A Phase 1b/2 Study of GS-5829 in Combination With Fulvestrant or Exemestane in Subjects With Advanced Estrogen Receptor Positive, HER2 Negative-Breast Cancer
Phase: PHASE1
Conditions: Advanced Estrogen Receptor Positive HER2- Breast Cancer
Sponsor: Gilead Sciences

CLINICAL STUDY PROTOCOL
Study Title:
A Phase 1b/2 Study of GS-5829 in Combination with Fulvestrant or 
Exemestane in Subjects with Advanced Estrogen Receptor Positive, 
HER2 Negative-Breast Cancer
Sponsor:
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City CA, 94404
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
124032 
2016-002365-63
NCT02983604
Indication:
Estrogen Receptor Positive HER2 Negative Breast Cancer
Protocol ID:
GS-US-350-1937
Clinical Program 
Manager:
Name:
Telephone:
Email:
Gilead Medical 
Monitor:
Name:
Work:
Cell:
Fax:
Email:
Protocol Version/Date:
Original:
17 June 2016
Amendment 1: 
10 August 2016
Amendment 2:
05 May 2017
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable Institutional 
Review Board or Independent Ethics Committee. The information is only to be used by you in 
connection with authorized clinical studies of the investigational drug described in the protocol. 
You will not disclose any of the information to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessary to obtain informed consent from those 
persons to whom the drug may be administered.
PPD
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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................5
LIST OF IN-TEXT FIGURES ......................................................................................................................................5
PROTOCOL SYNOPSIS ..............................................................................................................................................6
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS....................................................................19
1.
INTRODUCTION ..............................................................................................................................................22
1.1.
Background ............................................................................................................................................22
1.2.
GS-5829 .................................................................................................................................................23
1.2.1.
General Information .............................................................................................................23
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................23
1.2.3.
Clinical Experience of GS-5829...........................................................................................24
1.2.4.
Information about Exemestane.............................................................................................25
1.2.5.
Information about Fulvestrant..............................................................................................26
1.3.
Rationale for This Study ........................................................................................................................26
1.3.1.
Rationale for Dose Selection................................................................................................28
1.4.
Risk/Benefit Assessment for the Study..................................................................................................28
1.5.
Potential Benefits ...................................................................................................................................29
1.6.
Compliance ............................................................................................................................................29
2.
OBJECTIVES.....................................................................................................................................................30
3.
STUDY DESIGN................................................................................................................................................31
3.1.
Endpoints ...............................................................................................................................................31
3.2.
Study Design..........................................................................................................................................31
3.3.
Study Treatments ...................................................................................................................................34
3.4.
Duration of Treatment............................................................................................................................34
3.5.
Criteria for Discontinuation of Study Drug............................................................................................35
3.6.
Criteria for Removal from Study............................................................................................................35
4.
SUBJECT POPULATION..................................................................................................................................36
4.1.
Number of Subjects and Subject Selection ............................................................................................36
4.2.
Inclusion Criteria....................................................................................................................................36
4.3.
Exclusion Criteria...................................................................................................................................38
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................40
5.1.
Enrollment..............................................................................................................................................40
5.2.
Description and Handling of GS-5829...................................................................................................40
5.2.1.
Formulation..........................................................................................................................40
5.2.2.
Packaging and Labeling .......................................................................................................40
5.2.3.
Storage and Handling...........................................................................................................41
5.3.
Dosage and Administration of GS-5829, Exemestane and Fulvestrant..................................................41
5.3.1.
Dose Adjustment of GS-5829 ..............................................................................................42
5.3.2.
Dose Adjustment of Exemestane (Group A Phase 1b).........................................................45
5.3.3.
Dose Adjustment of Fulvestrant...........................................................................................45
5.4.
Prior and Concomitant Medications.......................................................................................................45
5.5.
Accountability for GS-5829, Exemestane and Fulvestrant ....................................................................46
5.5.1.
GS-5829, Exemestane (Group A Phase 1b) and Fulvestrant 
Investigational Medicinal Product Return or Disposal.........................................................46

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6.
STUDY PROCEDURES ....................................................................................................................................47
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................47
6.2.
Study Procedures Descriptions...............................................................................................................47
6.2.1.
Informed Consent.................................................................................................................47
6.2.2.
Medical History....................................................................................................................48
6.2.3.
Prior and Concomitant Medications.....................................................................................48
6.2.4.
Physical Examination...........................................................................................................48
6.2.5.
Vital Signs............................................................................................................................48
6.2.6.
Electrocardiogram................................................................................................................49
6.2.7.
Echocardiogram ...................................................................................................................49
6.2.8.
ECOG Performance Status...................................................................................................49
6.2.9.
Adverse Events.....................................................................................................................50
6.2.10.
Disease Assessments............................................................................................................50
6.2.11.
Laboratory Assessments.......................................................................................................51
6.2.12.
Pregnancy Test for Females of Childbearing Potential ........................................................52
6.2.13.
Vitamin D Assessment.........................................................................................................53
6.2.14.
Pharmacokinetic & Pharmacodynamic Samples..................................................................53
6.3.
Biomarker Testing..................................................................................................................................53
6.3.1.
Biomarker Samples to Address the Study Objectives:.........................................................53
6.3.2.
Biomarker Samples for Optional Future Research...............................................................55
6.3.3.
Biomarker Samples for Optional Genomic Research...........................................................56
6.4.
Re-Screening Criteria.............................................................................................................................57
6.5.
Treatment Assessments..........................................................................................................................57
6.6.
Post-treatment Assessments ...................................................................................................................57
6.7.
Long-Term Survival Follow-Up ............................................................................................................58
6.8.
Unscheduled Visits.................................................................................................................................58
6.9.
Assessments for Premature Discontinuation from Study.......................................................................58
6.10.
Criteria for Discontinuation of Study Treatment....................................................................................58
6.11.
Post Study Care......................................................................................................................................58
6.12.
Replacement of Subjects........................................................................................................................59
6.13.
Protocol Deviations................................................................................................................................59
6.14.
End of Study...........................................................................................................................................59
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................60
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................60
7.1.1.
Adverse Events.....................................................................................................................60
7.1.2.
Serious Adverse Events........................................................................................................60
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................61
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................62
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................62
7.2.2.
Assessment of Severity ........................................................................................................62
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................63
7.4.
Gilead Reporting Requirements.............................................................................................................65
7.5.
Toxicity Management ............................................................................................................................65
7.6.
Special Situations Reports......................................................................................................................65
7.6.1.
Definitions of Special Situations..........................................................................................65
7.6.2.
Instructions for Reporting Special Situations.......................................................................66
8.
STATISTICAL CONSIDERATIONS................................................................................................................68
8.1.
Analysis Objectives and Endpoints........................................................................................................68
8.1.1.
Analysis Objectives..............................................................................................................68

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8.1.2.
Primary Endpoints................................................................................................................69
8.1.3.
Secondary Endpoints............................................................................................................69
8.2.
Analysis Conventions.............................................................................................................................70
8.2.1.
Analysis Sets ........................................................................................................................70
8.3.
Data Handling Conventions ...................................................................................................................71
8.4.
Demographic Data and Baseline Characteristics ...................................................................................71
8.5.
Efficacy Analysis ...................................................................................................................................71
8.5.1.
Primary Analysis..................................................................................................................71
8.5.2.
Secondary Analyses .............................................................................................................72
8.6.
Safety Analysis.......................................................................................................................................72
8.6.1.
Extent of Exposure...............................................................................................................72
8.6.2.
Adverse Events.....................................................................................................................72
8.6.3.
Laboratory Evaluations ........................................................................................................73
8.6.4.
Other Safety Evaluations......................................................................................................74
8.7.
Pharmacokinetic Analysis......................................................................................................................74
8.8.
Biomarker Analysis................................................................................................................................74
8.9.
Sample Size............................................................................................................................................75
9.
RESPONSIBILITIES..........................................................................................................................................76
9.1.
Investigator Responsibilities ..................................................................................................................76
9.1.1.
Good Clinical Practice..........................................................................................................76
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................76
9.1.3.
Informed Consent.................................................................................................................77
9.1.4.
Confidentiality......................................................................................................................77
9.1.5.
Study Files and Retention of Records ..................................................................................77
9.1.6.
Case Report Forms...............................................................................................................79
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................79
9.1.8.
Inspections............................................................................................................................80
9.1.9.
Protocol Compliance............................................................................................................80
9.2.
Sponsor Responsibilities ........................................................................................................................80
9.2.1.
Protocol Modifications.........................................................................................................80
9.2.2.
Study Report and Publications .............................................................................................80
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................81
9.3.1.
Payment Reporting...............................................................................................................81
9.3.2.
Access to Information for Monitoring..................................................................................81
9.3.3.
Access to Information for Auditing or Inspections ..............................................................81
9.3.4.
Study Discontinuation..........................................................................................................81
10.
REFERENCES ...................................................................................................................................................82
11.
APPENDICES ....................................................................................................................................................85
Appendix 1.
Investigator Signature Page....................................................................................................86
Appendix 2.
Study Procedures Table..........................................................................................................87
Appendix 3.
Pharmacokinetics, Pharmacodynamic Time Point Collection Tables ....................................91
Appendix 4.
Common Terminology Criteria for Adverse Events (CTCAE) v4.03....................................93
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................94
Appendix 6.
Performance Status Scoring System (ECOG) ........................................................................96
Appendix 7.
RECIST 1.1 ............................................................................................................................97
Appendix 8.
Exemestane (Aromasin®) Prescribing Information ................................................................98
Appendix 9.
Fulvestrant (Faslodex®) Prescribing Information...................................................................99
Appendix 10.
Bayesian Logistic Regression Model ...................................................................................100

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LIST OF IN-TEXT TABLES
Table 5-1.
Dose Reduction of GS-5829...................................................................................................42
Table 5-2.
Dose Reduction of GS-5829...................................................................................................44
Table 5-3.
Examples of Concomitant Medications Prohibited in this Study ...........................................45
Table 6-1.
Analytes..................................................................................................................................52
Table 7-1.
Grading of Adverse Event Severity........................................................................................63
LIST OF IN-TEXT FIGURES
Figure 1-1.
Mechanism of Action of GS-5829 to Reduce Transcription of ER Target Genes in 
Cancer Cells ...........................................................................................................................27
Figure 3-1.
Randomized Phase 2 Dose Expansion....................................................................................34

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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City CA, 94404
Study Title: 
A Phase 1b/2 Study of GS-5829 in Combination with Fulvestrant or 
Exemestane in Subjects with Advanced Estrogen Receptor Positive, 
HER2 Negative-Breast Cancer
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
124032
2016-002365-63
NCT02983604
Study Centers 
Planned:
Approximately 50 centers in the USA and Europe
Objectives:
The primary objective:
Phase 1b Dose Escalation

To characterize the safety and tolerability of GS-5829 in 
combination with fulvestrant and exemestane in subjects with 
advanced estrogen receptor positive, HER2 negative breast cancer 
(ER+/HER2- BrCa)

To determine the Maximum Tolerated Dose (MTD), or the 
recommended Phase 2 Dose (RP2D) of GS-5829 in combination 
with fulvestrant in subjects with advanced ER+/HER2- BrCa
Randomized Phase 2 Dose Expansion

To evaluate the efficacy of GS-5829 in combination with 
fulvestrant compared to fulvestrant alone in subjects with advanced 
ER+/HER2- BrCa as measured by progression-free survival (PFS). 
Secondary objectives: 
Phase 1b Dose Escalation

To evaluate the pharmacokinetics of GS-5829 in combination with 
fulvestrant in subjects with advanced ER+/HER2- BrCa
Randomized Phase 2 Dose Expansion 

To evaluate the efficacy of GS-5829 in combination with 
fulvestrant compared to fulvestrant alone in subjects with advanced 
ER+/HER2- BrCa, as measured by overall response rate (ORR) and 

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clinical benefit rate (CBR) evaluated according to Response 
Evaluation Criteria in Solid Tumors (RECIST) v. 1.1. ORR is 
defined as the proportion of subjects with response (complete 
response [CR], or partial response [PR]). CBR is defined as 
proportion of subjects with CR, PR, or stable disease (SD) that lasts 
for ≥ 24 weeks

To evaluate the safety and tolerability of GS-5829 in combination 
with fulvestrant compared to fulvestrant alone in subjects with 
advanced ER+/HER2- BrCa 

To evaluate the overall survival (OS) for subjects with advanced 
ER+/HER2- BrCa who receive GS-5829 in combination with 
fulvestrant compared to fulvestrant alone
Exploratory objectives:
 
 
Study Design:
Phase 1b Dose Escalation: 
Cohorts of postmenopausal women with advanced ER+/HER2- BrCa, 
for whom no standard curative therapy exists and who are candidates 
for exemestane or fulvestrant, will be sequentially enrolled at 
progressively higher dose levels of oral GS-5829 in combination with 
standard doses of exemestane or fulvestrant. Up to 30 subjects will be 
enrolled for the Phase 1b Dose Escalation portion of the study. The 
starting dose of GS-5829 has been determined to be 4 mg once daily 
based on safety information, pharmacokinetic and biomarker data from 
two ongoing GS-5829 studies (GS-US-350-1599, GS-US-350-1604) 
and the recommendation by the Bayesian Logistic Regression Model 
(BLRM) of dose-dose limiting toxicity (DLT) relationship 
(Section 1.3.1).   
Eligible subjects will be assigned to either Group A or B based on prior 
treatment.  Group A will initiate with GS-5829 orally once daily on 
Cycle 1 Day 1 (C1D1) combined with 25 mg of exemestane 
administered orally once daily (or in accordance with locally approved 
labeling). The subject may initiate exemestane any time prior to, or on, 
C1D1. 
Due to recent approvals of several CDK4/6 inhibitors in treatment of 
ER+/Her2- breast cancer, as well as unmet medical needs for subjects
PPD

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Group A and Group B will dose escalate independently of each other. 
Each dose escalation cohort will consist of 3 newly enrolled subjects 
who will be treated at the specified dose level. Enrollment in Group A 
has been stopped after completion of the 4 mg GS-5829 dose level 
safety assessments. Dose escalation in Group B will continue until 
identification of the MTD of GS-5829, or until a RP2D is reached (see 
rationale above).
After all the subjects in each cohort have been followed for at least 
28 days after C1D1 of GS-5829 and are evaluable, a dose- DLT model 
(see Appendix 10) utilizing all available GS-5829 safety data will be 
built and will provide estimates of DLT rates at all dose levels. The 
recommended dose from the dose-DLT model for the next cohort will 
be the one having the highest probability that the DLT rate falls in the 
target interval (16.7%, 33.3%), and a probability of < 25% that the 
DLT rate exceeds 33.3%.
The dose escalation decision and the final decision for the RP2D will 
be made by the Safety Review Team (SRT), following a review of the 
model recommendation and all relevant data including safety 
information, pharmacokinetics, biomarkers and clinical data from 
evaluable subjects.
The recommended dose of GS-5829 to be combined with fulvestrant in 
the Randomized Phase 2 Dose Expansion part of this study will be 
determined based on the data available in the Phase 1b Dose Escalation 
portion of this study and from studies GS-US-350-1599 and 
GS-US-350-1604. The recommended dose will not exceed the MTD 
identified by the Phase 1b Dose Escalation from this study. At least 6 
subjects should have already been treated and evaluated at that dose 
level prior to enrolling subjects in the Randomized Phase 2 Dose 
Expansion.
Dose Limiting Toxicity (DLT) Definition
A DLT is a toxicity defined below and considered possibly related to 
GS-5829 if occurring during the DLT assessment window (Day 1 
through Day 28) in each combination therapy cohort:

Grade ≥ 4 neutropenia (absolute neutrophil count [ANC] 
< 500/mm3)

Grade ≥ 3 neutropenia (ANC < 1000/mm3) with fever (a single 
temperature of  > 38.3°C or a sustained temperature of ≥38°C for 
more than one hour)

Grade ≥ 3 thrombocytopenia

Grade ≥ 2 bleeding (e.g. gastrointestinal, respiratory, epistaxis, 
purpura)

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
Grade ≥ 3 or higher non-hematologic toxicity, except:
○
Grade 3 nausea or emesis with maximum duration of 48 hours 
on adequate medical therapy
○
Grade 3 diarrhea which persists for < 72 hours in the absence of 
adequate medical therapy

Grade ≥ 2 non-hematologic treatment-emergent adverse event 
(TEAE) that in the opinion of the investigator is of potential clinical 
significance such that further dose escalation would expose subjects 
to unacceptable risk

Treatment interruption of ≥7 days due to unresolved toxicity
For certain toxicities, such as laboratory assessments without a clear 
clinical correlate, a discussion between the investigator and the Gilead 
medical monitor may take place to determine if this adverse event (AE) 
should be assessed as a DLT. However, any Grade 3 or Grade 4 
elevation in aspartate transaminase (AST) or alanine transaminase 
(ALT) associated with a Grade 2 elevation in bilirubin that is at least 
possibly related to study drug will be considered a DLT. See 
Section 3.2 for details.
Randomized Phase 2 Dose Expansion:
Approximately 120 female subjects who are post-menopausal with 
ER+/HER2- BrCa and who have had disease progression following 
endocrine therapy will be randomized in a 2:1 ratio to receive 
fulvestrant + GS-5829 or fulvestrant alone. Randomization will be 
stratified by prior cyclin-dependent kinase 4/6 (CDK4/6) inhibitor plus 
aromatase inhibitor (AI) status (naïve vs. progressed). The target 
number of subjects in each of the 2 strata will be approximately 60
(40 for GS-5829 in combination with fulvestrant and 20 for fulvestrant 
alone). GS-5829 and fulvestrant will be initiated on C1D1. Each cycle 
consists of 28 days.
Study Schema: Randomized Phase 2 Dose Expansion:
*  
Randomization will be stratified by prior CDK4/6 inhibitor plus AI status (naïve vs. 
progressed). The target number of subjects in each of the 2 strata will be approximately 60
(40 for GS-5829 in combination with fulvestrant and 20 for fulvestrant alone).
N=120*
Arm 1:  GS-5829 + Fulvestrant 
(N = 80)
Arm 2: Fulvestrant  
(N = 40)
Randomization
2:1

