
X
X
X
AEsd
X
X
X
X
X
X
CT or MRIe
X
X
X
Collect Archival 
Tumor Tissuef
X
Sample Collection
Chemistry
X
Xh
X
X
X
X
Hematology
X
Xh
X
X
X
X
Coagulation
X
Xh
X
X
X
Urinalysis
X
Xh
X
X


Andecaliximab
Protocol GS-US-296-1884
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 124
14 July 2017
Cohort 3: Combination Therapy Andecaliximab and SOX
Study Phase
Screening
Each Cycle 
(21 Days)
Every 9 Weekss
EOTt
EOSu
30-Day Safety 
Follow-Up 
Visitv
5-Year LTFUw
Cycle Day
Screening
1
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1r
± 5
N/A
N/A
± 7
N/A
Pregnancy testg
X
Xh
X
X
Andecaliximab 
Concentrationi
X
X
X
Anti-Andecaliximab 
Antibodiesj
X
X
X
X
Blood Biomarkersk
X
X
X
X
X
Tumor Tissue 
Biopsyl
X
X
Normal Gastric 
Tissue Biopsym
X
Endoscopic 
Evaluationn
X
Overall Survival 
and Other 
Antitumor Therapy
X (Every 
3 months)
Dosing
Andecaliximab IV 
Dosingo
X
S-1 Dosingp
X
Oxaliplatin Dosingq
X
EOS = End of Study (visit); EOT = End of treatment (visit); LTFU = Long Term Follow Up; PE = physical examination; PK = pharmacokinetics
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.


Andecaliximab
Protocol GS-US-296-1884
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 125
14 July 2017
b
A complete PE will be performed at screening. A modified PE capturing changes from prior exams will be performed on Day 1 of each 21-day cycle and at the EOT visit, at 
the EOS visit, and at the 30-day safety follow-up visit. 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 andecaliximab dosing during applicable visits. 
e
Tumor evaluation by CT or MRI will be performed during screening (scans taken as part of standard medical practice within 28 days of Day 1 are acceptable), every 9 weeks, 
and at the EOS visit (if not conducted within the previous 28 days). The same radiographic procedure used to define measurable lesions must be used throughout the study for 
each subject. 
f
Archival tumor tissue will be collected from all subjects with available tissue. Efforts to acquire archival tissue should begin on Cycle 1 Day 1.
g
For females of childbearing potential, a serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Pre Dose on Day 1of each 21-day 
cycle, at the EOS visit, and at the 30-day safety follow-up visit.
h
Day 1 pre dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit. 
i
Plasma samples for andecaliximab PK in Cycle 1 will be collected 30 (± 15) minutes after the end of andecaliximab infusion on Day 1. Additionally, plasma samples for 
andecaliximab PK will be collected prior to andecaliximab dosing and 30 (± 15) minutes after the end of infusion on Day 1 of Cycles 2, 3, 5, 7, and every 3 cycles thereafter
and anytime at the EOT visit (if not conducted in the last 2 weeks), and EOS visit. 
j
Blood samples for anti-andecaliximab antibodies will be collected prior to dosing on Day 1 of Cycles 1, 2, 3, 5, 7, and every 3 cycles thereafter; at the EOT visit (if not 
conducted in the last 2 weeks), at the EOS visit, and at the 30-day safety follow-up visit. 
k
Blood samples for biomarkers will be collected Pre Dose on Day 1 of every cycle, and every 9 weeks; at the EOT visit (if not conducted in the last 2 weeks), and at the EOS 
visit. 
l
Tumor tissue biopsy must be collected within 28 days prior to or on Day 1 of Cycle 1 Pre Dose and at EOS with documented disease progression. 
m
Normal gastric tissue biopsy must be collected within 28 days prior to or on Day 1 of Cycle 1 Pre Dose. Do not collect if stomach is free of tumor. 
n
An endoscopic evaluation must be performed alongside tissue biopsy collection 28 days prior to or on Day 1 of Cycle 1 Pre Dose. Do not perform if stomach is free of tumor. 
o
Andecaliximab to be administered via IV infusion over 30 (± 5) minutes
p
S-1 to be administered orally twice daily for the first 14 days of the 21-day cycle
q
Oxaliplatin to be administered by IV infusion over 2 hours on Day 1 of each 21-day cycle
r
C1D1 must occur within 3 days following enrollment in IWRS. A ± 1 day window applies to visits following Cycle 1 Day 1.
s
Every 9 Weeks (± 5 days) assessments will be performed for subjects continuing treatment, or subjects who discontinue all treatment prior to disease progression but remain 
on study. 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), and blood samples for chemistry, hematology, coagulation, and blood biomarkers (if not collected in the last 2 weeks) every 9 weeks until disease progression.
t
EOT assessments will be requested from subjects who discontinue all treatment prior to disease progression. These assessments should be completed as soon as possible after 
the decision is made. Every attempt should be made to keep the subject in the study and continue to perform tumor evaluation by CT or MRI every 9 weeks until disease 
progression. Blood samples for hematology, coagulation, chemistry, blood biomarkers, andecaliximab concentration and anti-andecaliximab antibodies should only be 
collected if not conducted in the last 2 weeks.
u
EOS assessments will be completed when the subject meets at least 1 criterion for study discontinuation in Section 3.7. 
v
A safety follow-up visit will be performed 30 days (± 7 days) after the last dose of andecaliximab. The 30-day safety follow-up visit may be substituted by a scheduled study
visit if it occurs within the same window.
w
LTFU for OS 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 of long 
term survival status and record of any other anti-cancer therapy, cancer-related surgery for up to 5 years after the EOS visit. 


Andecaliximab
Protocol GS-US-296-1884
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 126
14 July 2017
Appendix 5.
Study Procedures Table – Cohort 4: Combination Therapy Andecaliximab and Nivolumab
Cohort 4: Combination Therapy Andecaliximab and Nivolumab
Study Phase
Screening
Each Cycle 
(28 Days)
Cycle 1
Every 
8 Weekss
EOTt
EOSu
30-Day 
Safety 
Follow-
Upv
5-Month 
Safety 
Follow-
Upw
5-Year 
LTFUx
Cycle Day
Screening
1
15
8
N/A
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1r
± 1
± 1 
± 5
N/A
N/A
± 7
± 7
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
X
X
X
Vital Signsc
X
X
X
X
X
X
X
12-Lead ECG
X
X
X
ECOG Performance 
Status
X
X
X
X
X
X
X
Prior/Concomitant Meds
X
X
X
X
X
X
X
X
X
AEsd
X
X
X
X
X
X
X
X
X
CT or MRIe
X
X
X
Collect Archival Tumor 
Tissuef
X
Sample Collection
Chemistry
X
Xh
X
X
X
X
X
X
X
Hematology
X
Xh
X
X
X
X
X
X
X
Coagulation
X
Xh
X
X
X
X
Urinalysis
X
Xh
X
X
X
X
Pregnancy testg
X
Xh
X
X
X
X


Andecaliximab
Protocol GS-US-296-1884
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 127
14 July 2017
Cohort 4: Combination Therapy Andecaliximab and Nivolumab
Study Phase
Screening
Each Cycle 
(28 Days)
Cycle 1
Every 
8 Weekss
EOTt
EOSu
30-Day 
Safety 
Follow-
Upv
5-Month 
Safety 
Follow-
Upw
5-Year 
LTFUx
Cycle Day
Screening
1
15
8
N/A
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1r
± 1
± 1 
± 5
N/A
N/A
± 7
± 7
N/A
Thyroid Function Tests 
(TSH, T3, free T4)i
X
X
X
X
X
X
Andecaliximab 
Concentrationj
X
X
X
X
X
Anti-Andecaliximab 
Antibodiesk
X
X
X
X
X
Blood Biomarkersl
X
X
X
X
X
X
X
X
X
Tumor Tissue Biopsym
X
X
X
Normal Gastric Tissue 
Biopsyn
X
Endoscopic Evaluationo
X
X
Overall Survival and 
Other Antitumor 
Therapy
X (Every 
3 months)
Dosing
Andecaliximab IV 
Dosingp
X
X
Nivolumab Dosingq
X
X
EOS = End of Study (visit); EOT = End of treatment (visit); LTFU = Long Term Follow Up; PE = physical examination; PK = pharmacokinetics; TSH = thyroid-stimulating 
hormone
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 on Day 1 and 15 of each 28-day cycle and at the EOT 
visit, at the EOS visit, and at the 30-day safety follow-up visit. 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.


Andecaliximab
Protocol GS-US-296-1884
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 128
14 July 2017
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 andecaliximab dosing during applicable visits. 
e
Tumor evaluation by CT or MRI will be performed during screening (scans taken as part of standard medical practice within 28 days of Day 1 are acceptable), every 8 weeks, 
and at the EOS visit (if not conducted within the previous 28 days). The same radiographic procedure used to define measurable lesions must be used throughout the study for 
each subject. 
f
Archival tumor tissue will be collected from all subjects with available tissue. Efforts to acquire archival tissue should begin on Cycle 1 Day 1.
g
For females of childbearing potential, a serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Pre Dose on Days 1 and 15 of 
each cycle, at the EOS visit and at the 30-day and 5-month safety follow-up visits.
h
Day 1 pre dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit. 
i
Blood samples for thyroid function tests will be collected at screening, every 8 weeks (± 5 days) if not performed in the last 2 weeks, at the EOT visit, at the EOS visit, and at 
the 30-day and 5-month safety follow-up visits. 
j
Plasma samples for andecaliximab PK in Cycle 1 will be collected 30 (± 15) minutes after the end of andecaliximab infusion on Day 1, anytime on Day 8, and prior to 
andecaliximab dosing and 30 (± 15) minutes after the end of infusion on Day 15. Additionally, plasma samples for andecaliximab PK will be collected prior to andecaliximab
dosing and 30 (± 15) minutes after the end of infusion on Day 1 and Day 15 of Cycles 2, 3, 5, 7, and every 3 cycles thereafter and anytime at the EOT visit (if not conducted 
in the last 2 weeks), and EOS visit. 
k
Blood samples for anti-andecaliximab antibodies will be collected prior to dosing on Day 1 of Cycles 1, 2, 3, 5, 7, and every 3 cycles thereafter; at the EOT visit (if not 
conducted in the last 2 weeks), at the EOS visit, and at the 30-day and 5-month safety follow-up visits. 
l
Blood samples for biomarkers will be collected Pre Dose on Day 1 of every cycle, Day 8 of Cycle 1, Day 15 of Cycles 1 and 2, every 8 weeks, at the EOT visit (if not 
conducted in the last 2 weeks), at the EOS visit, at the 30-day safety follow-up visit, and at the 5-month safety follow-up visit. 
m
Tumor tissue biopsy must be collected within 28 days prior to or on Day 1 of Cycle 1 Pre Dose and at 6 weeks (± 1 week) after the first dose of andecaliximab. The on-
treatment tumor tissue biopsy and endoscopic evaluation are performed at 6 weeks (± 1 week) after the first dose of andecaliximab. These assessments are not repeated at each 
Cycle Day 15 visit. 
n
Normal gastric tissue biopsy must be collected within 28 days prior to or on Day 1 of Cycle 1 Pre Dose. Do not collect if stomach is free of tumor. 
o
An endoscopic evaluation must be performed alongside tissue biopsy collection 28 days prior to or on Day 1 of Cycle 1 Pre Dose and between 5 and 8 weeks after the first 
dose of andecaliximab. Do not perform if stomach is free of tumor. 
p
Andecaliximab to be administered via IV infusion over 30 (± 5 minutes)
q
Following administration of andecaliximab, administer nivolumab via IV infusion over approximately 60 (± 5) minutes
r
C1D1 must occur within 3 days following enrollment in IWRS. A ± 1 day window applies to visits following Cycle 1 Day 1. 
s
Every 8 Weeks (± 5 days) assessments will be performed for subjects continuing treatment, or subjects who discontinue all treatment prior to disease progression but remain 
on study. 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), and blood samples for chemistry, hematology, coagulation, thyroid function tests, and blood biomarkers (if not collected in the last 2 weeks) every 8 weeks until 
disease progression.
t
EOT assessments will be requested from subjects who discontinue all treatment prior to disease progression. These assessments should be completed as soon as possible after 
the decision is made. Every attempt should be made to keep the subject in the study and continue to perform tumor evaluation by CT or MRI every 8 weeks until disease 
progression. Blood samples for hematology, coagulation, chemistry, blood biomarkers, andecaliximab concentration and anti-andecaliximab antibodies should only be 
collected if not conducted in the last 2 weeks.
u
EOS assessments will be completed when the subject meets at least 1 criterion for study discontinuation in Section 3.7. 
v
A safety follow-up visit will be performed 30 days (± 7 days) after the last dose of andecaliximab. The 30-day safety follow-up visit may be substituted by a scheduled study
visit if it occurs within the same window.
w
A safety follow-up visit will be performed 5 months (± 7 days) following the last dose of nivolumab. The 5-month follow-up visit may be substituted by a scheduled study 
visit if it occurs within the same window.
x
LTFU for OS 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 of long 
term survival status and record of any other anti-cancer therapy, cancer-related surgery for up to 5 years after the EOS visit. 
CCI


