Clinical trial NCT02864381
Conditions: Gastric Adenocarcinoma Gastroesophageal Junction Adenocarcinoma
Sponsor: Gilead Sciences
Start date: 2016-09-01; Completion date: 2019-08-23
Enrollment: 144 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate and compare the efficacy of andecaliximab (GS-5745) in combination with nivolumab versus nivolumab alone in adults with recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Detailed description:

Arms: arm 1: Andecaliximab 800 mg plus nivolumab 3 mg/kg administered every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent (up to 34 weeks at the time of the primary efficacy analysis; up to 101 weeks at the time of the safety follow-up analysis). arm 2: Nivolumab 3 mg/kg administered every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent (up to 41 weeks at the time of the primary efficacy analysis; up to 97 weeks at the time of the safety follow-up analysis).
Interventions: intervention 1: Andecaliximab intervention 2: Nivolumab
Intervention descriptions: intervention 1: 800 mg administered via IV infusion intervention 2: 3 mg/kg administered via IV infusion

Protocol documents:
SAP_002.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 2, Open-Label, Randomized Study to Evaluate the 
Efficacy and Safety of Andecaliximab (GS-5745) Combined 
with Nivolumab versus Nivolumab Alone in Subjects with 
Unresectable or Recurrent Gastric or Gastroesophageal 
Junction Adenocarcinoma
Name of Test Drug:
Andecaliximab (GS-5745)
Study Number:
GS-US-296-2013
Protocol Version (Date):
Amendment 3
Analysis Type:
Follow-up Analysis
Analysis Plan Version:
1.0
Analysis Plan Date:
28 June 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
1.
INTRODUCTION ................................................................................................................................................7
1.1.
Study Objectives ......................................................................................................................................7
1.2.
Study Design............................................................................................................................................7
1.3.
Sample Size and Power............................................................................................................................8
2.
TYPE OF PLANNED ANALYSIS ......................................................................................................................9
2.1.
Interim Analyses ......................................................................................................................................9
2.2.
Primary Analysis......................................................................................................................................9
2.3.
Follow-up Analysis ..................................................................................................................................9
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................10
3.1.
Analysis Sets..........................................................................................................................................10
3.1.1.
Intent-to-Treat Analysis Set .................................................................................................10
3.1.2.
Safety Analysis Set...............................................................................................................10
3.1.3.
Pharmacokinetic Analysis Set..............................................................................................10
3.1.4.
Immunogenicity Analysis Set ..............................................................................................10
3.2.
Subject Grouping ...................................................................................................................................11
3.3.
Strata and Covariates..............................................................................................................................11
3.4.
Examination of Subject Subgroups........................................................................................................11
3.5.
Multiple Comparisons............................................................................................................................13
3.6.
Missing Data and Outliers......................................................................................................................13
3.6.1.
Missing Data ........................................................................................................................13
3.6.2.
Outliers.................................................................................................................................14
3.7.
Data Handling Conventions and Transformations .................................................................................14
3.8.
Analysis Visit Windows.........................................................................................................................15
3.8.1.
Definition of Study Day .......................................................................................................15
3.8.2.
Analysis Visit Windows.......................................................................................................15
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window................................................................................................................................17
4.
SUBJECT DISPOSITION ..................................................................................................................................18
4.1.
Subject Enrollment and Disposition.......................................................................................................18
4.2.
Extent of Study Drug Exposure and Adherence.....................................................................................19
4.2.1.
Duration of Exposure to Study Drug....................................................................................19
4.2.2.
Adherence to Study Drug.....................................................................................................19
4.3.
Protocol Deviations................................................................................................................................20
5.
BASELINE CHARACTERISTICS....................................................................................................................21
5.1.
Demographics ........................................................................................................................................21
5.2.
Other Baseline Characteristics ...............................................................................................................21
5.3.
Medical History......................................................................................................................................21
5.3.1.
Disease History ....................................................................................................................21
5.4.
Chemotherapy and Radiotherapy Therapy.............................................................................................22
6.
EFFICACY ANALYSES ...................................................................................................................................23


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6.1.
Primary Efficacy Endpoint.....................................................................................................................23
6.1.1.
Statistical Hypothesis for the Primary Efficacy Endpoint....................................................25
6.1.2.
Analysis for the Primary Efficacy Endpoint.........................................................................25
6.2.
Secondary Efficacy Endpoint.................................................................................................................25
6.2.1.
Progression-Free Survival ....................................................................................................25
6.2.2.
Overall Survival ...................................................................................................................27
6.2.3.
Duration of Response...........................................................................................................27
6.3.
Exploratory Efficacy Endpoints.............................................................................................................27
7.
SAFETY ANALYSES........................................................................................................................................28
7.1.
Adverse Events and Deaths....................................................................................................................28
7.1.1.
Adverse Event Dictionary ....................................................................................................28
7.1.2.
Adverse Event Severity........................................................................................................28
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................28
7.1.4.
Serious Adverse Events........................................................................................................28
7.1.5.
Treatment-Emergent Adverse Events...................................................................................28
7.1.6.
Summaries of Adverse Events and Deaths...........................................................................29
7.2.
Laboratory Evaluations ..........................................................................................................................30
7.2.1.
Graded Laboratory Values ...................................................................................................31
7.2.2.
Shifts Relative to the Baseline Value ...................................................................................31
7.3.
Body Weight and Vital Signs.................................................................................................................31
7.4.
Concomitant Medications ......................................................................................................................32
7.4.1.
Prior Medications .................................................................................................................32
7.4.2.
Concomitant Medications.....................................................................................................32
7.5.
Electrocardiogram Results .....................................................................................................................33
7.5.1.
Investigator Electrocardiogram Assessment ........................................................................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
8.2.
Statistical Analysis Methods ..................................................................................................................34
9.
IMMUNOGENICITY ANALYSES...................................................................................................................35
9.1.
ADA Sample Collection.........................................................................................................................35
9.2.
Statistical Analysis Methods ..................................................................................................................35
10.
BIOMARKER ANALYSES...............................................................................................................................36
11.
REFERENCES ...................................................................................................................................................37
12.
SOFTWARE.......................................................................................................................................................38
13.
SAP REVISION..................................................................................................................................................39
14.
APPENDIX.........................................................................................................................................................40
Appendix 1.
List of Laboratory Tests for Safety Analysis..........................................................................41
Appendix 2.
Schedule of Assessments........................................................................................................42
CCI-


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LIST OF TABLES
Table 1.
Analysis Visit Windows for Chemistry, Hematology and Vital Signs...................................16
Table 2.
Analysis Visit Windows for Urinalysis, Pregnancy Test, ECG, and ECOG ..........................16
Table 3.
Analysis Visit Windows for Thyroid Function Tests (TSH, T3, free T4)..............................16
Table 4.
Analysis Visit Windows for Tumor Assessments ..................................................................17
Table 5.
Confirmed Overall Response Derivation................................................................................24
Table 6.
Biomarkers and Assay Testing Methods ................................................................................36
LIST OF FIGURES
Figure 1.
Study Design ............................................................................................................................8


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LIST OF ABBREVIATIONS
ADA
anti-drug antibody
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
ATC
Anatomical Therapeutic Chemical
BLQ
below the limit of quantitation
BMI
body mass index
CFR
Code of Federal Regulations
CI
confidence interval
CK
creatine kinase
CMH
Cochran-Mantel-Haenszel
CR
complete response
CRF
case report form
CSR
clinical study report
CT
Computerized Tomography
CTCAE
Common Toxicity Criteria for Adverse Events
CV
coefficient of variation
DCR
disease control rate
DMC
data monitoring committee
DOR
duration of response
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form(s)
EOS
end of study
EOT
end of treatment
FAS
full analysis set
GEJ
gastroesophageal junction
Hb
hemoglobin
HLT
high-level term
ICH
International Conference on Harmonization (of Technical Requirements for Registration of 
Pharmaceuticals for Human Use)
ID
identification
IHC
immunohistochemistry
ITT
intent to treat
LLOQ
lower limit of quantitation
LOQ
limit of quantitation
MedDRA
Medical Dictionary for Regulatory Activities
MMR
mismatch repair
MRI
Magnetic Resonance Imaging


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MedDRA
Medical Dictionary for Regulatory Activities
NE
non-evaluable
NN
non-CR/non-PD
ORR
objective response rate
OS
overall survival
PD
progressive disease
PD-L1
programmed death ligand 1
PR
partial response
PT
preferred term
Q1, Q3
first quartile, third quartile
QRS
electrocardiographic deflection between the beginning of the Q wave and termination of the 
S wave representing time for ventricular depolarization
QT
electrocardiographic interval between the beginning of the Q wave and termination of the 
T wave representing the time for both ventricular depolarization and repolarization to occur
QTc
QT interval corrected for heart rate
QTcF
QT interval corrected for heart rate using Fridericia’s formula
RECIST
Response Evaluation Criteria in Solid Tumors
RR
electrocardiographic interval representing the time measurement between the R wave of 
one heartbeat and the R wave of the preceding heartbeat
SAE
serious adverse event
SAP
statistical analysis plan
SD
stable disease
StD
standard deviation
SI (units)
international system of units
SOC
system organ class
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
ULN
upper limit of normal
VR
ventricular rate
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the follow-up analysis for Study 
GS-US-296-2013. This SAP is based on the study protocol Amendment 3 dated 16 June 2017
and the electronic case report form (eCRF). The SAP will be finalized before database 
finalization. Any changes made after the finalization of the SAP will be documented in the CSR.
At the time of primary analysis, no clinical study report (CSR) was written. The synoptic CSR 
for GS-US-296-2013 will be based on the follow-up analysis SAP except for the analysis of 
efficacy, which will be based on the primary analysis, as described in the SAP for primary 
analysis.
1.1.
Study Objectives
The primary objective of this study is as follows:

To evaluate and compare the efficacy of andecaliximab (GS-5745) in combination with 
nivolumab versus nivolumab alone in subjects with recurrent gastric or gastroesophageal 
junction (GEJ) adenocarcinoma
The secondary objectives of this study are as follows:

To characterize and compare safety and tolerability of andecaliximab (GS-5745) in 
combination with nivolumab versus nivolumab alone in subjects with recurrent gastric or 
GEJ adenocarcinoma

To characterize the pharmacokinetics (PK) of andecaliximab (GS-5745) in combination with 
nivolumab
1.2.
Study Design
This is a Phase 2, open-label, randomized study comparing andecaliximab (GS-5745) in 
combination with nivolumab in recurrent gastric and GEJ adenocarcinoma versus nivolumab
alone. Approximately 120 subjects will be randomized in a 1:1 manner through an interactive 
response system (IWRS) to either Treatment Arm A: andecaliximab (GS-5745) + nivolumab or 
Treatment Arm B: nivolumab alone. The centralized randomization will be stratified by 
programmed death ligand 1 (PD-L1) positive (≥1% tumor cell staining) versus PD-L1 negative
(< 1% tumor cell staining).
Subjects randomized to Arm A will receive 800 mg of andecaliximab on Day 1 and every 
2 weeks thereafter via intravenous (IV) infusion over approximately 30 minutes in advance of 
nivolumab. Nivolumab (3 mg/kg) will be administered via IV infusion over approximately 
60 minutes following the completion of andecaliximab administration. Subjects meeting 
eligibility randomized to Arm B will receive 3 mg/kg nivolumab via IV infusion over 
approximately 60 minutes on Day 1 and every 2 weeks thereafter.


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Contrast-enhanced computerized tomography (CT) (without contrast if use of contrast is 
contraindicated) or gadolinium-enhanced magnetic resonance imaging (MRI) of the chest, 
abdomen, and pelvis will be performed at screening, every 8 weeks during the study and at the 
EOS visit if one has not been performed within the last 8 weeks. RECIST 1.1 will be used for 
assessment of tumor responses with some modifications to account for atypical responses which 
may occur with immune-based therapies.
Long term follow-up for OS begins once a subject discontinues study for reasons other than 
death. Subjects will be contacted via phone call every 3 months for determination of long-term 
survival status.
Figure 1.
Study Design
1.3.
Sample Size and Power
Assuming the Objective Response Rate (ORR) for subjects treated with nivolumab alone is 
25%, 120 subjects in total are needed to detect an improvement of 20% in ORR for subjects
treated with andecaliximab (GS-5745) and nivolumab with approximately 83% power at the 
one-sided significance level of 10% using a Cochran-Mantel-Haenszel (CMH) test with an 
assumption of common odds ratio for all strata. The assumption of nivolumab ORR is based on 
the upper bound of the 95% confidence interval of the estimated ORR in CheckMate-032 Study
{Le 2016}.
I 
I Arm A 
: N=60 
GS-5745 + Nivolumab 
u to 2 ears 
Arm B 
Nivolumab 
Long-Term Follow-Up :> 
1 N=60 L--~U:.i:.;t~o~2:..i.;e~a~r~s .... 1 
1L_.'.:L~o!.!!ng~-...:.Te::,:r...:.m:.:....:...Fo=.;l~lo:..:w.;..-....:U-"p--> 
I 
Stratifi~ation and 
Randomization 
Disease 
progression or 
study stopped 


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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.
An external multidisciplinary Data Monitoring Committee (DMC) will review the progress of 
the study and perform interim reviews of the safety data in order to protect subject welfare and 
preserve study integrity. To ensure the best interests of the participants, the DMC will
recommend to the sponsor if the nature, frequency, and severity of adverse effects associated 
with the study treatment warrant the early termination of the study, the continuation of the study, 
or the continuation of the study with modifications.
The initial review will be conducted after 20 subjects have completed through Week 8. 
Thereafter, review of safety data will be conducted every 6 months.
The DMC’s role and responsibilities and the scope of analysis to be provided to the DMC are in 
a mutually agreed upon charter, which defines the DMC membership, meeting logistics, and 
meeting frequency.
2.2.
Primary Analysis
The primary analysis will occur when the last subject is treated for 6 months or discontinued, 
whichever is earlier.
2.3.
Follow-up Analysis 
After the primary analysis, updated analyses of study data including efficacy and safety will be 
performed to provide long-term efficacy (overall survival) and safety follow-up. P-values for the 
updated analyses of efficacy are for display purposes only, and no formal hypothesis testing will 
be conducted.


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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 Intent-to-Treat (ITT) 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 randomized 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 treatment group.
3.1.1.
Intent-to-Treat Analysis Set
The ITT Analysis Set includes all subjects who were randomized in the study.
This is the primary analysis set for efficacy analyses. 
3.1.2.
Safety Analysis Set
The Safety Analysis Set includes all subjects who took at least 1 dose of study drug
(andecaliximab or nivolumab). This is the primary analysis set for safety analyses,
3.1.3.
Pharmacokinetic Analysis Set
The Pharmacokinetic (PK) Analysis Set will include all randomized subjects who took at least 
1 dose of andecaliximab and have at least 1 nonmissing post dose concentration value reported 
by the PK laboratory. This is the primary analysis set for all PK analyses.
3.1.4.
Immunogenicity Analysis Set
The Immunogenicity Analysis Set will include all randomized subjects who took at least 1 dose 
of andecaliximab and have at least 1 nonmissing postdose antidrug antibody (ADA) status
reported. This is the primary analysis set for all immunogenicity analyses.


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3.2.
Subject Grouping
For analyses based on the ITT Analysis Set, subjects will be grouped according to the treatment 
to which they were randomized. For analyses based on the Safety Analysis Set, subjects will be 
grouped according to the actual treatment received. The actual treatment received will differ 
from the randomized treatment only when the actual treatment differs from randomized 
treatment for the entire treatment duration.
For the PK Analysis Set and Immunogenicity Analysis Set, subjects will be grouped according to 
the actual treatment they received.
3.3.
Strata and Covariates
Subjects will be randomly assigned to treatment groups via the interactive voice or web response 
system (IXRS) in a 1:1 ratio using a stratified randomization schedule. Stratification will be 
based on the following variables:

PD-L1 positive (≥1% tumor cell staining) versus PD-L1 negative (< 1% tumor cell staining)
If there are discrepancies in stratification factor values between the IXRS and the Covance lab
database, the values recorded in the Covance lab database will be used for analyses.
Efficacy endpoints will be evaluated using stratification factors as covariates or stratification 
variables for analyses, as specified in Section 6. 
In the situation where there is insufficient information in a stratum (ie, if there are < 6 subjects or 
there is no informative event in a stratum by combined treatment arms), the stratification by 
PD-L1 will not be applied.
3.4.
Examination of Subject Subgroups
Primary (ORR) and key secondary (PFS and OS) efficacy endpoints will be examined in the 
following subgroups if there is sufficient sample size in the subgroup:

Stratification factor PD-L1 status
< 1% tumor cell staining
≥1% tumor cell staining

Overall cell PD-L1 staining at baseline
< 1% tumor cell and associated immune cell PD-L1 staining
≥1% tumor cell and associated immune cell PD-L1 staining


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
Mismatch repair (MMR) status at baseline
MMR deficient (Subjects with one or more positive in MSH2, MSH6, MLH1, and PMS2 
mutation tests are considered MMR deficient.)
MMR proficient (Subjects with all negative in MSH2, MSH6, MLH1, and PMS2 
mutation tests are considered MMR proficient.)

Primary Site of Tumor
Gastric
GEJ

Number of Prior Anticancer Therapies
1
2
3
4 and above

Histological Type
Diffuse
Other

Age group
< 65
≥65

Gender
Male
Female


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
Race
White
Non-White
Adverse events and lab abnormalities will be examined in the following subgroups:

Age group
< 65
≥65

Gender
Male
Female

Race
White
Non-White
In the situation where there is no responder in a subgroup, odds ratio of ORR within subgroups 
will not be estimated.
To graphically display treatment effect changes across subsets, a forest plot of odds ratios and 
hazard ratios by subject subgroup will be produced.
3.5.
Multiple Comparisons
All endpoint tests will be done at the one-sided significance level of 0.1 with no multiplicity 
adjustment in this proof-of-concept study.
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.


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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 is described in Section 7.1.5.2., for prior 
and concomitant medications in Section 7.4, and for initiation of new anticancer therapy in 
Section 6.3.1.
3.6.2.
Outliers
Outliers will not be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted. All data will be included in the data analysis.
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 “01” 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 randomization will be used for analyses and presentation 
in listings. For screen failures, the date the informed consent was signed will be used for age 
calculation. 
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.

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 transformed data or nonparametric analysis methods may be used, 
as appropriate.


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Natural logarithm transformation will be used for plasma/blood concentrations. Plasma 
concentration values that are below the limit of quantitation (BLQ) will be presented as “BLQ” 
in the concentration data listing. Values that are BLQ will be treated as 0 at predose time points, 
and one-half the value of the LOQ at postdose time points for determination of summary and 
order statistics.
The following conventions will be used for the presentation of summary and order statistics:

If at least 1 subject has a concentration value of BLQ for the time point, the minimum value 
will be displayed as “BLQ.”

If more than 25% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum and Q1 values will be displayed as “BLQ.”

If more than 50% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, and median values will be displayed as “BLQ.”

If more than 75% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, median, and Q3 values will be displayed as “BLQ.”

If all subjects have concentration data values of BLQ for a given time point, all order 
statistics (minimum, Q1, median, Q3, and maximum) will be displayed as “BLQ.”
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study day will be calculated from the first dosing date of study drug andecaliximab or nivolumab
and derived as follows:

For post dose study days: Assessment Date – First Dosing Date + 1

For days prior to the first dose: Assessment Date – First Dosing Date
Therefore, study day 1 is the day of first dose of study drug administration.
3.8.2.
Analysis Visit Windows
Subject visits might not occur on protocol-specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows.
The analysis windows for chemistry, hematology and vital signs are provided in Table 1. The 
analysis windows for urinalysis, pregnancy test, ECG, and ECOG are provided in Table 2. The 
analysis windows for Thyroid Function Tests (TSH, T3, and free T4) are provided in Table 3. 
The analysis windows for tumor assessments are provided in Table 4.


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Table 1.
Analysis Visit Windows for Chemistry, Hematology and Vital Signs
Analysis Visit
Study Day
Lower Limit (inclusive)
Upper Limit (inclusive)
Baseline
1
-28 
1 (before 1st dose)
Week 2
15
1 (after first dose)
21
Week 4
29
22
35
Week 6
43
36
49
Week X=8, 10, …
7*x+1
7x-6
7*x + 7
Safety Follow-up
max (andecaliximab end date,
Nivo end date) + 1
max(andecaliximab end date + 30 days,
Nivo end date + 5 months)
Table 2.
Analysis Visit Windows for Urinalysis, Pregnancy Test, ECG, and 
ECOG
Analysis Visit
Study Day
Lower Limit (inclusive)
Upper Limit (inclusive)
Baseline
1
-28
1 (before 1st dose)
Week 4
29
1 (after first dose)
42
Week 8
57
43
70
Week 12
85
71
98
Week X=16, 20, …
7*x+1
7x-13
7*x + 14
Safety Follow-up
max (andecaliximab end date,
Nivo end date) + 1
max(andecaliximab end date + 30 days,
Nivo end date + 5 months)
Note. For pregnancy test, use results from serum test for screening and results from urine test for post-screening visit. 
Table 3.
Analysis Visit Windows for Thyroid Function Tests (TSH, T3, 
free T4)
Analysis Visit
Study Day
Lower Limit (inclusive)
Upper Limit (inclusive)
Baseline
1
-28
1 (before 1st dose)
Week 8
57
1 (after first dose)
84
Week 16
113
85
140
Week 24
169
141
196
Week 32, 40,  ….
7*x+1
7x-27
7*x + 28
Safety Follow-up
max (andecaliximab end date,
Nivo end date) + 1
max (andecaliximab end date + 30 days,
Nivo end date + 5 months)


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Table 4.
Analysis Visit Windows for Tumor Assessments
Analysis Visit
Nominal Study Day
Lower Limit (inclusive)
Upper Limit (inclusive)
Baseline
-28
Randomization date - 60
Randomization date
Week 8
57
1
84
Week 8 confirmatory
Day of Week 8 visit + 28
Day of Week 8 visit + 28
Week 16
113
85
140
Week 16 confirmatory
Day of Week 16 visit + 28
Day of Week 16 visit + 28
Week 24
169
141
196
Week 24 confirmatory
Day of Week 24 visit + 28
Day of Week 24 visit + 28
Week X=32, 40, …
7*x+1
7x-27
7*x + 28
Week X=32, 40, … 
confirmatory
Day of Week 32, 40, … 
visit +28
Day of Week 32, 40, … 
visit +28
Note: In the rare cases where the screening assessments are after the randomization date but prior to the first dose of study drug, 
the assessments will be considered as baseline.
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time-to-event analysis would not require 1 value per analysis window.
If multiple valid, nonmissing, measurements exist in an analysis window, records will be chosen 
based on the following rules if a single value is needed:

For baseline, the last nonmissing value on or prior to the first dosing date of study drug will 
be selected, unless specified differently. If there are multiple records with the same time or 
no time recorded on the same day, the baseline value will be the average of the measurements 
for continuous data, or the measurement with the lowest severity (eg, normal will be selected 
over abnormal for safety electrocardiogram [ECG] findings) for categorical data.

For post baseline values:
The record closest to the nominal day for that visit will be selected.
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.
If there is more than 1 record on the selected day, the average will be taken for 
continuous data and the worse severity will be taken for categorical data, unless 
otherwise specified, unless otherwise specified.


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
A summary of subject enrollment will be provided by treatment group for each country, 
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 similar enrollment table will be provided by randomization stratum. The denominator for the 
percentage of subjects in the stratum will be the total number of enrolled subjects. If there are 
discrepancies in the value used for stratification assignment between the IXRS and the clinical 
database, the value collected in the clinical database will be used for the summary. A listing of 
subjects with discrepancies in the value used for stratification assignment between the IXRS and 
the clinical database at the time of data finalization will be provided.
The randomization schedule used for the study will be provided as an appendix to the CSR.
A summary of subject disposition will be provided by treatment group. This summary will 
present the number of subjects screened, the number of subjects enrolled, and the number of 
subjects in each of the categories listed below:

Safety Analysis Set

Randomized but never dosed

Completed study drug

Did not complete study drug with reasons for discontinuation of study drug

Completed tumor assessment

Discontinued tumor assessment before Disease Progression

Completed long-term follow-up

Did not complete long-term follow-up with reasons for discontinuation of long-term 
follow-up
For the status of study drug and study completion and reasons for 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 ITT Analysis Set corresponding 
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The following by-subject listings will be provided by subject identification (ID) number in 
ascending order to support the above summary tables:

Reasons for study drug, tumor assessment, and long-term follow-up discontinuation
4.2.
Extent of Study Drug Exposure and Adherence
Extent of exposure to study drug will be examined by assessing the total duration of exposure to 
study drug and the level of adherence relative to the study drug regimen specified in the protocol
by component (andecaliximab/nivolumab).
4.2.1.
Duration of Exposure to Study Drug
Total duration of exposure to study drug will be defined as last dosing date minus first dosing 
date plus 14, regardless of any 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 date 
is missing, the latest date among the study drug end date, clinical visit date, laboratory sample 
collection date, and vital signs assessment date that occurred during the on-treatment period will 
be used for subjects included in the final analyses.
The total duration of exposure to study drug will be summarized using descriptive statistics.
Summaries will be provided by treatment group for the Safety Analysis Set.
4.2.2.
Adherence to Study Drug
The total number of doses administered will be summarized using descriptive statistics. 
4.2.2.1.
On-Treatment Adherence
The level of on-treatment adherence to the study drug regimen will be determined by the total 
amount of study drug administered relative to the total amount of study drug expected to be 
administered during a subject’s actual on-treatment period based on the study drug regimen, 
Investigator-prescribed interruption, reductions and escalations as specified in the protocol will 
be taken into account.
The level of on-treatment adherence will be expressed as a percentage using the following 
formula:
Total Amount of Study Drug Administered
On-Treatment Adherence (%) = 
 x 100
Study Drug Expected to be Administered on Treatment








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Descriptive statistics for the level of on-treatment adherence with the number and percentage of 
subjects belonging to adherence categories (e.g., {< 75%, ≥ 75 to < 90%, ≥ 90%}) will be 
provided by treatment group for the Safety Analysis Set.
No formal statistical testing is planned.
A by-subject listing of study drug administration will be provided by subject ID number 
(in ascending order) and visit (in chronological order).
4.3.
Protocol Deviations 
Subjects who did not meet the eligibility criteria for study entry, but enrolled in the study will be 
summarized regardless of whether they were exempted by the sponsor or not. The summary will 
present the number and percentage of subjects who did not meet at least 1 eligibility criterion and 
the number of subjects who did not meet specific criteria by treatment group based on the ITT
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 treatment group for the ITT 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
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 
treatment group 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 ITT 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
Other baseline characteristics include, ECOG, PD-L1 status, and MMR status at screening. 
These baseline characteristics will be summarized by treatment group and overall using 
descriptive statistics for continuous variables and using number and percentage of subjects for 
categorical variables. The summary of baseline characteristics will be provided for the ITT 
Analysis Set. No formal statistical testing is planned.
A by-subject listing of other baseline characteristics will be provided by subject ID number in 
ascending order.
5.3.
Medical History
General medical history data will be collected at screening and listed only. General medical 
history data will not be coded.
A by-subject listing of general medical history will be provided by subject ID number in 
ascending order.
5.3.1.
Disease History
A summary of disease-specific medical history will be provided by treatment and overall for the 
ITT Analysis Set. No formal statistical testing is planned. Variables to be summarized include:

Primary tumor site

Histology of gastric cancer

Disease stage at screening

Differentiation at screening

Time since diagnosis (months)


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The denominator for the percentage of histology of gastric cancer is the number of subjects with 
gastric cancer. The denominators for the percentage of other variables are the number of subjects 
in the ITT analysis set corresponding to that column. 
A by-subject listing of disease history and surgical procedures will be provided by subject ID 
number in ascending order. 
5.4.
Chemotherapy and Radiotherapy Therapy
Prior (neoadjuvant, adjuvant, and metastatic) chemotherapy and radiotherapy will be 
summarized using descriptive statistics by treatment arm using ITT analysis set. 
A by-subject listing of prior anticancer therapy and radiotherapy will be provided by subject ID 
number in ascending order. A by-subject listing of post-treatment chemotherapy will be provided 
by subject ID number and time in ascending order.
A by-subject listing of all radiotherapy will be provided by subject ID number and time in 
ascending order.


