Clinical trial NCT03954704
Conditions: Advanced Solid Tumors
Sponsor: Gilead Sciences
Start date: 2019-06-03; Completion date: 2021-04-15
Enrollment: 22 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
For Phase 1a Part A, the primary objectives are to assess safety and tolerability and to define the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of dalutrafusp alfa (formerly GS-1423) monotherapy in participants with advanced solid tumors.

For Phase 1a Part B, the primary objective is to assess safety and tolerability of dalutrafusp alfa monotherapy in participants with advanced solid tumors.

For Phase 1b Cohort 1 safety run-in, the primary objective is to assess safety and tolerability and to define the DLT and MTD or RP2D of dalutrafusp alfa in combination with a chemotherapy regimen in participants with advanced gastric or gastroesophageal junction adenocarcinoma.

For Phase 1b Cohort 1 post safety run-in, the primary objective is to assess the preliminary efficacy of dalutrafusp alfa in combination with a chemotherapy regimen in participants with advanced gastric or gastroesophageal junction adenocarcinoma, as assessed by the confirmed objective response rate (ORR).

For Phase 1b Cohort 2, the primary objective is to assess safety and tolerability of dalutrafusp alfa monotherapy in participants with advanced solid tumors.

Detailed description:

Arms: arm 1: Part A will consist of dose escalation by an accelerated dosing design and a 3+3 dose escalation scheme. Participants will receive escalating dose levels dalutrafusp alfa of up to 45 mg/kg on Day 1 of each 2-week cycle (Q2W) until the participant meets study treatment discontinuation criteria or for up to 1 year. arm 2: Part B will consist of 3 adaptive cohorts. Based on PK, pharmacodynamics, and safety results from the Part A study, participants will be administered a flat dose of dalutrafusp alfa on Day 1 of each cycle QW, Q2W and/or every 3 weeks (Q3W) until the participant meets study treatment discontinuation criteria or for up to 1 year. arm 3: Safety run-in: A standard 3+3 dose escalation design will be used to determine the DLT and MTD or RP2D of dalutrafusp alfa in combination with mFOLFOX6. The planned starting dose of dalutrafusp alfa will be targeted to achieve the exposure at -1 dose of RP2D monotherapy (Q2W) determined from Phase 1a. Dalutrafusp alfa will be administered in combination with mFOLFOX6.

Post safety run-in: Approximately 70 participants will be enrolled to receive dalutrafusp alfa at the dose level determined from the safety run-in period, in combination with mFOLFOX6 regimen.

Participants will receive dalutrafusp alfa on Day 1 of each 14-day cycle up to 2 years until PD, or unacceptable toxicity, substantial noncompliance with study procedures or study drug, study discontinuation or withdrawal from study. Participants will also receive mFOLFOX6 regimen Q2W for up to 12 cycles. arm 4: Participants will receive dalutrafusp alfa at the dose level determined from Phase 1a Q2W until the participants meets study treatment discontinuation criteria or for up to 1 year.
Interventions: intervention 1: Dalutrafusp alfa intervention 2: mFOLFOX6 Regimen intervention 3: Dalutrafusp alfa
Intervention descriptions: intervention 1: Administered intravenously intervention 2: Chemotherapy regimen of oxaliplatin, 5-fluorouracil \[5-FU\], and leucovorin intervention 3: Administered intravenously

Protocol documents:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL
Study Title:
A Phase 1a/1b Study of GS-1423, an Anti-CD73-TGFβ-Trap 
Bifunctional Antibody, as Monotherapy or in Combination with a 
Chemotherapy Regimen in Subjects with Advanced Solid Tumors
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
142793
2019-004938-41
NCT03954704
Indication:
Advanced solid tumors
Protocol ID:
GS-US-505-5452
Contact Information:
The medical monitor name and contact information will be provided 
on the Key Study Team Contact List.
Protocol Version/Date:
Original:
25 March 2019
Amendment 1:
19 November 2019
Amendment 2:
29 April 2020
This study will be conducted under US Food and Drug Administration IND regulations 
(21 CFR Part 312); however, sites located in the European Economic Area, United Kingdom,
and Switzerland are not included under the IND and are considered non-IND sites.
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable Institutional 
Review Board or Independent Ethics Committee. The information is only to be used by you in 
connection with authorized clinical studies of the investigational drug described in the protocol. 
You will not disclose any of the information to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessary to obtain informed consent from those 
persons to whom the drug may be administered.
(r) GILEAU 


GS- 1423 
Protocol GS-US-505-5452 
Gilead Sciences, lnc. 
Final 
Amendment2 
TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................................. 2 
LIST OF IN-TEXTTABLES ........................................................................................................................................ 5 
LIST OF IN-TEXT FIGURES ...................................................................................................................................... 6 
PROTOCOL SYNOPSIS .............................................................................................................................................. 7 
GLOSSARY OF ABBREVIATIONS AN D DEFINITION OF TERMS .................................................................... 23 
I. 
INTRODUCTION .............................................................................................................................................. 27 
1.1. 
Background ............................................................................................................................................ 27 
1.2. 
Investigational Medicinal Product GS-1423 .......................................................................................... 27 
1.2.1. 
General Information ............................................................................................................. 27 
1.2.2. 
Preclinical Pharmacology and Toxicology ........................................................................... 28 
1.2.3. 
Clinical Studies ofGS-1423 ................................................................................................. 30 
1.3. 
Information About Comparator or Reference Products ......................................................................... 30 
1.4. 
Rationale for This Study ........................................................................................................................ 30 
1.4.1. 
Rationale for Phase I a and Phase I b Cohort 2 (Dose Escalation, Flat 
Dose Regimens and Paired Biopsy) ..................................................................................... 30 
1.4.2. 
Rationale for Phase I b Cohort I (Gastric Cancer) ............................................................... 30 
1.5. 
Rationale for Dose Selection of GS- 1423 in Phase la Dose Escalation ................................................ 3 1 
1.6. 
Risk/Benefit Assessment for the Study .................................................................................................. 33 
1.7. 
Compliance ............................................................................................................................................ 34 
2. 
OBJECTIVES ..................................................................................................................................................... 35 
2.1. 
Phase la .................................................................................................................................................. 35 
2.2. 
Phase lb ................................................................................................................................................. 35 
3. 
STUDY DESIGN ................................................................................................................................................ 37 
3.1. 
3.2. 
3.3. 
3.4. 
3.5. 
3.6. 
3.7. 
Endpoints ............................................................................................................................................... 37 
Study Design .......................................................................................................................................... 37 
3.2.1. 
Phase la ................................................................................................................................ 37 
3.2.2. 
Phase lb ............................................................................................................................... 38 
3 .2.3. 
Dose Escalation .................................................................................................................... 38 
3.2.4. 
Safety Review Team ............................................................................................................ 46 
Study Treatments ................................................................................................................................... 46 
Duration ofTreatment ............................................................................................................................ 47 
Study Discontinuation Criteria ............................................................................................................... 48 
Post Study Care ...................................................................................................................................... 48 
Source Data ............................................................................................................................................ 48 
4. 
SUBJECT POPULATION .................................................................................................................................. 50 
4.1. 
Number of Subjects and Subject Selection ............................................................................................ 50 
4.1.1. 
Subject Replacement ............................................................................................................ 50 
4.2. 
Inclusion Criteria .................................................................................................................................... 50 
4.3. 
Exclusion Criteria ................................................................................................................................... 52 
5. 
INVESTIGATIONAL MEDICINAL PRODUCTS ........................................................................................... 55 
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5.1.
Enrollment and Blinding........................................................................................................................55
5.1.1.
Enrollment............................................................................................................................55
5.1.2.
Blinding................................................................................................................................55
5.2.
Description and Handling of GS-1423...................................................................................................55
5.3.
Formulation............................................................................................................................................55
5.3.1.
GS-1423 ...............................................................................................................................55
5.3.2.
mFOLFOX6 .........................................................................................................................56
5.3.3.
Packaging and Labeling .......................................................................................................56
5.3.4.
Storage and Handling...........................................................................................................56
5.4.
Dosage and Administration of Study Drugs...........................................................................................57
5.4.1.
GS-1423 Monotherapy: Phase 1a and Phase 1b Cohort 2....................................................57
5.4.2.
GS-1423 + mFOLFOX6: Phase 1b Cohort 1 .......................................................................57
5.5.
Dose Modifications and Treatment Delay..............................................................................................58
5.5.1.
Dose Modifications ..............................................................................................................58
5.5.2.
Treatment Delay...................................................................................................................59
5.5.3.
Treatment of Infusion-Related Reactions.............................................................................59
5.5.4.
Management of Potential Immune-Related Adverse Events................................................61
5.5.5.
Criteria to Resume Treatment ..............................................................................................68
5.5.6.
Permanent Treatment Discontinuation.................................................................................69
5.5.7.
Treatment Beyond Initial Progressive Disease.....................................................................71
5.6.
Prior and Concomitant Medications.......................................................................................................72
5.6.1.
Acceptable Concomitant Medications..................................................................................72
5.6.2.
Prohibited and/or Restricted Treatments ..............................................................................73
5.6.3.
Other Restrictions and Precautions ......................................................................................74
5.7.
Accountability for Study Drug...............................................................................................................74
5.7.1.
Investigational Medicinal Product Return or Disposal.........................................................74
6.
STUDY PROCEDURES ....................................................................................................................................75
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................75
6.2.
Pretreatment Assessments......................................................................................................................75
6.2.1.
Screening..............................................................................................................................75
6.2.2.
Re-screening Criteria............................................................................................................78
6.2.3.
Medical History and Baseline Assessments .........................................................................78
6.2.4.
Vital Signs, Weight, and Height...........................................................................................79
6.2.5.
Physical Examination...........................................................................................................79
6.2.6.
Electrocardiogram................................................................................................................79
6.2.7.
Echocardiogram or MUGA Scan .........................................................................................80
6.2.8.
Prior and Concomitant Medications.....................................................................................80
6.2.9.
Clinical Laboratory Assessments .........................................................................................80
6.3.
Randomization .......................................................................................................................................81
6.4.
Treatment Assessments..........................................................................................................................81
6.5.
Unscheduled Visits.................................................................................................................................82
6.6.
Pharmacokinetic 
 Assessments.......................................................................................82
6.6.1.
Pharmacokinetic Assessments..............................................................................................82
6.6.2.
Immunogenicity Assessment................................................................................................87
6.7.
End of Study...........................................................................................................................................95
6.8.
Posttreatment Assessments ....................................................................................................................95
6.8.1.
End-of-Treatment Phase Visits.............................................................................................95
6.8.2.
Posttreatment Follow-up Phase Visits..................................................................................95
6.8.3.
Survival Follow-up...............................................................................................................96
6.9.
Assessments for Early Discontinuation from Study...............................................................................96
6.10.
Criteria for Discontinuation from Treatment or Study...........................................................................96
6.10.1.
Criteria for Discontinuation from Treatment........................................................................96
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6.10.2.
Discontinuation from Disease Response Evaluation............................................................98
6.10.3.
Criteria for Discontinuation from Study...............................................................................98
6.11.
Efficacy Assessments.............................................................................................................................98
6.11.1.
Response Assessment...........................................................................................................98
6.11.2.
Tumor Assessments..............................................................................................................99
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT.............................................................................102
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events...............................102
7.1.1.
Adverse Events...................................................................................................................102
7.1.2.
Serious Adverse Events......................................................................................................102
7.2.
Assessment of Adverse Events and Serious Adverse Events...............................................................104
7.2.1.
Assessment of Causality for Study Drugs and Procedures.................................................104
7.2.2.
Assessment of Severity ......................................................................................................105
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.....................................................................................................................105
7.3.1.
Adverse Events...................................................................................................................105
7.3.2.
Serious Adverse Events......................................................................................................106
7.4.
Gilead Reporting Requirements...........................................................................................................107
7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or 
Serious Adverse Events........................................................................................................................107
7.6.
Toxicity Management ..........................................................................................................................107
7.7.
Special Situations Reports....................................................................................................................108
7.7.1.
Definitions of Special Situations........................................................................................108
7.7.2.
Instructions for Reporting Special Situations.....................................................................108
8.
STATISTICAL CONSIDERATIONS..............................................................................................................111
8.1.
Analysis Objectives and Endpoints......................................................................................................111
8.1.1.
Analysis Objectives............................................................................................................111
8.1.2.
Primary Endpoints..............................................................................................................111
8.1.3.
Secondary Endpoints..........................................................................................................111
8.2.
Planned Analyses .................................................................................................................................113
8.2.1.
Interim Analysis .................................................................................................................113
8.2.2.
Final Analysis.....................................................................................................................113
8.3.
Analysis Conventions...........................................................................................................................114
8.3.1.
Analysis Sets ......................................................................................................................114
8.4.
Data Handling Conventions .................................................................................................................115
8.5.
Demographic and Baseline Characteristics..........................................................................................115
8.6.
Efficacy Analysis .................................................................................................................................115
8.6.1.
Categorical Endpoints ........................................................................................................115
8.6.2.
Time-to-Event Endpoints ...................................................................................................115
8.7.
Safety Analysis.....................................................................................................................................116
8.7.1.
Extent of Exposure.............................................................................................................116
8.7.2.
Adverse Events...................................................................................................................116
8.7.3.
Laboratory Evaluations ......................................................................................................116
8.7.4.
Other Safety Evaluations....................................................................................................117
8.8.
Pharmacokinetic Analysis....................................................................................................................117
8.9.
Immunogenicity Analysis ....................................................................................................................117
8.11.
Sample Size..........................................................................................................................................118
9.
RESPONSIBILITIES........................................................................................................................................119
9.1.
Investigator Responsibilities ................................................................................................................119
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9.1.1.
Good Clinical Practice........................................................................................................119
9.1.2.
Financial Disclosure...........................................................................................................119
9.1.3.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval.........................................................................................................119
9.1.4.
Informed Consent...............................................................................................................119
9.1.5.
Confidentiality....................................................................................................................120
9.1.6.
Study Files and Retention of Records ................................................................................120
9.1.7.
Case Report Forms.............................................................................................................121
9.1.8.
Investigator Inspections......................................................................................................122
9.1.9.
Protocol Compliance..........................................................................................................122
9.2.
Sponsor Responsibilities ......................................................................................................................122
9.2.1.
Protocol Modifications.......................................................................................................122
9.2.2.
Study Report and Publications ...........................................................................................122
9.3.
Joint Investigator/Sponsor Responsibilities .........................................................................................123
9.3.1.
Payment Reporting.............................................................................................................123
9.3.2.
Access to Information for Monitoring................................................................................123
9.3.3.
Access to Information for Auditing or Inspections ............................................................123
9.3.4.
Study Discontinuation........................................................................................................124
10.
REFERENCES .................................................................................................................................................125
11.
APPENDICES ..................................................................................................................................................128
Appendix 1.
Investigator Signature Page..................................................................................................129
Appendix 2.
Study Procedures Tables ......................................................................................................130
Appendix 3.
Response Evaluation Criteria in Solid Tumors (RECISTVersion 1.1).................................139
Appendix 4.
NCI CTCAE v5.0 Grading Scale for Severity of Adverse Events and Laboratory 
Abnormalities .......................................................................................................................143
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................144
Appendix 6.
Dose Modification Tables for mFOLFOX6 .........................................................................147
LIST OF IN-TEXT TABLES
Table 1-1.
Calculation of GS-1423 Starting Dose from MABEL and Determination of Safety 
Margin ....................................................................................................................................32
Table 3-1.
Phase 1a Part A GS-1423 Dose Levels and Cohorts ..............................................................39
Table 3-2.
Phase 1b Cohort 1 Safety Run-in GS-1423 Dose Levels .......................................................43
Table 3-3.
Phase 1a Part B Dose Levels..................................................................................................47
Table 5-1.
Dose Modificationa for mFOLFOX6......................................................................................58
Table 5-2.
GS-1423 Infusion-Related Reactions Management Guidelines .............................................61
Table 5-3.
Dermatological irAE Management Algorithm .......................................................................62
Table 5-4.
Gastrointestinal irAE Management Algorithm.......................................................................63
Table 5-5.
Pulmonary irAE Management Algorithm ..............................................................................64
Table 5-6.
Hepatic irAE Management Algorithm....................................................................................65
Table 5-7.
Endocrine irAE Management Algorithm................................................................................66
Table 5-8.
Renal irAE Management Algorithm.......................................................................................67
Table 5-9.
Neurological irAE Management Algorithm ...........................................................................68
Table 5-10.
Drug-Related Adverse Events Requiring Discontinuation of GS-1423 .................................69
Table 6-1.
Analytes..................................................................................................................................81
Table 6-2.
Schedule of Pharmacokinetic Assessments for QW Dosing Schedule in Phase 1a 
Cohorts ...................................................................................................................................83


GS- 1423 
Protocol GS-US-505-5452 
Gilead Sciences, lnc. 
Final 
Amendment2 
Table 6-3. 
Table 6-4. ---
Table 6-8. 
Table 6-9. 
Table 6-10. ---
Table 6-18. 
Figure 1- 1. 
Figure 3- 1. 
Figure 3-2. 
CONFIDENTIAL 
Schedule of Phannacokinetic Assessments for Q2W Dosing Schedule in Phase la 
Cohorts ................................................................................................................................... 84 
Schedule of Phannacokinetic Assessments for Q3W Dosing Schedule in Phase la 
Cohorts ................................................................................................................................... 85 
Sc e u e o ADA Assessments or QW ................................................................................. 7 
Schedule of ADA Assessments for Q2W ............................................................................... 87 
Schedule of ADA Assessments for 3W ............................................................................... 88 
LIST OF IN-TEXT FIGURES 
GS- 1423 Design ..................................................................................................................... 27 
Accelerated Dose Escalation Scheme ..................................................................................... 40 
3+3 Dose Escalation Scheme ................................................................................................. 41 
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Study Title: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Study Centers 
Planned: 
Objectives 
(Phase la): 
CONFIDENTIAL 
PROTOCOL SYNOPSIS 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
Final 
Amendment2 
A Phase la/lb Study of GS-1423, an Anti-CD73-TGFP-Trap 
Bifunctional Antibody, as Monotherapy or in Combination with a 
Chemotherapy Regimen in Subjects with Advanced Solid Tumors 
142793 
2019-004938-41 
NCT03954704 
Approximately 35 centers in the United States, Europe, and rest of 
world 
The primary objectives are: 
• 
Part A (dose escalation): To assess safety and tolerability and to 
define the dose limiting toxicity (DL T) and maximum tolerated 
dose (MTD) or recommended Phase 2 dose (RP2D) of GS-1423 
monotherapy in subjects with advanced solid tumors 
• 
Part B (flat dose regimens): To assess safety and tolerability of 
GS-1423 monotherapy in subjects with advanced solid tumors 
The secondary objectives are: 
• 
To characterize GS-1423 phannacokinetics (PK) 
• 
To evaluate GS-1423 immunogenicity 
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GS- 1423 
Protocol GS-US-505-5452 
Gilead Sciences, lnc. 
Objectives 
(Phase lb): 
CONFIDENTIAL 
Final 
Amendment2 
Cohort 1 (gastric cancer): GS-1423 in combination with a 
chemotherapy regimen in advanced (unresectable, recurrent or 
metastatic) gastric and gastroesophageal junction adenocarcinoma 
For safety run-in, the primary objective is: 
• 
To assess safety and tolerability and to define the DLT and MTD 
or RP2D of GS-1423 in combination with a chemotherapy regimen 
in subjects with advanced gastric or gastroesophageal junction 
adenocarcinoma 
For post safety run-in, the primary objective is: 
• 
To assess the preliminary efficacy of GS-1423 in combination with 
a chemotherapy regimen in subjects with advanced gastric or 
gastroesophageal junction adenocarcinoma, as determined by the 
confinned objective ORR 
For post safety run-in, the secondary objective is: 
• 
To assess safety and tolerability of GS-1423 in combination with a 
chemotherapy regimen in subjects with advanced gastric or 
gastroesophageal junction adenocarcinoma 
I 
I 
I 
I 
I 
Cohort 2 (paired biopsy): GS-1423 monotherapy in subjects with 
advanced solid tumors accessible for biopsy 
The primary objective is: 
• 
To assess safety and tolerability of GS-1423 monotherapy in 
subjects with advanced solid tumors 
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Protocol GS-US-505-5452 
Gilead Sciences, lnc. 
Study Design 
(Phase la) 
CONFIDENTIAL 
I 
I 
I 
I 
I 
I 
Part A - Dose escalation 
Final 
Amendment2 
This is an open-label, Phase la study to evaluate the safety, 
tolerability, and PK profiles of GS-1423 and to define the DLT and 
MTD or RP2D of GS-1423 monotherapy in subjects with advanced 
solid tumors. 
This study will be conducted in an accelerated titration, followed by a 
3+3 dose escalation design. GS-1423 will be administered on Day 1 of 
each 2-week cycle (Q2W) for up to 1 year or until any progressive 
disease (PD) or unacceptable toxicity. The starting dose was selected 
to be 0.3 mg/kg derived from minimally anticipated biologic effect 
level (MABEL). A Safety Review Team (SRT) will be established to 
assess safety and decide on dose escalation. 
Starting at Cohort 4 (10 mg/kg), if no DLT is observed during the 28-
day DL T observation period in the first 3 subjects, 3 additional 
subjects ma~
ective dose level to obtain more 
safety, PK,-
data. If~ 2 subjects have 
experienced DL Ts in the last 3 ( of 6) subjects, dose escalation will halt 
and up to 3 additional subjects will be enrolled at the preceding dose 
level (if there were only 3 subjects in that cohort) for DLT assessment. 
If 6 subjects were already evaluated, the preceding dose level will be 
considered as MTD. 
Part B - Flat dose regimens 
Part B will consist ofup to 3 adaptive cohorts (every week [QW], 
Q2W and/or, every 3 weeks [Q3W]) to evaluate the safety, tolerability, 
and PK profiles of GS-1423 monotherapy with flat dose regimens. 
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Based on PK, 
 and safety results from the Part A 
study, the target exposures for the Phase 1b study will be determined. 
Subsequently, 6 to 12 subjects per cohort may be enrolled to explore 
the flat dose(s) and dosing interval(s) that will achieve the target
exposures. The doses evaluated in these subjects will be selected such 
that they do not result in exposures that are higher than the maximum 
tolerated exposures and match the exposures for RP2D determined 
based on the dose escalation portion of the study. Gilead may choose 
not to initiate any or all of the adaptive cohorts if it is deemed 
unnecessary.
Study Design 
(Phase 1b) 
This is an open-label, Phase 1b study with 2 cohorts.
Cohort 1 (Gastric)
Cohort 1 will assess safety and tolerability and define the DLT and 
MTD or RP2D of GS-1423 in combination with a chemotherapy 
regimen (oxaliplatin, 5-fluorouracil [5-FU], and leucovorin; 
mFOLFOX6) in subjects with advanced (unresectable, recurrent or 
metastatic) gastric or gastroesophageal junction adenocarcinoma who 
have not previously received systemic therapy for advanced disease.
Safety run-in: A standard 3+3 dose escalation design will be used to 
define the DLT and MTD or RP2D of GS-1423 in combination with 
mFOLFOX6. An SRT will assess safety and decide on dose 
escalation.
After the MTD or RP2D of GS-1423 in combination with 
mFOLFOX6 has been determined, the cohort will be expanded by 
adding approximately 70 subjects to explore the potential efficacy. 
One futility interim analysis may be performed after approximately 
50% of subjects have been enrolled and are able to complete study 
treatment for at least 6 months post safety run-in.
Cohort 2 (Paired Biopsy)
Cohort 2 will assess safety and tolerability of GS-1423 
monotherapy in multiple tumor types. Cohort 2 will enroll subjects 
until 15 evaluable paired tumor biopsies (baseline and any on 
treatment) have been collected, including a minimum of 5 biopsies 
from non-small-cell lung carcinoma (NSCLC) (non-squamous 
adenocarcinoma) and 5 colorectal cancer (CRC) or pancreatic 
cancer subjects.
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Number of Subjects 
Planned:
Approximately 213 subjects will be enrolled

Phase 1a: 
(Part A): Up to 53 subjects 
(Part B): Up to 40 subjects

Phase 1b:
Cohort 1: Up to 90 subjects
Cohort 2: Up to 30 subjects
Target Population:
Phase 1a (Parts A and B): Subjects who are ≥18 years with a 
histologically or cytologically confirmed diagnosis of a locally 
advanced or metastatic solid tumor for which no standard therapy is 
available or standard therapy has failed
Phase 1b: 
Cohort 1: Subjects who are ≥18 years with a histologically or 
cytologically confirmed advanced (unresectable, recurrent or 
metastatic) gastric or gastroesophageal junction adenocarcinoma who 
have not previously received systemic therapy for advanced disease
Cohort 2: Subjects who are ≥18 years with a histologically or 
cytologically confirmed diagnosis of a locally advanced or metastatic 
solid tumor for which no standard therapy is available or standard 
therapy has failed and from whom biopsies can be obtained prior to 
study treatment and on-treatment
Duration of 
Treatment:
Phase 1a (all cohorts) and Phase 1b (Cohort 2): Subjects will continue 
GS-1423 for up to 1 year (maximum 52 cycles for QW, 26 cycles for 
Q2W and 17 cycles for Q3W) or until the subject meets study 
treatment discontinuation criteria. 
Phase 1b (Cohort 1): Subjects will continue GS-1423 for up to 2 years 
(maximum 52 cycles) or until PD, unacceptable toxicity, substantial 
noncompliance with study procedures or study treatment regimen, 
study discontinuation or withdrawal from study. mFOLFOX6 will be 
administered for up to 12 cycles with the option of maintenance 
therapy with 5-FU and leucovorin per Investigator’s discretion until 
the subject meets study treatment discontinuation criteria or for up to 2 
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Diagnosis and 
Eligibility Criteria:
Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible 
for participation in this study:
1) Voluntarily agree to participate by giving a signed written 
informed consent
2) Age ≥18 years 
3) Diagnosis: 
a) Phase 1a and Phase 1b Cohort 2: Have a histologically or 
cytologically confirmed diagnosis of a locally advanced or 
metastatic solid tumor for which no standard therapy is 
available or standard therapy has failed
b) Phase 1b Cohort 1 (gastric cancer): Have histologically or 
cytologically confirmed advanced (unresectable, recurrent or 
metastatic) gastric or gastroesophageal junction 
adenocarcinoma who have not previously received systemic 
therapy for advanced disease (perioperative, neoadjuvant, and 
adjuvant chemotherapy regimens will not count as a prior 
regimen, unless PD has occurred during or within 6 months of 
neoadjuvant/adjuvant chemotherapy). Gastroesophageal 
junction adenocarcinoma is defined as tumors with epicenters 
no more than 2 cm into the gastric cardia.
i)
Is human epidermal growth factor receptor 2 (HER2)/neu 
negative
ii) Has not received prior treatment with an immune
checkpoint inhibitor within 2 years of day 1 of study 
treatment 
4) Have measurable disease on imaging based on Response 
Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 
5) Have a life expectancy of at least 3 months and an Eastern 
Cooperative Oncology Group (ECOG) performance status of 
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6) Have adequate organ function as indicated by the following 
laboratory values:
System
Laboratory Valuea
Hematologicalb
Absolute Neutrophil Count 
(ANC)
≥ 1.5 x 109/L 
≥2 109/L (for Phase 1b Cohort 1 only)
Platelets
≥ 100 x 109/L
Hemoglobin
≥9 g/dL
Renal
Creatinine clearance
≥ 50 mL/min by the Cockcroft-Gault method
Hepatic
Total bilirubin
≤ 1.5 x ULN
AST (SGOT) and ALT
(SGPT)
≤ 2.5 x ULN 
Coagulationc
International Normalized 
Ratio (INR) or Prothrombin 
Time (PT)
Activated Partial 
Thromboplastin Time 
(aPTT)
≤ 1.5 x ULN unless the subject 
is receiving anticoagulant 
therapy
≤ 1.5 x ULN unless the subject 
is receiving anticoagulant 
therapy
a
All screening laboratory tests must be reviewed by the investigator and be acceptable prior 
to randomization.
b
Hematologic laboratory values must be met at screening visit and maintained without 
transfusion and growth factors prior to the first study drug dose
c
Subjects on full dose oral anticoagulation, must be on a stable dose (minimum duration 
14 days). Subjects on low molecular weight heparin will be allowed. In subjects receiving 
warfarin, the recommended INR is ≤ 3.0 with no active bleeding (ie, no bleeding within 
14 days prior to first dose of study drug).
7) Tissue criteria:
a) Phase 1a and Phase 1b Cohort 1: Subjects must have available,
sufficient, and adequate formalin-fixed tumor tissue sample (as 
specified in the Laboratory Manual) preferably from a biopsy 
of a tumor lesion obtained either at the time of or after the 
diagnosis of advanced disease has been made and from a site 
not previously irradiated. Alternatively, subjects must agree to 
have a biopsy taken prior to entering the study to provide 
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needle or excisional biopsy or resected tissue is required.
b) Phase 1b Cohort 2: Subjects must have a tumor lesion that 
biopsies can be obtained from prior to treatment and 
on-treatment. The biopsies for each subject should be taken 
from the same lesion.
8) A negative serum pregnancy test is required for female subjects 
(unless permanently sterile or greater than 2 years postmenopausal 
as described in Appendix 5).
9) Male subjects and female subjects of childbearing potential who 
engage in heterosexual intercourse must agree to use 
protocol-specified method(s) of contraception and refrain from egg 
or sperm donation as described in Appendix 5.
10) Lactating females must agree to discontinue nursing before the 
study drug is administered.
11) Is willing and able to comply with the requirements of the protocol
Exclusion Criteria:
Subjects who meet any of the following exclusion criteria are not to be 
enrolled in this study:
1) Is currently participating and receiving study therapy or has 
participated in a study of an investigational agent and received 
study therapy or used an investigation device within 3 weeks of the 
first dose of treatment
2) Has received prior systemic cytotoxic chemotherapy, biological 
therapy, radiotherapy, or major surgery within 3 weeks; a 1-week 
washout is permitted for palliative radiation to non-central nervous 
system (CNS) disease with Gilead approval
3) Has persisting toxicity related to prior therapy of National Cancer 
Institute Common Terminology Criteria for Adverse Events 
Version 5.0 (NCI CTCAE v5.0) Grade > 1 severity
Note: Alopecia and sensory neuropathy of Grade ≤ 2 is 
acceptable.
4) Is expected to require any other form of systemic or localized 
anticancer therapy while on study (including maintenance therapy 
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5) Has known severe hypersensitivity reactions (NCI CTCAE 
Grade ≥3) to fully human monoclonal antibodies, GS-1423 
formulation excipient, or severe reaction to immuno-oncology 
agents, such as colitis or pneumonitis requiring treatment with 
corticosteroids, any history of anaphylaxis, or uncontrolled asthma
6) Is receiving systemic corticosteroid therapy 1 week prior to the 
first dose of study treatment or receiving any other form of 
systemic immunosuppressive medication 
Note: The following corticosteroid uses are permitted:  use as 
premedication for known hypersensitivity reactions (e.g. IV contrast, 
IV drug infusions); intraocular, intranasal, inhaled, and/or topical 
corticosteroids; and/or prednisone at doses of up to 10 mg per day or 
equivalent.
7) Has concurrent active malignancy other than nonmelanoma skin 
cancer, carcinoma in situ of the cervix, or superficial bladder 
cancer who has undergone potentially curative therapy with no 
evidence of disease. Subjects with other previous malignancies are 
eligible if disease free for > 2 years
8) Has a known CNS metastasis(es), unless metastases are treated 
and stable and the subject does not require systemic corticosteroids
for management of CNS symptoms at least 7 days prior to study 
treatment. Subjects with history of carcinomatous meningitis are 
excluded regardless of clinical stability.
9) Has active or history of autoimmune disease that has required 
systemic treatment within 2 years of the start of study treatment 
(ie, with use of disease-modifying agents, corticosteroids, or 
immunosuppressive drugs)
Note: Subjects with diabetes type 1, vitiligo, psoriasis, 
hypothyroid disease, or hyperthyroid disease not requiring 
immunosuppressive treatment are eligible.
10) Has had an allogeneic tissue/solid organ transplant
11) Has or had interstitial lung disease (ILD)
12) Has a serious systemic fungal, bacterial, viral, or other infection 
that is not controlled or requires IV antibiotics
13) Has known history of human immunodeficiency virus (HIV) 
14) Has known active hepatitis B virus (HBV) and/or hepatitis C virus 
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15) Subjects with cardiovascular disease/abnormalities will be 
excluded per the following criteria:
a) Has clinically significant (ie, active) cardiovascular disease: 
cerebral vascular accident/stroke or myocardial infarction 
within 6 months of enrollment, unstable angina, congestive 
heart failure (New York Heart Association class ≥II), or 
serious uncontrolled cardiac arrhythmia requiring medication
b) Has a mean QT interval corrected for heart rate using the 
Fridericia formula (QTcF) ≥470 ms
c) Has systolic dysfunction defined as ejection fraction < 50% 
measured by echocardiogram (or multigated acquisition 
[MUGA] scan) at baseline
16) Has a history or current evidence of any condition, therapy, or 
laboratory abnormality that might confound the results of the 
study, interfere with the subject's participation for the full duration 
of the study, or is not in the best interest of the subject to 
participate, in the opinion of the treating investigator
17) Has known psychiatric or substance abuse disorders that would 
interfere with cooperation with the requirements of the study
18) Is legally incapacitated or has limited legal capacity
19) Taking biotin supplements within 72 hours of screening
20) Positive serum pregnancy test (Appendix 5)
21) Has had prior treatment with anti-cluster of differentiation (CD)73 
or transforming growth factor beta (TGFβ) therapies
22) Breastfeeding female
23) Phase 1b Cohort 2: Has melanoma 
24) Phase 1b Cohort 2: Has any tumor from which 2 biopsies cannot 
be obtained. Bone biopsies and ascites are not acceptable tumor 
samples for the study
Study Procedures/
Frequency:
Screening:
Screening will commence with obtaining the subject’s signed 
informed consent and will occur up to 28 days prior to the first dosing 
of study drug. Screening procedures will include the following: 
medical history review, physical examination, vital signs, height and 
weight, 12-lead electrocardiogram (ECG), echocardiogram (or MUGA 
scan), ECOG performance status, prior/concomitant medication 
review, blood collection for pregnancy test (females of childbearing 
potential), serum chemistry, 
, 
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hematology, endocrine function, coagulation, HBV and HCV 
serology, urinalysis, adverse event (AE) assessment, computed 
tomography or magnetic resonance imaging, and tumor tissue. For 
Phase 1b Cohort 2, screening will include an assessment of if 2 
biopsies (pretreatment and on treatment) can be obtained from the 
same lesion. Baseline tumor lesions will be measured and 
characterized prior to enrollment to assess the subject’s disease status 
prior to beginning treatment.
Treatment
Phase 1a:
Part A Dose escalation
GS-1423 will be administered Q2W with associated evaluations and 
procedures that must be performed at specific time points. Each cycle
begins with the administration of GS-1423 on Day 1 of a 2-week cycle 
(timing of doses may be adjusted for management of AEs). Subjects 
will be treated for up to 1 year or until any PD or unacceptable 
toxicity.
Part B
Flat dose regimens
GS-1423 monotherapy may also be evaluated at a flat dose 
administered QW, Q2W, and/or Q3W. Based on safety data and 
available PK 
data from Part A, Part B will be 
initiated at or below the exposures of the highest dose for which data 
are available from Part A. Part B cohorts may be initiated in parallel 
with cohorts from Part A of the study if the dose/exposure under 
evaluation is at or below a dose/exposure that has already been 
evaluated and considered as safe. 
Phase 1b:
Cohort 1 (gastric): GS-1423 will be administered Q2W for up to 
2 years or until PD or unacceptable toxicity. The chemotherapy 
regimen mFOLFOX6 will be administered Q2W for up to 12 cycles.
After 12 cycles, subjects may continue to receive 5-FU and leucovorin 
at the investigator’s discretion until the subject meets study treatment 
discontinuation criteria.
Cohort 2 (paired biopsy): GS-1423 will be administered every 2 weeks 
(Q2W) for up to 1 year or until PD or unacceptable toxicity. If an 
alternate dosing schedule is recommended after Phase 1a, this dosing 
schedule may also be adapted to this cohort.
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Tumor Assessment:
Tumor assessments will be conducted at 6, 12, 18, and 24 weeks (± 7
days) from the first treatment and then every 12 weeks thereafter until 
PD as assessed by investigator, unexpected toxicity occurs, or a new 
line of therapy is initiated for up to 1 year (Phase 1a and Phase 1b 
Cohort 2) or 2 years (Phase 1b Cohort 1).
Test Product, Dose, 
and Mode of 
Administration:
Phase 1a
Part A Dose escalation
GS-1423 will be administered through IV infusion over 60 minutes. 
The planned dose cohorts are 0.3, 1, 3, 10, 20, 30, and 45 mg/kg as 
monotherapy.
The dose escalation will be conducted in an accelerated titration, 
followed by a 3+3 dose escalation design. At each of the first 2 dose 
levels of 0.3 mg/kg and 1 mg/kg, if 2 or more drug-related AEs of 
Grade 2 or higher or at least 1 DLT are observed during the 28-day 
DLT observation period, the 3+3 escalation scheme will be used at 
that dose and subsequent doses. Gilead may choose not to enroll any 
cohort if it is deemed unnecessary.
Part A: GS-1423 Dose Levels and Cohorts
Cohort
No. of Subjects
Escalation Type
Dose of GS-1423 
(mg/kg)
1
1 or 3 6
Accelerated titration
0.3
2
1 or 3 6
Accelerated titration
1
3
3 6
3+3
3
4
3 6
3+3
10
5
3 6
3+3
20
6
3 6
3+3
30
7
3 6
3+3
45
An additional 6 subjects may be enrolled at a dose level at or below maximum tolerated dose
to obtain additional safety, pharmacokinetics, and 
information. 
Part B
Flat dose regimens
After the target exposures for the Phase 1b study has been determined, 
an additional 6 to 12 subjects per cohort may be enrolled to explore the 
RP2D at flat dose(s) and dosing interval(s) that will achieve the target
exposures from Part A. The doses/schedules evaluated in these 
subjects will be selected as such that the expected exposures will not 
exceed the maximum tolerated exposures determined in the dose 
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escalation portion of the study. Gilead may choose not to initiate any 
or all of the adaptive cohorts if it is deemed unnecessary.
Part B: GS-1423 Dose Levels and Cohorts
Adaptive Cohort
No. of Subjects
Dose of GS-1423 
(mg)
8
6 12
Dose 1 (Q2W)
9
6 12
Dose 2 (QW) 
10
6 12
Dose 3 (Q3W)
QW  every week; Q2W  every 2 weeks; Q3W  every 3 weeks 
Phase 1b 
Cohort 1 (Gastric)
Safety run-in: The planned starting dose of GS-1423 will be targeted 
to achieve the exposure at -1 dose level of RP2D monotherapy (Q2W) 
determined from Phase 1a. GS-1423 will be administered in 
combination with mFOLFOX6.
Phase 1b Cohort 1 Safety Run-in GS-1423 Dose Levels and Cohorts
Regimen
No. of Subjects
Escalation Type
Dose of GS-1423 
(mg)
GS 1423 + 
mFOLFOX6
3 6
3+3
1 Dose 1 Q2W
GS 1423 + 
mFOLFOX6
3 6
3+3
Dose 1 Q2W
5 FU  5 fluorouracil; Q2W  every 2 weeks; 
The mFOLFOX6 regimen consists of l leucovorin/dl leucovorin 200/400 mg/m2 and 
oxaliplatin 85 mg/m2 followed by bolus 5 FU 400 mg/m2 and a 46 hour infusion of 5 FU 
2400 mg/m2. Administration of mFOLFOX6 will follow administration of GS 1423 on Day 1 
of each cycle.
1 Dose 1: Will be targeted to achieve the exposure at 1 dose level of RP2D monotherapy 
(Q2W) determined based on cumulative data from Phase 1a.
Dose 1: Will be targeted to achieve the exposure at the dose level of RP2D monotherapy 
(Q2W) determined based on cumulative data from Phase 1a.
An additional 6 subjects may be enrolled at a dose level at or below 
MTD to obtain additional safety, PK, 
 
information. 
Following the safety run-in, approximately 70 subjects will be enrolled 
to receive GS-1423 at the dose level determined from the safety run-in 
period, in combination with mFOLFOX6 regimen.
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Cohort 2 (Paired Biopsy)
GS-1423 is planned to be administered at Dose 1 Q2W in this cohort. 
However, other dose/dosing schedule may be selected upon review of 
cumulative data from Phase 1a. The planned dose/dosing schedule of 
GS-1423 will be targeted to achieve the exposure at the dose level of 
the RP2D monotherapy (Q2W) determined from Phase 1a.
Regimen
No. of Subjects
Dose of GS-1423 
(mg)
GS 1423 
15 with evaluable paired 
biopsies
Dose 1
     
Reference Therapy, 
Dose, and Mode of 
Administration:
The mFOLFOX6 dosing regimen consists of l-LV 200 mg/m2 or 
dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5-FU 
400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2. 
Administration of mFOLFOX6 will follow administration of GS-1423 
on Day 1 of each 2-week cycle.
Criteria for 
Evaluation:
Safety:
Safety will be assessed by evaluating occurrence of DLTs in subjects 
in dose escalation during the first 28 days of treatment, incidence of 
AEs for all dose groups for the duration of the study, assessment of 
clinical laboratory test findings, physical examination, 12-lead ECG, 
echocardiogram or MUGA scan, ECOG performance status, and vital 
signs measurements. Adverse events will be graded using NCI 
CTCAE v5.0. 
Efficacy:
Response assessment will be performed according to RECIST 1.1. 
Radiology assessment will be performed at 6, 12, 18, and 24 
weeks (± 7 days) from first treatment dose, and then every 12 weeks 
thereafter.
Pharmacokinetics:
Plasma drug concentrations will be analyzed. The PK parameters to be 
estimated and reported may include, but may not be limited to, 
maximum observed drug concentration (Cmax), area under the 
concentration versus time curve over the dosing interval (AUCtau),
observed drug concentration at the trough (Ctrough), time to maximum 
observed concentration (Tmax), systemic clearance (CL), volume of 
distribution (Vd), if applicable. 
The immunogenicity assessment will be conducted to detect and 
measure anti-drug antibodies against GS-1423 (ADA).