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Number of 
Subjects Planned:
Phase 1b Dose Escalation: Up to 30 subjects will be enrolled
Randomized Phase 2 Dose Expansion: Approximately 120 subjects will 
be enrolled  
Target Population:
Phase 1b Dose Escalation: Postmenopausal women with histologically
or cytologically confirmed ER+/HER2- BrCa who have progressed 
after treatment with an anti-estrogen or an aromatase inhibitor (AI) 
therapy and are candidates for fulvestrant or exemestane therapy.  
Randomized Phase 2 Dose Expansion: Postmenopausal women with
histologically or cytologically confirmed ER+/HER2- BrCa who had 
disease progression during treatment or within 12 months of 
completion of endocrine therapy (tamoxifen, and/or an AI) in the
adjuvant setting, or disease progression during treatment or within 1 
month post-treatment with endocrine therapy (tamoxifen, AI or
CDK4/6 inhibitor plus AI) for advanced/metastatic disease. Subjects 
may have had unlimited prior hormonal therapy, but must be naïve to 
fulvestrant in the metastatic setting. A total of 2 prior chemotherapies 
are allowed, however, only one for metastatic disease is permitted.
Duration of 
Treatment:
Subjects may continue receiving GS-5829 once daily until disease 
progression (clinical or radiographic), unacceptable toxicity, withdrawal
of consent, or death whichever comes first (Section 3.5).
Diagnosis and 
Main Eligibility 
Criteria:
Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible 
for participation in this study:
1) 18 years of age, female
2) Histologically or cytologically confirmed breast cancer with 
evidence of metastatic or locally advanced disease not amenable to 
resection or radiation therapy with curative intent and who have 
progressed during treatment with at least one prior hormonal 
therapy 
a) Phase 1b Dose Escalation - Subjects may have had unlimited 
prior hormonal therapy and a total of 2 prior chemotherapy 
regimens (adjuvant chemotherapy is considered 1 regimen).
Subjects may have progressed on fulvestrant or exemestane.
b) Randomized Phase 2 Dose Expansion - Subjects may have 
disease progression during treatment or within 12 months of 
completion of endocrine therapy (tamoxifen, and/or AI) in the
adjuvant setting, or disease progression during treatment with 
endocrine therapy (tamoxifen, AI or CDK4/6 inhibitor plus AI) 
for advanced/metastatic disease. Subjects may have had 

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unlimited prior hormonal therapy, but must be naïve to 
fulvestrant in the metastatic setting. A total of 2 prior 
chemotherapies are allowed, however, only one for metastatic
disease is permitted. 
3) Documentation of ER positive breast cancer (≥ 1% positive stained 
cells by local standards) based on the most recent tumor biopsy, 
unless bone-only disease
4) Documented HER2-negative tumor based on local testing on most 
recent tumor biopsy (immunohistochemistry score 0/1+ or negative 
by in situ hybridization HER2/CP17 ratio < 2 or for single probe 
assessment HER2 copy number < 4)
5) Post-, pre- or peri-menopausal subjects considered to be in the 
post-menopausal state as defined by one of the following:
a.
Age ≥ 60 years
b. Age < 60 years and cessation of regular menses for at least 
12 consecutive months in the absence of chemotherapy, 
tamoxifen, toremifene, or ovarian suppression and serum 
estradiol and follicle-stimulating hormone (FSH) level within 
the post-menopausal range
c.
Prior bilateral oophorectomy
d. Pre-/peri-menopausal women can be enrolled if amenable to be 
treated with the luteinizing-hormone releasing hormone 
(LHRH) agonist, goserelin. Subjects must have commenced 
treatment with goserelin or an alternative LHRH agonist at 
least 4 weeks prior to C1D1. If subjects have received an 
alternative LHRH agonist prior to study entry, they must 
switch to goserelin on or before C1D1 for the duration of the 
study
6) Measurable disease defined per RECIST v. 1.1, or bone-only 
disease must have a lytic or mixed lytic blastic lesion that can be 
accurately assessed by computed tomography (CT) or magnetic
resonance imaging (MRI). Subjects with bone-only disease and 
blastic-only metastases are not eligible
7) All acute toxic effects of any prior antitumor therapy resolved to 
Grade ≤ 1 before the start of study drug dosing (with the exception 
of alopecia [Grade 1 or 2 permitted] and neurotoxicity [Grade 1 or 
2 permitted])
8) Eastern Cooperative Oncology Group (ECOG) Performance Status 
of  ≤ 1
9) Life expectancy of  ≥ 3 months, in the opinion of the investigator

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10) Adequate organ function defined as follows:
a.
Hematologic:  Platelets ≥ 100 x 109/L; Hemoglobin ≥9.0 g/dL; 
ANC ≥ 1.5 x 109/L (without platelet transfusion or any 
granulocytic growth factors within previous 7 days of the 
hematologic laboratory values obtained at screening visit)
b. Hepatic: AST / ALT ≤ 2.5 x upper limit of normal (ULN) 
(if liver metastases are present, ≤ 5 x ULN); total or conjugated 
bilirubin ≤ 1.5 x ULN
c.
Renal: Serum Creatinine ≤ 1.5 x ULN or creatinine clearance 
(CrCl) ≥ 60 mL/min as calculated by the Cockroft-Gault 
method
11) Coagulation: International Normalized Ratio (INR) ≤1.2 
12) Negative serum pregnancy test (Appendix 5)
13) Female subjects of childbearing potential who engage in 
heterosexual intercourse must agree to use protocol specified 
method(s) of contraception as described in Appendix 5
14) Females who are nursing must agree to discontinue nursing before 
C1D1
15) Able and willing to provide written informed consent to participate 
in the study
Exclusion Criteria:
Subjects who meet any of the following exclusion criteria are not to be 
enrolled in this study:
1) History or evidence of clinically significant disorder, condition, or 
disease that, in the opinion of the investigator or the Gilead medical
monitor would pose a risk to subject safety or interfere with the 
study evaluations, procedures, or completion
2) Known brain metastasis or leptomeningeal disease. Note: if treated 
and stable at least 6 months prior to enrollment, subject is eligible.
3) Uncontrolled intercurrent illness including, but not limited to, 
active uncontrolled infection, active or chronic bleeding event 
within 28 days prior to C1D1 of study drug, uncontrolled cardiac 
arrhythmia, or psychiatric illness/social situation that would limit 
compliance with study requirements as judged by treating physician
4) Myocardial infarction, symptomatic congestive heart failure 
(New York Heart Association Classification > Class II), unstable 
angina, or serious uncontrolled cardiac arrhythmia within 6 months 
of C1D1
5) Major surgery, defined as any surgical procedure that involves 

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general anesthesia and a significant incision (i.e., larger than what is 
required for placement of central venous access, percutaneous 
feeding tube) within 28 days of C1D1
6) Impairment of gastrointestinal (GI) function or GI disease that may 
significantly alter the absorption of GS-5829, including any 
unresolved nausea, vomiting, or diarrhea that is Common 
Terminology Criteria for Adverse Events (CTCAE) V 4.03 
Grade > 1
7) Minor surgical procedure(s) within 7 days of enrollment or 
randomization, or not yet recovered from prior surgery (placement 
of central venous access device, fine needle aspiration, or 
endoscopic biliary stent ≥ 1 day before enrollment or randomization 
is acceptable)
8) History of a concurrent or second malignancy, except for: 
adequately treated local basal cell or squamous cell carcinoma of 
the skin; cervical carcinoma in situ; superficial bladder cancer; 
adequately treated Stage 1 or 2 cancer currently in complete 
remission; any other cancer that has been in complete remission for 
≥ 5 years
9) Anti-tumor therapy (chemotherapy, chemoradiation, radiation, 
molecular targeted therapy) within 21 days or 5 half-lives 
whichever is longer of C1D1 (6 weeks for nitrosoureas, 
mitomycin C, or molecular agents with t1/2 > 10 days); 5 half-lives 
of any investigational drug. Concurrent use of goserelin for 
pre-/peri-menopausal breast cancer and exemestane or fulvestrant
per the protocol are permitted
10) History of long QT syndrome or whose corrected QT interval 
(QTc) measured (Fridericia method) at screening is prolonged 
(> 470 ms). Subjects who screen fail due to this criterion are not 
eligible to be re-screened
11) Prior exposure to any bromodomain (BET) inhibitors  
12) Known hypersensitivity to the study drugs (GS-5829, fulvestrant or 
exemestane), the metabolites, or formulation excipients
13) Immunotherapy within 6 months of C1D1
14) Evidence of bleeding diathesis or clinically significant 
bleeding, within 28 days of C1D1 or history of hemoptysis of 
> 2.5 mL/1 teaspoon within 6 months of C1D1
15) Anticoagulation/antiplatelet therapy within 7 days of C1D1, 
including acetylsalicylic acid, low molecular weight heparin, or 
warfarin
16) Known human immunodeficiency virus (HIV) infection

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17) Hepatitis B surface Antigen (HBsAg) positive
18) Hepatitis C virus (HCV) antibody positive with HCV RNA positive
19) Use of moderate/strong cytochrome P450 (CYP)3A4 inhibitors or 
moderate/strong CYP3A4 inducers within 2 weeks prior to C1D1
20) History of high grade esophageal or gastric varices
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 on C1D1. Screening procedures will include the following:
medical history review, physical exam, vital signs, 12-lead
electrocardiogram (ECG), echocardiogram (ECHO), ECOG
Performance Status, prior/concomitant medication review, chemistry, 
hematology and coagulation, hepatitis B and hepatitis C virus 
(HBV)/(HCV) testing, human immunodeficiency virus (HIV) testing, 
serum pregnancy β-HCG (serum estradiol and FSH for subjects 
< 60 years old and who have been amenorrheic for at least 
12 consecutive months), and CT or MRI and bone scans. Scans that 
meet protocol requirements that are obtained as part of standard
medical practice up to 28 days prior to C1D1 are acceptable as long as: 
(1) tests were performed using the method requirements outlined in 
RECIST v.1.1, (2) the same technique/modality can be used to follow 
identified lesions throughout the trial for a given subject, and 
(3) appropriate documentation indicating that these radiographic tumor 
assessments were performed as standard of care is available in the 
subject’s source notes. Baseline tumor lesions per RECIST 1.1 will be
measured and characterized prior to C1D1 to assess the subject’s
disease status prior to beginning treatment.
Treatment:
Phase 1b Dose Escalation with Exemestane or Fulvestrant 
Subjects who meet eligibility criteria will receive GS-5829 orally once 
daily combined with either 25 mg of exemestane orally once daily 
or with fulvestrant intramuscularly on Day 1, 15 (for whom C1D1 is 
the subject’s first dose of fulvestrant), 29 and then every 28 days 
(± 3 days). Subjects in the Phase 1b Dose Escalation portion may 
initiate exemestane (Group A) or fulvestrant (Group B) any time prior 
to, or on, C1D1. Each cycle will consist of 28 days. Safety and efficacy
assessments will occur on an outpatient basis including an assessment
of tumor response, physical exam, vitals, ECG, collection of blood
samples (for routine safety labs, GS-5829
pharmacokinetic/pharmacodynamic markers, and biomarkers
atapplicable visits), and assessment of AEs. In addition, subjects will

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undergo a computed tomography (CT) scan (or magnetic resonance 
imaging [MRI]) scan every 8 weeks for the first year, then every 
12 weeks. 
A subject who does not show evidence of disease progression may
continue receiving GS-5829 once daily and exemestane (Group A) or 
fulvestrant (Group B) until disease progression (clinical or 
radiographic), unacceptable toxicity, withdrawal of consent, or death 
whichever comes first.
Following treatment discontinuation, subjects will be followed for 
safety for 30 days from the last dose of study drug. Pharmacokinetic
and pharmacodynamic samples for GS-5829 will be collected on Day 1 
and Day 15 of Cycle 1 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours 
post-dose and anytime on Day 1 of Cycles 2 through 6.  
Randomized Phase 2 Dose Expansion
Sparse pharmacokinetics and pharmacodynamic samples will be 
collected at pre-dose and anytime between 1 to 4 hours post-dose on 
Day 1 and Day 15 of Cycle 1 and at pre-dose on Day 1 of Cycles 3 and 
6. Note: pharmacokinetic samples will only be collected for subjects
who are randomized to a GS-5829 in combination with fulvestrant arm
(Arm 1). 
Subjects in the Randomized Phase 2 Dose Expansion portion of the 
study will also be followed for up to two years for OS. 
Test Product, Dose, 
and Mode of 
Administration:
GS-5829 will be supplied as round, plain-faced tablets containing 1 mg 
or 5 mg GS-5829. GS-5829 tablets will be self-administered orally 
once daily, beginning on C1D1 of the study and thereafter at 
approximately the same time each day until end of treatment (EOT).
For subjects in Group A of the Phase 1b Dose Escalation, 25 mg 
exemestane tablets will be self-administered orally once daily (or in 
accordance with locally approved labeling), beginning on C1D1 of the 
study and thereafter at approximately the same time each day until the 
EOT.  
For subjects in Group B of the Phase 1b Dose Escalation or subjects in 
Arm 2 of the Randomized Phase 2 Dose Expansion, fulvestrant will be 
administered intramuscularly (in accordance with locally approved 
labeling) by the clinic staff approximately every 28 days (± 3 days) 
until the EOT.  
For subjects in the Phase 1b Dose Escalation or subjects in the 
Randomized Phase 2 Dose Expansion part of the study for whom are 
treatment naïve (in metastatic setting) and for all subjects for whom 
C1D1 is the subject’s first dose of fulvestrant, a one-time additional 
dose of 500mg fulvestrant will be administered on Cycle 1, Day 15 
(± 3 days).  

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Reference Therapy, 
Dose, and Mode of 
Administration:
The reference therapy in the Randomized Phase 2 Dose Expansion 
portion of the study is fulvestrant alone.
For subjects in the Randomized Phase 2 Dose Expansion, fulvestrant
will be administered intramuscularly (in accordance with locally 
approved labeling) by the clinic staff approximately every 28 days 
(±3 days) until the EOT. For  subjects in the dose expansion Phase
whom are treatment naïve (in metastatic setting) and for all subjects in 
the dose escalation phase for whom C1D1 is the subject’s first dose of 
fulvestrant, a one-time additional dose of 500 mg fulvestrant will be 
administered on Cycle 1 Day 15 (± 3 days).
Criteria for 
Evaluation:
Phase 1b Dose Escalation and Randomized Phase 2 Dose 
Expansion
Safety:
Safety will be evaluated by assessment of clinical laboratory tests, 
physical examination, 12-lead ECG, vital signs measurements, and the 
documentation of AEs
Efficacy:
PFS – defined as the interval from date of randomization to the earlier 
of the first documented confirmed disease progression or death from 
any cause
ORR – defined as the proportion of subjects who achieve CR or PR, 
based on RECIST v. 1.1 
CBR - defined as the proportion of subjects who achieve a CR or PR or 
SD that lasts for ≥ 24 weeks based on RECIST v. 1.1 
OS - defined as interval from date of randomization to date of death 
from any cause
Pharmacokinetics:
Phase 1b Dose Escalation: The pharmacokinetic parameters for 
GS-5829 will be calculated as applicable: [e.g., Cmax, and AUCtau ]
Statistical Methods:
Analysis Methods
Phase 1b Dose Escalation: The incidence of DLTs, AEs, serious 
adverse events (SAEs), and clinically significant laboratory 
abnormalities in subjects treated with GS-5829 in combination with 
exemestane or fulvestrant will be evaluated.
Randomized Phase 2 Dose Expansion: The Intent-to-Treat (ITT) 
analysis set includes all subjects who are randomized, regardless of 
whether subjects receive any study drug(s) or receive a different 
regimen from the regimen they were randomized to. Treatment 
assignment will be designated according to randomization. The analysis 
of PFS based on the ITT analysis set will be considered the primary 
analysis of the study. PFS will also be analyzed for each of the 2 strata 
separately.

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A Safety Analysis Set for this study consists of all subjects who receive 
≥ 1 dose of study drug. Other analysis sets (DLT evaluable analysis set, 
pharmacokinetics analysis set, and biomarker analysis set) will be used 
for the corresponding analyses.
Subject characteristics and study results will be described and 
summarized by dose level, treatment arm and study visit for the 
relevant analysis sets. Descriptive summaries will be prepared to show 
sample size, mean, standard deviation (StD), 95% confidence intervals 
(CIs) on the mean, median, minimum and maximum for continuous 
variables, and counts, percentages and 95% CIs on the percentage for 
categorical variables.
Kaplan-Meier estimates and plots will be provided for PFS and OS. 
The log-rank test will be used to compare PFS and OS between 
subjects who received GS-5829 + fulvestrant and those who received 
fulvestrant alone. ORR and CBR will be calculated along with the 95% 
CIs based on exact method and compared between treatment arms by 
Fisher’s exact test. Based on the Safety Analysis Set, information 
regarding study drug administration, study drug compliance and safety 
variables will be described and summarized.
Using data from the relevant Analysis Sets, GS-5829 plasma 
concentrations will be summarized. Pharmacodynamic markers will 
also be described and summarized. Plasma concentrations of GS-5829 
metabolite(s), fulvestrant and exemestane may also be determined.
Sample Size
Up to approximately 30 subjects will be enrolled in the Phase 1b Dose 
Escalation portion of the study.
Total enrollment will be approximately 120 subjects in Randomized 
Phase 2 Dose Expansion portion. Approximately 80 subjects will be 
randomized to receive GS-5829 in combination with fulvestrant and 
40 subjects will receive fulvestrant alone in a 2:1 ratio. One hundred 
twenty subjects will provide 88 events in total and greater than 90% 
power to detect the difference in PFS between the two treatment arms 
with 0.1 one-sided significance level, assuming a median PFS of 
4 months for subjects who receive fulvestrant alone, a median PFS of 
8 months in subjects who receive GS-5829 in combination with 
fulvestrant, accrual period of 9 months and total study duration of 
19 months and a drop-out rate of 10% by 12 months. Within each 
stratum of naïve or progressed prior CDK4/6 inhibitor subjects, the 
power will be 80% with target number of 60 subjects (44 events).
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
AAG
alpha-1 acid glycoprotein
AE
adverse event
AI
aromatase inhibitor
ALT
alanine transaminase
ANC
absolute neutrophil count
AR
androgen receptor
AST
aspartate transaminase
AUCtau
area under the plasma concentration-time curve
BCRP
breast cancer resistance protein
BET
bromodomain and extra-terminal
BRD
bromodomain
CBC
complete blood count
CBR
CDK4/6 inhibitor
Clinical benefit rate
Cyclin-dependent kinase 4/6 inhibitor
Cmax
maximum concentration observed
Ctau
concentration at the end of the dosing interval
CFR
Code of Federal Regulations
CI
confidence interval
CR
complete response
CrCl
creatinine clearance
CRF
case report form
CRO
contract research organization
CRP
c-reactive protein
CRPC
castrate-resistant prostate cancer
CT
computed tomography
CTC
circulating tumor cells
CTCAE
Common Terminology Criteria for Adverse Events
CYP
cytochrome P450
DDI
drug-drug interaction
DLBCL
diffuse large B-cell lymphoma
DLT
dose limiting toxicity
DNA
deoxyribonucleic acid
DSPH
Drug Safety and Public Health
ECHO
echocardiogram
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EOT
end of treatment

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ER
estrogen receptor
eSAE
electronic serious adverse events
FAS
full analysis set
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GI
gastrointestinal
HBsAg
Hepatitis B surface Antigen
HBV
Hepatitis B virus
HCV
Hepatitis C virus
HIV
Human Immunodeficiency Virus
HNSTD
highest non-severely toxic dose
IB
ICH
Investigator’s brochure
International Conference on Harmonization
IEC
Independent Ethics Committee
INR
IP
International Normalized Ratio
investigational product
IRB
Institutional Review Board
IxRS
Interactive voice/web Response System
LHRH
luteinizing-hormone releasing hormone
mCRPC
metastatic castrate-resistant prostate cancer
MedDRA
Medical Dictionary for Regulatory Activities
MRI
magnetic resonance imaging
MTD
maximum tolerated dose
MYC
myelocytomatosis viral oncogene homolog
MUGA
multigated acquisition scan
NCI
National Cancer Institute
ORR
overall response rate
OS
overall survival
PD
Progressive Disease
PFS
progression-free survival
PK
pharmacokinetics
PR
partial response
QD
every day
QTc
corrected QT interval
RECIST
Response Evaluation Criteria in Solid Tumors
RNA
ribonucleic acid
RNAPII
RNA polymerase II
SADR
serious adverse drug reaction
SAE
serious adverse event