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6.
EFFICACY ANALYSES
Efficacy analysis will be performed based on the ITT Analysis Set. The investigator assessments 
will be used for analyses of efficacy endpoints. 
P-values for the updated analyses of efficacy are for display purposes only, and no formal 
hypothesis testing will be conducted. Formal hypothesis testing had been conducted at the 
primary analysis per the SAP for primary analysis. Efficacy results in the CSR will be based on 
the primary analysis.
6.1.
Primary Efficacy Endpoint
The primary efficacy endpoint of this study is objective response rate (ORR), defined as the 
proportion of subjects with best overall response of complete response (CR) or partial response 
(PR) after starting study drug but before starting any new chemotherapy or radiotherapy based on 
revised RECIST 1.1. 
As sensitivity analysis, confirmed ORR, defined as the proportion of subjects with best overall 
response of confirmed CR or confirmed partial response (PR) after starting study drug but before 
starting any new anti-cancer therapy based on revised RECIST 1.1, will also be analyzed. The 
confirmatory response is required at least 4-week later after the initial CR/PR for confirmed 
ORR.
Overall response for each visit is derived in the following process. The rules should be applied 
by the order listed below.

Response assessments occurring after new anticancer therapy (including radiation therapy),
after missing two previous consecutive tumor scans, or after confirmed progressive disease 
(PD) will not be included for ORR analysis.

If overall response for the first time point of a visit is an imaging PD, in order to differentiate 
“pseudo-progression (pseudo-PD)” from “definitive progression”, the first imaging PD 
requires confirmation either by another imaging PD at the confirmatory visit at least 4 weeks
apart or by the subsequent clinical PD/ radiation therapy. The first imaging PD will be 
considered as “confirmed PD” by any of the following:
The overall response at the confirmatory visit is also PD;
No more tumor assessment is available that is 4 weeks apart;
The overall response at the confirmatory visit is non-evaluable (NE) and no more tumor 
assessments follow the confirmatory visit;
First imaging PD is followed by subsequent clinical PD or radiation therapy.


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Otherwise, the first imaging PD will be “Pseudo PD”. 

Both clinical PD and radiation therapy are considered as PD, and no confirmation is required. 
The best overall response for each subject across the time points is derived based on the rank CR 
> PR > SD > pseudo-PD > PD (including clinical PD, confirmed imaging PD, and radiation 
therapy) > NE.
For confirmed overall response for each visit, in addition to the rules listed above, the following 
rules should also be applied.

If overall response of a visit is CR or PR, a confirmatory visit at least 4 weeks later is 
required. Overall response for the visit is derived based on overall response at the first time 
point and overall response at the confirmatory visit. 

If overall response of a visit is SD/NE, no confirmatory visit is required and the overall 
response for the visit is SD/NE correspondingly.
The rule for deriving confirmed overall response at each visit is specified in Table 5. The best 
confirmed overall response for each subject across the time points is derived based on the rank 
CR confirmed > PR confirmed > CR not confirmed > PR not confirmed > SD > pseudo-PD > PD
(including clinical PD, confirmed imaging PD, and radiation therapy) > NE.
Table 5.
Confirmed Overall Response Derivation
Overall Response 
at First Visit 
Overall Response at Confirmatory 
Visit 
Overall Response for 
the Time Point
Date of Response
CR
CR
CR confirmed
First visit
Responses other than CR or there is no 
confirmatory visit
CR not confirmed
First visit
PR
CR/PR
PR confirmed
First visit
Responses other than CR/PR or there is 
no confirmatory visit
PR not confirmed
First visit
PD
PD/ clinical PD/ radiation therapy, or 
there is no confirmatory visit
PD
First visit
NE
PD
First visit
Responses other than PD/clinical PD/ 
radiation therapy/NE
pseudo-PD
First Visit
NE
Not required
NE
First visit
SD 
Not required
SD
First visit
Note: Response after treatment discontinuation does not need to be confirmed.


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6.1.1.
Statistical Hypothesis for the Primary Efficacy Endpoint
The primary efficacy hypothesis is that there is no difference between Treatment Group 
(Group T) and Control Group (Group C) in ORR. Using RT and RC to denote the objective 
response rate of Treatment Group (Group T) and Control Group (Group C), respectively, the 
statistical hypotheses to be tested in this study will be:
H0: RT = RC
H1: RT > RC (Group T is superior to Group C in terms of ORR)
6.1.2.
Analysis for the Primary Efficacy Endpoint
The ORR endpoint will be tested at a two-sided alpha level of 0.2. The ORR will be presented 
with corresponding 2-sided 80% and 95% exact confidence intervals (CIs) calculated using the 
Clopper-Pearson method. Odds ratio will also be presented with corresponding 80% and 95% 
CIs be calculated using the exact CMH Chi-square test stratified by screening PD-L1 status. 
Subjects who do not have sufficient baseline or on-study tumor assessments to characterize 
response will be counted as non-responders and included in the denominator only.
In addition, the confirmed ORR, defined as the proportion of subjects with best overall response 
of confirmed CR/confirmed PR will also be presented as a sensitivity analysis. The same 
analysis methods as for ORR mentioned above will be applied for confirmed ORR.
The analysis for the ORR and confirmed ORR will be performed based on the ITT Analysis Set.
6.2.
Secondary Efficacy Endpoint
6.2.1.
Progression-Free Survival
Progression free survival (PFS), defined as the interval from the date of randomization to the 
earlier of the first definitive PD (as defined in Section 6.2.1) or death from any cause. The first 
definitive PD is defined as the first radiation therapy, the first clinical PD, and the first confirmed 
imaging PD, whichever comes first. Pseudo-PD will not be considered as definitive PD.
Data will be censored on the date of last adequate tumor assessment for subjects (including 
assessments with a NE outcome):

who do not have definitive PD or die before study discontinuation, or 

who start new anticancer therapy prior (radiation therapy excluded) to definitive PD or death, 
or

who have ≥ 2 consecutive missing tumor assessments before definitive PD or death.


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Subjects without any adequate baseline tumor assessment are censored on the randomization 
date. The adequate baseline tumor assessment is defined as the window from (randomization 
date - 35 days) to randomization date. 
PFS in months will be calculated as (date of event/censoring – date of randomization + 1) / 
30.4375.
Survival function of PFS is estimated using Kaplan-Meier method and compared using the 
log-rank test stratified by PD-L1 status at screening. PFS rates at 1, 2, 3, 6, 9, 12 months, and the 
median with 95% CIs will be derived using Kaplan-Meier methods by treatment arm. 
Kaplan-Meier curves will also be provided. In addition, hazard ratio (HR) and corresponding 
95% CI will be estimated for PFS using the Cox proportional hazards regression model stratified 
by PD-L1 status at screening.
Follow-up time in months for PFS will be summarized as a continuous variable with descriptive 
statistics.

For a subject who is censored from PFS and has discontinued from tumor assessment, 
duration of PFS follow-up = (Date of Censoring – randomization date +1)/30.4375

For subjects with a definitive PFS event and censored subject with ongoing tumor 
assessment, duration of PFS follow-up = ( Date of last tumor assessment in the database –
randomization date +1)/30.4375
For subjects who have imaging examinations on various dates that are nevertheless assigned to 
the same nominal visit, the following rules apply for the calculation of the endpoint date:

The response date will be the last date associated with that particular imaging time point.

The progression date will be the first date associated with that particular imaging time point.
Incomplete or missing dates of initiation of anticancer therapy other than the study treatment are 
imputed as follows:

If the day is missing but the month and year are available, then the imputed day will be the 
last day of the month.

If day and month are missing but year is available, then the imputed day and month will be 
01Jan or the last day of the month for the last adequate disease assessment if they have the 
same year, whichever is later.
The analysis of PFS will be performed based on the ITT Analysis Set.


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Overall Survival 
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Overall survival (OS) is defined as interval from the date of randomization to death from any 
cause. Subjects alive are censored at the last time the subject was known alive. 
The survival function of OS is estimated using Kaplan-Meier method and compared using the 
log-rank test stratified by PD-Ll status at screening. The median, Ql, Q3 estimate of OS and 
probability of survival at 3, 6, 12, 18, and 24 months from randomization will be provided along 
with the con esponding 95% CI. In addition, hazard ratio (HR) and conesponding 95% CI will be 
estimated using Cox propo1iional hazard regression method stratified by screening PD-Ll status. 
Follow-up time in months for OS will be summarized as a continuous variable with descriptive 
statistics by treatment aim. 
• 
For subjects who discontinued study without death event, duration of OS follow-up = 
(date oflast follow-up- randomization date + 1)/30.4375 
• 
For subjects who died, duration of OS follow-up = last available date in the database -
randomization date + 1 
The analysis of OS will be perfo1med based on the ITT Analysis Set. 
6.2.3. 
Duration of Response 
Duration of response (DOR) is defined for subjects in the ITT analysis set who are CR/PR prior 
to new anti-cancer therapy (including radiation therapy) as the interval from the date of the first 
objective response achieved to the earlier of the first definitive disease progression or death from 
any cause. The first definitive disease progression is defined in Section 6.2.1. The same 
censoring mles as for PFS will be applied to DOR. 
DOR in months = (date of event/censoring - date of first response [CR or PR] + 1) / 30.4375. 
Median DOR and 95% Cls will be estimated using Kaplan-Meier methods by treatment aim. 
Kaplan-Meier curves will also be provided. 
6.3. 
Exploratory Efficacy Endpoints 
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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) and preferred term (PT) 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 toxicity 
criteria specified in the protocol. 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 as determined by the investigator. 
SAEs captured and stored in the clinical database will be reconciled with the SAE database from 
the Gilead Drug Safety and Public Health 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 both of the following:

Any AEs with an onset date on or after the study drug start date and up to 30 days after 
permanent discontinuation of andecaliximab or 5 months after permanent discontinuation of 
nivolumab

Any AEs leading to premature discontinuation of andecaliximab or 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 andecaliximab or 5 months after 
the date of the last dose of nivolumab
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.
The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC, HLT, PT, and treatment group. For other AEs described below, summaries 
will be provided by SOC, PT, and treatment group:

All TE treatment-related AEs

TEAEs of Grade 3 or higher (by maximum severity)

TE Treatment-related AEs of Grade 3 or higher (by maximum severity)

All TE SAEs

All TE treatment-related SAEs 

All TEAEs leading to discontinuation of any study drug

All TEAEs leading to study treatment interruption or dose interruption

All TEAEs leading to death 
A brief, high-level summary of AEs described above will be provided by treatment group and by 
the number and percentage of subjects who experienced the above AEs. 


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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, and then by
PT in descending order of total frequency within each SOC. For summaries by severity grade, 
the most severe grade will be used for those AEs that occurred more than once in an individual 
subject during the study. 
In addition to the above summary tables, all TEAEs and TE treatment-related AEs will be 
summarized by PT only, in descending order of total frequency.
Deaths will be summarized by whether it is considered treatment emergent and the cause of the 
death (AE, due to PD, or other reasons).
In addition, data listings will be provided for the following:

All AEs, indicating whether the event is treatment emergent

AEs with Grade 3 or higher

SAEs

AEs leading to death

All deaths

AEs leading to discontinuation of study drug 

AEs leading to treatment interruption/dose modification
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed using qualitative methods. Shift from 
baseline to worst post-baseline assessment and Grade 3 or higher lab abnormalities will be 
summarized for the Safety Analysis Set and will include data collected up to the last dose of 
andecaliximab plus 30 days for subjects who have permanently discontinued andecaliximab or 
up to the last dose of nivolumab plus 5 months for subjects who have permanently discontinued 
nivolumab. Severity grade for lab abnormalities are defined by CTCAE 4.03. 
Only central lab results will be used in the analyses.
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, urinalysis, coagulation, and 
thyroid function 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.


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7.2.1.
Graded Laboratory Values
The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities CTCAE 
Version 4.03 will be used to assign 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. 
7.2.1.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last 
dose of andecaliximab plus 30 days or nivolumab plus 5 months for subjects who permanently 
discontinued study drug, or the last available date in the database snapshot for subjects who were 
still on treatment at the time of an interim analysis. If the relevant baseline laboratory value is 
missing, any abnormality of at least Grade 1 observed within the time frame specified above will 
be considered treatment emergent.
7.2.1.2.
Summaries of Laboratory Abnormalities
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group; subjects will be categorized 
according to the most severe postbaseline abnormality grade for a given lab test:

Graded laboratory abnormalities

Grade 3 or 4 laboratory abnormalities
A by-subject listing of treatment-emergent Grade 3 or 4 laboratory abnormalities will be 
provided by subject ID number and time point 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.
7.2.2.
Shifts Relative to the Baseline Value
Shift tables will be presented by showing change in severity grade from baseline to worst post 
baseline assessment.
7.3.
Body Weight and Vital Signs
Descriptive statistics will be provided by treatment group for body weight and vital signs as 
follows:

Baseline value

Values at each postbaseline visit

Change from baseline at each postbaseline visit


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A baseline value will be defined as the last available value collected on or prior to the date/time 
of first dose of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value. 
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3. No formal statistical testing is planned.
A by-subject listing of vital signs and body weight will be provided by subject ID number and 
time point in chronological order. Body weight will be included in the vital signs listing, if space 
permits. If not, they will be provided separately.
7.4.
Concomitant Medications
Medications collected during the study will be coded using the current version of the 
[Gilead-modified] World Health Organization (WHO) Drug dictionary.
7.4.1.
Prior Medications
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. Use 
of concomitant medications will be summarized by Anatomical Therapeutic Chemical (ATC) 
drug class Level 2 and preferred name using the number and percentage of subjects for each 
treatment group. A subject reporting the same medication more than once will be counted only 
once when calculating the number and percentage of subjects who received that medication. The 
summary will be ordered alphabetically by ATC medical class and then by preferred term in 
descending overall frequency within each ATC medical class. For drugs with the same 
frequency, sorting will be done alphabetically.
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 prior 
to the date of first dosing date of study drug or a start date 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.


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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 Results
7.5.1.
Investigator Electrocardiogram Assessment
A by-subject listing for ECG assessment results will be provided by subject ID number and visit
in chronological order.
7.6.
Other Safety Measures
No additional safety measures are specified in the protocol.
7.7.
Changes From Protocol-Specified Safety Analyses
There are no deviations from the protocol-specified safety analyses.


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8.
PHARMACOKINETIC (PK) ANALYSES
8.1.
PK Sample Collection
PK plasma samples will be collected for Arm A only for andecaliximab PK at 30(± 15) min after 
the end of infusion on Day 1; prior to dosing and 30(± 15) min after the end of infusion on Day 1 
of Weeks 4, 8, 16, 24, every 3 months thereafter, and at the end of treatment (EOT) and end of 
study (EOS) visits.
8.2.
Statistical Analysis Methods
Individual subject concentration for andecaliximab will be listed and summarized using 
descriptive statistics by treatment. Summary statistics (n, mean, StD, coefficient of variation 
[%CV], median, min, max, Q1, and Q3) will be presented for individual subject concentration 
data by time point.
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 
non-missing concentration data at that time point. The number of subjects with concentration 
BLQ will be presented for each time point. For summary statistics, BLQ values will be treated as 
0 at predose and one-half of the lower limit of quantitation (LLOQ) for postdose time points. 
The following tables will be provided for andecaliximab:

Individual subject concentration data and summary statistics
The following listing will be provided

PK sampling details by subject, including procedures, differences in scheduled and actual 
draw times, and sample age will be provided in listings.


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9.
IMMUNOGENICITY ANALYSES
9.1.
ADA Sample Collection
For Arm A only serum samples for anti-andecaliximab antibody will be collected prior to dosing 
on Day 1 of Week 1, 4, 8, 16, 24, and every 3 months thereafter, EOT, EOS.
9.2.
Statistical Analysis Methods
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.


Andecaliximab (GS-5745) 
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10. 
BIO MARKER ANALYSES 
Version 1.0 
The following biomarkers will be evaluated for whether they are predictive for treatment 
efficacy. These analyses are explorato1y. 
I 
I 
I 
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11.
REFERENCES
Le DT, Bendell JC, Calvo E, Kim JW, Ascierto PA, Sharma P, et al. Safety and activity of 
nivolumab monotherapy in advanced and metastatic (A/M) gastric or 
gastroesophageal junction cancer (GC/GEC): Results from the CheckMate-032 
study [Abstract 06]. J Clin Oncol (ASCO Annual Meeting Abstracts) 2016.


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12.
SOFTWARE
SAS® Software Version 9.X. SAS Institute Inc., Cary, NC, USA.
nQuery Advisor(R) Version X.0. Statistical Solutions, Cork, Ireland.


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


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14.
APPENDIX
Appendix 1.
List of Laboratory Tests for Safety Analysis
Appendix 2.
Schedule of Assessments


Andecaliximab (GS-5745) 
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Statistical Analysis Plan - Follow-up Analysis 
Appendix 1. 
List of Laboratory Tests for Safety Analysis 
Chemistry 
U1·inalysis 
Hematology 
Other 
Albumin 
Color and appearance 
WBC 
Serum P-hCG or urine 
Alkaline phosphatase 
Specific gravity pH 
Hemoglobin 
pregnancy test 
ALT 
Occult blood 
Hematocrit 
Thyroid Function Tests 
AST 
Protein 
Platelet 
(TSH, T3, and free T4/ 
Bicarbonate 
Glucose Bilirnbin 
ANC 
BUN 
Leukocyte esterase 
Calcium 
Nitrite 
Differential 
Chloride 
Urobilinogen 
Eosinophils 
Creatinine• 
Ketones Microscopicb 
Lymphocytes 
Monocytes 
Glucose 
Neutrophils 
Lipase 
Coagulation 
Amylase 
Magnesium 
PT/INR 
Phosphorns 
aPTT 
Potassium 
Sodium 
Total bilirnbin 
Direct bilirnbin 
Total protein 
CEA 
CA125 
Version 1.0 
ANC = absolute neutrophil count; ALT = alanine aminotransferase; aPTT = Activated Partial TI1romboplastin Time; 
AST = aspa1tate aminotransferase; BUN = blood urea nitrogen; CEA=carcinoembryonic antigen; j3-hCG = beta-human chorionic 
gonadotropin; INR = Intemational No1malized Ratio; PT = Prothrombin Time; WBC = white blood cell; CA125 = Carbohydrate 
Antigen 125; TSH = thyroid stimulating hormone; T3 = triiodothyronine; Free T4 = free thyroxine 
a 
Estimated creatinine clearance (CLc,)/glomemlar filtration rate will be calculated based on the Cockroft-Gault formula using 
actual body weight: CLcr (mL/min) = (140 - age [years])• weight (kg) I (semm creatinine [mg/dL]•72). If the subject is 
female, multiply the quantity by 0.85. 
b 
Reflex testing based on other abnomialities. 
c 
Females of child-bearing potential only. Serum pregnancy will be conducted at Screening. Urine pregnancy will be 
conducted pre-dose on Day 1, eve1y 4 weeks thereafter, at EOT, and EOS, 30-day, and 5-month Safety Follow-up 
d 
TSH, T3, and free T4 w'ill be tested by the central laborato1y at screening. From Week 8 and beyond, T3 and T4 will be 
tested reflexively based on abno1mal TSH results. 
CONFIDENTIAL 
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Appendix 2.
Schedule of Assessments
Period
Screening
Randomization a
Treatment
EOTm
Disease Progression
EOSn
30 day Safety
Follow-upo
5-month Safety
Follow-Upp
Long Term
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14 to 50
Week
-4
Day 1
2
4
6
8
10
12
14
16
18
20
22
24 to 96
Window (day)
-28
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±7
±7
±7
Informed Consent
X
Medical and Medication 
History
X
Physical Examinationb
X
X
X
X
X
X
X
Xs
X
X
X
Vital Signs & Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECOG Performance
Statusc
X
Xc
X
X
X
X
X
Xs
X
X
X
12-lead ECG
X
X
X
X
X
X
X
Xs
X
X
Adverse events/ 
Concomitant 
Medicationsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IWRS Registration
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study Drug/ Nivolumab 
Administratione
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Thyroid Function Tests 
(TSH, T3, free T4)
X
X
X
Xt
X
X
X
X


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Period
Screening
Randomization a
Treatment
EOTm
Disease Progression
EOSn
30 day Safety
Follow-upo
5-month Safety
Follow-Upp
Long Term
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14 to 50
Week
-4
Day 1
2
4
6
8
10
12
14
16
18
20
22
24 to 96
Window (day)
-28
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±7
±7
±7
Coagulation
X
X
X
Urinalysis
X
X
X
X
X
X
X
Xs
X
X
X
X
Pregnancy Testf
X
X
X
X
X
X
X
Xs
X
X
X
X
Andecaliximab PKg
X
X
X
X
Xr
X
X
Anti-Andecaliximab
Antibodyh
X
X
X
X
Xr
X
X
Blood Biomarkersi
X
X
X
X
X
X
Xr
Xi
Xi
Oral Sampling
X
CT or MRI & Treatment 
Response Assessmentk
X
X
X
Xt
Xq
X
Tumor Biopsyl
Xl
Xl
(Wk 5 through Wk 9)
Xl
Overall Survival and 
Other Antitumor Therapy
Xu
a
Day 1 visit must occur within 3 days following randomization.
b
Complete physical examination (PE) to be performed at Screening, EOT and EOS. A modified PE capturing changes from prior exams will be performed at subsequent visits.
Height is required at Screening only.
c
ECOG performance status on Day 1 may be waived if has been conducted during screening within 4 days of Day 1.
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d
Adverse events will be assessed and concomitant medications will be recorded at each clinic visit from Screening up to and including the 30-day Safety Follow-up visit or
EOS visit whichever is later.
e
For Arm A: Study drug andecaliximab (800 mg) will be administered via IV infusion every 2 weeks over 30 (± 5) min. Nivolumab (3 mg/kg) will be administered via IV 
infusion following the completion of andecaliximab every 2 weeks over 60 (± 5) min. For Arm B: Nivolumab alone (3 mg/kg) will be administered via IV infusion every
2 weeks over 60 (± 5) min.
f
If applicable (females of child bearing potential). Serum pregnancy testing will be conducted at Screening. Urine pregnancy testing will be conducted pre-dose on Day 1 and 
every then every 4 weeks, at EOT, and EOS, 30-day, and 5-month Safety Follow-up.
g
For Arm A only, plasma samples will be collected for andecaliximab PK at 30(± 15) min after the end of infusion on Day 1. For Weeks 4, 8, 16, and 24 and every 3 months 
thereafter, PK will be collected prior to dosing and 30(± 15) min after the end of infusion. It will also be collected at EOT and EOS.
h
For Arm A only,  serum samples for anti-andecaliximab antibody will be collected prior to dosing on Day 1, Week 4, Week 8, Week 16, Week 24, and every 3 months
thereafter, EOT and EOS.
i
Blood biomarkers will be collected at screening and prior to dosing on Day 1; Week 2; Week 4; Week 8; Week 16; Week 24 and every 3 months thereafter and at progression 
or EOS.
k
Tumor evaluation by CT or MRI will be performed during screening and approximately every 8 weeks regardless of visit week or dose interruption. Scan at EOS visit is not 
necessary if restaging scan is performed within the prior 8 weeks. Treatment response assessment will be per RECIST v1.1. For subjects who stop study treatment in the 
absence of disease progression (eg. experienced unexpected toxicity) and remain on study for follow-up for progression-free survival, tumor evaluation by CT or MRI should 
continue approximately every 8 weeks until disease progression or initiation of non-study specific anti-neoplastic therapy in the absence of progression, whichever occurs 
earlier.
l
A pretreatment biopsy is requested if archival tumor sample provided to meet Inclusion Criterion #6 is from before the last line of therapy. An on-treatment biopsy is required 
between Week 5 and Week 9. A biopsy at disease progression is requested, if medically feasible. The sample should be collected by the last clinic visit on study ie EOS or
30 Day Safety Follow-up visit. All biopsies are requested to be from gastric lesions if possible (non-gastric metastatic lesions ok if no gastric lesions possible). See laboratory
manual for biopsy specifications and procedures.
m
End of treatment (EOT) assessments will be completed only 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 
approximately every 8 weeks until disease progression.
n
End of study (EOS) assessments will be completed when a subject meets at least 1 of the criteria for study discontinuation (Protocol Section 3.7).
o
The 30-day safety follow-up visit will be performed following the last dose of andecaliximab.
p
The 5-month safety follow-up visit will be performed following the last dose of nivolumab.
q
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 (see Protocol Section 6.2.9).
r
Starting at Week 24, perform every 12 weeks until EOT/EOS.
s
Starting at Week 24, perform every 4 weeks until EOT/EOS.
t
Starting at Week 24, perform every 8 weeks until EOT/EOS.
u
Perform every 3 months until 5 years.
CCII 

Prot_000.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Clinical Program 
Manager: 
Gilead Medical 
Monitor: 
Protocol Version/Date: 
(rJ GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase 2, Open-Label, Randomized Study to Evaluate the Efficacy 
and Safety of GS-5745 Combined with Nivolumab versus Nivolumab 
Alone in Subjects with Unresectable or RecmTent Gastric or 
Gastroesophageal Junction Adenocarcinoma 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
116561 
2016-001402-41 
NCT02864381 
Gastric Adenocarcinoma 
GS-US-296-2013 
Name: 
PD 
Telephone: 
PD 
Email: 
PU 
Name: 
PD 
Telephone: 
PD 
Fax: 
PD 
Cell: 
PD 
Email: 
PU 
Original: 
30 March 2016 
Amendment 1: 
13 June 2016 
Amendment 2: 
2 August 2016 
Amendment 3: 
16 June 2017 
CONFIDENTIALITY STATEMENT 
The info1mation contained in this document, paiiicularly 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, yow- 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 dmg 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 necessaiy to obtain infonned consent from those 
persons to whom the dmg may be administered. 