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Protocol GS-US-505-5452 
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Statistical Methods: 
CONFIDENTIAL 
Analysis Methods 
Final 
Amendment2 
Safety and efficacy data will be summarized by dose level/cohort for 
subjects in the Safety Analysis Set and the Full Analysis Set, 
respectively. In general, for categorical and ordinal data, count and 
percent of subjects will be summarized. For continuous data, sample 
size, mean, standard deviation, minimum, quartiles, median, and 
maximum values will be smmnarized. Time-to-event endpoints, such 
as progression-free survival (PFS), overall survival (OS) and duration 
of response (DOR), will be analyzed using Kaplan-Meier methods. 
The plasma concentration data and the PK parameters will be 
summarized using descriptive statistics ( eg, sample size, arithmetic 
mean, geometric mean, % coefficient of variation, standard deviation, 
median, minimmn, and maximmn) by dose level/cohort for subjects in 
the PK Analysis Set. 
Number and percentage of positive or negative ADA results at each 
specified time point will be smmnarized by dose level/cohort for 
subjects in the hmnunogenicity Analysis Set. 
Sample Size 
Phase la 
Part A Dose escalation 
Assuming that up to 7 pla1med dose levels for escalation will be tested 
with up to 6 subjects per dose level (42 subjects for escalation) and 
10% of subjects are not evaluable, and 6 additional subjects may be 
enrolled at a dose level at or below MTD to obtain additional safety, 
PK, an 
, up to 53 subjects will be 
enrolled. 
Part B 
Flat dose Regimens 
~
subjects are not evaluable for 
-
assessments in the first 28 days on and after the 
first dosing of GS-1423, up to 40 subjects may be enrolled to obtain 12 
evaluable subjects per cohort. 
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Phase 1b
Cohort 1 (gastric) safety run-in: Assuming that up to 2 planned dose 
levels for escalation will be tested with up to 6 subjects per dose level 
(12 subjects for escalation) and 10% of subjects are not evaluable, and 
6 additional subjects may be enrolled at a dose level at or below MTD 
to obtain additional safety, 
 
 information, 
up to 20 subjects will be enrolled.
Cohort 1 (gastric) post safety run-in: In a randomized Phase 3 study, 
the ORR of mFOLFOX6 as first-line treatment in subjects with 
advanced gastric or gastroesophageal junction adenocarcinoma was 
approximately 40%. Phase 1b Cohort 1 post safety run-in will be a
single-arm study. The null hypothesis of a 35% confirmed ORR will 
be tested against the alternative hypothesis of a 50% confirmed ORR 
with GS-1423 in combination with mFOLFOX6. A sample size of 70 
subjects will provide at least 85% power at a 1-sided significance level 
of 0.1 using a binomial test.
Cohort 2 (paired biopsy): This cohort will enroll subjects until 
evaluable paired biopsies from at least 15 subjects are obtained, with 
at least 5 of which NSCLC subjects and 5 CRC or pancreatic cancer 
subjects.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.
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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
β-hCG
beta-human chorionic gonadotropin
5-FU
5-fluorouracil
ADA
anti-drug antibody against GS-1423
ADL
activities of daily living
AE
adverse event
AJCC-8
eighth edition of the American Joint Committee on Cancer staging manual
ALT
alanine aminotransferase
ANC
absolute neutrophil count
aPTT
activated partial thromboplastin time
AR
accumulation ratio
ASCO
American Society of Clinical Oncology
AST
aspartate aminotransferase
AUCtau
area under the concentration versus time curve over the dosing interval
BUN
blood urea nitrogen
C1D1
Cycle 1 Day 1 
CD
cluster of differentiation
CFR
Code of Federal Regulations
CI
confidence interval
CL
systemic clearance
CLcr
estimated creatinine clearance
Cmax
maximum observed drug concentration
CNS
central nervous system
CR
complete response
CRC
colorectal cancer
CRF
case report form
CRO
contract research organization
CRP
C-reactive protein
CRS
cytokine release syndrome
CT
computed tomography
Ctrough
observed minimal drug concentration during the dosing interval
CTCAE
Common Terminology Criteria for Adverse Events
DCR
disease control rate
DLT
dose limiting toxicity
DNA
deoxyribonucleic acid


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DOR
duration of response
EC90
90% effective concentration
ECD
extracellular domain
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EDC
electronic data capture
EMT
epithelial-to-mesenchymal transition
EOT
End of Treatment
FIH
first-in-human
Free T4
free thyroxine
GCP
Good Clinical Practice
G-CSF
granulocyte colony-stimulating factor
GGT
gamma-glutamyltransferase
GLP
Good Laboratory Practice
HBV
hepatitis B virus
HCV
hepatitis C virus
HED
human equivalent dose
HER2
human epidermal growth factor receptor 2
HIV
human immunodeficiency virus
IB
investigator’s brochure
ICH
International Council for Harmonisation (of Technical Requirements for 
Pharmaceuticals for Human Use)
IEC
independent ethics committee
IgG1
immunoglobulin G1
IHC
immunohistochemistry 
ILD
interstitial lung disease
INR
international normalized ratio
irAE
immune-related adverse event
IRB
institutional review board
ISH
in situ hybridization
IV
intravenous(ly)
IXRS
interactive voice/web response system
KM
Kaplan-Meier
LDH
lactate dehydrogenase
LFT
liver function test


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LLN
lower limit of normal
MABEL
minimally anticipated biologic effect level
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MedDRA
Medical Dictionary for Regulatory Activities
mFOLFOX6
oxaliplatin, 5-fluorouracil, and leucovorin
MRI
magnetic resonance imaging
MRSD
maximum recommended starting dose
MTD
maximum tolerated dose
MUGA
multigated acquisition
NCI
National Cancer Institute
NHP
non-human primate
NOAEL
no observed adverse effect level
NSAID
nonsteroidal anti-inflammatory drug
NSCLC
non-small-cell lung carcinoma
ORR
objective response rate
OS
overall survival
PBMC
peripheral blood mononuclear cell
PD
progressive disease
PD-1
programmed cell death protein 1
PD-L1
ligand 1 of programmed cell death protein 1
PFS
progression-free survival
PK
pharmacokinetic(s)
PLT 
platelet
PO
orally
PR
partial response
PT
prothrombin time
PVE
Pharmacovigilance and Epidemiology
QW
every week
Q2W
every 2 weeks
Q3W
every 3 weeks
QTcF
QT interval corrected for heart rate using the Fridericia formula
RBC
red blood cell
RECIST 1.1
Response Evaluation Criteria in Solid Tumors Version 1.1


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RNA
ribonucleic acid
RP2D
recommended Phase 2 dose
SAE
serious adverse event
SmPC
Summary of Product Characteristics
SOP
standard operating procedure
SSR
Special Situations Report
SRT
Safety Review Team
SUSAR
suspected unexpected serious adverse reaction
t1/2
terminal elimination half-life 
TGFβ
transforming growth factor beta
Tmax
time to maximum observed concentration
TSH
thyroid-stimulating hormone
ULN
upper limit of normal
US
United States
Vd
volume of distribution 
Vdss
volume of distribution at steady-state
WBC
white blood cell


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1.
INTRODUCTION
1.1.
Background
GS-1423 is a bifunctional humanized aglycosylated immunoglobulin G1 (IgG1)κ antibody that 
selectively antagonizes 2 prominent resistance pathways for cancer immunotherapy: Cluster of 
differentiation (CD)73-adenosine and transforming growth factor beta (TGFβ). GS-1423 is 
comprised of a high-affinity adenosinergic anti-CD73 antibody with a single TGFβRII 
extracellular domain (ECD) fused to the CH3 constant region of each antibody heavy chain via a 
glycine-serine (G4S)4G linker (Figure 1-1).
Figure 1-1.
GS-1423 Design
CD  cluster of differentiation; ECD  extracellular domain; TGFβ  transforming growth factor beta
An illustration of the anti CD73 and TGFβ cytokine trap bifunctional antibody GS 1423. The ECD of TGFβRII is fused to the 
CH3 domain of each anti CD73 heavy chain via a (G4S)4G linker. The anti CD73 antibody portion of GS 1423 is aglycosylated 
using a single asparagine to alanine mutation at position 297 to reduce the potential for undesired effector function.
1.2.
Investigational Medicinal Product GS-1423
1.2.1.
General Information
For further information on GS-1423, refer to the current investigator’s brochure (IB).
CD73 antagonism 
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u,,., 
Ul>Of 
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-I 
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"Tl 
"Tl 
= = 
'--"v--' 
TGFP neutralization 


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1.2.2.
Preclinical Pharmacology and Toxicology
CD73-generated adenosine (referred to as CD73-adenosine) and TGFrepresent 2 major 
immunoregulatory and pro-tumorigenic mechanisms responsible for therapeutic resistance and 
progressive disease (PD) in a wide range of cancer patients {Massague 2008}. Extracellular 
adenosine is produced via a cascade of enzymatic reactions with soluble and membrane-bound 
CD73 (ecto-5’ nucleotidase, NT5E) rate-limiting the catalysis of adenosine monophosphate into 
adenosine {Ohta 2001}. TGFproteins are multipotent growth factors present in a variety of 
tissues that become activated following proteolytic release from latent complexes {Morikawa 
2016}. CD73-adenosine and TGFmediate regulatory effects through interactions with a distinct 
set of cell surface receptors, namely adenosine receptors (ie, A1R, A2AR, A2BR, and A3) and 
TGFreceptors (ie, TGFRI, TGFRII, and TGFRIII), each with differential expression 
patterns and affinities for cognate ligands {David 2018, Sheth 2014}. Under physiological 
conditions, CD73-adenosine and TGFβ are highly regulated and serve to maintain tissue 
homeostasis {Antonioli 2013, Arjaans 2012, Li 2006}. However, under conditions of stress, both 
pathways are utilized to combat excessive inflammatory responses and tissue damage. These 
functional characteristics are often co-opted by cancers, leading to a pro-tumor 
microenvironment resulting in abrogated antitumor immune responses, and subsequent tumor 
escape {Bullen 2016, Massague 2008, Massague 2000, Reinhardt 2017, Ryzhov 2014, Samanta 
2018}.
The potential clinical utility of antagonizing the CD73-adenosine and TGFpathways for the 
treatment of cancer is supported by several lines of preclinical evidence. Several studies support 
the use of anti-CD73 antibodies or small molecule inhibitors targeting individual or multiple 
adenosine receptors to enhance conventional (ie, radiotherapy and chemotherapy), targeted 
therapies, and immunotherapeutic interventions for cancer {Allard 2013, Stagg 2010, Young 
2016}. Similarly, a myriad of preclinical studies underscores the importance of TGFinhibition 
for effective anticancer treatment, and the prevention of therapeutic resistance {Holmgaard 2018, 
Lan 2018, Ravi 2018, Takaku 2010}. Consistent with these findings, evaluation of the 
independent pathways has been an active area of clinical interest {Barnhart 2016, Geoghegan 
2016, Knudson 2018, Siu 2018, Strauss 2018}.
While the evidence for intervention of the CD73-adenosine and TGFpathways is encouraging, 
it is important to consider that due to the prevalence of both in human cancers, targeting just 
one of these pathways may not be sufficient to enable effective therapeutic responses. 
GS-1423 binds to both CD73 and TGFwith high affinity. The anti-CD73 portion of GS-1423 
binds to human CD73 with an estimated affinity (KD) of 0.07 nanomolar (nM). The TGFRII 
cytokine trap moiety of GS-1423 binds human TGF1, TGF2, and TGF3 with estimated 
affinities (KD) of 0.002, 1.6, and 0.004 nM, respectively. Importantly, binding to CD73 or TGF
is not compromised by the presence of TGFRII or anti-CD73 domains, respectively. GS-1423 
acts as a potent functional antagonist with the capacity to attenuate CD73 enzymatic activity, 
TGFsignaling, and associated invasive properties of cancer cells, as well as rescue of T-cell 
functional activity under immunosuppressive and exhaustive conditions. Similar to its effects on 
human cells, GS-1423 binds to non-human primate (NHP) cynomolgus monkey CD73 with a 


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less than 2-fold difference and demonstrates similar inhibition of cynomolgus monkey CD73 
enzymatic activity. The active forms of TGF1, TGF2, and TGF3 are 100% conserved 
between humans and NHP. Thus, GS-1423 exhibits analogous binding and function in humans 
and NHP. GS-1423 also binds rodent TGFwith a similar affinity to that of humans. By 
contrast, GS-1423 demonstrates reduced (> 60-fold vs. human) cross-reactivity to rat and no 
cross-reactivity to mouse CD73, therefore cynomolgus monkey NHP was considered the most 
relevant species to evaluate the pharmacological and toxicological impact of GS-1423.
Consistent with an engineered, aglycosylated human IgG1 Fc region, GS-1423 shows reduced
binding to cell-expressed FcRs as compared to conventional IgG1. A fresh human whole blood 
cytokine release assay was used to evaluate the potential risk of GS-1423 eliciting adverse 
pro-inflammatory infusion reactions in soluble and complexed (plate-bound) formats. GS-1423
does not induce cytokines in whole blood that in vivo would be predictive of cytokine release 
syndrome (CRS) in patients. Taken together, the pharmacologic properties of GS-1423 illustrate 
its suitability for clinical development.
Two repeat dose toxicology studies have been undertaken in the most appropriate species, the 
cynomolgus monkey. The first study was a dose range finding investigation, which facilitated the 
design of a Good Laboratory Practice (GLP) study. The test and control articles were 
administered to the 20 female cynomolgus monkeys at dose levels of 0, 25, or 75 mg/kg, via 
slow bolus intravenous (IV) injection once weekly on Days 1, 8, 15, and 22 (unpublished data 
TRL-0175). There were no GS-1423-related mortalities, nor were there any effects noted in 
clinical observations, body weight, urinalysis, hematology, gross pathology, organ weights or 
histopathology. At the highest dose (75 mg/kg/week), decreased total protein, calcium, and 
albumin:globulin ratio in serum were noted with no known toxicological consequences. The no 
observed adverse effect level (NOAEL) was considered to be 75 mg/kg/week for 4 doses in 
4 weeks. 
A 4-week GLP toxicology study was conducted in 20 male and 20 female cynomolgus monkeys 
administered 5 weekly IV bolus infusions of GS-1423 or vehicle control over 29 days at doses of 
0, 10, 25, or 75 mg/kg/dose and included a 4-week recovery period (unpublished data 
TRL-0179). 
There were no treatment related effects on macroscopic appearance or organ weights for brain, 
heart, kidney, liver, lung, spleen, and thymus. There were no GS-1423-related microscopic 
changes noted.
GS-1423 caused no ocular effects, abnormal electrocardiographic findings, changes in body 
temperature, blood pressure, or heart rate during this study. There were no changes in any of the 
neurological parameters evaluated.
In a human tissue cross-reactivity study (unpublished data TRL-0165), GS-1423 produced 
widespread immunoreactivity in the human tissue panel examined. However, the majority of the 
staining was cytoplasmic in nature, and monoclonal antibody binding to cytoplasmic sites in 
tissue cross-reactivity studies generally is considered of little to no toxicologic significance due 
to the limited ability of antibody drugs to access the cytoplasmic compartment in vivo.


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Although the subcellular localization of the neuropil staining in the spinal cord could not be 
identified at the resolution of a light microscope, this staining is also not anticipated to be 
toxicologically significant. 
Membrane binding with GS-1423 was only evident in decidual cells in the placenta and 
spindloid cells in the cervix, which was considered expected reactivity of the test article due to 
the reported expression of TGFβ in placental decidual cells and both CD73 and TGFβ in 
fibroblasts.
1.2.3.
Clinical Studies of GS-1423
This is a first-in-human (FIH) clinical study conducted with this investigational product.
1.3.
Information About Comparator or Reference Products
Not applicable.
1.4.
Rationale for This Study
1.4.1.
Rationale for Phase 1a and Phase 1b Cohort 2 (Dose Escalation, Flat Dose 
Regimens and Paired Biopsy)
GS-1423 is a novel bifunctional molecule comprised of an anti-CD73 antibody fused to a 
TGFβRII-based cytokine trap. Analogous to the format of GS-1423, neutralization of TGFβ 
using TGFβRII-ECD fusion (“cytokine trap”) molecules have yielded promising results in 
preclinical tumor models and in cancer patients {Knudson 2018, Lan 2018, Ravi 2018, Strauss 
2018}. Inhibition of both pathways will be leveraged to address these 2 prominent 
cancer-associated pathways, potentially providing an advantage over strategies targeting 
individual therapeutic resistance pathways by addressing this issue from multiple angles.
These parts of the study aim to evaluate the safety and preliminary efficacy of GS-1423 as 
monotherapy in subjects with advanced solid tumors
 
. Nonclinical pharmacology and toxicology data of 
GS-1423 justify its investigation in clinical studies for the development of a potential treatment 
for subjects with advanced solid tumors. The evaluation of various dose schedules of GS-1423 is 
important in the Phase 1a dose finding part of the study to identify an optimal recommended 
Phase 2 dose (RP2D) regimen for future clinical development of GS-1423.
1.4.2.
Rationale for Phase 1b Cohort 1 (Gastric Cancer)
Gastric cancer remains one of the most common and deadly cancers worldwide, accounting for 
the third leading cause of cancer deaths worldwide, especially among older males {Rawla 2019}. 
The 5-year survival rate for all gastric cancer is 31% in the United States (US) and Stage IIIC 
tumors treated with surgery had a 5-year survival rate of 18%. Current first-line treatment for 
metastatic gastric cancer consists of combination chemotherapy, most often including doublet or 
triplet platinum/fluoropyrimidine combinations. Response rates of combination chemotherapies 
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in these patients are generally in the range of 40% to 50%, and median overall survival (OS) is 
approximately 10 to 12 months {Kim 2012}. Despite recent advancement in treatment, the 
clinical outcome for patients with advanced (unresectable, recurrent or metastatic) disease has 
remained unsatisfactory and alternative treatment options with improved efficacy are sought to
address this unmet medical need.
GS-1423 has the potential to cooperate or synergize with a range of approved cancer therapies 
including radiotherapy, chemotherapy, and immune-based therapies {Allard 2013, Samanta 
2018}. Treatment of cancer cells with certain chemotherapies (such as platinum based) has been 
shown to induce immunogenic cell death, characterized by increased extracellular adenosine
triphosphate levels and upregulation of CD73, leading to the enhanced generation of adenosine 
(commonly referred to as the “purinergic halo”) {Stagg 2010}. Consistent with this 
immunosuppressive mechanism, CD73 expression, potently transcriptionally regulated via 
hypoxia-inducible factor-1, has been established as a negative prognostic marker across a range 
of tumor indications, including gastric carcinoma, and is also associated with chemotherapy 
resistance. High TGFβ levels have been associated with PD, lymph node metastasis, and poor 
prognosis in gastric cancer. TGFβ, together with hypoxia in the tumor microenvironment, has 
been implicated in inducing gastric tumor cell epithelial-to-mesenchymal transition (EMT), a 
process by which epithelial cells lose their polarity and cell-cell adhesion and gain migratory and 
invasive properties {Syed 2016}. GS-1423 is designed to inhibit CD73-mediated adenosine 
production and neutralize active TGFβ signaling within the tumor microenvironment. Dual 
antagonism of these broadly immunosuppressive barriers is anticipated to facilitate antitumor 
immunity and inhibit tumor intrinsic proliferation and EMT transition (unpublished data).
The mFOLFOX6 regimen (oxaliplatin, 5-fluorouracil [5-FU], and leucovorin) is commonly used 
and is acceptable in the first-line setting to treat advanced gastric and gastroesophageal junction 
adenocarcinoma {Kim 2012}. In this Phase 1b study, GS-1423 in combination with mFOLFOX6 
will be evaluated in subjects with advanced gastric and gastroesophageal junction 
adenocarcinoma who have not received prior systemic therapy for advanced disease.
1.5.
Rationale for Dose Selection of GS-1423 in Phase 1a Dose Escalation 
The Phase 1a dose escalation part of this study is proposed for GS-1423 with a starting dose of 
0.3 mg/kg once every 2 weeks (Q2W). The estimate for the starting dose for the proposed 
GS-1423 FIH study (GS-US-505-5452) is based on minimally anticipated biologic effect level 
(MABEL; International Council for Harmonisation [of Technical Requirements for 
Pharmaceuticals for Human Use] [ICH] S9) derived from 90% effective concentration (EC90) 
from the most biologically-relevant assay. An EC90 value was selected because GS-1423 is not 
expected to directly stimulate the immune system, but rather relieve suppression mediated by 
CD73-adenosine and TGFβ pathways. Thus, EC90 may provide the most favorable benefit-to-risk 
ratio for patients in balancing unforeseen toxicity that may result from a high starting dose versus 
a non-effective dose that misses an opportunity to provide clinical benefit to patients. This is 
supported by an 83.3-fold safety margin as compared to the human equivalent dose (HED) 
derived from the NOAEL, which is described in detail below.


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The single dose plasma GS-1423 toxicokinetic data from a cynomolgus monkey non-GLP 
toxicology study were analyzed by noncompartmental analysis using the software WinNonlin. 
Pharmacokinetic (PK) parameters were allometrically scaled to obtain estimates of human 
volume of distribution at steady-state (Vdss), half-life, and accumulation ratio (AR). MABEL 
(EC90 geometric mean of 3.28 μg/mL) and volume of distribution (Vd) (7840 mL of standard 
70 kg human body weight) were converted to a calculated human dose of 0.367 mg/kg. This dose 
was rounded down to a final GS-1423 starting dose of 0.3 mg/kg (Table 1-1). Further, 
25.0 mg/kg is the HED based on a NOAEL of 75 mg/kg in cynomolgus monkey (ie, determined 
to be the most appropriate species for toxicological evaluation) and scaling using the mean 
2.5 kg cynomolgus monkey body weight to a 70 kg human body weight. The difference between 
HED (at NOAEL) and MABEL-derived starting dose demonstrates that the starting dose 
provides an 83.3-fold margin-of-safety (Table 1-1). For this FIH study, the proposed GS-1423 
dosing interval of Q2W is supported by the predicted 9.06-day half-life scaled to human and the 
calculated AR of 1.52.Thus, the proposed GS-1423 starting dose of 0.3 mg/kg Q2W takes into 
consideration of the acceptable risk-to-benefit profile outlined in this protocol and is expected to 
be pharmacologically active in humans as demonstrated by the EC90 values in a human in vitro
assay. 
The highest dose of GS-1423 to be evaluated in subjects is 45 mg/kg Q2W, which is projected to 
provide exposure margins corresponding to ≥ 4.7-fold of the rat NOAEL/STD10 and ≥ 4.0-fold 
of the monkey NOAEL/HNSTD, assuming dose proportionality after 10 mg/kg. 
Table 1-1.
Calculation of GS-1423 Starting Dose from MABEL and 
Determination of Safety Margin
Starting Dose
MABEL
Relevant assay
Cell proliferation
EC90 
0.00328 mg/mL
Vdss for 70 kg human
7840 mL
Calculated dose/70 kg human
25.7 mg
Calculated MABEL dose
0.367 mg/kg
MRSD-MABEL, rounded down
0.3 mg/kg
HED NOAEL
NOAEL dose group (cynomolgus monkey)
75 mg/kg
HED based on NOAEL
25 mg/kg
Safety margin (HED/starting dose MABEL)
83.3 fold
EC90
90% effective concentration; GLP  Good Laboratory Practice; HED 
human equivalent dose; MRSD 
maximum 
recommended starting dose; MABEL 
minimally anticipated biologic effect level; NOAEL
no observed adverse effect level;
starting dose  maximum recommended starting dose; Vdss
volume of distribution at steady state.
MABEL calculated from a physiologically relevant assay (Agenus Document TRL 0135). Preliminary plasma GS 1423 
toxicokinetic data from a cynomolgus monkey non GLP toxicology study were analyzed by noncompartmental analysis using the 
software WinNonlin. Pharmacokinetic parameters were allometrically scaled to obtain estimates of human clearance (CL), Vdss, 
half life (t1/2), and accumulation ratio (AR).
GS-1423 starting dose based on MABEL approach = 0.00328 mg/mL*7840 mL  25.7 mg/70 kg  0.367 mg/kg (rounded
down to 0.3 mg/kg).
HED
D(a)*(BW(a)/BW(human))^(1 b), where D(a)  animal dose in amount/kg, BW(a)  animal body weight in kg, 
BW(human)  human body weight in kg, b  0.67. HEDs calculated from cynomolgus monkey doses of 0, 10, and 75 mg/kg 
(using mean 2.5 kg cynomolgus monkey body weight) were scaled to HED doses of 0, 3.33, and 25mg/kg, respectively. GS 1423 
NOAEL derived from 75 mg/kg dose group from a cynomolgus monkey GLP toxicology study.


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1.6.
Risk/Benefit Assessment for the Study
The proposed Phase 1a dose escalation study aims to evaluate GS-1423 in patients with 
advanced malignancies as a single agent to evaluate safety and to define a pharmacologically 
active dose in relation to antibody PK. Nonclinical investigations were conducted in support of 
the FIH study to provide sufficient evidence that cancer patients administered GS-1423 would 
not be exposed to unreasonable risks in an early stage.
When tested in vitro, GS-1423 inhibited cell-expressed and soluble CD73 enzymatic activity and 
promoted internalization of CD73, thereby preventing extracellular functional activity; inhibited 
TGFβ signaling and its downstream pro-metastatic process of tumor cell EMT; and rescued 
proliferation of primary T-cells that have been suppressed by adenosine monophosphate and/or 
TGFβ as compared to anti-CD73 and TGFβ cytokine trap tested individually. Additionally, a 
package of toxicity studies involving IV administration of GS-1423 to cynomolgus monkey 
demonstrated that treatment was well-tolerated with an acceptable toxicokinetic profile. GS-1423 
did not induce cytokine release in a whole blood cytokine release assay indicating minimal risk 
of CRS. A human tissue cross-reactivity study showed specific reactivity of GS-1423 with 
mononuclear cells in a variety of tissues, consistent with the expected expression on T-cell 
subsets.
Taken together, the pharmacologic properties of GS-1423 demonstrate its suitability for clinical 
development. No major concerns have been identified that preclude evaluation of GS-1423 in an 
FIH study to evaluate safety and assess exploratory clinical pharmacology endpoints in cancer 
patients. An integrated assessment of data from a collection of in vitro and in vivo assays 
indicates that a safe starting dose for a patient with advanced malignancy would be 0.3 mg/kg
Q2W.
The Phase 1b Cohort 1 study will evaluate safety and preliminary efficacy of GS-1423 in 
combination with mFOLFOX6 regimen. A safety run-in to define the RP2D of GS-1423 in 
combination with mFOLFOX6 will be conducted prior to the general enrollment (post safety 
run-in). The addition of GS-1423 to mFOLFOX6 may potentially increase antitumor activity 
over mFOLFOX6 alone by utilizing a wholly different mechanism of action. However, this 
combination regimen may introduce other toxicities, such as infusion reactions and dermatologic 
AEs (e.g., rashes) due to immune-related reactions. Please refer to GS-1423 IB, and oxaliplatin 
and 5-FU Summary of Product Characteristics (SmPCs) for more information. As summarized in 
Section 1.4.2, the ORR for mFOLFOX6, the standard of care in gastric cancer, remains 
low. Although there is a theoretical overlap in toxicities, this combination may offer the potential 
to improve upon the response in this cancer type. Strategies to mitigate risks for these toxicities 
include incorporating safety run-in to evaluate dosing of GS-1423 in combination with 
mFOLFOX6 and close monitoring of lab values and AEs. Parameters for dose delay and 
discontinuation of study drugs are also defined in the protocol. Based on available information, 
the benefit/risk balance for this study is considered positive.


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1.7.
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
2.1.
Phase 1a
The primary objectives are:

Part A (dose escalation): To assess safety and tolerability and to define the dose limiting 
toxicity (DLT) and maximum tolerated dose (MTD) or RP2D of GS-1423 monotherapy in 
subjects with advanced solid tumors 

Part B (flat dose regimens): To assess safety and tolerability of GS-1423 monotherapy in 
subjects with advanced solid tumors
The secondary objectives are:

To characterize GS-1423 PK

To evaluate GS-1423 immunogenicity 
2.2.
Phase 1b
Cohort 1 (gastric cancer): GS-1423 in combination with a chemotherapy regimen in advanced 
(unresectable, recurrent or metastatic) gastric and gastroesophageal junction adenocarcinoma
For safety run-in, the primary objective is:

To assess safety and tolerability and to define the DLT and MTD or RP2D of GS-1423 in 
combination with a chemotherapy regimen in subjects with advanced gastric or 
gastroesophageal junction adenocarcinoma
For post safety run-in, the primary objective is:

To assess the preliminary efficacy of GS-1423 in combination with a chemotherapy regimen 
in subjects with advanced gastric or gastroesophageal junction adenocarcinoma, as 
determined by the confirmed ORR
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For post safety run-in, the secondary objective is: 
Final 
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To assess safety and tolerability of GS-1423 in combination with a chemotherapy regimen in 
subjects with advanced gastric or gastroesophageal junction adenocarcinoma 
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Cohort 2 (paired biopsv): GS-1423 monotherapy in subjects with advanced solid tumors 
accessible for biopsy 
The primary objective is: 
• 
To assess safety and tolerability of GS-1423 monotherapy in subjects with advanced solid 
tumors 
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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
3.2.1.
Phase 1a
Part A – Dose escalation
This is an open-label, Phase 1a study to evaluate the safety, tolerability, and PK profiles of 
GS-1423, a novel bifunctional molecule comprised of an adenosinergic anti-CD73 antibody 
fused to a TGFβRII-based “cytokine trap”, and to assess the MTD or RP2D of GS-1423 
monotherapy in subjects with advanced solid tumors. 
The dose escalation will be conducted in an accelerated titration (Cohorts 1 and 2), followed by a 
3+3 dose escalation design starting with Cohort 3 (Figure 3-1 and Figure 3-2). GS-1423 will be 
administered on Day 1 of each 2-week cycle (Q2W) until the subject meets study treatment 
discontinuation criteria or for up to 1 year.
The starting dose was selected to be 0.3 mg/kg derived from MABEL.
Part B – Flat dose regimens
Part B will consist of up to 3 adaptive cohorts (every week [QW], Q2W, and/or every 3 weeks 
[Q3W]) to evaluate the safety, tolerability, and PK profiles of GS-1423 monotherapy with flat 
dose regimens. GS-1423 will be administered on Day 1 of each cycle (QW, Q2W, or Q3W) until 
the subject meets study treatment discontinuation criteria or for up to 1 year.
The target exposure for the Phase 1b study will be determined based on PK, 
 
and safety results from the Part A (dose escalation) study. Subsequently, 6 to 12 subjects per 
cohort may be enrolled to explore the flat dose(s) and dosing interval(s) that will achieve the 
target exposure. The doses evaluated in these subjects will be selected as such that they do not 
result in exposures that exceed the maximum tolerated exposures based on the dose escalation 
portion of the study. Gilead may choose not to initiate any or all of the adaptive cohorts if it is 
deemed unnecessary.
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3.2.2.
Phase 1b 
This is an open-label, multi-center, single-arm, Phase 1b study with 2 cohorts.
GS-1423 + mFOLFOX6: Cohort 1 (gastric cancer)
Cohort 1 will assess safety and tolerability and define the DLT and MTD or RP2D of GS-1423 
in combination with a chemotherapy regimen (mFOLFOX6) in subjects with advanced 
(unresectable, recurrent or metastatic) gastric or gastroesophageal junction adenocarcinoma who 
have not previously received systemic therapy for advanced disease. GS-1423 and mFOLFOX6 
will be administered starting on Day 1 of each 2-week cycle (Q2W). GS-1423 will be 
administered for up to 2 years and mFOLFOX6 will be administered for up to 12 cycles with 
option to continue leucovorin and 5-FU Q2W at investigator’s discretion until the subject meets 
study treatment discontinuation criteria or for up to 2 years.
A standard 3+3 dose escalation design will be used to determine the DLT and MTD or RP2D of 
GS-1423 in combination with mFOLFOX6. A Safety Review Team (SRT) will assess safety and 
decide on dose escalation.
After the MTD or RP2D of GS-1423 in combination with mFOLFOX6 has been determined, the 
cohort will be expanded by adding approximately 70 subjects to explore the potential efficacy. 
One futility interim analysis will be performed after approximately 50% of subjects have been 
enrolled and are able to complete study treatment for at least 6 months post safety run-in.
GS-1423 Monotherapy: Cohort 2 (Paired Biopsy)
Cohort 2 will assess safety and tolerability of GS-1423 monotherapy in multiple tumor types. 
GS-1423 will be administered on Day 1 of each cycle until the subject meets study treatment 
discontinuation criteria or for up to 1 year.
Cohort 2 will enroll subjects until 15 evaluable paired tumor biopsies (baseline and any 
on-treatment) have been collected, including a minimum of 5 biopsies from non-small-cell lung 
carcinoma (NSCLC) (non-squamous adenocarcinoma) and 5 colorectal cancer (CRC) or 
pancreatic cancer subjects.
3.2.3.
Dose Escalation
3.2.3.1.
Dose Escalation Procedure (Phase 1a Part A)
Subjects with advanced solid tumors who have failed or are intolerant to standard therapy or for 
whom no standard therapy exists will be sequentially enrolled at progressively higher dose levels 
to receive GS-1423.
The initial starting dose will be 0.3 mg/kg and the first cohort will be enrolled to confirm safety 
at this level. Subsequent doses of 1, 3, 10, 20, 30 and 45 mg/kg are planned. 