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SD
stable disease
StD
standard deviation
SOC
system organ class
SOP
standard operating procedure
SRT
safety review team
STD
severely toxic dose
SUSAR
suspected unexpected serious adverse reactions
t1/2
terminal phase half-life
TEAE
treatment-emergent adverse event
ULN
upper limit of normal
US
United States
WBC
white blood cell

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1.
INTRODUCTION
1.1.
Background
GS-5829 is a small-molecule inhibitor of the highly conserved bromodomain pockets of the 
bromodomain and extraterminal (BET) proteins. Bromodomain and extraterminal proteins 
regulate specific gene expression by enhancing ribonucleic acid (RNA) polymerase II (RNAPII)
mediated transcription. Signal transduction pathways recruit BET proteins to target genes 
through posttranslational modification of histone proteins in the form of lysine acetylation
{Belkina 2012, Hargreaves 2009}. The tandem bromodomain motifs of BET proteins 
specifically recognize acetylated histones and, in turn, recruit protein factors that regulate 
RNAPII {Shi 2014}. The BET family includes bromodomain-containing proteins 2, 3, 4, and T 
(BRD2, 3, 4, and T). BRD2, 3 and 4 are widely expressed and regulate gene transcription in 
diverse cell types, including malignant cells, whereas BRDT expression is restricted to the testes.  
BRD2, 3, 4 are essential regulators of the expression or activity of several key oncogenic 
transcription factors, including v MYC avian myelocytomatosis viral oncogene homolog (MYC) 
and the androgen receptor (AR) {Shi 2014}. Transcription of the MYC gene is dependent on 
BET proteins in many cells {Mertz 2011}. Androgen receptor-dependent transcription of target 
genes requires BET proteins in prostate cancer cells {Asangani 2014}. Cancer cells addicted to 
MYC and AR are highly sensitive to BET protein inhibition {Asangani 2014, Delmore 2011, 
Mertz 2011}, which provides the basic therapeutic rationale for BET inhibition with GS-5829 for 
the treatment of cancer.
MYC promotes cell proliferation, cell survival, and metabolic adaptation and is frequently 
overexpressed in human cancers {Dang 2012}. Data generated at Gilead demonstrated MYC 
overexpression to be prevalent in 76% of prostate cancer (n = 60), 67% of diffuse large B-cell 
lymphoma (DLBCL) (n = 98), 65% of multiple myeloma (MM, n=30), 73% of colorectal cancer 
(n = 60), and 80% of ovarian cancer (n = 60) cases examined (PC-350-2083). These data are
consistent with literature that reports a high incidence of MYC expression in these and other 
cancers {Affer 2014, Barrans 2010, Chesi 2008, Chng 2011, Glitza 2014, Hawksworth 2010, 
Nesbit 1999, Nupponen 1998, Perry 2014}. The AR is a nuclear hormone receptor that is nearly
ubiquitously expressed in prostate cancer (PC-350-2083) and activates growth and survival 
signals both by binding to androgen, its natural ligand, and through androgen-independent 
mechanisms {Yuan 2014}.
A number of orally administered, BET-directed compounds (TEN-010, CPI-0610, OTX015, 
ZEN-3365, and GSK525762) are currently in early-stage clinical development for the treatment 
of solid tumors or hematologic cancers {Filippakopoulos 2014, Ghoshal 2016}. Initial evidence 
of clinical activity at tolerated doses has been reported for the BET inhibitor OTX015 in subjects 
with refractory hematological cancers {Amorim 2016, Berthon 2016}. GS-5829 is an orally 
available small-molecule inhibitor of BET proteins that is being developed by Gilead Sciences, 
Inc. for the treatment of solid tumors, including castrate-resistant prostate cancer (CRPC), 
estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) 
breast cancer (BrCa) (ER+/HER2- BrCa), and hematologic malignancies. In nonclinical studies, 

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GS-5829 inhibited cell growth and induced apoptosis of solid tumor and hematological cancer 
cells by inhibiting BET protein-dependent transcription of MYC and other oncogenic pathways, 
including transcription mediated by the AR in prostate cancer cells.
1.2.
GS-5829
1.2.1.
General Information
For further information on the GS-5829, refer to the current investigator’s brochure for GS-5829.
1.2.2.
Preclinical Pharmacology and Toxicology
1.2.2.1.
Absorption, Distribution, Metabolism, and Elimination 
GS-5829 shows moderate plasma protein binding and volumes of distribution in nonclinical 
species that are similar to or slightly higher than total body water. Systemic clearance in 
nonclinical species is generally well predicted from the rates of metabolism by hepatocytes.  
Since GS-5829 has high metabolic stability with human hepatic material in vitro, it is likely to 
show low clearance in humans. The major route of metabolism of GS-5829 involves 
hydroxylation of the 5-methyl moiety on the 3, 4-dimethly isoxazole ring catalyzed primarily by 
CYP3A4 and CYP3A5 enzymes in humans.  
Consistent with the moderate to high bioavailability seen in nonclinical species, GS-5829 shows 
high forward permeability across Caco-2 monolayers, and low efflux, but GS-5829 is a substrate 
of human P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).
GS-5829 has relatively high unbound fraction in cell culture medium containing fetal bovine 
serum.  Competitive dialysis between cell culture median and human, dog and mouse plasma 
yielded a ratio of unbound fractions of 5.7, 15.2 and 13.2 respectively.  
GS-5829 is unlikely to cause clinical interaction through inhibition of CYP1A2, CYP2C9, 
CYP2C19, or CYP2D6, CYP2B6, CYP2C8, CYP3A or UGT1A1, so the potential for causing 
drug interactions through inhibition of those enzymes is low.  GS-5829 is also a weak inhibitor 
of the human efflux transporters, P-gp and BCRP, and the uptake transporters, OATP1B1 and 
OATP1B3. 
1.2.2.2.
Nonclinical Toxicology
Nonclinical safety pharmacology and toxicology studies have characterized the safety of 
GS-5829 through single and repeat dose toxicology studies. All pivotal toxicology studies were 
conducted in full compliance with Good Laboratory Practice regulations (21 CFR 58). The scope 
of the nonclinical safety evaluation is consistent with the guidance issued by the International 
Conference on Harmonisation (ICH). 
In nonclinical pharmacology studies, GS-5829 showed no significant adverse effects on central 
nervous, respiratory or cardiovascular system functioning at the projected exposure and human 
target dose of 25 mg once daily.  

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The following target organs/systems were identified in the nonclinical toxicology studies: 
hematopoietic and male reproductive system (mice and dogs), the adrenal and skin (mice), and 
the gastrointestinal tract, respiratory and cardiac (dogs). With the exception of the adrenals in the 
mouse and the respiratory and cardiac hemorrhages observed in dogs, target organs are as 
expected based on the known pharmacology of GS-5829. The dog was the more sensitive 
species, with the no-observed-adverse-effect levels in the mouse and dog being 10 and 
0.03 mg/kg/day respectively. The severely toxic dose in 10% of mice and the highest 
non-severely toxic dose (HNSTD) in dogs were 25 and 0.1 mg/kg/day, respectively.  
Hematopoietic effects include decreases in white blood cells (WBC), lymphocytes, platelets and 
reticulocyte counts as well as mild reduced cellularity in the marrow in mice at doses of 
≥10 mg/kg/day. Minimal to marked decrease in bone marrow cellularity, decrease in 
lymphocytes in the lymphoid tissues (spleen, thymus, lymph nodes and gastrointestinal 
associated lymphoid tissue), decrease in neutrophils and platelets were observed at 
0.3 mg/kg/day in dogs. Elevated fibrinogen was also noted at 0.3 mg/kg/day in dogs. 
Mild to moderate alveolar (lung) hemorrhage was observed at ≥ 0.1 mg/kg/day in dogs. Mild 
hemorrhage in the left atrioventricular valve of the heart was seen at 0.3 mg/kg/day in 1 of 
6 dogs. The mechanism for the hemorrhage is not known.  Prothrombin time and partial 
thromboplastin time measurements were normal. The anatomic pattern of the hemorrhage in the 
lung field and microscopy was considered potentially consistent with pneumonia, however 
bacteria were not identified.  
In the male reproductive system, decreased testes weight with oligospermia/aspermia were 
observed in both mouse and dog studies at 25 and 0.3 mg/kg/day respectively. Minimal to 
moderate vacuolation of the seminiferous tubules occurred at ≥ 0.1 mg/kg/day in the dog. These 
changes are consistent with the known effects of a bromodomain inhibitor on the testes.
The gastrointestinal findings in the dog included minimal to mild mucosal atrophy, mucosal 
hemorrhage and crypt hyperplasia in the stomach or intestines at ≥ 0.1 mg/kg/day. Adrenal gland 
weight decreases were noted at 25 mg/kg/day and cytoplasmic vacuolation at ≥10 mg/kg/day in 
the mouse studies, of unknown cause. QT prolongation is not expected based on hERG, rodent 
and dog studies.  
1.2.3.
Clinical Experience of GS-5829
As of April 2017, 2 clinical studies have been initiated in which subjects have been dosed with 
GS-5829: a Phase 1 clinical study (GS-US-350-1599) in subjects with advanced solid tumors and 
lymphomas (initiated in March 2015) and a Phase 1b/2 clinical study (GS-US-350-1604) in 
subjects with metastatic castrate-resistant prostate cancer (mCRPC) (initiated in January 2016).  
The following summary was based on November 11, 2016 data cut unless specified otherwise.
1.2.3.1.
Study GS-US-350-1599
Study GS-US-350-1599 is an open label, Phase 1 study that includes subjects with advanced 
solid tumors, ER+/Her2- breast cancer, and lymphomas. This study is an ongoing, multicenter, 

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sequential dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and 
pharmacodynamics of GS-5829 in subjects with advanced solid tumors and lymphomas. This 
study includes a cohort of subjects with advanced stage breast cancer who receive GS-5829 
combined with exemestane or fulvestrant. Doses planned for this study are 0.6, 1.4, 2, 3, 4, 6, 9, 
and 12 mg once daily. 
Based on the data collected so far for GS-350-1599,  the most frequently reported AEs, occurring 
in ≥ 20% of the subjects in either group include abdominal pain, nausea, decreased appetite, 
fatigue, dehydration, diarrhea, hypotension, and vomiting. The majority of AEs have been 
≤Grade 2. Two out of 24 subjects (8.3%) have discontinued GS-5829 due to AEs.
Two DLTs were reported as of 11 November 2016: a DLT of Grade 3 thrombocytopenia was 
reported in 1 subject at 3 mg, and a second DLT of adrenal hemorrhage was reported in 1 subject
at 4 mg. Following the data-cut-off of 11 November 2016, two dose-limiting toxicities (grade 3 
thrombocytopenia, grade 3 AST elevation) occurred in two out of 3 subjects who were dosed at 
the 6 mg dose level. Therefore, the single agent MTD of GS-5829 from the dose escalation 
portion of Group 1 of this study was determined to be 4 mg daily.  
Additional information for Group 2 subjects with ER+/HER2- breast cancer are as follows: 
Treatment-emergent AEs were reported for 6 of the 7 subjects in Group 2: 3 in the 2-mg + 
exemestane group and 3 in the 2-mg + fulvestrant group. Adverse events reported by 2 or more 
subjects total in Group 2 included nausea (3 subjects), and vomiting, diarrhea, dehydration, and 
hypotension (2 subjects each). One event of vomiting was considered by the investigator to be 
Grade 3, and the remainder of the AEs were ≤ Grade 2. All remaining AEs occurred in ≤ 1 
subject per treatment group. No TEAE reported in Group 2 has led to study drug discontinuation. 
Enrollment to this cohort has been stopped when GS-US-350-1937 was being initiated.
1.2.3.2.
Study GS-US-350-1604
Study GS-US-350-1604 is an open-label, multicenter, sequential dose-escalation study to 
evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of GS-5829 as a 
single agent and combined with enzalutamide in subjects with mCRPC. The doses planned for 
this study are 1.4, 2, 3, 4, 6, and 9 mg once daily. One DLT of G3 fatigue, asthenia, and fall has 
been reported as of 11 November 2016.
Please refer to the current GS-5829 investigator’s brochure (IB) for additional details.
1.2.4.
Information about Exemestane
Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural 
substrate androstenedione. It acts as a false substrate for the aromatase enzyme and is processed 
to an intermediate that binds irreversibly to the active site of the enzyme, causing its inactivation, 
an effect also known as “suicide inhibition.” Exemestane significantly lowers circulating 
estrogen concentrations in post-menopausal women. In the US, exemestane is approved for the 
treatment of advanced breast cancer in postmenopausal women whose disease has progressed 
following tamoxifen therapy. For current information about exemestane (Aromasin ®) refer to 

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the regional prescribing information Appendix 8 or the summary of product characteristics in the 
pharmacy binder. 
1.2.5.
Information about Fulvestrant
Fulvestrant is an estrogen receptor antagonist that binds to the estrogen receptor in a competitive 
manner with affinity comparable to that of estradiol and down-regulates the ER protein in human 
breast cancer cells. In vitro studies demonstrated that fulvestrant is a reversible inhibitor of the 
growth of tamoxifen resistant as well as estrogen sensitive human breast cancer cell lines. In vivo 
tumor studies demonstrated that fulvestrant delayed the establishment of tumors from xenografts 
of human breast cancer MCF-7 cells in nude mice. Fulvestrant inhibited the growth of 
established MCF7 xenografts and of tamoxifen resistant breast tumor xenografts.  In the US, 
fulvestrant is approved for the treatment of hormone receptor (HR) positive metastatic breast 
cancer in postmenopausal women with disease progression following anti-estrogen therapy.  
1.3.
Rationale for This Study
Among all breast cancers, ER+ and HER2- tumors constitute the largest proportion,
approximately 65 to 70% {Howell 2010, Tan 2010}. These breast cancer subtypes are 
characterized by expressing the ER, a nuclear hormone receptor and transcription factor that 
promotes the expression of genes involved in cell growth and survival {Clark 1984}. 
Anti-estrogen endocrine therapies, such as aromatase inhibitors (AIs) and tamoxifen are the 
primary treatments for early stage ER+ BrCa, but many women relapse during or after 
completing these adjuvant hormonal therapies. In the metastatic setting, single-agent treatment 
with AIs, tamoxifen, or the selective ER degrader, fulvestrant, has limited benefit. When 
combined with other targeted therapies such as the cyclin-dependent kinase (CDK) 4/6 inhibitor, 
palbociclib, the first-line anti-estrogen therapy significantly improves progression-free survival 
(PFS). Standard of care includes sequential administration of endocrine therapies until hormone 
resistance occurs, at which time patients have no standard of care options and are usually 
transitioned to chemotherapy. Therefore, the development of effective therapies that improve 
response to endocrine therapy and prevent or reverse resistance continues to be of clinical 
importance.
Resistance to endocrine therapy is mediated by several mechanisms that enable reactivation of
ER-driven transcription under conditions of low estrogen (ie, estrogen-independent transcription
by the ER). These mechanisms include ER overexpression, activating ER mutations, increased
expression of ER co-activators, or increased expression of ER-target genes such as MYC and
cyclin D1 {Osborne 2011}. Importantly, BET proteins are required for both estrogen-dependent
and estrogen-independent transcription by the ER receptor. BRD4 and BRD3 are recruited to ER
target genes, including MYC, where they promote transcription by RNA polymerase II
{Nagarajan 2014, Sengupta 2015}. In preclinical studies, the BET inhibitor JQ1 decreased
ER-mediated gene transcription and inhibited the growth of ER+ tumors {Alluri 2014, Nagarajan 
2014, Sengupta 2015}. In addition, combination of JQ1 with fulvestrant significantly increased
time to disease progression in an endocrine-resistant ER+ xenograft mouse breast tumor {Feng 
2014}.

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The potency of GS-5829 and fulvestrant as single agents and in combination to reduce growth of 
estrogen-dependent breast cancer cell lines impact on cell growth was evaluated in colony 
survival assays and the results were summarized in IB Section 3.1.1.1.6. Consistent with the 
reported activity of BET inhibitors in ER+ BrCa, in cell lines dependent on estrogen for growth, 
cell viability was reduced with GS-5829 treatment, and the magnitude of the effect was increased 
with fulvestrant. These data suggest that BET proteins impact ER-dependent cell viability in 
vitro, and may combine well with fulvestrant in patients failing AI therapy.
We hypothesize that the combination of GS-5829 and an anti-estrogen such as fulvestrant may 
increase the efficacy of endocrine therapy in patients with advanced ER+ BrCa by targeting 
orthogonal mechanisms. The combination is expected to lead to overall greater inhibition of 
ER-dependent transcription by blocking distinct aspects of ER signaling (reduced
ligand-dependent ER activation with AI, reduced ER protein stability with fulvestrant, and
reduced BET-dependent transcription of ER target genes with GS-5829). By directly inhibiting
the transcription of ER target genes such as MYC, GS-5829 is hypothesized to block established
mechanisms of resistance to endocrine therapy. BET proteins also promote transcription of
several ER-independent cell cycle genes, including CDK6, which may additionally contribute to
the combination activity in ER+ BrCa cells. Data generated by Gilead have demonstrated that a
combination of fulvestrant and GS-5829 inhibits growth of ER+ cell BrCa lines in vitro to a
greater extent than either agent alone.
Figure 1-1.
Mechanism of Action of GS-5829 to Reduce Transcription of ER 
Target Genes in Cancer Cells