Andecaliximab (formerly GS-5745)
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Amendment 3
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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....................................................................14
1.
INTRODUCTION ..............................................................................................................................................17
1.1.
Background ............................................................................................................................................17
1.1.1.
Gastric Adenocarcinoma ......................................................................................................18
1.1.2.
MMP9 Expression in Oncology...........................................................................................20
1.1.3.
General Information .............................................................................................................20
1.1.4.
Preclinical Pharmacology and Toxicology...........................................................................21
1.1.5.
Clinical Trials of Andecaliximab .........................................................................................27
1.1.6.
Information about Nivolumab ..............................................................................................28
1.2.
Rationale for this Study..........................................................................................................................28
1.3.
Risk/Benefit Assessment for the Study..................................................................................................29
1.4.
Compliance ............................................................................................................................................30
2.
OBJECTIVES.....................................................................................................................................................31
3.
STUDY DESIGN................................................................................................................................................32
3.1.
Endpoints ...............................................................................................................................................32
3.2.
Study Design..........................................................................................................................................32
3.3.
Study Treatments ...................................................................................................................................33
3.4.
Duration of Treatment............................................................................................................................33
3.5.
Discontinuation Criteria from Treatment ...............................................................................................33
3.5.1.
Discontinuation Criteria for Nivolumab...............................................................................34
3.6.
Premature Discontinuation from Study Treatment.................................................................................34
3.7.
Discontinuation Criteria from Study ......................................................................................................35
3.8.
Long-Term Follow-Up for Overall Survival..........................................................................................35
3.9.
Source Data............................................................................................................................................35
3.10.
Biomarker Testing..................................................................................................................................36
3.10.1.
Biomarker Samples to Address the Study Objectives:.........................................................36
3.10.2.
Biologic Samples for Optional Future Research ..................................................................39
4.
SUBJECT POPULATION..................................................................................................................................40
4.1.
Number of Subjects and Subject Selection ............................................................................................40
4.2.
Inclusion Criteria....................................................................................................................................40
4.3.
Exclusion Criteria...................................................................................................................................41
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................44
5.1.
Randomization .......................................................................................................................................44
5.2.
Description and Handling of Study Treatments .....................................................................................44
5.2.1.
Formulation..........................................................................................................................44
5.2.2.
Packaging and Labeling .......................................................................................................44
5.2.3.
Storage and Handling...........................................................................................................45
5.3.
Dosage and Administration of Study Drug ............................................................................................45
5.3.1.
Dose Adjustments ................................................................................................................45
5.4.
Prior and Concomitant Medications.......................................................................................................46
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Amendment 3
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5.4.1.
Acceptable Concomitant Medications..................................................................................46
5.4.2.
Prohibited Concomitant Medications...................................................................................46
5.5.
Accountability for Study Drug...............................................................................................................47
5.5.1.
Study Drug Return or Disposal ............................................................................................48
6.
STUDY PROCEDURES ....................................................................................................................................49
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................49
6.2.
Study Procedure Descriptions ................................................................................................................49
6.2.1.
Informed Consent.................................................................................................................49
6.2.2.
Re-Screening Criteria...........................................................................................................50
6.2.3.
Medical & Medication History.............................................................................................50
6.2.4.
Physical Examination...........................................................................................................50
6.2.5.
Vital Signs & Weight ...........................................................................................................50
6.2.6.
Electrocardiogram Assessment ............................................................................................51
6.2.7.
Performance Status...............................................................................................................51
6.2.8.
Laboratory Assessments.......................................................................................................51
6.2.9.
Disease and Response Assessment.......................................................................................54
6.2.10.
Study Drug Administration ..................................................................................................57
6.2.11.
Adverse Events.....................................................................................................................58
6.3.
Assessments for Premature Discontinuation from Study.......................................................................58
6.4.
Criteria for Discontinuation of Study Treatment....................................................................................58
6.5.
End of Treatment....................................................................................................................................58
6.6.
End of Study...........................................................................................................................................58
6.7.
30-Day Safety Follow-Up ......................................................................................................................59
6.8.
5-Month Safety Follow-Up ....................................................................................................................59
6.9.
Long-Term Follow-Up...........................................................................................................................59
6.10.
Unscheduled visits .................................................................................................................................59
6.11.
Protocol Deviations................................................................................................................................59
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................60
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................60
7.1.1.
Adverse Events.....................................................................................................................60
7.1.2.
Serious Adverse Events........................................................................................................60
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................61
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................62
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................62
7.2.2.
Assessment of Severity ........................................................................................................62
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................63
7.3.1.
Adverse Events.....................................................................................................................63
7.3.2.
Serious Adverse Events........................................................................................................63
7.4.
Gilead Reporting Requirements.............................................................................................................64
7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or 
Serious Adverse Events..........................................................................................................................64
7.6.
Toxicity Management ............................................................................................................................65
7.7.
Special Situations Reports......................................................................................................................65
7.7.1.
Definitions of Special Situations..........................................................................................65
7.7.2.
Instructions for Reporting Special Situations.......................................................................66
8.
STATISTICAL CONSIDERATIONS................................................................................................................68
8.1.
Analysis Objectives and Endpoints........................................................................................................68
8.1.1.
Analysis Objectives..............................................................................................................68
8.1.2.
Primary Endpoint .................................................................................................................68


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8.1.3.
Secondary Endpoint .............................................................................................................68
8.1.4.
Other Endpoints of Interest ..................................................................................................69
8.2.
Analysis Conventions.............................................................................................................................69
8.2.1.
Analysis Sets ........................................................................................................................69
8.3.
Data Handling Conventions ...................................................................................................................70
8.4.
Demographic Data and Baseline Characteristics ...................................................................................71
8.5.
Efficacy Analysis ...................................................................................................................................71
8.5.1.
Primary Analysis..................................................................................................................71
8.5.2.
Secondary Analyses .............................................................................................................71
8.6.
Safety Analysis.......................................................................................................................................71
8.6.1.
Extent of Exposure...............................................................................................................71
8.6.2.
Adverse Events.....................................................................................................................72
8.6.3.
Laboratory Evaluations ........................................................................................................72
8.6.4.
Other Safety Evaluations......................................................................................................72
8.7.
Pharmacokinetic Analysis......................................................................................................................72
8.8.
Biomarker Analysis................................................................................................................................73
8.9.
Interim Safety Analysis..........................................................................................................................73
8.10.
Sample Size............................................................................................................................................73
8.11.
Data Monitoring Committee ..................................................................................................................73
9.
RESPONSIBILITIES..........................................................................................................................................74
9.1.
Investigator Responsibilities ..................................................................................................................74
9.1.1.
Good Clinical Practice..........................................................................................................74
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................74
9.1.3.
Informed Consent.................................................................................................................74
9.1.4.
Confidentiality......................................................................................................................75
9.1.5.
Study Files and Retention of Records ..................................................................................75
9.1.6.
Case Report Forms...............................................................................................................76
9.1.7.
Study Drug Accountability and Return ................................................................................77
9.1.8.
Inspections............................................................................................................................77
9.1.9.
Protocol Compliance............................................................................................................77
9.2.
Sponsor Responsibilities ........................................................................................................................78
9.2.1.
Protocol Modifications.........................................................................................................78
9.2.2.
Study Report and Publications .............................................................................................78
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................78
9.3.1.
Payment Reporting...............................................................................................................78
9.3.2.
Access to Information for Monitoring..................................................................................79
9.3.3.
Access to Information for Auditing or Inspections ..............................................................79
9.3.4.
Study Discontinuation..........................................................................................................79
10.
REFERENCES ...................................................................................................................................................80
11.
APPENDICES ....................................................................................................................................................85
Appendix 1.
Investigator Signature Page....................................................................................................86
Appendix 2.
Study Procedures Table..........................................................................................................87
Appendix 3.
ECOG Performance Status.....................................................................................................91
Appendix 4.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................92
Appendix 5.
Revised RECIST Guideline (version 1.1) ..............................................................................95


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LIST OF IN-TEXT TABLES
Table 3-1.
Biomarker Objectives and Testing .........................................................................................38
Table 6-1.
Analytes..................................................................................................................................52
Table 6-2.
Imaging and Treatment after First Radiologic Evidence of Progressive Disease...................56
LIST OF IN-TEXT FIGURES
Figure 1-1.
Examples of MMP9 Expression in Gastric Adenocarcinoma (IHC)......................................20
Figure 1-2.
Summary of Pro-Tumorigenic Activities of MMP9...............................................................21
Figure 1-3.
Changes in Tumor-Associated Fibrillar Collagen ..................................................................22
Figure 1-4.
Effect of MMP9 Inhibition in the HCT-116 Orthotopic Model of CRC................................23
Figure 1-5.
Hypothesis for Andecaliximab and Nivolumab......................................................................24
Figure 1-6.
Inhibition of MMP9 in Orthotopic HC11-NeuT Model of Breast Cancer..............................24
Figure 1-7.
Changes in Tumor-Associated Fibrillar Collagen ..................................................................25
Figure 1-8.
Transcriptome and Pathway Analysis of the HC11-NeuT Model..........................................26


Andecaliximab (fo1medy GS-5745) 
Protocol GS-US-296-2013 
Final 
Amendment3 
Gilead Sciences, Inc. 
Study Title: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Study Centers 
Planned: 
Objectives: 
CONFIDENTIAL 
PROTOCOL SYNOPSIS 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
A Phase 2, Open-Label, Randomized Study to Evaluate the Efficacy and 
Safety of GS-5745 Combined with Nivolumab versus Nivolumab Alone 
in Subjects with Umesectable or RecmTent Gastric or Gastroesophageal 
Junction Adenocarcinoma 
116561 
2016-001402-41 
NCT02864381 
Approximately 50 centers in Austrnlia, North America, and Em-ope 
The prima1y objective of this study is: 
• 
To evaluate and compare the efficacy of andecaliximab (fo1merly 
GS-5745) in combination with nivolumab versus nivolumab alone in 
subjects with recmTent gastric or gastroesophageal junction (GEJ) 
adenocarcinoma 
The secondaiy objectives of this study are: 
• 
To chai·acterize and compai·e safety and tolerability of 
andecaliximab in combination with nivolumab versus nivolumab 
alone in subjects with recunent gastric or GEJ adenocarcinoma 
• 
To chai·acterize the phaimacokinetics (PK) of andecaliximab in 
combination with nivolumab 
The explorato1y objectives of this study are: 
I 
I 
I 
I 
I 
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Study Design:
This is a Phase 2, open-label, randomized study comparing 
andecaliximab in combination with nivolumab in recurrent gastric 
adenocarcinoma versus nivolumab alone. Approximately 120 subjects 
will be randomized to either Treatment Arm A: andecaliximab + 
nivolumab or Treatment Arm B: nivolumab alone. 
To evaluate combination drug safety, an independent Data Monitoring 
Committee (DMC) will be charged with overseeing the study safety. 
After the first 20 subjects are treated for 12 weeks, the DMC will review 
all safety data to evaluate for any unexpected toxicities. If the DMC 
recommends that the combination demonstrates acceptable tolerability, 
enrollment and randomization will proceed with continued safety 
oversight from the DMC. Thereafter, review of safety data will be 
performed at regular intervals as described in the DMC charter.
Randomized study:
Treatment Groups:

Arm A: andecaliximab + nivolumab

Arm B: nivolumab
Randomization and Stratification:

1:1 allocation to andecaliximab + nivolumab versus nivolumab alone 
through an interactive web response system (IWRS)

Fixed-block centralized randomization stratified by: 
PD-L1 positive versus PD-L1 negative
Number of 
Subjects Planned:
Approximately 120 subjects 
Screening 
I 
I Arm A 
: N=60 
Arm B 
I N=60 
I 
I 
Stratifi~ation and 
Randomization 
GS-5745 + Nivolumab 
u to 2 ears 
Nivolumab 
u to 2 ears 
Long-Term Follow-Up > 
L_.::Lo~n~g~-.:.: 
lie::r.:.:m.:...:...;Fo:..:l:..:lo-'-w_-_U.:...p __ > 
Disease 
progression or 
study stopped 


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Target 
Population:
Subjects who are ≥18 years or older with a histologically confirmed 
inoperable locally advanced or metastatic adenocarcinoma of the 
stomach or the gastroesophageal junction (GEJ) and who have 
progressed on at least 1 prior systemic therapy or line of treatment for 
unresectable/metastatic disease
Duration of 
Treatment:
Treatment will be given every 2 weeks and will continue until disease 
progression, unacceptable toxicity, or withdrawal of consent to a 
maximum of 2 years duration
Eligibility 
Criteria:
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible 
for participation in this study:
1) Age ≥18 years 
2) Histologically confirmed inoperable locally advanced or metastatic 
adenocarcinoma of the stomach or GEJ which have progressed on at 
least 1 prior systemic therapy or line of treatment for 
unresectable/metastatic disease
3) Eastern Cooperative Oncology Group (ECOG) ≤1
4) Measurable disease according to RECIST v1.1
5) Tumor sites that can be accessed for repeat biopsies 
6) Archival tumor tissue, preferably obtained from the most recent 
available biopsy; there must be adequate tissue for a PD-L1 
stratification test, as assessed by central pathologist
7) All toxicities attributed to prior anti-cancer therapy other than 
alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE 
version 4) or baseline
8) Subjects not receiving anticoagulant medication must have an 
international normalized ratio (INR) ≤1.5 and activated partial 
thromboplastin (aPTT) ≤1.5 x upper limit of normal (ULN) prior to 
randomization. The use of full-dose oral or parenteral anticoagulants 
is permitted as long as the INR or aPTT is within therapeutic limits 
(according to the medical standard in the institution) and the subject 
has been on a stable dose of anticoagulants for at least 1 week at the 
time of randomization
9) Adequate hematologic function
a) neutrophils ≥1.5 x 109/L
b) platelets ≥100 x 109/L
c) hemoglobin ≥9 g/dL


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10) Adequate hepatic function
a) Direct or total bilirubin ≤1.5 x ULN
b) ALT and AST ≤ 2.5 x ULN
11) 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
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, for 90 days following 
the last dose of andecaliximab and at least 5 months after the last 
dose of nivolumab, unless the subject chooses continuous 
heterosexual abstinence as a lifestyle-choice (see Appendix 4 for 
more information)
13) For male subjects of reproductive potential having intercourse with 
females of childbearing potential, willingness to use a protocol 
recommended method of contraception and to refrain from sperm 
donation from the start of study drug, throughout the study treatment 
period, and for 90 days after administration of the last dose of 
andecaliximab or nivolumab (see Appendix 4 for more information)
14) Breastfeeding females must agree to discontinue nursing before 
study drug administration
15) In the judgment of the investigator, participation in the protocol 
offers an acceptable benefit-to-risk ratio when considering current 
disease status, medical condition, and the potential benefits and risks 
of alternative treatments for the subject’s cancer
16) Willingness to comply with scheduled visits, drug administration 
plan, imaging studies, laboratory tests, other study procedures, and 
study restrictions
17) Evidence of a signed informed consent prior to implementation of 
any protocol specific procedure
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be 
enrolled in this study:
1) Subjects that have received only neoadjuvant or adjuvant therapy for 
gastric adenocarcinoma
2) Radiotherapy within 28 days of randomization; subjects given 
palliative radiotherapy to peripheral sites (eg, bone metastasis) may 
enter the study before 28 days have elapsed provided the radiated 
sites do not contain lesions which may be used to evaluate response, 
and must have recovered from any acute, reversible effects


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3) Uncontrolled intercurrent illness including, but not limited to, active 
uncontrolled infection, active gastrointestinal bleeding, uncontrolled 
cardiac arrhythmia, or psychiatric illness/social situation that would 
limit compliance with study requirements as judged by the treating 
physician
4) 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 
randomization; adequately treated Stage 1 or 2 cancer currently in 
complete remission; or any other cancer that has been in complete 
remission for ≥ 5 years
5) Major surgery, defined as any surgical procedure that involves 
general anesthesia and a significant incision (ie, larger than what is 
required for placement of central venous access, percutaneous 
feeding tube, or biopsy), within 28 days of first dose of study drug
6) Known positive status for human immunodeficiency virus (HIV)
7) Known acute or chronic-active infection with hepatitis B virus 
(HBV) or hepatitis C virus (HCV)
8) Chronic daily treatment with oral corticosteroids 
(dose of > 10 mg/day prednisone equivalent) or other 
immunosuppressive medications within 14 days of randomization. 
Inhaled steroids and short courses of oral steroids for anti-emesis or 
as an appetite stimulant are allowed
9) Known or suspected central nervous system metastases
10) Known alcohol or drug abuse or any other medical or psychiatric 
condition which contraindicates participation in the study
11) Documented myocardial infarction or unstable/uncontrolled cardiac 
disease (ie, unstable angina, congestive heart failure [New York 
Heart Association > Class II]) within 6 months of randomization
12) Serious systemic fungal, bacterial, viral, or other infection that is not 
controlled or requires intravenous antibiotics
13) Pregnant or breastfeeding women (pregnancy needs to be excluded 
by testing of beta-human chorionic gonadotropin [β-hCG])
14) Experimental medical treatment within 28 days prior to randomization
15) Known hypersensitivity to andecaliximab or nivolumab or 
excipients or to Chinese hamster ovary cell products or to 
recombinant human or humanized antibodies


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16) Prior treatment with anti-CTLA-4 agents (ipilimumab), anti-PD-1 or 
anti-PD-L1 agents (pembrolizumab, nivolumab), anti-PD-L2 agents, 
anti-MMP agents, or other immunomodulatory therapies
17) Previous severe hypersensitivity reaction to treatment with another 
monoclonal antibody therapy
18) Subject is expected to require any other form of systemic or 
localized antineoplastic therapy while on study
19) Prior therapy with anti-tumor vaccines or other immune-modulatory
antitumor agents
20) Current or history of pneumonitis or interstitial lung disease
21) 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
22) History of bone marrow, stem cell, or allogeneic organ 
transplantation
Study Procedures/
Frequency:
Screening will commence with obtaining the subject’s signed informed 
consent and will occur up to 28 days prior to randomization on Day 1.
Screening procedures will include the following: medical history 
review, physical exam, vital signs, 12-lead ECG, ECOG performance 
status, prior/concomitant medication review, blood collection for 
pregnancy test (females), chemistry, hematology, and coagulation, 
adverse event (AE) assessment, archival or recent biopsy FFPE tissue 
block collection, and computed tomography (CT) or magnetic resonance 
imaging (MRI). Baseline tumor lesions will be measured and 
characterized prior to randomization to assess the subject’s disease 
status prior to beginning treatment. Archival tumor tissue adequate for 
PD-L1 immunohistochemical stratification test is required at screening.
Treatment:
Treatment will occur every 2 weeks.  Subjects who meet eligibility will 
undergo CT scans or MRI every 8 weeks. Starting on Day 1, subjects
randomized to Arm A: andecaliximab + nivolumab will receive 
andecaliximab via intravenous infusion (IV) over 30 minutes.  
Nivolumab will be administered via IV over 60 minutes after 
andecaliximab. Subjects randomized to Arm B: nivolumab only will 
receive nivolumab via IV over 60 minutes.
Treatment will continue every 2 weeks in the absence of disease 
progression or toxicity warranting discontinuation of therapy, for up to 
2 years. Tumor response may be assessed prior to the specified every 
8 weeks, if clinically indicated.


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Test Therapy, Dose, 
and Mode of 
Administration:
Arm A: 800 mg andecaliximab via IV infusion over approximately 
30 minutes in advance of nivolumab 3 mg/kg via IV infusion over 
approximately 60 minutes on Day 1 and every 2 weeks thereafter. 
Arm B: nivolumab 3 mg/kg via IV infusion over approximately 
60 minutes on Day 1 and every 2 weeks thereafter.
Criteria for 
Evaluation:
All subjects who meet eligibility criteria, have signed a consent form,
and have begun treatment, will be evaluated for response.
Safety:
Safety will be evaluated by assessment of clinical laboratory tests, 
physical examination, 12-lead ECG, vital sign measurements, and by the 
incidence of AEs.  
Efficacy:

Objective response rate (ORR) will be determined from the subjects’ 
best response during treatment.

Progression free survival (PFS) will be defined as the interval from 
the date of randomization to the earlier of the first documentation of 
definitive disease progression or death from any cause.

Duration of response (DOR) will be defined as the interval from the 
date the first response (CR or PR) is achieved to the earlier of the 
first documentation of definitive disease progression or death from 
any cause.

Overall survival (OS) will be defined as the interval from date of 
randomization to death from any cause.
Pharmacokinetics:

Blood samples to measure andecaliximab will be collected at the 
time points specified in the protocol.

Blood samples to measure anti-andecaliximab antibodies will also be 
collected at the time points specified in the protocol.
Statistical Methods:
Analysis 
Methods:
Appropriate analyses sets will be defined.
In general, categorical and ordinal data will be summarized by count and 
percent of subjects. Continuous data will be summarized by descriptive 
summary statistics (mean, standard deviation, minimum, quartiles, 
median and maximum).
For the analysis of ORR, a Cochran-Mantel-Haenszel (CMH) 
Chi-square test on odds ratio will be performed to compare the 
2 treatment groups.


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The Kaplan-Meier (KM) method and stratified log-rank test will be used 
to compare the 2 treatment groups for time-to-event endpoints (ie, OS 
and PFS). A Cox proportional hazard model will be used to estimate the 
hazard ratio and corresponding 95% confidence interval (CI). DOR will 
be analyzed using the KM method.
Interim Analysis:
After approximately 20 subjects are treated for 12 weeks, an 
independent DMC will review safety data on these subjects and 
recommend to Gilead whether the treatment has demonstrated 
acceptable tolerability. Thereafter, review of safety data will be 
performed at regular intervals as described in the DMC charter.
Sample Size:
Assuming the ORR for subjects treated with nivolumab alone is 25%, 
120 subjects in total are needed to detect an improvement of 20% in 
ORR for subjects treated with andecaliximab and nivolumab with
approximately 83% power at one-sided significance level of 10% using 
a CMH test with an assumption of common odds ratio for all strata. The 
assumption of nivolumab ORR is based on the upper bound of the 
95% confidence interval of the estimated ORR in CheckMate-032 Study
{Le 2016}.
This study will be conducted in accordance with the guidelines of Good Clinical Practices
(GCPs) including archiving of essential documents.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
β-hCG
beta-human chorionic gonadotropin
λz
terminal elimination rate constant; estimated by linear regression of the terminal 
elimination phase of the log serum/plasma/PBMC concentration versus time curve of the 
drug
5-FU
5-fluorouracil
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
AUC
area under the concentration versus time curve
AUClast
area under the plasma/serum/PBMC concentration versus time curve from time zero to the 
last quantifiable concentration
AUCtau
area under the plasma/serum/PBMC concentration versus time curve over the dosing 
interval
BSA
body surface area
Cmax
maximum observed concentration of drug
CFR
Code of Federal Regulations
CI
confidence interval
Clast
last observed quantifiable serum/plasma/PBMC concentration of the drug
CLcr
creatinine clearance
Cmax
maximum observed serum/plasma/PBMC concentration of drug
CR
complete response
CRO
contract research organization
CT
computed tomography
Ctau
observed drug concentration at the end of the dosing interval
CTCAE
Common Terminology Criteria for Adverse Events
DCR
disease control rate
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DOR
duration of response
DSPH
Drug Safety and Public Health
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic Case Report Form
EOS
end of study
EOT
end of treatment
eSAE
electronic serious adverse event
EU
European Union
FDA
Food and Drug Administration


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GCP
good clinical practice
GEJ
gastroesophageal junction
HBV
hepatitis B virus
HCV
hepatitis C virus
HER2
human epidermal growth factor receptor 2
HIV
human immunodeficiency virus
HLT
high-level term
HR
hazard ratio
IB
investigator’s brochure
IC50
concentration necessary to achieve 50% inhibition of target
ICH
International Conference on Harmonisation
IHC
immunohistochemistry
IMP
investigational medicinal product
INR
international normalized ratio
IRB/IEC
institutional review board or independent ethics committee
ISH
in situ hybridization
ITT
intent-to-treat
IUD
intrauterine device
IWRS
interactive web response system
KM
Kaplan-Meier
LV
leucovorin
LTFU
long-term follow-up
MMP
matrix metalloproteinases
MRI
magnetic resonance imaging
MSS
musculoskeletal syndrome
ORR
objective response rate
OS
overall survival
PD
progressive disease
PD-1
programmed death-1
PFS
progression-free survival
PK
pharmacokinetic
PR
partial response
PRO
patient-reported outcomes
RECIST
Response Evaluation Criteria In Solid Tumors
PT
preferred term
RNA
ribonucleic acid
SADR
serious adverse drug reactions
SAE
serious adverse event
SD
stable disease
SOC
system organ class


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SOP
standard operating procedure
SUSAR
suspected unexpected serious adverse reactions
t½
estimate of the terminal elimination half-life of the drug in serum/plasma/PBMC, 
calculated by dividing the natural log of 2 by the terminal elimination rate constant (λz)
TIMPs
tissue inhibitors of metalloproteinases
Tlast
time (observed time point) of Clast
TTR
time to response
ULN
upper limit of normal


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1.
INTRODUCTION
1.1.
Background
Matrix metalloproteinases (MMP) comprise a family of at least 23 Zn2+-dependent proteases 
which are involved in the degradation and remodeling of the extracellular matrix and basement 
membranes in and activation or degradation of growth factors, cytokines and chemokines 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 MMP2 and MMP9, sometimes referred to as 
type IV collagenases, which are named for their ability to degrade type IV or basement 
membrane collagen and gelatin, {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}. Various substrates have been identified for MMP9, and the active enzyme can 
release cytokines, growth factors, and bioactive fragments which in turn modulate inflammation, 
neovascularization, tumorigenesis 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}.
The disease-associated induction and functions of MMP9 render it an attractive therapeutic 
target.  In oncology, MMP9 can contribute to tumor growth through a variety of mechanisms, 
including remodeling of the microenvironment, promotion of pro-tumorigenic and 
pro-angiogenic signaling pathways, and blunting of anti-tumor immune responses.
Checkpoint inhibitors, including therapeutic antibodies targeting programmed death-1 (PD-1) 
receptor such as nivolumab, have shown dramatic and sustained clinical benefit in melanoma, 
renal cell carcinoma, and subsets of other diverse solid tumors. These findings highlight the 
importance of immunomodulation in tumorigenesis. However, the response rate to these 
inhibitors remains limited in some of tumors such as gastric adenocarcinoma {Antonia 2015}. 
Factors contributing to limitations in response could include access of T cells to tumor cells due 
to the collagenous tumor desmoplastic reaction and tumor angiogenesis, in addition to repression 
of anti-tumor T-cell responses in the local tumor microenvironment resulting from the increased 
presence and activity of myeloid suppressor cells (MSC) and their associated cytokines, 


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chemokines, and growth factors. The combination of andecaliximab with nivolumab offers an 
opportunity to broaden and deepen responses in gastric adenocarcinoma. Treatment with 
andecaliximab may result in productive remodeling of the tumor microenvironment to enable 
both T-cell and drug access, and the inhibition of both MSC recruitment and activation by 
andecaliximab may further inhibit tumor growth and promote anti-tumor immunity in 
combination with nivolumab. 
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}. Approximately 22,220 patients are 
diagnosed annually in the United States, of whom 10,990 are expected to die. While the 
incidence of distal gastric adenocarcinoma has recently declined in the United States, gastric 
adenocarcinoma remains quite frequent in certain minority populations and it is still the 
second most common cause of cancer death worldwide. In addition, adenocarcinoma of the 
gastroesophageal junction (GEJ) is one of the most rapidly increasing solid tumors in the 
United States and Western Europe.
Most patients with gastric adenocarcinoma in the United States are symptomatic and already 
have advanced incurable disease at the time of presentation. At diagnosis, approximately 
50 percent have disease that extends beyond locoregional confines, and only one-half of those 
who appear to have locoregional tumor involvement can undergo a potentially curative resection. 
Surgically curable early gastric adenocarcinomas are usually asymptomatic and only infrequently 
detected outside the realm of a screening program. Screening is not widely performed, except in 
countries which have a very high incidence, such as Japan, Venezuela, and Chile. The common 
presenting symptoms and diagnostic approaches to gastric adenocarcinoma include weight loss 
(usually results from insufficient 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 adenocarcinoma called linitis plastica, from poor distensibility of the 
stomach. They may also present with a gastric outlet obstruction from an advanced distal tumor.
Gastric and esophageal adenocarcinomas are chemotherapy sensitive diseases, with several 
active drug therapy classes, including platinum, fluoropyrimidines, topoisomerases inhibitors, 
taxanes, and anthracyclines. Despite significant differences in epidemiology and molecular 
characteristics, cytotoxic chemotherapy combinations have not demonstrated significant 
differences in efficacy across gastric adenocarcinoma. {Chau 2009}.