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Table 3-1.
Phase 1a Part A GS-1423 Dose Levels and Cohorts
Cohort
No. of Subjects
Escalation Type
Dose of GS-1423
(mg/kg)
1 (starting dose)
1 or 3-6
Accelerated titration
0.3
2
1 or 3-6
Accelerated titration
1
3
3-6
3+3
3
4
3-6
3+3
10
5
3-6
3+3
20
6
3-6
3+3
30
7
3-6
3+3
45
Note: An additional 6 subjects may be enrolled at a dose level at or below maximum tolerated dose to obtain additional safety, 
pharmacokinetics, and 
 information. Gilead may choose not to enroll any cohort if it is deemed 
unnecessary.
This part of study will utilize an accelerated titration design schema of dosing 1 subject each at 
the first 2 dose levels of 0.3 mg/kg and 1 mg/kg and with subsequent dosing conducted in a 
3+3 dose escalation format (Figure 3-1 and Figure 3-2). At the first 2 dose levels of 0.3 mg/kg 
and 1 mg/kg, if 2 or more drug-related adverse events (AEs) of Grade 2 or higher or at least 1 
DLT are observed during the 28-day DLT observation period, the 3+3 escalation scheme will be 
used at that dose and subsequent doses. Each subject will stay on the dose level and schedule 
assigned at study entry.
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Figure 3-1.
Accelerated Dose Escalation Scheme
AE  adverse event; DLT
 dose limiting toxicity
Enroll I subject at dose level 0.3 mg/kg 
0 or 1 Grade>= 2 
drug-related AEs 
and NoDLT 
Enter 1 subject at dose 
level 1 mg/kg 
0 or 1 Grade>= 2 
drug-related AE s 
and ro DLT 
Enroll 3 subjects at dose 
level 3 mg/kg (Cohort 3) 
2 or more Grade>= 2 
drug-related AEs or 
>= 1 DLT 
Enter 2 more subjects at 
the same dose level 


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Figure 3-2.
3+3 Dose Escalation Scheme
DLT  dose limiting toxicity; MTD  maximum tolerated dose
Enroll 2 more subjects (Phase la Cohorts 1 and 2) or 3 subjects 
(Phase la Cohort 3 to 
Phase lb Cohort 1 Safety Run-in) 
Escalate to the 
next higher 
dose le,·el 
Enroll 3 more 
subjects at the same 
dose le,·el 
1 subject out 
of6 had DLT 
2 or more 
subjects out of 
6 had DLTs 
De-escalate to lower 
dose le,·el 
De-escalate 
to the lower 
dose le,·el 
0 or 1 subject 
out of6 had 
DLT 
2 or more 
subjects out of 
6 hadDLT 
STOP ~ITD = Current 
dose le,·el 


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Note: If MTD is attained at the first dose level, discussion with investigators and medical 
monitor to change dose or schedules in a protocol amendment
In each dosing cohort of more than 1 subject, the enrollment of the second subject will not 
proceed unless the first subject tolerated the therapy without DLT within the first 7 days 
following the first infusion. Thereafter, within each cohort in the dose escalation phase, 
consecutively enrolled subjects may initiate treatment ≥24 hours after the prior enrolled subject 
initiated treatment. Each subject will be observed for a DLT observation period of 28 days from 
the initial dose of GS-1423, and 3 subjects must be able to receive and tolerate the first 2 doses 
of GS-1423 without DLTs during this observation period before the dose will be escalated and 
the next cohort begins enrollment. 
If 1 of the first 3 evaluable subjects enrolled has a DLT within the first 28 days, then 3 additional 
subjects will be enrolled at the same dose level. If no DLTs are observed in the additional 
3 subjects, dose escalation will occur. If a DLT occurs in ≥2 subjects in the total cohort of 
6 subjects, the MTD will be deemed to be exceeded, and the prior dose level will be evaluated to 
determine the MTD by increasing enrollment to 6 subjects. If the prior dose level was already 
deemed to be safe (ie, 0 or 1 DLT) and enrolled 6 subjects, then it will be defined as the MTD. If 
2 or more subjects have DLTs within the first 28 days, dose de-escalation to a lower dose will 
occur. The MTD is the highest dose level with an incidence of DLTs of 0 or 1 out of 6 subjects 
during the first 28 days of study drug dosing. A minimum of 6 subjects need to be treated at a 
dose level before this dose level can be deemed as the MTD. A subject who is withdrawn from 
the study before the completion of the first 28 days for a reason other than a DLT will be 
replaced.
The SRT will review safety and relevant clinical data after all subjects in a cohort have reached 
the end of the DLT observation period of 28 days and make the dose escalation/stay/de-
escalation decision. Source data verification is not required to be performed prior to dose
escalation/SRT meetings. Alternative data quality control checks that are performed on data used 
to make dose escalation decisions are described in the SRT Charter.
Starting at Cohort 4 (10 mg/kg), if no DLT is observed during the 28-day DLT observation 
period in the first 3 subjects, 3 additional subjects may be enrolled at the respective dose level to 
obtain more safety, PK, and 
 data. If ≥2 subjects have experienced DLTs in 
the last 3 (of 6) subjects, dose escalation will halt and up to 3 additional subjects will be enrolled 
at the preceding dose level (if there were only 3 subjects in that cohort) for DLT assessment. If 
6 subjects were already evaluated, the preceding dose level will be considered as MTD.
If 0.3 mg/kg exceeds the MTD (ie, does not pass DLT evaluation), Gilead and investigators may
consider alternative dose schedules based on available safety data. If needed, PK, and 
 data will be reviewed as well; this will require a protocol amendment. If an 
alternate schedule is tested and determined to be safe, re-escalation of GS-1423 will proceed 
according to the protocol amendment. Otherwise, dose escalation will continue until the MTD is 
reached or dosing with the maximum planned dose level (45 mg/kg) is completed without 
meeting the criteria for MTD.
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The RP2D will be determined by Gilead based on all available relevant clinical data. The RP2D 
will not exceed the maximum tolerated dose evaluated in this study.
3.2.3.2.
Dose Escalation/Safety Run-in for Phase 1b
Cohort 1 (gastric cancer)
Safety run-in: This part of study will utilize a 3+3 dose escalation scheme. The planned starting 
dose of GS-1423 will be targeted to achieve the exposure at -1 dose level of RP2D monotherapy 
(Q2W) determined from Phase 1a. GS-1423 will be administered in combination with 
mFOLFOX6. In each dose level, the enrollment of the second subject will not proceed unless the 
first subject tolerated the therapy without DLT within the first 7 days following the first infusion. 
Thereafter, within each dose level in the safety run-in phase, consecutively enrolled subjects may 
initiate treatment ≥24 hours after the prior enrolled subject initiated treatment.
Each subject will be observed for a DLT observation period of 28 days from the initial dose of 
GS-1423, and 3 subjects must be able to receive and tolerate the first 2 doses of GS-1423 in 
combination with mFOLFOX6 without DLTs during this observation period before the dose will 
be escalated and the next dose level begins enrollment. The SRT will review safety and relevant 
clinical data after all subjects at a dose level have reached the end of the DLT observation period 
of 28 days and make the dose escalation/stay/de-escalation decision.
Table 3-2.
Phase 1b Cohort 1 Safety Run-in GS-1423 Dose Levels 
Regimen
No. of Subjects
Escalation Type
Dose of GS-1423 
(mg)
GS-1423 + mFOLFOX6
3-6
3+3
−1 Dose 1 (Q2W)
GS-1423 + mFOLFOX6
3-6
3+3
Dose 1 (Q2W)
5 FU  5 fluorouracil; Q2W  every 2 weeks; RP2D 
recommended Phase 2 dose
The mFOLFOX6 regimen consists of l LV 200 mg/m2 or dl LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5 FU 
400 mg/m2 and a 46 hour infusion of 5 FU 2400 mg/m2. Administration of mFOLFOX6 will follow administration of GS 1423 
on Day 1 of each cycle.
1 Dose 1: Will be targeted to achieve the exposure at 1 dose level of RP2D monotherapy (Q2W) determined based on 
cumulative data from Phase 1a.
Dose 1: Will be targeted to achieve the exposure at the dose level of RP2D monotherapy (Q2W) determined based on cumulative 
data from Phase 1a.
An additional 6 subjects may be enrolled at a dose level at or below MTD to obtain additional 
safety, PK, and 
 information.
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3.2.3.3.
Definition of Dose Limiting Toxicity
Toxicity will be graded according to National Cancer Institute Common Terminology Criteria 
for Adverse Events Version 5.0 (NCI CTCAE v5.0). A DLT is a toxicity observed in the first 28 
days as defined below and considered possibly related to GS-1423.
A DLT may lead to permanent withdrawal of GS-1423 for the subject after discussion between 
the Investigator and Gilead.
Hematologic

Grade 3 thrombocytopenia with clinically significant bleeding (ie, requires hospitalization, 
transfusion of blood products, or other urgent medical intervention)

Grade ≥3 febrile neutropenia (absolute neutrophil count [ANC] < 1.0 × 109/L and fever 
> 101°F/38.3°C)

Any Grade 4 hematologic laboratory abnormalities/AEs regardless of duration will be 
considered DLTs with the exception of
Grade 4 lymphopenia
Grade 4 neutropenia lasting ≤ 7 days that is not associated with fever (the use of growth 
factors is permitted)
Grade 4 anemia explained by underlying disease
Non-Hematologic

Grade 4 non-hematologic (laboratory and non-laboratory) AEs will be considered DLT 
regardless of the duration

Any ≥ Grade 2 uveitis, blurred vision, eye pain, and/or reduction of visual acuity that does 
not respond to topical therapy and does not improve to Grade 1 severity within 2 weeks of 
the initiation of topical therapy OR requires systemic treatment will be considered as a DLT

The following Grade 3 non-hematologic AEs will be considered as DLTs:
Any Grade 3 AE of unknown etiology consistent with an immune phenomenon that does 
not resolve to ≤Grade 1 or to baseline with immunosuppressive therapy within 3 weeks 
of its onset
Any Grade 3 central nervous system (CNS)-related AE of unknown etiology consistent 
with an immune phenomenon regardless of duration or reversibility
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation 
≥3 × upper limit of normal (ULN), also showing elevation of serum total bilirubin of
> 2 × ULN, without initial findings of cholestasis (elevated serum alkaline phosphatase)


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
Any other non immune-related Grade 3 AE except:
Any Grade 3 endocrinopathy that is adequately controlled by hormonal replacement
Grade 3 AE of tumor flare (defined as local pain, irritation, or rash localized at sites of 
known or suspected tumor)
Transient (≤3 days) Grade 3 fatigue, local reactions, headache, nausea, emesis, or 
diarrhea that are controlled with medical management and/or resolves to Grade ≤1
Transient (≤3 days) Grade 3 flu-like symptoms or fever, which are controlled with 
medical management
An event clearly associated with the underlying disease, PD, a concomitant medication, 
or comorbidity.
Dosing/procedures-related toxicities

Inability to receive the first 2 doses of GS-1423 because of related toxicity, even if the 
toxicity does not meet DLT criteria defined above (regardless of dosing schedule)
Note: Exceptions include DLT exclusions mentioned above.

Greater than a 2-week delay in starting the next cycle of therapy due to a treatment-related 
toxicity, even if the toxicity does not meet the DLT criteria determined above
Grade 5 event (ie, death) 
3.2.3.4.
Stopping Rules for Toxicity
The SRT will meet to review any cohort under evaluation as well as the safety of all cohorts. In 
cohorts with more than 1 subject, should > 33% subjects on any dose level have toxicities that 
meet DLT criteria after the DLT observation period of 28 days or in subjects not included in the 
DLT analysis, the occurrences will be thoroughly evaluated by the committee. Subjects not 
included in the DLT analysis set are those who discontinued during the DLT period for reasons 
other than DLT. The SRT will then make recommendations to initiate any changes in study 
conduct.
If there is a subject death within 30 days of initial study drug administration (Day 1) for reasons 
directly related to study treatment, enrollment in the study and/or treatment will be put on hold as 
appropriate. The SRT will then evaluate the cause of the event and recommend the appropriate 
change in study conduct to be communicated with health authorities. If the event is determined to 
be related to study treatment, then a study amendment and/or other corrective action plan will be 
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3.2.4.
Safety Review Team
An SRT will be established to assess safety, make decisions on dose escalation, and define the 
DLT and MTD.
For any given cohort, Gilead may elect to hold dosing, select an intermediate dose, or stop study
enrollment at any time based on review of the preliminary safety data.
Based on review of relevant safety data by the SRT, as specified in Section 3.2.3.1, and in 
discussion with the investigator, escalation to a higher dose will occur only in the absence of 
> 1 DLTs per dose level and/or meeting any prespecified stopping criteria.
The SRT will consist of at least 1 investigator and the Gilead medical monitor. Others may be 
invited to participate as members of the SRT if additional expertise is desired (ie, representatives
from Pharmacovigilance and Epidemiology [PVE], Clinical Operations, Biostatistics, Clinical 
Pharmacology and Biomarker Sciences as applicable). The medical monitor serves as the chair 
of the SRT. An SRT Charter will be agreed by all SRT members prior to the first SRT meeting.
The data reviewed at the SRT to make dose escalation decisions will be defined in the SRT 
Charter. The quality control checks performed on the data reviewed and used for making dose 
escalation decisions will be described in the SRT Charter.
3.3.
Study Treatments
Formulation, packaging, and dosing regimens are further described in Section 5.3.
Phase 1a: 
Part A
Dose Escalation
This part of the study consists of an accelerated titration design scheme and a 3+3 dose 
escalation scheme with the following proposed escalating dose levels and schedules of GS-1423: 
0.3, 1, 3, 10, 20, 30, and 45 mg/kg administered Q2W.
Part B Flat Dose Regimens
GS-1423 monotherapy may also be evaluated at a flat dose QW, Q2W, and/or Q3W. Based on 
safety and available PK and 
 data from Part A, Part B will be initiated at or 
below the exposure of the highest dose for which data are available from Part A. Part B cohorts 
may be initiated in parallel with cohorts from Part A of the study if the dose/exposure under 
evaluation is at or below a dose/exposure that has already been evaluated and considered as safe. 
Six to 12 subjects per cohort will be enrolled to explore the flat dose(s) and dosing interval(s).
Gilead may choose not to initiate any or all of the adaptive cohorts if it is deemed unnecessary.
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Table 3-3.
Phase 1a Part B Dose Levels
Adaptive Cohort
No. of Subjects
Dose of GS-1423 (mg)
8
6-12
Dose 1 (Q2W)
9
6-12
Dose 2 (QW)
10
6-12
Dose 3 (Q3W)
QW  every week; Q2W  every 2 weeks; Q3W  every 3 weeks; 
Phase 1b:
Cohort 1 (Gastric Cancer): GS-1423 + mFOLFOX6
GS-1423 will be administered on Day 1 of each 14-day cycle via IV infusion. Subjects will also 
be administered mFOLFOX6 after administration of GS-1423 as described in Section 5.4.
Cohort 2 (Paired Biopsy): GS-1423 Monotherapy
GS-1423 will be administered on Day 1 of each cycle via IV infusion. The planned starting dose 
of GS-1423 will be targeted to achieve the exposure at the dose level of the RP2D monotherapy 
(Q2W) determined from Phase 1a. 
Regimen
No. of Subjects
Dose of GS-1423 (mg)
GS-1423 
15 with evaluable paired biopsies
Dose 1
Dose 1: Will be targeted to achieve the exposure at the dose level of RP2D monotherapy (Q2W) determined based on cumulative 
data from Phase 1a.
3.4.
Duration of Treatment
Cycle lengths are 7 days for QW, 14 days for Q2W, and 21 days for Q3W.
Phase 1a (all cohorts) and Phase 1b (Cohort 2): Subjects will continue GS-1423 for up to 1 year 
(maximum 52 cycles for QW, 26 cycles for Q2W, and 17 cycles for Q3W) or until the subject 
meets study treatment discontinuation criteria. 
Phase 1b (Cohort 1): Subjects will continue GS-1423 for up to 2 years (maximum 52 cycles) or 
until PD, unacceptable toxicity, substantial noncompliance with study procedures or study 
treatment regimen, study discontinuation or withdrawal from study. mFOLFOX6 will be 
administered for up to 12 cycles with the option of maintenance therapy with 5-FU and 
leucovorin per investigator’s discretion until the subject meets study treatment discontinuation 
criteria or for up to 2 years (maximum 52 cycles).


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3.5. 
Study Discontinuation Criteria 
The entire study may be discontinued in the event of any of the following: 
• 
New infonnation leading to unfavorable risk-benefit judgment of GS-1423 
• 
Gilead's decision 
Final 
Amendment2 
• 
Poor enrollment of subjects, making completion of the study within an acceptable timeframe 
unlikely 
• 
Discontinuation of development of GS-1423 
• 
The entire study may be tenninated or suspended upon request of health authorities. 
Health authorities and institutional review boards or independent ethics com1nittees (IRBs/lECs) 
will be infonned about study discontinuation in accordance with applicable regulations. 
Recruitment at a center may be stopped for reason that may include low recruitment, protocol 
violation, or inadequate data recording quality control and quality assurance. 
3.6. 
Post Study Care 
Upon withdrawal from study treatment, subjects will receive the care upon which they and their 
physicians agree. Subjects will be followed for survival and AEs as specified in Section 6.8. 
3.7. 
Source Data 
The source data for this study will be obtained from electronic d~ 
central 
laboratory, local laboratory, specialty laboratory (for PK and/or-
data), and 
interactive voice/web response system (IXRS). 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
This study will enroll approximately 213 adult subjects with advanced cancer (solid tumors). 

Phase 1a: GS:1423 monotherapy dose escalation and flat dose regimen:
(Part A dose escalation): Up to 53 subjects 
(Part B flat dose regimen): Up to 40 subjects

Phase 1b:
Cohort 1 (gastric cancer treated with GS-1423+mFOLFOX6): Up to 90 subjects
Cohort 2 (
 GS-1423 monotherapy): Up to 30 
subjects
4.1.1.
Subject Replacement
Subjects who do not complete the DLT observation period of 28 days after the first dose, for 
reasons other than a DLT, will be replaced.
For Phase 1a Part B, replacement subjects may be enrolled if subjects do not complete intensive 
PK and 
 collection in the first 28 days on and after the first dosing of
GS-1423 (including trough PK and 
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study:
1) Voluntarily agree to participate by giving written informed consent 
2) Age ≥18 years
3) Diagnosis: 
a) Phase 1a and Phase 1b Cohort 2: Have a histologically or cytologically confirmed 
diagnosis of a locally advanced or metastatic solid tumor for which no standard therapy is 
available (per local guidance) or standard therapy has failed
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b) Phase 1b Cohort 1 (gastric cancer): Have histologically or cytologically confirmed 
advanced (unresectable, recurrent or metastatic) gastric or gastroesophageal junction 
adenocarcinoma who have not previously received systemic therapy for advanced disease 
(perioperative, neoadjuvant, and adjuvant chemotherapy regimens will not count as a 
prior regimen, unless PD has occurred during or within 6 months of neoadjuvant/adjuvant 
chemotherapy). Gastroesophageal junction adenocarcinoma is defined as tumors with 
epicenters no more than 2 cm into the gastric cardia {Rice 2017}.
i)
Is human epidermal growth factor receptor 2 (HER2)/neu negative
ii) Has not received prior treatment with an immune checkpoint inhibitor within 2 years 
of day 1 of study treatment 
4) Have measurable disease on imaging based on Response Evaluation Criteria in Solid Tumors 
Version 1.1 (RECIST 1.1) (Appendix 3)
5) Have a life expectancy of at least 3 months and an Eastern Cooperative Oncology Group 
(ECOG) performance status of 0 or 1
6) Have adequate organ function as indicated by the following laboratory values:
System
Laboratory Valuea
Hematologicalb
Absolute Neutrophil Count (ANC)
≥ 1.5 109/L 
≥2 109/L (for Phase 1b Cohort 1 only)
Platelets
≥ 100 109/L
Hemoglobin
≥9 g/dL
Renal
Creatinine clearance
≥ 50 mL/min by the Cockcroft-Gault method
Hepatic
Total bilirubin
≤ 1.5 ULN
AST (SGOT) and ALT (SGPT)
≤ 2.5 ULN 
Coagulationc
International Normalized Ratio (INR) or 
Prothrombin Time (PT)
Activated Partial Thromboplastin Time 
(aPTT)
≤ 1.5 ULN unless the subject is receiving anticoagulant therapy
≤ 1.5 ULN unless the subject is receiving anticoagulant therapy
a
All screening laboratory tests must be reviewed by the investigator and be acceptable prior to randomization.
b
Hematologic laboratory values must be met at screening visit and maintained without transfusion and growth factors prior to 
the first study drug dose
c
Subjects on full dose oral anticoagulation, must be on a stable dose (minimum duration 14 days). Subjects on low molecular 
weight heparin will be allowed. In subjects receiving warfarin, the recommended INR is ≤ 3.0 with no active bleeding 
(ie, no bleeding within 14 days prior to first dose of study drug).


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7) Tissue criteria:
a) Phase 1a and Phase 1b Cohort 1: Subjects must have available, sufficient, and adequate 
formalin fixed tumor tissue sample (as specified in the Laboratory Manual) preferably 
from a biopsy of a tumor lesion obtained either at the time of or after the diagnosis of 
advanced disease has been made and from a site not previously irradiated. Alternatively, 
subjects must agree to have a biopsy taken prior to entering the study to provide adequate 
tissue. Fine needle aspirates are not acceptable. Core needle or excisional biopsy or 
resected tissue is required.
b) Phase 1b Cohort 2: Subjects must have a tumor lesion that biopsies can be obtained from 
prior to treatment and on treatment. The biopsies for each subject should be taken from 
the same lesion.
8) A negative serum pregnancy test is required for female subjects (unless permanently sterile 
or greater than 2 years postmenopausal as described in Appendix 5).
9) Male subjects and female subjects of childbearing potential who engage in heterosexual 
intercourse must agree to use protocol-specified method(s) of contraception and refrain from 
egg or sperm donation as described in Appendix 5.
10) Lactating females must agree to discontinue nursing before the study drug is administered.
11) Is willing and able to comply with the requirements of the protocol.
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
1) Is currently participating and receiving study therapy or has participated in a study of an 
investigational agent and received study therapy or used an investigation device within 
3 weeks of the first dose of treatment.
2) Has received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy or 
major surgery within 3 weeks; a 1-week washout is permitted for palliative radiation to 
non-CNS disease with Gilead approval.
3) Has persisting toxicity related to prior therapy of NCI CTCAE v5.0 Grade > 1 severity.
Note: Alopecia and sensory neuropathy of Grade ≤2 is acceptable.
4) Is expected to require any other form of systemic or localized anticancer therapy while on 
study (including maintenance therapy with another agent, radiation therapy, and/or surgical 
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5) Has known severe hypersensitivity reactions (NCI CTCAE Grade ≥3) to fully human 
monoclonal antibodies, GS-1423 formulation excipient, or severe reaction to immuno-
oncology agents, such as colitis or pneumonitis requiring treatment with corticosteroids, any 
history of anaphylaxis, or uncontrolled asthma
6) Is receiving systemic corticosteroid therapy 1 week prior to the first dose of study treatment 
or receiving any other form of systemic immunosuppressive medication.
Note: The following corticosteroid uses are permitted:  use as premedication for known 
hypersensitivity reactions (e.g. IV contrast, IV drug infusions); intraocular, intranasal, 
inhaled, and/or topical corticosteroids; and/or prednisone at doses of up to 10 mg per day or 
equivalent.
7) Has concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of 
the cervix, or superficial bladder cancer who has undergone potentially curative therapy with 
no evidence of disease. Subjects with other previous malignancies are eligible if disease free 
for > 2 years.
8) Has a known CNS metastasis(es), unless metastases are treated and stable and the subject 
does not require systemic corticosteroids for management of CNS symptoms at least 7 days 
prior to study treatment.  Subjects with history of carcinomatous meningitis are excluded 
regardless of clinical stability.
9) Has active or history of autoimmune disease that has required systemic treatment within 
2 years of the start of study treatment (ie, with use of disease-modifying agents, 
corticosteroids, or immunosuppressive drugs).
Note: Subjects with diabetes type 1, vitiligo, psoriasis, hypothyroid disease, or hyperthyroid 
disease not requiring immunosuppressive treatment are eligible.
10) Has had an allogeneic tissue/solid organ transplant
11) Has or had interstitial lung disease (ILD)
12) Has a serious systemic fungal, bacterial, viral, or other infection that is not controlled or 
requires IV antibiotics
13) Has known history of human immunodeficiency virus (HIV)
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15) Subjects with cardiovascular disease/abnormalities will be excluded per the following 
criteria:
a.
Has clinically significant (ie, active) cardiovascular disease: cerebral vascular 
accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, 
congestive heart failure (New York Heart Association class ≥II), or serious uncontrolled 
cardiac arrhythmia requiring medication
b. Has a mean QT interval corrected for heart rate (QTc) using the Fridericia formula
(QTcF) ≥470 ms
c.
Has systolic dysfunction defined as ejection fraction < 50% measured by echocardiogram 
(or multigated acquisition [MUGA] scan) at baseline
16) Has a history or current evidence of any condition, therapy, or laboratory abnormality that 
might confound the results of the study, interfere with the subject’s participation for the full 
duration of the study, or is not in the best interest of the subject to participate, in the opinion 
of the treating investigator
17) Has known psychiatric or substance abuse disorders that would interfere with cooperation 
with the requirements of the study
18) Is legally incapacitated or has limited legal capacity
19) Taking biotin supplements within 72 hours of screening
20) Has positive serum pregnancy test (Appendix 5)
21) Has had prior treatment with anti-CD73 or TGFβ therapies
22) Breastfeeding female
23) Phase 1b Cohort 2: Has melanoma
24) Phase 1b Cohort 2: Has any tumor from which 2 biopsies cannot be obtained. Bone biopsies 
and ascites are not acceptable tumor samples for the study


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Enrollment and Blinding
5.1.1.
Enrollment
An IXRS will be employed to manage the conduct of the study. The IXRS will be used to 
maintain a central log documenting enrollment, to assess current inventories of study drug, to 
initiate any necessary resupply of study drug, and to document discontinuation of study drug. 
Subjects who meet eligibility criteria will be enrolled starting on Day 1 and assigned a subject 
number by IXRS.
5.1.2.
Blinding
Blinding of treatment assignments or data will not be performed in this study.
5.2.
Description and Handling of GS-1423
GS-1423 is a bifunctional, Fc-engineered (N297A, aglycosylated) IgG1κ antibody that 
selectively antagonizes 2 prominent resistance pathways for cancer immunotherapy: 
CD73-adenosine and TGFβ.
GS-1423 consists of 4 polypeptide chains with 2 identical heavy chains of 603 amino acids each 
and 2 identical kappa light chains of 214 amino acids each. The heavy chains are linked through 
2 disulfide bonds, and each heavy chain/light chain pair is linked through a single interchain 
disulfide bond. Included in each heavy chain is an extracellular domain of TGFβRII 
(cytokine trap moiety, 136 amino acids), fused to the carboxy-terminus of the CH3 domain with a 
glycine-serine linker of 22 amino acids ((G4S)4G). Additional information may be found in the 
investigator’s brochure.
5.3.
Formulation
5.3.1.
GS-1423
GS-1423 drug product is supplied as a sterile, single-use solution for IV infusion in a US
Pharmacopeia-compliant Type 1 borosilicate glass vial. Each drug product vial contains, at 
minimum, 50 mg of GS-1423 in a formulation buffer containing 10 mM L-histidine, 145 mM 
sodium chloride, 0.01% polysorbate 80, pH 6.0. The excipients in the formulation of GS-1423 
are compendial, and there are no novel excipients or excipients of human or animal origin used 
in the production or formulation of GS-1423. Detailed information can be found in the Pharmacy 
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5.3.2.
mFOLFOX6
The mFOLFOX6 dosing regimen will consist of dl-LV or l-LV, oxaliplatin, and 5-FU.
5.3.2.1.
dl-Leucovorin and l-Leucovorin
dl-Leucovorin and l-LV is commercially sourced. Information regarding the formulation can be 
found in the current prescribing information.
5.3.2.2.
Oxaliplatin
Oxaliplatin is commercially sourced. Information regarding the formulation can be found in the 
current prescribing information.
5.3.2.3.
5-Fluorouracil
5-Fluorouracil is commercially sourced. Information regarding the formulation can be found in 
the current prescribing information.
5.3.3.
Packaging and Labeling
Packaging and labeling will be in accordance with applicable local and national regulatory 
requirements and applicable Good Manufacturing Practice guidelines. All study drugs must be 
kept in a secure place under appropriate storage conditions. Gilead or its representatives must be 
granted access on reasonable request to check drug storage, dispensing procedures, and 
accountability records.
MFOLFOX6 may be supplied by Gilead per local country regulations for certain regions.
5.3.4.
Storage and Handling
GS-1423 will be shipped frozen in temperature appropriate containers ( 20°C ± 5°C) that are 
monitored with temperature-controlled devices.
GS-1423 drug product vials must be stored at 20°C ± 5°C (with a temperature log maintained 
daily) and protected from light. Caution should be taken to ensure that GS-1423 drug product 
vials are not placed in freezers set to lower temperatures, in order to avoid cracking of the glass. 
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 in 
which they are supplied until dosing to the subject. Instructions for preparation of GS-1423 drug 
product for administration can be found in the Pharmacy Manual.
Information regarding the storage and handling of dl-LV/l-LV, oxaliplatin, and 5-FU can be 
found in the current prescribing information.


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5.4.
Dosage and Administration of Study Drugs
Relevant clinical laboratory results essential for subject management decisions (hematology, 
serum chemistry, coagulation) must be available and reviewed before administration of 
GS-1423.
Premedications should not be administered routinely prior to dosing of GS-1423. Refer to 
Section 5.5.3 for subsequent premedication recommendations following GS-1423 related 
infusion reactions.
GS-1423 should be administered IV over approximately 60 minutes (-10/+20 minutes) at the 
research clinic by a qualified staff member on Day 1 of each treatment cycle. Infusions will be 
followed immediately with a saline flush of the IV line, per institutional guidelines. 
Modifications of the infusion rate due to infusion-related reactions are described in Section 5.5.3.
Subjects receiving GS-1423 should be monitored for infusion reactions. This includes the 
measurement of vital signs prior to each infusion commencing, at the end of each infusion, and 
for the first 2 cycles, 1 hour (± 15 minutes) after the end of the GS-1423 infusion. Thereafter, the 
final vital signs can be taken 30 minutes (-10/+20 minutes) after the end of the GS-1423 
infusion. Subjects will remain in the clinic under close supervision for the duration of this 
monitoring period.
5.4.1.
GS-1423 Monotherapy: Phase 1a and Phase 1b Cohort 2
Phase 1a, Part A will consist of dose escalation by an accelerated dosing design and a 3+3 dose 
escalation scheme with escalating dose levels of GS-1423 (0.3, 1, 3, 10, 20, 30, and 45 mg/kg) 
administered Q2W. Subjects in Phase 1a, Part B of the study will be administered a flat dose of 
GS-1423 at QW, Q2W, and/or Q3W. Subjects in Phase 1b Cohort 2 will be administered GS-
1423 at a flat dose/dosing schedule that matches the exposure of the RP2D determined based on 
cumulative data from Phase 1a.
5.4.2.
GS-1423 + mFOLFOX6: Phase 1b Cohort 1
GS-1423 will be administered on Day 1 of each 14-day treatment cycle.
Subjects in Phase 1b, Cohort 1 (gastric cancer) will also be administered mFOLFOX6 starting on 
Day 1 of each 14-day treatment cycle after administration of GS-1423. The mFOLFOX6 dosing
regimen will consist of l-LV 200 mg/m2 or dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed 
by bolus 5-FU 400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2 for up to 12 cycles. After 
12 cycles, subjects may continue to receive 5-FU and leucovorin at the Investigator’s discretion 
until the subject meets study treatment discontinuation criteria or up to 2 years. Minor 
modifications to the duration of the infusion time are permitted as per institutional standard. 
Adjustments to the dose of mFOLFOX6 are permitted in response to treatment-emergent AEs. 
Refer to the current prescribing information for care of subjects including contraindications, 
subject monitoring, and the medicinal products prohibited or to be used with care for all the 
components of mFOLFOX6.


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For Phase 1b Cohort 1, vital signs will be measured as per standard institutional guidelines for 
mFOLFOX6 infusion.
5.5.
Dose Modifications and Treatment Delay
If an AE is considered to be attributed to 1 or more study drugs (ie, GS-1423 or 1 or more 
component of mFOLFOX6), it is at the investigator’s discretion to withhold or discontinue the 
relevant study drug(s) for the safety of the subject at any time during the study. The subject may 
continue study treatment with the remainder of study drug regimen.
5.5.1.
Dose Modifications
5.5.1.1.
GS-1423
Intrasubject dose reduction of GS-1423 is not permitted; the need for a dose reduction is 
considered a DLT, and the subject will be discontinued from treatment.
Intrasubject dose escalation of GS-1423 is not permitted except for subjects enrolled in Phase 1b 
Cohort 1 1 Dose 1 Q2W (gastric cohort) where GS-1423 may be increased to RP2D dose with 
mFOLFOX6, once determined, at Investigator’s discretion.
5.5.1.2.
mFOLFOX6
Recommended dose modification  for the components of mFOLFOX6 is described in Table 5-1
and is based on the tables in Appendix 6. Sites may also follow their institutional practice for 
dose reductions. Leucovorin doses may be adjusted per institutional guidelines in the event of a 
supply shortage.
Subjects who permanently discontinue all components of mFOLFOX6 can continue GS-1423 
until meeting the discontinuation criteria.
Investigators should contact the Gilead medical monitor with any questions regarding study drug 
dose modification, interruption, or discontinuation.
Table 5-1.
Dose Modificationa for mFOLFOX6
Drug
Dose Level
Starting Dose
-1
-2b
Oxaliplatin
85 mg/m2
65 mg/m2
50 mg/m2
5-FU bolus
400 mg/m2
OMIT
OMIT
5-FU continuous infusion over 46 hours
2400 mg/m2
1900 mg/m2
1500 mg/m2
l-Leucovorin/dl-Leucovorinc
200/400 mg/m2
200/400 mg/m2
200/400 mg/m2
5 FU  5 fluorouracil; AE  adverse event
a
If an AE is believed likely to be due to 1 drug, it is permissible to decrease dose of that drug only.
b
Further dose levels ( 3, 4, etc) will be 20% dose reductions from the previous level for oxaliplatin and 5 FU continuous 
infusion. In addition, the bolus dose of 5 FU will continue to be omitted, and the l leucovorin/dl leucovorin dose will remain 
unadjusted at 200/400 mg/m2
c
Dosing of leucovorin will remain fixed at 100% of recommended dose.


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5.5.2.
Treatment Delay
For infusion-related reactions and immune-related AEs attributed to GS-1423, please follow 
Sections 5.5.3 and 5.5.4, respectively, for treatment delay guidance.  For AEs attributed to 
mFOLFOX6, please follow Appendix 6 for guidance. 
Study treatment may also be delayed due to any AE, laboratory abnormality, or intercurrent 
illness which, in the judgment of the investigator, warrants a delay.
If an AE is attributed to only one study drug, it is at the Investigator’s discretion to determine if 
the study drug(s) not attributed to the AE will be withheld based on the Investigator’s assessment 
of risk-benefit of withholding one or more study drugs.
Subjects who have drug-related toxicities that meet the criteria for dose delay should have study 
drug treatment delayed until criteria to resume treatment are met. It is recommended to restart 
study drug treatment at the next scheduled administration.
Note: GS-1423 should be discontinued in subjects who experience any Grade ≥ 3 skin drug-
related AE, suspected/confirmed Stevens-Johnson syndrome, or suspected/confirmed toxic 
epidermal necrolysis. See Section 5.5.6 for permanent treatment discontinuation criteria due to 
AEs.
5.5.3.
Treatment of Infusion-Related Reactions
Acute infusion reactions (which can include, CRS, angioedema, or anaphylaxis) are different 
from allergic/hypersensitive reactions, although some of the manifestations are common to both 
AEs. Signs and symptoms usually develop during or shortly after drug infusion and generally 
resolve completely within 24 hours of completion of infusion. Signs/symptoms may include 
allergic reaction/hypersensitivity (including drug fever); arthralgia (joint pain); bronchospasm; 
cough; dizziness; dyspnea (shortness of breath); fatigue (asthenia, lethargy, malaise); headache; 
hypertension; hypotension; myalgia (muscle pain); nausea; pruritus/itching; rash/desquamation; 
rigors/chills; sweating (diaphoresis); tachycardia; tumor pain (onset or exacerbation of tumor 
pain due to treatment); urticaria (hives, welts, wheals); and vomiting.
For individual subjects, once the GS-1423 infusion rate has been decreased by 50% or 
interrupted due to an infusion-related reaction, it must remain decreased for all subsequent 
infusions for that subject. If the subject has a second infusion-related reaction that is Grade ≥2 at
the slower infusion rate, infusion should be stopped, and the subject should discontinue 
treatment. If a subject experiences a Grade 3 or Grade 4 infusion-related reaction at any time, the 
subject must discontinue treatment (Table 5-2). If an infusion reaction occurs, all details about 
drug preparation and infusion must be recorded.
For the gastric cohort (Phase 1b Cohort 1), careful monitoring must be ensured for subjects with 
a history of allergic reactions to other platinum-based chemotherapy agents. In the event of 
anaphylactic shock symptoms, interrupt infusion immediately and initiate appropriate treatment. 
Resumption of oxaliplatin treatment following anaphylactic reaction is contraindicated.