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Overall, the pre-clinical studies demonstrate that GS-5829 is a potent and selective inhibitor of 
BET proteins and support the use of GS-5829 to treat solid tumors and hematological cancers. 
1.3.1.
Rationale for Dose Selection
As of 11 November 2016, a total of 27 subjects have been dosed with single agent GS-5829 
once daily in Studies GS-US-350-1599 and GS-US-350-1604 and are evaluable for DLT 
assessment: 2 subjects at 0.6 mg, 1 subject at 1.4 mg, 5 subjects at 2 mg, 10 subjects at 3 mg,
9 subject at 4 mg. A DLT of thrombocytopenia at the 3 mg dose level and a DLT of adrenal 
hemorrhage at the 4 mg dose level have been reported. In addition, 6 breast cancer subjects in 
Group 2 of Study GS-US-350-1599 have been dosed with 2 mg GS-5829 in combination with 
either exemestane (n=3) or fulvestrant (n=3) and are evaluable for DLT assessment, with no 
DLT being reported. Based on the BLRM model (see Appendix 10), the probabilities of under-
dosing (DLT rate<16.7%), falling in the target interval of DLT rate (between 16.7% and 33.3%) 
and overdosing (DLT rate>33.3%) will be about 70%, 18% and 12%, respectively, if the starting 
dose level is at 4.0 mg in the Phase 1b portion of this study. The probabilities will be about 89%,
10%, and 1%, respectively, if the starting dose is at 3.0 mg. This means that there is a high 
chance (89%) of underdosing at 3.0 mg of GS-5829 in combination with standard of care and a 
low chance (12%) of overdosing at 4.0 mg of GS-5829 in combination with standard of care.  
Pharmacokinetics of GS-5829 when administered in combination with fulvestrant appear to be 
generally similar to that of GS-5829 administered as monotherapy. Based on the clinical safety 
and pharmacokinetic/pharmacodynamic data collected so far for GS-5829 and the dose-DLT 
model prediction, the starting dose of GS-5829 was selected to be 4.0 mg in the Phase 1b Dose 
Escalation.  
The recommended dose of GS-5829 to be combined with fulvestrant in the Randomized Phase 2 
Dose Expansion part of this study will not exceed the maximum tolerated dose (MTD) identified 
by the Phase 1b dose escalation. A lower dose may be chosen for the Randomized Phase 2 Dose 
Expansion study based on emerging safety, pharmacokinetic, pharmacodynamic, and efficacy 
results from this study and including additional safety data generated from other ongoing Phase 1 
and 2 studies with GS-5829.
1.4.
Risk/Benefit Assessment for the Study
Based on the systemic concentrations of GS-5829 measured in the repeat dose toxicity studies in 
mice and dogs, the margins of exposure at the severely toxic dose in 10% of rodents (STD10) in 
mice and HNSTD in dog are approximately 6.3- and 1-fold, respectively, at the anticipated 
clinically efficacious exposure. Another bromodomain inhibitor in development has identified 
thrombocytopenia as the earliest signs of toxicity in human studies, a toxicity which may be 
easily monitored.  
As of November 2016, a total of 40 subjects have been dosed with GS-5829 as monotherapy or 
in combination with standard of care through two ongoing studies: GS-US-350-1599 and
GS-US-350-1604.  The drug is generally well tolerated.  Assessments for AEs and monitoring 
for laboratory abnormalities are specified in the protocol and include symptom and AE 
assessment on Days 1 and 15 of the first two 28 day cycles, Day 1 of the third 28 day cycle, and 

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then every 28 days until end of treatment (EOT) which will be followed by a 30-day Safety 
Follow-Up Visit. Physical examinations will occur on Day 1 of each 28-day cycle until EOT
which will be followed by a 30-day Safety Follow-Up Visit.
The safety monitoring frequency is considered sufficient to identify potential AEs as they 
emerge. In addition, mitigation strategies are incorporated into the study design. The inclusion 
and exclusion criteria are designed to ensure subjects have acceptable organ function to be 
eligible for this study, such that confounding significant co-morbidities are excluded. Study 
medications will continue until disease progression, unacceptable toxicity, consent withdrawal, 
or subject’s refusal of treatment.
Exemestane and fulvestrant have been approved for treatment of advanced breast cancer in 
postmenopausal women whose disease has progressed either following tamoxifen or 
anti-estrogen therapy. The known toxicities for exemestane for this patient population are hot 
flushes, nausea, fatigue, increase sweating, increased appetite (Appendix 8).The known toxicities 
for fulvestrant are increased hepatic enzymes (ALT, AST and ALP), injection side pain, nausea, 
bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, vomiting, 
anorexia, asthenia, musculoskeletal pain, cough, dyspnea and constipation (Appendix 9).
1.5.
Potential Benefits
The combination of GS-5829 with fulvestrant is expected to lead to overall greater inhibition of 
ER-dependent transcription by blocking distinct aspects of ER signaling (reduced ER protein 
stability with fulvestrant, and reduced BET-dependent transcription of ER target genes with 
GS-5829). By directly inhibiting the transcription of ER target genes such as MYC, GS-5829 is 
hypothesized to block established mechanisms of resistance to endocrine therapy. Although 
Fulvestrant + CDK4/6 inhibitor has been approved as standard of care for second line treatment 
for metastatic ER+ breast cancer, there is no reported benefit on overall survival comparing to 
fulvestrant alone.  In addition this study will enable patients in countries who don’t have access 
to CDK4/6 inhibitor to participate as well as to explore any clinical activities of GS-5829 in 
combination with fulvestrant in both CDK4/6 inhibitor progressed and CDK4/6 inhibitor naïve 
setting. 
1.6.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.

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2.
OBJECTIVES
The primary objectives:
Phase 1b Dose Escalation

To characterize the safety and tolerability of GS-5829 in combination with fulvestrant and 
exemestane in subjects with advanced ER+/HER2- BrCa

To determine the MTD, or the recommended Phase 2 dose (RP2D) of GS-5829 in 
combination with fulvestrant in subjects with advanced ER+/HER2- BrCa
Randomized Phase 2 Dose Expansion

To evaluate the efficacy of GS-5829 in combination with fulvestrant compared to fulvestrant
alone in subjects with advanced ER+/HER2- BrCa as measured by PFS
The secondary objectives:
Phase 1b Dose Escalation

To evaluate the pharmacokinetics of GS-5829 in combination with fulvestrant in subjects 
with advanced ER+/HER2- BrCa
Randomized Phase 2 Dose Expansion

To evaluate the efficacy of GS-5829 in combination with fulvestrant compared to fulvestrant
alone in subjects with advanced ER+/HER2- BrCa, as measured by ORR and CBR evaluated 
according to RECIST v. 1.1 criteria. ORR is defined as the proportion of subjects with 
response (CR, or PR). CBR is defined as proportion of subjects with CR, PR, or SD that lasts 
for ≥ 24 weeks

To evaluate the safety and tolerability of GS-5829 in combination with fulvestrant compared 
to fulvestrant alone in subjects with advanced ER+/HER2- BrCa

To evaluate OS in subjects with advanced ER+/HER2- BrCa who receive GS-5829 in 
combination with fulvestrant compared to fulvestrant alone 
The exploratory objectives:
 
 
PPD

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3.
STUDY DESIGN
3.1.
Endpoints
The endpoints for this study are described in Section 8.
3.2.
Study Design
Phase 1b Dose Escalation: 
Cohorts of postmenopausal women with advanced ER+/HER2- BrCa, for whom no standard 
curative therapy exists and who are candidates for exemestane or fulvestrant, will be sequentially 
enrolled at progressively higher dose levels of oral GS-5829 in combination with standard doses 
of exemestane or fulvestrant. Up to 30 subjects will be enrolled in the Phase 1b Dose Escalation
portion of the study. The starting dose of GS-5829 has been determined to be 4 mg once daily 
based on safety information, pharmacokinetic and biomarker data from two ongoing studies 
(GS-US-350-1599, GS-US-350-1604) and recommendation by the BLRM model of dose-DLT 
relationship (Section 1.3.1).   
Eligible subjects will be assigned to either Group A or Group B based on prior treatment. Group 
A will initiate with GS-5829 orally once daily on C1D1 combined with 25 mg of exemestane 
administered orally once daily (or in accordance with locally approved labeling). The subject 
may initiate exemestane any time prior to, or on, C1D1.
Due to recent approvals of several CDK4/6 inhibitors in the treatment of ER+/Her2- breast 
cancers, as well as unmet medical needs for subjects who have progressed from these, a cohort of 
patients (approximately 60) who have progressed on prior CDK4/6i (plus AI) will be included in 
phase 2 part of the study. In addition, the main objective of the phase 2 will be on evaluating
safety and efficacy of GS-5829 in combination with fulvestrant. Therefore, enrollment in Group 
A will be stopped after completion of the 4 mg GS-5829 dose level safety assessments. Subjects 
who were previously enrolled/treated in Group A will continue to be followed and managed 
according to the protocol as outlined below.
Group B will initiate GS-5829 orally once daily on C1D1 with fulvestrant administered 
intramuscularly every 28 days (± 3 days) (or in accordance with locally approved labeling). The 
subject may initiate fulvestrant any time prior to, or on, C1D1. For subjects whom are treatment 
naïve (in metastatic setting) and for all subjects for whom C1D1 is the subject’s first dose of 
fulvestrant, a one-time additional dose of 500 mg fulvestrant should be administered on Cycle 1 
Day 15 (C1D15).  
The doses of GS-5829 for each Dose Level are shown in the following table.

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from this study. At least 6 subjects should have already been treated and evaluated at that dose 
level prior to enrolling subjects in the Randomized Phase 2 Dose Expansion.
Dose Limiting Toxicity (DLT) Definition
A DLT is a toxicity defined below and considered possibly related to GS-5829 if occurring during
the DLT assessment window (Day 1 through Day 28) in each combination therapy cohort:

Grade ≥ 4 neutropenia (absolute neutrophil count [ANC] < 500/mm3)

Grade ≥ 3 neutropenia (ANC < 1000/mm3) with fever (a single temperature of > 38.3°C or a 
sustained temperature of ≥38°C for more than one hour)

Grade ≥ 3 thrombocytopenia

Grade ≥ 2 bleeding (e.g. gastrointestinal, respiratory, epistaxis, purpura)

Grade ≥ 3 or higher non-hematologic toxicity, except:
o
Grade 3 nausea or emesis with maximum duration of 48 hours on adequate medical 
therapy
o
Grade 3 diarrhea which persists for < 72 hours in the absence of adequate medical 
therapy

Grade ≥ 2 non-hematologic treatment-emergent adverse event (TEAE) that in the opinion of 
the investigator is of potential clinical significance such that further dose escalation would 
expose subjects to unacceptable risk

Treatment interruption of ≥7 days due to unresolved toxicity
For certain toxicities, such as laboratory assessments without a clear clinical correlate, a 
discussion between the investigator and the Gilead medical monitor may take place to determine 
if this AE should be assessed as a DLT. However, any Grade 3 or Grade 4 elevation in aspartate 
transaminase (AST) or alanine transaminase (ALT) associated with a Grade 2 elevation in 
bilirubin that is at least possibly related to study drug will be considered a DLT.
Randomized Phase 2 Dose Expansion:
Approximately 120 female subjects who are post-menopausal with ER+/HER2- BrCa and who 
have had disease progression following endocrine therapy will be randomized in a 2:1 ratio to 
receive fulvestrant + GS-5829 or fulvestrant alone. Randomization will be stratified by prior 
cyclin-dependent kinase 4/6 (CDK4/6) inhibitor plus AI status (naïve vs. progressed). The target 
number of subjects in each of the 2 strata will be approximately 60 (40 for GS-5829 in 
combination with fulvestrant and 20 for fulvestrant alone). GS-5829 and fulvestrant will be 
initiated on C1D1. Each cycle consists of 28 days.

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Figure 3-1.
Randomized Phase 2 Dose Expansion
*  
Randomization will be stratified by prior CDK4/6 inhibitor plus AI status (naïve vs. progressed).  The target number of 
subjects in each of the 2 strata will be approximately 60 (40 for GS-5829 in combination with fulvestrant and 20 for 
fulvestrant alone).
3.3.
Study Treatments
Subjects who meet eligibility criteria will receive GS-5829 orally once daily combined with either 
25 mg of exemestane orally once daily or with fulvestrant intramuscularly on Day 1, 15 (for 
whom C1D1 is the subject’s first dose of fulvestrant), 29 and then every 28 days (± 3 days). 
Subjects in the Phase 1b Dose Escalation portion may initiate exemestane (Group A) or 
fulvestrant (Group B) any time prior to, or on, C1D1. Each cycle will consist of 28 days. Safety
and efficacy assessments will occur on an outpatient basis including an assessment of tumor
response, physical exam, vitals, ECG, collection of blood samples (for routine safety labs,
GS-5829 pharmacokinetic, pharmacodynamic markers, and biomarkers at applicable visits), and
assessment of AEs. In addition, subjects will undergo a CT scan (or MRI) scan every 8 weeks for 
the first year, then every 12 weeks.  
Subjects who do not show evidence of disease progression may continue receiving GS-5829 
combined with either exemestane (Group A) or fulvestrant (Group B) until disease progression 
(clinical or radiographic), unacceptable toxicity, withdrawal of consent, or death, whichever 
comes first.  
Following treatment discontinuation, subjects will be followed for safety for 30 days from last 
dose of study drug. Subjects in the Randomized Phase 2 Dose Expansion portion of the study 
will also be followed for up to two years for OS from the last dose of study drug.
3.4.
Duration of Treatment
Subjects may continue receiving GS-5829 once daily until disease progression (clinical or 
radiographic), unacceptable toxicity, withdrawal of consent or death, whichever comes first. See 
Section 3.5 for criteria for study drug discontinuation.  

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3.5.
Criteria for Discontinuation of Study Drug
Study medication may be discontinued in the following instances:

Documented progression of malignant disease

Death

Investigator discretion 

Non-compliance with study drug

Important protocol deviation 

Pregnancy

Subject decision

Lost to follow-up

Study termination by the sponsor

Adverse Event
3.6.
Criteria for Removal from Study
Subjects may be removed from the study for the following reasons:

Documented progression of malignant disease

Death

Investigator discretion 

Withdrawal of consent 

Lost to follow-up

Important protocol deviation

Pregnancy

Study termination by the sponsor

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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Up to 30 subjects who meet the eligibility criteria will be enrolled in the Phase 1b Dose 
Escalation portion of the study. 
Up to 120 subjects who meet the eligibility criteria will be enrolled in the Randomized Phase 2 
Dose Expansion portion of the study. 
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study:
1) 18 years of age, female
2) Histologically or cytologically confirmed breast cancer with evidence of metastatic or locally 
advanced disease not amenable to resection or radiation therapy with curative intent and who 
have progressed during treatment with at least one prior hormonal therapy
a) Phase 1b Dose Escalation - Subjects may have had unlimited prior hormonal therapy and 
a total of 2 prior chemotherapy regimens (adjuvant chemotherapy is considered 1 
regimen). Subjects may have progressed on fulvestrant or exemestane 
b) Randomized Phase 2 Dose Expansion - Subjects may have disease progression during 
treatment or within 12 month of completion of endocrine therapy (tamoxifen, and/or AI) 
in the adjuvant setting, or disease progression during treatment with endocrine therapy 
(tamoxifen, AI or CDK4/6 inhibitor plus AI) for advanced/metastatic disease. Subjects 
may have had unlimited prior hormonal therapy, but must be naïve to fulvestrant in the 
metastatic setting.  A total of 2 prior chemotherapies are allowed, however, only one for 
metastatic disease is permitted.
3) Documentation of ER positive breast cancer (≥ 1% positive stained cells by local standards) 
based on the most recent tumor biopsy, unless bone-only disease
4) Documented HER2-negative tumor based on local testing on most recent tumor biopsy 
(immunohistochemistry score 0/1+ or negative by in situ hybridization HER2/CP17 ratio < 2 
or for single probe assessment HER2 copy number < 4)

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5) Post, pre or peri-menopausal subjects considered to be in the post-menopausal state as 
defined by one of the following:
a) Age ≥ 60 years
b) Age < 60 years and cessation of regular menses for at least 12 consecutive months in the 
absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and serum 
estradiol and follicle-stimulating hormone (FSH) level within the post-menopausal range
c) Prior bilateral oophorectomy
d) Pre-/peri-menopausal women can be enrolled if amenable to be treated with the
luteinizing-hormone releasing hormone (LHRH) agonist goserelin. Subjects must have 
commenced treatment with goserelin or an alternative LHRH agonist at least 4 weeks 
prior to C1D1. If subjects have received an alternative LHRH agonist prior to study entry,
they must switch to goserelin on or before C1D1 for the duration of the study
6) Measurable disease defined per RECIST v. 1.1 or bone-only disease must have a lytic or 
mixed lytic blastic lesion that can be accurately assessed by CT or MRI. Subjects with 
bone-only disease and blastic-only metastases are not eligible
7) All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before the start of
study drug dosing (with the exception of alopecia [Grade 1 or 2 permitted] and neurotoxicity
[Grade 1 or 2 permitted])
8) Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
9) Life expectancy of ≥3 months, in the opinion of the investigator
10) Adequate organ function defined as follows:
a) Hematologic:  Platelets ≥ 100 x 109/L; Hemoglobin ≥9.0 g/dL; ANC ≥ 1.5 x 109/L 
(without platelet transfusion or any granulocytic growth factors within previous 7 days of 
the hematologic laboratory values obtained at screening visit)
b) Hepatic: AST / ALT ≤ 2.5 x upper limit of normal (ULN) (if liver metastases are present, 
≤ 5 x ULN); total or conjugated bilirubin ≤ 1.5 x ULN
c) Renal: Serum Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min as 
calculated by the Cockroft-Gault method
11) Coagulation: International Normalized Ratio (INR) ≤1.2 
12) Negative serum pregnancy test (Appendix 5)
13) Female subjects of childbearing potential who engage in heterosexual intercourse must agree 
to use protocol specified method(s) of contraception as described in Appendix 5

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14) Females who are nursing must agree to discontinue nursing before C1D1
15) Able and willing to provide written informed consent to participate in the study
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
1) History or evidence of clinically significant disorder, condition, or disease that, in the opinion 
of the investigator or the Gilead medical monitor would pose a risk to subject safety or 
interfere with the study evaluations, procedures, or completion
2) Known brain metastasis or leptomeningeal disease. Note: if treated and stable at least 
6 months prior to enrollment, subject is eligible.
3) Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, 
active or chronic bleeding event within 28 days prior to C1D1, uncontrolled cardiac 
arrhythmia, or psychiatric illness/social situation that would limit compliance with study 
requirements as judged by treating physician
4) Myocardial infarction, symptomatic congestive heart failure (New York Heart Association
Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within
6 months of C1D1
5) Major surgery, defined as any surgical procedure that involves general anesthesia and a 
significant incision (i.e., larger than what is required for placement of central venous access, 
percutaneous feeding tube) within 28 days of C1D1
6) Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the 
absorption of GS-5829, including any unresolved nausea, vomiting, or diarrhea that is 
CTCAE Grade > 1
7) Minor surgical procedure(s) within 7 days of enrollment or randomization, or not yet 
recovered from prior surgery (placement of central venous access device, fine needle 
aspiration, or endoscopic biliary stent ≥ 1 day before enrollment or randomization is 
acceptable)
8) History of a concurrent or second malignancy, except for: adequately treated local basal cell 
or squamous cell carcinoma of the skin; cervical carcinoma in situ; superficial bladder 
cancer; adequately treated Stage 1 or 2 cancer currently in complete remission; any other 
cancer that has been in complete remission for ≥ 5 years

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9) Anti-tumor therapy (chemotherapy, chemoradiation, radiation, antibody therapy, molecular 
targeted therapy) within 21 days or 5 half-lives whichever is longer, of C1D1 (6 weeks for 
nitrosoureas, mitomycin C, or molecular agents with t1/2 > 10 days); 5 half-lives of any 
investigational drug. Concurrent use of goserelin for pre-/peri-menopausal breast cancer and 
exemestane or fulvestrant per the protocol are permitted
10) History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia 
method) at screening is prolonged (> 470 ms). Subjects who screen fail due to this criterion 
are not eligible to be re-screened
11) Prior exposure to any bromodomain (BET) inhibitors 
12) Known hypersensitivity to the study drugs (GS-5829, fulvestrant or exemestane), the 
metabolites, or formulation excipients
13) Immunotherapy within 6 months of C1D1
14) Evidence of bleeding diathesis or clinically significant bleeding, within 28 days of C1D1 or 
history of hemoptysis of > 2.5mL/1 teaspoon within 6 months of C1D1
15) Anticoagulation/antiplatelet therapy within 7 days of C1D1, including acetylsalicylic acid, 
low molecular weight heparin, or warfarin
16) Known human immunodeficiency virus (HIV) infection
17) Hepatitis B surface Antigen (HBsAg) positive
18) Hepatitis C virus (HCV) antibody positive with HCV RNA positive
19) Use of moderate/strong cytochrome P450 (CYP) 3A4 inhibitors or moderate/strong CYP3A4 
inducers within 2 weeks prior to C1D1
20) History of high grade esophageal or gastric varices

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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Enrollment
This is an open-label study. All baseline tests and procedures must be completed prior to the 
administration of the first dose of study drug on Day 1. It is the responsibility of the investigator 
to ensure that subjects are eligible for the study prior to enrollment. 
Up to 30 subjects will be enrolled in the Phase 1b Dose Escalation portion of the study, each 
subject will be assigned to either Group A (exemestane +GS-5829) or B (fulvestrant + GS-5829) 
based on prior treatment. Enrollment in Group A will be stopped after completion of the 4 mg 
GS-5829 dose level safety assessments. Subjects who were previously enrolled/treated in Group 
A will continue to be followed and managed according to the protocol as outlined below.
Approximately 120 female subjects who are post-menopausal with ER+/HER2- BrCa and who 
have had disease progression following endocrine therapy will be randomized in a 2:1 ratio to 
receive fulvestrant + GS-5829 or fulvestrant alone. Randomization will be stratified by prior 
CDK4/6 inhibitor status plus AI (naïve vs. progressed).  The target number of subjects in each of 
the 2 strata will be approximately 60 (40 for GS-5829 in combination with fulvestrant and 20 for 
fulvestrant alone). 
A subject will be considered enrolled once they have been registered in the Interactive Web 
Response System (IxRS).
5.2.
Description and Handling of GS-5829
5.2.1.
Formulation
GS-5829 will be supplied as round, plain-faced tablets containing 1 mg or 5 mg. The 1 mg tablet 
is film-coated gray and the 5 mg tablet is film-coated orange.
In addition to the active ingredient, 1 mg tablets contain the following commonly used 
excipients: microcrystalline cellulose, lactose monohydrate, crospovidone, magnesium stearate, 
polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and iron oxide black.  
In addition to the active ingredient, 5 mg GS-5829 tablets contain the following commonly used 
excipients: microcrystalline cellulose, lactose monohydrate, crospovidone, magnesium stearate, 
polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, FD&C yellow #6, and iron oxide
yellow.
5.2.2.
Packaging and Labeling
GS-5829 tablets are provided in white, high density polyethylene bottles with desiccant and 
polyester packing material. Each bottle contains 30 tablets and is enclosed with a white, 
continuous thread, child-resistant screw cap with an induction-activated, aluminum-faced liner.