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Chemotherapy clearly provides a survival advantage over best supportive care in both first-line
{Glimelius 1997, Murad 1993, Pyrhonen 1995, Scheithauer 1995} and second-line {Kang 2012, 
Thuss-Patience 2009} settings. A meta-analysis of first-line chemotherapy versus best supportive 
case studies reported a hazard ration (HR) of 0.39 (95% CI, 0.28-0.52;p<0.001) for overall 
survival in favor of chemotherapy. This translates to a benefit of a median of 6 months {Wagner 
2006}.
Performance status often declines after first-line therapy. Patients with esophageal cancer often 
have significant comorbidities, including obesity, heart disease, emphysema, which when 
coupled with progressive dysphagia and malnutrition, often limit therapeutic opportunities after 
first-line therapy. Gastric adenocarcinoma patients who develop peritoneal carcinomatosis often 
have decreased bowel function that then results in GI symptoms and a decline in functional 
status and therefore limiting treatment options substantially {Power 2010}. However 
administration of second-line therapy in patients who are sufficiently fit to receive it has 
demonstrated a survival advantage over supportive care alone. {Kang 2012, Thuss-Patience 
2009}. A meta-analysis of these studies demonstrated a HR for OS of 0.73 (95%CI, 058 – 0.960), 
and in highly functioning patients (ECOG performance status of 0 or 1) the HR was 
0.57 (95%CI 0.36-0.91).
For patients who retain an adequate performance status, there is no standard approach for 
second-line therapy after failure of the first-line regimen. Quality-of-life and minimization of 
side effects are key considerations when choosing the therapeutic approach. The choice of 
regimen is empiric. No single regimen has emerged as clearly superior and few trials have 
compared different regimens {Thallinger 2011, Wesolowski 2009}. Current NCCN guidelines 
suggest clinical trials in the relapsed setting, and immune checkpoint inhibitors have recently 
started in these patients.
There is emerging evidence that immunosurveillance is significantly altered in gastroesophageal 
malignancies {Kono 2006, Lu 2011, Ohigashi 2005}. PD-L1 is a transmembrane protein that 
was first identified for its role in the maintenance of self-tolerance and prevention of 
autoimmunity {Fife 2011}. Engagement of PD-L1 on dendritic cells with PD-1 receptor on 
T cells delivers an inhibitory signal that promotes T-cell anergy or apoptosis {Keir 2008}.Tumor 
cells overexpress PD-L1 resulting in T-cell anergy and escape from immunosurveillance. 
Blockade of the interaction between PD-L1 on tumor cells and PD-1 on T cells reverses T-cell 
suppression within tumors, thereby promoting effective antitumor immune responses. In 
esophageal cancer, tumor infiltrating lymphocytes correlated with improved survival {Kono 
2006, Lu 2011}. Of note, 70% of esophageal adenocarcinomas express PD-L1 and its expression 
is independently associated with worse survival {Lu 2011}. Immune checkpoint inhibitors are 
being actively investigated in gastric adenocarcinoma and have yielded promising results.
There has been early demonstration of activity of PD-1 antibody immune checkpoint inhibitors 
in upper GI cancers. Pembrolizumab seems to have some activity in patients with PD-L1 
expressing advanced gastric adenocarcinoma as reported at the European Society for Medical 
Oncology 2014 meeting {Muro 2014}. Of the 39 patients enrolled, 19 were from Asia and 
20 were from other areas of the world. At a median follow up of approximately 6 months, the 


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ORR was 31% in Asians and 30% in non-Asians, suggesting activity. Data more recently 
presented at ASCO GI in Jan 2016 also confirmed PD-1 inhibition by nivolumab as an effective 
possible treatment strategy for second-line gastric adenocarcinoma patients with an ORR of 12% 
and SD of 21%.{Antonia 2015}.
1.1.2.
MMP9 Expression in Oncology
Immunohistochemistry (IHC) studies conducted with validated reagents indicate that MMP9 
expression is highly prevalent across solid tumors, including gastric adenocarcinoma 
(≥90%, n ≥30 each for cases of North American, European, and Chinese origin). MMP9 is 
expressed heterogeneously by tumor epithelia and infiltrating inflammatory cells (predominantly 
of myeloid type), along with subsets of fibroblastic stroma, and tumor-associated endothelial 
cells. Heterogeneous expression is apparent within a single tumor, as well as across different 
tumors.  No particular associations with genetic background and MMP9 expression were 
apparent across different solid tumors.
Figure 1-1.
Examples of MMP9 Expression in Gastric Adenocarcinoma (IHC)
Panels on the left show examples of regions with high tumor cell epithelial positivity for MMP9, along with positive stromal 
areas. In panels on the right, there is less MMP9 expression evident in tumor epithelia, but stromal positivity is apparent. All 
cases contain MMP9-positive infiltrating inflammatory cells.  
1.1.3.
General Information
Andecaliximab (formerly GS-5745) is a recombinant chimeric IgG4 monoclonal antibody 
selective for MMP9. It has been engineered to remove T cell epitopes in an effort to reduce the 
risk of immunogenicity. 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. 


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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).
1.1.4.
Preclinical Pharmacology and Toxicology
1.1.4.1.
Pharmacology
MMP9 enzymatic activity contributes to tumor growth by several mechanisms (Figure 1-2).
MMP9 degrades basement membrane collagen and remodels other extracellular matrix (ECM) 
components and regulates the bioavailability of ECM-sequestered growth factors such as VEGF, 
FGF-2, as well as membrane-tethered EGF {Ardi 2009, Deryugina 2010, Kessenbrock 2010, 
Perng 2011}. Proteolytic breakdown of physical barriers to cell invasion plus liberation of 
factors that activate growth and angiogenesis paves the way for tumor expansion and metastasis, 
with the accompanying development of neovascularization to support tumor outgrowth. MMP9 
expression by tumor-associated myeloid suppressor cells (MSCs) such as macrophages (TAMs), 
neutrophils (TANs), and myeloid-derived suppressor cells (MDSC) is associated with local pro-
tumorigenic immunomodulation and angiogenesis {Farina 2014}. Cytokine and chemokine 
modulation by MMP9 in the tumor microenvironment promotes further recruitment of MSCs 
that both promote tumor growth and reduce anti-tumor immune responses by T and NK cells
(Figure 1-2) {Condeelis 2006, Heissig 2002, Shih 2006}.
Figure 1-2.
Summary of Pro-Tumorigenic Activities of MMP9
Summary of pro-tumorigenic activities of MMP9, which include promoting tumor growth, invasion, and metastasis via effects on 
both tumor epithelia and the microenvironment. Remodeling of the microenvironment alters the physical properties of tumors. In 
addition, the action of MMP9 on cytokines and chemokines in the local milieu promote recruitment and activation of myeloid 
suppressor cells and inhibit anti-tumor T-cell recruitment and responses.
_ 
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. 
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recruitment, 
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!CXCL11 
Alter MSC 
cytokines, 
chemokines 
Increase MSC 
recruitment, 
activation 
INFLAMMATORY FILTRATE 


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The therapeutic potential of inhibitory antibodies targeting human MMP9 (AB0041) and mouse 
MMP9 (AB0046) was evaluated in a surgical orthotopic xenograft mouse model of colorectal 
carcinoma in which tumors were derived from the human tumor cell line HCT116. While MMP9 
expression is limited in this tumor model as compared to human gastrointestinal tumors such as 
gastric and colorectal cancer, with patchy positivity in subsets of tumor epithelia and infiltrating 
myeloid cells observed, the model nonetheless enables exploration of MMP9 biology in each 
compartment. Treatment of established tumors with a cocktail of an anti-human MMP9 antibody 
(targeting MMP9 produced by tumor epithelia) and an anti-mouse MMP9 antibody (targeting 
MMP9 produced by infiltrating cells) significantly reduced growth of the primary tumor and 
reduced the incidence of metastases in multiple independent studies. Furthermore, treatment with 
either agent alone yielded significant anti-tumor efficacy highlighting important roles for both 
tumor epithelial-derived and stromal/infiltrate-derived MMP9 in primary tumor outgrowth. Of 
note, in addition to reduction in tumor growth, MMP9 inhibition was associated with changes in 
the tumor microenvironment, specifically a reduction in the tumor cell-associated fibrillar 
collagen as measured by second harmonic generation microscopy, a multiphoton method that 
specifically visualizes crystalline fibrillar collagen (Figure 1-3). Follow up studies in the 
orthotopic HCT-116 model provide further evidence that inhibition of MMP9-associated 
remodeling can promote delivery of agents to the tumor (in this example, modeled by injection 
and imaging of doxorubicin after 2 weeks of therapy with anti-MMP9, Figure 1-4). 
Figure 1-3.
Changes in Tumor-Associated Fibrillar Collagen
Changes in tumor-associated fibrillar collagen (second harmonic generation microscopy, white) with MMP9 inhibition in an 
orthotopic model of colorectal cancer (HCT-116-derived). T = tumor, N = normal. Fibrillar collagen adjacent to normal structures 
was not altered, but tumor-associated fibrillar collagen was reduced.
lgG control 
aMMP9 mAb 


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Figure 1-4.
Effect of MMP9 Inhibition in the HCT-116 Orthotopic Model of CRC
Exploring the effects of MMP9 inhibition in the HCT-116 orthotopic model of colorectal cancer, in which tumor cells are labeled 
with green fluorescent protein (GFP, in green) and the host is labeled with cyan fluorescent protein, with bias towards fibroblastic 
cells (CFP, in blue). After two weeks of treatment of established tumors with anti-MMP9 antibodies or an isotype control, 
doxorubicin is administered and its natural signal imaged 24 hours later (red). The merged image highlights changes in the 
physical tumor structure with anti-MMP9, along with evidence of improved delivery of doxorubicin.
These observations and published data suggest that inhibition of MMP9 could provide benefit 
with respect to anti-tumor immunity in 2 respects: improved access of both antibodies and 
T cells themselves to tumor cells to enable synapse formation and cell lysis as a result of 
remodeling of the tumor microenvironment, and re-balancing of a myeloid-rich tumor-associated 
cellular milieu to one that is less repressive to cytotoxic T-cell entry and activity (Figure 1-5). To 
experimentally explore these concepts, a syngeneic mouse model of breast cancer was utilized 
(HC11-NeuT [HER2]-driven tumors implanted in the mammary fat pad). IHC analysis of 
HC11-NeuT tumors indicated that MMP9 expression was restricted to the myeloid cell infiltrate 
with limited to no expression apparent in tumor epithelia (Figure 1-6). While this expression 
pattern underestimates the MMP9 profile that is observed in human tumors, it nonetheless 
affords an opportunity to examine the consequences of inhibiting myeloid-derived, 
tumor-associated MMP9 in mice with an intact immune system. As shown in Figure 1-6, 
therapeutic administration of anti-murine MMP9 antibody AB0046 resulted in significant 
inhibition of tumor growth, highlighting the role of myeloid cell-derived MMP9 in promoting 
tumorigenesis. Conversely, a murine inhibitory antibody targeting the T-cell checkpoint pathway 
via PD-L1 did not have any impact on tumor growth. The resistance to checkpoint therapy in this 
model is attributed to the presence of MSC. A combination of anti-MMP9 and anti-PD-1 did not 
further impact tumor volume in this model, perhaps in part due to the magnitude of effect of 
anti-MMP9 as a single agent.
Tumor (GFP) 
Doxorubicin 
Host (CFP) 
MERGE 


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Figure 1-5.
Hypothesis for 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.
Figure 1-6.
Inhibition of MMP9 in Orthotopic HC11-NeuT Model of Breast 
Cancer
Inhibition of MMP9 is efficacious in the syngeneic, orthotopic HC11-NeuT model of breast cancer. Treatment was initiated at an 
average tumor volume of 100 mm3. Test articles: vehicle (blue), Isotype control IgG (GS-645864, red), anti-MMP9 
(GS-622703 = AB0046, green), anti-PD-L1 (GS-696882, purple), combination of anti-MMP9 and anti-PD-L1 (orange). 
** p < 0.01, *** p < 0.005. Representative IHC for MMP9 expression in this model is shown in C, positive myeloid cell 
infiltrate.
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Collagen fibrils around tumors can impede delivery of therapies and the access of T cells to 
tumor cells, thus acting as a physical barrier to anti-tumor immunity and contributing to tumor 
progression. Analysis of tumor-associated fibrillar collagen by second harmonic microscopy was 
superimposed with images of nuclear staining (Sytox orange) and tumor cell staining 
(cytokeratin) to provide context for collagen fibril visualization .The cytokeratin staining 
revealed that the tumors grew in both large masses and small acinar structures and the collagen 
fibrils in and around both structures appeared to be diminished in the tumors treated with 
AB0046 (Figure 1-7). Quantification of fibrillar collagen intensity across entire images from this 
study confirmed the trend in decreased fibrillar collagen in the α-MMP9 treated tumors. 
Figure 1-7.
Changes in Tumor-Associated Fibrillar Collagen
Changes in tumor-associated fibrillar collagen (second harmonic generation microscopy, white) with MMP9 inhibition in an 
orthotopic syngeneic model of breast cancer. Tumor cells are stained with a pan-cytokeratin marker (pink), nuclei in DAPI 
(blue).
Transcript and pathway analysis of treated tumors revealed additional changes in the tumor 
microenvironment associated with MMP9 inhibition. The top 10 pathways analysis using C2
canonical pathways collections indicated that inhibition of MMP9 lead to an increase in overall 
immune signature pathways such as interferon gamma and alpha-beta signaling, 
immunoregulation, antigen processing and presentation, and CD8 and T-cell receptor signaling. 
For anti-PD-L1 treated tumors, an increase in immune signature was also observed, consistent 
with the known mechanism of action of this agent (immunoregulatory interactions between 
lymphoid and non-lymphoid cells, CD8 TCR pathway, TCR pathway, and T-cell signal 
transduction). As illustrated in Figure 1-8, upregulation of immunomodulatory pathways 
consistent with T-cell and possibly also NK cell activation was a notable feature of MMP9 
inhibition by different pathway analyses, and these patterns were also reflected in the PD-L1 and 
combination groups. These data are consistent with inhibition of myeloid-produced MMP9 
resulting in a microenvironment that is more favorable for T-cell infiltration and activation. 
lgG control 
aMMP9 mAb 


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Figure 1-8.
Transcriptome and Pathway Analysis of the HC11-NeuT Model
Primary pathways for MMP9 inhibition, from KEGG and Broad collections, reflect activation of T-cell and related 
immunomodulatory signaling pathways. 
The PD-1/PD-L1 axis defines an immune checkpoint that prevents the activation of T cells in the 
tumor microenvironment. Data from current clinical trials suggests that the tumors that respond 
most strongly to nivolumab are those that are either particularly immunogenic (eg, tumors with 
genomic instability) or those with infiltrated T cells in the tumor. For tumors that do not respond, 
despite the relief of the immune checkpoint by nivolumab, continued repression of T-cell 
activation due to an immunosuppressive environment may be a possible explanation. 
andecaliximab is hypothesized to remove the immunosuppressive environment through local 
suppression of or reduction of myeloid-derived suppressor cells, as well as local inflammation 
and immunosuppressive cytokines. Additionally, inhibition of MMP9 in the tumor 
microenvironment is expected to promote lymphocyte and therapeutic access. Thus, combination 
of andecaliximab with nivolumab is proposed to lead to more activated cytotoxic T cells and 
provide superior efficacy in advanced gastric cancer relative to nivolumab alone.
The major dose limiting toxicity 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 the non-clinical pharmacology are available in the andecaliximab IB.
A 
12 3 
1 = aPDL1 
2 = combination 
3= aMMP9 
123 
1 = aMMP9 
2 = com bi nation 
3=aPDL1 


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1.1.4.2.
Toxicology
The toxicology program consists of completed 4-week repeat-dose IV toxicity studies in both 
rats and monkeys. The 26-week toxicity studies in rats and cynomolgus monkeys included both 
IV and SC routes. The rat and rabbit embryo fetal development studies and the rat fertility study 
have also been completed. 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. Findings associated with andecaliximab treatment in the 
4-week repeat-dose toxicity studies have been limited to 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. The physeal hypertrophy in rats is 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 both mice and children, this is a transient finding that 
spontaneously regresses as the bone matures. The physeal hypertrophy noted in rats is not 
considered relevant to adult humans because the growth plates are closed and longitudinal bone 
growth is no longer ongoing in adults. In the 26-week studies, there were no findings of 
toxicological concern in rats or cynomolgus monkeys following weekly IV or SC administration 
at 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. The NOAEL in 
the rat and monkey 26-week studies was 100 mg/kg/dose (IV) (Rat Week 24 AUC0-168h 269,000; 
monkey Week 25 AUC0-168h 766,000 µg•h/mL) and 150 mg/kg/dose (SC), (Rat Week 24 
AUC0-168h 101,000 µg•h/mL; monkey Week 25 AUC0-168h 719,000 µg•h/mL), respectively, the
highest doses evaluated by each route of administration in each study.
1.1.5.
Clinical Trials of Andecaliximab
Andecaliximab is being investigated for the treatment of solid tumors, inflammatory bowel 
disease, rheumatoid arthritis, cystic fibrosis, and chronic obstructive pulmonary disease. Brief 
summaries of the solid tumor clinical trials are provided herein.
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.
As of January 12, 2016, Study GS-US-296-0101 had enrolled 40 subjects with metastatic gastric 
adenocarcinoma (14 remain on study). Grade 3 or higher treatment-emergent AEs (TEAEs) 
included neutropenia (18%), nausea (10%), and neutrophil count decreased (10%). The most 
common serious TEAEs were abdominal pain, GI hemorrhage, hyponatremia, nausea, pyrexia,
and septic shock each occurring in 2 subjects (5%). Median progression free survival (PFS) for 
all 40 subjects was 7.4 months (90% confidence interval (CI) = [5.0, 12.5]), with a median 
duration of response (DOR) of 9.4 months and an objective response rate (ORR) of 50%. Of 
those subjects, 30 were chemotherapy naïve (eg, first-line), and demonstrated a median PFS of 
12.0 (90% CI = [5.5, 18.0]) months, with a median DOR of 10.6 months and an ORR of 57%. 
Collagen neoepitope decreased with continued treatment, demonstrating on-target effects. 


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This efficacy data combined with the favorable safety profile continues to support evaluation of 
andecaliximab in a Phase 3 study of this fatal disease where therapeutic options are limited and 
non-curative.
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. A dose of 800 mg Q2W in 
combination with mFOLFOX6 is being evaluated globally at centers in the United States, 
Europe, Latin America, and Australia. 
Study GS US-296-1884 is a Phase 1b clinical study of Japanese subjects to evaluate safety and 
tolerability of GS5745 as monotherapy and in combination with chemotherapy.
Further details on the oncology studies with andecaliximab, as well as the clinical studies outside 
of oncology, can be found in the andecaliximab IB.
1.1.6.
Information about Nivolumab
Nivolumab (OPDIVO) is a programmed death receptor-1 (PD-1) blocking antibody indicated for 
the treatment of patients with:

Advanced (unresectable or metastatic) melanoma in adults

Metastatic non-small cell lung cancer whose disease progressed during or after 
platinum-based chemotherapy. (US FDA)

Advanced renal cell carcinoma who have received prior anti-angiogenic therapy (US FDA)
Please see local label for updated accurate information about nivolumab.
1.2.
Rationale for this Study
Andecaliximab is a monoclonal antibody that inhibits MMP9, an extracellular enzyme involved 
in matrix remodeling, tumor growth, and metastasis. Preclinical studies demonstrate that MMP9 
inhibition alters the tumor microenvironment, is associated with greater chemotherapy 
penetration, and improved anti-tumor immunity.
MMP9 has been shown to degrade and remodel basement membrane and extracellular matrix 
and vasculature. It can promote recruitment of tumor-associated macrophages and immune 
suppressor cells, and locally activate cytokines produced by these cells that impair anti-tumor 
immunity. The murine surrogate of andecaliximab (anti-MMP9 antibody) has shown significant 
anti-tumor activity in models in which MMP9 is produced by infiltrating myeloid cells. The 
anti-tumor activity is associated with reduction of tumor-associated fibrillar collagen, and 
alterations in the immune cell transcript profile in the treated tumors. PD-1 is a negative 
co-stimulatory receptor expressed primarily on activated T cells. Binding of a PD-1inhibitor to 
the PD-1 receptor will inhibit the inhibitory signal on T cells and will thus stimulate the 


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anti-tumor effect. Andecaliximab’s ability to alter the collagenous microenvironment may allow 
for greater infiltration of activated lymphocytes into the tumor and hence augment the anti-tumor 
effect offered by a PD-1 inhibitor alone. Thus, the combination of removing the negative 
stimulus on T cells by the PD-1 inhibitor and the enabling of activated T cells to gain access to 
the tumor cells by remodeling of the microenvironment and reduction of suppressive signals 
makes this a very attractive combination for cancer therapy. 
Nivolumab is a fully human anti-PD-1 IgG4 monoclonal antibody with a favorable safety profile 
and efficacy in melanoma, non–small-cell lung cancer, and renal cell carcinoma. The Phase 1/2, 
open-label CheckMate-032 study evaluated nivolumab ± ipilimumab in subjects with solid 
tumors. At GI ASCO 2016 data were presented for subjects with gastroesophageal or gastric 
adenocarcinoma receiving nivolumab monotherapy. Fifty-nine subjects were enrolled and treated 
with single-agent nivolumab; ORR was 12% (n = 7/58; 1 complete response, 6 partial responses, 
12 subjects [21%] had stable disease). Among responders, median duration of response was 
7.1 months (95% CI, 3.0–13.2) and OS was 6.8 months (95% CI, 3.3–12.4). Thirty-nine percent
of tumor samples were PD-L1 positive (≥ 1% cutoff). ORRs in subjects with PD-L1-positive and 
-negative tumors were 18% and 12%, respectively. The investigators concluded that nivolumab 
showed activity in second-line gastric adenocarcinoma and should be further investigated.
Somatic mutations have the potential to encode for “non-self” and serve as immunogenic 
antigens. Tumors with a large number of somatic mutations due to genomic instability have been 
found to be more susceptible to immune checkpoint blockade. In a trial of 41 subjects with 
progressive metastatic carcinoma with or without mismatch-repair deficiency, both PFS and OS 
were significantly improved for subjects treated with a PD-1 inhibitor alone and whose tumors 
were genomically unstable {Le 2015}.
Randomization in this study will be stratified by PD-L1 status.
1.3.
Risk/Benefit Assessment for the Study
There is no clear or demonstrably superior standard regimen for the treatment of advanced 
gastric adenocarcinoma especially for those who failed first-line chemotherapy; however, further 
therapy does improve OS.  Preliminary data shows that immune checkpoint inhibitors have 
activity in this difficult disease and with fewer side effects than chemotherapy. Furthermore, 
many patients cannot take second-line and beyond chemotherapy due to deterioration of 
performance status or other comorbid conditions and thus immune therapy presents an attractive 
option for them. Andecaliximab has the potential to augment the response by immune checkpoint 
inhibitors in 3 distinct ways: (1) allow greater penetration of activated T cells into the tumor bed 
by remodeling the extracellular matrix, (2) inhibit the MDSCs that are present due to MMP9 
physiologic activity, and (3) change the cytokine milieu to be predominantly anti-tumor. This 
preclinical hypothesis has been tested in mouse models and presents as strong rationale for 
efficacy in human cancer. 
Furthermore, andecaliximab thus far has shown limited toxicity in clinical trials. No MTD dose 
was reached in the dose-escalation monotherapy Phase 1 study, and the toxicity profile seen 
when combining andecaliximab with mFOLFOX chemotherapy is similar to that seen with 
chemotherapy alone.  To date there have been no additional toxicities ascribed to andecaliximab. 


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Preliminary clinical data point to activity of andecaliximab in combination with chemotherapy 
with a median PFS in chemotherapy-naive subjects of 12 months. Early data similarly shows 
activity of nivolumab as monotherapy in the refractory gastric adenocarcinoma population with 
durable response rates and a tolerable safety profile (Grade 3 or 4 treatment-related AEs in ~17% 
of subjects in the most recent public data from CheckMate-032). It is hypothesized that the 
2 agents together, andecaliximab and nivolumab, will have greater activity when combined. 
Potential risks are those inherent in participation in any clinical trial, including (but not limited to)
the potential for unforeseen toxicity from 1 or more of the study treatments, procedure-associated
risks for protocol-specified procedures, and potential to be treated with a less-active therapy 
regimen.
The favorable nonclinical and clinical data outweigh the risks associated with administration of 
andecaliximab and nivolumab and support the evaluation of andecaliximab in combination with 
nivolumab as a second-line treatment in subjects with advanced gastric or GEJ adenocarcinoma.
1.4.
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 prima1y objective of this study is: 
Final 
Amendment3 
• 
To evaluate and compare the efficacy of andecaliximab in combination with nivolumab 
versus nivolumab alone in subjects with recunent gastric or GEJ adenocarcinoma 
The secondaiy objectives of this study ai·e: 
• 
To chai·acterize and compai·e safety and tolerability of andecaliximab in combination with 
nivolumab versus nivolumab alone in subjects with recunent gastric or GEJ adenocai·cinoma 
• 
To chai·acterize the phannacokinetics (PK) of andecaliximab in combination with nivolumab 
The explorato1y objectives of this study ai·e: 
I 
I 
I 
I 
I 
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3.
STUDY DESIGN
3.1.
Endpoints
The endpoints of this study are described in Sections 8.1.2, 8.1.3, and 8.1.4. 
3.2.
Study Design
This is a Phase 2, open-label, randomized study comparing andecaliximab in combination with 
nivolumab versus nivolumab alone in recurrent gastric adenocarcinoma. One hundred and 
twenty subjects (60 per arm) will be randomized to either Treatment Arm A: 
andecaliximab + nivolumab or Treatment Arm B:  nivolumab alone. 
To evaluate combination drug safety, an independent Data Monitoring Committee (DMC) will 
be charged with overseeing the study safety. After the first 20 subjects are treated for 12 weeks, 
the DMC will review and evaluate all safety data for any unexpected toxicities. If the DMC 
determines the combination demonstrates acceptable tolerability, enrollment and randomization 
will proceed with continued safety oversight from the DMC. Thereafter, review of safety data 
will be performed at regular intervals as described in the DMC charter.
Treatment Groups:

Arm A: andecaliximab + nivolumab

Arm B: nivolumab
Randomization and Stratification:

1:1 allocation to andecaliximab + nivolumab versus nivolumab alone through an interactive 
web response system (IWRS)

Fixed-block centralized randomization with stratified by: 
PD-L1 positive versus PD-L1 negative
I 
1 Arm A 
I 
1 N=60 
GS-5745 + Nivolumab 
(Up to 2 years) 
:I 
Long-Term Follow-Up > 
I 
1 Arm B 
Nivolumab 
1 N=60 L_....J.,::.Uc..:;to:..::..&.
2e;;.;a;.;.rs;;..:.)_ 1 
I 
I 
StratifiJation and 
Randomization 
Disease 
progression or 
study stopped 
Long-Term Follow-Up > 


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3.3.
Study Treatments
Subjects meeting eligibility randomized to Arm A will receive 800 mg of andecaliximab on 
Day 1 and every 2 weeks thereafter via intravenous (IV) infusion over approximately 30 minutes
in advance of nivolumab. Nivolumab (3 mg/kg) will be administered via IV infusion over 
approximately 60 minutes following the completion of andecaliximab administration.
Subjects meeting eligibility randomized to Arm B will receive 3 mg/kg nivolumab via IV
infusion over approximately 60 minutes on Day 1 and every 2 weeks thereafter.
3.4.
Duration of Treatment
Starting on Day 1, treatment will be given every 2 weeks and will continue in the absence of 
disease progression or unacceptable toxicity, consent withdrawal or subject’s refusal of 
treatment, or up to 2 years. There will be a screening period of up to 28 days. Following 
completion of treatment, subjects will be followed for safety at 30 days after last dose of 
andecaliximab and 5 months post-treatment of nivolumab, and for survival status approximately 
every 3 months for up to 5 years total.
3.5.
Discontinuation Criteria from Treatment 
Andecaliximab and/or nivolumab will be discontinued for any of the following reasons:

Pregnancy during the study; refer to Appendix 4

Investigator decision to remove the subject from the study treatment, in consultation with the 
Gilead Medical Monitor whenever possible

Confirmed disease progression (see Section 6.2.9 Disease and Response Assessment)

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 

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

Subject request to discontinue treatment

Withdrawal of consent 

Death


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
Discontinuation of the study at the request of Gilead, a regulatory agency, or an 
institutional review board or independent ethics committee (IRB/IEC)

Lost to follow up

Subject non-compliance
Should any study medication discontinuation occur, the reason for discontinuation should be 
entered in the corresponding study drug completion eCRF. In addition, the subject should 
continue with the rest of the treatment regimen and the study related procedures per protocol.
3.5.1.
Discontinuation Criteria for Nivolumab
In addition to the discontinuation reasons outlined in Section 3.5, please refer to the current 
nivolumab label or SmPC for your respective region for full discontinuation criteria during 
treatment with nivolumab.
Nivolumab should also be discontinued for any dosing interruption lasting > 6 weeks with the 
following exceptions:

Dosing interruptions to allow for prolonged steroid tapers to manage drug-related AEs are 
allowed. Prior to re-initiating treatment in a subject with a dosing interruption lasting
> 6 weeks, the Sponsor Medical Monitor/Study Director must be consulted. Tumor
assessments should continue as per protocol even if dosing is interrupted.