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Clinically significant, abnormal 12-lead safety electrocardiograms (ECGs) should be repeated. 
Subjects who have 2 consecutive ECGs showing a new absolute QTcF (Fridericia correction) 
duration > 500 ms, or a QTc > 60 ms over the corresponding baseline value must discontinue 
any medications that could prolong the QT interval (including oxaliplatin). Subject’s 
concomitant medications should be reviewed to determine a potential etiology for the ECG 
changes. Appropriate intervention (ie, cardiology evaluation, telemetry monitoring, management 
of electrolyte abnormalities) in response to treatment-emergent QT interval prolongation should 
be initiated.
Should infusion reaction be considered a significant safety issue by the SRT, the SRT might 
decide to recommend premedication with an antihistamine and acetaminophen approximately 
30 to 60 minutes before each dose of GS-1423 (eg, 25-50 mg diphenhydramine, 500-1000 mg 
acetaminophen or equivalent dose of antipyretic).). This regimen may be modified based on local 
treatment standards and guidelines, as appropriate.
Table 5-2 shows treatment guidelines for subjects who experience an infusion reaction associated 
with administration of GS-1423.
Subjects receiving GS-1423 should be monitored for infusion reactions. This includes the 
measurement of vital signs prior to each infusion commencing, at the end of each infusion, and 
for the first 2 cycles, 1 hour (± 15 minutes) after the end of the GS-1423 infusion. Thereafter, the 
final vital signs can be taken 30 minutes (-10/+20 minutes) after the end of the GS-1423 
infusion. Subjects will remain in the clinic under close supervision for the duration of this 
monitoring period. Subjects with mild or moderate infusion reactions may receive GS-1423 with 
close monitoring. Premedication with an antipyretic or antihistamine for subsequent treatment 
administration may be considered. For severe infusion reactions, GS-1423 infusion must be 
discontinued, and appropriate medical therapy should be administered. 
Subjects who do not experience any infusion-related toxicity Grade 1 or higher during or after 
the infusion may be released from monitoring after 1 hour if they are otherwise stable. Subjects 
with any infusion-related toxicity must be managed as per the guidelines in Table 5-2, and 
monitoring will continue until any infusion-related toxicity has abated to less than Grade 1 and at 
least 1 hour has passed from the completion of the entire infusion and flushing the line. All 
subjects will be given information on and instructions regarding both infusion-related toxicity, 
which is expected to be most likely in the hour after completion of the infusion, and immune-
related AEs (irAEs) before leaving the study site.


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Table 5-2.
GS-1423 Infusion-Related Reactions Management Guidelines
CTCAE Grade
Treatment
Premedication at Subsequent 
Dose Administration
Grade 1
Mild transient reaction; infusion 
interruption not indicated; 
intervention not indicated.
Increase monitoring of vital signs as medically 
indicated until the subject is deemed medically stable 
in the opinion of the investigator.
None.
Grade 2
Requires infusion interruption but 
responds promptly to symptomatic 
treatment 
(eg, antihistamines, nonsteroidal 
anti inflammatory drugs 
[NSAIDs], narcotics, IV fluids); 
prophylactic medications indicated 
for ≤24 hours.
Stop infusion and monitor symptoms.
Additional appropriate medical therapy may include 
but is not limited to the following:
IV fluids
Antihistamines
NSAIDs
Acetaminophen
Narcotics
Increase monitoring of vital signs as medically 
indicated until the subject is deemed medically stable 
in the opinion of the investigator.
If symptoms resolve within 1 hour of stopping drug 
infusion, the infusion may be restarted at 50% of the 
original infusion rate. Otherwise, dose administration 
will be held until symptoms resolve, and the subject 
should be premedicated for the next scheduled dose.
Subjects who develop Grade 2 toxicity despite 
adequate premedication should be permanently 
discontinued from further study drug administration.
Subject may be premedicated 
prior to infusion with the 
following:
Diphenhydramine 25 50 mg 
PO (or equivalent dose of 
antihistamine).
Acetaminophen 500 1000 mg 
PO (or equivalent dose of 
antipyretic).
Grade 3 or 4
Grade 3
Prolonged (ie, not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms following 
initial improvement; 
hospitalization indicated for other 
clinical sequelae (eg, renal 
impairment, pulmonary infiltrates).
Grade 4
Life threatening; pressor or 
ventilatory support indicated.
Stop infusion.
Additional appropriate medical therapy may include 
but is not limited to:
IV fluids
Antihistamines
NSAIDs
Acetaminophen
Narcotics
Oxygen
Pressor
Corticosteroids
Epinephrine
Increase monitoring of vital signs as medically 
indicated until the subject is deemed medically stable 
in the opinion of the investigator.
Hospitalization may be indicated.
Subject is permanently discontinued from further study 
drug administration.
No subsequent dosing. 
CTCAE
Common Terminology Criteria for Adverse Events; IV
intravenous; NSAID  nonsteroidal anti inflammatory drug; 
PO  orally
5.5.4.
Management of Potential Immune-Related Adverse Events
Immune-related AEs may be associated with immuno-oncology agents such as GS-1423 and will 
be categorized as AEs of interest in this study. An irAE is defined as an AE of unknown 
etiology, that is potentially associated with study drug exposure and is consistent with an 
immune-mediated phenomenon. Efforts should be made to rule out other etiologies prior to 
labeling an AE of clinical interest. Early recognition and management of irAEs may mitigate 


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severe toxicity. Investigators should also monitor subjects closely for potential irAEs, which may 
manifest after weeks of treatment, at the earliest. Such events may consist of persistent rash, 
diarrhea, colitis, autoimmune hepatitis, pneumonitis, encephalitis, arthritis, glomerulonephritis, 
cardiomyopathy, or uveitis and other inflammatory eye conditions.
Management algorithms have been developed to assist investigators in assessing and managing 
the following groups of irAEs: dermatological, gastrointestinal, pulmonary, hepatic, endocrine 
renal, and neurological, among others. 
Adverse events (both non-serious and serious) associated with drug exposure and consistent with 
an immune phenomenon may represent an immunologic etiology. These irAEs may be predicted 
based on the nature of the study drugs, their mechanism of action, and reported experience with 
immunotherapies that have a similar mechanism of action. An irAE can occur any time from 
shortly after the first dose to several months after the last dose of treatment. Particular attention 
should be paid to AEs that may be suggestive of potential irAEs, as outlined below.
5.5.4.1.
Dermatological irAEs
Rule out non-inflammatory causes. If a non-inflammatory cause is identified, treat accordingly 
and continue therapy per protocol.
Table 5-3.
Dermatological irAE Management Algorithm
Dermatological irAEs
CTCAE Grade of Rash
Management
Follow-up
Grade 1-2
Covering ≤ 30% body surface area
Symptomatic therapy 
(eg, antihistamines, topical 
corticosteroids).
Continue GS-1423 therapy per 
protocol.
If persists > 1 to 2 weeks or recurs: 
Consider skin biopsy.
Delay GS-1423 therapy.
Consider 0.5-1 mg/kg/day 
methylprednisolone IV or oral 
equivalent. Once improving, taper 
corticosteroids over ≥1 month; 
consider prophylactic antibiotics for 
opportunistic infections; and resume 
GS-1423 therapy per protocol.
If worsens: Treat as Grade 3-4.
Grade 3-4
Covering > 30% body surface area; 
life-threatening consequences
Delay or discontinue GS-1423 
therapy per protocol.
Consider skin biopsy.
Dermatology consult
1-2 mg/kg/day methylprednisolone 
IV or IV equivalent.
If improves to Grade 1: Taper 
corticosteroids over ≥1 month; add 
prophylactic antibiotics for 
opportunistic infections.
Resume GS-1423 therapy per 
protocol.
CTCAE
Common Terminology Criteria for Adverse Events; irAE
immune related adverse event; IV  intravenous.


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5.5.4.2.
Gastrointestinal irAEs
Rule out non-inflammatory causes. If a non-inflammatory cause is identified, treat accordingly 
and continue therapy. Opiates/narcotics may mask symptoms of perforation. Infliximab should 
not be used in cases of perforation or sepsis.
Table 5-4.
Gastrointestinal irAE Management Algorithm
Gastrointestinal irAEs
CTCAE Grade of Diarrhea /
Colitis
Management
Follow-up
Grade 1
Diarrhea: < 4 stools/day over 
baseline.
Colitis: asymptomatic.
Continue GS-1423 therapy per 
protocol.
Symptomatic treatment.
Close monitoring for worsening 
symptoms.
Educate subject to report worsening 
immediately.
Consider symptomatic treatment 
including hydration, electrolyte 
replacement, dietary changes (eg, 
American Dietetic Association 
colitis diet), and loperamide.
If worsens: Treat as Grade 2 or 3-4.
Grade 2
Diarrhea: 4-6 stools per day over 
baseline; IV fluids indicated < 24 h; 
not interfering with activities of 
daily living (ADL).
Colitis: abdominal pain; blood in 
stool. 
Delay GS-1423 therapy per protocol.
Symptomatic treatment.
If improves to Grade 1: Resume 
GS-1423 therapy per protocol.
If persists > 5 to 7 days or recurs: 
0.5-1 mg/kg/day methylprednisolone 
or equivalent.
When symptoms improve to Grade 
1, taper corticosteroids over ≥
1 month; consider prophylactic 
antibiotics for opportunistic 
infections; resume GS-1423 therapy 
per protocol.
If worsens or persists > 3 to 5 days 
with oral corticosteroids: Treat as 
Grade 3-4.
Grade 3-4
Diarrhea (Grade 3): ≥7 stools per 
day over baseline; incontinence; IV 
fluids ≥ 24 h; interfering with ADL.
Colitis (Grade 3): severe abdominal 
pain, medical intervention indicated, 
peritoneal signs.
Grade 4: life-threatening, perforation
Discontinue GS-1423 therapy per 
protocol.
1-2 mg/kg/day methylprednisolone 
IV or equivalent.
Add prophylactic antibiotics for 
opportunistic infections.
Consider lower endoscopy.
If improves: Continue 
corticosteroids until Grade 1, then 
taper over ≥ 1 month.
If persists > 3 to 5 days or recurs 
after improvement: Add infliximab 
5 mg/kg (if no contraindication).
Note: Infliximab should not be used 
in cases of perforation or sepsis.
ADL  activities of daily living; CTCAE  Common Terminology Criteria for Adverse Events; irAE  immune related adverse 
event; IV  intravenous.


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5.5.4.3.
Pulmonary irAEs
Rule out non-inflammatory causes. If a non-inflammatory cause is identified, treat accordingly 
and continue therapy per protocol. Evaluate with imaging and pulmonary consultation.
Table 5-5.
Pulmonary irAE Management Algorithm
Pulmonary irAEs
CTCAE Grade of Pneumonitis
Management
Follow-up
Grade 1
Radiographic changes only.
Consider delay of GS-1423 therapy 
per protocol.
Monitor for symptoms every 
2-3 days.
Consider pulmonary and infectious 
disease consults.
Re-image every ≥3 weeks.
If worsens: Treat as Grade 2 or 
Grade 3-4.
Grade 2
Mild to moderate new symptoms.
Delay GS-1423 therapy per protocol.
Pulmonary and infectious disease 
consults.
Monitor symptoms daily; consider 
hospitalization.
1 mg/kg/day methylprednisolone IV 
or oral equivalent.
Consider bronchoscopy, lung biopsy.
Re-image every 1-3 days.
If improves: When symptoms return 
to near baseline, taper corticosteroids 
over ≥1 month, then resume GS-
1423 therapy per protocol, and 
consider prophylactic antibiotics.
If not improving after 2 weeks or 
worsening: Treat as Grade 3-4.
Grade 3-4
Severe new symptoms; new/ 
worsening hypoxia; life-threatening.
Discontinue GS-1423 therapy per 
protocol.
Hospitalize.
Pulmonary and infectious disease 
consults.
2-4 mg/kg/day methylprednisolone 
IV or IV equivalent.
Add prophylactic antibiotics for 
opportunistic infections.
Consider bronchoscopy, lung biopsy.
If improves to baseline: Taper 
corticosteroids over ≥6 weeks.
If not improving after 48 hours or 
worsening: Add additional 
immunosuppression (eg, infliximab, 
cyclophosphamide, IV 
immunoglobulin, mycophenolate 
mofetil).
CTCAE
Common Terminology Criteria for Adverse Events; irAE
immune related adverse event; IV
intravenous.


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5.5.4.4.
Hepatic irAEs
Rule out non-inflammatory causes. If a non-inflammatory cause is identified, treat accordingly 
and continue therapy per protocol. Consider imaging for obstruction.
Table 5-6.
Hepatic irAE Management Algorithm
Hepatic irAEs
CTCAE Grade of 
Liver Test Elevation
Management
Follow-up
Grade 1
AST or ALT > ULN to 3 × ULN or 
total bilirubin > ULN to 1.5 × ULN.
Continue GS-1423 therapy per 
protocol.
Continue liver function tests (LFT) 
monitoring per protocol.
If worsens: Treat as Grade 2 or 
Grade 3-4.
Grade 2
AST or ALT > 3 to ≤5 × ULN or 
total bilirubin > 1.5 to ≤ 3 × ULN.
Delay GS-1423 therapy per protocol.
Increase frequency of monitoring to 
every 3 days.
If subject has concurrent AST or 
ALT > 3 × ULN and total bilirubin >
2 × ULN > 7 days, discontinue GS-
1423 therapy per protocol.
If returns to baseline: Resume 
routine monitoring; resume GS-1423 
therapy per protocol.
If elevations persist > 5 to 7 days 
or worsen: 0.5-1 mg/kg/day 
methylprednisolone IV or oral 
equivalent. When LFT returns to 
Grade 1 or baseline, taper 
corticosteroids over ≥1 month, 
consider prophylactic antibiotics for 
opportunistic infections, and resume 
GS-1423 therapy per protocol.
Grade 3-4
AST or ALT > 5 × ULN and/or total 
bilirubin > 3 × ULN.
Discontinue GS-1423 therapy per 
protocol.
Increase frequency of monitoring to 
every 1-2 days.
1-2 mg/kg/day methylprednisolone 
IV or oral equivalent.a
Add prophylactic antibiotics for 
opportunistic infections.
Consult gastroenterology.
Consider obtaining MRI/CT scan of 
liver and liver biopsy if clinically 
warranted.
If returns to Grade 2: Taper 
corticosteroids over ≥1 month.
If does not improve in > 3 to 
5 days, worsens or rebounds: Add 
mycophenolate mofetil 1 g twice 
daily. If no response within an 
additional 3-5 days, consider other 
immunosuppressants per local 
guidelines.
ALT
alanine aminotransferase; AST
aspartate aminotransferase; CT
computed tomography; CTCAE
Common 
Terminology Criteria for Adverse Events; irAE
immune related adverse event; IV
intravenous; LFT  liver function test;
MRI
magnetic resonance imaging; ULN
upper limit of normal.
a
The recommended starting dose for Grade 4 hepatitis is 2 mg/kg/day methylprednisolone IV.


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5.5.4.5.
Endocrine irAEs
Rule out non-inflammatory causes. If a non-inflammatory cause is identified, treat accordingly 
and continue therapy per protocol. Consider visual field testing, endocrinology consultation, and 
imaging.
Table 5-7.
Endocrine irAE Management Algorithm
Endocrine irAEs
Endocrine Disorder
Management
Follow-up
Asymptomatic TSH abnormality.
Continue GS-1423 therapy per protocol.
If TSH < 0.5 × lower limit of normal (LLN) or TSH > 2 × ULN, or 
consistently out of range in 2 subsequent measurements: Include free 
thyroxine at subsequent cycles as clinically indicated; consider 
endocrinology consult.
Symptomatic endocrinopathy.
Evaluate endocrine function.
Consider pituitary scan.
Symptomatic with abnormal 
lab/pituitary scan: Delay GS-1423 
therapy per protocol; 1-2 mg/kg/day 
methylprednisolone IV or oral 
equivalent; initiate appropriate 
hormone therapy.
No abnormal lab/pituitary MRI 
scan but symptoms persist: Repeat 
labs in 1-3 weeks, MRI in 1 month.
If improves (with or without 
hormone replacement): Taper 
corticosteroids over ≥1 month and 
consider prophylactic antibiotics for 
opportunistic infections.
Resume GS-1423 therapy per 
protocol.
Subjects with adrenal insufficiency 
may need to continue corticosteroids 
with mineralocorticoid component.
Suspicion of adrenal crisis
(eg, severe dehydration, 
hypotension, shock out of proportion 
to current illness)
Delay or discontinue GS-1423 therapy per protocol.
Rule out sepsis.
Stress dose of IV corticosteroids with mineralocorticoid activity.
IV fluids.
Consult endocrinologist.
If adrenal crisis ruled out, treat as above for symptomatic endocrinopathy.
irAE
 immune related adverse event; IV  intravenous; LLN  lower limit of normal; MRI  magnetic resonance imaging; 
TSH
 thyroid stimulating hormone; ULN  upper limit of normal.


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5.5.4.6.
Renal irAEs
Rule out non-inflammatory causes. If a non-inflammatory cause is identified, treat accordingly 
and continue therapy per protocol.
Table 5-8.
Renal irAE Management Algorithm
Renal irAEs
CTCAE Grade of Creatinine 
Elevation
Management
Follow-up
Grade 1
Creatinine > ULN and > baseline but 
≤1.5 × baseline.
Continue GS-1423 therapy per 
protocol.
Monitor creatinine weekly.
If returns to baseline: Resume 
routine creatinine monitoring per 
protocol.
If worsens: Treat as Grade 2 or 
Grade 3-4.
Grade 2-3
Creatinine > 1.5 × baseline to 
≤6 × ULN.
Delay GS-1423 therapy per protocol.
Monitor creatinine every 2-3 days.
0.5-1.0 mg/kg/day 
methylprednisolone IV or oral 
equivalent.
Consider renal biopsy.
If returns to Grade 1: Taper 
corticosteroids over ≥1 month, 
consider prophylactic antibiotics for 
opportunistic infections, and resume 
GS-1423 therapy and routine 
creatinine monitoring per protocol.
If elevations persist > 7 days or 
worsen: Treat as Grade 4.
Grade 4
Creatinine > 6 × ULN
Discontinue GS-1423 therapy per 
protocol.
Monitor creatinine daily.
1.0-2.0 mg/kg/day 
methylprednisolone IV or IV 
equivalent.
Consult nephrologist.
Consider renal biopsy.
If returns to Grade 1: Taper 
corticosteroids over ≥1 month and 
add prophylactic antibiotics for 
opportunistic infections.
CTCAE  Common Terminology Criteria for Adverse Events; irAE  immune related adverse event; IV  intravenous; 
ULN
upper limit of normal.


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5.5.4.7.
Neurological irAEs
Rule out non-inflammatory causes. If a non-inflammatory cause is identified, treat accordingly 
and continue therapy per protocol.
Table 5-9.
Neurological irAE Management Algorithm
Neurological irAEs
CTCAE Grade of Neurological 
Toxicity
Management
Follow-up
Grade 1
Asymptomatic or mild symptoms; 
intervention not indicated.
Continue GS-1423 therapy per 
protocol
Continue to monitor subject.
If worsens: Treat as Grade 2 or 
Grade 3-4.
Grade 2
Moderate symptoms; limiting 
instrumental ADL.
Delay GS-1423 therapy per protocol.
Treat symptoms per local guidelines.
Consider 0.5-1.0 mg/kg/day 
methylprednisolone IV or oral 
equivalent.
If returns to baseline: Resume 
GS-1423 therapy per protocol.
If worsens: Treat as Grade 3-4.
Grade 3-4
Severe symptoms; limiting self-care 
ADL; life-threatening.
Discontinue GS-1423 therapy per 
protocol.
Obtain neurology consult.
Treat symptoms per local guidelines.
1.0-2.0 mg/kg/day 
methylprednisolone IV or IV 
equivalent.
Add prophylactic antibiotics for 
opportunistic infections.
If improves to Grade 2: Taper 
corticosteroids over ≥1 month.
If worsens or atypical 
presentation: Consider IV 
immunoglobulin or other 
immunosuppressive therapies per 
local guidelines.
ADL
activities of daily living; CTCAE
Common Terminology Criteria for Adverse Events; irAE
immune related adverse 
event; IV
intravenous.
5.5.5.
Criteria to Resume Treatment
Subjects may resume treatment with GS-1423 when drug-related AE(s) resolve(s) to Grade 1 or 
baseline value, with the following exceptions:

Subjects may resume treatment in the presence of Grade 2 fatigue.


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
Subjects with combined Grade 2 AST/ALT and total bilirubin values lasting > 7 days 
meeting discontinuation parameters (Section 5.5.6) should have treatment permanently 
discontinued.

Drug-related Grade 2 pulmonary toxicity or colitis must have resolved to baseline before 
treatment is resumed.

Drug-related endocrinopathies adequately controlled with only physiologic hormone 
replacement may resume treatment. (Exception: Study treatment does not need to be 
delayed/interrupted for subjects who experience immune-related hypothyroidism 
[Grades 1-2].)

Subjects who received systemic corticosteroids for management of any drug-related toxicity 
must be off corticosteroids or have tapered down to an equivalent dose of prednisone 
≤10 mg/day.
5.5.6.
Permanent Treatment Discontinuation
Study drug treatment must be discontinued for drug-related AEs described in Table 5-10.  Non-
AE reasons for study treatment discontinuation can be found in Section 6.10.1.
Table 5-10.
Drug-Related Adverse Events Requiring Discontinuation of GS-1423
Toxicity Category*
Qualifying Severity/Duration
Ophthalmic

Grade 2 uveitis, blurred vision, eye pain, and/or reduction of visual acuity that 
does not respond to topical therapy and does not improve to Grade 1 severity 
within 2 weeks OR requires systemic treatment

Grade 3 or higher uveitis 
Gastrointestinal

Grade 3 or higher diarrhea, colitis 
Neurologic 

Grade 3 or higher neurologic toxicities
Dermatologic 

Grade 3 or higher skin AE, suspected Stevens-Johnson syndrome, or toxic 
epidermal necrolysis
Pulmonary 

Grade 2 pneumonitis or interstitial lung disease that does not improve after 
2 weeks or worsening despite dose delay and systemic corticosteroids 
(see Table 5-5)

Grade 3 or higher pneumonitis
Endocrinopathies 

Grade 3 endocrinopathies not adequately controlled with physiologic hormone 
replacement

Grade 4 or higher endocrinopathies
Hypersensitivity

Grade 3 or higher bronchospasm, hypersensitivity reaction, or infusion-related 
reaction


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Toxicity Category*
Qualifying Severity/Duration
Laboratory
Thrombocytopenia

Grade 3 thrombocytopenia lasting > 7 days or associated with clinically 
significant bleeding (i.e. requires hospitalization, transfusion of blood 
products, or other urgent medical intervention)

Grade 4 thrombocytopenia
Neutropenia

Grade 4 neutropenia lasting > 7 days
Electrolyte Abnormalities

Grade 4 electrolyte abnormalities with clinical sequelae

Grade 4 electrolyte abnormalities unable to be corrected with 
supplementation/appropriate management within 72 hours of onset
Liver Function Abnormalities (see Table 5-6)

AST or ALT > 5 × ULN

Total bilirubin > 3 × ULN

Concurrent AST or ALT > 3 × ULN AND total bilirubin > 2 × ULN lasting > 
7 days
Other

Grade 2 or 3 adverse event (laboratory or non-laboratory) that does not resolve 
in ≤ 12 weeks

Recurrence of Grade 3 or higher adverse event (laboratory or non-laboratory)

Grade 4 non-hematologic adverse event
*
AE must be study drug related for discontinuation reasons to apply
5.5.6.1.
Treatment Compliance
Treatment delays from the protocol-specified treatment plan for greater than 4 weeks (QW or 
Q2W) or 6 weeks (Q3W) require consultation between the investigator and Gilead and written 
documentation of the collaborative decision on subject management.
Administration of study medications will be witnessed by the investigator and/or study staff. The 
total volume of study treatments infused will be compared with the total volume prepared to 
determine compliance with each dose administered.
Any reason for noncompliance should be documented. Drug treatment noncompliance is defined 
as a subject missing > 1 cycle of study treatment for non-medical reasons. If 1 cycle was missed 
and the interval between the subsequent treatment cycle and the last administered treatment cycle 
is longer than 4 weeks for non-medical reasons, criteria for insufficient compliance are met.


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5.5.7.
Treatment Beyond Initial Progressive Disease
Subjects who experience initial radiologic PD and are not doing well clinically will discontinue 
study drug treatment and no further imaging is required.
Subjects who experience initial radiologic PD and are doing well clinically are considered to 
have initial RECIST 1.1-defined PD and will be permitted, with Gilead’s approval, to continue 
with study drug treatment.  These subjects will be reevaluated using the same imaging modality 
no less than 4 weeks later to assess whether study drug treatment will be continued. To continue 
study drug treatment beyond initial RECIST 1.1-defined PD, they must meet the following 
criteria:

There is investigator-assessed clinical benefit from the treatment

Subject is clinically stable

Subject is tolerating study drug and

There is agreement with Gilead
The assessment of clinical benefit should take into account whether the subject is clinically 
deteriorating and unlikely to receive further benefit from continued treatment. The following 
criteria need to be taken into consideration:

Absence of clinical symptoms and signs (including worsening of laboratory values) 
indicating PD,

No decline in ECOG performance status attributed to underlying malignancy, and 

Absence of rapid progression of disease or of progressive tumor at critical anatomical sites 
(eg, spinal cord compression) requiring urgent alternative medical intervention.
5.5.7.1.
Subsequent Anticancer Therapy
The investigator or qualified designee will review all new anticancer therapy initiated after the 
last dose of study treatment. If a subject initiates a new anticancer therapy within 30 days after 
the last dose of study treatment, the 30-Day Follow-up Visit must occur before the first dose of 
the new therapy. Once new anticancer therapy has been initiated, subjects will move into the first 
posttreatment visit at 3 months from last treatment dose, then survival follow-up thereafter.


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5.6.
Prior and Concomitant Medications
5.6.1.
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. Concomitant medications, including all prescription, over-the-counter, herbal 
supplements, and IV medications and fluids received within 30 days before the first dose of 
study treatment through the 30-day follow-up visit should be recorded in the electronic case 
report form (eCRF). If changes occur during the study period, documentation of drug dosage, 
frequency, route, and date will also be included on the eCRF.
Palliative and supportive care is permitted during the course of the study for underlying medical 
conditions and management of symptoms.
Surgery for tumor control or symptom management is not permitted during the study. Palliative 
radiotherapy is permitted to a single lesion if considered medically necessary by the treating 
physician as long as the lesion is NOT a RECIST 1.1 defined target lesion and treatment is NOT 
administered for tumor control. Study therapy should be held during the course of palliative 
radiotherapy and should be resumed no earlier than the next scheduled administration of study 
therapy. The specifics of the radiation treatment, including the location, will be recorded.
5.6.1.1.
Rescue Medications and Supportive Care
Subjects should receive appropriate supportive care measures as deemed necessary by the 
treating investigator including but not limited to the items outlined below.
For guidelines for continuing treatment with GS-1423, see Section 5.5.5.

Diarrhea: Subjects should be carefully monitored for signs and symptoms of enterocolitis 
(such as diarrhea, abdominal pain, blood or mucus in stool, with or without fever) and of 
bowel perforation (such as peritoneal signs and ileus). In symptomatic subjects, infectious 
etiologies should be ruled out, and if symptoms are persistent and/or severe, endoscopic 
evaluation should be considered. All subjects who experience diarrhea should be advised to 
drink liberal quantities of clear fluids or rehydration solutions. If sufficient oral fluid intake is 
not feasible, fluid and electrolytes should be substituted via IV infusion.

Anemia: Transfusions may be utilized as clinically indicated for the treatment of anemia but 
should be clearly noted as concurrent medications or in a transfusion page. Consider a 
potential immunologic etiology and follow the American Society of Clinical Oncology
(ASCO) guidelines for use of erythropoietin or derivatives.

Neutropenia: Prophylactic use of colony-stimulating factors including granulocyte 
colony-stimulating factor (G-CSF), PEGylated G-CSF, or granulocyte macrophage 
colony-stimulating factor is not allowed in this study. Therapeutic use of G-CSF is allowed 
in subjects with Grade 3 to 4 febrile neutropenia. Consider a potential immunologic etiology.


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
Thrombocytopenia: Transfusion of platelets may be used if clinically indicated. Immune 
thrombocytopenia purpura should be ruled out before initiation of platelet transfusion.

Anti-infectives: Subjects with suspected or documented infectious complication should 
receive oral or IV antibiotics or other anti-infective agents as considered appropriate by the 
treating investigator for a given infectious condition, according to standard institutional 
practice.

Adverse events with a potential immunologic etiology (irAEs): Follow ASCO or local 
institutional practice guidelines for identification, evaluation, and management of adverse 
experiences of a potential immunologic etiology. Depending on the type and severity of an 
irAE, oral or IV treatment with a corticosteroid should be considered, in addition to 
appropriate symptomatic treatment of a given condition (see Section 5.5.4 for management 
algorithms guidance).
5.6.2.
Prohibited and/or Restricted Treatments
Subjects are prohibited from receiving the following therapies and treatments during the study. 
Study treatment will be discontinued in subjects who, in the assessment by the investigator, 
require the use of any of the following therapies and treatments for clinical management:

Immunotherapy not specified in this protocol

Chemotherapy

Investigational agents other than GS-1423

Corticosteroids are not permitted with the following exceptions:
As premedication for known hypersensitivity reactions (e.g. IV contrast, IV drug
infusion);
Note: Premedication should not be administered routinely prior to dosing of GS-1423. 
Refer to Section 5.5.3 for subsequent premedication recommendations following 
GS-1423-related infusion reactions.  Premedication for mFOLFOX6 should follow local 
SmPC or institutional guidance.
Intraocular, intranasal, inhaled, and/or topical corticosteroids; and/or 
Prednisone at doses of up to 10 mg per day or equivalent.

Live vaccines within 30 days prior to first dose of study therapy and while participating in 
study
There are no prohibited therapies during the Posttreatment Follow-up Phase.


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5.6.3.
Other Restrictions and Precautions
The following non-drug therapies must not be administered or performed during the study:

Major elective surgery

Herbal remedies with immunostimulating properties (eg, mistletoe extract) or that are known 
to potentially interfere with major organ function (eg, hypericin)

Subjects should not abuse alcohol or other drugs during the study
5.7.
Accountability for Study Drug
The investigator is responsible for ensuring adequate accountability of all used and unused study 
drug (kits, vials, diluent ampules, etc). This includes acknowledgment of receipt of each 
shipment of study drug (quantity and condition) and tracking of vials assigned/utilized for 
subject dosing. 
Each study site must keep accountability records that capture:

The date received and quantity of study drug vials

The date, subject number, and the study drug lot number dispensed

The date and quantity of used and unused study drug, along with the initials of the person 
recording the information
5.7.1.
Investigational Medicinal Product Return or Disposal
Gilead recommends that used and unused study drug supplies be destroyed at the site. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead, the site may destroy used (empty or partially empty) and unused study drug supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for the electronic trial master file. If study drug is destroyed on site, the investigator must 
maintain accurate records for all study drugs destroyed. Upon study completion, copies of the 
study drug accountability records must be filed at the site. Another copy will be returned to 
Gilead. 
If the site does not have an appropriate SOP for drug destruction, used and unused study drug
supplies are to be sent to the designated disposal facility for destruction. The study monitor will 
provide instructions for return.
The study monitor will review study drug supplies and associated records at periodic intervals.
Please refer to the current version of the Pharmacy Manuals for return and disposal instructions 
for GS-1423.   


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows. 
The investigator must document any deviation from the protocol procedures and notify Gilead or 
the CRO.
6.1.
Subject Enrollment and Treatment Assignment
Entry into screening does not guarantee enrollment into the study. In order to manage the total 
study enrollment, Gilead, at its sole discretion, may suspend screening and/or enrollment at any 
site or study-wide at any time.
6.2.
Pretreatment Assessments
6.2.1.
Screening 
Subjects will be screened within 28 days prior to the first dose of study treatment to determine 
eligibility for participation in the study. The following will be performed and documented during 
screening as per Appendix 2:

Within 28 days prior to first dose of study treatment:
Administrative procedures including
■
Obtain written informed consent 
■
Review of inclusion/exclusion criteria
■
Issue Emergency Medical Support and Subject Card
■
Obtain medical history and demographics
■
Review of baseline symptoms 
■
Review of prior and concomitant medications
■
Obtain cancer disease details and prior treatments
Tumor biopsy and/or archival tissue collection


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Obtain blood samples for serum chemistry, hematology, coagulation, endocrine function, 
HBV and HCV serologies 
■
For HBV serology, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody 
(HBsAb), and total hepatitis B core antibody (anti-HBc). For subjects where total 
anti-HBc-positive, HBV DNA by quantitative polymerase chain reaction will be 
required 
■
For HCV serology, HCV antibody. For subjects with positive HCV antibody, HCV 
RNA by quantitative polymerase chain reaction will be required 
Obtain urine for urinalysis
Blood pharmacogenomics sample may be collected from enrolled and consented subject
before or at Cycle 1, Day 1, predose
 
Phase 1b Cohort 1 (gastric cancer): HER2 Testing: Prior to randomization, the subject’s 
tumor should have been tested for HER2 status with approved immunohistochemistry 
(IHC) and in situ hybridization (ISH) kits. HER2 positivity is defined as IHC3+ or 
IHC2+/ISH+ (ISH positivity is defined as HER2:CEP17 ratio of ≥ 2.0). Results for HER2 
status obtained prior to signing informed consent are acceptable if obtained with 
approved IHC and ISH kits. HER2 status may be determined during screening by testing 
the tumor at the central laboratory or a local laboratory with approved IHC and ISH kits.
Tumor imaging, unless diagnostic quality tumor imaging is available for exams within 
28 days prior to the first dose of study treatment

Within 14 days prior to the first dose of study treatment:
Echocardiogram evaluation or MUGA scan

Within 7 days prior to the first dose of study treatment:
Full physical examination including vital signs, body weight, and height
ECOG performance status
12-lead ECG
CCI
CCI


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
Within 72 hours prior to the first dose of study treatment:
For women of reproductive potential, a serum pregnancy test will be performed within 
72 hours prior to first dose of study treatment. If a serum pregnancy test was performed 
during screening, but earlier than 72 hours prior to first dose, a urine pregnancy test may 
be performed prior to first dose. A negative pregnancy test collected within 72 hours
prior to first dose must be available prior to the administration of the first dose.
The investigator or qualified designee must obtain documented informed consent from each 
potential subject prior to participating in the clinical study.
Specimens that may be used for genetic testing include blood and tumor specimens collected 
during this study. 
After a subject signs an informed consent form, the subject will be assigned a unique, sequential 
subject number. Once a number is assigned, it cannot be reassigned if the original subject is 
found to be ineligible or withdraws consent.
All subjects will be given an Emergency Medical Support and Subject Card identifying them as 
participants in a research study. The card will contain study site contact information (including 
direct telephone numbers) to be utilized in the event of an emergency. The investigator or 
qualified designee will provide the subject with an Emergency Medical Support and Subject 
Card immediately after the subject provides written informed consent.
Subjects who fulfill all of the inclusion criteria and none of the exclusion criteria will be enrolled 
into the study within 28 days after screening. Subjects who do not meet the inclusion and 
exclusion criteria will be considered screen fails, and their demographic information and reason 
for screen failure should be documented.
During the screening period, attention must be given to washout periods for prior treatments and 
prohibited medications.
Results from assessments performed during the initial screening period are acceptable in lieu of 
repeating a screening test if performed within the specified period and the results meet the 
inclusion/exclusion criteria.
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious AEs (SAEs), as well as any AEs related to protocol-
mandated procedures on the AEs case report form (CRF/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 CRF/eCRF. See Section 7 Adverse Events and 
Toxicity Management for additional details.
Serum chemistry, hematology, and coagulation and hepatitis serologies performed at screening 
to assess subject eligibility will be determined by results received from the central lab. If time 
constraints do not allow for timely processing of tests through central lab, then, eligibility may 
be determined using local lab results, with documentation of local lab results and sponsor 
approval.