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Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the United States Food and Drug Administration 
(FDA), EU Guideline to Good Manufacturing Practice – Annex 13 (Investigational Medicinal 
Products), and/or other local regulations.
5.2.3.
Storage and Handling
GS-5829 tablets should be stored at controlled room temperature until required for 
administration. Controlled room temperature is defined as 25°C (77°F); excursions are permitted 
between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the label. 
Until dispensed to the subjects, all bottles of study drug should be stored in a securely locked 
area, accessible only to authorized site personnel. To ensure the stability and proper 
identification, the drug product should not be stored in a container other than the container in 
which it was supplied. Consideration should be given to handling, preparation, and disposal 
through measures that minimize drug contact with the body. Appropriate precautions should be 
followed to avoid direct eye contact or exposure when handling GS-5829 tablets.
Commercially available product of exemestane and fulvestrant will be used for the study.  
Further information regarding formulation is available in the Prescribing Information for 
commercial products.
5.3.
Dosage and Administration of GS-5829, Exemestane and Fulvestrant
GS-5829 tablets will be provided by Gilead Sciences, Inc. and will be taken orally. Initiation of 
treatment with the study drug will take place after enrollment and cohort assignment.  Subjects 
will take their dose of study drug at approximately 24-hour intervals. Tablets should be taken 
whole, they should not be chewed or crushed. To reduce inter-subject variability on efficacy and 
safety, subjects will be instructed to take GS-5829 approximately 1 hour before or 2 hours after a 
meal. Grapefruit juice is prohibited while on study drug.
GS-5829 tablets will be self-administered orally once daily, beginning on C1D1 of the study and 
thereafter at approximately the same time each day until EOT.
For subjects in Group A (Phase 1b), exemestane 25 mg tablets will be self-administered orally 
once daily (or in accordance with locally approved labelling), beginning on C1D1 of the study 
and thereafter at approximately the same time each day until the EOT. Exemestane will be 
dispensed to subjects at visits on the first day of each cycle. 
For subjects in Group B (Phase 1b) and in the Phase 2 Dose Expansion, fulvestrant will be 
administered intramuscularly (in accordance with locally approved labeling) by the clinic staff 
approximately every 28 days (± 3 days) until the EOT.  
For subjects in the Randomized Phase 2 Dose Expansion phase and for subjects in Group B of 
the Phase 1b Dose Escalation whom are treatment naïve (in metastatic setting) and for all 

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subjects for whom C1D1 is the subject’s first dose of fulvestrant, a one-time additional dose of 
500 mg fulvestrant will be administered on C1D15 (± 3 days).
5.3.1.
Dose Adjustment of GS-5829
If at any time in the study, a subject experiences a toxicity consistent with a Grade 4 AE that is 
deemed to be related to GS-5829, GS-5829 treatment will be discontinued permanently, with the 
exception of Grade 4 neutropenia, thrombocytopenia, or alopecia. If a subject experiences
non-hematologic Grade 3 toxicity consistent with a DLT (See Section 3.2), dosing with GS-5829 
will be postponed until the toxicity is resolved to Grade 0 or 1 (as defined by the CTCAE, 
version 4.03) or returns to the subject’s baseline value. If the toxicity resolves to Grade 0 or 1 or 
returns to the subject’s baseline value within 28 days from the start of the event, the subject may 
resume dosing of GS-5829 at a dose that is at least one dose level lower after discussion with the 
Gilead medical monitor (See Table 5-1). If a subject has Grade 4 neutropenia, Grade 3 
neutropenia with fever, or Grade 3 thrombocytopenia, GS-5829 should be interrupted for up to 
28 days and/or until the toxicity resolves to < Grade 1. If the Grade 4 neutropenia or Grade 3 
fever and neutropenia resolves within 4 days (7 days for Grade 3 thrombocytopenia), then the 
subject may resume dosing at the same dose. If the Grade 4 neutropenia or Grade 3 fever and 
neutropenia takes > 4 days (> 7 days for Grade 3 thrombocytopenia), but within 28 days to 
recover, then the dose of GS-5829 must be resumed at a lower dose. If the Grade 4 neutropenia, 
Grade 3 fever and neutropenia or Grade 3 or higher thromboctyopenia takes longer than 28 days 
to recover then GS-5829 must be permanently discontinued. Grade 4 thrombocytopenia observed 
at any time must be followed by a dose reduction.
If the recurrent toxicity is hematologic a second dose decrease is allowed (lowest dose allowed is
2 mg) in either total daily dose or by a change in schedule such that the total amount of GS-5829 
administered over a 28 day period is decreased by at least 25%.
Table 5-1.
Dose Reduction of GS-5829
HEMATOLOGICAL ADVERSE EVENTS
Neutropenia
Grade ≤ 3 Neutropenia
Maintain current dose level and schedule.
Grade 4 neutropenia (or occurrence of Grade 
≥ 3 neutropenia (ANC < 1000/mm3) with 
fever (a single temperature of > 38.3°C or a 
sustained temperature of ≥38°C for more 
than one hour) or infection
Hold dosing with GS-5829 until the toxicity is resolved to 
≤Grade 1. If the toxicity resolves to ≤Grade 1 within 4 days, the 
subject may resume dosing of GS-5829 at the same dose. If 
recovery to Grade ≤1 takes > 4 days, but within 28 days, then the 
subject may resume dosing of GS-5829 at a dose that is at least one 
dose level lower after discussion with the Gilead medical monitor.  
Granulocyte colony-stimulating factor (GCSF) is allowed (but not 
concurrent with GS-5829)

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HEMATOLOGICAL ADVERSE EVENTS
Thrombocytopenia
Grade ≤ 2 Thrombocytopenia
Maintain current dose level and schedule.
Grade 3 Thrombocytopenia 
Hold dosing with GS-5829 until the toxicity is resolved to 
≤Grade 1. If the toxicity resolves within 7 days, the subject may 
either resume at the same dose or a dose with is one level lower or at 
an intermittent dosing schedule (at least 25% less GS-5829 in a 
28 day dosing period) after discussion with the Gilead medical 
monitor. If the thrombocytopenia takes 7-28 days to recover then the 
subject must resume at a dose one level lower or at an intermittent 
dosing schedule after discussion with the Gilead medical monitor.
Grade 4 Thrombocytopenia
Hold dosing with GS-5829 until the toxicity is resolved to 
≤Grade 1. If the toxicity resolves within 28 days, the subject may 
either resume at a dose with is at least one level lower, or at 
intermittent dosing schedule (at least 25% less GS-5829 in a 28 day 
dosing period) after discussion with the Gilead medical monitor.
NON-HEMATOLOGICAL ADVERSE EVENTS
Hepatic Adverse Events (elevations in ALT or AST and/or bilirubin)
Grade 1
(ALT/AST ≤ 3 x ULN)
(Bilirubin ≤ 1.5 x ULN)
Maintain current dose level and schedule.
Grade 2
(ALT/AST > 3-5 x ULN)
(Bilirubin>1.5 -≤ 3 x ULN)
Maintain current dose level and schedule. Monitor ALT, AST, ALP, 
and bilirubin at least once a week.
Grade 3 
Hold dosing until ≤ Grade 2. 
Permanently discontinue if any Grade 3 or Grade 4 elevation in AST 
or ALT associated with a Grade 2 elevation in bilirubin
Grade 4
Permanently discontinue GS-5829
Non-Hepatic, Non-Hematologic Adverse Events
Grade ≤ 2
No change in dosing required. Dosing may be interrupted until 
Grade ≤ 1 or baseline
Grade 3
Hold dosing until ≤ Grade 1 and decrease dose by at least one dose 
level lower or at intermittent dosing schedule (at least 25% less 
GS-5829 in a 28 day dosing period) after discussion with the Gilead 
medical monitor.
Grade 4
Permanently discontinue GS-5829
For subjects only enrolled to Phase 2 part of the study: if a subject tolerates a reduced dose for > 
4 weeks, GS-5829 dose may be increased to the next higher dose level, at the discretion of the 
investigator and after discussion with Gilead medical monitor. Successive adjustments to 
progressively higher dose levels can be made at 4-weeks intervals up to the starting dose level.

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If the toxicity does not resolve or return to baseline, or subject experiences a recurrence of the 
toxicity after restarting study drug at a lower dose or if the toxicity does not resolve within 
28 days, study drug(s) GS-5829, exemestane (Group A Phase 1b) or fulvestrant will be 
permanently discontinued and the subject will return for an EOT and a 30-day Safety Follow-Up 
visit.  If a subject who is randomized to the combination arm discontinues one study drug for any 
reason, such as toxicity the other study drug will be discontinued as well.
If the subject was not receiving GS-5829 at the time disease progression was documented 
(e.g., due to reversible toxicity), after discussion with the Gilead medical monitor, GS-5829 may 
be re-started if the criteria for resuming treatment are met and the investigator feels it is in the 
subject’s best interest to do so.
If a subject develops a recurrence of the same Grade 3 or 4 hematologic or any non-hematologic 
toxicity that the investigator considers related to GS-5829 and is clinically significant at the 
lower dose, then the subject should be permanently discontinued from all study drug(s).
After the 28 day DLT period in the Phase 1b Dose Escalation and at any time in the Randomized 
Phase 2 Dose Expansion, in the event of a Grade 2 hematologic or non-hematologic toxicity the 
investigator considers related to GS-5829, GS-5829 may be interrupted per the investigator’s 
discretion for a maximum of 28 days and resumed at either the same or a lower dose. 
Subjects whose dose of exemestane (Group A Phase 1b) or fulvestrant is interrupted for a 
non-drug related toxicity for up to 28 days, or whose dose of GS-5829 is interrupted for up to
28 days, and are deemed by the investigator to be clinically benefiting from the combination 
treatment prior to dose interruption, may resume combination treatment. 
Non-drug related dose interruptions for longer than 15 or 28 days (exemestane or fulvestrant 
respectively), or longer than 28 days for GS-5829 in subjects who do not have disease 
progression may be considered for resumption of study drugs after discussion with the Gilead 
medical monitor.
No dose reduction of GS-5829 below 3 mg is allowed.  
Table 5-2.
Dose Reduction of GS-5829
Dose at time of toxicity (mg)
Restarting dose level (mg)
9
6
6
4
4*
3**
3
2
*
Dose level 1
**  Dose level -1

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5.3.2.
Dose Adjustment of Exemestane (Group A Phase 1b)
Since there is no anticipated drug-drug interaction between GS-5829 and exemestane, the dose, 
route and schedule for administration of exemestane in Group A is provided in package insert 
included in Appendix 8. Dose adjustment for GS-5829 is provided in Section 5.3.1.
5.3.3.
Dose Adjustment of Fulvestrant
Since there is no anticipated drug-drug interaction between GS-5829 and fulvestrant, the dose, 
route and schedule for administration of fulvestrant in the Phase 1 portion and the Phase 2 
portion is provided in package insert included in Appendix 9. Dose adjustment for GS-5829 is 
provided in Section 5.3.1.
5.4.
Prior and Concomitant Medications
Pre-/peri-menopausal subjects must have commenced treatment with goserelin or an alternative 
LHRH agonist at least 4 weeks prior to C1D1. If subjects have received an alternative LHRH 
agonist prior to study entry, they must switch to goserelin for the duration of the study on or 
before C1D1.
Subjects enrolling in the Phase 1b Dose Escalation portion of the study may have progressed on 
fulvestrant or exemestane.
Subjects enrolling in the Randomized Phase 2 Dose Expansion portion of the study may not have 
received prior fulvestrant.
In vitro data indicates GS-5829 is a substrate of CYP3A4. Co-administration of CYP3A4 
inhibitors may increase GS-5829 exposure. As such, co-administration of moderate and strong 
CYP3A4 inhibitors with study drug is prohibited in this study. Co-administration of CYP3A4 
inducers may decrease GS-5829 exposure. As such, moderate and potent CYP3A4 inducers are 
prohibited while subject is on study drug and within 2 weeks prior to study drug. Examples of 
moderate and strong CYP3A4 inhibitors and inducers are provided in the table below.
Table 5-3.
Examples of Concomitant Medications Prohibited in this Study
Moderate
Strong
CYP3A4 Inhibitor
aprepitant, ciprofloxacin, crizotinib, 
diltiazem, erythromycin, fluconazole, 
imatinib, verapamil
clarithromycin, conivaptan, grapefruit 
juice, itraconazole, ketoconazole, 
nefazodone, posaconazole, telithromycin, 
voriconazole
CYP3A4 Inducer
bosentan, modafinil, nafcillin
carbamazepine, phenytoin, rifampin, 
St. John’s wort

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Toxicology data from dogs demonstrated minimal to moderate gastrointestinal, pulmonary, 
muscular and intracardiac bleeding. The mechanism for the bleeding is not understood.  
Anticoagulant medications are prohibited on study. This includes vitamin K antagonists 
(e.g., warfarin), low molecular weight heparin, Factor Xa inhibitors, thrombin inhibitors and 
aspirin. If anticoagulation/antiplatelet therapy needs to be initiated while on study treatment, the 
investigator should consult with the Gilead medical monitor to determine if study treatment 
should be discontinued.
5.5.
Accountability for GS-5829, Exemestane and Fulvestrant
The investigator is responsible for ensuring adequate accountability of all used and unused 
investigational medicinal products (IMP). This includes acknowledgement of receipt of each 
shipment of IMP (quantity and condition). All used and unused IMP dispensed to subjects must 
be returned to the site.
Study drug (GS-5829 and fulvestrant (only for sites outside of US)) accountability records will 
be provided to each study site to:

Record the date received and quantity of study drug kits

Record the date, subject number, subject initials, the study drug kit number dispensed

Record the date, quantity of used and unused study drug returned, along with the initials of 
the person recording the information.
5.5.1.
GS-5829, Exemestane (Group A Phase 1b) and Fulvestrant Investigational 
Medicinal Product Return or Disposal
Study drugs should be retrieved from each subject at the end of each dispensing interval. The 
quantity of study drug and the date returned by the subject should be recorded in the study drug 
accountability records. Whenever possible, study drug returned by the subject should be retained 
for review by the study site monitor prior to destruction.
For additional information about study drug accountability, return and disposal, refer to 
Section 9.1.7. 

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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. Additional information is 
provided in the study procedures manual.
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
Safety and tolerability assessments will include regular monitoring of AEs, changes from 
baseline in laboratory variables, physical examinations, vital signs, and special safety 
assessments like ECGs. 
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any non-serious AEs 
related to protocol-mandated procedures on the AEs electronic case report form (eCRF). All 
other untoward medical occurrences observed during the Screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF. 
See Section 7 for additional details.
6.1.
Subject Enrollment and Treatment Assignment
Subjects will be assigned a unique screening number at the time of consent. Subject eligibility 
will be established at the conclusion of the screening evaluations. Once eligibility is confirmed, 
subjects will be assigned a unique subject number. The screening number and/or subject ID will 
be assigned for that individual subject by Gilead. The investigator will submit an enrollment 
form to Gilead and/or designee for review and approval prior to enrollment of the subject. 
It is the responsibility of the investigator to ensure that each subject is eligible for the study 
before start of treatment. 
6.2.
Study Procedures Descriptions
6.2.1.
Informed Consent
All subjects must sign and date the most recent Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC) approved informed consent form before any study procedures are 
performed.
 
PPD

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Subjects who screen fail must re-sign the informed consent, in the event any screening 
procedures will be performed outside of the 28-day screening window from the time of the first 
informed consent.
6.2.2.
Medical History
A complete medical history will be obtained by the investigator or qualified designee at 
screening and recorded on the eCRF. Medical history will include information on the subject’s 
significant past medical events (e.g., prior hospitalizations or surgeries), a review of the disease 
under study, prior anti-cancer therapies, and any concurrent illnesses. 
6.2.3.
Prior and Concomitant Medications
All medications taken up to 30 days prior to the screening visit will be recorded on the eCRF. In 
addition, supportive therapies given during the course of the study (e.g. blood transfusion, 
growth factor) should be collected and recorded on the eCRF.
At each study visit, the site will capture any and all medications taken by the subject since the 
last visit or during the visit (as applicable). Concomitant medications include prescription and 
non-prescription medications, pre-infusion medications (e.g. anti-emetics), and vitamins and 
minerals.
6.2.4.
Physical Examination
The investigator or qualified designee will perform a complete physical examination at 
designated time points during the study (Refer to Appendix 2). Pre-dose abnormal findings will 
be reported on the medical history page of the eCRF. Any changes from the pre-dose baseline 
physical examination that represent a clinically significant deterioration will be documented on 
the AE page of the eCRF. Screening and End of Treatment (EOT) physical examinations will be 
complete physical examinations. Beginning at C1D1, a modified physical examination will be 
performed to monitor for any changes, and will also include weight and assessment of 
disease-related clinical signs and symptoms.
Weight (without shoes) should be measured with each physical examination.
Height (without shoes) should be measured at screening only.
6.2.5.
Vital Signs
Vital signs will include blood pressure, respiratory rate, pulse, and temperature. All 
measurements will be recorded on the appropriate eCRF page with appropriate source 
documentation. Any abnormal measurements may be repeated and reported as AEs if 
appropriate. All measures of blood pressure will be performed using standard 
sphygmomanometry. Measurements of blood pressure should be taken per institutional 
guidelines.