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Appendix 6.
Proposed Regimen for Combination Therapy Andecaliximab and SP
  
  
  
  
  
 
 
 
 
 
 
 
 
 
 
 


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Appendix 7.
Regimen for Combination Therapy Andecaliximab and SOX
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendix 8.
Regimen for Combination Therapy Andecaliximab and Nivolumab
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
    
 
 
  
 
 
   
 
 
 
 


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Appendix 9.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Pregnancy and Contraception Requirements for Males and Females of Childbearing 
Potential
The risks of treatment with andecaliximab during pregnancy have not been evaluated in humans. 
The potential for genotoxicity and embryofetal toxicity is considered to be low based on 
nonclinical toxicological studies. In both the rat and rabbit definitive embryo-fetal developmental 
toxicity studies, there were no andecaliximab-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. 
Please refer to the latest version of the IB for additional information on andecaliximab. 
In addition, please also refer to the latest version of the regional prescribing information for the 
potential risks of treatment with S-1, cisplatin, oxaliplatin, and nivolumab.  
2) Definitions
a. Definition of Female of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.  
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. 
In addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy, and are without 
an alternative medical cause for amenorrhea.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
b. Definition of Male Fertility
For the purposes of this study, a male born subject is considered of fertile potential after the 
initiation of puberty unless permanently sterile by bilateral orchidectomy or medical 
documentation.
3) Contraception Requirements for Female Subjects
a. Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures, outlined below. They must have a negative serum pregnancy test at 
screening and a negative pregnancy test on the Cycle 1 Day 1 visit prior to the first dose of study 


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drug. Pregnancy tests will be performed at protocol specified intervals thereafter. Female 
subjects must agree to one of the following methods of birth control from screening and 
throughout the study until 90 days following the last dose of andecaliximab and S-1, 6 months 
following the last dose of cisplatin and oxaliplatin, and 5 months following the last dose of 
nivolumab, whichever occurs later.

Consistent and correct use of 1 of the following methods of birth control listed below: 
Intrauterine device (IUD) with a failure rate of <1% per year
Tubal sterilization
Essure micro-insert system (provided confirmation of success 3 months after procedure). 
This is not yet approved in Japan. 
Vasectomy in the male partner (provided that the partner is the sole sexual partner and 
had confirmation of surgical success 3 months after procedure)
OR

Consistent and correct use of 1 hormonal method and 1 barrier method: 
Hormonal methods
■
Oral contraceptives (either combined estrogen/progestin or progesterone only)
■
Injectable progesterone. This is not yet approved in Japan. 
■
Implants of levonorgestrel
■
Transdermal contraceptive patch. This is not yet approved in Japan. 
■
Contraceptive vaginal ring
Barrier methods
■
Male or female condom, with or without spermicide
■
Diaphragm with spermicide
■
Cervical cap with spermicide. This is not yet approved in Japan. 
■
Sponge with spermicide. This is not yet approved in Japan. 
Female subjects who utilize a hormonal contraceptive as one of their birth control methods must 
have consistently used the same method for at least three months prior to study dosing. Female 
subjects must also refrain from egg donation and in vitro fertilization during treatment and until 
at least 90 days following the last dose of andecaliximab and S-1, 6 months following the last 
dose of cisplatin and oxaliplatin, and 5 months following the last dose of nivolumab, whichever 
occurs later. 


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4) Contraception Requirements for Male Subjects
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 and until 90 days 
following the last dose of andecaliximab, nivolumab and S-1, 6 months following the last dose of 
cisplatin and oxaliplatin, whichever occurs later. Additional contraception recommendations 
should also be considered for the female partner if she is not pregnant.
Male subjects must also refrain from sperm donation during treatment and until at least 90 days 
following the last dose of andecaliximab, nivolumab and S-1, and 6 months following the last 
dose of cisplatin and oxaliplatin, whichever occurs later.
5) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (e.g., calendar, 
ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhea method (LAM). Female condom and male condom should not 
be used together.
6) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 90 days following the last dose of andecaliximab
and S-1, 6 months following the last dose of cisplatin and oxaliplatin, and 5 months following 
the last dose of nivolumab. Subjects who become pregnant or who suspect that they are pregnant 
during the study must report the information to the investigator and discontinue study drug 
immediately. Subjects whose partner has become pregnant or suspects she is pregnant during the 
study must report the information to the investigator.  Instructions for reporting pregnancy, 
partner pregnancy, and pregnancy outcome are outlined in Section 7.7.2.1.


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Appendix 10.
Revised RECIST Guideline (Version 1.1)
Please see reference (E.A. Eisenhauer, et al. New response evaluation criteria in solid tumours: 
Revised RECIST guideline (version 1.1) European Journal of Cancer 45(2009) 228-247.) for full 
RECIST guidelines.
Measurable Lesions:

Tumor ≥10 mm in longest diameter (LD) on an axial image on CT or MRI with ≤5 mm 
reconstruction interval If slice thickness >5 mm, LD must be at least 2 times the thickness

Tumor ≥20 mm LD by chest x-ray (if clearly defined & surrounded by aerated lung); CT is 
preferred (even without contrast)

Tumor ≥10 mm LD on clinical evaluation (photo) with electronic calipers; skin photos 
should include ruler Lesions which cannot be accurately measured with calipers should be
recorded as non-measurable

Lymph nodes ≥15 mm in short axis on CT (CT slice thickness no more than 5 mm)

Ultrasound cannot be used to measure lesions
Note: only patients with measureable disease at baseline should be enrolled onto the study.
Non-Measurable Lesions:

All other definite tumor lesions
Masses <10 mm
Lymph nodes 10-14 mm in short axis
Leptomeningeal disease
Ascites, pleural or pericardial effusion
Inflammatory breast disease
Lymphangitic involvement of skin or lung
Abdominal masses or organomegaly identified by physical exam which cannot be 
measured by reproducible imaging techniques

Benign findings are NEVER included. Also, do not include equivocal (“cannot exclude”) 
findings


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Target Lesions:

Choose up to 5 lesions (up to two (2) per organ)

Add up longest diameters (LD) of non-nodal lesions (axial plane)

Add short axis diameters of nodes

This is the “sum of the longest diameters” (SLD)
Time point response: patients with target (+/- non target) disease
Target lesions
Non-Target lesions
New lesions
Overall response
CR
CR
No
CR
CR
Non-CR/non-PD
No
PR
CR
Not evaluated
No
PR
PR
Non-PD or not all 
evaluated
No
PR
SD
Non-PD or not all 
evaluated
No
SD
Not all evaluated
Non-PD
No
NE
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
CR = complete response, PR = partial response, SD = stable disease, PD = Progressive disease, and NE = inevaluable.
Time point response: patients with non-target disease only
Non-target lesions
New lesions
Overall response
CR
No
CR
Non-CR/non-PD
No
Non-CR/Non-PDa
Not all evaluated
No
NE
Unequivocal PD
Yes or No
PD
Any
Yes
PD
CR = complete response, PD = Progressive disease, and NE = inevaluable.
a
“Non-CR/non-PD’ is preferred over “stable disease’ for non-target disease since SD is increasingly used as endpoint for 
assessment of efficacy in some trials so to assign this category when no lesions can be measured is not advised.


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Overall response
First time point
Overall response
Subsequent time point
BEST overall response
CR
CR
CR
PR
CR
SD, PD or PRa
CR
SD
SD provided minimum criteria for  SD duration met, otherwise, PD
CR
PD
SD provided minimum criteria for  SD duration met, otherwise, PD
CR
NE
SD provided minimum criteria for  SD duration met, otherwise NE
PR
CR
PR
PR
PR
PR
PR
SD
SD
PR
PD
SD provided minimum criteria for  SD duration met, otherwise, PD
PR
NE
SD provided minimum criteria for  SD duration met, otherwise NE
NE
NE
NE
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, and
NE = inevaluable.
a
If a CR is truly  met at first time point, then any disease seen at a subsequent time point, even disease meeting PR criteria
relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR). Best  response would 
depend on  whether minimum duration for SD was met. However, sometimes ‘CR’ may be claimed when subsequent scans 
suggest small lesions were likely still present and in fact the patient had PR, not CR at the first time point. Under these 
circumstances, the original CR should be changed to PR and the best response is PR. 
http://ctep.cancer.gov/protocolDevelopment/docs/recist_guideline.pdf. New response evaluation criteria in solid tumours: 
Revised RECIST guideline (version 1.1) E.A. Eisenhauer,*, P. Therasseb, J. Bogaertsc, L.H. Schwartzd, D. Sargente, R. Fordf, J. 
Danceyg, S. Arbuckh, S. Gwytheri, M. Mooneyg, L. Rubinsteing, L. Shankarg, L. Doddg, R. Kaplanj, D. Lacombec, J. Verweijk