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6.2.2.
Re-screening Criteria
Subjects who do not enroll 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 who 
are re-screened within 28 days, assessments with results that would exclude the subject will need 
to be repeated.
6.2.3.
Medical History and Baseline Assessments
A medical history will be obtained by the investigator or qualified designee. Medical history will 
include all active conditions; history of HBV, HCV, HIV, and/or human papillomavirus; and any 
condition diagnosed within the prior 10 years that is considered clinically significant by the 
Investigator. Medical history will also include an assessment of smoking history.
Baseline symptoms will be assessed for each subject at screening. Baseline symptoms will be 
graded and recorded according to NCI CTCAE v5.0. Baseline symptoms will be characterized in 
terms including seriousness, causality to previous treatment, toxicity grading, and action(s) taken 
if any.
6.2.3.1.
Cancer Disease Details and Prior Treatment
Cancer disease history will be recorded separately and not listed as medical history. Current 
cancer disease details and prior treatment will be obtained for all subjects including:

Detailed history of the tumor, including histopathological diagnosis, grading, and staging in 
accordance with the eighth edition of the American Joint Committee on Cancer staging 
manual (AJCC-8) tumor node metastasis classification at diagnosis

All therapy used for prior treatment of the tumor (including surgery, radiotherapy, 
chemotherapy, and immunotherapy)

Any other conditions treated with chemotherapy, radiation therapy, or immunotherapy

Current cancer signs and symptoms, and side effects from current and/or previous anticancer 
treatments

Current cancer disease status

Relevant somatic or germ line mutations detected

Smoking history


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
Chronic viral infection status, if available

Tumor markers, if indicated
6.2.4.
Vital Signs, Weight, and Height
The investigator or qualified designee will take vital signs at screening, prior to and following 
the administration of each dose of study treatment, and through the Follow-up period as specified 
in the Study Procedures Table (Appendix 2). Vital signs will only be measured while subject is 
in seated or semi-recumbent position. Vital signs include temperature, pulse, respiratory rate, and 
blood pressure. Weight should be assessed as specified in Appendix 2 prior to dosing, at the 
beginning of each cycle, and through the follow-up period. Height will be measured at screening
only.
6.2.5.
Physical Examination
6.2.5.1.
Full Physical Examination
The investigator or qualified designee will perform a complete physical examination during the 
screening period and at the End-of-Treatment Visit as specified in the Study Procedures Table 
(Appendix 2). Clinically significant abnormal findings should be recorded as medical history. 
After consent, new clinically significant abnormal findings should be recorded as AEs as per 
Section 7.3.
6.2.5.2.
Focused Physical Examination
For cycles that do not require a full physical examination as specified in the Study Procedures 
Table (Appendix 2), the investigator or qualified designee will perform a directed physical 
examination as clinically indicated prior to study treatment administration. New clinically 
significant abnormal findings should be recorded as AEs.
6.2.5.3.
Eastern Cooperative Oncology Group Performance Status
ECOG performance status will be assessed at screening, prior to the administration of each dose 
of study treatment and during the Follow-up period as specified in Appendix 2.
6.2.6.
Electrocardiogram
A standard 12-lead ECG will be performed using local standard procedures at screening and as 
specified in Appendix 2. For subjects in Cohorts 5 through 10, a triplicate ECG will be 
performed at Cycle 1, Day 1 predose, at end of infusion, at 24 hours postdose (Day 2), and 
168 hours postdose (Day 8). Clinically significant abnormal findings at screening should be 
recorded as medical history.


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6.2.7.
Echocardiogram or MUGA Scan
A full standard echocardiogram evaluation will be performed using local standard procedures at 
screening to establish a baseline and on Day 1 of every odd cycle, starting at Cycle 3. A MUGA 
scan is also allowed. Clinically significant abnormal findings at screening should be recorded as 
medical history and discussed with the medical monitor.
6.2.8.
Prior and Concomitant Medications
Prior medication taken by the subject within 30 days prior to screening visit will be recorded. In 
addition, record all treatments for a prior cancer other than current cancer even if taken greater 
than 30 days prior to screening. Prior treatments for the current cancer will be recorded 
separately and not listed as a prior medication.
Concomitant medications, if any, taken by the subject during the study from the date of consent 
through the 30-Day Follow-up Visit should be recorded. After the 30-Day Follow-up Visit, all 
medications related to reportable SAEs will be recorded as defined in Section 7.3.
6.2.9.
Clinical Laboratory Assessments
The central laboratory will be responsible for chemistry, hematology, coagulation, urinalysis, 
HBV and HCV serology, and serum pregnancy testing (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 laboratory results, will be reported on the eCRF. Gilead’s standard 
reference ranges will be used. 
Urine pregnancy test will be performed locally at the site. 
Laboratory tests for screening should be performed within 28 days prior to the first dose of study
treatment. After Cycle 1, predose laboratory procedures can be conducted up to 72 hours prior to 
dosing.
Results must be reviewed by the investigator or qualified designee and found to be acceptable 
prior to each dose of study treatment. The report of the results must be retained as a part of the 
subject’s medical record or source documents. Blood samples for study-related tests will be 
collected at time points specified in Appendix 2.


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Table 6-1.
Analytes
Chemistry
Urinalysis
Hematology 
Other 
Albumin
Alkaline phosphatase
ALT 
AST 
Bicarbonate
BUN/total urea
Calcium
Chloride
Serum Creatininea
CRP
GGT
Glucose
LDH
Lipase
Cholesterol
Tryglycerides
Amylase
Magnesium
Phosphorus/phosphates
Potassium
Sodium
Total bilirubinb
Direct bilirubin
Total protein
Uric acid
Color and appearance
Specific gravity
pH
Occult blood
Protein
Glucose
Bilirubin
Leukocyte esterase
Nitrite
Urobilinogen
Ketones
Microscopicb
WBC and differential absolute 
count
Eosinophils
Lymphocytes
Monocytes
ANC
Hemoglobin
Hematocrit
Platelet count
MCV
RBC
Serum β hCG or urine pregnancy 
testc
Endocrine Function Tests (TSH 
and freeT4d)
Basal cortisol
Hepatitis Serologyb
Coagulation
Prothrombin time (INR)
aPTT
β hCG  beta human chorionic gonadotropin; ALT  alanine aminotransferase; ANC  total absolute neutrophil count; aPTT  
activated partial thromboplastin time; AST
aspartate aminotransferase; BUN
blood urea nitrogen; CRP
C reactive protein;
Free T4  free thyroxine; GGT
gamma glutamyltransferase; INR
international normalized ratio; LDH
lactate 
dehydrogenase; MCH
mean corpuscular hemoglobin; MCHC
mean corpuscular hemoglobin concentration; MCV
mean 
corpuscular volume; RBC
red blood cell; PT
prothrombin time; TSH  thyroid stimulating hormone; WBC
white blood 
cell
a
Estimated creatinine clearance (CLcr)/glomerular filtration rate will be calculated based on the Cockcroft 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 childbearing potential only. Serum pregnancy will be conducted at screening within 72 hours of first treatment 
dose (if performed earlier in screening period then a urine pregnancy test may be performed prior to first dose); urine 
pregnancy test at all other indicated visits. 
d
TSH and free T4 will be tested by the central laboratory. T4 will be tested reflexively based on abnormal TSH results.
6.3.
Randomization
No randomization procedures will be applied to treatment assignment for the study.
6.4.
Treatment Assessments
Subject should continue to receive all assessments as defined in the Treatment Phase (Cycle 1 
Day 1 [C1D1] until End of Treatment) of the Study Procedures Table (Appendix 2) while they 
are actively receiving treatment.


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6.5.
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 in subject source documents and captured in the 
eCRFs.
6.6.
Pharmacokinetic 
6.6.1.
Pharmacokinetic Assessments
6.6.1.1.
Pharmacokinetic Parameters
GS-1423 concentrations will be determined by a validated method. The PK parameters to be 
estimated and reported may include, but may not be limited to, maximum observed drug 
concentration (Cmax), area under the concentration versus time curve over the dosing interval 
(AUCtau), observed drug concentration at the trough (Ctrough), time to maximum observed 
concentration (Tmax), systemic clearance (CL), and Vd as applicable. Unresolved missing data 
may be imputed when analysis integrity is affected. The conservative principle will be used for 
data imputation. Noncompartmental techniques will be used to analyze the PK. Compartmental 
modeling (eg, population PK) analysis may be conducted.
6.6.1.2.
PK Sample Collection
Blood sample collection for GS-1423 PK characterization will be conducted throughout the 
study. The time for collection of PK blood draws should always be referenced from the start of 
the infusion. It is important to record all infusion start dates/times, infusion end dates/times, 
infusion interruption(s) start and end dates/times, infusion flush end dates/times, and blood 
sample dates/times completely and accurately (and to the nearest minute).
Blood will be collected predose [within 0.5 hours predose] at specified time points (Table 6-2, 
Table 6-3 and Table 6-4) throughout the study. Additionally, blood will be collected at the 
30-Day Follow-up Visit (approximately 30 days after last dose) and at the first Posttreatment 
Follow-up Visit (approximately 3 months after last dose).
6.6.1.2.1.
PK Sample Collection for Phase 1a Cohorts
6.6.1.2.1.1.
PK Sample Collection for QW Dosing Schedule in Phase 1a Cohorts
At Cycles 1 and 6, blood will be collected predose [within 0.5 hours predose], and at end of 
infusion [+ 10 minutes], 2 hours [± 15 minutes], 6 hours [± 0.5 hours], Day 2 (24 hours) 
[± 2 hours], Day 3 (48 hours) [± 4 hours], and Day 5 (96 hours) [± 4 hours] post start of infusion.
At Cycle 6, blood will also be collected at Day 8 (168 hours) [± 4 hours] post start of infusion.
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Table 6-2.
Schedule of Pharmacokinetic Assessments for QW Dosing Schedule in 
Phase 1a Cohorts
Day 1
Day 2
(24 h)
Day 3
(48 h)
Day 5
(96 h)
Day 8
(168 h)
Cycle 1
Predose, end of 
infusion, 2 and 6 h 
post start of infusion
X
X
X
Cycle 2
Predose
Cycle 3
Predose
Cycle 6
Predose, end of 
infusion, 2 and 6 h 
post start of infusion
X
X
X
X b
Subsequent every 4 cycles up to 
1 year
Predose 
(and 2 ha post start of 
infusion for last even 
cycle only)
30-Day Follow-up Visit 
(30 days after last dose)
X
Posttreatment Follow-up Visit 
(3 months after last dose)
X
QW  every week
a
PK collection at 2 hours post start of infusion will only be conducted at the last even cycle visit.
b
Blood will be drawn at Cycle 6, Day 8 (± 4 hours) even if the subject discontinues treatment at Cycle 7.
6.6.1.2.1.2.
PK Sample Collection for Q2W Dosing Schedule in Phase 1a Cohorts
At Cycles 1 and 4, blood will be collected predose [within 0.5 hours predose], and at end of 
infusion [+ 10 minutes], 2 hours [± 15 minutes], 6 hours [± 0.5 hours], Day 2 (24 hours) 
[± 2 hours], Day 3 (48 hours) [± 4 hours], Day 5 (96 hours) [± 4 hours], and Day 8 (168 hours) 
[± 4 hours] post start of infusion. At Cycle 4, blood will also be collected at Day 15 (336 hours) 
[± 1 day] post start of infusion.


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Table 6-3.
Schedule of Pharmacokinetic Assessments for Q2W Dosing Schedule 
in Phase 1a Cohorts
Day 1
Day 2
(24 h)
Day 3
(48 h)
Day 5
(96 h)
Day 8
(168 h)
Day 15
(336 h)
Cycle 1
Predose, end of 
infusion, 2 and 6 h 
post start of infusion
X
X
X
X
Cycle 2
Predose
Cycle 3
Predose
Cycle 4
Predose, end of 
infusion, 2 and 6 h 
post start of infusion
X
X
X
X
Xb
Subsequent even cycles up to 1 
year
Predose (and 2 ha post 
start of infusion for 
last even cycle only)
30-Day Follow-up Visit 
(30 days after last dose)
X
Posttreatment Follow-up Visit 
(3 months after last dose)
X
Q2W  every 2 weeks
a
PK collection at 2 hours post start of infusion will only be conducted at the last even cycle visit.
b
Blood will be drawn at Cycle 4, Day 15 (± 1 day) even if the subject discontinues treatment at Cycle 5.
6.6.1.2.1.3.
Pharmacokinetic Sample Collection for Q3W Dosing Schedule in Phase 1a 
Cohorts
At Cycle 1 and Cycle 3, blood will be collected predose [within 0.5 hours predose], and at end of 
infusion [+ 10 minutes], 2 hours [± 15 minutes], 6 hours [± 0.50 hours], Day 2 (24 hours) 
[± 2 hours], Day 3 (48 hours) [± 4 hours], Day 5 (96 hours) [± 4 hours], Day 8 (168 hours) 
[± 4 hours], and Day 15 (336 hours) [± 1 day] post start of infusion. At Cycle 3, blood will also 
be collected at Day 22 (504 hours) [± 1 day] post start of infusion.


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Table 6-4. 
Schedule of Pharmacokinetic Assessments for Q3W Dosing Schedule 
in Phase l a Cohorts 
Day 2 
Day 3 
Day s 
Day 8 
Day 15 
Day 22 
Day 1 
(24 h) 
(48 h) 
(96 h) 
(168 h) 
(336 h) 
(504 h) 
Predose, end of infusion, 
Cycle 1 
2 and 6 h post start of 
X 
X 
X 
X 
X 
infusion 
Cycle 2 
Predose 
Predose, end of infusion, 
Cycle 3 
2 and 6 h post start of 
X 
X 
X 
X 
X 
Xb 
infusion 
Subsequent even 
Predose ( and 2 h• post 
start of infusion for last 
cycles up to 1 year 
even cycle only) 
30-Day Follow-up 
Visit 
X 
(30 days after last 
dose) 
Posttreatment 
Follow-up Visit 
X 
(3 months after 
last dose) 
Q3W every 3 weeks 
a 
PK collection at 2 hours post start of infusion will only be conducted at the last even cycle visit. 
b 
Blood will be drawn at Cycle 3, Day 22 (± 1 day) even if the subject discontinues treatment at Cycle 4. 
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6.6.2.
Immunogenicity Assessment
The immunogenicity assessment will be conducted to detect and measure anti-drug antibody 
against GS-1423 (ADA). Subjects will have ADA assessed at the designated time points as 
described below.
6.6.2.1.
Immunogenicity Assessment in Phase 1a Cohorts
Table 6-8.
Schedule of ADA Assessments for QW
Cycle 1 Day 1
Predose
Cycle 3 Day 1
Predose
Cycle 4 Day 1
Predose
Cycle 6 Day 1
Predose
Cycle 6 Day 8
168 h postdose
At Cycle 8 Day 1 and subsequent every 12 cycles 
Predose
30-Day Follow-up Visit (30 days after last dose)
X
Posttreatment Follow-up Visit (3 months 
after last dose)
X
ADA
 anti drug antibody against GS 1423; h  hour(s); QW  every week
Note: Blood will be drawn at Cycle 6, Day 8 (± 4 hours) even if the subject discontinues treatment at Cycle7.
Table 6-9.
Schedule of ADA Assessments for Q2W
Cycle 1 Day 1
Predose
Cycle 2 Day 1
Predose
Cycle 3 Day 1
Predose
Cycle 4 Day 1
Predose
Cycle 4 Day 15
336 h postdose
At Cycle 6 Day 1 and subsequent every 6 cycles
Predose
30-Day Follow-up Visit (30 days after last dose)
X
Posttreatment Follow-up Visit (3 months after 
last dose)
X
ADA
 anti drug antibody against GS 1423; Q2W  every 2 weeks
Note: Blood will be drawn at Cycle 4, Day 15 (± 1 day) even if the subject discontinues treatment at Cycle 5.


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Table 6-10. 
Schedule of ADA Assessments for Q3W 
Cycle I Day I 
Predose 
Cycle 2 Day I 
Predose 
Cycle3 Day I 
Predose 
Cycle 3 Day 22 
504 h postdose 
Cycle 6 Day I 
Predose 
At Cycle 8 Day I and subsequent every 4 cycles 
Predose 
30-Day Follow-up Visit (30 days after last dose) 
X 
Posttreatment Follow-up Visit (3 months after 
X 
last dose) 
ADA 
anti drng antibody against GS 1423; Q3W every 3 weeks 
Note: Blood will be drawn at Cycle 3, Day 22 (± I day) even if the subject discontinues treatment at Cycle 4. 
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End of study will be defined as when the last subject reaches the last scheduled follow-up time 
point (including posttreatment or survival), or lost to follow-up, withdraws from the study, dies, 
or the time at which Gilead closes the study. 
6.8. 
6.8.1. 
Posttreatment Assessments 
End-of-Treatment Phase Visits 
End-of-Treatment requirements are outlined in Appendix 2. There is an End-of-Treatment Visit 
within 7 days of last dose of study treatment and a 30-Day Follow-up Visit which occurs 30 days 
( ± 7 days) after last dose of study treatment. 
6.8.1.1. 
End-of-Treatment Visit 
The End-of-Treatment Visit should occur at the time all study drug is penn anently discontinued 
for any reason. If the End-of-Treatment Visit occurs 30 days from the last dose of study 
treatment, at the time of the mandatory 30-Day Follow-up Visit, procedures do not need to be 
repeated. Procedures at the time of discontinuation are detailed in 30-Day Follow-up Visit, 
Section 6.8.1.2. Subjects who discontinue from the study treatment for reasons other than PD 
will continue to have imaging/computed tomography (CT) scans at the predefined schedule m1til 
documented PD or initiation of a new anticancer treatment. 
6.8.1.2. 
30-Day Follow-up Visit 
The mandatory 30-Day Follow-up Visit should be conducted for all subjects approximately 
30 days after the last dose of study treatment or before the initiation of a new anticancer 
treatment, whichever comes first. Subjects with an AE of Grade > 1 will be further followed until 
the resolution of the AE to Grade 0 or 1 or until initiation of a new anticancer therapy, whichever 
occurs first. 
6.8.2. 
Posttreatment Follow-up Phase Visits 
All subjects who discontinue study treatment will have at least 1 posttreatment visit at 3 months 
(± 7 days) from last dose of study treatment. Subjects who discontinue all study treatment for 
any reason other than PD and/or start of new anticancer therapy will have imaging/CT scans at 
the predefined schedule until documented PD or initiation of a new anticancer treatment. 
Subjects who discontinue study drug treatment due to PD and/or start of a new anticancer 
therapy will not require imaging/CT scans and will move into Survival Follow-up thereafter. 
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Subjects who have discontinued all study drug treatment due to reasons other than PD and/or 
start of a new line of therapy should be followed with Posttreatment Follow-up Visits for up to 
12 months from last study treatment dose or until PD and/or start of a new line of therapy. Every 
effort should be made to collect subject information on the start of new anticancer therapy, PD, 
and death.
6.8.3.
Survival Follow-up
After the first Posttreatment Follow-up visit, subjects who present(ed) with PD and/or start(ed) a 
new anticancer therapy will move into Survival Follow-up. Subjects should be contacted by 
telephone to assess for survival status every 3 months for up to 12 months. No imaging 
assessment is required for Survival Follow-up. Information about deaths solicited during the 
Survival Follow-up Period should be reported, but will not be considered or reported as SAEs. 
Investigators should abide by the reporting obligations as stated in Section 7.
6.9.
Assessments for Early Discontinuation from Study
If a subject discontinues study dosing (for example, as a result of an AE), every attempt should 
be made to keep the subject in the study and continue to perform the required study-related 
follow-up and procedures (see Section 6.10.1, Criteria for Discontinuation of Study Treatment). 
If this is not possible or acceptable to the subject or investigator, the subject may be withdrawn 
from the study. 
6.10.
Criteria for Discontinuation from Treatment or Study
6.10.1.
Criteria for Discontinuation from Treatment
Discontinuation of treatment does not represent withdrawal from the study.
As certain data on clinical events beyond treatment discontinuation may be important to the 
study, they must be collected through the subject’s last scheduled follow-up (including 30-Day 
Follow-up or Posttreatment visits), even if the subject has discontinued treatment. Subjects may 
discontinue treatment at any time for any reason or be dropped from treatment at the discretion 
of the investigator should any untoward effect occur. In addition, a subject may be discontinued 
from treatment by the Investigator or by Gilead if treatment is inappropriate, the trial plan is 
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Specific details regarding procedures to be performed at treatment discontinuation are provided 
in the Study Procedures Tables (Appendix 2).  A subject must be discontinued from treatment 
but continue to be monitored in the trial for any of the following reasons:

The subject or subject’s legally acceptable representative requests to discontinue treatment 
for any reason.

Occurrence of an event that would have been considered an exclusion criterion prior to 
enrollment, that is clinically relevant and affects the subject’s safety, and if discontinuation is 
considered necessary by the investigator and/or Gilead.

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree.

Investigator’s decision to discontinue the subject

Initial PD, defined by RECIST 1.1 (Section 6.11.1), unless the subject is considered to derive 
clinical benefit from the treatment by the investigator, is clinically stable, and there is 
agreement with Gilead (Section 5.5.7).

Therapeutic failure (i.e. clinical disease progression)

Recurrence of previously treated malignancy or any occurrence of another malignancy that 
requires active treatment

Pregnancy during the study

Noncompliance with trial treatment or procedure requirements (Section 5.5.6.1)

Use of a non-permitted concomitant drug, as defined in Section 5.6.2, for which the 
predefined consequence is withdrawal from study drug (Gilead may be contacted to discuss 
whether study treatment must be discontinued).

Any requirement for > 10 mg of prednisone per day or equivalent for more than 6 weeks

Dose delay of GS-1423 which results in no GS-1423 dosing for more than 4 weeks (QW or 
Q2W) or 6 weeks (Q3W)

Discontinuation of the study at the request of Gilead, a regulatory agency, or an IRB/IEC

Any AE and/or laboratory abnormality in the judgment of the investigator, presents a 
substantial clinical risk to the subject with continued treatment

AEs specifically described in Section 5.5.6 must lead to study drug discontinuation.
NOTE: Tumor flare phenomenon, defined as local pain, irritation, or rash localized at sites of 
known or suspected tumor does not require treatment discontinuation.


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6.10.2.
Discontinuation from Disease Response Evaluation
Tumor evaluation will be discontinued if any of the following occurs:

In a subject who does not meet the criteria to continue study drug treatment beyond initial 
RECIST 1.1-defined PD (Section 5.5.7).

In a clinically stable subject (defined in Section 5.5.7), at the time of PD is assessed in a 
second, consecutive assessment (using the same imaging modality) no less than 4 weeks 
from previous imaging assessment.  

Initiation of new anticancer therapy
6.10.3.
Criteria for Discontinuation from Study
Subjects should be discontinued from the study for 1 or more of the following:

Withdrawal of consent

Lost to follow-up

Death

Subject noncompliance (Section 5.5.6.1)

Administrative study closure
6.11.
Efficacy Assessments
6.11.1.
Response Assessment
Response assessment will be performed according to RECIST 1.1 {Eisenhauer 2009}. 
For all subjects, tumor response assessment will be performed by CT or magnetic resonance 
imaging (MRI) of the chest/abdomen/pelvis (plus other regions as required for specific tumor 
types) and other established assessments of tumor burden if CT/MRI imaging is insufficient for 
the individual subject. All scans performed at baseline and other imaging performed as clinically 
required (other supportive imaging) will be repeated at subsequent visits. In general, lesions 
detected at baseline should be followed using the same imaging methodology and preferably the 
same imaging equipment at subsequent tumor evaluation visits.
For each subject, the investigator will designate 1 or more of the following measures of tumor 
status to follow for determining response: CT or MRI images of primary and/or metastatic tumor 
masses, physical examination findings, and results of other assessments. All available images 
collected during the study period will be considered. The most appropriate measures to evaluate 
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study must correspond to measures used to document progressive tumor status that qualifies the 
subject for enrollment. 
Subjects who experience initial radiologic PD and are doing well clinically are considered to 
have initial RECIST 1.1-defined PD and will be pennitted, with Gilead's approval, to continue 
with study drug treatment (see Section 6.11.2). These subjects will be reevaluated using the 
same imaging modality no less than 4 weeks later to assess whether study drug treatment will be 
continued. If initial progression is based on occurrence of a new lesion in an area not sca1med at 
baseline, an on-study scan no less than 4 weeks from initial observation of new lesion should be 
considered before perfonning the End-of-Treatment Visit. 
Tumor responses to treatment will be assigned based on evaluation of response of target, 
non-target, and new lesions according to RECIST 1.1 (all measurements should be recorded in 
metric notation; see {Eisenhauer 2009}). To assess objective response, tumor burden at baseline 
will be estimated and used for comparison with subsequent measurements. At baseline, tumor 
lesions will be categorized in target and non-target lesions as described in {Eisenhauer 2009}. 
Results for these evaluations will be recorded with as much specificity as possible so that 
pretreatment and posttreatment results will provide the best opportunity for evaluating tumor 
response. 
Any complete response (CR) or partial response (PR) should be confinned by CT or MRI scan as 
described in {Eisenhauer 2009} no less than 28 days after initial assessment. 
The investigator may perfonn scans in addition to a scheduled study scan for medical reasons or 
if PD is suspected. 
6.11.2. 
Tumor Assessments 
Tumor samples from archival tissues or biopsies will be collected. Subjects must have available 
tissue sam les to enter the stud . Altemativel 
· 
· 
· 
6.11.2.1. 
Tissue Collection 
Tumor tissue-
will be collected at the time of screening from a biopsy 
obtained pref~
e of or after the diagnosis of advanced disease has been 
made, and from a site not previously irradiated. 
If a tumor biopsy was obtained from a target lesion during eligibility assessment, it is preferred 
that a new baseline scan be obtained. 
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In Cohort 2 in Phase 1 b, pretreatment and C3D 1 biopsies are mandatory. 
For additional details and instructions regarding tissue requirements, collection, storage and 
shipment, refer to the study Laboratory Manual. 
6.11.2.2. 
Tumor Imaging 
Investigator-assessed imaging will be done at defined time points. The initial tumor imaging to 
establish baseline disease will be perfonned :S 28 days prior to first dose. Scans perfonned as 
part of routine clinical management are acceptable for use as screening scan if they are of 
diagnostic quality and :S 28 days prior to first dose. On-study imaging as listed on Table 6-18 
will be perfonned as specified below and in Appendix 2. 
Table 6-18. 
Postbaseline Imaging Schedule 
Duration of Tumor Imaging 
Cohort 
Postbaseline Imaging Schedule 
Assessments 
Phase I a ( all cohorts), 
Week 6, 12, 18, and 24 (± 7 days) from 
Until PD is assessed by investigator, new 
Phase I b Cohort 2 
the first treatment dose; then every 12 
line of therapy, or I year after first 
weeks thereafter 
treatment dose, whichever occurs first 
Phase I b Cohort I 
Week 6, 12, 18, and 24 (± 7 days) from 
Until PD is assessed by investigator, new 
the first treatment dose; then every 12 
line of therapy, or 2 years after first 
weeks thereafter 
treatment dose, whichever occurs first 
PD 
progressive disease 
Note: For subjects who pennanently discontinued all study drug(s) in the absence of PD (eg, 
experienced unexpected toxicity), CT or MRI imaging should continue to be perfonned until PD 
or initiation of a new anticancer therapy other than the study treatment, whichever occurs first 
(see Section 6.8.2). 
The timing of on-study treatment imaging should follow calendar days and should not be 
adjusted for delays in treatment administration or for visits. Additional imaging at the End-of-
Treatment Visit and 30-Day Follow-up Visit is not required provided imaging assessments have 
been perfonned per schedule and last imaging must be perfonned within less than 30 days. 
Subjects that discontinue from the study for any reason other than PD will continue to have 
imaging/CT scans at the predefined schedule m1til documented PD or initiation of a new 
anticancer treatment. 
The same imaging technique should be used in a subject throughout the study. In general, lesions 
detected at baseline should be followed using the same imaging methodology and preferably the 
same imaging equipment at subsequent tumor evaluation visits. The Investigator may perfonn 
scans in addition to a scheduled study scan for medical reasons or if PD is suspected. 
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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 an 
investigational 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 an investigational product, whether or not considered related to the 
investigational product. Adverse events may also include pretreatment or posttreatment 
complications that occur as a result of protocol-specified procedures or special situations 
(Section 7.7). 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. Adverse events 
should be reported as described in Section 7.3.
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 AE and must be reported.

Preexisting 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 (ie, hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (Section 7.7.1)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the informed consent form is signed and not related to a protocol-associated procedure 
is not an AE. It is considered to be preexisting and should be documented as medical history.
7.1.2.
Serious Adverse Events
An SAE is defined as an event that, at any dose, results in the following:

Death (Note:  In the case of death, the primary cause of death or the event leading to death 
should be recorded and reported as an SAE. “Fatal” will be recorded as the outcome of this 
respective event; death will not be recorded as separate event. Only if no cause of death can 
be reported (eg, sudden death, unexplained death), might the death per se be reported as an 
SAE. Please refer to Section 7.1.2.3 for exceptions.)


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
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.)

In-patient hospitalization or prolongation of existing hospitalization

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. 
7.1.2.1.
Protocol-Specific Adverse Event Instructions
Given the intended mechanism of action, particular attention should be given to AEs that may 
result from enhanced T-cell activation, such as dermatitis, colitis, hepatitis, uveitis, or other 
immune-related reactions. When clinically indicated, ophthalmologic examinations should be 
considered for signs or symptoms of uveitis.
An irAE may be defined as an AE of unknown etiology, associated with drug exposure and is 
consistent with an immune phenomenon. Efforts should be made to rule out neoplastic, 
infectious, metabolic, toxin, or other etiologic causes prior to labeling an AE as immune related. 
Immunological, serological, and histological (biopsy) data should be used to support the 
diagnosis of an immune-related toxicity. 
Complete, accurate, and consistent data on all AEs experienced for the duration of the reporting 
period (defined below) will be reported on an ongoing basis in the appropriate section of the 
eCRF. Any serious irAEs should be reported in accordance to Section 7.3.
It is important that each AE report include a description of the event, its duration (onset and 
resolution dates and times to be completed when it is important to assess time of AE onset 
relative to recorded treatment administration time), its severity, causal relationship with study
treatment, any other potential causal factors, any treatment administered, or other action taken 
(including dose modification or discontinuation of the study drug), and outcome. In addition, 
serious cases should be identified, and the appropriate seriousness criteria documented.
Specific guidance can be found in the eCRF Completion and Monitoring Conventions.


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7.1.2.2.
Events of Clinical Interest
Events of clinical interest, regardless of seriousness, are to be reported within 24 hours to Gilead
either by electronic media or paper. Gilead contact information can be found in the Investigator 
Study File Binder (or equivalent).
Events of clinical interest for this study include:

An elevated AST or ALT lab value ≥3 × ULN and an elevated total bilirubin lab value 
≥2 × ULN and, at the same time, an alkaline phosphatase lab value < 2 × ULN, as 
determined by way of protocol-specified laboratory testing or unscheduled laboratory testing.
Note: These criteria are based upon available regulatory guidance documents. The purpose 
of the criteria is to specify a threshold of abnormal hepatic tests that may require an 
additional evaluation for an underlying etiology.
7.1.2.3.
Disease Progression
In order to maintain the integrity of the study, the following events that are assessed as unrelated 
to study drugs will not be considered SAEs:

Disease progression of malignancy being studied

Death due to disease progression of malignancy being studied 
Disease progression and death due to disease progression of malignancy being studied should be 
reported as an SAE by the investigator only if it is assessed as related to study drug.
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 AE has an etiology other than the study drug. For SAEs, an 
alternative causality must be provided (ie, preexisting condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the study drug.
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of AE reporting. 


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The relationship to study procedures (ie, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the AE has an etiology other than the study procedure.

Yes: The AE occurred as a result of protocol procedures (ie, venipuncture).
7.2.2.
Assessment of Severity
Adverse events will be graded and recorded throughout the study and during the follow-up 
period according to NCI CTCAE v5.0. A general grading (severity/intensity) scale is provided at 
the beginning of the referenced document, and specific event Grades are also provided. If a 
particular AE severity/intensity is not specifically graded by the guidance document, the 
investigator is to revert to the general definitions of Grade 1 through Grade 5 and use his/her best 
medical judgment.
The 5 general Grades of AE severity are:

Grade 1:
Mild

Grade 2:
Moderate

Grade 3:
Severe

Grade 4:
Life-threatening or disabling

Grade 5:
Death related to AE
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
must be reported on the applicable eCRFs: all SAEs and AEs related to protocol-mandated 
procedures.
7.3.1.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until the study’s End-of-Treatment Safety Visit, 30 days after last administration of study drug
and they must be reported on the eCRFs as instructed.
All AEs should be followed up until resolution or until the AE is stable, if possible. Gilead may 
request that certain AEs be followed beyond the protocol-defined follow-up period.


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7.3.2. 
Serious Adverse Events 
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All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (ie, signing the infonned consent) and throughout the duration of the 
study, up to 30-Day Follow-up Visit, must be reported on the applicable eCRFs and to Gilead 
PYE as instructed below in this section. This also includes any SAEs resulting from protocol-
associated procedures perfonned after infonned consent is signed. 
Any SAEs and deaths that occur after the End-of-Treatment Visit but within 30 days of the last 
dose of study drug, 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 the protocol-defined follow-up 
period has concluded and the event is deemed relevant to the use of study drug, the investigator 
should promptly document and report the event to Gilead PYE. 
• 
All AEs and SAEs will be recorded in the eCRF database within 24 hours. 
Electronic Serious Adverse Event (eSAE) Reporting Process 
• 
Site perso1mel record all SAE data in the eCRF database and from there transmit the SAE 
infonnation to Gilead PYE within 24 hours of the investigator's knowledge of the event. 
Detailed instructions can be fom1d in the eCRF completion guidelines. 
• 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 SAE reporting fonn and submit 
within 24 hours to: 
Gilead PYE: 
Fax: 
E-maib 
• 
As soon as it is possible to do so, any SAE reported via paper must be transcribed into the 
eCRF database according to instructions in the eCRF completion guidelines. 
• If an SAE has been reported via a paper fonn because the eCRF database has been locked, 
no further action is necessary. 
• 
For fatal or life-threatening events, copies of hospital case reports, autopsy reports, 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 traceability of a docmnent to the subject identifiers. 
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
Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s CRF/eCRF and the event description section of the SAE
reporting form.
7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US Food and 
Drug Administration Code of Federal Regulations, the EU Clinical Trials Directive 
(2001/20/EC) and relevant updates, and other country-specific legislation or regulations, Gilead 
may be required to expedite to worldwide regulatory agencies reports of SAEs, serious adverse 
drug reactions, or suspected unexpected serious adverse reactions (SUSARs). In accordance with 
the EU Clinical Trials Directive (2001/20/EC), Gilead or a specified designee will notify 
worldwide regulatory agencies and the relevant IEC in concerned Member States of applicable 
SUSARs as outlined in current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study drug. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy. 
7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (ie, 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 (ie, ECG, x-rays, vital signs) that are associated with 
signs and/or symptoms must be recorded as an AE or SAE if they meet the definition of an AE 
or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory abnormality is part of a 
syndrome, record the syndrome or diagnosis (ie, anemia), not the laboratory result (ie, decreased 
hemoglobin).
7.6.
Toxicity Management
Severity should be recorded and graded according to NCI CTCAE v5.0 (Appendix 4).


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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 AEs 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 labeling. 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).

For monitoring purposes, any case of overdose, whether or not associated with an AE 
(serious or non-serious), must be reported to Gilead’s or designated CRO’s global drug safety 
department in an expedited manner using the Special Situations Report (SSR) form.

There is no data on GS-1423 overdose to date.

The investigator should use his/her clinical judgment when treating an overdose of GS-1423.
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.
7.7.2.
Instructions for Reporting Special Situations
7.7.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study medication and throughout the study, including the Posttreatment Follow-up 
Period, to Gilead PVE using the pregnancy report form within 24 hours of becoming aware of 
the pregnancy. 
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of pregnancy reporting.