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C1D1 vital signs will be taken within 15 min pre-GS-5829 dose and 2 and 4 hours post dose 
(+/- 15 min). At all subsequent visits, vital signs will be taken pre-GS-5829 dose only.
6.2.6.
Electrocardiogram 
12-lead electrocardiograms (ECGs) reporting ventricular rate, PR, QRS, QT, and QTc intervals 
will be obtained at the applicable study visits and transferred to a central vendor for storage. 
Triplicate ECGs will be collected at any time during the Screening window, C1D1, Day 1 of 
Cycles 2-6 (at pre-dose), and at EOT. In the Phase 1b Dose Escalation phase of the study, 
triplicate ECGs will be collected on C1D1 at pre-dose and 1-4 hrs post-dose and on C1D15 at 
pre-dose, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, and 8 hours post dose (+/- 20 min). In the 
Randomized Phase 2 Dose Expansion phase of the study, triplicate ECGs will be collected on 
C1D1 at pre-dose and 1-4 hrs post-dose and on C1D15 at pre-dose, 1 hour, 2 hours, 4 hours, and 
6 hours post dose (+/- 20 min).
ECGs should always be collected prior to pharmacokinetics (or any other blood draw) if they are 
to be collected at the same nominal time point. Subjects should be resting quietly and free of 
distraction (e.g., television, conversation) for 10 minutes prior to ECG collection and ECGs 
should be collected over a 5 minute window at each time point.
The investigator or qualified designee will review all ECGs. The ECG tracings will be 
maintained in the source documentation of each subject and the appropriate data reported on the 
eCRF.  
6.2.7.
Echocardiogram
Echocardiograms will be performed at the time points listed in the Study Procedures Table 
(Appendix 2). Multigated acquisition (MUGA) scans are also acceptable. However, the same 
modality must be used throughout study participation.
Abnormal echocardiogram findings that are considered clinically significant by the investigator 
should be reported as AEs and recorded in the AE eCRF if the finding meets the definition of an 
AE. 
6.2.8.
ECOG Performance Status
ECOG Performance Status is an investigator assessment of the impact of the disease on the 
subject’s activities of daily living. ECOG assessments will be performed at the time points listed 
in the Study Procedures Table (Appendix 2). ECOG will be scored using the scale index in
Appendix 6.

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6.2.9.
Adverse Events
Subjects will be assessed for AEs per guidelines in the National Cancer Institute (NCI) CTCAE 
(version 4.03) at the time points outlined in Appendix 4. Any AEs reported after informed 
consent is obtained and throughout the study will be recorded on the eCRF with appropriate 
source documentation. The subject will be assessed for AEs approximately 30 days after the last 
dose of study drug. Please refer to Appendix 4 CTCAE grading criteria.  
Please refer to Section 7 for additional information on AE reporting.
6.2.10.
Disease Assessments
6.2.10.1.
CT or MRI
Subjects will be assessed by CT scan with contrast (or MRI, if unable to tolerate CT contrast) of 
the chest, abdomen and pelvis to document metastatic disease, identify target lesions and to 
assess response as per RECIST 1.1 (refer to Appendix 7). The same assessment methods should 
be used for the subject throughout all treatment cycles. CT, or MRI scans will be obtained at the 
applicable study visits per the Study Procedures Table (Appendix 2) and transferred to a central 
vendor for storage.
In subjects who cannot tolerate iodinated contrast, a CT of the lung without contrast and MRI of 
the abdomen and pelvis should be performed. Imaging by CT scan (with contrast) or MRI or 
applicable scan will be performed at Screening (within 28 days before C1D1 if the scan was 
performed as part of standard medical practice) and every 8 weeks for the first year and then 
every 12 weeks during the treatment period regardless of cycle number or dose interruption. 
During the treatment, scans may be performed at time points other than 12 weeks, as clinically 
indicated, to assess tumor progression.
Tumor burden will be characterized at baseline and subsequent response assessments will be 
carried out according to the RECIST v. 1.1 (refer to Appendix 7). The same radiographic 
procedure and specification (e.g., the same contrast agent, slice thickness, etc.) used to define 
measurable lesions at baseline must be used throughout the study for each subject. 
Subjects who discontinue study treatment for reasons other than disease progression will
continue to have tumor assessments performed during the follow up visits every 8 weeks for the 
first year and then every 12 weeks until disease progression, initiation of new anti-cancer 
therapy, or discontinuation from the overall study participation (death, subject’s request, lost to 
follow-up) whichever happens first. Every effort should be made to perform a last tumor 
assessment before starting a new anti-cancer therapy. Additional unscheduled tumor assessments 
may be performed as clinically indicated at any time.
6.2.10.2.
Bone Scans
All subjects will undergo radionuclide bone scan at Screening (within 12 weeks prior to 
randomization). Bone scans performed before the signing of informed consent as routine 
procedures (but within 12 weeks before randomization) do not need to be repeated and may be 

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used as baseline assessments as long as (1) tests were performed using the method requirements 
outlined in RECIST v.1.1 (2) appropriately documentation indicating that these radiographic 
tumor assessments were performed as standard of care is available in the patient’s source notes. 
Any suspicious abnormalities (i.e., hotspots) identified on the bone scans at baseline and on 
subsequent bone scans MUST be confirmed by X-ray, CT scan with bone windows or MRI. The 
same modality must be used throughout the trial for confirmation for a given lesion/patient. Bone 
lesions identified at baseline will be followed up according to the same assessment schedule and 
every 8 weeks (±7 days) for the first year and then every 12 weeks (±7 days) from the date of 
C1D1 during the treatment period. Scans at the EOT visit are not necessary if the prior scan was 
performed within 4 weeks prior to the EOT visit date. Bone scans will be obtained at the 
applicable study visits per the Study Procedures Table (Appendix 2) and transferred to a central 
vendor for storage.
Bone lesions imaging:

If bone lesions were identified at baseline as the only sites of a subject’s disease the
following assessment must be performed:
○
CT scan/MRI every 8 weeks (±7 days) for the first year and then every 12 weeks (±7 
days) from the date of C1D1 and to confirm CR using the same modality used to confirm 
the bone lesions at baseline. Areas that have received palliative radiotherapy on study 
cannot be used to assess response to study treatment.

If no bone lesions were identified at baseline, or if bone is not the only site of a subject’s 
disease, bone scans will only be repeated as clinically indicated (i.e., subject describes new or 
worsening bone pain, or has increasing alkaline phosphatase level, or other signs and 
symptoms of new/progressing bone metastases) but are required to confirm CR. 
Abnormalities found on subsequent bone scans shall also be confirmed by X-ray, CT or MRI.
6.2.11.
Laboratory Assessments
Screening laboratory samples should be obtained within 28 days prior to C1D1 dose (GS-5829). 
Local laboratory complete blood count (CBC) assessments may be collected as required for dose 
adjustments throughout the study. Local laboratory assessments resulting in a dose change will 
be reported on the eCRF.
The central laboratory will be responsible for chemistry, hematology, and coagulation testing per 
Table 6-1 and storage of other study samples. If central laboratory results are not available, local 
laboratories may be used for dosing decision. Other tests listed in Table 6-1 will be performed by 
Gilead or a designated laboratory. Any sample collected per the Study Procedures Table 
(Appendix 2) may be analyzed for any tests necessary to ensure subject safety. Specific 
instructions for processing, labeling, and shipping samples will be provided in the central 
laboratory manual. The date and time of sample collection will be recorded in the subject’s 
source documentation and reported to the central laboratory.

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The date and time of previous GS-5829 dose will be recorded in the subject’s source 
documentation on days where pharmacokinetics is collected. WBC differentials will be reported 
as absolute counts. All laboratory tests must be reviewed for clinical significance by the 
investigator or qualified designee. Eligibility will be based on central laboratory assessments.
C1D1 pre-dose samples may be drawn up to 2 days prior to the visit.
The analytes listed in Table 6-1 will be tested.
Table 6-1.
Analytes
Serum Chemistry
Hematology
Other
Sodium
Potassium
Chloride
Glucose
BUN
Creatinine
Creatinine Clearancea
ALT
AST
Alkaline phosphatase
Total bilirubinb
Total protein
Albumin
Calcium
Magnesium
Phosphate
AAG
CRP
White Blood Cell (WBC) Count
Hemoglobin
Hematocrit
Platelet Count
Neutrophils (ANC)
Lymphocytes
Monocytes
Basophils
Eosinophils
Serum -hCG for pregnancy test
GS-5829 concentration
Concentrations of GS-5829 
metabolite(s), fulvestrant, and/or 
metabolites, as applicable, may be 
determined
 
Hepatitis B surface antigend
Hepatitis C antibody
FSH
Serum Estradiol
Hepatitis C RNA Reflex
26- hydroxyvitamin D
HIV
Urine pregnancy test
Coagulation
PT/INRc
aPTTc
a
Cockcroft-Gault using Actual Body Weight: CRCL (mL/min) = [(140-age(years)) * weight(kg)] / (serum creatinine 
(mg/dL)*72)
b
Includes direct bilirubin
c
Collected at Screening and pre-dose of C1D1, C1D15, C2D1
d
HCV RNA Reflex is required
6.2.12.
Pregnancy Test for Females of Childbearing Potential
All female subjects of childbearing potential (as defined in Appendix 5) will have serum 
pregnancy, estradiol and FSH testing throughout the study (refer to Appendix 2). The results 
must be confirmed as negative for pregnancy prior to continued administration of study drug.
Female subjects of childbearing potential must have commenced treatment with goserelin or an 
alternative LHRH agonist at least 4 weeks prior to C1D1. Additionally, subjects on goserelin will 
have serum pregnancy, serum estradiol, and FSH checked on the first day of Cycle 1 to Cycle 3, 
urine pregnancy test will be performed monthly thereafter.
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6.2.13.
Vitamin D Assessment 
Routine assessment of 25-hydroxy vitamin D levels prior to the start of exemestane (Group A 
Phase 1b) and fulvestrant treatment should be performed, due to the high prevalence of 
vitamin D deficiency in women with breast cancer. Women with vitamin D deficiency should 
receive supplementation with vitamin D.
6.2.14.
Pharmacokinetic & Pharmacodynamic Samples
Pharmacokinetic samples will be collected at the time points listed below for each Phase. 
GS-5829 plasma concentrations will be determined using a validated assay. Plasma 
concentrations of GS-5829 metabolites and/or exemestane (Group A Phase 1b) and/or fulvestrant 
metabolites may be determined. Plasma protein binding of analytes may be evaluated. 
Pharmacodynamics samples may be modified based on the emerging data. The date and clock 
time of GS-5829 and exemestane dosing (Group A Phase 1b), as applicable, will be collected 
prior to and on the day of pharmacokinetic sampling. The date and clock time of each fulvestrant 
dose will be recorded on eCRF, as applicable.
Modulation of the expression of CCR2 and HEXIM1 will be monitored in the pharmacodynamic
samples to confirm on target activity of GS-5829.
Phase 1b Dose Escalation 
Pharmacokinetic and pharmacodynamic samples for GS-5829 will be collected on Day 1 and 
Day 15 of Cycle 1 at pre-dose 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose and anytime on Day 1 
of Cycles 2 through 6. Refer to Appendix 3. All GS-5829 post-dose 
pharmacokinetic/pharmacodynamic samples have a ± 10 minute window. 
Randomized Phase 2 Dose Expansion
Sparse pharmacokinetic and pharmacodynamic samples will be collected at pre-dose and 
anytime between 1 to 4 hours post-dose on Day 1 and Day 15 of Cycle 1 and at pre-dose on 
Day 1 of Cycles 3 and 6. Refer to Appendix 3. Note: pharmacokinetic samples will only be 
collected for subjects who are randomized to GS-5829 combination arm.
6.3.
Biomarker Testing
6.3.1.
Biomarker Samples to Address the Study Objectives:
 
 
 
 
 
 
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6.3.2.
Biomarker Samples for Optional Future Research
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.3.3.
Biomarker Samples for Optional Genomic Research
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.4.
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 will be re-consented with new 
screening number, and will repeat the screening assessments. Subjects who do not meet QTc 
criteria are not allowed to re-screen (see Section 4.3). Gilead is to be informed prior to a subject 
re-screening.
6.5.
Treatment Assessments
Each on-study visit will be scheduled relative to C1D1. Visits will follow the schedule of 
assessments in Appendix 2 and Appendix 3.
Subjects who meet eligibility criteria will receive GS-5829 orally once daily combined with daily 
orally dosing of exemestane (Group A Phase 1b) or injection of fulvestrant intramuscularly on 
Day 1, Day 28 and then every 28 days (± 3 days). Subjects initiating fulvestrant on C1D1 should 
receive a single additional dose at C1D15. Subjects in the Phase 1b Dose Escalation phase of the 
study may initiate exemestane (Group A) or fulvestrant (Group B) any time prior to, or on, 
C1D1. Each cycle will consist of 28 days. Safety and efficacy assessments will occur on an
outpatient basis including an assessment of tumor response, physical exam, vitals, ECG, 
collection of blood samples (for routine safety labs, GS-5829 pharmacokinetic, pharmacodynamic 
markers, and biomarkers at applicable visits), and assessment of AEs. In addition, subjects will
undergo a CT scan (or MRI) scan every 8 weeks for the first year and then every 12 weeks. Bone 
scans may be repeated as clinically indicated or to confirm a CR.  
A subject who does not show evidence of disease progression may continue receiving GS-5829 
once daily and exemestane (Group A Phase 1b) or fulvestrant until disease progression (clinical
or radiographic), unacceptable toxicity, withdrawal of consent, or other reasons specified in
Section 3.5. If a subject who is randomized to the combination arm discontinues one study drug 
for any reason, such as toxicity the other study drug will be discontinued as well.
6.6.
Post-treatment Assessments
All subjects will complete the 30-Day Safety Follow-Up Visit (±5 days).  For Phase 1b Dose 
Escalation subjects, the 30-Day Safety Follow-Up will be the final study visit. Randomized 
Phase 2 Dose Expansion subjects will complete the 30-Day Safety Follow-Up Visit and proceed 
to Long Term Survival Follow-Up (LTFU) (See Section 6.7).
Subjects who discontinue study treatment for reasons other than disease progression will 
continue to have tumor assessments performed during the follow up visits before entering LTFU
every 8 weeks for the first year and then every 12 weeks until disease progression, initiation of 
new anti-cancer therapy, or discontinuation from the overall study participation (death, subject’s
request, lost to follow-up) whichever happens first. Every effort should be made to perform a last 
tumor assessment before starting a new anticancer therapy. Additional unscheduled tumor 
assessments may be performed as clinically indicated at any time.

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6.7.
Long-Term Survival Follow-Up
Randomized Phase 2 Dose Expansion subjects will participate in long-term survival follow-up.  
These subjects will be contacted via phone call every 3 months (+/- 7 days) for determination of 
long-term survival status and record of any other anti-cancer therapy for up to 2 years after the 
last dose of study drug. For subjects who discontinued the study for reasons other than disease 
progression, the investigator should obtain information on the subject’s post-study anti-cancer 
therapies, surgeries, and date of definitive disease progression (if known).
Subjects who are alive at the time the sponsor has made the determination the study will be 
ended will receive a final follow-up phone call to assess survival status and communicate the 
sponsor’s decision. These subjects will be censored on the date the subject was last contacted.
The investigator will make every effort to contact the subject or a close relative or caretaker by 
phone to collect survival information. The investigator should show due diligence by 
documenting in the source documents steps taken to contact the subject i.e., dates of phone calls, 
registered letters, etc.
6.8.
Unscheduled Visits
Unscheduled procedures may occur at any time during the study. Vital Signs, ECOG, ECHO, 
12-lead ECG, bone scan and CT or MRI, may be conducted at these visits and recorded on the 
applicable eCRFs.
6.9.
Assessments for Premature Discontinuation from Study
If a subject discontinues study dosing (for example, as a result of an AE), every attempt should 
be made to keep the subject in the study and continue to perform the required study-related 
follow-up and procedures (see Section 6.10, 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 of Study Treatment
See Section 3.5 for discontinuation criteria.  
6.11.
Post Study Care
If a subject has discontinued the study treatment due to toxicity, she should not have withdrawal 
of consent recorded as the reason for discontinuation. Instead, the reason for discontinuation 
must be recorded as due to AEs.
Every attempt should be made to keep the subject in the study and continue collecting CT or 
MRI scans for tumor assessment at every 8 weeks for the first year and then every 12 weeks 
from the date of C1D1 until disease progression or initiation of systemic anti-tumor therapy other 
than treatment per protocol. If this is not possible or acceptable to the subject or investigator, the 
subject may be withdrawn from the study. The subject will be asked to attend the post-treatment 

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follow-up assessment visit when discontinuing from the study treatment. Randomized Phase 2 
Dose Expansion subjects will participate in long-term survival follow-up. These subjects will be 
contacted via phone call every 3 months for determination of long- term survival status and 
record of any other anti-cancer therapy for up to 2 years after the last dose of study drug.
6.12.
Replacement of Subjects
If a subject in the Phase 1b portion of the study is withdrawn from the study for any reason other 
than a DLT prior to completion of the DLT assessment window, a replacement subject will be 
enrolled at the same dose level as the replaced subject. To be evaluable for the DLT observation, 
a subject must receive at least 21 doses of GS-5829, complete all safety procedures through 
Day 28, or experience a DLT prior to Day 28.
6.13.
Protocol Deviations
Gilead’s policy prohibits exemptions from protocol inclusion/exclusion criteria. In the event of a 
significant deviation related to gross non-compliance from the protocol or incidences that impose 
significant risk to subject safety, the investigator or designee must notify the sponsor and/or its 
designee immediately. The site will be required to document deviations in accordance with 
Gilead’s procedures and in accordance with the site’s procedures and processes.
6.14.
End of Study
End of study for a subject is defined as the date of the last study-related procedure or the date of 
death for an on-study subject. Randomized Phase 2 Dose Expansion subjects will participate in 
long-term survival follow-up. These subjects will be contacted via phone call every 3 months for 
determination of long-term survival status and record of any other anti-cancer therapy for up to 
2 years after the last dose of study drug.