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 1b Study to Evaluate the Safety and Tolerability of 
Andecaliximab (ADX) as Monotherapy and in Combination 
with Anti-Cancer Agents in Japanese Subjects with Gastric 
or Gastroesophageal Junction Adenocarcinoma
Name of Test Drug:
Andecaliximab (ADX)
Study Number:
GS-US-296-1884
Protocol Version (Date):
Amendment 3 (14 July 2017)
Analysis Type:
Final Analysis
Analysis Plan Version:
1.0
Analysis Plan Date:
02 December 2019
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(r) GILEAU 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF TABLES.........................................................................................................................................................4
LIST OF FIGURES.......................................................................................................................................................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..........................................................................................................................12
2.
TYPE OF PLANNED ANALYSIS ....................................................................................................................13
2.1.
Interim Analyses ....................................................................................................................................13
2.2.
Final Analysis ........................................................................................................................................13
2.3.
Follow-up Analysis ................................................................................................................................13
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................14
3.1.
Analysis Sets..........................................................................................................................................14
3.1.1.
All Enrolled Analysis Set.....................................................................................................14
3.1.2.
Safety Analysis Set...............................................................................................................14
3.1.3.
Dose-Limiting Toxicity (DLT) Analysis Set........................................................................14
3.1.4.
Pharmacokinetic Analysis Set..............................................................................................15
3.1.5.
Immunogenicity Analysis Set ..............................................................................................15
3.1.6.
Biomarker Analysis Set........................................................................................................15
3.2.
Subject Grouping ...................................................................................................................................15
3.3.
Strata and Covariates..............................................................................................................................15
3.4.
Examination of Subject Subgroups........................................................................................................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
4.
SUBJECT DISPOSITION ..................................................................................................................................19
4.1.
Subject Enrollment and Disposition.......................................................................................................19
4.2.
Extent of Study Drug Exposure .............................................................................................................20
4.2.1.
Exposure to Study Drug (ADX)...........................................................................................20
4.2.2.
Exposure to Chemotherapy ..................................................................................................21
4.2.3.
Exposure to Nivolumab........................................................................................................21
4.3.
Protocol Deviations................................................................................................................................21
5.
BASELINE CHARACTERISTICS....................................................................................................................22
5.1.
Demographics and Baseline Characteristics ..........................................................................................22
5.2.
Other Baseline Characteristics ...............................................................................................................22
5.3.
Medical History......................................................................................................................................22
5.4.
Prior Anti-cancer Therapy......................................................................................................................23


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6.
EFFICACY ANALYSES ...................................................................................................................................24
6.1.
Exploratory Efficacy Endpoints.............................................................................................................24
6.1.1.
Definition of the Exploratory Efficacy Endpoints................................................................24
6.1.2.
Analysis of the Exploratory Efficacy Endpoints ..................................................................25
6.2.
Change from Protocol-Specified Efficacy Analyses..............................................................................25
7.
SAFETY ANALYSES........................................................................................................................................26
7.1.
Adverse Events and Deaths....................................................................................................................26
7.1.1.
Adverse Event Dictionary ....................................................................................................26
7.1.2.
Adverse Event Severity........................................................................................................26
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................26
7.1.4.
Serious Adverse Events........................................................................................................26
7.1.5.
Treatment-Emergent Adverse Events...................................................................................26
7.1.6.
Summaries of Adverse Events and Deaths...........................................................................27
7.1.7.
Additional Analysis of Adverse Events ...............................................................................29
7.2.
Laboratory Evaluations ..........................................................................................................................30
7.2.1.
Summaries of Numeric Laboratory Results .........................................................................30
7.2.2.
Graded Laboratory Values ...................................................................................................30
7.2.3.
Shifts Relative to the Baseline Value ...................................................................................31
7.3.
Body Weight and Vital Signs.................................................................................................................31
7.4.
Prior and Concomitant Medications.......................................................................................................31
7.4.1.
Prior Medications .................................................................................................................31
7.4.2.
Concomitant Medications.....................................................................................................31
7.5.
Electrocardiogram (ECG) Results..........................................................................................................32
7.5.1.
Investigator Electrocardiogram Assessment ........................................................................32
7.5.2.
Corrected QT Intervals.........................................................................................................32
7.5.3.
PR and QRS Intervals...........................................................................................................33
7.6.
Other Safety Measures ...........................................................................................................................33
7.7.
Changes from Protocol-Specified Safety Analyses................................................................................33
8.
PHARMACOKINETIC (PK) ANALYSES........................................................................................................34
8.1.
PK Sample Collection............................................................................................................................34
8.1.1.
Estimation of PK Parameters ...............................................................................................34
8.1.2.
PK Parameters......................................................................................................................34
9.
IMMUNOGENICITY ANALYSES...................................................................................................................36
9.1.
ADA Sample Collection.........................................................................................................................36
9.2.
ADA Status ............................................................................................................................................36
10.
BIOMARKER ANALYSES...............................................................................................................................37
10.1.
Statistical Analysis Methods ..................................................................................................................37
11.
REFERENCES ...................................................................................................................................................38
12.
SOFTWARE.......................................................................................................................................................39
13.
SAP REVISION..................................................................................................................................................40
14.
APPENDICES ....................................................................................................................................................41
Appendix 1.
Study Procedures Table – Cohort 1 (Andecaliximab Monotherapy)......................................42
Appendix 2.
Study Procedures Table – Cohort 2: Combination Therapy Andecaliximab and SP..............45
Appendix 3.
Study Procedures Table – Cohort 3: Combination Therapy Andecaliximab and SOX..........48
Appendix 4.
Study Procedures Table – Cohort 4: Combination Therapy Andecaliximab and 
Nivolumab..............................................................................................................................51


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LIST OF TABLES
Table 8-1.
PK Parameters for Each Analyte............................................................................................34
LIST OF FIGURES
Figure 1–1.
Cohort 2 (Combination Therapy ADX and SP) Proposed Regimen ......................................11
Figure 1–2.
Cohort 3 (Combination Therapy ADX and SOX) Regimen...................................................12
Figure 1–3.
Cohort 4 (Combination Therapy ADX and Nivolumab) Regimen.........................................12


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LIST OF ABBREVIATIONS
ADA
Anti-Drug Antibody
ADX
andecaliximab
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil count
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
BLQ
below limit of quantitation
BUN
blood urea nitrogen
CA 19-9
carbohydrate antigen 19-9
CEA
carcinoembryonic antigen
CI
confidence interval
CR
complete response
CRF
case report form
CSR
clinical study report
CT
computed tomography scan
CTCAE
Common Terminology Criteria for Adverse Events
DCR
disease control rate
DLT
dose limiting toxicity
DOR
duration of response
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form(s)
EDC
electronic data capture
EOS
end-of-study
EOT
end of treatment
FDA
(United States) Food and Drug Administration
g
gram
GCP
Good Clinical Practice (Guidelines)
GEJ
gastroesophageal junction
-HCG
beta human chorionic gonadotropin
HLGT
high-level group term
HLT
high-level term
ICF
informed consent form
ID
identification
INR
international normalized ratio
IV
intravenous
Kg
kilogram


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L
liter
LLT
lower-level term
LTFU
long term follow-up
MedDRA
Medical Dictionary for Regulatory Activities
mg
milligram
min
minute
MRI
magnetic resonance imaging
NN
non-CR/non-PD
ORR
objective response rate
OS
overall survival
PD
progressive disease
PE
physical examination
PFS
progression-free survival
PK
pharmacokinetic
PK/PD
pharmacokinetic/pharmacodynamic
PR
partial response
PT
preferred term
PTT
partial thromboplastin time
Q2W
every two weeks
Q3W
every three weeks
RECIST
Response Evaluation Criteria in Solid Tumors
RNA
ribonucleic acid
SAE
serious adverse event
SD
stable disease
SE
standard error
SOC
system organ class
StD
standard deviation
TTR
time to response
ULN
upper limit of the normal range
WBC
white blood cell count


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PHARMACOKINETIC ABBREVIATIONS
AUClast
area under the concentration versus time curve
AUC0-336h
area under the concentration versus time curve over the dosing interval
Clast
last observed quantifiable concentration of the drug in plasma
Cmax
maximum observed concentration of drug in plasma
C336h
observed drug concentration at the end of the dosing interval
t1/2
estimate of the terminal elimination half-life of the drug in plasma, 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 plasma concentration of drug versus time curve


Andecaliximab (GS-5745) 
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Statistical Analysis Plan (Final Analysis) 
1. 
INTRODUCTION 
Version 1.0 
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-296-1884. This SAP is based on the study protocol amendment 3 
dated 14 July 2017 and the electronic case report fonn ( 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 objective of this study is as follows: 
• 
To characterize the safety and tolerability of ADX as monotherapy and in combination with 
anti-cancer agents in Japanese subjects with inoperable advanced or recurrent gastric or 
gastroesophageal junction (GEJ) adenocarcinoma 
The secondary objectives of this study are as follows: 
• 
To characterize the phannacokinetics (PK) of ADX 
• 
To evaluate the fonnation of anti-ADX antibodies 
The exploratory objectives of this study are as follows: 
I 
I 
I 
1.2. 
Study Design 
This is a Phase 1 b, open-label, multicenter study to evaluate the safety and tolerability of ADX 
as monotherapy and in combination with anti-cancer agents in Japanese subjects with inoperable 
advanced or recurrent gastric or GEJ adenocarcinoma. 
The study will comprise 4 cohorts, 1 monotherapy cohort and 3 combination therapy cohorts. 
• 
Cohort 1 is ADX monotherapy 
• 
Cohort 2 is combination therapy of ADX with S-1 and cisplatin (SP) 
• 
Cohort 3 is combination therapy of ADX with S-1 and oxaliplatin (SOX) 
• 
Cohort 4 is combination therapy of ADX with nivolumab 
CONFIDENTIAL 
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Cohort 1: ADX Monotherapy
Up to 6 Japanese subjects will be enrolled to receive ADX 800 mg via IV infusion over 
approximately 30 (± 5) minutes every two weeks (Q2W) until disease progression. The dose 
limiting toxicity (DLT) assessment window is 28 days. The safety and tolerability of the 800 mg 
dose will be assessed after all 6 subjects have been followed for at least 28 days after the first 
infusion of ADX. If 2 or more subjects within the cohort of 6 subjects experience DLTs during 
the first 28 days of ADX dosing, up to 6 additional subjects will be enrolled at a reduced dose of 
600 mg Q2W. If 2 additional DLTs occur at 600 mg, ADX will be considered unsafe and will be 
discontinued. Therefore, a total of up to 12 subjects may be enrolled in Cohort 1.
Once 6 subjects in Cohort 1 have completed the 28-day DLT assessment window and ≤1 out of 
6 subjects experienced DLTs, an internal safety review team (SRT) conduct a review of the 
safety and PK data from all subjects prior to proceeding with the combination therapy cohorts to 
evaluate ADX with other anti-cancer agents.
The SRT completed their review of all available clinical safety and PK data for 6 DLT-evaluable 
subjects in Cohort1 on 11 May 2017 and determined the dose for the combination therapy 
cohorts (Cohorts 2 and 4) to be 800 mg ADX Q2W, and Cohort 3 to be 1200 mg every 
three weeks (Q3W).
Cohort 2: combination therapy ADX and SP

ADX 800 mg via IV infusion over approximately 30 (± 5) minutes Q2W until disease 
progression. The dose is based on the safety data from Cohort 1. ADX treatment will be 
administered in 28-day cycles.