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The pregnancy itself is not considered an AE nor is an induced elective abortion to tenninate a 
pregnancy without medical reasons. 
Any premature tennination of pregnancy (ie, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE tenn. 
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3.2. Furthennore, any SAE occurring as an adverse pregnancy outcome post study 
must be reported to Gilead PYE. 
The subject should receive appropriate monitoring and care m1til the conclusion of the 
pregnancy. The outcome should be reported to Gilead PYE using the pregnancy outcome report 
fonn. If the end of the pregnancy occurs after the study has been completed, the outcome should 
be reported directly to Gilead PYE via: 
Gilead PYE: 
Fax: 
E-mail 
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant infonnation should be submitted to Gilead PYE using the 
pregnancy report and pregnancy outcome report fonns 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 PYE. 
Refer to Appendix 5 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements. 
7.7.2.2. 
Reporting Other Special Situations 
All other special situation reports must be reported on the SSR fonn and forwarded to Gilead 
PYE within 24 hours of the investigator beco1ning aware of the situation. These reports must 
consist of situations that involve study drug and/or Gilead conc01nitant medications but do not 
apply to non-Gilead conc01nitant medications. 
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the SSR fonn; however, for special situations that result in AEs due to a non-Gilead concomitant 
medication, the AE should be reported on the AE fonn. 
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. 
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Refer to Section 7.3 and 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 CRF/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.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The objectives of this study are described in Sections 2.1 and 2.2.
8.1.2.
Primary Endpoints
Phase 1a Part A, Phase 1b Cohort 1 Safety Run-in
The primary endpoint is the occurrence of DLTs in subjects (ie, percentage of subjects who had 
DLTs) in dose escalation during the first 28 days of treatment.
Phase 1b Cohort 1 Post Safety Run-in
The primary endpoint is the confirmed ORR per RECIST 1.1, as determined by investigator and
defined as the proportion of subjects who achieve best confirmed overall response of CR or PR 
as assessed by RECIST 1.1.
Phase 1a Part B, Phase 1b Cohort 2
The primary endpoints are:

Percentage of subjects with treatment-emergent AEs

Percentage of subjects with treatment-emergent Grade 3 or 4 laboratory abnormalities

Percentage of subjects with clinically significant abnormal 12-lead ECG
8.1.3.
Secondary Endpoints
The secondary endpoints of this study are:
Phase 1a Part A

Percentage of subjects with treatment-emergent AEs

Percentage of subjects with treatment-emergent Grade 3 or 4 laboratory abnormalities

Percentage of subjects with clinically significant abnormal 12-lead ECG

GS-1423 PK parameters (AUCtau) 

Percentage of subjects who developed ADA 


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• 
GS-1423 PK parameters (A UC.au) 
• 
Percentage of subjects who developed ADA 
Phase 1 b Cohort 1 
• 
Percentage of subjects with treatment-emergent AEs 
Final 
Amendment2 
• 
Percentage of subjects with treatment-emergent Grade 3 or 4 laboratory abnonnalities 
• 
Percentage of subjects with clinically significant abnonnal 12-lead ECG 
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8.2. 
8.2.1. 
8.2.1.1. 
Planned Analyses 
Interim Analysis 
Dose Escalation Analysis 
Final 
Amendment 2 
For the purpose of making the decision to escalate to the next dose level/cohort, interim analyses 
of relevant safety and PK (if available) data will be conducted by Gilead after all subjects in each 
cohort have completed dosing and the follow-up period as defined in Section 3.2.3. Safety 
assessments (ie, AEs, ECG, and laboratory results) will be displayed by dose level/cohort to 
facilitate the decision to dose escalate. 
8.2.1.2. 
Planned Internal Analysis 
For Phase 1 b Cohort 1 post safety run-in, one futility interim analysis may be perfonned after 
approximately 35 (ie, 50% of the planned sample size for this part of study) subjects have been 
enrolled and are able to complete study treatment for at least 6 months. The futility stopping 
boundary at the interim analysis will be detennined by assessing predictive power. Details for 
the futility interim analysis will be specified in the statistical analysis plan. The enrollment for 
Phase 1 b Cohort 1 will not be paused. 
8.2.2. 
Final Analysis 
The final analysis will be perfonned after all subjects have completed or discontinued from the 
study, outstanding data queries have been resolved or adjudicated as m1resolvable, and the data 
have been cleaned and finalized. 
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8.3. 
8.3.1. 
8.3.1.1. 
Analysis Conventions 
Analysis Sets 
All Enrolled Analysis Set 
Final 
Amendment2 
The All Enrolled Analysis Set includes all subjects who received a study subject identification 
number in the study after screening. This will be the primary analysis set for by-subject listings. 
8.3.1.2. 
DLT-Evaluable Analysis Set 
The DLT-Evaluable Analysis Set includes all subjects who were enrolled for dose escalation, 
received the protocol-specified treatment, and completed safety procedures through Day 28 
(inclusive) or experienced a DLT prior to Day 28. For Phase la Part A and Phase lb Cohort 1 
safety run-in, detennination of the DL T and/or MTD or RP2D will be based on the 
DLT-Evaluable Analysis Set. 
8.3.1.3. 
Safety Analysis Set 
The Safety Analysis Set includes all subjects who received at least 1 dose of study drug. This 
will be the primary analysis set for safety analyses. 
8.3.1.4. 
Full Analysis Set 
The Full Analysis Set includes all enrolled subjects who received at least 1 dose of study drug. 
This will be the primary analysis set for efficacy analyses. 
8.3.1.5. 
Phannacokinetics Analysis Set 
The PK Analysis Set includes all enrolled subjects who received at least 1 dose of study drug and 
have at least 1 non-missing postdose concentration value reported by the PK laboratory. This 
will be the primary analysis set for all PK analyses. 
8.3.1.6. 
Immm1ogenicity Analysis Set 
The bmnunogenicity Analysis Set includes all enrolled subjects who received at least 1 dose of 
study drug and had at least 1 ADA test. This will be the primary analysis set for iimnunogenicity 
data analyses. 
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8.4.
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, 90% confidence intervals (CIs) on the mean, 
median, minimum, and maximum. Summary tables for categorical variables will include: N, n, 
percentage, and 90% CIs on the percentage. Unless otherwise indicated, 90% CIs for binary 
variables will be calculated using the binomial distribution (exact method) and will be 2-sided. 
Data will be described and summarized by dose level/cohort, analysis set, and time point. 
As appropriate, changes from baseline to each subsequent time point will be described and 
summarized. Similarly, as appropriate, the best change from baseline during the study will also 
be described and summarized. Graphical techniques (ie, 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.
8.5.
Demographic and Baseline Characteristics
Demographic and baseline measurements will be summarized using standard descriptive 
methods.
Demographic summaries will include sex, race/ethnicity, and age.
Baseline data will include a summary of body weight, height, and body mass index.
8.6.
Efficacy Analysis
8.6.1.
Categorical Endpoints
Categorical endpoints, such as ORR and DCR will be summarized. The corresponding 90% 
exact CIs may be present if appropriate. The response at each scheduled tumor assessment will 
be listed for each subject.
8.6.2.
Time-to-Event Endpoints
Time-to-event endpoints, such as PFS, OS, and DOR, will be analyzed using KM methods.
The KM estimate of the survival function will be computed, and the results will be presented 
using KM curves. The median will be provided along with the corresponding 90% CI.


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8.7.
Safety Analysis
All safety data collected on or after the start of treatment up to 30 days after the last dose of 
study drug will be summarized by dose level/cohort for subjects in the Safety Analysis Set. Data 
for the pretreatment and posttreatment follow-up period will be included in data listings. 
For categorical safety data including incidence of AEs and categorizations of laboratory data, 
count and percent of subjects will be summarized. For continuous safety data including 
laboratory data, sample size, mean, standard deviation, minimum, quartiles, median, and 
maximum will be summarized.
8.7.1.
Extent of Exposure
A subject’s extent of exposure to GS-1423 data will be generated from the GS-1423
administration data. Exposure data will be summarized by dose level/cohort.
8.7.2.
Adverse Events
Clinical and laboratory AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). System organ class, high-level group term, high-level term, preferred 
term, and lower-level term 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 will be defined as any AE that begins on or after the date of first dose of study drug up to the 
last dose of study drug plus 30 days.
Summaries (number and percentage of subjects) of treatment-emergent AEs (by system organ 
class and preferred term) will be provided by treatment group.
8.7.3.
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 NCI CTCAE v5.0.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time point postbaseline will be summarized by dose 
level/cohort. If baseline data are missing, then any graded abnormality (ie, at least a Grade 1) 
will be considered treatment emergent.
Laboratory abnormalities that occur before the first dose of study drug or after the subject has 
been discontinued from treatment for at least 30 days will be included in a data listing.


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8.7.4. 
Other Safety Evaluations 
Final 
Amendment2 
Similar general approaches to the AE and clinical laboratory data will be utilized to smmnarize 
other safety measures. 
8.8. 
Pharmacokinetic Analysis 
Plasma concentrations for GS-1423 will be summarized by nominal sampling time using 
descriptive statistics (ie, sample size, arithmetic mean, geometric mean, % coefficient of 
variation, standard deviation, median, minimmn , and maximmn ) by dose level/cohort. Plasma 
concentrations of GS-1423 over time may be plotted in semi-logarithmic and linear fonn ats as 
mean ± standard deviation by dose level/cohort. 
Phannacokinetic parameters (AUC1au, Cmax, Ctrough, Tmax, CL, Yct, etc, as appropriate) will be 
listed and smmnarized using descriptive statistics by dose level/cohort. 
8.9. 
Immunogenicity Analysis 
bmnm1ogenicity to GS-1423 will be evaluated based upon the incidence of ADA fonn ation. 
Number and percentage of positive or negative ADA results at each specified time point will be 
summarized by dose level/cohort using the Immunogenicity Analysis Set. Supporting data 
including treatment, nominal sampling day, actual date and time of sampling, and ADA results, 
will be included in a listing . 
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8.11.
Sample Size
Phase 1a Part A
Assuming that up to 7 planned dose levels for escalation will be tested with up to 6 subjects per 
dose level (42 subjects for escalation) and 10% of subjects are not evaluable, and 6 additional 
subjects may be enrolled at a dose level at or below MTD to obtain additional safety, PK, and 
information, up to 53 subjects will be enrolled.
Phase 1a Part B
Assuming 10% of subjects are not evaluable for PK and 
 assessments in the 
first 28 days on and after the first dosing of GS-1423, up to 40 subjects may be enrolled to obtain 
12 evaluable subjects per cohort for up to 3 planned cohorts.
Phase 1b Cohort 1 Safety Run-in
Assuming that up to 2 planned dose levels for escalation will be tested with up to 6 subjects per 
dose level (12 subjects for escalation) and 10% of subjects are not evaluable, and 6 additional 
subjects may be enrolled at a dose level at or below MTD to obtain additional safety, 
 and 
 information, up to 20 subjects will be enrolled.
Phase 1b Cohort 1 Post Safety Run-in
In a randomized Phase 3 study, the ORR of mFOLFOX6 as first-line treatment in subjects with 
advanced gastric or gastroesophageal junction adenocarcinoma was approximately 40% {Lee 
2010}. Phase 1b Cohort 1 post safety run-in will be a single-arm study. The null hypothesis of a 
35% confirmed ORR will be tested against the alternative hypothesis of a 50% confirmed ORR 
with GS-1423 in combination with mFOLFOX6. A sample size of 70 subjects will provide at 
least 85% power at a 1-sided significance level of 0.1 using a binomial test.
Phase 1b Cohort 2 
This cohort will enroll subjects until evaluable paired biopsies from at least 15 subjects are 
available, with at least 5 of which NSCLC subjects and 5 CRC or pancreatic cancer subjects.
CCI
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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 ICH E6(R2) 
addendum to its guidelines for GCP and applicable laws and regulations.
9.1.2.
Financial Disclosure
The Investigator and subinvestigators will provide prompt and accurate documentation of their 
financial interest or arrangements with Gilead or proprietary interests in the investigational drug 
during the course of a clinical 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.
9.1.3.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval
The Investigator (or Gilead 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 approval, with the exception of those necessary to reduce 
immediate risk to study subjects.
9.1.4.
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 before undertaking any study-related procedures. The investigator 
must use the most current IRB/IEC approved informed 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 informed consent form will inform subjects about pharmacogenomic testing 


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and sample retention, and their right to receive clinically relevant pharmacogenomic analysis 
results.
9.1.5.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only an identification code and any other 
unique identifier(s) as allowed by local law (such as year of birth) will be recorded on any form 
or biological sample submitted to Gilead, 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 with details for all subjects screened and enrolled in the study, in accordance with 
the site procedures and regulations. 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’s brochure, this protocol, CRF/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.
9.1.6.
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, paper or electronic 
completed subject CRFs, 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 

Documentation that subject meets eligibility criteria, ie, medical history, physical 
examination, and confirmation of diagnosis (to support inclusion and exclusion criteria)

Documentation of the reason(s) a consented subject is not enrolled


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
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 AEs and other safety parameters (start and end date, causality and severity) and 
documentation that adequate medical care has been provided for any AE

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, US, 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.
9.1.7.
Case Report Forms
For each subject consented, an eCRF casebook will be completed by an authorized study staff 
member whose training for this function is completed in the EDC system. The eCRF will only 
capture the data required per the protocol schedule of events and procedures. The 
inclusion/exclusion criteria and enrollment eCRFs should be completed only after all data related 
to eligibility have been received. Data entry should be performed in accordance with the eCRF
Completion Guidelines provided by Gilead. Subsequent to data entry, a study monitor will 


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perform source data verification within the EDC system. System-generated or manual queries 
will be issued in the EDC system as data discrepancies are identified by the monitor or Gilead 
staff, who routinely review the data for completeness, correctness, and consistency. The site 
investigator or site coordinator or other designee 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). Original entries as 
well as any changes to data fields will be stored in the audit trail of the system. At a minimum, 
prior to any interim time points or database lock (as instructed by Gilead), 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. At the conclusion of the study, Gilead 
will provide the site investigator 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 9.1.6.
9.1.8.
Investigator Inspections
The investigator will make available all source documents and other records for this study to 
Gilead’s appointed study monitors, to IRB/IECs, or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB/IEC in 
accordance with local requirements and receive documented IRB/IEC approval before 
modifications can be implemented.
9.2.2.
Study Report and Publications
A clinical study report 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. 


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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 9.1.5).

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 (ie, attendance at investigator 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 study payments, meal, 
travel expenses or reimbursements, consulting fees, and any other transfer of value.
9.3.2.
Access to Information for Monitoring
The monitor is responsible for routine review of the CRF/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 in the CRF/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.


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9.3.4.
Study Discontinuation
Both Gilead 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 subjects, 
appropriate regulatory authority, IRBs, and ECs. In terminating the study, Gilead and the 
investigator will assure that adequate consideration is given to the protection of the subjects’ 
interests.


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10.
REFERENCES
Allard B, Pommey S, Smyth MJ, Stagg J. Targeting CD73 Enhances the Antitumor Activity of 
Anti-PD-1 and Anti-CTLA-4 mAbs. Clin Cancer Res 2013;19 (20):5626-35.
Antonioli L, Pacher P, Vizi ES, Hasko G. CD39 and CD73 in Immunity and Inflammation. 
Trends Mol Med 2013;19 (6):355-67.
Arjaans M, Oude Munnink TH, Timmer-Bosscha H, Reiss M, Walenkamp AM, Lub-de Hooge 
MN, et al. Transforming Growth Factor (TGF)-beta Expression and Activation 
Mechanisms as Potential Targets for Anti-Tumor Therapy and Tumor Imaging. 
Pharmacol Ther 2012;135:123-32.
Barnhart C, Sega E, Yamniuk A, Hatcher S, Lei M, Ghermazien H, et al. A Therapeutic 
Antibody that Inhibits CD73 Activity by Dual Mechanisms [Abstract 1476]. 
AACR 107th Annual Meeting 2016; 2016 16-20 April; New Orleans, LA. 
Bullen JW, Tchernyshyov I, Holewinski RJ, DeVine L, Wu F, Venkatraman V, et al. Protein 
Kinase A-Dependent Phosphorylation Stimulates the Transcriptional Activity of 
Hypoxia-Inducible Factor 1. Science signaling 2016;9 (430):ra56.
David CJ, Massague J. Contextual Determinants of TGFbeta Action in Development, Immunity 
and Cancer. Nature reviews. Molecular cell biology 2018.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New Response 
Evaluation Criteria in Solid Tumours: Revised RECIST Guideline (Version 1.1). 
Eur J Cancer 2009;45 (2):228-47.
Geoghegan JC, Diedrich G, Lu X, Rosenthal K, Sachsenmeier KF, Wu H, et al. Inhibition of 
CD73 AMP Hydrolysis by a Therapeutic Antibody with a Dual, Non-Competitive 
Mechanism of Action [Accepted Manuscript]. mAbs 2016.
Holmgaard RB, Schaer DA, Li Y, Castaneda SP, Murphy MY, Xu X, et al. Targeting the 
TGFbeta Pathway with Galunisertib, a TGFbetaRI Small Molecule Inhibitor, 
Promotes Anti-Tumor Immunity Leading to Durable, Complete Responses, as 
Monotherapy and in Combination with Checkpoint Blockade. Journal for 
immunotherapy of cancer 2018;6:47.
Kim HS, Kim JH, Kim HJ, Jang HJ, Kim JB, Kim JW, et al. Oxaliplatin, 5-fluorouracil and 
leucovorin (modified FOLFOX-6) as first-line chemotherapy for advanced gastric 
cancer patients with poor performance status. Oncology letters 2012;3 (2):425-8.
Knudson KM, Hicks KC, Luo X, Chen JQ, Schlom J, Gameiro SR. M7824, a Novel Bifunctional 
Anti-PD-L1/TGFbeta Trap Fusion Protein, Promotes Anti-Tumor Efficacy as 


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Monotherapy and in Combination with Vaccine [Accepted Manuscript]. 
Oncoimmunology 2018.
Lan Y, Zhang D, Xu C, Hance KW, Marelli B, Qi J, et al. Enhanced Preclinical Antitumor 
Activity of M7824, a Bifunctional Fusion Protein Simultaneously Targeting PD-
L1 and TGF-beta. Science translational medicine 2018;10:eaan5488.
Lee HH, Hur H, Kim SH, Park AR, Kim W, Jeon HM. Outcomes of Modified FOLFOX-6 as 
First Line Treatment in Patients with Advanced Gastric Cancer in a Single 
Institution; Retrospective Analysis. Cancer research and treatment : official 
journal of Korean Cancer Association 2010;42 (1):18-23.
Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA. Transforming Growth Factor-beta 
Regulation of Immune Responses. Annu Rev Immunol 2006;24:99-146.
Massague J. TGFbeta in Cancer. Cell 2008;134:215-30.
Massague J, Blain SW, Lo RS. TGFbeta Signaling in Growth Control, Cancer, and Heritable 
Disorders. Cell 2000;103:295-309.
Morikawa M, Derynck R, Miyazono K. TGF-beta and the TGF-beta Family: Context-Dependent 
Roles in Cell and Tissue Physiology. Cold Spring Harb Perspect Biol 
2016;8:a021873.
Ohta A, Sitkovsky M. Role of G-protein-coupled adenosine receptors in downregulation of 
inflammation and protection from tissue damage. Nature 2001;414 (6866):916-20.
Ravi R, Noonan KA, Pham V, Bedi R, Zhavoronkov A, Ozerov IV, et al. Bifunctional Immune 
Checkpoint-Targeted Antibody-Ligand Traps that Simultaneously Disable 
TGFbeta Enhance the Efficacy of Cancer Immunotherapy. Nature 
communications 2018;9:741.
Rawla P, Barsouk A. Epidemiology of Gastric Cancer: Global Trends, Risk Factors and 
Prevention. Gastroenterology Review 2019;14 (1):26-38.
Reinhardt J, Landsberg J, Schmid-Burgk JL, Ramis BB, Bald T, Glodde N, et al. MAPK 
Signaling and Inflammation Link Melanoma Phenotype Switching to Induction of 
CD73 during Immunotherapy. Cancer Res 2017;77 (17):4697-709.
Rice TW, Patil DT, Blackstone EH. 8th Edition AJCC/UICC Staging of Cancers of the 
Esophagus and Esophagogastric Junction: Application to Clinical Practice. Ann 
Cardiothorac Surg 2017;6 (2):119-30.
Ryzhov SV, Pickup MW, Chytil A, Gorska AE, Zhang Q, Owens P, et al. Role of TGF-beta 
signaling in generation of CD39+CD73+ myeloid cells in tumors. J Immunol 
2014;193 (6):3155-64.


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Samanta D, Park Y, Ni X, Li H, Zahnow CA, Gabrielson E, et al. Chemotherapy induces 
enrichment of CD47+/CD73+/ PDL1+ immune evasive triple-negative breast 
cancer cells. Proc Natl Acad Sci U S A 2018;115 (6):E1239-E48.
Sheth S, Brito R, Mukherjea D, Rybak LP, Ramkumar V. Adenosine receptors: expression, 
function and regulation. International journal of molecular sciences 2014;15 
(2):2024-52.
Siu LL, Burris H, Le DT, Hollebecque A, Steghs N, Delord J, et al. Preliminary phase 1 profile 
of BMS-986179, an anti-CD73 antibody, in combination with nivolumab in 
patients with advanced solid tumors [Abstract CT180]. Presented at: American 
Association for Cancer Research Annual Meeting; 2018 April 14-18; Chicago, IL. 
Cancer Res; 2018. 
Stagg J, Divisekera U, McLaughlin N, Sharkey J, Pommey S, Denoyer D, et al. Anti-CD73 
antibody therapy inhibits breast tumor growth and metastasis. Proc Natl Acad Sci 
U S A 2010;107 (4):1547-52.
Strauss J, Heery CR, Schlom J, Madan RA, Cao L, Kang Z, et al. Phase I Trial of M7824 
(MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFbeta, 
in Advanced Solid Tumors [Author Manuscript]. Clin Cancer Res 2018;24 
(6):1287-95.
Syed V. TGF-beta Signaling in Cancer. J Cell Biochem 2016;117:1279-87.
Takaku S, Terabe M, Ambrosino E, Peng J, Lonning S, McPherson JM, et al. Blockade of TGF-
beta enhances tumor vaccine efficacy mediated by CD8(+) T cells. Int J Cancer 
2010;126 (7):1666-74.
Young A, Ngiow SF, Barkauskas DS, Sult E, Hay C, Blake SJ, et al. Co-inhibition of CD73 and 
A2AR Adenosine Signaling Improves Anti-tumor Immune Responses. Cancer 
cell 2016;30 (3):391-403.


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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Tables
Appendix 3.
Response Evaluation Criteria in Solid Tumors (RECISTVersion 1.1)
Appendix 4.
NCI CTCAE v5.0 Grading Scale for Severity of Adverse Events and Laboratory 
Abnormalities
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 6.
Dose Modification Tables for mFOLFOX6


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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGMENT 
A Phase ta/lb Study of GS-1423, an Anti-CD73-TGFp-Trap Bifunctional Antibody, as 
Monotherapy or in Combination with a Chemotherapy Regimen in Subjects with 
Advanced Solid Tumors 
GS-US-505-5452, Protocol Amendment 2, 29 April 2020 
This protocol has been approved by Gilead Sciences Inc. The followin si nature documents 
this approval. 
PPD 
PPD 
Name (Printed) 
.:,1gm1mr 
Author 
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. 1 will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
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 129 
29 April 2020 


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Appendix 2.
Study Procedures Tables
Study Procedures Table for QW Dosing Schedule
Screening
Treatment Phase 
(For QWDosing Schedule)
End-of-Treatment
Posttreatment Follow-upa
Survival 
Follow-up
Cycle 1
Cycle 2 and 
3
Cycle 4 and 
every cycle 
until EOT
Cycle 4 and every 3 
cycles until EOT
End-of-Treatment 
Visit
30-Day 
Follow-up
Visit 1
Visit 2
Visits 3 
and4
Visits Schedule (days)
1
2
1
1
1
At 
End-of-Treatment
30 d from 
last dose
3m from 
lastdose
6m from 
lastdose
3m from 
lastvisit
3m from 
lastvisit
Schedule Window (days)b
2
2
± 2
± 2
≤ 7
± 7
± 7
± 7
± 7
± 7
Administrative Procedures
< -28 
days
Informed consent 
X
Review of inclusion/exclusion criteria
X
X
Issue Emergency Medical Support and Subject Card
X
Review of medical history and demographics
X
Review of baseline symptoms
X
X
Review of prior and concomitant medications
X
X
X
X
X
X
X
Cancer disease details and prior treatment
X
Subsequent anticancer therapy status
X
X
X
X
X
Clinical Procedures/Assessments
< -7 days
Review AEsc
X
X
X
X
X
X
X
Full Physical Examination
X
X
Focused Physical Examination
Xd
X
X
X
X
X
X
Vital Signs, Weight and Heighte
X
X
X
X
X
X
X
X
X
X
12 lead ECGf
X
Xf
Xf
Xf
X
X
X
Echocardiogram or MUGAg
Xg
Every 6 cycles
ECOG Performance Statusd
X
Xd
X
X
X
X
X
X
X
X


GS- 1423 
Protocol GS-US-505-5452 
Gilead Sciences, lnc. 
Visits Schedule (days) 
Schedule Window (daysl 
Imaging Assessmentsh 
Tm 10 11 a i gh 
Laboratory Procedures/Assessments• 
Semm chemistry'! 
Hematology testsq 
Coagulation testsq 
Endocrine function testsq 
Hepatitis Serolog~ 
Urinalysisq 
Semm pregnancy test 
Urine pregnancy tests 
CONFIDENTIAL 
Saumg 
C)del 
1 
2 
+ 2 
< -28 
days 
X 
< -28 
days 
X 
Xd 
X 
Xd 
X 
X 
X 
X 
X' 
X' 
Treiml!d Phase 
(.HrQWfuilgSchedje) 
C)de2lVXI C)de4lVXI 
3 
t.'\<"El)'C)cle 
miEOT 
1 
1 
+ 2 
± 2 
C)de4 lmt.'\<8)' 3 
C)dESmiEOT 
± 2 
Final 
Amendment2 
Stnn,~ 
F.m-of:.Tnmned 
~H~OW-tV 
FIA)\~ 
30-Day 
Yr.al 
FIA)\~ 
Vr.i2 
Vr.is3 
;m4 
30dmm 3mfrom 6mmm 3mmm 3mmm 
hltdose 
hlt<hie hlt<hie hlt\R 
hlt\t!i 
± 7 
± 7 
± 7 
± 7 
± 7 
Eve 
ee s (± 7 days) he firs 
assess11en s t en see foo note 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Every 6 cycles 
X 
X 
X 
X 
Every 6 cycles 
X 
X 
X 
Every 6 cycles 
X 
X 
X 
Page 131 
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Screening
Treatment Phase 
(For QWDosing Schedule)
End-of-Treatment
Posttreatment Follow-upa
Survival 
Follow-up
Cycle 1
Cycle 2 and 
3
Cycle 4 and 
every cycle 
until EOT
Cycle 4 and every 3 
cycles until EOT
End-of-Treatment 
Visit
30-Day 
Follow-up
Visit 1
Visit 2
Visits 3 
and4
Visits Schedule (days)
1
2
1
1
1
At 
End-of-Treatment
30 d from 
last dose
3m from 
lastdose
6m from 
lastdose
3m from 
lastvisit
3m from 
lastvisit
Schedule Window (days)b
2
2
± 2
± 2
≤ 7
± 7
± 7
± 7
± 7
± 7
Study drug administration
GS 1423t
X
X
X
Overall Survivalu
Xu
ADA
anti drug antibody against GS 1423; AEs
adverse events; CRF  case report form; ECG
electrocardiogram; eCRF  electronic case report form; ECOG
Eastern 
Cooperative Oncology Group; MUGA
multigated acquisition; PBMC
peripheral blood mononuclear cell; PD  progressive disease; PK
pharmacokinetics; QW  every  
week; SAE  serious adverse event
Note: Where applicable, assessments are to be performed prior to treatment unless otherwise indicated.
a
All subjects who discontinue treatment will have at least one 30 Day Follow up Visit 30 days (± 7 days) from last treatment dose. Subjects who discontinue due to PD and/or 
start of a new line of therapy will then enter the Survival Follow up Period for up to 12 months for survival status. Subjects who have discontinued treatment due to reasons 
other than PD and/or start of a new line of therapy will be in Posttreatment Follow up for up to approximately 12 months from last treatment dose or until PD and/or start of a 
new line of therapy. Every effort should be made to collect subject information on the start of new anticancer therapy, PD, and death.
b
Treatment administration and associated procedures for that visit may be delayed for treatment related AEs beyond the window and subsequent schedule adjusted 
accordingly.
c
After informed consent, but prior to initiation of study medication, the following types of events should be reported on the case report form (CRF/eCRF): all SAEs and AEs
related to protocol mandated procedures.
d
72 hour window for C1D1 physical examination, safety labs, and ECOG performance status collection.
e
Vital signs will only be measured while subject is in seated or semi recumbent position. Height only collected at screening. Vital signs are to be measured prior to each 
infusion commencing, at the end of each infusion, and for the first 2 cycles, 1 hour (± 15 minutes) after the end of the GS 1423 infusion. Thereafter, the final vital signs can 
be taken 30 minutes ( 10/+20 minutes) after the end of each GS 1423 infusion. Subjects will remain in the clinic under close supervision for the duration of this monitoring 
period. 
f
12 lead ECG on Cycle 1 Day 1, before and 2 hours ( 10/+20 minutes) after GS 1423 administration; on subsequent cycles, 12 lead ECG will be collected every 3 cycles on 
Day 1, at end of GS 1423 infusion ( 10/+20 minutes), or as indicated. For subjects in Cohort 9, a triplicate ECG will be performed at C1D1 (predose and at end of infusion), 
at C1D2 (24 hours postdose) and C2D1 (predose).
g
Complete echocardiogram assessment will be conducted at screening to determine baseline (may be done within 14 days prior to the first dose of study treatment).  For QW, 
echocardiogram assessment will be conducted every 6 cycles, on Day 1, starting at Cycle 4 (±3 days). A MUGA scan is allowed.
h
The initial tumor imaging will be performed within 28 days prior to first dose. Scans performed as part of routine clinical management are acceptable for use as screening 
scan if they are of diagnostic quality and < 28 days prior to first dose. On study imaging will be performed at 6, 12, 18, and 24 weeks (± 7 days) from first treatment dose and 
then every 12 weeks thereafter. Imaging assessments will continue until PD as assessed by the investigator, unexpected toxicity occurs, or a new line of therapy is initiated for 
up to 1 year. The timing of on study treatment imaging should follow calendar days and should not be adjusted for delays in treatment administration or for visits. The same 
imaging technique should be used in a subject throughout the study. In general, lesions detected at baseline should be followed using the same imaging methodology and 
preferably the same imaging equipment at subsequent tumor evaluation visits.


GS- 1423 
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Final 
Amendment2 
j 
k 
Unless otherwise specified, samples should be collected before treatment administration. Refer to the Laboratory Manual for instmctions and additional infom1ation. 
PK Assays: Refer to Section 6; Table 6 2 and Table 6 6 in the body of the protocol. 
ADA Assa s: Refer to Section 6· Table 6 8 in the bod of the rotocol. 
r 
Ill r 
I 
q 
Laboratory tests for screening should be perfom1ed within 28 days prior to the first dose of study treatment. After Cycle I, predose laboratory procedures can be conducted up 
to 72 hours prior to dosing. 
r 
Semm P human chorionic gonadotropin (P 1-ICG) pregnancy test for women of childbearing potential at screening within 72 hours of first treatment dose (if perfom1ed earlier 
in screening period, then a urine pregnancy test may be perfom1ed prior to first dose); urine pregnancy test at all other indicated visits; results must be available prior to 
dosing. 
s 
Urine pregnancy results to be obtained on site. 
t 
GS 1423 should be administered intravenously within 60 minutes ( 10/+20 minutes). Subjects must be observed for I hour postinfusion for infusion related reaction for the 
first 2 cycles and thereafter, 30 minutes after the end of the GS 1423 infusion. If administration of GS 1423 is delayed due to an AE, treatment visits may be delayed beyond 
the window of3 days and schedules for subsequent visits should be adjusted accordingly. 
u 
After the I posttreatment follow up visit, subjects who present(ed) with PD and/or start(ed) a new anticancer therapy will move into Survival Follow up. Subjects should be 
contacted by telephone to assess for survival status every 3 months for up to 12 months. No imaging assessment is re.quired for Survival Follow up. 
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Study Procedures Table for Q2W/Q3W Dosing Schedule
Screening
Treatment Phase 
(For Q2Wand Q3W Dosing Schedules)
End-of-Treatment
Posttreatment Follow-upa
Survival 
Follow-up
Cycle 1
Cycle 2
Every Subsequent 
Odd Cycle
Every Subsequent 
EvenCycle
End-of-
Treatment 
Visit
30-Day 
Follow-up
Visit 1
Visit 2
Visits 3 
and4
Visits Schedule (days)
1
2
8
1 2 8
1
1
At 
End-of-Treatment
30dfrom last 
dose
3m from 
lastdose
6m from 
lastdose
3m from 
lastvisit
3m from 
lastvisit
Schedule Window (days)b
2
2
2aa
2aa
≤ 7
± 7
± 7
± 7
± 7
± 7
Administrative Procedures
< -28 days
Informed consent 
X
Review of inclusion/exclusion criteria
X
X
Issue Emergency Medical Support and 
Subject Card
X
Review of medical history and demographics
X
Review of baseline symptoms
X
X
Review of prior and concomitant medications
X
X
X X X X X
X
X
X
X
Cancer disease details and prior treatment
X
Subsequent anticancer therapy status
X
X
X
X
X
Clinical Procedures/Assessments
< -7 days
Review AEsc
X
X
X X X X X
X
X
X
X
Full Physical Examination
X
X
Focused Physical Examination
Xd
X
X
X
X
X
X
X
Vital Signs, Weight and Heighte
X
X
X X X X X
X
X
X
X
X
X
X
12 lead ECGf
X
Xf Xf Xf
X
X
X
Echocardiogram or MUGAg
Xg
X
ECOG Performance Statusd
X
Xd X X X X X
X
X
X
X
X
X
X


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Screening
Treatment Phase 
(For Q2Wand Q3W Dosing Schedules)
End-of-Treatment
Posttreatment Follow-upa
Survival 
Follow-up
Cycle 1
Cycle 2
Every Subsequent 
Odd Cycle
Every Subsequent 
EvenCycle
End-of-
Treatment 
Visit
30-Day 
Follow-up
Visit 1
Visit 2
Visits 3 
and4
Visits Schedule (days)
1
2
8
1 2 8
1
1
At 
End-of-Treatment
30dfrom last 
dose
3m from 
lastdose
6m from 
lastdose
3m from 
lastvisit
3m from 
lastvisit
Schedule Window (days)b
2
2
2aa
2aa
≤ 7
± 7
± 7
± 7
± 7
± 7
Imaging Assessmentsh
< -28 days
Tumor Imagingh
X
Every 6 weeks (± 7 days) the first 4 assessments then see footnote.
Laboratory Procedures/Assessmentsi
< -28 days
Blood for PK Assaysj
X
X
X
Blood for ADA Assaysk
X
X
X
Blood for pharmacogenomics
Xp
Collection of required pretreatment biopsy 
(Phase 1b Cohort 2)z
X
Collection of required on treatment biopsy 
(Phase 1b Cohort 2)y
X
Serum chemistryt
X
Xd
X X
X
X
X
X
X
Hematology testst
X
Xd
X X
X
X
X
X
X
X
Coagulation testst
X
X
X
X
X
X
X
Endocrine function testst
X
X
X
X
X
X
X
Hepatitis Serology
X
Urinalysist
X
X X
X
X
X
X
X
CCI
CCI
CCI
CCI
CCI


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Screening
Treatment Phase 
(For Q2Wand Q3W Dosing Schedules)
End-of-Treatment
Posttreatment Follow-upa
Survival 
Follow-up
Cycle 1
Cycle 2
Every Subsequent 
Odd Cycle
Every Subsequent 
EvenCycle
End-of-
Treatment 
Visit
30-Day 
Follow-up
Visit 1
Visit 2
Visits 3 
and4
Visits Schedule (days)
1
2
8
1 2 8
1
1
At 
End-of-Treatment
30dfrom last 
dose
3m from 
lastdose
6m from 
lastdose
3m from 
lastvisit
3m from 
lastvisit
Schedule Window (days)b
2
2
2aa
2aa
≤ 7
± 7
± 7
± 7
± 7
± 7
Serum pregnancy test
Xu
Urine pregnancy testv,bb
Xu
X
X
X
X
Xbb
HER2 Testingcc
X
Study drug administration
GS 1423 (All cohorts)w
X
X
X
X
mFOLFOX6 (Phase 1b Cohort 1)x 
X
X
X
X
Overall Survival dd
X dd
5 FU  5 fluorouracil; ADA
anti drug antibody against GS 1423; AEs
adverse events; CRF  case report form; ECG
electrocardiogram; eCRF  electronic case report form; 
ECOG
Eastern Cooperative Oncology Group; HER2  human epidermal growth factor receptor 2; IHC  immunohistochemistry; ISH  in situ hybridization; MUGA  
multigated acquisition; PBMC
peripheral blood mononuclear cell; PD  progressive disease; PK
pharmacokinetics; Q2W  every 2 weeks; Q3W  every 3 weeks; SAE  
serious adverse event
Note: Where applicable, assessments are to be performed prior to treatment unless otherwise indicated.
a
All subjects who discontinue treatment will have at least one 30 Day Follow up Visit 30 days (± 7 days) from last treatment dose. Subjects who discontinue due to PD and/or 
start of a new line of therapy will then enter the Survival Follow up Period for up to 12 months for survival status. Subjects who have discontinued treatment due to reasons 
other than PD and/or start of a new line of therapy will be in Posttreatment Follow up for up to approximately 12 months from last treatment dose or until PD and/or start of a 
new line of therapy. Every effort should be made to collect subject information on the start of new anticancer therapy, PD, and death.
b
Treatment administration and associated procedures for that visit may be delayed for treatment related AEs beyond the window and subsequent schedule adjusted 
accordingly.
c
After informed consent, but prior to initiation of study medication, the following types of events should be reported on the case report form (CRF/eCRF): all SAEs and AEs
related to protocol mandated procedures.
d
72 hour window for C1D1 physical examination, safety labs, and ECOG performance status collection.
e
Vital signs will only be measured while subject is in seated or semi recumbent position. Height only collected at screening. Phase 1a and Phase 1b (Cohort 2): Vital signs are 
to be measured prior to each infusion commencing, at the end of each infusion, and for the first 2 cycles, 1 hour (± 15 minutes) after the end of the GS 1423 infusion. 
Thereafter, the final vital signs can be taken 30 minutes ( 10/+20 minutes) after the end of each GS 1423 infusion. Subjects will remain in the clinic under close supervision 
for the duration of this monitoring period. Phase 1b (Cohort 1): Additional vital signs for subjects being administered the mFOLFOX6 regimen will be measured as per 
standard institutional guidelines.