Dosing interruptions > 6 weeks that occur for non-drug-related reasons may be allowed if
approved by the Sponsor Medical Monitor/Study Director. Prior to reinitiating treatment in a 
subject with a dosing interruption lasting > 6 weeks, the Sponsor Medical Monitor/Study 
Director must be consulted. Tumor assessments should continue as per protocol even if 
dosing is interrupted.
If nivolumab therapy is permanently discontinued for any reason, subjects on Treatment Arm A 
should also permanently discontinue andecaliximab therapy at the same time.  Subjects enrolled 
on Treatment Arm A who discontinue andecaliximab for reasons other than progression may 
continue nivolumab after consultation with the Sponsor Medical Monitor/Study Director.
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 computed tomography (CT) or magnetic resonance imaging (MRI) 
every 8 weeks 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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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

Intercurrent illness that would, in the judgment of the investigator, affect assessments of
clinical status to a significant degree

Withdrawal of consent

Investigator decision to remove the subject from the study, in consultation with the Gilead 
Medical Monitor

Death

Discontinuation of the study at the request of Gilead, a regulatory agency, or an IRB/IEC

Lost to follow up
3.8.
Long-Term Follow-Up for Overall Survival 
Long-term follow-up (LTFU) will be initiated for subjects who discontinue participation in the 
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.
The end of the trial will be defined as when all subjects have completed LTFU or discontinued 
their participation in the study due to death, withdrawal of consent, or lost to follow-up.
3.9.
Source Data
The subject identification number and randomization number captured by the interactive
web response system (IWRS) are considered source data.


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Biomarker Testing 
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The PD-1/PD-Ll axis defines an immune checkpoint that prevents the activation of T cells in the 
tumor microenvironment. Nivolumab inhibits binding of T-cell PD-1 to PD-Ll present on tumor 
and stromal cells; thus nivolumab inhibits the checkpoint to allow activation of cytotoxic T cells 
by tumor immunogens. Data from cmTent clinical trials suggests that the tumors that respond 
most strongly to nivolumab are those that are either immunogenic (tumors with genomic 
instability) or those with infiltrated T cells in the tumor. For tumors that don't respond, despite 
the relief of the immune checkpoint by nivolumab, continued repression of T-cell activation due 
to an immunosuppressive environment may be a possible explanation. Andecaliximab is 
hypothesized to remove the immunosuppressive environment through local suppression of or 
reduction of myeloid suppressor cells, local inflammation, and immunosuppressive cytokines. 
Additionally, inhibition ofMMP9 in the tumor microenvironment is expected to promote 
lymphocyte and therapeutic agent access. Thus, combination of andecaliximab with nivolumab is 
proposed to lead to more activated cytotoxic T cells and provide superior efficacy in advanced 
gastric adenocarcinoma relative to nivolumab alone. The biomarker testing described below is 
designed to address, to the extent possible, these specific hypotheses and to investigate whether 
non-invasive biomarkers of response can be identified. 
3.10.1. 
Biomarker Samples to Address the Study Objectives: 
Biological specimens will be collected in this study and will be used to evaluate the association 
of explorato1y systemic and/or tissue specific biomarkers with study drng response, including 
efficacy and/or AEs and to increase knowledge and understanding of the biology of gastric 
adenocarcinoma and/or the validation of a companion diagnostic for andecaliximab. The specific 
analyses may include, but will not be limited to, the biomarkers and assays listed below. Because 
biomarker science is a rapidly evolving area of investigation, and AEs in paiiicular ai·e difficult 
to predict, it is not possible to specify prospectively all tests that will be done on the specimens 
provided. The testing is based upon the cmTent state of scientific knowledge. It may be modified 
dming 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 a1i knowledge. Any futme testing must be approved by local 
authorities as applicable according to specific local regulations. 
3.10.1.1. 
PD-Ll Biomarker Test for Stratification 
PD-Ll will be assessed by immunohistochemistiy (IHC). Archival tumor tissue is required, 
preferably from the most recent available biopsy or smgical resection. Archival FFPE blocks ai·e 
prefeITed. The centi·al laborato1y pathologist will ce1i ify the presence of sufficient tumor tissue. 
Tumor tissue is also requested for other biomai·ker tests in Table 3-1. 
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Phaimacodynamic Biomai·kers 
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Table 3-1. 
Biomarker Objectives and Testing 
SAMPLE TYPE 
Tissue Biopsy 
(archival): Most recently 
OBJECTIVE 
obtained archival tumor 
Stratification MANDATORY 
biopsy 
Required 
To evaluate potential baseline markers 
that con-elate with response 
Tissue Biopsy: 
On-treatment ( obtained 
To evaluate potential markers that 
betv.•een Weeks 5-9) 
con-elate with treatment and/or response 
Required 
Tissue Biopsy: At 
Progression 
To evaluate potential markers of acquired 
resistance 
If medically feasible 
To evaluate phannacodynamic markers 
of andecaliximab 
To evaluate inflammation and 
chemokines related to T-cell activation 
and other protein markers ofMMP9 
activity 
Blood 
To evaluate circulating immune cells 
To evaluate the impact of treatment 
and/or response on tumor heterogeneity 
To evaluate disease burden and identify 
mutations con-elated with resistance to 
therapy 
Oral sample 
To investigate oral microbiome diversity 
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TEST 
• 
PD-Ll IHC 
• 
MMP9, other MMPs and Immune Cells 
by IHC and other methods 
• 
Tumor gene expression (RNA); IFNy 
gene signature, immune cell signatures, 
• 
Genomic instability 
• 
Somatic tumor DNA mutations 
• 
MMP9, other MMPs, PD-Ll and 
Immune Cells (to include MDSCs and 
proliferating T cells) by IHC and other 
methods 
• 
Tumor gene expression pattems (RNA); 
IFNy signature, immune cell signatures, 
• 
MMP9, other MMPs and Immune Cells 
• 
Tumor gene expression pattems (RNA); 
IFNy signature, immune cell signatures 
• 
MMP9-mediated collagen cleavage 
products (ClM) 
• 
Circulating cytokines, chemokines and 
inflammatory markers 
• 
Immune cell phenotyping by flow 
cytometry 
• 
Immune cell repertoire 
• 
Genomic analysis of circulating tumor 
cells 
• 
Circulating tumor DNA (ctDNA) 
isolation and sequencing 
• 
Characterization of oral microbiome 
diversity 
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Biologic Samples for Optional Future Research 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 120 subjects will be randomized to receive open-label study drug.  The target 
population is subjects with histologically confirmed inoperable locally advanced or metastatic 
adenocarcinoma of the stomach or the GEJ and who have received at least1 prior line of 
therapy. 
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study:
1) Age ≥18 years 
2) Histologically confirmed inoperable locally advanced or metastatic adenocarcinoma of the 
stomach or GEJ which have progressed on at least 1 prior systemic therapy or line of 
treatment for unresectable/metastatic disease
3) Eastern Cooperative Oncology Group (ECOG) ≤1
4) Measurable disease according to RECIST v1.1
5) Tumor sites that can be accessed for repeat biopsies 
6) Archival tumor tissue, preferably obtained from the most recent available biopsy; there must 
be adequate tissue for a PD-L1 stratification test, as assessed by central pathologist
7) All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have 
resolved to grade 1 (NCI CTCAE version 4) or baseline
8) Subjects not receiving anticoagulant medication must have an international normalized ratio 
(INR) ≤1.5 and activated partial thromboplastin (aPTT) ≤1.5 x upper limit of normal 
(ULN). The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR 
or 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 
randomization
9) Adequate hematologic function
a) neutrophils ≥1.5 x 109/L
b) platelets ≥100 x 109/L
c) hemoglobin ≥9 g/dL


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10) Adequate hepatic function
a) Direct or total bilirubin ≤1.5 x ULN
b) ALT and AST ≤2.5 x ULN
11) 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
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, for 
90 days following the last dose of andecaliximab and at least 5 months after the last dose of 
nivolumab, unless the subject chooses continuous heterosexual abstinence as a lifestyle-
choice (see Appendix 4 for more information)
13) For male subjects of reproductive potential having intercourse with females of childbearing 
potential, willingness to use a protocol recommended method of contraception and to refrain 
from sperm donation from the start of study drug, throughout the study treatment period, and 
for 90 days after administration of the last dose of andecaliximab or nivolumab 
(see Appendix 4 for more information)
14) Breastfeeding females must agree to discontinue nursing before study drug administration
15) In the judgment of the investigator, participation in the protocol offers an acceptable 
benefit-to-risk ratio when considering current disease status, medical condition, and the 
potential benefits and risks of alternative treatments for the subject’s cancer
16) Willingness to comply with scheduled visits, drug administration plan, imaging studies, 
laboratory tests, other study procedures, and study restrictions
17) Evidence of a signed informed consent prior to implementation of any protocol specific 
procedure
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
1) Subjects who have received only neoadjuvant or adjuvant therapy for gastric adenocarcinoma
2) Radiotherapy within 28 days of randomization; subjects given palliative radiotherapy to 
peripheral sites (eg, bone metastasis) may enter the study before 28 days have elapsed 
provided the radiated sites do not contain lesions which may be used to evaluate response, 
and must have recovered from any acute, reversible effects
3) Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, 
active gastrointestinal bleeding, uncontrolled cardiac arrhythmia, or psychiatric illness/social 
situation that would limit compliance with study requirements as judged by treating 
physician


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4) 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 randomization; adequately treated Stage 1 or 2 cancer currently in complete 
remission; or any other cancer that has been in complete remission for ≥ 5 years
5) Major surgery, defined as any surgical procedure that involves general anesthesia and a 
significant incision (ie, larger than what is required for placement of central venous access, 
percutaneous feeding tube, or biopsy), within 28 days of first dose of study drug
6) Known positive status for human immunodeficiency virus (HIV)
7) Known acute or chronic-active infection with hepatitis B virus (HBV) or hepatitis C virus 
(HCV)
8) Chronic daily treatment with oral corticosteroids (dose of > 10 mg/day prednisone 
equivalent) or other immunosuppressive medications within 14 days of randomization. 
Inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant 
are allowed
9) Known or suspected central nervous system metastases
10) Known alcohol or drug abuse or any other medical or psychiatric condition which 
contraindicates participation in the study
11) Documented myocardial infarction or unstable/uncontrolled cardiac disease (ie, unstable 
angina, congestive heart failure [New York Heart Association > Class II]) within 6 months of 
randomization
12) Serious systemic fungal, bacterial, viral, or other infection that is not controlled or requires 
intravenous antibiotics
13) Pregnant or breastfeeding women (pregnancy needs to be excluded by testing of beta-human 
chorionic gonadotropin [β-hCG])
14) Experimental medical treatment within 28 days prior to randomization 
15) Known hypersensitivity to andecaliximab or nivolumab or excipients or to Chinese hamster 
ovary cell products or to recombinant human or humanized antibodies
16) Prior treatment with anti-CTLA-4 agents (ipilimumab), anti-PD-1 or anti-PD-L1 agents 
(pembrolizumab, nivolumab), anti-PD-L2 agents, anti-MMP agents, or other 
immunomodulatory therapies
17) Previous severe hypersensitivity reaction to treatment with another monoclonal antibody 
therapy


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18) Subject is expected to require any other form of systemic or localized antineoplastic therapy 
while on study
19) Prior therapy with anti-tumor vaccines or other immuno-modulatory antitumor agents
20) Current or history of pneumonitis or interstitial lung disease
21) 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
22) History of bone marrow, stem cell, or allogeneic organ transplantation


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization
This is an open-label, randomized study.  Randomization to Arm A:  andecaliximab + nivolumab 
or Arm B: nivolumab alone will be based on a randomization schedule prepared by Gilead 
and/or a designee before the start of the study. Eligible subjects will be randomized via an 
interactive web response system (IWRS).
The IWRS will be used to maintain a central log documenting screening, to implement 
randomization, to assess current inventories of study drug, to initiate any necessary resupply of 
study drug, and to document discontinuation of the study drug. 
The IWRS will assign kit numbers and provide instructions for dispensing of study drug 
(andecaliximab+nivolmab/nivolumab alone). It is anticipated that subjects will usually begin 
study drug immediately after randomization.
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.
Nivolumab
Nivolumab is commercially sourced.  Information regarding the formulation can be found in the 
current prescribing information.
5.2.2.
Packaging and Labeling
Study drug andecaliximab (labeled as GS-5745) solution will be supplied in 10 mL glass vials 
with coated elastomeric stoppers and aluminum crimp seals with flip-off caps.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the United States Food and Drug Administration 
(FDA), European Union (EU) guideline to Good Manufacturing Practice – Annex 13 
(investigational medicinal Product(s)), and/or other local requirements. Commercially available 
product of nivolumab will be used for this study.


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5.2.3.
Storage and Handling
Andecaliximab should be stored at 2 to 8 ºC. Storage conditions are specified on the study drug 
label. Until dispensed to the subject, all study drugs should be stored in a securely locked area, 
accessible only to authorized site personnel. To ensure stability and proper identification, the 
study drug should be stored in the containers and packaging in which they were supplied until 
dosing to the subject.
Commercial nivolumab will be used for the study. Further information regarding preparation,
storage, and handling are available in the Prescribing Information or SmPC for nivolumab.
Information regarding preparing andecaliximab IV infusions can be found in the pharmacy 
manual. 
5.3.
Dosage and Administration of Study Drug
For Arm A, andecaliximab will be administered 800 mg via IV infusion over approximately 
30 (± 5) minutes at the research clinic by a qualified staff member on Day 1 and every 2 weeks 
thereafter. Following administration of andecaliximab, nivolumab will be administered 3 mg/kg 
via IV infusion over approximately 60 (± 5) minutes on Day 1 and every 2 weeks thereafter.
For Arm B, nivolumab will be administered 3 mg/kg via IV infusion over approximately 
60 (± 5) minutes on Day 1 and every 2 weeks thereafter.
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.
5.3.1.
Dose Adjustments
If an AE is attributed to only 1 drug (andecaliximab or nivolumab), the investigator’s discretion 
will be used to determine if the drug not attributed to the adverse event will be withheld based on 
the investigator’s assessment of risk-benefit of withholding 1 or both drugs.
5.3.1.1.
Andecaliximab
If a subject experiences a Grade 3 toxicity or greater that is felt to be due to study drug 
andecaliximab, treatment will be postponed until the toxicity is resolved to Grade 0 or 1 
(as defined by CTCAE v 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, the subject may resume 
andecaliximab at the originally assigned dose level. If the subject experiences a recurrence of the 
Grade 3 or greater toxicity after restarting andecaliximab, treatment with andecaliximab will be 
discontinued.
5.3.1.2.
Nivolumab
Please refer to the current nivolumab label or SmPC for your respective region for recommended 
dose modification guidelines and full discontinuation criteria with nivolumab.


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5.4.
Prior and Concomitant Medications
At Screening, all medication taken up to 30 days prior to the screening visit will be recorded on 
the eCRF. At each study visit, the site will capture any and all medications taken by the subject 
since the last visit or during the visit (as applicable). Concomitant medications include 
prescription and non-prescription medications, pre-infusion medications (eg, anti-emetics), and 
vitamins and minerals. 
In addition, supportive therapies given during the course of the study (eg, blood transfusion, 
growth factor) will be collected and recorded on the eCRF. 
During the course of the clinical trial, study subjects are anticipated to continue the use of 
prescribed medications identified during the screening procedures, consistent with study 
inclusion and exclusion criteria. 
Non-study anticancer chemotherapy 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. 
5.4.1.
Acceptable Concomitant Medications
All treatments that the investigator considers necessary for a subject’s welfare may be 
administered at the discretion of the investigator in keeping with the community standards of 
medical care.  All concomitant medication will be recorded on the case report form (CRF) 
including all prescription, over-the-counter (OTC), herbal supplements, and IV medications and 
fluids.  If changes occur during the trial period, documentation of drug dosage, frequency, route, 
and date may also be included on the CRF.
All concomitant medications received within 30 days before the first dose of trial treatment and 
30 days after the last dose of trial treatment should be recorded. 
5.4.2.
Prohibited Concomitant Medications
Subjects are prohibited from receiving the following therapies during the Screening and 
Treatment Phase (including retreatment for post-complete response relapse) of this trial:

Antineoplastic chemotherapy or biological therapy not specified in the protocol

Immunotherapy not specified in this protocol

Investigational agents other than those specified by the protocol


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
Radiation therapy 
Note:  Radiation therapy to a symptomatic solitary lesion or to the brain may be 
considered on an exceptional case-by-case basis after consultation with the Sponsor.  The 
subject must have clear measurable disease outside the radiated field.  Administration of 
palliative radiation therapy will be considered clinical progression for the purposes of 
determining PFS.

Live vaccines within 30 days prior to the first dose of trial treatment and while participating 
in the trial.  Examples of live vaccines include, but are not limited to, the following: measles, 
mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. 
Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed. 
However, intranasal influenza vaccines (eg, Flu - Mist®) are live attenuated vaccines, and 
are not allowed.

Systemic glucocorticoids for any purpose other than to modulate symptoms from an event of 
suspected immunologic etiology.  The use of physiologic doses of corticosteroids may be 
approved after consultation with the Sponsor.
Note:  Inhaled steroids are allowed for management of asthma.
Subjects who, in the assessment by the investigator, require the use of any of the aforementioned 
treatments for clinical management should be removed from the trial.  Subjects may receive 
other medications that the investigator deems to be medically necessary.
The Exclusion Criteria describes other medications that are prohibited in this trial.
There are no prohibited therapies during the Post-Treatment Follow-up Phase.
5.5.
Accountability for Study Drug
The investigator or designee (eg, pharmacist) is responsible for ensuring adequate accountability 
of all used and unused investigational medicinal product during the study. This includes 
acknowledgement of receipt of each shipment of study drug (quantity and condition) and 
tracking of vials assigned/utilized for subject dosing.
Study drug (andecaliximab and or nivolumab) accountability records will be provided to each 
study site to:

Record the date received and quantity of study drug vials

Record the date, subject number, subject initials, the vial number dispensed

Record the date, quantity of used and unused vials returned, along with the initials of the 
person recording the information.


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Dispensing records will include the initials of the person dispensing the study drug or supplies. 
5.5.1.
Study Drug Return or Disposal
The study drugs (andecaliximab and nivolumab) should be disposed of at the site as per local 
standard operating procedures. Please see pharmacy binder for additional instructions (See 
Section 9.1.7 for details). 


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6_ 
STUDY PROCEDURES 
Final 
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The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular fonn in Appendix 2 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 laborato1y variables, physical examinations, vital signs, and special safety 
assessments such as ECGs. 
From the time of obtaining infonned consent through the first administration of study diug, 
record all SAEs, as well as any non-serious AEs related to protocol-mandated procedures on the 
AEs eCRF. All other untoward medical occmTences observed dming the Screening period, 
including exacerbation or changes in medical histo1y are to be captured on the medical histo1y 
eCRF. 
6.1. 
Subject Enrollment and Treatment Assignment 
Subject eligibility will be established at the conclusion of the screening evaluations. The 
screening number and/or subject ID will be assigned for that individual subject by the designated 
IWRS. Subject eligibility must be detennined by results received from the central lab as 
described in Sections 6.2.2 and 6.2.8. 
It is the responsibility of the investigator to ensme that each subject is eligible for the study 
before randoinization. A subject will be considered enrolled once he or she has completed 
randoinization. 
Subjects will undergo procedures defined in Appendix 2. Details regarding randomization and 
treatment assignment are in Section 5 .1. 
6.2. 
Study Procedure Descriptions 
The following sections describe the individual study procedmes outlined in subsequent sections 
and the schedule of assessments. During the treatment period, all visits may be perfo1med within 
the windows identified in Appendix 2. 
6.2.1. 
Informed Consent 
All subjects must sign and date the most recent IRB/IEC-approved infonned consent f01m before 
any study specific procedures are erfonned exce t where noted in the rotocol in relation to 
standard of care rocedmes. 
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6.2.2.
Re-Screening Criteria
Subjects who do not randomize within 28 days of screening will be screen failed. 
Re-screening may be allowed. Subjects who are re-screened after 28 days must be re-consented 
with a new screening number and the screening assessments must be repeated. For subjects that 
are re-screened within 28 days, assessments with results that would exclude the subject will need 
to be repeated.
Subject eligibility must be determined by results received from the central lab. However, if there 
has been at least 1 failed attempt to obtain test results from the central lab, eligibility may be 
determined using local lab results, with documentation of failed attempts, local lab results, and 
sponsor approval.
6.2.3.
Medical & Medication History
A complete medical and surgical history will be obtained by the investigator or designee at 
screening, including disease history, and recorded on the eCRF.
All medications taken within 30 days prior to screening and during the screening period will be 
obtained prior to randomization and 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, 
vitamins and minerals. 
In addition, supportive therapies given during the course of the study (eg, blood transfusion, 
growth factor) should be collected and recorded on the eCRF.
6.2.4.
Physical Examination
A physical examination (PE) will be performed at screening, end of treatment (EOT), and EOS. 
This will include assessment of clinical signs and symptoms. The exam will be performed by a 
physician, a physician’s assistant, or nurse practitioner qualified to perform assessments. Breast, 
genital, and rectal examinations are not required, unless warranted in opinion of the healthcare 
provider. 
A modified physical exam capturing changes from prior exams will be performed on Day 1 and
every 4 weeks thereafter, and at the 30-day Safety Follow-up. Height will be collected at 
Screening only.
6.2.5.
Vital Signs & Weight
Vital signs including blood pressure, heart rate, respiratory rate, and oral temperature will be 
measured by the investigator or qualified designee as per standard institutional guidelines at each 
study visit as indicated in Appendix 2. Weight will be collected at the same visits vital signs are 
taken.


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6.2.6.
Electrocardiogram Assessment
A single 12-lead electrocardiogram (ECG) will be collected at Screening, Day 1, and every 
4 weeks thereafter at subsequent visits, and at the EOT and EOS visits, as indicated in 
Appendix 2. The investigator will review all ECGs and retain the tracing with the source 
documents.
6.2.7.
Performance Status
Performance status will be scored using the ECOG performance status scale index 
(refer to Appendix 3), at Screening, Day 1 and every 4 weeks thereafter, EOT, EOS, and 30-day 
Safety Follow-up visits. ECOG used to determine eligibility must be the performance status 
during the screening period. ECOG performance status on Day 1 may be waived if it was 
conducted during screening within 4 days of Day 1. 
6.2.8.
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. The date and time of sample collection will be reported to the 
central laboratory.
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 AE assessment, which is 
not supported by central lab results, will be reported on the eCRF.
Urine pregnancy test will be performed locally at the site. 


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Table 6-1.
Analytes
Chemistry
Urinalysis
Hematology 
Other 
Albumin
Alkaline phosphatase
ALT 
AST 
Bicarbonate
BUN
Calcium
Chloride
Creatininea
Glucose
Lipase
Amylase
Magnesium
Phosphorus
Potassium
Sodium
Total bilirubin
Direct bilirubin
Total protein
CEA
CA125
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-hCG or urine 
pregnancy testc
Thyroid Function Tests (TSH, 
T3, freeT4)d
Coagulation
PT/INR
aPTT
ANC = absolute neutrophil count; ALT = alanine aminotransferase; aPTT = Activated Partial Thromboplastin Time; 
AST = aspartate aminotransferase; BUN = blood urea nitrogen; CEA=carcinoembryonic antigen; β-hCG = beta-human
chorionic gonadotropin; INR = International Normalized Ratio; PT = Prothrombin Time; WBC = white blood cell; 
CA125 = Carbohydrate Antigen 125; TSH = thyroid stimulating hormone; T3 = triiodothyronine; Free T4 = free thyroxine
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 will be 
conducted pre-dose on Day 1, every 4 weeks thereafter, at EOT, and EOS, 30-day, and 5-month Safety Follow-up
d
TSH, T3, and free T4 will be tested by the central laboratory at screening. From Week 8 and beyond, T3 and T4 will be 
tested reflexively based on abnormal TSH results.
Screening laboratory samples should be obtained within 28 days prior to randomization. Blood 
samples will be obtained for hematology, chemistry, coagulation, thyroid function, and 
pregnancy testing for female subjects. A urine sample will also be obtained at screening for 
urinalysis.
Blood samples for hematology and chemistry will be obtained at pre-dose on Day 1 and every 
2 weeks thereafter, EOT, EOS, 30-day, and 5-month Safety Follow-up. Blood samples for 
Thyroid Function Tests (TSH, T3, free T4) will be collected every 8 weeks, and at EOT, EOS, 
30-day, and 5-month Safety Follow-up. A urine sample for urinalysis and pregnancy testing for 
female subjects will also be obtained on Day 1 and every 4 weeks thereafter, EOT, EOS, 30-day,
and 5-month Safety Follow-up. Blood samples for coagulation will be obtained at EOT and EOS.


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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.
6.2.8.1.
Pregnancy Test
All females of childbearing potential (see Appendix 4) will have a serum pregnancy test at 
screening. Urine pregnancy tests will be performed every 4 weeks starting on Day 1, EOT, EOS, 
30-day, and 5-month Safety Follow-up.
6.2.8.2.
Pretreatment, On-treatment and Progression Biopsies

If biopsies are endoscopic gastric, at least 4 biopsies at each time-point (pre-treatment, 
on-treatment, and at progression) should be obtained. If biopsies are from other sites, core 
needle biopsies, excisional, resections, incisional, or punch biopsies are acceptable. For core 
needle biopsies, at least 3 cores should be collected. Refer to the laboratory manual for tissue 
processing instructions. It is preferred that on treatment and progression biopsies be taken 
from primary (gastric or GEJ tissue) lesions and/or the same site as the pre-treatment (or
archival) tissue.  If tissue is not available or accessible from the primary lesion (gastric or 
GEJ tissue), biopsies of metastatic lesions are acceptable.  Pre-treatment: To be obtained
within the screening window or any time after last line of therapy; The pretreatment biopsy is
requested if archival tumor sample provided to meet Inclusion Criterion #6 is from before the 
last line of therapy

On-treatment: To be obtained anytime within the window of Week 5 through Week 9

At progression: To be obtained at disease progression (if medically feasible)
6.2.8.3.
Anti-Andecaliximab Antibody
For Arm A only, blood samples for anti-andecaliximab antibody will be collected prior to dosing 
at the following visits: Day 1, Weeks 4, 8, 16, 24, and every 3 months thereafter, and at the EOT 
and EOS visits. 
6.2.8.4.
Andecaliximab Pharmacokinetics
For Arm A only, blood plasma samples will be collected for andecaliximab PK at 30 (± 
15) minutes after the end of infusion on Day 1, prior to dosing, and 30 (± 15) minutes after the 
end of infusion at Weeks 4, 8, 16, 24, and every 3 months thereafter, and at the EOT and EOS 
visits. 