S-1 administered orally twice daily: dosage and regimen will be based on subject condition, 
investigator discretion, institutional practice and/or the in-country label (Figure 1 1)

Cisplatin administered by IV infusion on Day 8 of every 5 weeks: dosage and regimen will 
be based on subject condition, investigator discretion, institutional practice and/or the in-
country label (Figure 1 1)
Cohort 3: combination therapy ADX and SOX

ADX 1200 mg via IV infusion over approximately 30 (± 5) minutes Q3W until disease 
progression. The dose is based on safety data from Cohort 1 and other ongoing Phase 1 
studies of ADX. ADX treatment will be administered in 21-day cycles.

S-1 administered orally twice daily at 80 mg/day for body surface area (BSA) < 1.25m2,
100 mg/day for BSA ≥1.25 to < 1.5m2, and 120 mg/day for BSA ≥1.5m2 for the first
14 days of the 21-day cycle (Figure 1 2)

Oxaliplatin administered by IV infusion at 100 mg/m2 over 2 hours on Day 1 of each 21-day 
cycle (Figure 1 2)


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Cohort 4: combination therapy ADX and nivolumab

ADX 800 mg via IV infusion over approximately 30 (± 5) minutes Q2W until disease 
progression. The dose is based on safety data from Cohort 1. ADX treatment will be 
administered over in 28-day cycles.

Nivolumab 3mg/kg Q2W via IV infusion over 60 (± 5) minutes following the completion of 
ADX administration (Figure 1 3). Dose is adjusted if the weight changes more than 10% 
from the baseline dosing weight.
For Cohorts 1, 2, and 4, computed tomography (CT) or magnetic resonance imaging (MRI) scans 
will be performed every 8 weeks to evaluate response to treatment according to RECIST v1.1. 
For Cohort 4, response to treatment will also be evaluated using immune related response criteria 
recommendations {Wolchok 2009}. For Cohort 3, CT or MRI scans will be performed every 
9 weeks to evaluate response to treatment according to RECIST v1.1.
Long term follow-up (LTFU) for overall survival (OS) begins after the end-of-study (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 of long-term survival status.
Key Inclusion Criteria:
1) Male or female 20 years of age
2) Subjects must have been born in Japan and must not have lived outside of Japan for a period 
>1 year in the 5 years prior to Day 1
3) Histologically confirmed inoperable advanced gastric adenocarcinoma (including 
adenocarcinoma of the GEJ) or relapsed gastric adenocarcinoma
4) Cohorts 1 (ADX monotherapy), 2 (combination therapy ADX and SP) and 3 (combination 
therapy ADX and SOX): Human Epidermal Growth Factor Receptor 2 (HER2)-negative 
tumor (primary tumor or metastatic lesion). Enrollment in Cohort 4 (combination therapy 
ADX and nivolumab) is not restricted by HER2 status (subjects with HER2-positive, 
HER2-negative, or unknown HER2 status are eligible).
5) Cohort 1 (ADX monotherapy): Prior antitumor therapy or cytotoxic chemotherapy is 
acceptable. Subjects who are not eligible to receive standard treatments should enroll on the 
study. All acute toxic effects of any prior antitumor therapy must be resolved to Grade ≤1 
(or baseline) before the start of ADX dosing (with the exception of alopecia [Grade 1 or 2 
permitted] and neurotoxicity [Grade 1 or 2 permitted]).
6) Cohorts 2 (combination therapy ADX and SP) and 3 (combination therapy ADX and SOX): 
Prior antitumor therapy or cytotoxic chemotherapy for metastatic disease is not acceptable. 
Subjects must be chemo-naive in the metastatic setting. Subjects who relapse during adjuvant 
chemotherapy or within 180 days after adjuvant chemotherapy for their gastric cancer should 
not be enrolled.


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7) Subjects in Cohort 4 must meet all of the following additional inclusion criteria:
a) Measurable gastric or GEJ adenocarcinoma according to RECIST v1.1
b) Subject must have progressed on at least 1 prior systemic therapy or line of treatment for 
unresectable/metastatic disease. All toxicities attributed to prior anti-cancer therapy other 
than alopecia or fatigue must have resolved to Grade ≤1 (NCI CTCAE Version 4) or 
baseline
Key Exclusion Criteria:
1) Cohort 1 (ADX monotherapy): Anti-tumor therapy (chemotherapy, antibody therapy, 
molecular targeted therapy) within 28 days or 5 half-lives, whichever is shorter, of Day 1 
(6 weeks for nitrosoureas, mitomycin C, or molecular agents with t½ > 10 days)
2) In addition to the applicable criteria above, subjects in Cohort 4 (combination therapy ADX
and nivolumab) who meet any of the following exclusion criteria will not be enrolled in this 
study:
a) Subjects who have received only neoadjuvant or adjuvant therapy for gastric 
adenocarcinoma
b) Chronic daily treatment with oral corticosteroids (dose of > 10 mg/day prednisone 
equivalent) or other immunosuppressive medications within 14 days of Day 1. Inhaled 
steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are 
allowed
c) Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy) within
28 days or 5 half-lives, whichever is shorter, of Day 1 (6 weeks for nitrosoureas, 
mitomycin C, or molecular agents with t½ > 10 days)
d) Prior treatment with anti-CTLA-4 agents (eg, ipilimumab), anti-PD-1 or anti-PD-L1 
agents (eg, pembrolizumab, nivolumab, atezolizumab), anti-PD-L2 agents, anti-MMP 
agents, or other immunomodulatory therapies
e) Prior therapy with anti-tumor vaccines or other immuno-modulatory antitumor agents
Figure 1–1.
Cohort 2 (Combination Therapy ADX and SP) Proposed Regimen


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Figure 1–2.
Cohort 3 (Combination Therapy ADX and SOX) Regimen
Figure 1–3.
Cohort 4 (Combination Therapy ADX and Nivolumab) Regimen
For the details of the schedule of assessments, please refer to Appendix 1 through Appendix 4.
1.3.
Sample Size and Power
The sample size of 6 subjects in the monotherapy cohort allows a relatively high probability 
(> 65%) to observe 2 or more subjects with DLT when the true underlying probability of DLT is 
greater than 33.3% at current dose level.
Up to 6 subjects will be enrolled in Cohort 1 to receive 800 mg ADX Q2W, and based on safety 
assessments, an additional 6 subjects may be enrolled in Cohort 1 to receive 600mg ADX Q2W 
prior to proceeding with the combination therapy cohorts. Therefore, a total of up to 12 subjects 
may be enrolled in Cohort 1.
Based on the dose level selected by Cohort 1, up to 6 subjects will be enrolled in Cohort 2 
(combination therapy ADX and SP), and up to 10 subjects will be enrolled in Cohorts 3 
(combination therapy ADX and SOX) and 4 (combination therapy ADX and nivolumab), 
respectively.
Therefore, up to 38 subjects will be enrolled in the study.
Cycle 1 
ecaliximab 
3weeks 
,to xatiplatin 
Day 1 • 
Cycle 2 
t Oxaliplatin 
Cycle 1 
Day 15 
Day 1 
• • 
Cycle 3 
1 week-off 
t Oxaliplatin 
Cycle 2 
Day 15 • 
GS-5745 & 
GS-5745 & 
GS-5745 & 
GS-5745 & 
nlllOlumab 
nrvolumab 
nrvolumab 
nrvolumab 
'-.__/ 
'-.__/ 
'-.__/ 
2weeks 
2 weeks 
2 weeks 


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
No formal interim efficacy analysis, which may lead to early termination for efficacy or futility,
is planned.
2.2.
Final Analysis
After all subjects have completed/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 ANALYSES
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 
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 eligible for inclusion will be 
summarized by cohort and overall.
A listing of reasons for exclusion from analysis sets will be provided by subject.
3.1.1.
All Enrolled Analysis Set
All Enrolled Analysis Set includes all subjects who received a study subject identification 
number in the study after screening.
3.1.2.
Safety Analysis Set
The Safety Analysis Set includes all subjects who took at least 1 dose of study drug. This is the 
primary analysis set for safety analyses.
3.1.3.
Dose-Limiting Toxicity (DLT) Analysis Set
DLTs will only be evaluated for subjects in Cohort 1. The DLT Analysis Set includes Cohort 1 
subjects in the Safety Analysis Set who complete all study treatment and have safety assessments 
through the protocol specified DLT assessment window, Day 28, inclusive, or have experienced 
a DLT prior to Day 28, exclusive. This is the primary analysis set for analyses related to DLTs in 
Cohort 1. Safety assessments relevant to the DLT analysis set definition will include serum 
chemistry, hematology and coagulation tests as specified in the protocol.


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3.1.4.
Pharmacokinetic Analysis Set
The Pharmacokinetic (PK) Analysis Set will include all enrolled subjects who took at least 
1 dose of study drug and have at least 1 nonmissing postdose concentration value reported by the 
PK laboratory. This is the primary analysis set for all PK analyses.
3.1.5.
Immunogenicity Analysis Set
The Immunogenicity Analysis Set will include all subjects who took at least 1 dose of study drug
and have at least 1 nonmissing postdose antidrug antibody (ADA) status reported. This is the 
primary analysis set for all immunogenicity analyses.
3.1.6.
Biomarker Analysis Set
The Biomarker Analysis Set will include subjects who took at least 1 dose of study drug and 
have at least 1 evaluable biomarker measurement available.
3.2.
Subject Grouping
Unless otherwise specified, subjects will be grouped by cohort for analyses:

Cohort 1: 800 mg Q2W ADX monotherapy

Cohort 2: combination therapy of ADX 800 mg Q2W with S-1 and cisplatin 

Cohort 3: combination therapy of ADX 1200 mg Q3W with S-1 and oxaliplatin 

Cohort 4: combination therapy of ADX 800 mg Q2W with nivolumab
For summaries where the cohorts will be aggregated, the summary results will be presented 
under the “Total” column.
3.3.
Strata and Covariates
This study does not use a stratified randomization schedule when enrolling subjects. 
No covariates will be included in analyses.
3.4.
Examination of Subject Subgroups
There are no prespecified subject subgroupings for analyses.
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, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document.
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 AE onset date is 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
The following conventions will be used for the imputation of date of birth when it is partially 
missing or not collected:

If only month and year of birth is collected, then “15” will be imputed as the day of birth.

If only year of birth is collected, then “01 July” will be imputed as the day and month of 
birth.

If year of birth is missing, then date of birth will not be imputed.
In general, age (in years) on the date of the first dose of study drug will be used for analyses and 
presented 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 
first informed consent was signed will be used for the age derivation. 
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 to calculate descriptive statistics if the 
datum is reported in the form of “x” (where x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate summary statistics. 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 to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.


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
The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).
If methods 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 logarithm transformation will be used for analyzing plasma concentrations and PK 
parameters. Plasma concentration values that are below 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 summary 
purposes. The following conventions will be used for the presentation of summary and order 
statistics for PK concentrations:

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) 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 (ADX) 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 ADX administration.


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3.8.2.
Analysis Visit Windows
The nominal visit as recorded on the case report form (CRF) will be used when data are 
summarized by visit.
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 the 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.

Data collected on an end of treatment (EOT) visit will be summarized as a separate visit, 
labeled as “End of Treatment Visit”.

Data collected on an EOS visit will be summarized as a separate visit, labeled as “End of 
Study Visit”.

Data collected on a 30-day safety follow-up visit will be summarized as a separate visit, 
labeled as “30-Day Safety Follow-Up Visit”.