GS- 1423 
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Final 
Amendment2 
f 
12 lead ECG on Cycle I Day I, before and 2 hours ( 10/+20 minutes) after GS 1423 administration; on subsequent cycles, 12 lead ECG will be collected every odd cycle, on 
Day I, at end of GS 1423 infusion( I 0/+20 minutes), or as indicated. For subjects in Cohorts 5 through 8 and Cohort I 0, a triplicate ECG will be perfom1ed at Cycle I, Day I 
predose, at end of infusion, at 24 hours postdose (Day 2), and 168 hours postdose (Day 8). 
g 
Complete echocardiogram assessment will be conducted at screening to detem1ine baseline (may be done within 14 days prior to the first dose of study treatment); and at 
every odd cycle, on Day I, starting at Cycle 3 (±3 days). A MUGA scan is allowed. 
h 
The initial tumor imaging will be perfom1ed within 28 days prior to first dose. Scans perfom1ed as part of routine clinical management are acceptable for use as screening 
scan if they are of diagnostic quality and < 28 days prior to first dose. On study imaging will be perfom1ed at 6, 12, 18, and 24 weeks (± 7 days) from first treatment dose and 
then every 12 weeks thereafter. Imaging assessments will continue until PD as assessed by the investigator, unexpected toxicity occurs, or a new line of therapy is initiated for 
up to I year (Phase I a and Phase I b Cohort 2) or 2 years (Phase I b Cohort I. The timing of on study treatment imaging should follow calendar days and should not be 
adjusted for delays in treatment administration or for visits. The same imaging technique should be used in a subject throughout the study. In general, lesions detected at 
baseline should be followed using the same imaging methodology and preferably the same imaging equipment at subsequent tumor evaluation visits. 
Unless otherwise specified, samples should be collected before treatment administration. Refer to the Laboratory Manual for instmctions and additional infom1ation. 
j 
PK Assays: Refer to Section 6; Table 6 3, Table 6 4, Table 6 5 and Table 6 7 in the body of the protocol. 
k 
ADA Assays: Refer to Section 6; Table 6 9 and Table 6 10 in the body of the protocol. 
I 
Not applicable (This footnote is obsolete with Amendment I.) 
m 
Not applicable (This footnote is obsolete with Amendment I.) 
n 
Not a 
licable This footnote is obsolete with Amendment I. 
r 
f 
r 
r 
a oratory tests for screening should be perfom1ed within 28 days prior to the first dose of study treatment. After Cycle I, predose laboratory procedures can be conducted up 
to 72 hours prior to dosing. 
u 
Semm P human chorionic gonadotropin (P 1-ICG) pregnancy test for women of childbearing potential at screening within 72 hours of first treatment dose (if perfom1ed earlier 
in screening period, then a urine pregnancy test may be perfom1ed prior to first dose); urine pregnancy test at all other indicated visits; results must be available prior to 
dosing. 
v 
Urine pregnancy results to be obtained on site. 
w 
GS 1423 should be administered intravenously within 60 minutes ( 10/+20 minutes). Subjects must be observed for I hour postinfusion for infusion related reaction for the 
first 2 cycles and thereafter, 30 minutes after the end of the GS 1423 infusion. If administration of GS 1423 is delayed due to an AE, treatment visits may be delayed beyond 
the window of3 days and schedules for subsequent visits should be adjusted accordingly. 
x 
The mFOLFOX6 regimen consists of I leucovorin/d/ leucovorin 200/400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5 FU 400 mg/m2 and a 46 hour infusion of 5 FU 
2400 mg/m2. Administration of mFOLFOX6 will follow administration of GS 1423 on Day I of each cycle. The chemotherapy regimen mFOLFOX6 will be administered 
Q2W for up to 12 cycles (6 months). After 12 cycles, subjects may continue to receive 5 FU and leucovorin at the investigator's discretion until the subject meets study 
treatment discontinuation criteria. 
y 
Required on treatment biopsy should be collected at CJD I or up to I week prior on Q2W treatment cycle. 
z 
Required pretreatment biopsy must be obtained prior to C ID I on a tumor from which 2 biopsies can be obtained ( I pretreatment and I on treatment). 
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aa
Treatment Phase visit window starting at Cycle 4 until End of Treatment is ± 2 days.
bb
This will only be performed for subjects receiving mFOLFOX6. Urine pregnancy tests will be performed at 4 months and 6 months after the last dose of mFOLFOX6.
cc
For subjects in Phase 1b Cohort 1 (gastric cohort) tumor tissue will be tested for HER2 status, if unknown, with an approved IHC and ISH kit.
dd
After the 1 posttreatment follow up visit, subjects who present(ed) with PD and/or start(ed) a new anticancer therapy will move into Survival Follow up. Subjects should be 
contacted by telephone to assess for survival status every 3 months for up to 12 months. No imaging assessment is required for Survival Follow up.


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Amendment 2
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Appendix 3.
Response Evaluation Criteria in Solid Tumors (RECISTVersion 1.1)
Measurability of tumor at baseline
Definitions: At baseline, tumor lesions/lymph nodes will be categorized measurable or 
non-measurable as follows:
Measurable Tumor lesions: Must be accurately measured in at least one dimension 
(longest diameter in the plane of measurement is to be recorded) with a minimum size of:
10 mm by CT scan (CT scan slice thickness no greater than 5 mm).
10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured with 
calipers should be recorded as non-measurable).
20 mm by chest X-ray.
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph 
node must be P15 mm in short axis when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis will 
be measured and followed. See also notes below on ‘Baseline documentation of target and 
non-target lesions’ for information on lymph node measurement.
Non- measurable: All other lesions, including small lesions (longest diameter <10 mm or 
pathological lymph nodes with ≥10 to < 15 mm short axis) as well as truly non-measurable 
lesions. Lesions considered truly non-measurable include: leptomeningeal disease, ascites, 
pleural or pericardial effusion, inflammatory breast disease, lymphangitic involvement of skin or 
lung, abdominal masses/abdominal organomegaly identified by physical examination that is not 
measurable by reproducible imaging techniques.
Bone lesions:
Bone scan, PET scan or plain films are not considered adequate imaging techniques to measure 
bone lesions. However, these techniques can be used to confirm the presence or disappearance of 
bone lesions.
Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, that 
can be evaluated by cross sectional imaging techniques such as CT or MRI can be considered as 
measurable lesions if the soft tissue component meets the definition of measurability described 
above.
Blastic bone lesions are non-measurable.
Cystic lesions:
Lesions that meet the criteria for radiographically defined simple cysts should not be considered 
as malignant lesions (neither measurable nor non-measurable) since they are, by definition, 
simple cysts.


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‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable lesions, 
if they meet the definition of measurability described above. However, if noncystic lesions are 
present in the same subjects, these are preferred for selection as target lesions.
Lesions with prior local treatment:
Tumor lesions situated in a previously irradiated area, or in an area subjected to other 
loco-regional therapy are usually not considered measurable unless there has been demonstrated 
progression in the lesion. Study protocols should detail the conditions under which such lesions 
would be considered measurable.
Baseline documentation of ‘target’ and ‘non-target’ lesions
When more than one measurable lesion is present at baseline all lesions up to a maximum of 
5 lesions total (and a maximum of 2 lesions per organ) representative of all involved organs 
should be identified as target lesions and will be recorded and measured at baseline (this means 
in instances where subjects have only one or 2 organ sites involved a maximum of 2 and 
4 lesions respectively will be recorded).
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements. It may be the case that, on occasion, the largest lesion does 
not lend itself to reproducible measurement in which circumstance the next largest lesion which 
can be measured reproducibly should be selected.
Lymph nodes merit special mention since they are normal anatomical structures which may be 
visible by imaging even if not involved by tumor. Pathological nodes which are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
≥15 mm by CT scan. Only the short axis of these nodes will contribute to the baseline sum. The 
short axis of the node is the diameter normally used by radiologists to judge if a node is involved 
by solid tumor. Nodal size is normally reported as 2 dimensions in the plane in which the image 
is obtained (for CT scan this is almost always the axial plane; for MRI the plane of acquisition 
may be axial, sagittal or coronal). The smaller of these measures is the short axis. For example, 
an abdominal node which is reported as being 20 mm x 30 mm has a short axis of 20 mm and 
qualifies as a malignant, measurable node. In this example, 20 mm should be recorded as the 
node measurement. All other pathological nodes (those with short axis ≥10 mm but <15 mm) 
should be considered non-target lesions. Nodes that have a short axis <10 mm are considered 
non-pathological and should not be recorded or followed.
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease.


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All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
non-target lesions and should also be recorded at baseline. Measurements are not required, and 
these lesions should be followed as ‘present’, ‘absent’, or in rare cases ‘unequivocal progression’ 
(more details to follow). In addition, it is possible to record multiple non-target lesions involving 
the same organ as a single item on the case record form (e.g. ‘multiple enlarged pelvic lymph 
nodes’ or ‘multiple liver metastases’).
Tumor response evaluation
Evaluation of target lesions
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking 
as reference the baseline sum diameters.
Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an 
absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also 
considered progression).
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study.
Evaluation of non-target lesions
Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor 
marker level. All lymph nodes must be non-pathological in size (<10mm short axis).
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits.
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits.
Progressive Disease (PD): Unequivocal progression of existing non-target lesions. (Note: the 
appearance of one or more new lesions is also considered progression).


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Appendix Table 1.
Time point response: patients with target (+/- non-target) disease
Target lesions
Non-target lesions
New lesions
Overall response
CR
CR
No
CR
CR
Non-CR/non-PD
No
PR
CR
Not evaluated
No
PR
PR
Non-PD or not all evaluated
No
PR
SD
Non-PD or not all evaluated
No
SD
Not all evaluated
Non-PD
No
NE
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
CR  complete response, PR  partial response, SD  stable disease, PD  progressive disease, and NE  not evaluable.
Appendix Table 2.
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
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 studies so to assign this category when no lesions can be measured is not advised.


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Appendix 4.
NCI CTCAE v5.0 Grading Scale for Severity of Adverse Events and 
Laboratory Abnormalities
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_8.5x11.pdf


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Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a. Definition of Childbearing Potential
For the purposes of this study, a female-born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming postmenopausal, unless 
permanently sterile or with medically documented ovarian failure.
Women are considered to be in a postmenopausal state when they are ≥54 years of age with 
cessation of previously occurring menses for ≥12 months without an alternative cause. In 
addition, women of any age with amenorrhea of ≥12 months may also be considered 
postmenopausal if their follicle stimulating hormone level is in the postmenopausal range and 
they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
b. Definition of Male Fertility
For the purposes of this study, a male born subject is considered of fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2) Contraception Requirements for Female Subjects
a. Study Drug Effects on Pregnancy and Hormonal Contraception
GS-1423 is contraindicated in pregnancy as the potential to cause malformations is unknown. A 
clinically relevant interaction between GS-1423 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 mFOLFOX6.
3) Contraceptive Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures from the screening/randomization visit throughout the study period and 
throughout the protocol-defined follow-up period. They must have a negative serum pregnancy 
test at screening and a negative pregnancy test on the Cycle 1, Day 1 visit prior to enrollment. 
Pregnancy tests will be performed at regular intervals thereafter (as described in the protocol). 


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Female subjects must agree to one of the following from screening until 90 days following 
last dose of GS-1423 or for 4 months after the last dose of oxaliplatin or 6 months after the last 
dose of 5-FU, whichever occurs later.

Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual 
lifestyle.

Female subjects who wish to use a hormonally based method must use it in conjunction with 
a barrier method, preferably a male condom. Female subjects who utilize a hormonal 
contraceptive as one of their birth control methods must have consistently used the same 
method for at least 3 months prior to study dosing. Hormonally based contraceptives and 
barrier methods permitted for use in this protocol are as follows: 

Barrier methods (each method must be used with a hormonal method) 
Male condom (with or without spermicide) 
Female condom (with or without spermicide) 
Diaphragm with spermicide 
Cervical cap with spermicide 
Sponge with spermicide 

Hormonal methods (each method must be used with a barrier method, preferably male 
condom) 
Oral contraceptives (either combined or progesterone only) 
Injectable progesterone 
Implants of levonorgestrel 
Transdermal contraceptive patch 
Contraceptive vaginal ring 
Female subjects must also refrain from egg donation, egg harvesting for the purpose of 
fertilization, and in vitro fertilization during treatment and until at least 90 days after the 
last dose of GS-1423 or for 4 months after the last dose of oxaliplatin or 6 months following the 
last dose of 5-FU, whichever occurs later.


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4) Contraception Requirements for Male Subjects
It is theoretically possible that a relevant systemic concentration may be achieved in a female 
partner from exposure of the male subject’s seminal fluid. Therefore, male subjects with female 
partners of childbearing potential must use condoms from the screening visit until 90 days after 
the administration of the last dose of GS-1423 or for 6 months after the last dose of oxaliplatin or 
6 months after the last dose of 5-FU, whichever occurs later.
Male subjects must also refrain from sperm donation during treatment and until at least 90 days 
after last administration of GS-1423 and for 6 months after the last dose of oxaliplatin or 
6 months after the last dose of 5-FU, whichever occurs later.
5) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (ie, calendar, ovulation, 
symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method. Female condom and male condom should not be used together.
6) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study or if they become pregnant within 90 days of last study drug dose (GS-1423) and 
within 4 months (or 6 months for the partner of male subjects) of the last dose of oxaliplatin, or 
6 months after last dose of 5-FU, whichever occurs later. Subjects who become pregnant or who 
suspect that they are pregnant during the study must report the information to the investigator 
and discontinue study drug immediately. Subjects whose partner has become pregnant or 
suspects she is pregnant during the study must report the information to the investigator. 
Instructions for reporting pregnancy, partner pregnancy, and pregnancy outcome are outlined in 
Section 7.7.2.1.


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29 April 2020
Appendix 6.
Dose Modification Tables for mFOLFOX6
Appendix Table 3.
Recommended Dose Modifications for Oxaliplatin, 5-Fluorouracil, 
and Leucovorina
NCI CTCAE v5.0
System Organ Classb
Adverse Event
Dose Level for 
Subsequent Cycles
Based on Interval 
Adverse Events
At Time of 
Retreatment
All Adverse Events < 1
Maintain dose level
Maintain dose level
Blood and lymphatic 
system disorders:
Hemolytic uremic syndromec
> Grade 3
Discontinue oxaliplatin
Discontinue oxaliplatin
Investigations:
Neutrophil count decreased
If ANC < 1500/mm3 at 
start of cycle, hold and 
check weekly then treat 
based on interval 
adverse event. If ANC 
< 1500/mm3 after 
4 weeks, discontinue 
therapy.
ANC < LLN 1500/mm3
Maintain dose level
ANC < 1500 1000/mm3
Maintain dose level
ANC < 1000 500/mm3
Omit bolus 5
FU and decrease 1 oxaliplatin 
dose level
ANC < 500/mm3
Omit bolus 5 FU and 
decrease both infusion 5 FU 
and oxaliplatin 1 dose level
Platelet count decreased
If PLT < 75,000/mm3 at 
start of cycle, hold and 
check weekly then treat 
based on interval 
adverse event. If PLT 
< 75,000/mm3 after 
4 weeks, discontinue 
therapy.
PLT < LLN 75,000/mm3
Maintain dose level
PLT < 75,000 50,000/mm3
Maintain dose level
PLT < 50,000 25,000/mm3
Omit bolus 5 FU and decrease 
1 oxaliplatin dose level
PLT < 25,000/mm3
Omit bolus 5 FU and decrease 
2 oxaliplatin dose levels
Gastrointestinal 
disorders:
Diarrhea
If Grade 2 at start of 
cycle, hold and check 
weekly then treat based 
on interval adverse 
event. If Grade 2 after 
4 weeks, discontinue 
therapy.
Grade 1, 2
Maintain dose level
Grade 3
Decrease one 5 FU dose level
Grade 4
Decrease both 5 FU and 
oxaliplatin 1 dose level
Mucositis oral
Grade 1, 2
Maintain dose level
Grade 3
Decrease one 5 FU dose level
Grade 4
Decrease one 5 FU dose level
Vomiting
Grades 1, 2
Maintain dose level
Grade 3
Decrease oxaliplatin 1 dose 
level
Grade 4
Decrease both 5 FU and 
oxaliplatin 1 dose level


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Amendment 2
CONFIDENTIAL
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NCI CTCAE v5.0
System Organ Classb
Adverse Event
Dose Level for 
Subsequent Cycles
Based on Interval 
Adverse Events
At Time of 
Retreatment
Metabolism and 
nutrition disorders:
Hypomagnesemia
Note: Dose reduction is not required for hypomagnesemia 
unless symptoms are present. If Grade 2 after 4 weeks, 
discontinue therapy.
Neurology:
Do not use CTCAE.
See Appendix Table 4 for adverse event scale and 
oxaliplatin dose modifications.
Respiratory, thoracic, 
and mediastinal 
disorders:
Cough Grade 3
Dyspnea Grade 3
Hypoxia Grade 3
Pneumonitis Grade 3
Hold oxaliplatin until interstitial lung disease is 
ruled out. If interstitial lung disease, oxaliplatin 
should be permanently
discontinued.
Other non-hematologic 
adverse eventsd,e:
Grades 1, 2
Maintain dose level
Grades 3, 4
Decrease offending agent 1 dose level
5 FU  5 fluorouracil; ANC  absolute neutrophil count; FDP 
fibrin degradation products; LLN  lower limit of normal; NCI 
CTCAE  National Cancer Institute Common Terminology Criteria for Adverse Events; PLT  platelet 
a
The dose of leucovorin will not be adjusted due to adverse event. It should remain at 400 mg/m2 of dl leucovorin or 
200 mg/m2 of leucovorin for all courses. Leucovorin will be given immediately prior to each 5 FU dose; thus, if 5 FU is 
delayed, leucovorin will be delayed. Leucovorin doses may be adjusted per institutional guidelines in the event of a supply 
shortage.
b
For NCI CTCAE v5.0 Grade 2 toxicity not described above, maintain dose level of agent.
c
Recommended evaluation of suspected hemolytic uremic syndrome: Evaluation should include complete blood count
differential, platelets, prothrombin time, partial thromboplastin time, fibrinogen, FDP, Anti thrombin III, Von Willebrand 
factor, anti nuclear antibody, rheumatoid factor, Compliment Cascade C3, C4, and CH50, anti platelet antibodies, platelet
associated immunoglobulin G, and circulating immune complexes. Renal evaluation should include creatinine, blood urea 
nitrogen, and urinalysis with microscopic examination. Other laboratory and hematologic evaluations as appropriate should 
also be obtained, including peripheral blood smear and free hemoglobin.
d
Exceptions: Fatigue, anorexia, nausea/vomiting if can be controlled by antiemetics, and viral infections.
e
Dose modifications for other non hematologic adverse events at the start of subsequent courses of therapy, and at time of 
retreatment are also based on NCI CTCAE v5.0 criteria.


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

SAP_001.pdf: 
Study Title: 
Name of Test Drug: 
Study Number: 
Protocol Version (Date): 
Analysis Type: 
Analysis Plan Version: 
Analysis Plan Date: 
Analysis Plan Author(s): 
(r} GILEAU 
STATISTICAL ANALYSIS PLAN 
A Phase la/l b Study of GS-1423, an Anti-CD73-TGF~-Trap 
Bifunctional Antibody, as Monotherapy or in Combination with 
a Chemotherapy Regimen in Subjects with Advanced Solid 
Tumors 
GS-1423 
GS-US-505-5452 
Amendment 2 (29 April 2020) 
Final Analysis 
Version 1.0 
13 July 2021 
PD 
PD 
CONFIDENTIAL AND PROPRIETARY INFORMATION 


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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................................................2
LIST OF IN-TEXT TABLES .........................................................................................................................................4
LIST OF IN-TEXT FIGURES........................................................................................................................................4
LIST OF ABBREVIATIONS.........................................................................................................................................5
PHARMACOKINETIC ABBREVIATIONS.................................................................................................................6
1.
INTRODUCTION..................................................................................................................................................7
1.1.
Study Objectives........................................................................................................................................7
1.2.
Study Design .............................................................................................................................................7
1.3.
Sample Size and Power ...........................................................................................................................11
2.
TYPE OF PLANNED ANALYSIS......................................................................................................................12
2.1.
Interim Analyses......................................................................................................................................12
2.1.1.
Dose Escalation Analysis ......................................................................................................12
2.2.
Final Analysis..........................................................................................................................................12
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES.............................................................................13
3.1.
Analysis Sets ...........................................................................................................................................13
3.1.1.
All Enrolled Analysis Set ......................................................................................................13
3.1.2.
Full Analysis Set....................................................................................................................13
3.1.3.
Safety Analysis Set................................................................................................................13
3.1.4.
Dose-Limiting Toxicity (DLT) Analysis Set ........................................................................13
3.1.5.
Pharmacokinetic Analysis Set ...............................................................................................14
3.1.6.
Immunogenicity Analysis Set................................................................................................14
3.2.
Subject Grouping.....................................................................................................................................14
3.3.
Strata and Covariates...............................................................................................................................14
3.4.
Examination of Subject Subgroups .........................................................................................................15
3.5.
Multiple Comparisons .............................................................................................................................15
3.6.
Missing Data and Outliers.......................................................................................................................15
3.6.1.
Missing Data..........................................................................................................................15
3.6.2.
Outliers ..................................................................................................................................15
3.7.
Data Handling Conventions and Transformations ..................................................................................15
3.8.
Analysis Visit Windows..........................................................................................................................16
3.8.1.
Definition of Study Day ........................................................................................................16
3.8.2.
Analysis Visit Windows........................................................................................................17
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...............................................................................................................19
4.2.1.
Exposure to GS-1423 ............................................................................................................19
4.2.1.1.
Duration of Exposure.......................................................................................19
4.2.1.2.
Number of Doses .............................................................................................19
4.2.1.3.
Actual Dose Amount .......................................................................................19
4.3.
Protocol Deviations .................................................................................................................................19
4.4.
Assessment of COVID-19 Impact...........................................................................................................20
4.4.1.
Study Drug or Study Discontinuation Due to COVID-19.....................................................20
4.4.2.
Protocol Deviations Due to COVID-19 ................................................................................20
4.4.3.
Missed and Virtual Visits Due to COVID-19 .......................................................................20


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4.4.4. 
Adverse Events Due to COVID-19 ....................................................................................... 20 
5. 
BASELINE CHARACTERISTICS ..................................................................................................................... 21 
5.1. 
Demographics and Baseline Characteristics ........................................................................................... 21 
5.2. 
Medical Histoiy ....................................................................................................................................... 21 
5.3. 
Prior Anti-cancer Therapy and Radiotherapy .......................................................................................... 21 
5.4. 
Concomitant Cancer Related Sw-geries and Procedw-es ......................................................................... 22 
I 
7. 
SAFETY ANALYSES ......................................................................................................................................... 26 
7.1. 
7.2. 
7.3. 
7.4. 
7.5. 
7.6. 
7.7. 
7.8. 
Adverse Events and Deaths ..................................................................................................................... 26 
7.1. 1. 
Adverse Event Dictiona1y ..................................................................................................... 26 
7.1.2. 
Adverse Event Severity ......................................................................................................... 26 
7.1.3. 
Relationship of Adverse Events to Study Dmg ..................................................................... 26 
7.1.4. 
Serious Adverse Events ......................................................................................................... 26 
7.1.5. 
Treatinent-Emergent Adverse Events .................................................................................... 26 
7 .1.5.1. 
Definition of Treatment-Emergent Adverse Events ........................................ 26 
7.1.5.2. 
Inco1nplete Dates ............................................................................................. 27 
7.1.6. 
SW'lllllaries of Adverse Events and Deaths ............................................................................ 27 
7.1.6.1. 
Sw-nmaries of AE Incidence by Severity ......................................................... 27 
7 .1.6.2. 
SW'lllna1y of Deaths ......................................................................................... 29 
7.1.6.3. 
Dose Limiting Toxicity .................................................................................... 29 
Laborato1y Evaluations ........................................................................................................................... 29 
7.2.2.2. 
SW'lllnaries ofLaborat01y Abnonnalities ........................................................ 31 
Body Weight, Body Mass Index and Vital Signs .................................................................................... 31 
Prior and Concoinitant Medications ........................................................................................................ 32 
7.4.1. 
Prior Medications .................................................................................................................. 32 
7.4.2. 
Conco1nitant Medications ...................................................................................................... 32 
Electrocardiogra1n Results ....................................................................................................................... 33 
7 .5.1. 
Investigator Electi·ocardiogram Assessment ......................................................................... 33 
7 .5.2. 
Co1Tected QT Intervals .......................................................................................................... 33 
Other Safety Measw-es ............................................................................................................................ 34 
7.6.1. 
Post Treatment Anti-cancer Therapies .................................................................................. 34 
Echocardiogram ....................................................................................................................................... 34 
Changes From Protocol-Specified Safety Analyses ................................................................................ 34 
8. 
PHARMA CO KINETIC (PK) ANALYSES ......................................................................................................... 35 
8.1. 
PK Sample Collection ............................................................................................................................. 35 
8.2. 
Statistical Analysis Methods ................................................................................................................... 35 
8.2.1. 
GS-1423 Plasma Concenti·ation ............................................................................................ 35 
8.2.2. 
GS-1423 PK Para1neters ........................................................................................................ 35 
9. 
IMMUNOGENICITY ANALYSES .................................................................................................................... 37 
9.1. 
ADA Sa1nple Collection .......................................................................................................................... 37 
9.2. 
Statistical Analyses Methods ................................................................................................................... 37 
CONFIDENTIAL 
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11.
REFERENCES.....................................................................................................................................................39
12.
SOFTWARE.........................................................................................................................................................40
13.
APPENDICES......................................................................................................................................................41
Appendix 1.
Schedule of Assessments.........................................................................................................42
Appendix 2.
COVID-19 SMQ with Broad Scope........................................................................................46
Appendix 3.
Determining Missing and Virtual Visits Due to COVID-19...................................................47
Appendix 4.
List of laboratory Tests for Safety Summary ..........................................................................48
LIST OF IN-TEXT TABLES
Table 1.
Phase 1a Part A GS-1423 Dose Levels and Cohorts.................................................................8
Table 2.
PK Parameters for GS-1423 ....................................................................................................36
LIST OF IN-TEXT FIGURES
Figure 1.
Accelerated Dose Escalation Scheme........................................................................................9
Figure 2.
3+3 Dose Escalation Scheme ..................................................................................................10
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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
CI
confidence interval
CRF
case report form
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
FAS
Full Analysis Set
HLT
high-level term
LLT
lower-level term
LOQ
limit of quantitation
MedDRA
Medical Dictionary for Regulatory Activities
PK
Pharmacokinetic
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
StD
standard deviation
SOC
system organ class
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
WHO
World Health Organization


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PHARMACOKINETIC ABBREVIATIONS
AUClast
area under the concentration versus time curve from time zero to the last quantifiable 
concentration
AUCtau
area under the concentration versus time curve over the dosing interval
Clast
last observed quantifiable concentration of the drug 
Cmax
maximum observed concentration of drug 
Ctau
observed drug concentration at the end of the dosing interval
Ctrough
plasma [serum] concentration at the end of the dosing interval
CLss
steady-state clearance
Tlast
time (observed time point) of Clast
Tmax
time (observed time point) of Cmax
Vss
volume of distribution at steady state


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the synoptic clinical study 
report (sCSR) for Study GS-US-505-5452. This SAP is based on the study protocol 
Amendment 2 dated 29 April 2020 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. The study was terminated early at the completion of Phase 1a Part A 
(dose escalation). Phase 1a Part B (flat dose regimens) and Phase 1b (expansion cohorts) will not 
be initiated. The following SAP includes study design components and statistical analysis plans 
associated with Phase 1a Part A only.
1.1.
Study Objectives
Objectives for Phase 1a (Part A dose escalation only)
The primary objective(s) are:

To assess safety and tolerability and to define the dose limiting toxicity (DLT) and maximum 
tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of GS-1423 monotherapy in 
subjects with advanced solid tumors 
The secondary objectives are:

To characterize GS-1423 pharmacokinetics (PK)

To evaluate GS-1423 immunogenicity 
 
1.2.
Study Design
Study design for Phase 1a
Part A – Dose escalation
Part A is a Phase 1 open-label study to evaluate the safety, tolerability, and PK profile of 
GS-1423 and to define the DLT and MTD or RP2D of GS-1423 monotherapy in subjects with 
advanced solid tumors.
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In Part A, an accelerated titration design schema will be used by enrolling 1 subject each at the 
first 2 dose levels of 0.3 mg/kg and 1 mg/kg, followed by a 3+3 dose escalation design (Table 1). 
At the first 2 dose levels of 0.3 mg/kg and 1 mg/kg, if 2 or more drug-related adverse events 
(AEs) of Grade 2 or higher or at least 1 DLT are observed during the 28-day DLT observation 
period, the 3+3 escalation scheme will be used at that dose and subsequent doses. Each subject 
will stay on the dose level and schedule assigned at study entry. GS-1423 will be administered 
on Day 1 of each 2-week cycle (Q2W) for up to 1 year or until any progressive disease (PD) or 
unacceptable toxicity. The starting dose was selected to be 0.3 mg/kg derived from minimally 
anticipated biologic effect level (MABEL). A Safety Review Team (SRT) will be established to 
assess safety and decide on dose escalation. 
Table 1.
Phase 1a Part A GS-1423 Dose Levels and Cohorts
Cohort
No. of Subjects
Escalation Type
Dose of GS-1423
(mg/kg)
1 (starting dose)
1 or 3-6
Accelerated titration
0.3
2
1 or 3-6
Accelerated titration
1
3
3-6
3+3
3
4
3-6
3+3
10
5
3-6
3+3
20
6
3-6
3+3
30
7
3-6
3+3
45
Note: An additional 6 subjects may be enrolled at a dose level at or below maximum tolerated dose to obtain additional safety, 
pharmacokinetics, and 
 information. Gilead may choose not to enroll any cohort if it is deemed 
unnecessary.
The initial block of each dose in 3+3 escalation scheme consists of 3 subjects. Dose escalation 
will occur if no subjects experience a DLT during the first 28 days of study drug dosing. If 2 or 
more subjects experience DLTs within the first 28 days, dose de-escalation to a lower dose will 
occur. If 1 of the first 3 evaluable subjects enrolled has a DLT within the first 28 days, then 3 
additional subjects will be enrolled at the same dose level. If no DLTs are observed in the 
additional 3 subjects, dose escalation will occur. If a DLT occurs in ≥ 2 subjects in the total 
cohort of 6 subjects, the MTD will be deemed to be exceeded, and the prior dose level will be 
evaluated to determine the MTD by increasing enrollment to 6 subjects. If the prior dose level 
was already deemed to be safe (ie, 0 or 1 DLT) and enrolled 6 subjects, then it will be defined as 
the MTD. The MTD is the highest dose level with an incidence of DLTs of 0 or 1 out of 6 
subjects during the first 28 days of study drug dosing. A minimum of 6 subjects need to be 
treated at a dose level before this dose level can be deemed as the MTD. A subject who fails to 
receive all GS-1423 treatments or fails to complete all safety assessments in the DLT period for 
reasons other than DLT will be replaced.
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Figure 1.
Accelerated Dose Escalation Scheme
  
 
 
 
 
 
 
 
  
  
 
 
 
 
 
  
 
 
 
  
 
 
  
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
  
 
  
 
  
 
 
 
 
 
 
 


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Figure 2.
3+3 Dose Escalation Scheme
Legend: DLT= dose limiting toxicity; MTD = maximum tolerated dose
Note: if MTD is attained at the 1st dose level, discussion with investigators and medical monitor to change dose or schedules in a 
protocol amendment
  
 
  
 
 
  
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 


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Starting at Cohort 4 (10 mg/kg), if no DLT is observed during the 28-day DLT observation 
period in the first 3 subjects, 3 additional subjects may be enrolled at the respective dose level to 
obtain more safety, PK, and 
 data. If ≥ 2 subjects have experienced DLTs in 
the last 3 (of 6) subjects, dose escalation will halt and up to 3 additional subjects will be enrolled 
at the preceding dose level (if there were only 3 subjects in that cohort) for DLT assessment. If 
6 subjects were already evaluated, the preceding dose level will be considered as MTD.
Efficacy Assessment Schedule
For Phase 1a Part A, tumor response assessment will be performed per RECIST 1.1  at baseline (
≤ 28 days prior to first dose), every 6 weeks(± 7 days) for the first 24 weeks from the first 
treatment dose and then every 12 weeks thereafter until PD is assessed by investigator, initiation 
of new line of therapy, or 1 year after first treatment dose, whichever occurs first. Any CR or PR 
should be confirmed by CT or MRI scan no less than 28 days after initial assessment. The 
investigator may perform scans in addition to a scheduled study scan for medical reasons or if 
PD is suspected.
The Schedule of Assessments is located in Appendix 1.
1.3.
Sample Size and Power
Phase 1a Part A
Assuming that up to 7 planned dose levels for escalation will be tested with up to 6 subjects per 
dose level (42 subjects for escalation) and 10% of subjects are not evaluable, and 6 additional 
subjects may be enrolled at a dose level at or below MTD to obtain additional safety, PK, and 
 information, up to 53 subjects will be enrolled.
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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
2.1.1.
Dose Escalation Analysis
For the purpose of making the decision to escalate to the next dose level/cohort, interim analyses 
of relevant safety and PK (if available) data will be conducted by Gilead after all subjects in each 
cohort have completed dosing and the 28-day DLT observation period. Safety assessments (ie, 
AEs, ECG, and laboratory results) will be displayed by dose level/cohort to facilitate the decision 
to dose escalate.
2.2.
Final Analysis
The final analysis will be performed after all subjects have completed or discontinued from the 
study, outstanding data queries have been resolved or adjudicated as unresolvable, and the data 
have been cleaned and finalized. The final analysis of this study will include Phase 1a Part A 
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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each category will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (StD) or standard error (SE), median, first 
quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
By-subject listings will be presented for all subjects in the All Enrolled Analysis Set and sorted 
by subject ID number, visit date, and time (if applicable). Data collected on log forms, such as 
AEs, will be presented in chronological order within the subject. The treatment group to which 
subjects were initially assigned will be used in the listings. Age, sex at birth, race, and ethnicity 
will be included in the listings, as space permits.
3.1.
Analysis Sets
Analysis sets define the subjects to be included in an analysis. Analysis sets and their definitions 
are provided in this section. The analysis set will be identified and included as a subtitle of each 
table, figure, and listing.
For each analysis set, the number and percentage of subjects eligible for inclusion, will be 
summarized by dose cohort.
A listing of reasons for exclusion from analysis sets will be provided by subject.
3.1.1.
All Enrolled Analysis Set
All Enrolled Analysis Set includes all subjects who received a study subject identification 
number in the study after screening.
The All Enrolled Analysis Set will be used for subject enrollment summary and for data listings, 
unless otherwise specified.
3.1.2.
Full Analysis Set
The Full Analysis Set (FAS) includes all enrolled subjects who were administered any amount of 
GS-1423. This is the primary analysis set for efficacy analyses.
3.1.3.
Safety Analysis Set
The Safety Analysis Set includes all enrolled subjects who were administered any amount of 
GS-1423. This is the primary analysis set for safety analyses.
3.1.4.
Dose-Limiting Toxicity (DLT) Analysis Set
The DLT Analysis Set includes all subjects in the Safety Analysis Set who complete all study 
treatment and have safety assessments through the protocol specified DLT assessment window, 
Day 28, inclusive, or have experienced a DLT prior to Day 28. 


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During the DLT observation window, if a subject was not administered both of first 2 GS-1423 
doses for reasons other than DLT, another subject was to be enrolled at the same dose level for 
replacement. Subjects who are replaced but received at least 1 dose of study drug will be 
included in the Safety Analysis Set and not in the DLT Analysis Set.
The DLT Analysis Set will be used for analyses related to DLT in Part A of Phase 1a.
3.1.5.
Pharmacokinetic Analysis Set
The Pharmacokinetic (PK) Analysis Set will include all subjects in the Safety Analysis Set who 
have at least 1 nonmissing postdose concentration value reported by the PK laboratory. This is 
the primary analysis set for all PK analyses. 
3.1.6.
Immunogenicity Analysis Set
The Immunogenicity Analysis Set will include all subjects in the Safety Analysis Set who have 
at least 1 nonmissing postdose antidrug antibody (ADA) status reported. This is the primary 
analysis set for all immunogenicity analyses.
3.2.
Subject Grouping
For analyses based on the Full Analysis Set (FAS), subjects will be grouped according to the 
treatment to which they were assigned. 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 assigned treatment only when their actual treatment differs from the assigned 
treatment for the entire treatment duration.
For the PK Analysis Set, subjects will be grouped according to the actual treatment they 
received.
In Phase 1a Part A, The subjects will be grouped by cohorts (dose levels):
Cohort 1: 0.3 mg/kg
Cohort 2: 1 mg/kg
Cohort 3: 3 mg/kg
Cohort 4: 10 mg/kg
Cohort 5: 20 mg/kg
Cohort 6: 30 mg/kg
Cohort 7: 45 mg/kg
3.3.
Strata and Covariates
This study does not use a stratified randomization schedule when enrolling subjects. 
No covariates will be included in efficacy and safety analyses.


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3.4.
Examination of Subject Subgroups
There are no prespecified subject subgroupings for efficacy and safety analyses.
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 4.2.1.1. The 
handling of missing or incomplete dates for the completion of last prior anti-cancer therapy is in 
Section 5.3, for the start date of new anti-cancer therapy is in Section 6.1.3, for date of death in 
Section 6.1.4, for AE onset in Section 7.1.5.2, and for prior and concomitant medications in 
Section 7.4.
3.6.2.
Outliers
Outliers will 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
In general, the subject’s age collected at Day 1 (in years) will be used for analyses and presented 
in listings. If age at Day 1 is not available for a subject, then age derived based on date of birth 
and the Day 1 visit date will be used instead. If an enrolled subject was not dosed with any study 
drug, the enrollment date will be used instead of the Day 1 visit date. For screen failures, the date 
the first informed consent was signed will be used for the age derivation. 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. 
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 
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
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 log-transformed data or nonparametric analysis methods may be 
used, as appropriate.
Sparse PK concentration values that are below the limit of quantitation (BLQ) will be presented 
as “BLQ” in the data listing.
Natural logarithm transformation will be used for analyzing concentrations and PK parameters in 
intensive PK samples. Concentration values that are 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 at 
postdose time points for summary purposes. The following conventions will be used for the 
presentation of summary and order statistics for intensive PK concentrations: 

If at least 1 subject has a concentration value of BLQ for the time point, the minimum value 
will be displayed as “BLQ.”

If more than 25% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum and Q1 values will be displayed as “BLQ.”

If more than 50% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, and median values will be displayed as “BLQ.”

If more than 75% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, median, and Q3 values will be displayed as “BLQ.”

If all subjects have concentration data values of BLQ for a given time point, all order 
statistics (minimum, Q1, median, Q3, and maximum) will be displayed as “BLQ.”
PK parameters that are BLQ will be excluded from log transformation or statistical model fitting.
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study day will be calculated from the first dosing date of study drug and derived as follows:

For postdose study days: Assessment Date – First Dosing Date + 1

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Therefore, study day 1 is the day of first dose of study drug.
3.8.2.
Analysis Visit Windows
The nominal visit as recorded on the CRF will be used when data are summarized by visit. Any 
data relating to unscheduled visits will not be assigned to a particular visit or time point. 
However, the following exceptions will be made:

An unscheduled visit prior to the first dosing of study drug may be included in the calculation 
of the baseline value, if applicable.