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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An AE is any untoward medical occurrence in a clinical study subject administered a medicinal 
product, which does not necessarily have a causal relationship with the treatment. An AE can 
therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated 
with the use of a medicinal product, whether or not considered related to the medicinal product.
AEs may also include pre- or post-treatment complications that occur as a result of protocol 
specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or occupational 
exposure. Preexisting events that increase in severity or change in nature during or as a 
consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion.
The condition that led to the procedure may be an AE and must be reported

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae 

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history CRF
7.1.2.
Serious Adverse Events
A SAE is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements
7.1.2.1.
Protocol-Specific Serious Adverse Event Instructions
To maintain the integrity of the study, disease progression and death from disease progression 
should be reported as SAEs by the investigator only if it is assessed that the study drugs caused 
or contributed to the disease progression (i.e., by a means other than lack of effect). Unrelated 
disease progression should be captured on the eCRF.
In addition, events that are indicative of the following disease-related SAEs that are assessed as 
unrelated to study drugs will not be reported as expedited reports by Gilead during the study:

Progression of disease

Death related to disease progression
These events will be exempt from global expedited reporting requirements for the duration of the 
study as they are the primary endpoints of this study. They will be reported as appropriate in the 
final clinical study report as well as any relevant aggregate safety report.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (e.g., clinical chemistry, hematology) that require medical or 
surgical intervention or lead to IMP interruption, modification, or discontinuation must be 
recorded as an AE, as well as an SAE, if applicable. In addition, laboratory or other abnormal 
assessments (e.g., electrocardiogram, x-rays, vital signs) that are associated with signs and/or 
symptoms must be recorded as an AE or SAE if they meet the definition of an AE or SAE as 
described in Sections 7.1.1 and 7.1.2. If the laboratory abnormality is part of a syndrome, record 
the syndrome or diagnosis (e.g., anemia), not the laboratory result (i.e., decreased hemoglobin).

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For specific information on handling of clinical laboratory abnormalities in this study, please 
refer to Section 5.3.1.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified sub-investigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified sub-investigator is responsible for assessing the relationship to IMP 
therapy using clinical judgment and the following considerations:

No: Evidence exists that the AE has an etiology other than the IMP. For SAEs, an alternative 
causality must be provided (e.g., pre-existing condition, underlying disease, intercurrent 
illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the IMP.
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of AE reporting. 
The relationship to study procedures (e.g., 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, (e.g., venipuncture).
7.2.2.
Assessment of Severity
The severity of AEs will be graded using the CTCAE, Version 4.03 (Appendix 4).
For each episode, the highest severity grade attained should be reported.
If a CTCAE criterion does not exist, the investigator should use the grade or adjectives: 
Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or 
Grade 5 (fatal) to describe the maximum intensity of the AE. For purposes of consistency with 
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Table 7-1.
Grading of Adverse Event Severity
Grade
Adjective
Description
Grade 1
Mild
Sign or symptom is present, but it is easily tolerated, is not expected to have a 
clinically significant effect on the subject’s overall health and well-being, does not 
interfere with the subject’s usual function, and is not likely to require medical 
attention.
Grade 2
Moderate
Sign or symptom causes interference with usual activity or affect clinical status, 
and may require medical intervention.
Grade 3
Severe
Sign or symptom is incapacitating or significantly affects clinical status and likely 
requires medical intervention and/or close follow-up.
Grade 4
Life-threatening
Sign or symptom results in a potential threat to life.
Grade 5
Fatal
Sign or symptom results in death.
The distinction between the seriousness and the severity of an AE should be noted. Severe is a 
measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For example, a
headache may be severe in intensity, but would not be classified as serious unless it met one of 
the criteria for serious events listed in Section 7.1.2.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead 
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the case report form (CRF/eCRF): all SAEs, and AEs related to 
protocol-mandated procedures.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 30-days after last administration of study IMP must be reported to the eCRF database as 
instructed.
All AEs should be followed up until resolution or until the AE is stable, if possible. Gilead 
Sciences may request that certain AEs be followed beyond the protocol defined follow up period.

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Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (i.e., signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
CRF/eCRF database and Gilead DSPH as instructed. This also includes any SAEs resulting from 
protocol-associated procedures performed after informed consent is signed.
Any SAEs and deaths that occur after the post treatment follow-up visit but within 30 days of the 
last dose of study IMP, regardless of causality, should also be reported.
Investigators are not obligated to actively seek SAEs after the protocol defined follow up period, 
however, if the investigator learns of any SAEs that occur after study participation has concluded 
and the event is deemed relevant to the use of IMP, he/she should promptly document and report 
the event to Gilead DSPH.

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline. 
Electronic Serious Adverse Event (eSAE) Reporting Process

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to Gilead DSPH within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If for any reason it is not possible to record the SAE information electronically, i.e., the 
eCRF database is not functioning, record the SAE on the paper SAE reporting form and 
submit within 24 hours to:
Gilead DSPH:
Fax: 
Email: 

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 form 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 document 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 
form.
7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or the relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy. 
7.5.
Toxicity Management 
Treatment-emergent toxicities will be noted by the investigator and brought to the attention of 
the Gilead medical monitor or designee. Whether or not considered treatment-related, all subjects 
experiencing AEs must be monitored periodically until symptoms subside, any abnormal 
laboratory values have resolved or returned to baseline levels or they are considered irreversible, 
or until there is a satisfactory explanation for the changes observed.
Grade 3 or 4 clinically significant laboratory abnormalities should be confirmed by repeat testing 
as soon as practical to do so, and preferably within 3 calendar days after receipt of the original 
test results. Any questions regarding toxicity management should be directed to the Gilead 
medical monitor or designee.
7.6.
Special Situations Reports
7.6.1.
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.  

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Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.  
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
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 post study drug follow-up 
period, to Gilead DSPH using the pregnancy report form within 24 hours of becoming aware of 
the pregnancy.
Refer to eCRF completion guidelines for full instructions on the mechanism of pregnancy 
reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (e.g., 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 term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.1.2 Furthermore, any SAE occurring as an adverse pregnancy outcome post study must 
be reported to Gilead DSPH.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead DSPH using the pregnancy outcome report 
form. If the end of the pregnancy occurs after the study has been completed, the outcome should 

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be reported directly to Gilead DSPH. Gilead DSPH contact information is as follows: Email: 
 and Fax: 
Refer to Appendix 5 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead DSPH within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead concomitant medications does not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form. 
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to eCRF completion guidelines for full instructions on the mechanism of special situations 
reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.
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8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary objective:
Phase 1b Dose Escalation

To characterize the safety and tolerability of GS-5829 in combination with fulvestrant and 
exemestane in subjects with advanced ER+/HER2- BrCa

To determine the MTD or RP2D of GS-5829 in combination with fulvestrant in subjects with 
advanced ER+/HER2- BrCa
Randomized Phase 2 Dose Expansion

To evaluate the efficacy of GS-5829 in combination with fulvestrant compared to fulvestrant
alone in subjects with advanced ER+/HER2- BrCa, as measured by PFS
Secondary objectives: 
Phase 1b Dose Escalation

To evaluate the pharmacokinetics of GS-5829 in combination with fulvestrant in subjects 
with advanced ER+/HER2- BrCa
Randomized Phase 2 Dose Expansion  

To evaluate the efficacy of GS-5829 in combination with fulvestrant compared to fulvestrant
alone in subjects with advanced ER+/HER2- BrCa, as measured by ORR and CBR evaluated 
according to RECIST v. 1.1. ORR is defined as the proportion of subjects with response (CR 
or PR). CBR is defined as proportion of subjects with CR, PR, or SD that lasts for ≥ 24 
weeks

To evaluate the safety and tolerability of GS-5829 in combination with fulvestrant compared 
to fulvestrant alone in subjects with advanced ER+/HER2- BrCa

To evaluate OS for subjects with advanced ER+/HER2- BrCa who received GS-5829 in 
combination with fulvestrant compared to fulvestrant alone 

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Exploratory objectives:
 
8.1.2.
Primary Endpoints
Phase 1b Dose Escalation: 

Safety profile and tolerability of the combination of GS-5829 and fulvestrant as assessed by 
DLTs through Day 28 at each dose level of GS-5829
Randomized Phase 2 Dose Expansion: 

PFS defined as the interval from date of randomization to the earlier of the first documented 
confirmed disease progression or death from any cause
8.1.3.
Secondary Endpoints
Phase 1b Dose Escalation: 

GS-5829 pharmacokinetic parameters (e.g., Cmax, AUCtau)
Randomized Phase 2 Dose Expansion: 

Overall safety profile will be characterized by the type, frequency, severity, timing of onset, 
duration, and relationship to study treatment of any AEs or abnormalities in laboratory tests 
or ECGs 

ORR, defined as the proportion of subjects who achieve CR or PR, based on RECIST v. 1.1 

CBR, defined as the proportion of subjects who achieve CR, PR or SD that lasts for 
>24 weeks based on RECIST v. 1.1 

OS, defined as interval from date of randomization to date of death from any cause
PPD

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8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
Intent-to-Treat (ITT) Analysis Set
The ITT analysis set includes all subjects who are randomized in the Randomized Phase 2 Dose 
Expansion phase of the study regardless of whether subjects receive any study drug(s), or receive 
a different regimen from the regimen they were randomized to. Treatment assignment will be 
designated according to randomization.
The analysis of PFS based on the ITT analysis set will be considered the primary analysis of the 
study. PFS will also be analyzed for each of the 2 strata separately.
This analysis set will be used in the analyses of PFS, ORR, CBR and OS. Subjects in the ITT 
analysis set who do not have sufficient baseline or on-study tumor status information to be 
adequately assessed for response status will be included in the denominators in the calculation of 
ORR and CBR.
8.2.1.2.
The Per-Protocol (PP) analysis set
The PP analysis set includes data from subjects in the ITT analysis set who meet the general 
criteria defining the target population for this study: those who are adherent to the protocol, are 
compliant with study drug treatment, and are evaluable for relevant efficacy endpoints. 
Treatment assignment will be designated according to the actual treatment received. The PP 
analysis set will be used in sensitivity analyses of efficacy endpoints.
8.2.1.3.
Safety Analysis Set
The Safety Analysis Set includes subjects who receive ≥ 1 dose of study drug. This analysis set 
will be used for the analyses of safety endpoints, study treatment administration and study drug 
compliance. 
8.2.1.4.
DLT-Evaluable Analysis Set
The DLT-Evaluable Analysis Set includes all Phase 1b Dose Escalation subjects in the Safety 
Analysis Set who complete all treatment and safety procedures through Day 28, or experienced a 
DLT prior to Day 28. Subjects who are not evaluable for DLT determination may be replaced.
8.2.1.5.
Pharmacokinetics and Pharmacodynamics Analysis Sets
The pharmacokinetics and pharmacodynamics Analysis Sets will consist of all subjects in the 
Safety Analysis Set who have the necessary baseline and on-study measurements to provide 
interpretable results for the specific parameters of interest.

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8.2.1.6.
Biomarker Analysis Set
The Biomarker Analysis Sets include data from subjects in the Safety analysis set who have the 
necessary baseline and on-study measurements to provide interpretable results for the specific 
parameters of interest.
8.3.
Data Handling Conventions
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 (StD), 95% confidence intervals (CIs) on the 
mean, median, the first and third quartiles, minimum, and maximum. Summary tables for 
categorical variables will include: N, n, percentage, and 95% CIs on the percentage. Unless 
otherwise indicated, 95% CIs for binary variables will be calculated using the binomial 
distribution (exact method) and will be 2-sided. Data will be described and summarized by 
relevant dose level (Phase 1b Dose Escalation), time point and treatment group for the 
corresponding analysis sets. As appropriate, changes from baseline to each subsequent time point 
will be described and summarized by dose level and treatment group. Similarly, as appropriate, 
the best change from baseline during the study will also be described and summarized by dose 
level and treatment group. Graphical techniques (e.g., waterfall plots, Kaplan-Meier curves, line 
plots) may be used when such methods are appropriate and informative.
The baseline value will be the last (most recent) pre-treatment 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.
8.4.
Demographic Data and Baseline Characteristics
Subject demographic and baseline characteristics will be listed and summarized by dose level
(Phase 1b Dose Escalation) and by treatment group for the Safety Analysis Set.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The difference in PFS between the treatment arms will be assessed in the ITT analysis set using 
the log-rank test. Kaplan-Meier estimates and plots, hazard ratios and corresponding 95% CIs
will be presented. 
Subjects who withdraw from the study or are lost to follow-up without disease progression or 
death will be censored on the date of the last visit when lack of disease progression was 
documented. Subjects who have progression or die after ≥ 2 consecutive missing tumor 
assessments will be censored at the last time prior to the missing assessments that lack of 

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definitive progression was objectively documented. Subjects without any adequate post-baseline 
disease assessment will be censored on the date of first study dose.
8.5.2.
Secondary Analyses
The best overall response will be summarized by each response category as CR, PR, SD and PD 
by treatment arms. Fisher’s exact test will be used to compare ORR and CBR between treatment 
arms. The 2-sided 95% CIs for ORR and CBR will be calculated based on exact method. The 
difference in OS between the treatment arms will be assessed using the log-rank test. Kaplan-
Meier estimates and plots, hazard ratios and corresponding 95% CIs will be presented.
8.6.
Safety Analysis
Safety will be evaluated by assessment of clinical laboratory tests, physical examination, 12-lead 
ECG, vital signs measurements and documented AEs as described in the Study Procedures Table 
(Appendix 2). All safety data collected on or after the date that study drug was first dispensed up 
to the date of last dose of study drug plus 30 days will be summarized by dose level (Phase 1b 
Dose Escalation) and visit where appropriate and by treatment group for subjects in the Safety 
Analysis Set. AEs occurred in pretreatment will be included in data listings.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to GS-5829 and fulvestrant will be reported. Exposure data and 
study drug compliance will be summarized by dose level and treatment group for subjects in the 
safety analysis set.
GS-5829 compliance will be described in terms of the amount actually taken based on returned 
pill count relative to the amount that was dispensed (taking into account physician-prescribed 
reductions and interruptions).
Fulvestrant compliance will be described in terms of the number of doses actually administered 
relative to the expected number of doses planned.
8.6.2.
Adverse Events
The focus of AE summarization will be on treatment-emergent AEs. Treatment-emergent AEs 
(TEAEs) are events in a given study period that meet one of the following criteria:

Events with onset dates on or after the start of treatment and up to 30 days after the
permanent discontinuation of the study treatment.

AEs resulting in treatment discontinuation after the start of treatment.
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA)
(http://www.meddramsso.com) with descriptions by System Organ Class (SOC), High-Level
Group Term, High-Level Term, Preferred Term, and Lower-Level Term. The severity of AEs 
will be graded by the investigator according to the CTCAE, Version 4.03, whenever possible. If 

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a CTCAE criterion does not exist for a specific type of AE, the grade corresponding to the 
appropriate adjective will be used by the investigator to describe the maximum intensity of the 
AE: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life threatening), or Grade 5 
(fatal). The relationship of the AE to the study drug will be categorized as related or unrelated. 
TEAEs will be summarized by dose level (Phase 1b Dose Escalation) and treatment group. 
Summary tables will be presented to show the number of subjects reporting treatment-emergent 
AEs by severity grade and corresponding percentages.
Following summaries (number and percentage of subjects) of TEAEs will be provided:
1) All AEs
2) AEs related to study drug
3) AEs that are Grade ≥ 3 in severity
4) AEs leading to study drug modification (interruption/reduction)
5) AEs leading to study drug discontinuation
6) AEs leading to death
7) SAEs
Summaries of TEAEs (by SOC and PT) will be provided by dose level (Phase 1b Dose 
Escalation) and treatment group. A subject who reports multiple treatment-emergent AEs within 
the same Preferred Term (or SOC) is counted only once for that Preferred Term (or SOC) using 
the worst severity grade.
All AEs will be listed.
8.6.3.
Laboratory Evaluations
All central laboratory results will be listed. Selected laboratory data will be summarized using 
only observed data. Laboratory results and change from baseline at all scheduled time points will 
be summarized.
The focus of laboratory data summarization will be on treatment-emergent laboratory 
abnormalities. A treatment-emergent laboratory abnormality is defined as an abnormality that, 
compared to baseline, worsened by ≥ 1 grade in the period from C1D1 to 30 days after the last 
dose of study drug. If baseline measurement is missing, then any graded abnormality (i.e., an 
abnormality that is Grade ≥ 1 in severity) will be considered treatment emergent.
Hematology and serum biochemistry will be graded according to CTCAE 4.03 severity grade, 
when applicable. For parameters for which a CTCAE scale does not exist, reference ranges from 
the central laboratory will be used to determine whether a laboratory value is below, within, or 
above the normal range for the subject’s age, sex, etc.

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Hematology and serum biochemistry test results and their changes from baseline will be 
summarized by dose level (Phase 1b Dose Escalation), visit and treatment group. Laboratory 
abnormalities will be summarized for each relevant assay to show the number of subjects by 
CTCAE severity grade with corresponding percentages. For parameters for which a CTCAE 
scale does not exist, the frequency of subjects with values below, within, and above the normal 
ranges will be summarized. Subjects will be characterized only once for a given assay, based on 
their worst severity grade observed during a period of interest (e.g., during the study or from 
baseline to a particular visit).
Shift tables for hematology and serum biochemistry will be presented by showing change in 
CTCAE severity grade from baseline to the worst grade post-baseline. Separate listings and 
summaries will be prepared for laboratory abnormalities that are Grade ≥ 3 in severity.
8.6.4.
Other Safety Evaluations
Dose limiting toxicities will be listed for all dose levels. 
8.7.
Pharmacokinetic Analysis
In the Phase 1b Dose Escalation portion of study, the plasma concentration of GS-5829 will be 
summarized by nominal sampling time using descriptive statistics by dose cohorts. 
Pharmacokinetic parameters will be determined using standard non-compartmental methods. 
Pharmacokinetic parameters (such as Cmax and, AUCtau), will be listed and summarized using 
descriptive statistics (e.g., sample size, arithmetic mean, geometric mean, coefficient of variation 
(%) StD, median, minimum, and maximum) by dose cohorts. Plasma concentrations over time
will be plotted in semi-logarithmic and linear formats as mean ± StD, and median (Q1, Q3) if 
applicable. In the Randomized Phase 2 Dose Expansion portion of study, plasma concentrations 
will be summarized by nominal sampling time using descriptive statistics by treatment arm.
8.8.
Biomarker Analysis
Descriptive statistics of baseline and change from baseline in biomarkers will be provided at 
each sampling time for all subjects, and by treatment arms.
 
 
 
 
 
 
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8.9.
Sample Size
The sample size of the Phase 1b Dose Escalation portion of the study will be determined based 
on the number of dose levels evaluated and the emerging drug-related toxicities, and may enroll 
up to approximately 30 subjects. 
Approximately 120 subjects will be enrolled in the Randomized Phase 2 Dose Expansion portion 
of this study. Approximately 80 subjects will be randomized to receive GS-5829 in combination 
with fulvestrant and 40 subjects to receive fulvestrant alone in a 2:1 ratio. The sample size of 
120 subjects will provide 88 events in total and greater than 90% power to detect the difference 
in PFS between the two treatment arms with 0.1 one-sided significance level, assuming a median 
PFS of 4 months for subjects who receive fulvestrant alone, a median PFS of 8 months in 
subjects who receive GS-5829 in combination with fulvestrant, accrual period of 9 months and
total study duration of 19 months and a drop-out rate of 10% by 12 months. Within each stratum 
of naïve or progressed prior CDK4/6 inhibitor plus AI subjects, the power will be 80% with 
target number of 60 subjects (44 events).