Data collected on a 5-month safety follow-up visit will be summarized as a separate visit, 
labeled as “5-Month Safety Follow-Up Visit”.


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
A summary of subject enrollment will be provided by 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 cohort and overall, as appropriate. This 
summary will present the number of subjects screened and the number of subjects enrolled, and 
the number of subjects in each of the categories listed below:

Safety Analysis Set

Treated with study drug (ADX) (all cohorts)
Treatment discontinued
■
Reasons for discontinuation

Treated with S-1 (cohorts 2 and 3)
Treatment discontinued
■
Reasons for discontinuation

Treated with oxaliplatin (cohort 2)
Treatment discontinued
■
Reasons for discontinuation

Treated with cisplatin (cohort 3)
Treatment discontinued
■
Reasons for discontinuation

Treated with nivolumab (cohort 4)
Treatment discontinued
■
Reasons for discontinuation

Completed lesion assessment

Discontinued lesion assessment before disease progression


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Reasons for lesion assessment discontinuation

Discontinued study (including long-term follow-up for overall survival)
Reasons for study discontinuation
For the status of study drug, lesion assessment completion, study completion and reasons for 
premature discontinuation, 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.
The following by-subject listings will be provided by subject identification (ID) number in 
ascending order to support the above summary tables:

Reasons for premature study drug or study discontinuation

Reasons for screen failure (will be provided by screening ID number in ascending order)
4.2.
Extent of Study Drug Exposure
Extent of exposure to study drug will be examined by assessing the total duration of exposure to 
study drug specified in the protocol.
4.2.1.
Exposure to Study Drug (ADX)
Exposure to ADX will be summarized by 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 ADX will be summarized using descriptive statistics. 
Number of Doses
The total number of doses of ADX that each subject received during the study will be 
summarized using descriptive statistics. A subject is said to have received a dose of ADX if 
he/she received any amount of the planed dose of ADX (ie, actual dose > 0) at a visit. 
Additionally, the number and percentage of subjects receiving a given number of doses category
will be summarized, as appropriate.


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Actual Dose Amount
In addition, the total and average actual dose amount of ADX in mg that each subject received 
will be summarized using descriptive statistics.
The average actual dose amount of ADX 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 (ADX) 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 interruption (if 
applicable).
4.2.2.
Exposure to Chemotherapy
Exposure to chemotherapy agents, including cisplatin, oxaliplatin and nivolumab, will be listed.
Duration of exposure and the total number of doses that each subject received during the study 
will be summarized for each agent in a similar manner as for ADX. Chemotherapy received prior 
to study enrollment and after the start of other anti-cancer therapy will not be included in the 
summary.
S-1 was administered orally twice daily. A by-subject listing of S-1 administration will be 
provided by subject ID number (in ascending order), including dose per administration, dose 
frequency, start and stop date, and reason for dose interruption or modification (if applicable).
4.2.3.
Exposure to Nivolumab
Exposure to nivolumab will be listed. Duration of exposure to nivolumab and the total number of 
doses of nivolumab that each subject received during the study will be summarized in a similar 
manner as for ADX.
4.3.
Protocol Deviations
Subjects who did not meet the eligibility criteria for study entry but were 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 cohort and 
overall for 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 cohort and overall 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
Subject demographic variables (ie, age, sex, race, and ethnicity) and baseline characteristics 
(body weight [in kg], height [in cm], body mass index [BMI; in kg/m2]) will be summarized by 
cohort and overall using descriptive statistics for continuous variables and using number and 
percentage of subjects for categorical variables. The summary of demographic data will be 
provided for the Safety Analysis Set.
A by-subject demographic listing, including the informed consent date, will be provided by 
subject ID number in ascending order.
5.2.
Other Baseline Characteristics
No other baseline characteristics will be summarized.
5.3.
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 for the variables listed below, 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. No formal statistical testing is planned.
Variables to be summarized include:

Type of cancer

Pathological subtype of gastric cancer

Disease stage at diagnosis

Disease stage at screening

Differentiation

Time since diagnosis
The denominators for the percentage will be the numbers of subjects in the Safety Analysis Set 
corresponding to that column, except that for pathological subtype of gastric cancer, percentages 
will be calculated based on the number of subjects with gastric cancer in that column.
A by-subject listing of disease-specific medical history will be provided by subject ID number in 
ascending order.


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General medical history data will be collected at screening and listed only. General medical 
history data will not be coded.
5.4.
Prior Anti-cancer Therapy
Prior anti-cancer therapies will be summarized based on the Safety Analysis Set.
Number of subjects who received prior anti-cancer therapies and the number of prior regimens 
that each subject received will be summarized by cohort and overall using descriptive statistics. 
The regimens and prior therapies that the subjects received will be summarized by cohort and 
overall.
Number of subjects who received prior radiotherapies and the number of prior radiotherapies that 
each subject received will be summarized by cohort and overall.
Number of subjects who received prior surgeries or procedures and the prior surgeries or 
procedures that the subjects received will be summarized by cohort and overall.
By-subject listings will be provided for prior and post study anti-cancer therapies, radiotherapies, 
and surgery or procedures by subject ID number in ascending order.


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EFFICACY ANALYSES 
6.1. 
Exploratory Efficacy Endpoints 
6.1.1. 
Definition of the Exploratory Efficacy Endpoints 
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6.2. 
Change from Protocol-Specified Efficacy Analyses 
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7.
SAFETY ANALYSES
7.1.
Adverse Events and Deaths
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 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 summary presentation.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE 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 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if the AEs met the 
definitions of SAEs that were specified in the study protocol. SAEs captured and stored in the 
clinical database will be reconciled with the SAE database from the Gilead Pharmacovigilance 
and Epidemiology Department before data finalization.
7.1.5.
Treatment-Emergent Adverse Events 
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the date that ADX and if applicable, nivolumab was 
first administered and no later than 30 days after permanent discontinuation of ADX, or if 
applicable, 5 months after permanent discontinuation of nivolumab (whichever is later).

Any AEs leading to premature discontinuation of ADX and if applicable, nivolumab.


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7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The AE onset is the same as or after the month and year (or year) of the first dosing date of 
study drug, and

The AE onset date is the same as or before the month and year (or year) of the date 
corresponding to 30 days after the date of the last dose of ADX, or if applicable, 5 months 
after the last dose of nivolumab (whichever is later).
An AE with completely missing onset 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 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 and Deaths
Treatment-emergent AEs will be summarized based on the Safety Analysis Set.
7.1.6.1.
Summaries of AE Incidence by Severity 
The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC, HLT (if applicable), PT, and cohort. For the AE categorizes described 
below, summaries will be provided by SOC, PT, maximum severity, and cohort:

TEAEs

TEAEs with Grade 3 or higher

TEAEs related to ADX

TEAEs related to S-1

TEAEs related to oxaliplatin

TEAEs related to cisplatin

TEAEs related to nivolumab

TEAEs related to ADX with Grade 3 or higher  

TE SAEs


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
TE SAEs related to ADX

TE SAEs related to S-1

TE SAEs related to oxaliplatin

TE SAEs related to cisplatin

TE SAEs related to nivolumab

TEAEs leading to premature discontinuation of ADX

TEAEs leading to premature discontinuation of S-1

TEAEs leading to premature discontinuation of oxaliplatin

TEAEs leading to premature discontinuation of cisplatin

TEAEs leading to premature discontinuation of nivolumab

TEAEs leading to death (summarize by SOC and PT as all TEAEs leading to death will be 
Grade 5.)

TEAEs leading to dose modification or temporary interruption of ADX

TEAEs leading to dose modification or temporary interruption of S-1

TEAEs leading to dose modification or temporary interruption of oxaliplatin

TEAEs leading to dose modification or temporary interruption of cisplatin

TEAEs leading to dose modification or temporary interruption of nivolumab
A brief, high-level summary of AEs described above will be provided by cohort and by the 
number and percentage of subjects who experienced the above AEs.
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC and HLT within each SOC (if applicable) 
and then by PT in descending order of total frequency within each SOC. For summaries by 
severity, the most severe severity will be used for those AEs that occurred more than once in a 
given subject during the study.
In addition to the above summary tables, all TEAEs, TEAEs of Grade 3 or higher, TE SAEs and 
TE ADX-related AEs will be summarized by PT only in descending order of total frequency.


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In addition, data listings will be provided as follows:

All AEs, indicating whether the event is treatment emergent

All AEs with Grade 3 or higher

All SAEs

All AEs leading to death

All AEs leading to premature discontinuation of any study drug (ADX, S-1, oxaliplatin, 
cisplatin and nivolumab)

All AEs leading to dose modification or temporary interruption of any study drug (ADX, S-1, 
oxaliplatin, cisplatin and nivolumab)

All AEs related to any study drug (ADX, S-1, oxaliplatin, cisplatin and nivolumab)

All AEs with Grade 3 or higher related to ADX

All deaths
7.1.6.2.
Summaries of Deaths 
A summary (number and percentage of subjects) of deaths will be provided by cohort. The 
summary will include the following categories:

All deaths

Deaths within 30 days of the last dosing of ADX, or if applicable, 5 months after the last 
dose of nivolumab (whichever is later)

Deaths beyond 30 days of the last dosing of ADX, or if applicable, 5 months after the last 
dose of nivolumab (whichever is later)
All death will be summarized by the cause of the death (AE, PD, or other reasons).
7.1.7.
Additional Analysis of Adverse Events
7.1.7.1.
Dose Limiting Toxicity
A listing of the DLT AEs will be provided.
A summary of DLTs will be presented by SOC and decreasing frequency of preferred term 
within SOC using the DLT Analysis Set for Cohort 1.


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7.2.
Laboratory Evaluations
Laboratory data collected during the study, scheduled and unscheduled, will be analyzed and 
summarized using qualitative method. 
The analysis will be based on values reported in conventional units. When values are below the 
LOQ, they will be listed as such.
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, coagulation, and urinalysis
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 formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
No summaries of numerical laboratory results will be provided.
7.2.2.
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. For laboratory tests with criteria for both increased and decreased levels, analyses for 
each direction (ie, increased, decreased) will be presented separately. Local labs will be graded
based on the central lab normal ranges with in-house macro. In the event where both central and 
local lab results are collected in the clinical database, baseline flag, worst toxicity and toxicity 
shift should be derived using both central and local lab results. All central and local laboratory 
values will be listed.
7.2.2.1.
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 
ADX, or if applicable, 5 months after the last dose of nivolumab (whichever is later). 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.
7.2.2.2.
Summaries of Laboratory Abnormalities
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and cohort; subjects will be categorized according to 
the most severe postbaseline abnormality grade for a given lab test:

Worst treatment-emergent laboratory abnormalities postbaseline grade (Grade 1 to 4 
separately, Grade 3 or 4, and Grade 1 to 4)


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For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
nonmissing postbaseline values up to 30 days after the last dose of ADX, or if applicable, 
5 months after the last dose of nivolumab (whichever is later).
A by-subject listing of treatment-emergent Grade 3 or 4 laboratory abnormalities will be 
provided by subject ID number and visit in chronological order. This listing will include all test 
results that were collected throughout the study for the lab test of interest, with all applicable 
severity grades and abnormal flags displayed.
7.2.3.
Shifts Relative to the Baseline Value
Shift tables will be presented for each cohort by showing change in CTCAE grade from baseline 
to the worst post-baseline grade. 
7.3.
Body Weight and Vital Signs
A by-subject listing of vital signs will be provided by subject ID number and time point in 
chronological order. High or low values for vital signs will be flagged. Body weight will be 
included in the vital signs listing, if space permits. If not, they will be provided separately.
7.4.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the World Health Organization (WHO) Drug dictionary.
7.4.1.
Prior Medications
Prior medications are defined as any medications begun before a subject took the first study drug
(ADX).
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.
7.4.2.
Concomitant Medications
Concomitant medications are defined as medications taken while a subject took study drug
(ADX). 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 cohort. 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.