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6.2.8.5. 
Biomarkers 
Final 
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Samples for biomarker analysis as listed in Table 3-1 will be collected as follows and in 
Appendix 2: 
• 
Blood biomarker samples will be collected at screening, prior to dosing on Day 1, Weeks 2, 
4, 8, 16, 24, and eve1y 3 months thereafter, and at EOS or at disease progression. 
• 
An oral sample (saliva or other) for characterization of oral microbiome diversity will be 
collected prior to dosing on Day 1. 
I 
6.2.9. 
6.2.9.1. 
Disease and Response Assessment 
Efficacy Measurement 
RECIST version 1.1 {Eisenhauer 2009} [ Appendix 5] 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 anti tumor 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-I 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, RECIST 1.1 will be used [Appendix 5] with the following adaptations: 
If imaging shows a CR or PR, tumor imaging should be repeated at least 4 weeks (~4 weeks) 
later to confnm response, per RECIST 1.1 guidelines. Subjects will then return to regular 
scheduled imaging eve1y 8 weeks staii ing with the next protocol-specified imaging time-point. 
Subjects who obtain a confnmato1y scan do not need to undergo scheduled imaging assessment 
:S2 weeks later (eg, if a subject obtains a scan at Week 22 to confnm 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 confnm 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 confmnation. The decision to 
continue a subject on study while awaiting PD confnmation will be based on clinical judgment 
of a subject's overall clinical condition, including perfonnance status, clinical symptoms, and 
laborato1y data. 
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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 
(eg, cord compression) requiring urgent alternative medical intervention
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 6.2.9.2).
When feasible, subjects should not be discontinued until progression is confirmed; investigators 
should discuss with the Gilead Medical Monitor prior to subject discontinuation.  
6.2.9.2.
Tumor Imaging 
Contrast-enhanced CT (without contrast if use of contrast is contraindicated) or gadolinium-
enhanced MRI of the chest, abdomen, and pelvis will be performed at screening, every 8 weeks 
during the study and at the EOS visit if one has not been performed within the last 8 weeks. CT 
is the preferred imaging modality for this study. Tumor burden will be evaluated solely based on 
radiographic imaging per RECIST v 1.1, with the modifications noted in Section 6.2.9.1. Chest 
x-ray, ultrasound, endoscopy, laparoscopy, positron-emission tomography, radionuclide scans, or 
tumor markers will not be considered for response assessment.


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For radiographic evaluations, it is recommended that 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. Local site study team reading (investigator assessment with site 
radiology reading) based on RECIST 1.1 will be used to determine subject eligibility.
Scans taken as part of standard medical practice up to 28 days prior to randomization can be used 
for Screening as long as they are of diagnostic quality and meet all study requirements. During 
the treatment phase, scans may be performed at time points other than every 8 weeks as 
clinically indicated to assess tumor progression. 
For subjects who stop study treatment in the absence of disease progression (eg, experienced 
unexpected toxicity), scans should continue to be collected approximately every 8 weeks until 
disease progression or initiation of systemic anti-tumor therapy other than the study treatment, 
whichever is earlier. 
All relevant clinical and radiographic information required to make each assessment must be 
made available for source verification and submission to a central reader. 
 
Disease progression 
will be determined by the investigator or qualified designee.
Imaging should be continued at protocol-specified intervals until whichever of the following 
occurs first: 

Initial site-assessed disease progression is confirmed

The start of new anti-cancer treatment

Withdrawal of consent

Death 

The end of the study
6.2.10.
Study Drug Administration 
For Arm A, andecaliximab will be administered via IV infusion over approximately 30 (± 
5) minutes on Day 1 and every 2 weeks thereafter. Following andecaliximab dosing, subjects 
will also be administered nivolumab via IV infusion over approximately 60 (± 5) minutes. 
For Arm B, nivolumab will be administered via IV infusion over approximately 
60 (± 5) minutes.  
Study drug dosing must be documented on the eCRF.
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6.2.11.
Adverse Events
From the time of obtaining informed consent through the first administration of study drug, 
record all SAEs as well as any AEs related to protocol-mandated procedures on the AE 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.
From the time of the first administration of study drug through 30 days post the last 
administration of andecaliximab and 5 months post-treatment of nivolumab, record any SAEs, 
and AEs including exacerbation or changes in medical history, on the AE eCRF.
See Section 7 Adverse Events and Toxicity Management for additional details.
6.3.
Assessments for Premature Discontinuation from Study
If a subject has discontinued all study treatments prior to definitive disease progression, the 
subject shall remain on study for follow-up for progression-free survival (see Sections 3.5 and 
3.6). 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. Subjects will remain on study until disease 
progression or initiation of non-study specific anti-neoplastic therapy in the absence of 
progression, whichever occurs earlier.
If it is not possible to keep the subject on study, or acceptable to the subject or investigator, the 
subject may be withdrawn. 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.
6.4.
Criteria for Discontinuation of Study Treatment
See Section 3.5 for discontinuation criteria.
6.5.
End of Treatment
End of treatment (EOT) assessments will be completed only by subjects who discontinue all 
treatment for reasons other than progressive disease, initiation of new anti-neoplastic therapy, or 
full withdrawal of consent.  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.   
6.6.
End of Study
End of study (EOS) assessments will be completed when the subject meets at least 1 of the 
criteria for study discontinuation (Section 3.7).


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6.7.
30-Day Safety Follow-Up
A Safety Follow-up visit will be performed 30 days (7 days) following 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.
6.8.
5-Month Safety Follow-Up
A Safety Follow-up visit will be performed 5 months (7 days) following the last dose of 
nivolumab. The 5-Month Safety Follow-up visit may be substituted by a scheduled study visit if 
it occurs within the same window.
6.9.
Long-Term Follow-Up
Long term follow-up for OS begins once a subject discontinues study for reasons other than 
death. Subjects will be contacted via phone call every 3 months for determination of long-term 
survival status and recording of any other anti-cancer therapy and cancer related surgery 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. 
The investigator will make every effort to contact the subject or a close relative or caretaker by 
phone to collect survival information. The investigator should show due diligence by 
documenting in the source documents steps taken to contact the subject (ie, dates of phone calls, 
registered letters, etc).
6.10.
Unscheduled visits
Unscheduled visits may occur at any time while the subject is enrolled on study. Data generated 
during an unscheduled visit will be collected on the eCRF.
6.11.
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 
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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 

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 adenocarcinoma

Death related to disease progression
These events will be exempt from global expedited reporting requirements for the duration of the 
study as they are key 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 7.6.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified subinvestigator 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 subinvestigator 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 study drug. For 
SAEs, an alternative causality must be provided (eg, pre-existing condition, underlying 
disease, intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.
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
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the eCRF: 

All SAEs and adverse events related to protocol-mandated procedures
7.3.1.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 30 days after last administration of study drug 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 study drug 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. 
7.3.2.1.
Electronic Serious Adverse Event (eSAE) Reporting Process

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to Gilead DSPH within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.


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• If for any reason it is not possible to record the SAE infonnation electronically (ie, the eCRF 
database is not functioning) record the SAE on the paper serious adverse event repo1ting 
fo1m and submit within 24 hours to: 
Gilead DSPH: 
Fax: 
Email: 
• 
As soon as it is possible to do so, any SAE repo1ted via paper must be transcribed 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 repo1ts, autopsy repo1ts, and other 
documents are also to be submitted by e-mail or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the ti·aceability of a document to the subject identifiers. 
• 
Additional infonnation may be requested to ensure the timely completion of accurate safety 
repo1ts. 
• 
Any medications necessaiy for ti·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. 
7.4. 
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 countiy-specific legislation or regulations, Gilead may be required to expedite 
to worldwide regulato1y agencies repo1ts of SAEs, SAD Rs, 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 regulato1y agencies and the relevant IEC in 
concerned Member States of applicable SUSARs as outlined in cmTent regulations. 
Assessment of expectedness for SAEs will be dete1mined by Gilead using reference safety 
info1mation specified in the IB or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR repo1ts associated 
with any study dmg. The investigator should notify the IRB/IEC of SUSAR repo1ts as soon as is 
practical, where this is required by local regulato1y 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 
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. Please see Section 5.3 and refer to the regional prescribing 
information for details of toxicity management with nivolumab.
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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7.7.2.1. 
Instructions for Reporting Special Situations 
Instiuctions for Repo1iing Pregnancies 
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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 abo1iion 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 abo1iion 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 or Gilead DSPH using the pregnancy outcome 
repo1i fonn. 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: 
Fax: 
Email: 
PD 
PD 
Refer to Appendix 4 for Pregnancy Precautions, Definition for Female of Childbeai·ing Potential, 
and Contraceptive 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 concomitant medications. 
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Special situations involving non-Gilead concomitant medications does 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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8.1. 
8.1.1. 
STATISTICAL CONSIDERATIONS 
Analysis Objectives and Endpoints 
Analysis Objectives 
The prima1y objective of this study is: 
Final 
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• 
To evaluate and compare the efficacy of andecaliximab in combination with nivolumab 
versus nivolumab alone in subjects with recunent gastric adenocarcinoma 
The secondaiy objectives of this study ai·e: 
• 
To chai·acterize and compai·e safety and tolerability of andecaliximab in combination with 
nivolumab versus nivolumab alone in subjects with recmTent gastric adenocarcinoma 
• 
To chai·acterize the PK of andecaliximab in combination with nivolumab 
The explorato1y objectives of this study are: 
I 
I 
I 
I 
I 
8.1.2. 
Primary Endpoint 
The prima1y endpoint of this study is ORR. ORR will be detennined from the subjects' best 
response dming treatment. 
8.1.3. 
Secondary Endpoint 
The secondaiy endpoints of this study are: 
• 
Progression free smvival, defined as the interval from the date of randomization to the earlier 
of the first documentation of definitive disease progression or death from any cause. 
• 
Overall survival, defined as the interval from date of randomization to death from any cause. 
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• 
Duration ofresponse, defined as the interval from the date of the first response (CR or PR) is 
achieved to the earlier of the first docmnentation of definitive disease progression or death 
from any cause. 
• 
OccmTence of adverse events and laborato1y abno1malities during treatment. 
8.1.4. 
Other Endpoints of Interest 
The explorato1y endpoints of this study are: 
I 
I 
8.2. 
8.2.1. 
8.2.1.1. 
Analysis Conventions 
Analysis Sets 
Intent-to-Treat (ITT) Analysis Set 
The ITT analysis set includes data from all randomized subjects. Study diu g assignment will be 
designated according to randomization. 
This analysis set will be used in the analyses of subject characteristics, OS, PFS, and ORR. The 
analysis of ORR based on the ITT analysis set will be considered the primaiy analysis of the 
study. The analyses of DOR will be based on the subjects in the ITT analysis set who achieve a 
CR or PR. 
Subjects in the ITT analysis set who do not have sufficient baseline or on-study tumor status 
info1mation to be adequately assessed for response status (ie, those with best overall responses of 
not evaluable [NE] or not detected [ND]) will be included in the denominators in calculations of 
response rates. 
8.2.1.2. 
Safety Analysis Set 
The Safety Analysis Set will include data from all subjects who receive 1 dose of study 
treatment, with treatment assignments designated according to the actual treatment received. 
This analysis set will be used in the analysis of safety vai·iables as well as study treatment 
administration. All data collected up to 30 days after the last dose of andecaliximab or 5 months 
post-treatment of nivolmnab, whichever is later, will be included in the safety sUllllllaries. 
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8.2.1.3.
Pharmacodynamic and Pharmacokinetic Analysis Sets
The Pharmacodynamics and PK Analysis Sets will include data from subjects in the Safety 
Analysis Set who have the necessary baseline and on-study measurements to provide 
interpretable results for the specific parameters of interest.
8.3.
Data Handling Conventions
By-subject listings will be created for important variables from each eCRF module. Summary
tables for continuous variables will contain the following statistics: N (number in population), n 
(number with data), mean, standard deviation, 95% confidence intervals (CIs) on the mean,
median, minimum, and maximum. Summary tables for categorical variables will include: N, n,
percentage, and 95% CIs on the percentage. Unless otherwise indicated, 95% 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 or inadequate 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 or inadequate tumor 
assessments will be censored at the last time prior to the missing assessments that lack of 
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8.4.
Demographic Data and Baseline Characteristics
Demographic summaries will include sex, race/ethnicity, randomization stratification group, and 
age.
Baseline characteristics will include a summary of body weight, height, and body mass index.
Demographic and baseline characteristics will be summarized using standard descriptive 
methods.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The null hypothesis is that addition of andecaliximab to nivolumab will not improve ORR. The 
alternative hypothesis is that addition of andecaliximab to nivolumab will improve ORR.
The Cochran-Mantel-Haenszel (CMH) Chi-square test adjusting for stratification factors will be 
performed to compare the 2 treatment groups. Subjects who do not have sufficient baseline or 
on-study tumor assessment to characterize response will be counted as failures. Odds ratios and 
the corresponding 80% and 95% CIs will be presented.
8.5.2.
Secondary Analyses
The KM method and the stratified log-rank test will be used to compare the 2 treatment groups 
for PFS and OS. A Cox proportional hazard model with the same stratification factors will be 
used to estimate the hazard ratio and corresponding 95% CI. DOR will be analyzed using the 
KM method.
8.6.
Safety Analysis
All safety data collected on or after the date that andecaliximab/nivolumab was first 
administered up to 30 days after the last dose of andecaliximab or 5 months post-treatment of 
nivolumab, whichever is later, will be summarized by treatment group (according to the 
treatment received). Data for the pre-treatment and post-treatment follow-up period will be 
included in data listings.
In general, count and percent of subjects will summarize categorical and ordinal data. 
Mean, standard deviation, minimum, quartiles, median, and maximum will summarize 
continuous data.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to andecaliximab and nivolumab will be generated from the study 
drug administration eCRF page. Exposure data will be summarized by treatment group.


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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 (PT), 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 
AE is defined as any AE with onset date on or after the date of first dose of study drug up to 
30 days after permanent study drug discontinuation or any adverse events leading to premature 
study drug discontinuation.
Summaries (number and percentage of subjects) of treatment-emergent AEs (by SOC and PT) 
will be provided by treatment group
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). Maximum 
post-baseline grade will be summarized by count and percent of subjects with each grade.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time post-baseline, will be summarized by treatment group. 
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 study drug will be included in data 
listings.
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 concentrations 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). Plasma concentrations of 
the study drug over time may be plotted in semi logarithmic and linear formats as mean 
standard deviation.
Exposure-response analysis may be explored as appropriate.


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The number and percentage of positive or negative anti-andecaliximab antibody values at each 
specified time-point will be summarized. The effect of anti-andecaliximab antibody on 
andecaliximab PK, safety, and efficacy may be evaluated. 
8.8. 
Biomarker Analysis 
Descriptive statistics of baseline and chan e in biomarkers will be 
time for all sub· ects b treatment aim s. 
8.9. 
Interim Safety Analysis 
After approximately 20 subjects ai·e treated for 12 weeks, a DMC will review safety data on 
these subjects and recommend to Gilead whether the treatment has demonstrated acceptable 
tolerability. Thereafter, review of safety data will be peifonned at regulai· intervals as described 
in the DMC chaiier. 
8.10. 
Sample Size 
Assuming the ORR for subjects ti·eated with nivolumab alone is 25%, 120 subjects in total are 
needed to detect an improvement of20% in ORR for subjects treated with andecaliximab and 
nivolumab with approximately 83% power at one-sided significance level of 10% using a CMH 
test. The assumption of nivolumab ORR is based on the upper bound of the 95% CI of the 
estimated ORR in CheckMate-032 Study {Le 2016}. 
8.11. 
Data Monitoring Committee 
In addition to the review of the interim safety analysis after approximately 20 subjects are ti·eated 
12 weeks, a DMC will review the progress of the study and perfo1m interim reviews of safety 
data at inte1vals as described in the DMC chaiier and provide recommendations to Gilead 
whether the nature, frequency, and severity of adverse effects associated with study ti·eatment 
wairnnt the eai·ly te1mination of the study in the best interests of the paiiicipants, whether the 
study should continue as planned, or the study should continue with modifications. The DMC 
may also provide recommendations as needed regai·ding study design. 
The DMC's specific activities will be defined by a mutually agreed chaiier, which will define the 
DMC's membership, conduct, and meeting schedule. 
While the DMC will be asked to advise Gilead regarding future conduct of the study, including 
possible eai·ly study tennination, Gilead retains final decision-making authority on all aspects of 
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. These standards are consistent with the European Union Clinical 
Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
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 any modifications made to the protocol or any accompanying material to be 
provided to the subject after initial IRB/IEC 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. 


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The investigator must use the most current IRB/IEC approved consent form for documenting 
written 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 genomic testing and sample retention, 
and their right to receive clinically relevant genomic 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 study drug, and any other study information, 
remain the sole and exclusive property of Gilead during the conduct of the study and thereafter. 
This information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following 2 categories: (1) investigator’s study file, and (2) subject 
clinical source documents.
The investigator’s study file will contain the protocol/amendments, 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, physical examination, 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 study drug, 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. The eCRF 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 


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eligibility have been received.  Subsequent to data entry, a study monitor will perform source 
data 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 (eg, 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.
Study Drug Accountability and Return
Gilead recommends that used and unused study drug supplies be returned to the shipping facility 
from which it came for eventual destruction. The study monitor will provide instructions for 
return. If return is not possible, the study monitor will evaluate each study center’s study drug 
disposal procedures and provide appropriate instruction for destruction of unused study drug
supplies. If the site has an appropriate standard operating procedure (SOP) for drug destruction
as determined by Gilead, the site may destroy used (empty or partially empty) and unused 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. 
If study drug is destroyed on site, the investigator must maintain accurate records for all study 
drug destroyed. 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.
The study monitor will review study drug supplies and associated records at periodic intervals.
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 IRB/IEC, 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/IECapproval 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
Appendix 3.
ECOG Performance Status
Appendix 4.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 5.
Revised RECIST Guideline (version 1.1)


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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
Final 
Amendment 3 
A Phase 2, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of GS-5745 
Combined with Nivolumab versus Nivolumab Alone in Subjects with Unresectable or 
Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma 
GS-US-296-2013, Amendment 3, 16 June 2017 
This protocol has been approved by Gilead Sciences, Inc. The foJlowing signature documents 
this approval. 
PD 
PPD 
(Printed) 
PPD 
Gilead Sciences 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 aJl study personnel under my supervision copies of the protocol and access to all 
infonnation 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 
Page 86 
16 June 2017 


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Appendix 2.
Study Procedures Table
Period
Screening
Randomization a
Treatment
EOTm
Disease 
Progression
EOSn
30 day Safety 
Follow-upo
5-month Safety 
Follow-Upp
Long Term 
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14 to 50
Week
-4
Day 1
2
4
6
8
10
12
14
16
18
20
22
24 to 96
Window (day)
-28
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±7
±7
±7
Informed Consent
X
Medical and 
Medication History 
X
Physical 
Examinationb
X
X
X
X
X
X
X
Xs
X
X
X
Vital Signs & 
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECOG Performance 
Statusc
X
Xc
X
X
X
X
X
Xs
X
X
X
12-lead ECG
X
X
X
X
X
X
X
Xs
X
X
Adverse events/
Concomitant 
Medicationsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IWRS Registration
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study Drug/
Nivolumab 
Administratione
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


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Period
Screening
Randomization a
Treatment
EOTm
Disease 
Progression
EOSn
30 day Safety 
Follow-upo
5-month Safety 
Follow-Upp
Long Term 
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14 to 50
Week
-4
Day 1
2
4
6
8
10
12
14
16
18
20
22
24 to 96
Window (day)
-28
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±7
±7
±7
Chemistry
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Thyroid Function 
Tests (TSH, T3, free 
T4)
X
X
X
Xt
X
X
X
X
Coagulation
X
X
X
Urinalysis 
X
X
X
X
X
X
X
Xs
X
X
X
X
Pregnancy Testf
X
X
X
X
X
X
X
Xs
X
X
X
X
Andecaliximab PKg
X
X
X
X
Xr
X
X
Anti-Andecaliximab
Antibodyh
X
X
X
X
Xr
X
X
Blood Biomarkersi
X
X
X
X
X
X
Xr
Xi
Xi
Oral Sampling
X
CT or MRI & 
Treatment Response 
Assessmentk
X
X
X
Xt
Xq
X
CCI


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Amendment 3
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Period
Screening
Randomization a
Treatment
EOTm
Disease 
Progression
EOSn
30 day Safety 
Follow-upo
5-month Safety 
Follow-Upp
Long Term 
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14 to 50
Week
-4
Day 1
2
4
6
8
10
12
14
16
18
20
22
24 to 96
Window (day)
-28
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±7
±7
±7
Tumor Biopsyl
Xl
Xl
(Wk 5 through Wk 9)
Xl
Overall Survival and 
Other Antitumor 
Therapy
Xu
a
Day 1 visit must occur within 3 days following randomization.
b
Complete physical examination (PE) to be performed at Screening, EOT and EOS. A modified PE capturing changes from prior exams will be performed at subsequent visits. 
Height is required at Screening only.
c
ECOG performance status on Day 1 may be waived if has been conducted during screening within 4 days of Day 1. 
d
Adverse events will be assessed and concomitant medications will be recorded at each clinic visit from Screening up to and including the 30-day Safety Follow-up visit or 
EOS visit whichever is later.  
e
For Arm A: Study drug andecaliximab (800 mg) will be administered via IV infusion every 2 weeks over 30 (± 5) min. Nivolumab (3 mg/kg) will be administered via IV 
infusion following the completion of andecaliximab every 2 weeks over 60 (± 5) min. For Arm B: Nivolumab alone (3 mg/kg) will be administered via IV infusion every 
2 weeks over 60 (± 5) min.
f
If applicable (females of child bearing potential). Serum pregnancy testing will be conducted at Screening. Urine pregnancy testing will be conducted pre-dose on Day 1 and 
then every 4 weeks, at EOT, and EOS, 30-day, and 5-month Safety Follow-up.
g
For Arm A only, plasma samples will be collected for andecaliximab PK at 30(± 15) min after the end of infusion on Day 1.  For Weeks 4, 8, 16, and 24 and every 3 months
thereafter, PK will be collected prior to dosing and 30(± 15) min after the end of infusion.  It will also be collected at EOT and EOS.      
h
For Arm A only,  serum samples for anti-andecaliximab antibody will be collected prior to dosing on Day 1, Week 4, Week 8, Week 16, Week 24, and every 3 months 
thereafter, EOT and EOS.
i
Blood biomarkers will be collected at screening and prior to dosing on Day 1; Week 2; Week 4; Week 8; Week 16; Week 24 and every 3 months thereafter and at progression 
or EOS.
k
Tumor evaluation by CT or MRI will be performed during screening and approximately every 8 weeks regardless of visit week or dose interruption. Scan at EOS visit is not 
necessary if restaging scan is performed within the prior 8 weeks. Treatment response assessment will be per RECIST v1.1.
For subjects who stop study treatment in the absence of disease progression (eg. experienced unexpected toxicity) and remain on study for follow up for progression-free 
survival, tumor evaluation by CT or MRI should continue approximately every 8 weeks until disease progression or initiation of non-study specific anti-neoplastic therapy in 
the absence of progression, whichever occurs earlier.
CCII 


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l
A pretreatment biopsy is requested if archival tumor sample provided to meet Inclusion Criterion #6 is from before the last line of therapy. An on-treatment biopsy is required 
between Week 5 and Week 9. A biopsy at disease progression is requested, if medically feasible. The sample should be collected by the last clinic visit on study ie EOS or 
30 Day Safety Follow up visit. All biopsies are requested to be from gastric lesions if possible (non-gastric metastatic lesions ok if no gastric lesions possible). See laboratory 
manual for biopsy specifications and procedures.
m
End of treatment (EOT) assessments will be completed only by subjects who discontinue all treatment for reasons other than progressive disease, initiation of new anti-
neoplastic treatment, or full withdrawal of consent.  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 approximately every 8 weeks until disease progression.
n
End of study (EOS) assessments will be completed when a subject meets at least 1 of the criteria for study discontinuation (Section 3.7).
o
The 30-day safety follow up visit will be performed following the last dose of andecaliximab.  
p
The 5-month safety follow up visit will be performed following the last dose of nivolumab. 
q
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 (see section 6.2.9).
r
Starting at Week 24, perform every 12 weeks until EOT/EOS.
s
Starting at Week 24, perform every 4 weeks until EOT/EOS.
t
Starting at Week 24, perform every 8 weeks until EOT/EOS.
u
Perform every 3 months until 5 years.


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Appendix 3.
ECOG Performance Status
Grade
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all self-care but unable to carry out any work activities.
Up and about more than 50% of waking hours
3
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5
Dead
Reference for ECOG {Oken 1982}


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Appendix 4.
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 is not expected given that andecaliximab is a monoclonal 
antibody. 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. A 
clinically relevant interaction between andecaliximab and contraceptive steroids is not expected 
because of their distinct metabolic pathways and therefore, hormonal contraception may be used 
as part of the birth control methods.
Please refer to the latest version of the investigator’s brochure for additional information.
Please refer to the regional prescribing information for information on the potential risks of 
treatment with nivolumab. 
2) Definition of Female of Childbearing Potential
For the purposes of this study, a female subject of childbearing potential is a woman who has not 
had a hysterectomy, bilateral oophorectomy, or medically documented ovarian failure. This 
definition includes pubertal females regardless of whether or not she has had a menses 
(premenarchal, Tanner Stage 3) and perimenopausal women who have had a spontaneous 
menses in the last 12 months. A woman who has had a tubal sterilization is considered to be of 
childbearing potential.

Women ≤ 54 years of age with amenorrhea of any duration will be considered to be of 
childbearing potential unless they have had a hysterectomy, bilateral oophorectomy, or 
medically documented ovarian failure.

Women > 54 years of age with cessation (for ≥12 months) of previously occurring menses 
due to ovarian failure will not be considered to be of childbearing potential.
3) Contraceptive Requirements for Females
Female subjects of childbearing potential must agree to use protocol specified highly effective 
method(s) of contraception from the screening/randomization visit throughout the study period, 
90 days following the last dose of study drug andecaliximab and 5 months after the last dose of 
nivolumab unless the subject chooses continuous heterosexual abstinence as a lifestyle choice. 
The investigator should counsel subjects on the protocol specified method(s) for avoiding 
pregnancy during the study. See the listed below for the protocol specified contraceptive 
methods. 


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Female study subjects who are not heterosexually active must have periodic confirmation of 
continued abstinence from heterosexual intercourse and regular pregnancy testing while taking 
study drug. The investigator should counsel subjects on the protocol specified method(s) for 
avoiding pregnancy in case the subject chooses to engage in heterosexual intercourse.
Female subjects of childbearing potential must have a negative serum pregnancy test at screening 
and a negative urine pregnancy test every 4 weeks starting on Day 1, prior to receiving the dose 
of study drug. Lactating females must discontinue nursing before study drug administration.
Protocol specified contraceptive methods:

Complete abstinence from intercourse. Periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) is not permitted.
Or

Consistent and correct use of 1 of the following methods of birth control listed below, 
in addition to a male partner who correctly uses a condom from the date of Screening until
90 days after last dose of study drug andecaliximab and 5 months after the last dose of 
nivolumab:
intrauterine device (IUD) with a failure rate of < 1% per year
female barrier method: cervical cap or diaphragm with spermicidal agent
tubal sterilization
vasectomy in male partner
implants of levonorgestrel
injectable progesterone
oral contraceptives (either combined or progesterone only)
contraceptive vaginal ring
transdermal contraceptive patch
Female subjects must agree to refrain from egg donation or egg harvesting for the purpose of 
fertilization during the course of the study for at least 90 days after the last dose of 
andecaliximab and 5 months after the last dose of nivolumab.


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Amendment 3
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4) Contraceptive Requirements for Males
Male subjects must agree to use condoms and avoid sperm donation from the 
screening/randomization visit throughout the study period, and for at least 90 days after 
administration of the last dose of study drug andecaliximab or nivolumab.
5) Procedures to be Followed in the Event of Pregnancy
Subjects should be instructed to notify the investigator if they (or their partner) become pregnant 
at any time during the study, or if they become pregnant within 90 days following the last dose 
of andecaliximab and within 5 months after 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. The investigator should report all 
pregnancies to the CRO Safety Department using the pregnancy report form within 24 hours of 
becoming aware of the pregnancy. The investigator should counsel the subject regarding the 
possible effects of prior study drug exposure on the fetus and the need to inform the study site of 
the outcome of the pregnancy. Subjects whose partner has become pregnant or suspects she is 
pregnant during the study must report the information to the investigator. Instructions for 
reporting partner pregnancy, pregnancy and pregnancy outcome are outlined in Section 7.7.2.1.