Unscheduled visits after the first dosing of study drug will be included in determining the 
maximum postbaseline toxicity grade.
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 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 
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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
A summary of subject enrollment will be provided by treatment group and overall. The summary 
will present the number and percentage of subjects enrolled. For each column, the denominator 
for the percentage calculation will be the total number of subjects analyzed for that column.
A summary of subject disposition will be provided by dose cohort. The summary will present the 
number of subjects in each of the following categories:

Screened

Enrolled

DLT Analysis Set 

Safety Analysis Set 

Full Analysis Set

GS-1423 completion status
Completed study drug dosing as specified per protocol
Discontinued study drug dosing with reasons

Study completion status 
Completed the protocol-planned duration of the study
Discontinued the study with reasons
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 Safety Analysis Set 
corresponding to that column. In addition, a flowchart will be provided to depict the disposition.
The following by-subject listing will be provided by subject identification (ID) number in 
ascending order to support the above summary tables:

Reasons for premature study drug or study discontinuation

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4.2.
Extent of Study Drug Exposure
Extent of exposure to study drug will be examined by assessing the total duration of exposure to 
study drug, total number of doses, and the actual dose amount.
4.2.1.
Exposure to GS-1423
A listing of GS-1423 administration will be provided by subject ID number (in ascending order) 
and visit (in chronological order), including dosing date/time, planned dosage, actual dosage 
administered, infusion outcome and reason that entire dose was delayed or not administered.  
Exposure to GS-1423 will be summarized by cohort for the safety analysis set.
4.2.1.1.
Duration of Exposure
Total duration of exposure to study drug will be defined as (last dosing date - first dosing 
date + 1)/7, 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.
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. The number and 
percentage of subjects who have dose interruptions, and the reasons, will be summarized by 
treatment.
4.2.1.2.
Number of Doses
The number of doses subjects were exposed to study drug will be summarized using descriptive 
statistics, as well as the number and percentage of subjects exposed to the following number of 
doses: ≥1, ≥2, ≥4 , ≥6, ≥8, ≥10 dose(s). A subject is said to have received a dose of GS-1423 if 
he/she received any amount of the planned dose of GS-1423.
4.2.1.3.
Actual Dose Amount
In addition, the total and average actual dose amount received for GS-1423 in mg will be 
summarized using descriptive statistics (N, mean, StD, median, Q1, Q3, minimum, and 
maximum). The average actual dose amount of GS-1423 is defined as (total actual dose amount 
received in mg) / (number of doses given), regardless of whether the doses were 
interrupted/completed. 
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 
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Enrolled Analysis Set. A by-subject listing will be provided for those subjects who did not meet 
at least 1 eligibility (inclusion or exclusion) criterion. The listing will present the eligibility 
criterion (or criteria if more than 1 deviation) that subjects did not meet and related comments, if 
collected.
Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. The number and percentage of subjects with important protocol deviations by 
deviation reason (eg, nonadherence to study drug, violation of select inclusion/exclusion criteria) 
will be summarized by cohorts for the All Enrolled Analysis Set. A by-subject listing will be 
provided for those subjects with important protocol deviation.
4.4.
Assessment of COVID-19 Impact
This study was ongoing during the novel coronavirus (COVID-19) pandemic which has an 
impact on the study conduct. Some subjects were unable to attend onsite visits due to shelter in 
place guidelines, site closures, or other reasons. This section describes how special situations due 
to COVID-19 will be handled in the analysis.
4.4.1.
Study Drug or Study Discontinuation Due to COVID-19
A by-subject listing of reasons for premature study drug or study discontinuation due to 
COVID-19 will be created.
4.4.2.
Protocol Deviations Due to COVID-19
A by-subject listing will be provided for subjects with important protocol deviation related to 
COVID-19. A separate listing will be provided for subjects with non-important protocol 
deviation related to COVID-19.
4.4.3.
Missed and Virtual Visits Due to COVID-19
A by-subject listing of subjects with missed or virtual visits due to COVID-19 will be provided 
by subject ID number in ascending order.
Information regarding virtual or missed visits due to COVID-19 was collected as free text in the 
CRF comment fields. The determination of missing or virtual visits due to COVID-19 was done 
using Natural Language Processing (NLP) to search the CRF comment fields. A detailed 
explanation of the algorithm is given in Appendix 3.
4.4.4.
Adverse Events Due to COVID-19
AEs of COVID-19 will be included in analyses of AEs if applicable, which will be determined 
through COVID-19 SMQ broad search (Appendix 2). A by-subject listing of AEs of COVID-19 
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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Subject demographic variables (ie, age, sex, race, and ethnicity) and baseline characteristics 
(body weight [in kg], height [in cm], body mass index [BMI; in kg/m2], Eastern Cooperative 
Oncology Group (ECOG) Performance Status at baseline) will be summarized by dosage cohort 
and overall using descriptive statistics for continuous variables and using number and percentage 
of subjects for categorical variables. The ECOG status at baseline is the ECOG status at 
screening. The summary of demographic data will be provided for the Safety Analysis Set.
A by-subject demographic listing, including the informed consent date, will be provided by 
subject ID number in ascending order. A by-subject baseline characteristics will also be provided 
by subject ID number in ascending order.
5.2.
Medical History
Medical history will be collected at screening for disease-specific and general conditions 
(ie, conditions not specific to the disease being studied).
A by-subject listing of disease-specific medical history and general medical history will be 
provided by subject ID number in ascending order. General medical history will not be coded.
5.3.
Prior Anti-cancer Therapy and Radiotherapy
Number of prior regimens, time since the completion of last regimen, and time since progression 
in the last regimen will be summarized by treatment group using descriptive statistics based on 
the Safety Analysis Set.
Time since the completion of last regimen (months) will be calculated by (first dosing date of 
study drug – date of completion of last regimen) /30.4375. Time since progression of last 
regimen (months) will be calculated by (first dosing date of study drug – date of progression in 
last regimen)/30.4375. In deriving the time since the completion of last regimen and time since 
progression in the last regimen, all partial dates of last regimen will be identified, and the partial 
dates will be imputed as follows:

If day and month are missing but year is available, then the imputed day and month will be 
01 January.

If day is missing but the month and year are available, then the imputed day will be the first 
day of the month.

Partial date will not be imputed if the year is missing.
The details of prior anti-cancer therapy will be listed including line of therapy, type of regimen, 
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The details of prior radiotherapy and surgery will also be listed.
5.4.
Concomitant Cancer Related Surgeries and Procedures
A listing of concomitant cancer related surgeries and procedures will be provided for the All 
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7.
SAFETY ANALYSES
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the current version of 
MedDRA. System organ class (SOC), high-level group term (HLGT), high-level term (HLT), 
preferred term (PT), and lower-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1, 2, 3, 4, or 5 according to CTCAE 
Version 5.0. The severity grade of events for which the investigator did not record 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 case report form 
(CRF) to the question of “Related to Study Treatment.” Relatedness will always default to the 
investigator’s choice, not that of the medical monitor. Events for which the investigator did not 
record 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 from that captured on the 
CRF.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if the AEs met the 
definitions of SAEs that were specified in the study protocol. SAEs captured and stored in the 
clinical database will be reconciled with the SAE database from the Gilead Global Patient Safety 
Department before data finalization.
7.1.5.
Treatment-Emergent Adverse Events 
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the study drug start date and no later than 30 days 
after permanent discontinuation of study drug

Any AEs leading to premature discontinuation of study drug.


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7.1.5.2.
Incomplete Dates
All AEs with incomplete onset dates will be imputed  for TEAE determination. The imputation 
rules are as follows: 

If the day is missing but the month and year are available, then the imputed day will be the 
first day of the month or the first dosing date if they have the same month and year, 
whichever is later.

If the day and month are missing but year is available, then the imputed day and month will 
be 01 January or the first dosing date if they have the same year, whichever is later.
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of study drug, will be considered to be treatment emergent. In 
addition, an AE with the onset date missing and incomplete stop date with the same or later 
month and year (or year alone if month is not recorded) as the first dosing date of study drug will 
be considered treatment emergent.
7.1.6.
Summaries of Adverse Events and Deaths
Treatment-emergent AEs will be summarized based on the Safety Analysis Set.
7.1.6.1.
Summaries of AE Incidence by Severity 
A brief, high-level summary of number and percentage of subjects who experienced the 
following TEAEs will be provided by treatment group:

Any TEAE;

Any grade 1 or 2 TEAE;

Any grade 3 or 4 TEAE;

Any TEAE related to GS-1423;

Any grade 1 or 2 TEAE related to GS-1423;

Any grade 3 or 4 TEAE related to GS-1423;

Any TE SAE;

Any grade 1 or 2 TE SAE;

Any grade 3 or 4 TE SAE;

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
Any TE SAE related to GS-1423;

Any TEAE leading to premature discontinuation of GS-1423;

Any TEAE leading to temporary interruption of GS-1423;

Any grade 1 or 2 TEAE leading to temporary interruption of GS-1423;

Any grade 3 or 4 TEAE leading to temporary interruption of GS-1423;

Any dose limiting toxicity
For the AE categorizes described below, the number and percentage of subjects who experienced 
at least 1 TEAE summaries will be provided by SOC, PT, maximum severity, and treatment 
group:

TEAEs

TE treatment related AEs
Summary tables (number and percentage of subjects) of treatment-emergent AEs (by SOC and 
PT) will be provided by cohort and overall as follows:

TEAEs

TEAEs with Grade 3 or higher

TE treatment-related AEs

TE Treatment-related AEs with Grade 3 or higher

TE SAEs

TE treatment-related SAEs

TEAEs leading to premature discontinuation of  GS-1423

TEAEs leading to temporary interruption of  GS-1423

TEAEs leading to deaths
The above TEAEs excluding TEAEs leading to deaths will also be summarized by PT only in 
descending order of total frequency. Additionally, all TEAEs will be summarized by PT and 
severity.
Multiple events will be counted only once per subject in each summary. Adverse events will be 
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total frequency within each SOC. For summaries by severity, the most severe severity will be 
used for those AEs that occuned more than once in a given subject during the study. 
In addition, data listings will be provided for the following: 
• 
All AEs, indicating whether the event is treatment emergent and related to study diug 
• 
All AEs with Grade 3 or higher 
• 
All SAEs 
• 
All AEs leading to death 
• 
All AEs leading to premature discontinuation of study diug 
• 
TEAEs leading to tempora1y intenuption of study diug 
7.1.6.2. 
Summaiy of Deaths 
A summaiy (nlllllber and percentage of subjects) of deaths will be provided by treatment group 
and overall, with the cause of the death (AE, PD, or other reasons). The summa1y will include 
the following categories: 
• 
All deaths 
• 
Deaths within 30 days of the last dosing of study diug 
• 
Deaths after 30 days of the last dosing of study dmg 
A list of all deaths with primaiy cause of death will be provided. 
7.1.6.3. 
Dose Limiting Toxicity 
A listing of the DL T AEs will be provided by coho1i including coho1i number with dose level, 
subject identification, actual dose amount prior to or on the staii date of the AE, DLT tenn from 
the investigator as well as CTCAE te1m and associated severity grade, if available. 
A summaiy of DL T will be presented by PT. 
Late onset AEs meeting DLT definition occuning beyond the 28-day DLT observation period 
will be listed and sUllllllarized by PT as well. 
7.2. 
Laboratory Evaluations 
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Treatment-Emergent Laborato1y Abno1malities 
Treatment-emergent laborato1y abno1malities 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 study dmg plus 30 days subjects who pennanently discontinued study dmg. If the 
relevant baseline laborato1y value is missing, any abno1mality of at least Grade 1 observed 
within the time frame specified above will be considered treatment emergent. 
7.2.2.2. 
Summaries of Laborato1y Abno1malities 
The summaries (number and percentage of subjects) for treatment-emergent laborato1y 
abno1malities will be provided by lab test and dose cohort; subjects will be categorized according 
to the most severe postbaseline abnonnality grade for a given lab test: 
• 
Graded TE laborato1y abnonnalities 
• 
TE Grade 3 or 4 laborato1y abnonnalities 
For all summaries of laborato1y abno1malities, the denominator is the number of subjects with 
nonmissing postbaseline values up to 30 days after the last dosing date. 
A by-subject listing of treatment-emergent Grade 3 or 4 laborato1y abno1malities will be 
provided by subject ID number and visit in chronological order. This listing will include all test 
results that were collected throughout the study for the lab test of interest, with all applicable 
severity grades displayed. 
7.3. 
Body Weight, Body Mass Index and Vital Signs 
Descriptive statistics will be provided by dose cohort for body weight, body mass index (BMI) 
and vital signs as follows: 
• 
Baseline value 
• 
Postbaseline maximum value 
• 
Postbaseline minimum value 
• 
Change and percentage change from baseline to postbaseline maximum value 
• 
Change and percentage change from baseline to postbaseline minimum value 
A baseline value will be defined as the last available value collected on or prior to the date/time 
of first dose of study diug. Weight, BMI and each vital signs measmement (including 
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temperature, pulse, respiratory rate, and blood pressure) will be summarized. 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 will be provided by subject ID number and visit in 
chronological order. Body weight and BMI will be included in the vital signs listing, if space 
permits. If not, they will be provided separately.
7.4.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the World Health Organization (WHO) Drug dictionary.
7.4.1.
Prior Medications
Prior medications are defined as any medications taken before a subject was administered the 
first dose of study drug.
Prior 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 dose cohort 
and overall. A subject reporting the same medication more than once will be counted only once 
within each ATC drug class when calculating the number and percentage of subjects who 
received that medication. [Medications may appear under multiple ATC drug classes.] The 
summary will be ordered alphabetically by ATC medical class and then by preferred term in 
order of 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 medication with a start date prior to the first dosing date of 
study drug will be included in the prior medication summary regardless of when the stop date is. 
If a partial start date is entered the medication will be considered prior unless the month and year 
(if day is missing) or year (if day and month are missing) of the start date are after the first 
dosing date. Medications with a completely missing start date will be included in the prior 
medication summary, unless otherwise specified.
Summaries will be based on the Safety Analysis Set. No formal statistical testing is planned.
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) 
classification Level 2 (therapeutic subgroup) and preferred name using the number and 
percentage of subjects for each dose cohort and overall. A subject reporting the same medication 
more than once within each ATC drug class will be counted only once when calculating the 
number and percentage of subjects who received that medication. Medications may appear under 
multiple ATC drug classes. The summary will be ordered alphabetically by ATC classification 


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and by preferred term in descending overall frequency within each ATC classification. For drugs 
with the same frequency, sorting will be performed 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.
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
Electrocardiogram (ECG) analysis results are intended to identify meaningful changes in the QT 
interval. If potential abnormalities of interest are identified, further analyses may be conducted. 
Investigator assessment of ECG readings and ECG data will be provided for the Safety Analysis 
Set for each scheduled time point. No formal statistical testing is planned.
7.5.1.
Investigator Electrocardiogram Assessment
A shift table of the investigators’ assessment of ECG results at worst outcome during study 
compared with baseline values will be presented by dose cohort using the following categories: 
normal; abnormal, not clinically significant; abnormal, clinically significant; or missing. The 
number and percentage of subjects in each cross-classification group of the shift table will be 
presented. Subjects with a missing value at baseline or postbaseline will not be included in the 
denominator for percentage calculation. No formal statistical testing is planned.
A by-subject listing for ECG assessment results will be provided by subject ID number and visit 
in chronological order.
7.5.2.
Corrected QT Intervals
The QT interval (measured in millisecond [msec]) is a measure of the time between the start of 
the Q wave and the end of the T wave in the heart’s electrical cycle. The QT interval represents 
electrical depolarization and repolarization of the ventricles. The QT interval is affected by heart 
rate, and a number of methods have been proposed to correct QT for heart rate. 


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Corrected QT (QTc) intervals will be derived using Fridericia’s correction (QTcF) as follows: 
𝑄𝑇𝑐𝐹= 𝑄𝑇
3 𝑅𝑅
where QT is measured in msec; RR = 60/Heart Rate (beats per min [bpm]) and RR is 
measured in seconds
QTcF will be listed by-subject.
7.6.
Other Safety Measures
No additional safety measures are specified in the protocol.
7.6.1.
Post Treatment Anti-cancer Therapies
All post treatment anti-cancer therapies will be provided in a by-subject listing sorted by subject 
ID number and administration date in chronological order.
7.7.
Echocardiogram
A by-subject listing will be provided for echocardiogram and multigated acquisition (MUGA) 
scan results by subject ID number and visit/time point in chronological order.
7.8.
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
Blood samples will be collected to measure concentrations and to estimate PK parameters of GS-
1423 at protocol specified time points.
8.2.
Statistical Analysis Methods
8.2.1.
GS-1423 Plasma Concentration
Plasma concentration for GS-1423 will be summarized using descriptive statistics (n, arithmetic 
mean, StD, coefficient of variation [%CV], median, min, max, Q1, Q3, geometric mean and 95% 
CI) for subjects in the PK Analysis Set by sampling time point and visit. Subjects in different 
dose cohorts will be presented separately. The sample size for each time point will be based on 
the number of subjects with nonmissing concentration data at that time point. The number of 
subjects with concentration BLQ will be presented for each time point. For summary statistics, 
BLQ values will be treated as 0.
The following table will be provided by dose level:
Individual subject concentration data and summary statistics
The following figures may be provided by dose level:
Mean (± StD) concentration data versus time (on linear and semilogarithmic scales)
Median (Q1, Q3) concentration data versus time (on linear and semilogarithmic scales) 
GS-1423 plasma concentration data and PK sampling details will be listed for all subjects in the 
PK Analysis Set. Mean and median postdose concentration values that are ≤ LOQ, if any, will 
not be displayed in the figures and remaining points connected.
8.2.2.
GS-1423 PK Parameters
For subjects in Phase 1a Part A, relevant PK parameters will be estimated using Phoenix 
WinNonlin® software and utilizing standard noncompartmental methods. The linear up log down 
rule will be applied in conjunction with the appropriate noncompartmental model, with input 
values for dose level, dosing time, plasma concentration, and corresponding real time values, 
based on drug dosing times whenever possible. Descriptive statistics will be presented for PK 
parameters of GS-1423 by dose level/cohort.
All predose sample times before time-zero will be converted to 0. For area under the curve 
(AUC), samples BLQ of the bioanalytical assays occurring prior to the achievement of the first 
quantifiable concentration will be assigned a concentration value of 0 to prevent overestimation 
of the initial AUC. Samples that are BLQ at all other time points will be treated as missing data 
in WinNonlin. The nominal time point for a key event or dosing interval (τ) may be used to 


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permit direct calculation of AUC over specific time intervals. The appropriateness of this 
approach will be assessed by the PK scientist on a profile by profile basis.
Pharmacokinetic parameters such as λz and t1/2 are dependent on an accurate estimation of the 
terminal elimination phase of drug. The appropriateness of calculating these parameters will be 
evaluated upon inspection of PK data on a profile-by-profile basis by the PK scientist.
The PK parameters for GS-1423 presented in Table 2 will be computed for all subjects in the PK 
Analysis Set using profiles from Cycle 1 [predose through Cycle 2 predose (Cycle 1 Day 15)]  
and Cycle 4 [predose through Cycle 5 predose (Cycle 4 Day 15)], as applicable.
Table 2.
PK Parameters for GS-1423
Analyte
Parameters
GS-1423
AUCtau, Cmax, Ctrough, Tmax, CLss, Vss, Clast, Tlast, AUClast, AUCtau/Dose, Cmax/Dose, and 
Ctrough/Dose, if applicable   
Individual subject PK parameter data will be listed and summarized using descriptive statistics 
(n, arithmetic mean, StD, coefficient of variation [%CV], median, min, max, Q1, Q3, geometric 
mean, 95% CI, mean and StD of the natural log-transformed values) for all subjects for whom 
PK parameter(s) can be derived. The sample size for each PK parameter will be based on the 
number of subjects with nonmissing data for that PK parameter.
The following table will be provided by dose level:

Individual subject plasma PK parameters and summary statistics will be presented for PK 
parameters of GS-1423 by dose cohort.
Individual data on determination of half life and corresponding intra-subject correlation 
coefficient will be listed.


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9.
IMMUNOGENICITY ANALYSES
9.1.
ADA Sample Collection
Plasma samples will be collected to measure anti-drug antibody (ADA) against GS-1423 at 
protocol specified time points.
9.2.
Statistical Analyses Methods
Immunogenicity data will be summarized for all subjects by different dose cohorts and across 
dose cohorts in the Immunogenicity Analysis Set. Immunogenicity of GS-1423 will be evaluated 
based upon the incident of ADA. The number and proportion of subjects exhibiting positive 
ADA status, defined as ADA presence in plasma confirmed in validated assay and reported by 
bioanalytical laboratory, will be summarized at each specified time point. The number and 
proportion of subjects exhibiting positive ADA status at any post-baseline time point will also be 
summarized. 
A by-subject listing for ADA status at each time point, along with treatment, nomimal sampling 
day, actual date and time of sampling, and reason of sample not collected and titer for subjects 
with positive ADA status will be provided by subject ID number and time point in chronological 
order.


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11.
REFERENCES
Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, U.S. Department of 
Health and Human Services, National Institutes of Health, National Cancer Institute, 27 
November 2017.  
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
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12.
SOFTWARE
SAS® Software Version 9.X. SAS Institute Inc., Cary, NC, USA.


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13.
APPENDICES
Appendix 1.
Schedule of Assessments
Appendix 2.
COVID-19 SMQ with Broad Scope
Appendix 3.
Determining Missing and Virtual Visits Due to COVID-19
Appendix 4.
List of laboratory Tests for Safety Summary


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Appendix 1.
Schedule of Assessments
Study Procedures Table for Q2W/Q3W Dosing Schedule
Screening
Treatment Phase 
(For Q2W and Q3W Dosing Schedules)
End-of-Treatment
Posttreatment Follow-upa
Survival 
Follow-up
Cycle 1
Cycle 2
Every 
Subsequent 
Odd Cycle
Every 
Subsequent 
Even Cycle
End-of-
Treatment 
Visit
30 -Day 
Follow-up Visit 1
Visit 2
Visits 3 
and 4
Visits Schedule (days)
1
2
8
1
2
8
1
1
At 
End-of-Treatment
30d from 
last dose
3 m 
from 
last dose
6 m 
from 
last dose
3 m 
from 
last visit
3 m from 
last visit
Schedule Window (days)b
 2
 2
 2aa
 2aa
≤ 7
± 7
± 7
± 7
± 7
± 7
Administrative Procedures
< -28 days
Informed consent 
X
Review of inclusion/exclusion criteria
X
X
Issue Emergency Medical Support and 
Subject Card
X
Review of medical history and demographics
X
Review of baseline symptoms
X
X
Review of prior and concomitant medications
X
X
X X X
X
X
X
X
X
X
Cancer disease details and prior treatment
X
Subsequent anticancer therapy status
X
X
X
X
X
Clinical Procedures/Assessments
< -7 days
Review AEsc
X
X
X X X
X
X
X
X
X
X
Full Physical Examination
X
X
Focused Physical Examination
Xd
X
X
X
X
X
X
X
Vital Signs, Weight and Heighte
X
X
X X X
X
X
X
X
X
X
X
X
X
12-lead ECGf
X
Xf
Xf Xf
X
X
X
Echocardiogram or MUGAg
Xg
X
ECOG Performance Statusd
X
Xd
X X X
X
X
X
X
X
X
X
X
X
Imaging Assessmentsh
< -28 days
Tumor Imagingh
X
Every 6 weeks (± 7 days) the first 4 assessments then see footnote.


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Screening
Treatment Phase 
(For Q2W and Q3W Dosing Schedules)
End-of-Treatment
Posttreatment Follow-upa
Survival 
Follow-up
Cycle 1
Cycle 2
Every 
Subsequent 
Odd Cycle
Every 
Subsequent 
Even Cycle
End-of-
Treatment 
Visit
30 -Day 
Follow-up Visit 1
Visit 2
Visits 3 
and 4
Visits Schedule (days)
1
2
8
1
2
8
1
1
At 
End-of-Treatment
30d from 
last dose
3 m 
from 
last dose
6 m 
from 
last dose
3 m 
from 
last visit
3 m from 
last visit
Schedule Window (days)b
 2
 2
 2aa
 2aa
≤ 7
± 7
± 7
± 7
± 7
± 7
Laboratory Procedures/Assessmentsi
< -28 days
Blood for PK Assaysj
X
X
X
Blood for ADA Assaysk
X
X
X
Blood for pharmacogenomics
Xp
Collection of required pretreatment biopsy 
(Phase 1b Cohort 2)z
X
Collection of required on-treatment biopsy 
(Phase 1b Cohort 2)y
X
Serum chemistryt
X
Xd
X X
X
X
X
X
X
Hematology testst
X
Xd
X X
X
X
X
X
X
X
Coagulation testst
X
X
X
X
X
X
X
Endocrine function testst
X
X
X
X
X
X
X
Hepatitis Serology 
X
Urinalysist
X
X X
X
X
X
X
X
Serum pregnancy test
Xu
Urine pregnancy testv,bb
Xu
X
X
X
X
Xbb
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Screening
Treatment Phase 
(For Q2W and Q3W Dosing Schedules)
End-of-Treatment
Posttreatment Follow-upa
Survival 
Follow-up
Cycle 1
Cycle 2
Every 
Subsequent 
Odd Cycle
Every 
Subsequent 
Even Cycle
End-of-
Treatment 
Visit
30 -Day 
Follow-up Visit 1
Visit 2
Visits 3 
and 4
Visits Schedule (days)
1
2
8
1
2
8
1
1
At 
End-of-Treatment
30d from 
last dose
3 m 
from 
last dose
6 m 
from 
last dose
3 m 
from 
last visit
3 m from 
last visit
Schedule Window (days)b
 2
 2
 2aa
 2aa
≤ 7
± 7
± 7
± 7
± 7
± 7
HER2 Testingcc
X
Study drug administration
GS-1423 (All cohorts)w
X
X
X
X
mFOLFOX6 (Phase 1b Cohort 1)x 
X
X
X
X
5-FU = 5-fluorouracil; ADA = anti-drug antibody against GS-1423; AEs = adverse events; CRF = case report form; ECG = electrocardiogram; eCRF = electronic case report form; 
ECOG = Eastern Cooperative Oncology Group; HER2 = human epidermal growth factor receptor 2; IHC = immunohistochemistry; ISH = in situ hybridization; MUGA = 
multigated acquisition; PBMC = peripheral blood mononuclear cell; PD = progressive disease; PK = pharmacokinetics; Q2W = every 2 weeks; Q3W = every 3 weeks; SAE = 
serious adverse event
Note: Where applicable, assessments are to be performed prior to treatment unless otherwise indicated.
a
All subjects who discontinue treatment will have at least one 30-Day Follow-up Visit 30 days (± 7 days) from last treatment dose. Subjects who discontinue due to PD and/or 
start of a new line of therapy will then enter the Survival Follow-up Period for up to 12 months for survival status. Subjects who have discontinued treatment due to reasons 
other than PD and/or start of a new line of therapy will be in Posttreatment Follow-up for up to approximately 12 months from last treatment dose or until PD and/or start of a 
new line of therapy. Every effort should be made to collect subject information on the start of new anticancer therapy, PD, and death.
b
Treatment administration and associated procedures for that visit may be delayed for treatment-related AEs beyond the window and subsequent schedule adjusted 
accordingly.
c
After informed consent, but prior to initiation of study medication, the following types of events should be reported on the case report form (CRF/eCRF): all SAEs and AEs 
related to protocol-mandated procedures.
d
72-hour window for C1D1 physical examination, safety labs, and ECOG performance status collection.
e
Vital signs will only be measured while subject is in seated or semi-recumbent position. Height only collected at screening. Phase 1a and Phase 1b (Cohort 2): Vital signs are 
to be measured prior to each infusion commencing, at the end of each infusion, and for the first 2 cycles, 1 hour (± 15 minutes) after the end of the GS-1423 infusion. 
Thereafter, the final vital signs can be taken 30 minutes (-10/+20 minutes) after the end of each GS-1423 infusion. Subjects will remain in the clinic under close supervision 
for the duration of this monitoring period. Phase 1b (Cohort 1): Additional vital signs for subjects being administered the mFOLFOX6 regimen will be measured as per 
standard institutional guidelines.
f
12-lead ECG on Cycle 1 Day 1, before and 2 hours (-10/+20 minutes) after GS-1423 administration; on subsequent cycles, 12-lead ECG will be collected every odd cycle, on 
Day 1, at end of GS-1423 infusion(-10/+20 minutes), or as indicated. For subjects in Cohorts 5 through 8 and Cohort 10, a triplicate ECG will be performed at Cycle 1, Day 1 
predose, at end of infusion, at 24 hours postdose (Day 2), and 168 hours postdose (Day 8).
g
Complete echocardiogram assessment will be conducted at screening to determine baseline (may be done within 14 days prior to the first dose of study treatment); and at 
every odd cycle, on Day 1, starting at Cycle 3 (±3 days). A MUGA scan is allowed.
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h 
TI1e initial tumor iniaging will be pe1fo1med within 28 days prior to first dose. Scans pe1fo1med as pait of rnutine clinical management are acceptable for use as screening 
scan if they are of diagnostic quality and < -28 days prior to first dose. On-study imaging will be pe1fo1med at 6, 12, 18, and 24 weeks(± 7 days) from first treatment dose and 
then every 12 weeks thereafter. hnaging assessments will continue until PD as assessed by the investigator, unexpected toxicity occurs, or a new line of therapy is initiated for 
up to 1 year (Phase la and Phase lb Cohoit 2) or 2 years (Phase lb Coho,t 1. The tiniing of on-study treatment imaging should follow calendar days and should not be 
adjusted for delays in treatment administration or for visits. TI1e same imaging technique should be used in a subject thrnughout the study. In general, lesions detected at 
baseline should be followed using the same iniaging methodology and preferably the same iniaging equipment at subsequent tumor evaluation visits. 
Unless otherwise specified, samples should be collected before treatment administration. Refer to the Laboratory Manual for instmctions and additional information. 
J 
PK Assays: Refer to Section 6; Table 6-3, Table 6-4, Table 6-5 and Table 6-6 in the body of the prntocol. 
k 
ADA Assays: Refer to Section 6; Table 6-9 and Table 6-10 in the body of the prntocol. 
1 
Not applicable (This footnote is obsolete with Amendment 1.) 
m 
Not applicable (This footnote is obsolete with Amendment 1.) 
n 
Not a licable 
us footnote is obsolete with Amendment 1. 
r i· 
r 
r 
a oratory tests for screening should be pe1fo1med within 28 days prior to the first dose of study treatment. After Cycle 1, predose laborato,y procedures can be conducted up 
to 72 hom·s prior to dosing. 
u 
Serum ~-hmuan chorionic gonadotropin (~-HCG) pregnancy test for women of childbearing potential at screening within 72 hom·s of first treatment dose (if pe1fo1med earlier 
in screening period, then a mine pregnancy test may be performed prior to first dose); mine pregnancy test at all other indicated visits; results must be available prior to 
dosing. 
v 
U,ine pregnancy results to be obtained on site. 
w 
GS-1423 should be administered intravenously within 60 minutes (-10/+20 niinutes). Subjects must be observed for 1 hom· postinfusion for infusion-related reaction for the 
first 2 cycles and thereafter, 30 minutes after the end of the GS-1423 infusion. If administration of GS-1423 is delayed due to an AE, treatment visits may be delayed beyond 
the window of 3 days and schedules for subsequent visits should be adjusted accordingly. 
x 
TI1e mFOLFOX6 regimen consists ofleucovorin 200 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5-FU 400 mg/m2 and a 46-hom· infusion of 5-FU 2400 mg/m2. 
Administration of mFOLFOX6 will inimediately follow administration of GS-1423 on Day 1 of each cycle. TI1e chemotherapy regimen mFOLFOX6 will be adniinistered 
Q2W for up to 12 cycles (6 months). After 12 cycles, subjects may continue to receive 5-FU and leucovo,in at the investigator's discretion until the subject meets study 
treatment discontinuation criteria. 
y 
Required on-treatment biopsy should be collected at C3Dl or up to 1 week prior on Q2W treatment cycle. 
z 
Required pretreatment biopsy must be obtained prior to ClDl on a tumor from which 2 biopsies can be obtained (1 pretreatment and 1 on treatment). 
aa 
Treatment Phase visit window sta,ting at Cycle 4 until End of Treatment is ± 2 days. 
bb TI1is will only be pe1fo1med for subjects receiving mFOLFOX6. U,ine pregnancy tests will be performed at 4 months and 6 months after the last dose of mFOLFOX6. 
For sub'ects in Phase lb Coho,t 1 oastric coho,t tumor tissue will be tested for HER2 status if unknown with an a 
roved IHC and ISH kit. 
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Appendix 2.
COVID-19 SMQ with Broad Scope
Note: The list presented below is based on MedDRA Version 23.1. The actual list will be up-
versioned to the MedDRA version used at the time of database finalization.
MedDRA Preferred Term
PT Code
Asymptomatic COVID-19
10084459
Coronavirus infection
10051905
Coronavirus test positive
10070255
COVID-19
10084268
COVID-19 immunisation
10084457
COVID-19 pneumonia
10084380
COVID-19 prophylaxis
10084458
COVID-19 treatment
10084460
Exposure to SARS-CoV-2
10084456
Multisystem inflammatory syndrome in children
10084767
Occupational exposure to SARS-CoV-2
10084394
SARS-CoV-2 antibody test positive
10084491
SARS-CoV-2 carrier
10084461
SARS-CoV-2 sepsis
10084639
SARS-CoV-2 test false negative
10084480
SARS-CoV-2 test positive
10084271
SARS-CoV-2 viraemia
10084640
Suspected COVID-19
10084451
Antiviral prophylaxis
10049087
Antiviral treatment
10068724
Coronavirus test
10084353
Coronavirus test negative
10084269
Exposure to communicable disease
10049711
Pneumonia viral
10035737
SARS-CoV-2 antibody test
10084501
SARS-CoV-2 antibody test negative
10084509
SARS-CoV-2 test
10084354
SARS-CoV-2 test false positive
10084602
SARS-CoV-2 test negative
10084273


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Appendix 3.
Determining Missing and Virtual Visits Due to COVID-19
This appendix describes the clinical trial site collection of COVID-19 data pertaining to 
missed/virtual visits and the data processing algorithm used to determine which visits were 
missing and which visits were virtual.
Data collection
A COVID-19 supplement to the eCRF Completion Guidelines (CCG) was provided by data 
management to instruct clinical trial sites with respect to data entry expectations pertaining to 
scenarios related to the COVID-19 pandemic.  If a visit was missed, sites should enter “Visit 
missed due to COVID-19.”  If an in-person visit was conducted virtually, sites should enter 
“Virtual visit due to COVID-19.”  
Determination of Missed and Virtual visits
NLP was used to search the CRF comment fields to identify instances of “COVID-19” (or 
synonyms, see the table below) and “Virtual” (or synonyms, see the table below).  The search 
terms are maintained in a global lookup table and can be modified to tune the NLP model.  For 
any comments with COVID-19 search terms, assign “Missed visit” or “Virtual visit” as follows:
i. If COVID-19 terms are identified through NLP and the visit date is missing, then 
result is “Missed Visit”
ii. If COVID-19 and Virtual terms are identified through NLP for a visit, then result is 
“Virtual Visit”. When there are multiple records for the same subject and the same 
visit, NLP will be based on multiple records to ensure 1 unique category per subject 
per visit
iii. Otherwise result is missing
Examples of Search Terms for “COVID-19” and “Virtual” Used to Identify Missed and 
Virtual Visits
Search Terms for “COVID-19”
Search Terms for “Virtual”
COVID19
CORONA
CORONAVIRUS
PANDEMIC
OUTBREAK
CRISIS
LOCKDOWN
QUARANTINE
SHELTER
VIRTUAL
TELEMED
TELEHEALTH
TELEPHONE
REMOTE
TELEMEDICINE 
TELECONSULTATION
TELEPHONICALLY
PHONE
HOME VISIT
ZOOM
SKYPE


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Appendix 4.
List of laboratory Tests for Safety Summary
Chemistry
Urinalysis
Hematology 
Other 
WBC and differential absolute 
count
Eosinophils
Lymphocytes
Monocytes
ANC
Hemoglobin
Hematocrit
Platelet count
MCV
RBC
Albumin
Alkaline phosphatase
ALT 
AST 
Bicarbonate
BUN/total urea
Calcium
Chloride
Serum Creatininea
CRP
GGT
Glucose
LDH
Lipase
Cholesterol
Tryglycerides
Amylase
Magnesium
Phosphorus/phosphates
Potassium
Sodium
Total bilirubinb
Direct bilirubin
Total protein
Uric acid
Color and 
appearance
Specific gravity
pH
Occult blood
Protein
Glucose
Bilirubin
Leukocyte esterase
Nitrite
Urobilinogen
Ketones
Microscopicb
Coagulation
Prothrombin time (INR)
aPTT
Serum β-hCG or urine 
pregnancy testc
Endocrine Function Tests 
(TSH and freeT4d)
Basal cortisol
Hepatitis Serologyb
β-hCG = beta-human chorionic gonadotropin; ALT = alanine aminotransferase; ANC = total absolute neutrophil count; aPTT = 
activated partial thromboplastin time; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CRP = C-reactive protein; 
Free T4 = free thyroxine; GGT = gamma-glutamyltransferase; INR = international normalized ratio; LDH = lactate 
dehydrogenase; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin concentration; MCV = mean 
corpuscular volume; RBC = red blood cell; PT = prothrombin time; TSH = thyroid-stimulating hormone; WBC = white blood 
cell
a
Estimated creatinine clearance (CLcr)/glomerular filtration rate will be calculated based on the Cockcroft-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 childbearing potential only. Serum pregnancy will be conducted at screening within 72 hours of first treatment 
dose (if performed earlier in screening period then a urine pregnancy test may be performed prior to first dose); urine 
pregnancy test at all other indicated visits. 
d
TSH and free T4 will be tested by the central laboratory. T4 will be tested reflexively based on abnormal TSH results.


GS-US-505-5452 SAP
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Clinical Research eSigned
16-Jul-2021
14:59:14
Biostatistics eSigned
20-Jul-2021
07:05:40
PPD
PPD