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For the purposes of analysis, any medications with a start date prior to or on the first dosing date 
of study drug and continued to be taken after the first dosing date or started after the first dosing 
date but prior to or on the last dosing date of study drug will be considered concomitant 
medications. 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, 
unless otherwise specified. Summaries will be based on the Safety Analysis Set. No formal 
statistical testing is planned.
All prior and concomitant medications (other than per-protocol study drugs) will be provided in a 
by-subject listing sorted by subject ID number and administration date in chronological order.
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.
ECG data collected up to 30 days after the last dose of ADX, or if applicable, 5 months after the 
last dose of nivolumab (whichever is later), will be included in the summary analysis. 
Analyses of ECG data will be provided by cohort using the Safety Analysis set. 
7.5.1.
Investigator Electrocardiogram Assessment
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.


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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
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 cohort:

VR > 100 bpm

PR interval > 200 msec

QRS interval > 110 msec
7.6.
Other Safety Measures
All post treatment anti-cancer therapies (other than those allowed per-protocol) will be provided 
in a by-subject listing sorted by subject ID number and administration date in chronological 
order. A summary of post treatment anti-cancer therapies will not be provided.
A data listing will be provided for the results of all pregnancy tests conducted in the study.
7.7.
Changes from Protocol-Specified Safety Analyses
Continuous safety data including laboratory data will not be summarized. 


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8.
PHARMACOKINETIC (PK) ANALYSES
8.1.
PK Sample Collection
Plasma samples will be collected to measure concentrations of ADX at protocol specified time 
points.
8.1.1.
Estimation of PK Parameters
For subjects in Cohort 1, relevant PK parameters will be estimated using Phoenix WinNonlin® 
software and utilizing standard noncompartmental methods. The linear/log trapezoidal rule will 
be used 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 
ADX by 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.
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.
8.1.2.
PK Parameters
The PK parameters for ADX presented in the table below will be computed for all subjects in the 
PK Analysis Set, as applicable.
The analytes and parameters presented in Table 8-1 will be used to evaluate the PK objectives of 
the study. The primary PK parameters are AUClast and Cmax of ADX. The PK parameters to be 
estimated in this study are listed and defined in the PK Abbreviations section.
Table 8-1.
PK Parameters for Each Analyte
Analyte
PK Parameters
ADX
Ceoi, Cmax, Tmax, AUClast, AUC0-336h, , C336h, Clast, Tlast, λz, T1/2


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Individual subject concentration data and individual subject PK parameters for ADX will be 
listed and summarized using descriptive statistics by cohort. Summary statistics (n, mean, StD, 
coefficient of variation [%CV], median, min, max, Q1, and Q3) will be presented for both 
individual subject concentration data by time point and individual subject PK parameters by 
treatment. Moreover, the geometric mean, 95% CI, and the mean and StD of the natural 
log-transformed values will be presented for individual subject PK parameter data.
Individual concentration data listings and summaries will include all subjects with concentration 
data. 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.
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 tables will be provided for each analyte by cohort:

Individual subject concentration data and summary statistics

Individual subject plasma PK parameters and summary statistics for Cohort 1
The following figures will be provided for each analyte for Cohort 1:

Mean (± StD) concentration data versus time (on linear and semilogarithmic scales)

Median (Q1, Q3) concentration data versus time (on linear and semilogarithmic scales)
Individual, mean, and median postdose concentration values that are ≤LLOQ will not be 
displayed in the figures and remaining points connected.
The following listings will be provided:

PK sampling details by subject, including procedures, differences in scheduled and actual 
draw times, and sample age

Individual data on determination of serum half-life and corresponding regression correlation 
coefficient


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9.
IMMUNOGENICITY ANALYSES
9.1.
ADA Sample Collection
Serum samples will be collected to measure anti-ADX antibody (ADA) at protocol specified 
time points.
9.2.
ADA Status
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.
Immunogenicity data will be listed for all subjects in the Immunogenicity Analysis Set.


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10.
BIOMARKER ANALYSES
Binding of ADX to MMP9 will be evaluated in the periphery and additional biomarkers will be 
explored in blood and tumor tissue. 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.
Tables will be provided for the following:

Descriptive Statistics for free and total MMP9 by visit for Cohort 1

Descriptive Statistics for the baseline level for biomarkers including EBV, MMR, and PD-L1
for Cohort 4
Figures will be provided for the following:

Mean (± StD) Plot for free and total MMP9 over time for Cohort 1

Median (Q1, Q3) Plot for free and total MMP9 over time for Cohort 1
Listings will be provided for the following:

Free and total MMP9 for Cohort 1

EBV, MMR, and PD-L1 for Cohort 4


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11.
REFERENCES
Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbe C, et al. Guidelines for the 
Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related 
Response Criteria. Clin Cancer Res 2009;15 (23):7412-20.


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12.
SOFTWARE
SAS® Software Version 9.4. (SAS Institute Inc., Cary, NC, USA.) is to be used for all 
programming of tables, listings, and figures.
WinNonlin® (Pharsight Corporation, Mountain View, CA, USA.) is to be used for all PK 
analyses.


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13.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision


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14.
APPENDICES
Appendix 1.
Study Procedures Table – Cohort 1 (Andecaliximab Monotherapy)
Appendix 2.
Study Procedures Table – Cohort 2: Combination Therapy Andecaliximab and SP
Appendix 3.
Study Procedures Table – Cohort 3: Combination Therapy Andecaliximab and SOX
Appendix 4.
Study Procedures Table – Cohort 4: Combination Therapy Andecaliximab and 
Nivolumab


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SCHEDULE OF ASSESSMENTS
Appendix 1.
Study Procedures Table – Cohort 1 (Andecaliximab Monotherapy)
Cohort 1 (Andecaliximab Monotherapy)
Study Phase
Screening
Each Cycle
(28 Days)
Cycle 1
Every 
8 Weeksk
EOTl
EOS
30-Day Safety 
Follow-Upm
5-Year 
LTFUr
Cycle Day
Screening
1
15
2
4
8
29/Cycle 2 
Day 1q
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1
± 1
± 1
± 5
N/A
N/A
± 7
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
X
X
X
X
Vital Signsc
X
X
X
X
X
X
X
X
X
X
12-Lead ECG
X
X
X
X
ECOG Performance 
Status
X
X
X
X
X
X
X
X
X
X
Prior/Concomitant 
Meds
X
X
X
X
X
X
X
X
X
X
X
AEsd
X
X
X
X
X
X
X
X
X
X
X
CT or MRIe
X
X
X
Collect Archival 
Tumor Tissue 
(if available)f
X


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Cohort 1 (Andecaliximab Monotherapy)
Study Phase
Screening
Each Cycle
(28 Days)
Cycle 1
Every 
8 Weeksk
EOTl
EOS
30-Day Safety 
Follow-Upm
5-Year 
LTFUr
Cycle Day
Screening
1
15
2
4
8
29/Cycle 2 
Day 1q
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1
± 1
± 1
± 5
N/A
N/A
± 7
N/A
Sample Collection
Chemistry
X
Xh
X
X
X
X
X
X
X
Hematology
X
Xh
X
X
X
X
X
X
X
Coagulation
X
Xh
X
X
X
X
X
Urinalysis
X
Xh
X
X
X
X
Pregnancy testg
X
Xh
X
X
Andecaliximab 
Concentrationi
X
X
X
X
X
X
X
X
X
Anti-Andecaliximab 
Antibodiesj
X
X
X
X
Blood Biomarkersn
X
X
X
X
X
X
X
X
X
X
Tumor Tissue 
Biopsyo
X
X
Normal Gastric 
Tissue Biopsyp
X
Overall Survival 
and Other 
Antitumor Therapy
X (Every 
3 months)
Study Drug Dosing
Andecaliximab IV 
Dosing
X
X
X


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EOS  End of Study (visit); EOT  End of treatment (visit); LTFU  Long Term Follow Up; PE  physical examination; PK: pharmacokinetics
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 on Day 1 and 15 of each 28 day cycle, and at the EOT 
visit, at the EOS visit, and at the 30 day safety follow up visit. 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 andecaliximab dosing during applicable visits.
e.
Tumor evaluation by CT or MRI will be performed during screening (scans taken as part of standard medical practice within 28 days of Day 1 are acceptable), every 8 weeks, 
and at the EOS visit (if not conducted within the previous 28 days). The same radiographic procedure used to define measurable lesions must be used throughout the study for 
each subject. 
f.
Archival tumor tissue FFPE blocks will be collected from all subjects. Efforts to acquire archival tissue block should begin on Cycle 1 Day 1.
g.
For females of childbearing potential, a serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Cycle 1 Day 1 Pre Dose, at the 
EOS visit, and at the 30 day safety follow up visit. 
h.
Day 1 pre dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit. 
i.
Plasma samples for andecaliximab PK will be collected prior to andecaliximab dosing and 30 (15) minutes after the end of infusion on Day 1 of Cycles 2, 3, 5, 7, and every 
3 cycles thereafter, at the EOT visit (if not conducted in the last 2 weeks), and EOS visit. Additionally, PK plasma samples will be collected at the following time points in 
Cycle 1 only: 30 (15) minutes after the end of infusion on Day 1; anytime on Days 2, 4, and 8; prior to dosing and 30 (15) minutes after the end of infusion on Day 15
j.
Blood samples for anti andecaliximab antibodies will be collected prior to dosing on Day 1 of Cycles 1, 2, 3, 5, 7, and every 3 cycles thereafter, at the EOT visit (if not 
conducted in the last 2 weeks), at the EOS visit, and at the 30 day safety follow up visit. 
k.
Every 8 Weeks (± 5 days) assessments will be performed for subjects continuing treatment, or subjects who discontinue all treatment prior to disease progression but remain 
on study. 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), and blood samples for chemistry, hematology, coagulation, and blood biomarkers (if not collected in the last 2 weeks) every 8 weeks until disease progression.
l.
EOT assessments will be requested by subjects who discontinue all treatment prior to disease progression. These assessments should be completed as soon as possible after 
the decision is made. Every attempt should be made to keep the subject in the study and continue to perform tumor evaluation by CT or MRI every 8 weeks until disease
progression. Blood samples for hematology, coagulation, chemistry, blood biomarkers, andecaliximab concentration and anti andecaliximab antibodies should only be 
collected if not conducted in the last 2 weeks.
m.
A safety follow up visit will be performed 30 days (± 7 days) after the last dose of andecaliximab. The 30 day safety follow up visit may be substituted by a scheduled study 
visit if it occurs within the same window. 
n.
Blood samples for biomarkers will be collected Pre Dose on Day 1 of each cycle, Day 15 of Cycles 1 and 2, and every 8 weeks, at the EOT (if not conducted in the last 
2 weeks) visit, and EOS visit. Additionally, blood samples for biomarkers will be collected on Days 2, 4, and 8 of Cycle 1.
o.
Tumor tissue biopsy must be collected within 28 days prior to first dose and on Cycle 2 Day 15 (+ 5 days). Endoscopic samples (minimum 4, but 6 8 encouraged) to be 
processed as described in the laboratory manual.
p.
Normal gastric tissue biopsy must be collected within 28 days prior to first dose (Day 1 of Cycle 1 Pre Dose). Endoscopic samples (minimum 4, but 6 8 encouraged) to be 
processed as described in the laboratory manual.
q.
The Cycle 1 Day 29 visit, which overlaps with the Cycle 2 Day 1 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 dose of GS 5745, completed all safety procedures through Day 28, or have experienced a DLT prior to Day 28. 
Assessments should follow schedule for Day 1 of each 28 day cycle. 
r.
LTFU for OS 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 of long 
term survival status and record of any other anti cancer therapy, cancer related surgery for up to 5 years after the EOS visit. 