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Appendix 5.
Revised RECIST Guideline (version 1.1)
Please see reference (E.A. Eisenhower, 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
SD
SD
Non-PD or not all 
evaluated
No
NE
Not all evaluated
Non-PD
No
PD
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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Amendment 3
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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 2, Open-Label, Randomized Study to Evaluate the 
Efficacy and Safety of Andecaliximab (GS-5745) Combined 
with Nivolumab versus Nivolumab Alone in Subjects with 
Unresectable or Recurrent Gastric or Gastroesophageal 
Junction Adenocarcinoma
Name of Test Drug:
Andecaliximab (GS-5745)
Study Number:
GS-US-296-2013
Protocol Version (Date):
Amendment 3
Analysis Type:
Final
Analysis Plan Version:
1.0
Analysis Plan Date:
06 Dec 2017
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
1.
INTRODUCTION ................................................................................................................................................7
1.1.
Study Objectives ......................................................................................................................................7
1.2.
Study Design............................................................................................................................................7
1.3.
Sample Size and Power............................................................................................................................8
2.
TYPE OF PLANNED ANALYSIS ......................................................................................................................9
2.1.
Interim Analyses ......................................................................................................................................9
2.2.
Primary Analysis......................................................................................................................................9
2.3.
Follow-up Analysis ..................................................................................................................................9
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................10
3.1.
Analysis Sets..........................................................................................................................................10
3.1.1.
Intent-to-Treat Analysis Set .................................................................................................10
3.1.2.
Safety Analysis Set...............................................................................................................10
3.1.3.
Per-Protocol Analysis Set.....................................................................................................10
3.1.4.
Pharmacokinetic Analysis Set..............................................................................................11
3.1.5.
Immunogenicity Analysis Set ..............................................................................................11
3.2.
Subject Grouping ...................................................................................................................................11
3.3.
Strata and Covariates..............................................................................................................................11
3.4.
Examination of Subject Subgroups........................................................................................................12
3.5.
Multiple Comparisons............................................................................................................................14
3.6.
Missing Data and Outliers......................................................................................................................14
3.6.1.
Missing Data ........................................................................................................................14
3.6.2.
Outliers.................................................................................................................................14
3.7.
Data Handling Conventions and Transformations .................................................................................14
3.8.
Analysis Visit Windows.........................................................................................................................15
3.8.1.
Definition of Study Day .......................................................................................................15
3.8.2.
Analysis Visit Windows.......................................................................................................15
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window................................................................................................................................17
3.9.
Date of Time Point Response and Progression ......................................................................................18
4.
SUBJECT DISPOSITION ..................................................................................................................................19
4.1.
Subject Enrollment and Disposition.......................................................................................................19
4.2.
Extent of Study Drug Exposure and Adherence.....................................................................................20
4.2.1.
Duration of Exposure to Study Drug....................................................................................20
4.2.2.
Adherence to Study Drug.....................................................................................................20
4.3.
Protocol Deviations................................................................................................................................21
5.
BASELINE CHARACTERISTICS....................................................................................................................22
5.1.
Demographics ........................................................................................................................................22
5.2.
Other Baseline Characteristics ...............................................................................................................22
5.3.
Medical History......................................................................................................................................22
5.3.1.
Disease History ....................................................................................................................22
5.4.
Chemotherapy and Radiotherapy Therapy.............................................................................................23


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6.
EFFICACY ANALYSES ...................................................................................................................................24
6.1.
Primary Efficacy Endpoint.....................................................................................................................24
6.1.1.
Statistical Hypothesis for the Primary Efficacy Endpoint....................................................26
6.1.2.
Analysis for the Primary Efficacy Endpoint.........................................................................26
6.2.
Secondary Efficacy Endpoint.................................................................................................................26
6.2.1.
Progression-Free Survival ....................................................................................................26
6.2.2.
Overall Survival ...................................................................................................................27
6.2.3.
Duration of Response...........................................................................................................28
6.3.
Exploratory Efficacy Endpoints.............................................................................................................28
7.
SAFETY ANALYSES........................................................................................................................................29
7.1.
Adverse Events and Deaths....................................................................................................................29
7.1.1.
Adverse Event Dictionary ....................................................................................................29
7.1.2.
Adverse Event Severity........................................................................................................29
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................29
7.1.4.
Serious Adverse Events........................................................................................................29
7.1.5.
Treatment-Emergent Adverse Events...................................................................................29
7.1.6.
Summaries of Adverse Events and Deaths...........................................................................30
7.2.
Laboratory Evaluations ..........................................................................................................................31
7.2.1.
Graded Laboratory Values ...................................................................................................32
7.2.2.
Shifts Relative to the Baseline Value ...................................................................................32
7.3.
Body Weight and Vital Signs.................................................................................................................33
7.4.
Concomitant Medications ......................................................................................................................33
7.4.1.
Prior Medications .................................................................................................................33
7.4.2.
Concomitant Medications.....................................................................................................33
7.5.
Electrocardiogram Results .....................................................................................................................34
7.5.1.
Investigator Electrocardiogram Assessment ........................................................................34
7.6.
Other Safety Measures ...........................................................................................................................34
7.7.
Changes From Protocol-Specified Safety Analyses...............................................................................34
8.
PHARMACOKINETIC (PK) ANALYSES........................................................................................................35
8.1.
PK Sample Collection............................................................................................................................35
8.2.
Statistical Analysis Methods ..................................................................................................................35
9.
IMMUNOGENICITY ANALYSES...................................................................................................................36
9.1.
ADA Sample Collection.........................................................................................................................36
9.2.
Statistical Analysis Methods ..................................................................................................................36
10.
BIOMARKER ANALYSES...............................................................................................................................37
11.
REFERENCES ...................................................................................................................................................38
12.
SOFTWARE.......................................................................................................................................................39
13.
SAP REVISION..................................................................................................................................................40
14.
APPENDIX.........................................................................................................................................................41
Appendix 1.
List of Laboratory Tests for Safety Analysis..........................................................................42
Appendix 2.
Schedule of Assessments........................................................................................................43
CCI-


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LIST OF TABLES
Table 1.
Analysis Visit Windows for Chemistry, Hematology and Vital Signs...................................16
Table 2.
Analysis Visit Windows for Urinalysis, Pregnancy Test, ECG, and ECOG ..........................16
Table 3.
Analysis Visit Windows for Thyroid Function Tests (TSH, T3, free T4)..............................16
Table 4.
Analysis Visit Windows for Tumor Assessment....................................................................17
Table 5.
Confirmed Overall Response Derivation................................................................................25
Table 6.
Biomarkers and Assay Testing Methods ................................................................................37
LIST OF FIGURES
Figure 1.
Study Design ............................................................................................................................8


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LIST OF ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BLQ
below the limit of quantitation
BMI
body mass index
CFR
Code of Federal Regulations
CI
confidence interval
CK
creatine kinase
CRF
case report form
CSR
clinical study report
CTCAE
Common Toxicity Criteria for Adverse Events
DCR
Disease Control Rate
DMC
data monitoring committee
ECG
electrocardiogram
ET
early termination
FAS
Full Analysis Set
GEJ
gastroesophageal junction
Hb
hemoglobin
HLT
high-level term
ICH
International Conference on Harmonization (of Technical Requirements for Registration of 
Pharmaceuticals for Human Use)
ITT
intent to treat
LTT
lower-level term
LOQ
limit of quantitation
MedDRA
Medical Dictionary for Regulatory Activities
MMR
Mismatch Repair
ORR
Objective Response Rate
PP
per protocol
PT
preferred term
Q1, Q3
first quartile, third quartile
QRS
electrocardiographic deflection between the beginning of the Q wave and termination of the 
S wave representing time for ventricular depolarization
QT
electrocardiographic interval between the beginning of the Q wave and termination of the T wave 
representing the time for both ventricular depolarization and repolarization to occur
QTc
QT interval corrected for heart rate
QTcF
QT interval corrected for heart rate using Fridericia’s formula
RR
electrocardiographic interval representing the time measurement between the R wave of 
one heartbeat and the R wave of the preceding heartbeat
SAP
statistical analysis plan


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StD
standard deviation
SI (units)
international system of units
SOC
system organ class
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
ULN
upper limit of normal
VR
ventricular rate
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the interim analysis and clinical 
study report (CSR) for Study GS-US-296-2013. This SAP is based on the study protocol 
Amendment 3 dated 16 June 2017 and the electronic case report form (eCRF). The SAP will be 
finalized before database finalization. Any changes made after the finalization of the SAP will be 
documented in the CSR.
1.1.
Study Objectives
The primary objective of this study is as follows:

To evaluate and compare the efficacy of andecaliximab (GS-5745) in combination with 
nivolumab versus nivolumab alone in subjects with recurrent gastric or gastroesophageal 
junction (GEJ) adenocarcinoma
The secondary objectives of this study are as follows:

To characterize and compare safety and tolerability of andecaliximab (GS-5745) in 
combination with nivolumab versus nivolumab alone in subjects with recurrent gastric or 
GEJ adenocarcinoma

To characterize the pharmacokinetics (PK) of andecaliximab (GS-5745) in combination with 
nivolumab
1.2.
Study Design
This is a Phase 2, open-label, randomized study comparing andecaliximab (GS-5745) in 
combination with nivolumab in recurrent gastric and GEJ adenocarcinoma versus nivolumab
alone. Approximately 120 subjects will be randomized to either Treatment Arm A: 
andecaliximab (GS-5745) + nivolumab or Treatment Arm B: nivolumab alone. The primary 
analysis will be conducted approximately 6 months after the last subject started treatment, when
all subjects would have had disease progression or discontinued from the study.
To evaluate safety of the combination drug, an independent Data Monitoring Committee (DMC) 
will be charged with overseeing the safety of the study. After the first 20 subjects are treated for 
8 weeks, the DMC will review all safety data to evaluate for any unexpected toxicities. If the 
DMC recommends that the combination demonstrates acceptable tolerability, enrollment and 
randomization will proceed with continued safety oversight from the DMC. Thereafter, review of 
safety data will be performed at regular intervals as described in the DMC charter.


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Randomized study:
Treatment Groups:

Arm A: Andecaliximab + Nivolumab

Arm B: Nivolumab
Figure 1.
Study Design
Randomization and Stratification:

1:1 allocation to andecaliximab (GS-5745) + nivolumab versus nivolumab alone through an 
interactive web response system (IWRS)

Fixed-block centralized randomization stratified by: 
PD-L1 positive (>=1% tumor cell staining) versus PD-L1 negative (<1% tumor cell 
staining)
1.3.
Sample Size and Power
Assuming the Objective Response Rate (ORR) for subjects treated with nivolumab alone is 25%, 
120 subjects in total are needed to detect an improvement of 20% in ORR for subjects treated 
with andecaliximab (GS-5745) and nivolumab with approximately 83% power at the one-sided 
significance level of 10% using a Cochran-Mantel-Haenszel (CMH) test with an assumption of 
common odds ratio for all strata. The assumption of nivolumab ORR is based on the upper 
bound of the 95% confidence interval of the estimated ORR in CheckMate-032 Study
{Le 2016}.
I Arm A 
: N=60 
GS-5745 + Nivolumab 
(Up to 2 years) 
Arm B 
Nivolumab 
1 N=GO L_....J.(:::.Ui:..::
pto:.;2:.Y
,1,,;e;;.;;a;.;..;rs""')_, 
I 
Stratifi~ation and 
Randomization 
Disease 
progression or 
study stopped 
Long-Term Follow-Up > 
Long-Term Follow-Up > 


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
No formal interim efficacy analysis is planned.
An external multidisciplinary Data Monitoring Committee (DMC) will review the progress of 
the study and perform interim reviews of the safety data in order to protect subject welfare and 
preserve study integrity. To ensure the best interests of the participants, the DMC will
recommend to the sponsor if the nature, frequency, and severity of adverse effects associated 
with the study treatment warrant the early termination of the study, the continuation of the study, 
or the continuation of the study with modifications.
The initial review will be conducted after 20 subjects have completed through Week 8. 
Thereafter, review of safety data will be conducted every 6 months.
The DMC’s role and responsibilities and the scope of analysis to be provided to the DMC are in 
a mutually agreed upon charter, which defines the DMC membership, meeting logistics, and 
meeting frequency.
2.2.
Primary Analysis
The primary analysis will occur when the last subject is treated for 6 months or discontinued, 
whichever is earlier.
2.3.
Follow-up Analysis 
After the primary analysis, additional analyses of efficacy and safety may be performed to 
provide long-term efficacy (overall survival) and safety follow-up.


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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 Intent-to-Treat (ITT) 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 randomized 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 treatment group.
3.1.1.
Intent-to-Treat Analysis Set
The intent-to-treat (ITT) Analysis Set includes all subjects who were randomized in the study.
Subjects will be grouped by the treatment to which they were randomized.
The ITT analysis set will be used for subject baseline and disease characteristics and efficacy 
analyses.
3.1.2.
Safety Analysis Set
The Safety Analysis Set includes all subjects who took at least 1 dose of study drug
(andecaliximab or nivolumab). Subjects will be grouped by the actual treatment received. It will 
be used for study drug administration and safety analyses.
3.1.3.
Per-Protocol Analysis Set
The per-protocol (PP) analysis set includes subjects in the ITT and excludes those who meet any 
one of the following criteria: 

No documented diagnosis of histologically confirmed adenocarcinoma of the stomach or
GEJ with inoperable, locally advanced or metastatic disease, not amenable to curative 
therapy

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
Did not receive study treatment

Subjects who have received only neoadjuvant or adjuvant therapy for gastric adenocarcinoma

Prior treatment with anti-CTLA-4 agents (ipilimumab), anti-PD-1 or anti-PD-L1 agents 
(pembrolizumab, nivolumab), anti-PD-L2 agents, anti-MMP agents, or other 
immunomodulatory therapies
The PP analysis set is the secondary analysis set for selected efficacy analyses. 
3.1.4.
Pharmacokinetic Analysis Set
The Pharmacokinetic (PK) Analysis Set will include all randomized subjects who took at least 
1 dose of andecaliximab and have at least 1 nonmissing post dose concentration value reported 
by the PK laboratory. It will be used for all PK analyses.
3.1.5.
Immunogenicity Analysis Set
The Immunogenicity Analysis Set will include all randomized subjects who took at least 1 dose 
of andecaliximab and have at least 1 nonmissing postdose antidrug antibody (ADA) status
reported. This is the primary analysis set for all immunogenicity analyses.
3.2.
Subject Grouping
For analyses based on the ITT Analysis Set, subjects will be grouped according to the treatment 
to which they were randomized. For analyses based on the Safety Analysis Set, subjects will be 
grouped according to the actual treatment received. The actual treatment received will differ 
from the randomized treatment only when the actual treatment differs from randomized 
treatment for the entire treatment duration.
For the PK Analysis Set and Immunogenicity Analysis Set, subjects will be grouped according to 
the actual treatment they received.
3.3.
Strata and Covariates
Subjects will be randomly assigned to treatment groups via the interactive voice or web response 
system (IXRS) in a 1:1 ratio using a stratified randomization schedule. Stratification will be 
based on the following variables:

PD-L1 positive (>=1% tumor cell staining) versus PD-L1 negative (<1% tumor cell staining)
If there are discrepancies in stratification factor values between the IXRS and the Covance lab
database, the values recorded in the Covance lab database will be used for analyses.
Efficacy endpoints will be evaluated using stratification factors as covariates or stratification 
variables for analyses, as specified in Section 6. 


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In the situation where there is insufficient information in a stratum (ie, if there are < 6 subjects or 
there is no informative event in a stratum by combined treatment arms), the stratification by 
PD-L1 will not be applied.
3.4.
Examination of Subject Subgroups
Primary (ORR) and key secondary (PFS and OS) efficacy endpoints will be examined in the 
following subgroups if there is sufficient sample size in the subgroup:

Stratification factor PD-L1 status
<1% tumor cell staining
>=1% tumor cell staining

Overall cell PD-L1 staining at baseline
<1% overall cell PD-L1 staining
>=1% overall cell PD-L1 staining

MMR status at baseline
MMR deficient (Subjects with one or more positive in MSH2, MSH6, MLH1, and PMS2 
mutation tests are considered MMR deficient.)
MMR proficient (Subjects with all negative in MSH2, MSH6, MLH1, and PMS2 
mutation tests are considered MMR proficient.)

Primary Site of Tumor
Gastric
GEJ

Number of Prior Anticancer Therapies
1
2
3
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
Histological Type
Diffuse
Other

Age group
< 65
>= 65

Gender
Male
Female

Race
White
Non-White
Adverse events and lab abnormalities will be examined in the following subgroups:

Age group
< 65
>= 65

Gender
Male
Female

Race
White
Non-White
In the situation where there is no responder in a subgroup, odds ratio of ORR within subgroups 
will not be estimated.


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3.5.
Multiple Comparisons
There are no adjustments for multiplicity in this study.
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 is described in Section 7.1.5.2, and for
prior and concomitant medications in Section 7.4.
3.6.2.
Outliers
Outliers will not be identified during the data management and data analysis process. All data 
will be included in the data analysis.
3.7.
Data Handling Conventions and Transformations
In general, age (in years) on the date of randomization will be used for analyses and presentation 
in listings. For screen failures, the date the informed consent was signed will be used for age 
calculation. If only the birth year is collected on the CRF, “01 July” will be used for the 
unknown birth day and month for the purpose of age calculation. If only birth year and month are 
collected, “01” will be used for the unknown birth day.
Non-PK data that are continuous in nature but are less than the lower limit of quantitation (LOQ)
or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used 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.

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).


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If methods based on the assumption that the data are normally distributed are not adequate, 
analyses may be performed on transformed data or nonparametric analysis methods may be used, 
as appropriate.
Natural logarithm transformation will be used for plasma/blood concentrations. Plasma 
concentration values that are below the limit of quantitation (BLQ) will be presented as “BLQ” 
in the concentration data listing. Values that are BLQ will be treated as 0 at predose time points, 
and one-half the value of the LOQ at postbaseline time points.
The following conventions will be used for the presentation of summary and order statistics:

If at least 1 subject has a concentration value of BLQ for the time point, the minimum value 
will be displayed as “BLQ.”

If more than 25% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum and Q1 values will be displayed as “BLQ.”

If more than 50% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, and median values will be displayed as “BLQ.”

If more than 75% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, median, and Q3 values will be displayed as “BLQ.”

If all subjects have concentration data values of BLQ for a given time point, all order 
statistics (minimum, Q1, median, Q3, and maximum) will be displayed as “BLQ.”
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study day will be calculated from the first dosing date of study drug andecaliximab or nivolumab
and derived as follows:

For post dose study days: Assessment Date – First Dosing Date + 1

For days prior to the first dose: Assessment Date – First Dosing Date
Therefore, study day 1 is the day of first dose of study drug administration.
3.8.2.
Analysis Visit Windows
Subject visits might not occur on protocol-specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows.
The analysis windows for chemistry, hematology and vital signs are provided inTable 1. The 
analysis windows for urinalysis, pregnancy test, ECG, and ECOG are provided in Table 2. The 
analysis windows for Thyroid Function Tests (TSH, T3, free T4) are provided in Table 3. The 
analysis windows for tumor assessment are provided in Table 4.


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Table 1.
Analysis Visit Windows for Chemistry, Hematology and Vital Signs
Analysis Visit
Study Day
Lower Limit (inclusive)
Upper Limit (inclusive)
Baseline
1
-28 
1 (before 1st dose)
Week 2
15
1 (after first dose)
21
Week 4
29
22
35
Week 6
43
36
49
Week X=8, 10, 
…
7*x+1
7x-6
7*x + 7
Safety Follow-up
max (andecaliximab end date, 
Nivo end date) + 1
max(andecaliximab end date + 30 days, 
Nivo end date + 5 months)
Table 2.
Analysis Visit Windows for Urinalysis, Pregnancy Test, ECG, and 
ECOG
Analysis Visit
Study Day
Lower Limit (inclusive)
Upper Limit (inclusive)
Baseline
1
-28
1 (before 1st dose)
Week 4
29
1 (after first dose)
42
Week 8
57
43
70
Week 12
85
71
98
Week X=16, 20, 
…
7*x+1
7x-13
7*x + 14
Safety Follow-up
max (andecaliximab end date, 
Nivo end date) + 1
max(andecaliximab end date + 30 days, 
Nivo end date + 5 months)
Note. For pregnancy test, use results from serum test for screening and results from urine test for post-screening visit. 
Table 3.
Analysis Visit Windows for Thyroid Function Tests (TSH, T3, 
free T4)
Analysis Visit
Study Day
Lower Limit (inclusive)
Upper Limit (inclusive)
Baseline
1
-28
1 (before 1st dose)
Week 8
57
1 (after first dose)
84
Week 16
113
85
140
Week 24
169
141
196
Week 32, 40,  ….
7*x+1
7x-27
7*x + 28
Safety Follow-up
max (andecaliximab end date, 
Nivo end date) + 1
max (andecaliximab end date + 30 days, 
Nivo end date + 5 months)


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Table 4.
Analysis Visit Windows for Tumor Assessment
Analysis Visit
Nominal Study Day
Lower Limit (inclusive)
Upper Limit (inclusive)
Baseline
-28
Randomization date - 42
Randomization date
Week 8
57
1
84
Week 8 confirmatory
Day of Week 8 visit + 28
Day of Week 8 visit + 28
Week 16
113
85
140
Week 16 confirmatory
Day of Week 16 visit + 28
Day of Week 16 visit + 28
Week 24
169
141
196
Week 24 confirmatory
Day of Week 24 visit + 28
Day of Week 24 visit + 28
Week X=32, 40, …
7*x+1
7x-27
7*x + 28
Week X=32, 40, … 
confirmatory
Day of Week 32, 40, … 
visit +28
Day of Week 32, 40, … 
visit +28
Note: In the rare cases where the screening assessments are after the randomization date but prior to the first dose of study drug, 
the assessments will be considered as baseline.
The analysis visit will be used when data are summarized by visit. Any data relating to 
unscheduled visits will be assigned to a particular visit or time point.

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 dose of study drug will be included in determining the 
maximum postbaseline toxicity grade.
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time-to-event analysis would not require 1 value per analysis window.
If multiple valid, nonmissing, continuous measurements exist in an analysis window, records 
will be chosen based on the following rules if a single value is needed:

In general, the baseline value will be the last nonmissing value on or prior to the first dosing 
date of study drug, unless specified differently. If multiple measurements occur on the same 
day, the last nonmissing value prior to the time of first dosing of study drug will be 
considered as the baseline value. If these multiple measurements occur at the same time or 
the time is not available, the average of these measurements (for continuous data) will be 
considered the baseline value.


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
For post baseline values:
The record closest to the nominal day for that visit will be selected.
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.
If there is more than 1 record on the selected day, the average will be taken, unless 
otherwise specified.
If multiple valid, nonmissing, categorical measurements exist in an analysis window, records 
will be chosen based on the following rules if a single value is needed:

For baseline, the last available record on or prior to the date of the first dose of study drug 
will be selected. If there are multiple records with the same time or no time recorded on the 
same day, the value with the lowest severity will be selected (normal will be selected over 
abnormal for safety ECG findings).

For post baseline visits, if there are multiple records with the same time or no time recorded 
on the same day, the value with the worst severity within the window will be selected 
(abnormal will be selected over normal for safety ECG findings).
3.9.
Date of Time Point Response and Progression
For subjects who have imaging examinations on various dates that are nevertheless assigned to 
the same nominal visit window, the following rules apply for the calculation of the endpoint 
date:

The response date will be the last date associated with that particular imaging time point.

The progression date will be the first date associated with that particular imaging time point.


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
A summary of subject enrollment will be provided by treatment group for each country, 
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 similar enrollment table will be provided by randomization stratum. The denominator for the 
percentage of subjects in the stratum will be the total number of enrolled subjects. If there are 
discrepancies in the value used for stratification assignment between the IXRS and the clinical 
database, the value collected in the clinical database will be used for the summary. A listing of 
subjects with discrepancies in the value used for stratification assignment between the IXRS and 
the clinical database at the time of data finalization will be provided.
The randomization schedule used for the study will be provided as an appendix to the CSR.
A summary of subject disposition will be provided by treatment group. This summary will 
present the number of subjects screened, the number of subjects enrolled, and the number of 
subjects in each of the categories listed below:

Safety Analysis Set

Randomized but never dosed

Continuing study drug

Completed study drug

Did not complete study drug with reasons for discontinuation of study drug

Continuing in tumor assessment

Completed tumor assessment

Discontinued tumor assessment before Disease Progression

Continuing long-term follow-up

Completed long-term follow-up

Did not complete long-term follow-up with reasons for discontinuation of long-term 
follow-up


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For the status of study drug and study completion and reasons for 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 ITT Analysis Set corresponding 
to that column. 
The following by-subject listings will be provided by subject identification (ID) number in 
ascending order to support the above summary tables:

Reasons for study drug, tumor assessment, and long-term follow-up discontinuation
4.2.
Extent of Study Drug Exposure and Adherence
Extent of exposure to study drug will be examined by assessing the total duration of exposure to 
study drug and the level of adherence to the study drug specified in the protocol by component 
(andecaliximab/nivolumab).
4.2.1.
Duration of Exposure to Study Drug
Total duration of exposure to study drug will be defined as last dosing date minus first dosing 
date plus 14, regardless of any temporary interruptions in study drug administration, and will be 
expressed in weeks using up to 1 decimal place (e.g., 4.5 weeks). If the last study drug dosing 
date is missing, the latest date among the study drug end date, clinical visit date, laboratory 
sample collection date, and vital signs assessment date that occurred during the on-treatment 
period will be used.
The total duration of exposure to study drug will be summarized using descriptive statistics.
Summaries will be provided by treatment group for the Safety Analysis Set.
4.2.2.
Adherence to Study Drug
The total number of doses administered will be summarized using descriptive statistics. 
4.2.2.1.
On-Treatment Adherence
The level of on-treatment adherence to the study drug regimen will be determined by the total 
amount of study drug administered relative to the total amount of study drug expected to be 
administered during a subject’s actual on-treatment period based on the study drug regimen, 
assuming there is no interruption.


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The level of on-treatment adherence will be expressed as a percentage using the following 
formula:
Total Amount of Study Drug Administered
On-Treatment Adherence (%) = 
 x 100
Study Drug Expected to be Administered on Treatment






Descriptive statistics for the level of on-treatment adherence with the number and percentage of 
subjects belonging to adherence categories (e.g., {< 75%, ≥ 75 to < 90%, ≥ 90%}) will be 
provided by treatment group for the Safety Analysis Set.
No formal statistical testing is planned.
A by-subject listing of study drug administration will be provided by subject ID number 
(in ascending order) and visit (in chronological order).
4.3.
Protocol Deviations 
Subjects who did not meet the eligibility criteria for study entry, but enrolled in the study will be 
summarized regardless of whether they were exempted by the sponsor or not. The summary will 
present the number and percentage of subjects who did not meet at least 1 eligibility criterion and 
the number of subjects who did not meet specific criteria by treatment group based on the ITT
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 (e.g., nonadherence to study drug, violation of select inclusion/exclusion 
criteria) will be summarized by treatment group for the ITT 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
Subject demographic variables (i.e., age, sex, race, and ethnicity) will be summarized by 
treatment group and overall using descriptive statistics for age, and using number and percentage 
of subjects for sex, race, and ethnicity. The summary of demographic data will be provided for 
the ITT 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
Other baseline characteristics include body weight (in kg), height (in cm), body mass index 
(BMI; in kg/m2), ECOG, PD-L1 status, and mismatch repair (MMR) status at screening. These 
baseline characteristics will be summarized by treatment group and overall using descriptive 
statistics for continuous variables and using number and percentage of subjects for categorical 
variables. The summary of baseline characteristics will be provided for the ITT Analysis Set.
No formal statistical testing is planned.
A by-subject listing of other baseline characteristics will be provided by subject ID number in 
ascending order.
5.3.
Medical History
General medical history data will be collected at screening and listed only. General medical 
history data will not be coded.
A by-subject listing of general medical history will be provided by subject ID number in 
ascending order.
5.3.1.
Disease History
A summary of disease-specific medical history will be provided by treatment and overall for the 
ITT Analysis Set. No formal statistical testing is planned. Variables to be summarized include:

Primary Tumor Site

Histology of gastric cancer

Disease stage at screening

Differentiation at screening

Time since diagnosis (months)


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The denominator for the percentage of histology of gastric cancer is the number of subjects with 
gastric cancer. The denominators for the percentage of other variables are the number of subjects 
in the ITT analysis set corresponding to that column. 
A by-subject listing of disease history and surgical procedures will be provided by subject ID 
number in ascending order. 
5.4.
Chemotherapy and Radiotherapy Therapy
Prior (neoadjuvant, adjuvant, and metastatic) chemotherapy and radiotherapy will be 
summarized using descriptive statistics by treatment arm using ITT analysis set. 
A by-subject listing of prior anticancer therapy and radiotherapy will be provided by subject ID 
number in ascending order. A by-subject listing of post-treatment chemotherapy will be provided 
by subject ID number and time in ascending order.
A by-subject listing of all radiotherapy will be provided by subject ID number and time in 
ascending order.