Andecaliximab (GS-5745)
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Version 1.0
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Appendix 2.
Study Procedures Table – Cohort 2: Combination Therapy Andecaliximab and SP
Cohort 2: Combination Therapy Andecaliximab and SP
Study Phase
Screening
Each Cycle 
(28 Days)
Every 
8 Weeksr
EOTs
EOSt
30-Day Safety 
Follow-Upu
5-Year 
LTFUv
Cycle Day
Screening
1
15
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1q
± 1
± 5
N/A
N/A
± 7
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
X
X
X
Vital Signsc
X
X
X
X
X
X
12-Lead ECG
X
X
X
ECOG Performance 
Status
X
X
X
X
X
X
Prior/Concomitant 
Meds
X
X
X
X
X
X
X
AEsd
X
X
X
X
X
X
X
CT or MRIe
X
X
X
Collect Archival 
Tumor Tissuef
X
Sample Collection
Chemistry
X
Xh
X
X
X
X
X
Hematology
X
Xh
X
X
X
X
X
Coagulation
X
Xh
X
X
X
X
Urinalysis
X
Xh
X
X
X


Andecaliximab (GS-5745)
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Version 1.0
CONFIDENTIAL
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Cohort 2: Combination Therapy Andecaliximab and SP
Study Phase
Screening
Each Cycle 
(28 Days)
Every 
8 Weeksr
EOTs
EOSt
30-Day Safety 
Follow-Upu
5-Year 
LTFUv
Cycle Day
Screening
1
15
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1q
± 1
± 5
N/A
N/A
± 7
N/A
Pregnancy testg
X
Xh
X
X
X
Andecaliximab 
Concentrationi
X
X
X
X
Anti-Andecaliximab 
Antibodiesj
X
X
X
X
Blood Biomarkersk
X
X
X
X
X
X
Tumor Tissue Biopsyl
X
X
Normal Gastric 
Tissue Biopsym
X
Endoscopic 
Evaluationn
X
Overall Survival and 
Other Antitumor 
Therapy
X (Every 
3 months)
Dosing
Andecaliximab IV 
Dosingo
X
X
S-1 Dosingp
Cisplatin Dosingp


Andecaliximab (GS-5745)
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Version 1.0
CONFIDENTIAL
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EOS  End of Study (visit); EOT  End of treatment (visit); LTFU  Long Term Follow Up; PE  physical examination; PK  pharmacokinetics
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 on Day 1 and 15 of each 28 day cycle, at the EOT visit, 
at the EOS visit, and at the 30 day safety follow up visit. 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 andecaliximab dosing during applicable visits. 
e.
Tumor evaluation by CT or MRI will be performed during screening (scans taken as part of standard medical practice within 28 days of Day 1 are acceptable), every 8 weeks, 
and at the EOS visit (if not conducted within the previous 28 days). The same radiographic procedure used to define measurable lesions must be used throughout the study for 
each subject. 
f.
Archival tumor tissue will be collected from all subjects with available tissue. Efforts to acquire archival tissue should begin on Cycle 1 Day 1.
g.
For females of childbearing potential, a serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Pre Dose on Days 1 and 15 of 
each cycle, at the EOS visit, and at the 30 day safety follow up visit
h.
Day 1 pre dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit. 
i.
Plasma samples for andecaliximab PK in Cycle 1 will be collected 30 (± 15) minutes after the end of infusion on Day 1 and prior to andecaliximab dosing on Day 15. 
Additionally, plasma samples for andecaliximab PK will be collected prior to andecaliximab dosing and 30 (± 15) minutes after the end of infusion on Day 1 of Cycles 2, 3, 5, 
7, and every 3 cycles thereafter and anytime at the EOT visit (if not conducted in the last 2 weeks), and EOS visit. 
j.
Blood samples for anti andecaliximab antibodies will be collected prior to dosing on Day 1 of Cycles 1, 2, 3, 5, 7, and every 3 cycles thereafter; at the EOT visit (if not 
conducted in the last 2 weeks), at the EOS visit, and at the 30 day safety follow up visit.
k.
Blood samples for biomarkers will be collected Pre Dose on Day 1 of every cycle, Day 15 of Cycles 1 and 2, and every 8 weeks; at the EOT visit (if not conducted in the last 
2 weeks), and at the EOS visit. 
l.
Tumor tissue biopsy must be collected within 28 days prior to or on Day 1 of Cycle 1 Pre Dose and at EOS with documented disease progression. 
m.
Normal gastric tissue biopsy must be collected within 28 days prior to or on Day 1 of Cycle 1 Pre Dose. Do not collect if stomach is free of tumor. 
n.
An endoscopic evaluation must be performed alongside tissue biopsy collection 28 days prior to or on Day 1 of Cycle 1 Pre Dose. Do not perform if stomach is free of tumor. 
o.
Andecaliximab to be administered by IV infusion over 30 (± 5) minutes 
p.
The dosage and regimen of S 1 and cisplatin will be based on subject condition, investigator discretion, institutional practice and/or in the in country label. Due to expected 
variation in administration schedules, chemotherapy dosing may or may not take place on Days 1 and 15 of each 28 day cycle. See Appendix 6 of the Study Protocol for 
proposed regimen.
q.
C1D1 must occur within 3 days following enrollment in IWRS. A ± 1 day window applies to visits following Cycle 1 Day 1. 
r.
Every 8 Weeks (± 5 days) assessments will be performed for subjects continuing treatment, or subjects who discontinue all treatment prior to disease progression but remain 
on study. 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), and blood samples for chemistry, hematology, coagulation, and blood biomarkers (if not collected in the last 2 weeks) every 8 weeks until disease progression.
s.
EOT assessments will be requested from subjects who discontinue all treatment prior to disease progression. These assessments should be completed as soon as possible after 
the decision is made. Every attempt should be made to keep the subject in the study and continue to perform tumor evaluation by CT or MRI every 8 weeks until disease 
progression. Blood samples for hematology, coagulation, chemistry, blood biomarkers, andecaliximab concentration and anti andecaliximab antibodies should only be 
collected if not conducted in the last 2 weeks.
t.
EOS assessments will be completed when the subject meets at least 1 criterion for study discontinuation in Section 3.7 of the Study Protocol.
u.
A safety follow up visit will be performed 30 days (± 7 days) after the last dose of andecaliximab. The 30 day safety follow up visit may be substituted by a scheduled study 
visit if it occurs within the same window. 
v.
LTFU for OS 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 of long 
term survival status and record of any other anti cancer therapy, cancer related surgery for up to 5 years after the EOS visit.


Andecaliximab (GS-5745)
GS-US-296-1884 
Statistical Analysis Plan (Final Analysis)
Version 1.0
CONFIDENTIAL
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02 December 2019
Appendix 3.
Study Procedures Table – Cohort 3: Combination Therapy Andecaliximab and SOX
Cohort 3: Combination Therapy Andecaliximab and SOX
Study Phase
Screening
Each Cycle 
(21 Days)
Every 9 Weekss
EOTt
EOSu
30-Day Safety 
Follow-Up 
Visitv
5-Year LTFUw
Cycle Day
Screening
1
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1r
± 5
N/A
N/A
± 7
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
X
X
Vital Signsc
X
X
X
X
X
12-Lead ECG
X
X
X
ECOG Performance 
Status
X
X
X
X
X
Prior/Concomitant 
Meds
X
X
X
X
X
X
AEsd
X
X
X
X
X
X
CT or MRIe
X
X
X
Collect Archival 
Tumor Tissuef
X
Sample Collection
Chemistry
X
Xh
X
X
X
X
Hematology
X
Xh
X
X
X
X
Coagulation
X
Xh
X
X
X
Urinalysis
X
Xh
X
X


Andecaliximab (GS-5745)
GS-US-296-1884 
Statistical Analysis Plan (Final Analysis)
Version 1.0
CONFIDENTIAL
Page 49
02 December 2019
Cohort 3: Combination Therapy Andecaliximab and SOX
Study Phase
Screening
Each Cycle 
(21 Days)
Every 9 Weekss
EOTt
EOSu
30-Day Safety 
Follow-Up 
Visitv
5-Year LTFUw
Cycle Day
Screening
1
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1r
± 5
N/A
N/A
± 7
N/A
Pregnancy testg
X
Xh
X
X
Andecaliximab 
Concentrationi
X
X
X
Anti-Andecaliximab 
Antibodiesj
X
X
X
X
Blood Biomarkersk
X
X
X
X
X
Tumor Tissue 
Biopsyl
X
X
Normal Gastric 
Tissue Biopsym
X
Endoscopic 
Evaluationn
X
Overall Survival 
and Other 
Antitumor Therapy
X (Every 
3 months)
Dosing
Andecaliximab IV 
Dosingo
X
S-1 Dosingp
X
Oxaliplatin Dosingq
X


Andecaliximab (GS-5745)
GS-US-296-1884 
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Version 1.0
CONFIDENTIAL
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EOS  End of Study (visit); EOT  End of treatment (visit); LTFU  Long Term Follow Up; PE  physical examination; PK  pharmacokinetics
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 on Day 1 of each 21 day cycle and at the EOT visit, at 
the EOS visit, and at the 30 day safety follow up visit. 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 andecaliximab dosing during applicable visits. 
e.
Tumor evaluation by CT or MRI will be performed during screening (scans taken as part of standard medical practice within 28 days of Day 1 are acceptable), every 9 weeks, 
and at the EOS visit (if not conducted within the previous 28 days). The same radiographic procedure used to define measurable lesions must be used throughout the study for 
each subject. 
f.
Archival tumor tissue will be collected from all subjects with available tissue. Efforts to acquire archival tissue should begin on Cycle 1 Day 1.
g.
For females of childbearing potential, a serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Pre Dose on Day 1of each 21 day 
cycle, at the EOS visit, and at the 30 day safety follow up visit.
h.
Day 1 pre dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit. 
i.
Plasma samples for andecaliximab PK in Cycle 1 will be collected 30 (± 15) minutes after the end of andecaliximab infusion on Day 1. Additionally, plasma samples for 
andecaliximab PK will be collected prior to andecaliximab dosing and 30 (± 15) minutes after the end of infusion on Day 1 of Cycles 2, 3, 5, 7, and every 3 cycles thereafter 
and anytime at the EOT visit (if not conducted in the last 2 weeks), and EOS visit. 
j.
Blood samples for anti andecaliximab antibodies will be collected prior to dosing on Day 1 of Cycles 1, 2, 3, 5, 7, and every 3 cycles thereafter; at the EOT visit (if not 
conducted in the last 2 weeks), at the EOS visit, and at the 30 day safety follow up visit. 
k.
Blood samples for biomarkers will be collected Pre Dose on Day 1 of every cycle, and every 9 weeks; at the EOT visit (if not conducted in the last 2 weeks), and at the EOS 
visit. 
l.
Tumor tissue biopsy must be collected within 28 days prior to or on Day 1 of Cycle 1 Pre Dose and at EOS with documented disease progression.
m.
Normal gastric tissue biopsy must be collected within 28 days prior to or on Day 1 of Cycle 1 Pre Dose. Do not collect if stomach is free of tumor. 
n.
An endoscopic evaluation must be performed alongside tissue biopsy collection 28 days prior to or on Day 1 of Cycle 1 Pre Dose. Do not perform if stomach is free of tumor. 
o.
Andecaliximab to be administered via IV infusion over 30 (± 5) minutes
p.
S 1 to be administered orally twice daily for the first 14 days of the 21 day cycle
q.
Oxaliplatin to be administered by IV infusion over 2 hours on Day 1 of each 21 day cycle
r.
C1D1 must occur within 3 days following enrollment in IWRS. A ± 1 day window applies to visits following Cycle 1 Day 1.
s.
Every 9 Weeks (± 5 days) assessments will be performed for subjects continuing treatment, or subjects who discontinue all treatment prior to disease progression but remain 
on study. 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), and blood samples for chemistry, hematology, coagulation, and blood biomarkers (if not collected in the last 2 weeks) every 9 weeks until disease progression.
t.
EOT assessments will be requested from subjects who discontinue all treatment prior to disease progression. These assessments should be completed as soon as possible after 
the decision is made. Every attempt should be made to keep the subject in the study and continue to perform tumor evaluation by CT or MRI every 9 weeks until disease 
progression. Blood samples for hematology, coagulation, chemistry, blood biomarkers, andecaliximab concentration and anti andecaliximab antibodies should only be 
collected if not conducted in the last 2 weeks.
u.
EOS assessments will be completed when the subject meets at least 1 criterion for study discontinuation in Section 3.7 of the Study Protocol.
v.
A safety follow up visit will be performed 30 days (± 7 days) after the last dose of andecaliximab. The 30 day safety follow up visit may be substituted by a scheduled study 
visit if it occurs within the same window. 
w.
LTFU for OS 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 of long 
term survival status and record of any other anti cancer therapy, cancer related surgery for up to 5 years after the EOS visit. 


Andecaliximab (GS-5745)
GS-US-296-1884 
Statistical Analysis Plan (Final Analysis)
Version 1.0
CONFIDENTIAL
Page 51
02 December 2019
Appendix 4.
Study Procedures Table – Cohort 4: Combination Therapy Andecaliximab and Nivolumab
Cohort 4: Combination Therapy Andecaliximab and Nivolumab
Study Phase
Screening
Each Cycle 
(28 Days)
Cycle 1
Every 
8 Weekss
EOTt
EOSu
30-Day 
Safety 
Follow-Upv
5-Month 
Safety 
Follow-Upw
5-Year 
LTFUx
Cycle Day
Screening
1
15
8
N/A
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1r
± 1
± 1 
± 5
N/A
N/A
± 7
± 7
N/A
Study Assessments
Informed Consent
X
Medical Historya
X
Physical Examb
X
X
X
X
X
X
Vital Signsc
X
X
X
X
X
X
X
12-Lead ECG
X
X
X
ECOG Performance 
Status
X
X
X
X
X
X
X
Prior/Concomitant Meds
X
X
X
X
X
X
X
X
X
AEsd
X
X
X
X
X
X
X
X
X
CT or MRIe
X
X
X
Collect Archival Tumor 
Tissuef
X
Sample Collection
Chemistry
X
Xh
X
X
X
X
X
X
X
Hematology
X
Xh
X
X
X
X
X
X
X
Coagulation
X
Xh
X
X
X
X
Urinalysis
X
Xh
X
X
X
X
Pregnancy testg
X
Xh
X
X
X
X


Andecaliximab (GS-5745)
GS-US-296-1884 
Statistical Analysis Plan (Final Analysis)
Version 1.0
CONFIDENTIAL
Page 52
02 December 2019
Cohort 4: Combination Therapy Andecaliximab and Nivolumab
Study Phase
Screening
Each Cycle 
(28 Days)
Cycle 1
Every 
8 Weekss
EOTt
EOSu
30-Day 
Safety 
Follow-Upv
5-Month 
Safety 
Follow-Upw
5-Year 
LTFUx
Cycle Day
Screening
1
15
8
N/A
N/A
N/A
N/A
N/A
N/A
Window (Days)
−28
± 1r
± 1
± 1 
± 5
N/A
N/A
± 7
± 7
N/A
Thyroid Function Tests 
(TSH, T3, free T4)i
X
X
X
X
X
X
Andecaliximab 
Concentrationj
X
X
X
X
X
Anti-Andecaliximab 
Antibodiesk
X
X
X
X
X
Blood Biomarkersl
X
X
X
X
X
X
X
X
X
Tumor Tissue Biopsym
X
X
X
Normal Gastric Tissue 
Biopsyn
X
Endoscopic Evaluationo
X
X
Overall Survival and 
Other Antitumor Therapy
X (Every 
3 months)
Dosing
Andecaliximab IV 
Dosingp
X
X
Nivolumab Dosingq
X
X
EOS  End of Study (visit); EOT  End of treatment (visit); LTFU  Long Term Follow Up; PE  physical examination; PK  pharmacokinetics; TSH  thyroid stimulating 
hormone 
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 on Day 1 and 15 of each 28 day cycle and at the EOT 
visit, at the EOS visit, and at the 30 day safety follow up visit. 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.


Andecaliximab (GS-5745)
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Version 1.0
CONFIDENTIAL
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d.
AEs will be assessed before and after andecaliximab dosing during applicable visits. 
e.
Tumor evaluation by CT or MRI will be performed during screening (scans taken as part of standard medical practice within 28 days of Day 1 are acceptable), every 8 weeks, 
and at the EOS visit (if not conducted within the previous 28 days). The same radiographic procedure used to define measurable lesions must be used throughout the study for 
each subject. 
f.
Archival tumor tissue will be collected from all subjects with available tissue. Efforts to acquire archival tissue should begin on Cycle 1 Day 1.
g.
For females of childbearing potential, a serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Pre Dose on Days 1 and 15 of 
each cycle, at the EOS visit and at the 30 day and 5 month safety follow up visits.
h.
Day 1 pre dose samples for the specified assessments may be drawn up to 2 days prior to the Day 1 visit. 
i.
Blood samples for thyroid function tests will be collected at screening, every 8 weeks (± 5 days) if not performed in the last 2 weeks, at the EOT visit, at the EOS visit, and at 
the 30 day and 5 month safety follow up visits. 
j.
Plasma samples for andecaliximab PK in Cycle 1 will be collected 30 (± 15) minutes after the end of andecaliximab infusion on Day 1, anytime on Day 8, and prior to 
andecaliximab dosing and 30 (± 15) minutes after the end of infusion on Day 15. Additionally, plasma samples for andecaliximab PK will be collected prior to andecaliximab 
dosing and 30 (± 15) minutes after the end of infusion on Day 1 and Day 15 of Cycles 2, 3, 5, 7, and every 3 cycles thereafter and anytime at the EOT visit (if not conducted 
in the last 2 weeks), and EOS visit. 
k.
Blood samples for anti andecaliximab antibodies will be collected prior to dosing on Day 1 of Cycles 1, 2, 3, 5, 7, and every 3 cycles thereafter; at the EOT visit (if not 
conducted in the last 2 weeks), at the EOS visit, and at the 30 day and 5 month safety follow up visits. 
l.
Blood samples for biomarkers will be collected Pre Dose on Day 1 of every cycle, Day 8 of Cycle 1, Day 15 of Cycles 1 and 2, every 8 weeks, at the EOT visit (if not 
conducted in the last 2 weeks), at the EOS visit, at the 30 day safety follow up visit, and at the 5 month safety follow up visit. 
m.
Tumor tissue biopsy must be collected within 28 days prior to or on Day 1 of Cycle 1 Pre Dose and at 6 weeks (± 1 week) after the first dose of andecaliximab. The on
treatment tumor tissue biopsy and endoscopic evaluation are performed at 6 weeks (± 1 week) after the first dose of andecaliximab. These assessments are not repeated at each 
Cycle Day 15 visit. 
.
n.
Normal gastric tissue biopsy must be collected within 28 days prior to or on Day 1 of Cycle 1 Pre Dose. Do not collect if stomach is free of tumor.
o.
An endoscopic evaluation must be performed alongside tissue biopsy collection 28 days prior to or on Day 1 of Cycle 1 Pre Dose and between 5 and 8 weeks after the first 
dose of andecaliximab. Do not perform if stomach is free of tumor.
p.
Andecaliximab to be administered via IV infusion over 30 (± 5 minutes).
q.
Following administration of andecaliximab, administer nivolumab via IV infusion over approximately 60 (± 5) minutes
r.
C1D1 must occur within 3 days following enrollment in IWRS. A ± 1 day window applies to visits following Cycle 1 Day 1. 
s.
Every 8 Weeks (± 5 days) assessments will be performed for subjects continuing treatment, or subjects who discontinue all treatment prior to disease progression but remain 
on study. 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), and blood samples for chemistry, hematology, coagulation, thyroid function tests, and blood biomarkers (if not collected in the last 2 weeks) every 8 weeks until 
disease progression.
t.
EOT assessments will be requested from subjects who discontinue all treatment prior to disease progression. These assessments should be completed as soon as possible after 
the decision is made. Every attempt should be made to keep the subject in the study and continue to perform tumor evaluation by CT or MRI every 8 weeks until disease 
progression. Blood samples for hematology, coagulation, chemistry, blood biomarkers, andecaliximab concentration and anti andecaliximab antibodies should only be 
collected if not conducted in the last 2 weeks.
u.
EOS assessments will be completed when the subject meets at least 1 criterion for study discontinuation in Section 3.7 of the Study Protocol.
v.
A safety follow up visit will be performed 30 days (± 7 days) after the last dose of andecaliximab. The 30 day safety follow up visit may be substituted by a scheduled study 
visit if it occurs within the same window. 
w.
A safety follow up visit will be performed 5 months (± 7 days) following the last dose of nivolumab. The 5 month follow up visit may be substituted by a scheduled study 
visit if it occurs within the same window.
x.
LTFU for OS 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 of long 
term survival status and record of any other anti cancer therapy, cancer related surgery for up to 5 years after the EOS visit.
CCI