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6.
EFFICACY ANALYSES
Efficacy analysis will be performed based on the ITT Analysis Set. The investigator assessments 
will be used for analyses of efficacy endpoints. 
6.1.
Primary Efficacy Endpoint
The primary efficacy endpoint of this study is objective response rate (ORR), defined as the 
proportion of subjects with best overall response of complete response (CR) or partial response 
(PR) after starting study drug but before starting any new chemotherapy or radiotherapy based on 
revised RECIST 1.1. 
As sensitivity analysis, confirmed ORR, defined as the proportion of subjects with best overall 
response of confirmed complete response (CR) or confirmed partial response (PR) after starting 
study drug but before starting any new anti-cancer therapy based on revised RECIST 1.1, will 
also be analyzed. The confirmatory response is required at least 4-week later after the initial 
CR/PR for confirmed ORR.
Overall response for each visit is derived in the following process. The rules should be applied 
by the order listed below.

Response assessments occurring after new anticancer therapy (including radiation therapy),
after missing two previous consecutive tumor scans, or after confirmed PD will not be 
included for ORR analysis.

If overall response for the first time point of a visit is an imaging PD, in order to differentiate 
“pseudo-progression (pseudo-PD)” from “definitive progression”, the first imaging PD 
requires confirmation either by another imaging PD at the confirmatory visit at least 4 weeks
apart or by the subsequent clinical PD/ radiation therapy. The first imaging PD will be 
considered as “confirmed PD” by any of the following:
The overall response at the confirmatory visit is also PD;
No more tumor assessment is available that is 4 weeks apart;
The overall response at the confirmatory visit is non-evaluable (NE) and no more tumor 
assessments follow the confirmatory visit;
First imaging PD is followed by subsequent clinical PD or radiation therapy.
Otherwise, the first imaging PD will be “Pseudo PD”. 

Both clinical PD and radiation therapy are considered as PD, and no confirmation is required. 


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The best overall response for each subject across the time points is derived based on the rank CR 
> PR > SD > pseudo-PD > PD (including clinical PD, confirmed imaging PD, and radiation 
therapy) > NE.
For confirmed overall response for each visit, in addition to the rules listed above, the following 
rules should also be applied.

If overall response for the first time point of a visit (e.g., Week 8) is CR or PR, a 
confirmatory visit at least 4 weeks later is required. Overall response for the visit is derived 
based on overall response at the first time point and overall response at the confirmatory 
visit. 

If overall response for the first time point of a visit is SD/NE, no confirmatory visit is 
required and the overall response for the visit is SD/NE correspondingly.
The rule for deriving confirmed overall response at each visit is specified in Table 5. The best 
confirmed overall response for each subject across the time points is derived based on the rank 
CR confirmed > PR confirmed > CR not confirmed > PR not confirmed > SD > pseudo-PD > PD
(including clinical PD, confirmed imaging PD, and radiation therapy) > NE.
Table 5.
Confirmed Overall Response Derivation
Overall response 
at first visit 
Overall response at confirmatory visit 
Overall response for 
the time point
Date of Response
CR
CR
CR confirmed
First visit
Responses other than CR or there is no 
confirmatory visit
CR not confirmed
First visit
PR
CR/PR
PR confirmed
First visit
Responses other than CR/PR or there is 
no confirmatory visit
PR not confirmed
First visit
PD
PD/ clinical PD/ radiation therapy, or 
there is no confirmatory visit
PD
First visit
NE
PD
First visit
Responses other than PD/clinical PD/ 
radiation therapy/NE
pseudo-PD
First Visit
NE
Not required
NE
First visit
SD 
Not required
SD
First visit
Note: Response after treatment discontinuation does not need to be confirmed.


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6.1.1.
Statistical Hypothesis for the Primary Efficacy Endpoint
The primary efficacy hypothesis is that there is no difference between Treatment Group 
(Group T) and Control Group (Group C) in ORR. Using RT and RC to denote the objective 
response rate of Treatment Group (Group T) and Control Group (Group C), respectively, the 
statistical hypotheses to be tested in this study will be:
H0: RT = RC
H1: RT > RC (Group T is superior to Group C in terms of ORR)
6.1.2.
Analysis for the Primary Efficacy Endpoint
The ORR endpoint will be tested at a two-sided alpha level of 0.2. The ORR will be presented 
with corresponding 2-sided 80% and 95% exact confidence intervals (CIs) calculated using the 
Clopper-Pearson method. Odds ratio will also be presented with corresponding 80% and 95% 
CIs be calculated using the exact Cochran-Mantel-Haenszel (CMH) Chi-square test stratified by 
screening PD-L1 status. Subjects who do not have sufficient baseline or on-study tumor 
assessments to characterize response will be counted as non-responders and included in the 
denominator only.
In addition, the confirmed ORR, defined as the proportion of subjects with best overall response 
of confirmed CR/confirmed PR will also be presented as a sensitivity analysis. The same 
analysis methods as for ORR mentioned above will be applied for confirmed ORR.
The analysis for the ORR and confirmed ORR will be performed based on both the ITT Analysis 
Set and Per Protocol Analysis Set.
6.2.
Secondary Efficacy Endpoint
6.2.1.
Progression-Free Survival
Progression free survival (PFS), defined as the interval from the date of randomization to the 
earlier of the first definitive PD (as defined in section 6.2.1) or death from any cause. The first 
definitive PD is defined as the first radiation therapy, the first clinical PD, and the first confirmed 
imaging PD, whichever comes first. Pseudo-PD will not be considered as definitive PD.
Data will be censored on the date of last adequate tumor assessment for subjects (including 
assessments with a NE outcome):

who do not have definitive PD or die before study discontinuation, or 

who start new anticancer therapy prior (radiation therapy excluded) to definitive PD or death, 
or

who have ≥ 2 consecutive missing tumor assessments before definitive PD or death.


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Subjects without any adequate baseline tumor assessment are censored on the randomization 
date. The adequate baseline tumor assessment is defined as the window from (randomization 
date -35) to randomization date. 
PFS in months will be calculated as (date of event/censoring – date of randomization + 1) / 
30.4375.
Survival function of PFS is estimated using Kaplan-Meier method and compared using the 
log-rank test stratified by PD-L1 status at screening. PFS rates at 1, 2, 3, 6, 9, 12 months, and the 
median with 95% CIs will be derived using Kaplan-Meier methods by treatment arm. 
Kaplan-Meier curves will also be provided. In addition, hazard ratio (HR) and corresponding 
95% CI will be estimated for PFS using the Cox proportional hazards regression model stratified 
by PD-L1 status at screening.
Follow-up time in months for PFS will be summarized as a continuous variable with descriptive 
statistics.

For a subject who is censored from PFS and has discontinued from tumor assessment, 
duration of PFS follow-up = (Date of Censoring – randomization date +1)/30.4375

For subjects with a definitive PFS event and censored subject with ongoing tumor 
assessment, duration of PFS follow-up = (Date of analysis cut-off date – randomization date 
+1)/30.4375
Incomplete or missing dates of initiation of anticancer therapy other than the study treatment are 
imputed as follows:

If the day is missing but the month and year are available, then the imputed day will be the 
last day of the month.

If day and month are missing but year is available, then the imputed day and month will be 
01Jan or the last day of the month for the last adequate disease assessment if they have the 
same year, whichever is later.
The analysis of PFS will be performed based on both the ITT Analysis Set and Per Protocol 
Analysis Set.
6.2.2.
Overall Survival
Overall survival (OS) is defined as interval from the date of randomization to death from any 
cause. Subjects alive are censored at the last time the subject was known alive.
The survival function of OS is estimated using Kaplan-Meier method and compared using the 
log-rank test stratified by PD-L1 status at screening. The median, Q1, Q3 estimate of OS and 
probability of survival at 3, 6, 12, 18, and 24 months from randomization will be provided along 
with the corresponding 95% CI. In addition, hazard ratio (HR) and corresponding 95% CI will be 
estimated using Cox proportional hazard regression method stratified by screening PD-L1 status.


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Follow-up time in months for OS will be summarized as a continuous variable with descriptive 
statistics by ti·eatment aim. 
• 
For subjects who discontinued study due to lost to follow-up or withdraw of consent, 
duration of OS follow-up = (Date oflast follow-up - randomization date+ 1)/30.4375 
• 
For subjects who died and subjects still alive at the time of analysis, duration of OS follow-
up = Date of analysis cut-off date - randomization date + 1 
The analysis of OS will be perfo1med based on both the ITT Analysis Set and Per Protocol 
Analysis Set. 
6.2.3. 
Duration of Response 
Duration of response (DOR) is defined for subjects in the ITT analysis set who are CR/PR prior 
to new anti-cancer therapy (including radiation therapy) as the interval from the date of the first 
objective response achieved to the earlier of the first definitive disease progression or death from 
any cause. The first definitive disease progression is defined in section 6.2.1. The same censoring 
rnles as for PFS will be applied to DOR. 
DOR in months= (date of event/censoring - date of first response [CR or PR] + 1) / 30.4375. 
Median DOR and 95% Cls will be estimated using Kaplan-Meier methods by u-eatment aim. 
Kaplan-Meier curves will also be provided. 
6.3. 
Exploratory Efficacy Endpoints 
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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) and preferred term (PT) 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 toxicity 
criteria specified in the protocol. 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 as determined by the investigator. 
SAEs captured and stored in the clinical database will be reconciled with the SAE database from 
the Gilead Drug Safety and Public Health 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 both of the following:

Any AEs with an onset date on or after the study drug start date and up to 30 days after 
permanent discontinuation of andecaliximab or 5 months after permanent discontinuation of 
nivolumab

Any AEs leading to premature discontinuation of andecaliximab or 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 andecaliximab or 5 months after 
the date of the last dose of nivolumab
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.
The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC, HOC, PT, and treatment group. For other AEs described below, summaries 
will be provided by SOC, PT, and treatment group:

All TE treatment-related AEs

TEAEs of Grade 3 or higher (by maximum severity)

TE Treatment-related AEs of Grade 3 or higher (by maximum severity)

All TE SAEs

All TE treatment-related SAEs 

All TEAEs leading to discontinuation of any study drug

All TEAEs leading to study treatment interruption or dose interruption

All TEAEs leading to death 
A brief, high-level summary of AEs described above will be provided by treatment group and by 
the number and percentage of subjects who experienced the above AEs. 


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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 HT within each SOC, and then by PT 
in descending order of total frequency within each SOC. For summaries by severity grade, the 
most severe grade will be used for those AEs that occurred more than once in an individual 
subject during the study. 
In addition to the above summary tables, all TEAEs and TE treatment-related AEs will be 
summarized by PT only, in descending order of total frequency.
Deaths will be summarized by whether it is considered treatment emergent and the cause of the 
death (AE, due to PD, or other reasons).
In addition, data listings will be provided for the following:

All AEs, indicating whether the event is treatment emergent

AEs with Grade 3 or higher

SAEs

AEs leading to death

All deaths

AEs leading to discontinuation of study drug 

AEs leading to treatment interruption/dose modification
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed using qualitative methods. Shift from 
baseline to worst post-baseline assessment and Grade 3 or higher lab abnormalities will be 
summarized for the Safety Analysis Set and will include data collected up to the last dose of 
andecaliximab plus 30 days for subjects who have permanently discontinued andecaliximab or 
up to the last dose of nivolumab plus 5 months for subjects who have permanently discontinued 
nivolumab. Severity grade for lab abnormalities are defined by CTCAE 4.03. 
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, urinalysis, coagulation, and 
thyroid function 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.


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7.2.1.
Graded Laboratory Values
The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities CTCAE 
Version 4.03 will be used to assign 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 (i.e., increased, decreased) will be presented separately. 
7.2.1.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last 
dose of andecaliximab plus 30 days or nivolumab plus 5 months for subjects who permanently 
discontinued study drug, or the last available date in the database snapshot for subjects who were 
still on treatment at the time of an interim analysis. If the relevant baseline laboratory value is 
missing, any abnormality of at least Grade 1 observed within the time frame specified above will 
be considered treatment emergent.
7.2.1.2.
Summaries of Laboratory Abnormalities
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group; subjects will be categorized 
according to the most severe postbaseline abnormality grade for a given lab test:

Graded laboratory abnormalities

Grade 3 or 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
nonmissing postbaseline values up to 30 days after last dosing date of GS5745 or up to 5 months 
after last dosing date of nivolumab.
A by-subject listing of treatment-emergent Grade 3 or 4 laboratory abnormalities will be 
provided by subject ID number and time point 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.
7.2.2.
Shifts Relative to the Baseline Value
Shift tables will be presented by showing change in severity grade from baseline to worst post 
baseline assessment.


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7.3.
Body Weight and Vital Signs
Descriptive statistics will be provided by treatment group for body weight and vital signs as 
follows:

Baseline value

Values at each postbaseline visit

Change from baseline at each postbaseline visit
A baseline value will be defined as the last available value collected on or prior to the date/time 
of first dose of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value. 
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3. No formal statistical testing is planned.
A by-subject listing of vital signs and body weight will be provided by subject ID number and 
time point in chronological order. Body weight will be included in the vital signs listing, if space 
permits. If not, they will be provided separately.
7.4.
Concomitant Medications
Medications collected during the study will be coded using the current version of the 
[Gilead-modified] World Health Organization (WHO) Drug dictionary.
7.4.1.
Prior Medications
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. Use 
of concomitant medications will be summarized by Anatomical Therapeutic Chemical (ATC) 
drug class Level 2 and preferred name using the number and percentage of subjects for each 
treatment group. A subject reporting the same medication more than once will be counted only 
once when calculating the number and percentage of subjects who received that medication. The 
summary will be ordered alphabetically by ATC medical class and then by preferred term in 
descending overall frequency within each ATC medical class. For drugs with the same 
frequency, sorting will be done alphabetically.
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 prior 


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to the date of first dosing date of study drug or a start date 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 Results
7.5.1.
Investigator Electrocardiogram Assessment
A by-subject listing for ECG assessment results will be provided by subject ID number and visit
in chronological order.
7.6.
Other Safety Measures
No additional safety measures are specified in the protocol.
7.7.
Changes From Protocol-Specified Safety Analyses
There are no deviations from the protocol-specified safety analyses.


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8.
PHARMACOKINETIC (PK) ANALYSES
8.1.
PK Sample Collection
PK plasma samples will be collected for Arm A only for andecaliximab PK at 30(± 15) min after 
the end of infusion on Day 1; prior to dosing and 30(± 15) min after the end of infusion on Day 1 
of Weeks 4, 8, 16, 24, and every 3 months thereafter, at the EOT and EOS visits.
8.2.
Statistical Analysis Methods
Individual subject concentration for andecaliximab will be listed and summarized using 
descriptive statistics by treatment. Summary statistics (n, mean, StD, coefficient of variation 
[%CV], median, min, max, Q1, and Q3) will be presented for individual subject concentration 
data by time.
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 
non-missing concentration data at that time point. The number of subjects with concentration 
BLQ will be presented for each time point. For summary statistics, BLQ values will be treated as 
0 at predose and one-half of the lower limit of quantitation (LLOQ) for postdose time points. 
The following tables will be provided for andecaliximab:

Individual subject concentration data and summary statistics
The following figures may be provided for andecaliximab by treatment:

Mean (± StD) concentration data versus time (on linear and semilogarithmic scales)

Median (Q1, Q3) concentration data versus time (on linear and semilogarithmic scales)

Individual subject concentration 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 listing will be provided

PK sampling details by subject, including procedures, differences in scheduled and actual 
draw times, and sample age will be provided in listings.


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9.
IMMUNOGENICITY ANALYSES
9.1.
ADA Sample Collection
For arm A only serum samples for anti-andecaliximab antibody will be collected prior to dosing 
on Day 1 of week 1, 4, 8, 16, 24, and every 3 months thereafter, EOT, EOS.
9.2.
Statistical Analysis Methods
Immunogenicity of andecaliximab will be evaluated based upon the positive ADA rate. The 
number and percentage of subjects exhibiting positive ADA status, defined as ADA presence in 
serum confirmed in validated assay and reported by bioanalytical laboratory, will be summarized 
at each specified time point. The number and percentage of subjects exhibiting positive ADA 
status at any post-andecaliximab time point will also be summarized. 
The time to ADA onset will also be assessed. It is defined as the time interval from the date of 
first dose of andecaliximab to the date positive ADA status is first achieved. The analyses of 
time to ADA onset will be based on the subjects in the immunogenicity analysis set who have 
negative ADA status at baseline and achieve positive ADA status at post baseline. Summary 
statistics (n, mean, StD, coefficient of variation [%CV], median, min, max, Q1, and Q3) will be 
presented.
Impact of ADA on andecaliximab PK may be evaluated as appropriate. Individual subject 
andecaliximab predose concentration data may be summarized using descriptive statistics by 
ADA status (positive or negative) of the same time point. Summary statistics (n, mean, StD, 
coefficient of variation [%CV], median, min, max, Q1, and Q3) will be presented by ADA 
status. 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. Individual subject andecaliximab
predose concentration data versus ADA results may be plotted (on linear and semilogarithmic 
scales). PK plasma samples meeting below criteria will be included in this analysis:

Collected after Week 8 Day 1 or later

Collected 288 – 384 hours (12 to 16 days) post most recent dose
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.


Andecaliximab (GS-5745) 
GS-US-296-2013 
Statistical Analysis Plan 
10. 
BIO MARKER ANALYSES 
Version 1.0 
The following biomarkers will be evaluated whether they are predictive for ti·eatment efficacy. 
These analyses are explorato1y. 
I 
I 
I 
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Andecaliximab (GS-5745)
GS-US-296-2013
Statistical Analysis Plan
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11.
REFERENCES
Le DT, Bendell JC, Calvo E, Kim JW, Ascierto PA, Sharma P, et al. Safety and activity of 
nivolumab monotherapy in advanced and metastatic (A/M) gastric or 
gastroesophageal junction cancer (GC/GEC): Results from the CheckMate-032 
study [Abstract 06]. J Clin Oncol (ASCO Annual Meeting Abstracts) 2016.


Andecaliximab (GS-5745)
GS-US-296-2013
Statistical Analysis Plan
Version 1.0
CONFIDENTIAL
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12.
SOFTWARE
SAS® Software Version 9.X. SAS Institute Inc., Cary, NC, USA.
nQuery Advisor(R) Version X.0. Statistical Solutions, Cork, Ireland.


Andecaliximab (GS-5745)
GS-US-296-2013
Statistical Analysis Plan
Version 1.0
CONFIDENTIAL
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13.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision


Andecaliximab (GS-5745)
GS-US-296-2013
Statistical Analysis Plan
Version 1.0
CONFIDENTIAL
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14.
APPENDIX
Appendix 1.
List of Laboratory Tests for Safety Analysis
Appendix 2.
Schedule of Assessments


Andecaliximab (GS-5745) 
GS-US-296-2013 
Statistical Analysis Plan 
Version 1.0 
Appendix 1. 
List of Laboratory Tests for Safety Analysis 
Chemistry 
U1·inalysis 
Hematology 
Other 
Albumin 
Color and appearance 
WBC Hemoglobin 
Serum P-hCG or mine 
Alkaline phosphatase 
Specific gravity pH 
Hematocrit Platelet 
pregnancy testc 
ALT AST Bicarbonate 
Occult blood Protein 
ANC 
Thyroid Function Tests 
BUN Calcium Chloride 
Glucose Bilimbin 
(TSH, T3, fre.eT4/ 
Creatinine• 
Leukocyte esterase 
Differential 
Glucose 
Nitrite Urobilinogen 
Eosinophils 
Lipase 
Ketones Microscopicb 
Lymphocytes 
Amylase Magnesium 
Monocytes 
Phosphoms Potassium 
Neutrophils 
Sodium 
Coagulation 
Total bilimbin Direct 
bilimbin Total protein 
PT/INR 
CEA 
aPTI 
CA125 
ANC = absolute neutrophil count; ALT = alanine aminotransferase; aPTT = Activated Partial Thromboplastin Time; 
AST = aspa1tate aminotransferase; BUN = blood urea nitrogen; CEA=carcinoemb1yonic antigen; j3-hCG = beta-human chorionic 
gonadotropin; INR = lntemational No1malized Ratio; PT = Prothrombin Time; WBC = white blood cell; CA125 = Carbohydrate 
Antigen 125; TSH = thyroid stimulating hormone; T3 = triiodothyronine; Free T4 = free thyroxine 
I 
a 
Estimated creatinine clearance (CLc,)/glomemlar filtration rate will be calculated based on the Cocla-oft-Gault formula using 
actual body weight: CLcr (mL/min) = (140 - age [years])• weight (kg) I (semm 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 will be 
conducted pre-dose on Day 1, eve1y 4 weeks thereafter, at EOT, and EOS, 30-day, and 5-month Safety Follow-up 
d 
TSH, T3, and free T4 w-ill be tested by the central laborato1y at screening. From Week 8 and beyond, T3 and T4 will be 
tested reflexively based on abno1mal TSH results. 
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GS-US-296-2013
Statistical Analysis Plan
Version 1.0
CONFIDENTIAL
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Appendix 2.
Schedule of Assessments
Period
Screening
Randomization a
Treatment
EOTm
Disease Progression
EOSn
30 day Safety
Follow-upo
5-month Safety
Follow-Upp
Long Term
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14 to 50
Week
-4
Day 1
2
4
6
8
10
12
14
16
18
20
22
24 to 96
Window (day)
-28
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±7
±7
±7
Informed Consent
X
Medical and Medication 
History
X
Physical Examinationb
X
X
X
X
X
X
X
Xs
X
X
X
Vital Signs & Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECOG Performance
Statusc
X
Xc
X
X
X
X
X
Xs
X
X
X
12-lead ECG
X
X
X
X
X
X
X
Xs
X
X
Adverse events/ 
Concomitant 
Medicationsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IWRS Registration
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study Drug/ Nivolumab 
Administratione
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Thyroid Function Tests 
(TSH, T3, free T4)
X
X
X
Xt
X
X
X
X


Andecaliximab (GS-5745)
GS-US-296-2013
Statistical Analysis Plan
Version 1.0
CONFIDENTIAL
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06 December 2017
Period
Screening
Randomization a
Treatment
EOTm
Disease Progression
EOSn
30 day Safety
Follow-upo
5-month Safety
Follow-Upp
Long Term
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14 to 50
Week
-4
Day 1
2
4
6
8
10
12
14
16
18
20
22
24 to 96
Window (day)
-28
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±7
±7
±7
Coagulation
X
X
X
Urinalysis
X
X
X
X
X
X
X
Xs
X
X
X
X
Pregnancy Testf
X
X
X
X
X
X
X
Xs
X
X
X
X
Andecaliximab PKg
X
X
X
X
Xr
X
X
Anti-Andecaliximab
Antibodyh
X
X
X
X
Xr
X
X
Blood Biomarkersi
X
X
X
X
X
X
Xr
Xi
Xi
Oral Sampling
X
CT or MRI & Treatment 
Response Assessmentk
X
X
X
Xt
Xq
X
Tumor Biopsyl
Xl
Xl
(Wk 5 through Wk 9)
Xl
Overall Survival and 
Other Antitumor Therapy
Xu
a
Day 1 visit must occur within 3 days following randomization.
b
Complete physical examination (PE) to be performed at Screening, EOT and EOS. A modified PE capturing changes from prior exams will be performed at subsequent visits.
Height is required at Screening only.
c
ECOG performance status on Day 1 may be waived if has been conducted during screening within 4 days of Day 1.
d
Adverse events will be assessed and concomitant medications will be recorded at each clinic visit from Screening up to and including the 30-day Safety Follow-up visit or
EOS visit whichever is later.
CCI


Andecaliximab (GS-5745)
GS-US-296-2013
Statistical Analysis Plan
Version 1.0
CONFIDENTIAL
Page 45
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e
For Arm A: Study drug andecaliximab (800 mg) will be administered via IV infusion every 2 weeks over 30 (± 5) min. Nivolumab (3 mg/kg) will be administered via IV 
infusion following the completion of andecaliximab every 2 weeks over 60 (± 5) min. For Arm B: Nivolumab alone (3 mg/kg) will be administered via IV infusion every 2
weeks over
60 (± 5) min.
f
If applicable (females of child bearing potential). Serum pregnancy testing will be conducted at Screening. Urine pregnancy testing will be conducted pre-dose on Day 1 and 
every then every 4 weeks, at EOT, and EOS, 30-day, and 5-month Safety Follow-up.
g
For Arm A only, plasma samples will be collected for andecaliximab PK at 30(± 15) min after the end of infusion on Day 1. For Weeks 4, 8, 16, and 24 and every 3 months 
thereafter, PK will be collected prior to dosing and 30(± 15) min after the end of infusion. It will also be collected at EOT and EOS.
h
For Arm A only,  serum samples for anti-andecaliximab antibody will be collected prior to dosing on Day 1, Week 4, Week 8, Week 16, Week 24, and every 3 months
thereafter, EOT and EOS.
i
Blood biomarkers will be collected at screening and prior to dosing on Day 1; Week 2; Week 4; Week 8; Week 16; Week 24 and every 3 months thereafter and at progression 
or EOS.
k
Tumor evaluation by CT or MRI will be performed during screening and approximately every 8 weeks regardless of visit week or dose interruption. Scan at EOS visit is not 
necessary if restaging scan is performed within the prior 8 weeks. Treatment response assessment will be per RECIST v1.1. For subjects who stop study treatment in the 
absence of disease progression (eg. experienced unexpected toxicity) and remain on study for follow-up for progression-free survival, tumor evaluation by CT or MRI should 
continue approximately every 8 weeks until disease progression or initiation of non-study specific anti-neoplastic therapy in the absence of progression, whichever occurs 
earlier.
l
A pretreatment biopsy is requested if archival tumor sample provided to meet Inclusion Criterion #6 is from before the last line of therapy. An on-treatment biopsy is required 
between Week 5 and Week 9. A biopsy at disease progression is requested, if medically feasible. The sample should be collected by the last clinic visit on study ie EOS or
30 Day Safety Follow-up visit. All biopsies are requested to be from gastric lesions if possible (non-gastric metastatic lesions ok if no gastric lesions possible). See laboratory
manual for biopsy specifications and procedures.
m
End of treatment (EOT) assessments will be completed only 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 
approximately every 8 weeks until disease progression.
n
End of study (EOS) assessments will be completed when a subject meets at least 1 of the criteria for study discontinuation (Protocol Section 3.7).
o
The 30-day safety follow-up visit will be performed following the last dose of andecaliximab.
p
The 5-month safety follow-up visit will be performed following the last dose of nivolumab.
q
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 (see Protocol section 6.2.9).
r
Starting at Week 24, perform every 12 weeks until EOT/EOS.
s
Starting at Week 24, perform every 4 weeks until EOT/EOS.
t
Starting at Week 24, perform every 8 weeks until EOT/EOS.
u
Perform every 3 months until 5 years.
CCII