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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), ICH guidelines, or with the laws and regulations of the country in which the 
research is conducted, whichever affords the greater protection to the study subject. These 
standards are consistent with the European Union Clinical Trials Directive 2001/20/EC and GCP
Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of GCP, as outlined in 
21 CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, part 50, 1998, 
and 21 CFR, part 56, 1998.
The investigator and all applicable sub-investigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any sub-investigator’s) participation in the study. The investigator and 
sub-investigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, informed consent form, and any accompanying material to be provided to the subject 
(such as advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) to an IRB/IEC. The investigator will not begin any study subject activities 
until approval from the IRB/IEC has been documented and provided as a letter to the 
investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/IEC any modifications made to the protocol or any accompanying material to be 
provided to the subject after initial IRB/IEC approval, with the exception of those necessary to 
reduce immediate risk to study subjects.

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9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 
investigator must use the most current IRB or IEC approved consent form for documenting 
written informed consent. Each informed consent (or assent as applicable) will be appropriately 
signed and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by local 
requirements. The consent form will inform subjects about genomic testing and sample retention, 
and their right to receive clinically relevant genomic analysis results.
9.1.4.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, date of birth, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form or biological sample submitted to the Sponsor, IRB or IEC, or laboratory. Laboratory 
specimens must be labeled in such a way as to protect subject identity while allowing the results 
to be recorded to the proper subject. Refer to specific laboratory instructions. NOTE: The 
investigator must keep a screening log showing codes, names, and addresses for all subjects 
screened and for all subjects enrolled in the trial. Subject data will be processed in accordance 
with all applicable regulations
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator brochure, this protocol, eCRF, the IMP, and any other study information, remain the 
sole and exclusive property of Gilead during the conduct of the study and thereafter. This 
information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, CRF and query forms, IRB 
or IEC and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.

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The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender);

Documentation that subject meets eligibility criteria, i.e., history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);

Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);

Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of IMP, including dates of dispensing and return;

Record of all AEs and other safety parameters (start and end date, and including causality
and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (i.e., United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and regulatory 
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.

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9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRFs should be 
completed on the day of the subject visit to enable the sponsor to perform central monitoring of 
safety data. The Eligibility Criteria eCRF should be completed only after all data related to 
eligibility have been received. Subsequent to data entry, a study monitor will perform source data 
verification within the EDC system. Original entries as well as any changes to data fields will be 
stored in the audit trail of the system. Prior to database lock (or any interim time points as 
described in the clinical data management plan), the investigator will use his/her log in 
credentials to confirm that the forms have been reviewed, and that the entries accurately reflect 
the information in the source documents. The eCRF capture the data required per the protocol 
schedule of events and procedures. System-generated or manual queries will be issued to the 
investigative site staff as data discrepancies are identified by the monitor or internal Gilead staff, 
who routinely review the data for completeness, correctness, and consistency. The site 
coordinator is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry, and providing the reason 
for the update (e.g. data entry error). At the conclusion of the trial, Gilead will provide the site 
with a read-only archive copy of the data entered by that site. This archive must be stored in 
accordance with the records retention requirements outlined in Section 9.1.5.
9.1.7.
Investigational Medicinal Product Accountability and Return
Where possible, study drug(s) should be destroyed at the site. At the start of the study, the study 
monitor will evaluate each study center’s study drug disposal procedures and provide appropriate 
instruction for disposal or return of unused study drug supplies. If the site has an appropriate 
standard operating procedure (SOP) for drug destruction as determined by Gilead Sciences, the 
site may destroy used (empty or partially empty) and unused study drug supplies as long as 
performed in accordance with the site’s SOP. This can occur only after the study monitor has 
performed drug accountability during an on-site monitoring visit. 
A copy of the site’s study drug disposal SOP or written procedure (signed and dated by the PI 
or designee) will be obtained for Gilead site files. If the site does not have acceptable 
procedures in place, arrangements will be made between the site and Gilead Sciences 
(or Gilead Sciences’ representative) for return of unused study drug supplies. 
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.
The study monitor will review study drug supplies and associated records at periodic intervals.

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9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRBs, IECs, or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
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 or IEC 
in accordance with local requirements and receive documented IRB or IEC approval before 
modifications can be implemented.
9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(ies). Gilead 
will ensure that the report meets the standards set out in the ICH Guideline for Structure and 
Content of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in 
certain cases.
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly media only after the following conditions have been met:

The results of the study in their entirety have been publicly disclosed by or with the consent 
of Gilead in an abstract, manuscript, or presentation form or the study has been completed at 
all study sites for at least 2 years.

The investigator will submit to Gilead any proposed publication or presentation along with 
the respective scientific journal or presentation forum at least 30 days before submission of 
the publication or presentation. 

No such communication, presentation, or publication will include Gilead’s confidential 
information.

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.

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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, e.g. attendance at Investigator's Meetings. If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.
9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
eCRF.
The monitor is responsible for routine review of the eCRF at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the eCRF. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies), IRBs, and IECs. In terminating the study, Gilead and the investigator 
will assure that adequate consideration is given to the protection of the subjects’ interests.

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10.
REFERENCES
Affer M, Chesi M, Chen WD, Keats JJ, Demchenko YN, Tamizhmani K, et al. Promiscuous 
rearrangements of the MYC locus  hijack enhancers but mostly super-enhancers 
to dysregulate MYC expression in multiple myeloma. Leukemia 2014:1-43.
Alluri PG, Asangani IA, Chinnaiyan AM. BETs abet Tam-R in ER-positive breast cancer. Cell 
research 2014;24 (8):899-900.
Amorim S, Stathis A, Gleeson M, Iyengar S, Magarotto V, Leleu X, et al. Bromodomain 
inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-
escalation, open-label, pharmacokinetic, phase 1 study. Lancet Haematol 2016;3 
(4):e196-204.
Asangani IA, Dommeti VL, Wang X, Malik R, Cieslik M, Yang R, et al. Therapeutic targeting 
of BET bromodomain proteins in castration-resistant prostate cancer. Nature 
2014;510 (7504):278-82.
Barrans S, Crouch S, Smith A, Turner K, Owen R, Patmore R, et al. Rearrangement of MYC is 
associated with poor prognosis in patients with diffuse large B-cell lymphoma 
treated in the era of rituximab. J Clin Oncol 2010;28 (20):3360-5.
Belkina AC, Denis GV. BET domain co-regulators in obesity, inflammation and cancer. Nature 
reviews. Cancer 2012;12 (7):465-77.
Berthon C, Raffoux E, Thomas X, Vey N, Gomez-Roca C, Yee K, et al. Bromodomain inhibitor 
OTX015 in patients with acute leukaemia: a dose-escalation, phase 1 study. 
Lancet Haematol 2016;3 (4):e186-95.
Chesi M, Robbiani DF, Sebag M, Chng WJ, Affer M, Tiedemann R, et al. AID-dependent 
activation of a MYC transgene induces multiple myeloma in a conditional mouse 
model of post-germinal center malignancies. Cancer cell 2008;13 (2):167-80.
Chng WJ, Huang GF, Chung TH, Ng SB, Gonzalez-Paz N, Troska-Price T, et al. Clinical and 
biological implications of MYC activation: a common difference between MGUS 
and newly diagnosed multiple myeloma. Leukemia 2011;25 (6):1026-35.
Clark GM, Osborne CK, McGuire WL. Correlations between estrogen receptor, progesterone 
receptor, and patient characteristics in human breast cancer. J Clin Oncol 1984;2 
(10):1102-9.
Cytel Inc. East Software Version 6.4 Cambridge, MA: 2016:
Dang CV. MYC on the path to cancer. Cell 2012;149 (1):22-35.

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Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. BET bromodomain 
inhibition as a therapeutic strategy to target c-Myc. Cell 2011;146 (6):904-17.
Feng Q, Zhang Z, Shea MJ, Creighton CJ, Coarfa C, Hilsenbeck SG, et al. An epigenomic 
approach to therapy for tamoxifen-resistant breast cancer. Cell research 2014;24 
(7):809-19.
Filippakopoulos P, Knapp S. Targeting bromodomains: epigenetic readers of lysine acetylation. 
Nat Rev Drug Discov 2014;13 (5):337-56.
Ghoshal A, Yugandhar D, Srivastava AK. BET inhibitors in cancer therapeutics: a patent review. 
Expert Opin Ther Pat 2016;26 (4):505-22.
Glitza IC, Lu G, Shah R, Bashir Q, Shah N, Champlin RE, et al. Chromosome 8q24.1/c-MYC 
abnormality: a marker for high-risk myeloma. Leuk Lymphoma 2014:1-6.
Hargreaves DC, Horng T, Medzhitov R. Control of inducible gene expression by signal-
dependent transcriptional elongation. Cell 2009;138 (1):129-45.
Hawksworth D, Ravindranath L, Chen Y, Furusato B, Sesterhenn IA, McLeod DG, et al. 
Overexpression of C-MYC oncogene in prostate cancer predicts biochemical 
recurrence. Prostate cancer and prostatic diseases 2010;13 (4):311-5.
Howell SJ, Howell A. Diseases of the Breast - Chapter 73: Treatment of Metastatic Breast 
Cancer: Endorcine Therapy. 2010. 
Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S, Mele DA, et al. Targeting 
MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad 
Sci U S A 2011;108 (40):16669-74.
Nagarajan S, Hossan T, Alawi M, Najafova Z, Indenbirken D, Bedi U, et al. Bromodomain 
protein BRD4 is required for estrogen receptor-dependent enhancer activation and 
gene transcription. Cell reports 2014;8 (2):460-9.
Nesbit CE, Tersak JM, Prochownik EV. MYC oncogenes and human neoplastic disease. 
Oncogene 1999;18 (19):3004-16.
Neuenschwander B, Branson M, Gsponer T. Critical aspects of the Bayesian approach to phase I 
cancer trials. Stat Med 2008;27 (13):2420-39.
Nupponen NN, Kakkola L, Koivisto P, Visakorpi T. Genetic alterations in hormone-refractory 
recurrent prostate carcinomas. Am J Pathol 1998;153 (1):141-8.
Osborne CK, Schiff R. Mechanisms of endocrine resistance in breast cancer. Annu Rev Med 
2011;62:233-47.

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Perry AM, Alvarado-Bernal Y, Laurini JA, Smith LM, Slack GW, Tan KL, et al. MYC and 
BCL2 protein expression predicts survival in patients with diffuse large B-cell 
lymphoma treated with rituximab. Br J Haematol 2014;165 (3):382-91.
Sengupta S, Biarnes MC, Clarke R, Jordan VC. Inhibition of BET proteins impairs estrogen-
mediated growth and transcription in breast cancers by pausing RNA polymerase 
advancement. Breast Cancer Res Treat 2015;150 (2):265-78.
Shi J, Vakoc CR. The mechanisms behind the therapeutic activity of BET bromodomain 
inhibition. Mol Cell 2014;54 (5):728-36.
Tan SH, Wolff AC. Diseases of the Breast - Chapter 74: Treatment of Metastatic Breast Cancer: 
Chemotherapy. 2010. 
Yuan X, Cai C, Chen S, Yu Z, Balk SP. Androgen receptor functions in castration-resistant 
prostate cancer and mechanisms of resistance to new agents targeting the 
androgen axis. Oncogene 2014;33 (22):2815-25.

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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table
Appendix 3.
Pharmacokinetics, Pharmacodynamic Time Point Collection Tables
Appendix 4.
Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 6.
Performance Status Scoring System (ECOG)
Appendix 7.
RECIST 1.1
Appendix 8.
Exemestane (Aromasin®) Prescribing Information
Appendix 9.
Fulvestrant (Faslodex®) Prescribing Information
Appendix 10.
Bayesian Logistic Regression Model

PPDPPD
PPD

PPD

PPD

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13
C1D1 pre-dose samples may be drawn up to 2 days prior to the visit.
14
Coagulation assessment includes PT/INR, aPTT to be done at Screening and predose of: C1D1, C1D15 and C2D1 
15
Subjects who are on goserelin will have serum pregnancy, serum estradiol, and FSH checked first day of Cycle 1 to Cycle 3, and a urine pregnancy test will be performed
monthly thereafter starting cycle 4
16
HCV RNA Reflex is required
17
If available, paraffin embedded archival tumor tissue block or freshly sectioned unstained slides will be requested to be shipped to Gilead or designee. These samples will be
requested on or after C1D1. 
18
Tumor burden as assessed by RECIST v. 1.1 Guidelines (refer to Appendix 7).
19
The same radiographic procedure used to define measurable lesions must be used throughout the study for each subject. CT/MRI to be done at EOT visit if not done within the 
previous 4 weeks. Subjects who discontinue study treatment for reasons other than disease progression will continue to have tumor assessments performed during the follow 
up visits every 8 weeks for the first year and then every 12 weeks until disease progression, initiation of new anti-cancer therapy, or discontinuation from the overall study 
participation (death, subject’s request, lost to follow-up) whichever happens first. Every effort should be made to perform a last tumor assessment before starting a new 
anti-cancer therapy. Additional unscheduled tumor assessments may be performed as clinically indicated at any time.
20
All subjects will also undergo a bone scan during Screening (within 12 weeks prior to randomization). Bone scans performed before the signing of informed consent as 
routine procedures (but within 12 weeks before randomization) do not need to be repeated and may be used as baseline assessments as long as (1) tests were performed using 
the method requirements outlined in RECIST v.1.1 (2) appropriate documentation indicating that these radiographic tumor assessments were performed as standard of care is 
available in the patient’s source notes. Any suspicious abnormalities identified on the bone scans at baseline and on subsequent bone scans MUST be confirmed by X-ray, CT 
scan with bone windows or MRI. The same modality must be used throughout the trial for confirmation for a given lesion/patient. Bone lesions identified at baseline will be 
followed up according to the same assessment schedule every 8 weeks (±7 days) for the first year and then every 12 weeks (±7 days) from the date of randomization.
21
Subjects who discontinue study treatment for reasons other than disease progression will continue to have tumor assessments performed during the follow up visits every 8 
weeks for the first year and then every 12 weeks until disease progression, initiation of new anti-cancer therapy, or discontinuation from the overall study participation (death, 
subject’s request, lost to follow-up) whichever happens first. Every effort should be made to perform a last tumor assessment before starting a new anticancer therapy. 
Additional unscheduled tumor assessments may be performed as clinically indicated at any time.
 
 
PPD

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Appendix 4.
Common Terminology Criteria for Adverse Events (CTCAE) v4.03
CTCAE v 4.03 can be assessed from the link below:
http://www.hrc.govt.nz/sites/default/files/CTCAE%20manual%20-%20DMCC.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 post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.  
Subjects with breast cancer who are also receiving hormonal therapies, women are considered to 
be in a postmenopausal state when they are > 60 years of age with cessation of previously 
occurring menses for > 12 months without an alternative cause. In addition, women of any age 
with amenorrhea of > 12 months may also be considered postmenopausal if their follicle 
stimulating hormone (FSH) level is in the postmenopausal range and they are not using hormonal 
contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
In addition, pre/perimenopausal women are considered in a postmenopausal state due to 
treatment with the LHRH agonist goserelin. Subjects must have commenced treatment with 
goserelin or an alternative LHRH agonist at least 4 weeks prior to C1D1, leading to a reduction 
in luteinizing hormone production and consequent reduction of sex steroid hormones to 
castration levels by the time of exposure to study drugs.
b. Definition of Male Fertility
For the purposes of this study, a partner of a female study subject is considered to be fertile after 
the initiation of puberty unless permanently sterile by bilateral orchiectomy or medical 
documentation.
2) Contraception Requirements for Female Subjects
a. Study Drug Effects on Pregnancy and Hormonal Contraception
GS-5829 is contraindicated in pregnancy as any potential for human teratogenicity/fetotoxicity in 
early pregnancy is currently unknown. GS-5829 has insufficient data to exclude the possibility of 
a clinically relevant interaction with hormonal contraception that results in reduced contraception 
efficacy. Therefore, contraceptive steroids are not recommended as a contraceptive method 
either solely or as a part of a contraceptive regimen. Please refer to the latest version of the 
investigator’s brochure for additional information.

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b. Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects who are pre/peri-menopausal and treated with goserelin or an 
alternative LHRH agonist starting at least 4 weeks prior to C1D1 and throughout the duration of 
the study (per the above definition) of childbearing potential requires the use of highly effective 
contraceptive measures. They must also not rely on hormone-containing contraceptives as a form 
of birth control during the study. They must have a negative serum pregnancy test at Screening 
and a negative pregnancy test on the Baseline/Day 1 visit prior to initial randomization. 
Pregnancy tests will be performed at protocol-specified dates thereafter. Female subjects must 
agree to one of the following from Screening until 30 days following the end of relevant 
systemic exposure.

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.
Or

Consistent and correct use of 1 of the following methods of birth control listed below. 
Intrauterine device (IUD) with a failure rate of <1% per year
Tubal sterilization
Vasectomy in the male partner (provided that the partner is the sole sexual partner and 
had confirmation of surgical success 3 months after procedure)
Subjects must also refrain from egg donation and in vitro fertilization during treatment and until 
at least 30 days after the end of relevant systemic exposure.
3) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (e.g., calendar, 
ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhea method (LAM). Female condom and male condom should not 
be used together.
4) 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 30 days of last study drug dose. 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 they are pregnant during the study must report the information 
to the investigator. Instructions for reporting pregnancy, partner pregnancy, and pregnancy 
outcome are outlined in Section 7.6.2.1.

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Appendix 6.
Performance Status Scoring System (ECOG)
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, e.g., light house work, office work
2
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and 
about more than 50% of waking hours
3
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5
Dead

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Appendix 7.
RECIST 1.1
E.A. Eisenhauera, et al. New response evaluation criteria in solid tumors:
Revised RECIST guideline (version 1.1). European Journal of Cancer 45 (2009) 228-247.

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Appendix 8.
Exemestane (Aromasin®) Prescribing Information 
http://www.pfizer.com/products/product-detail/aromasin

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Appendix 9.
Fulvestrant (Faslodex®) Prescribing Information
http://www.faslodexhcp.com/home.html

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Appendix 10.
Bayesian Logistic Regression Model
Determination of the MTD will be based on the posterior probability of DLT rate estimated by a 
2-parameter BLRM with overdose control {Neuenschwander 2008} and calculated using East 
software {Cytel Inc 2016}.
Let π[di] be the probability of DLT at dose level di of GS-5829. The statistical model describing 
dose-toxicity relationship will have the following form:
ߨሾ݀௜ሿൌ
expሺlog ሺߙሻ൅ߚlog ሺ݀௜
݀∗ሻሻ
1 ൅expሺlog ሺߙሻ൅ߚlog ሺ݀௜
݀∗ሻሻ
where α, β > 0 and d* is the reference dose level. The prior specification of the model parameters 
is provided below. The estimate of parameters will be updated as data are accumulated and the 
toxicity probability at each dose level will be calculated based on the posterior distributions of 
the model parameters. The estimated posterior probability of DLT rate at each dose level will be 
summarized using the following intervals:
Under dosing: [0.00, 0.167)
Targeted toxicity: [0.167, 0.333]
Excessive toxicity: (0.333, 1.00]
The overdose control criterion is set as the posterior probability of excessive toxicity less than 
25%. The dose level recommended for the next cohort will be the dose cohort at which the 
posterior probability for the target toxicity interval is maximum among all dose candidates 
satisfying the overdose control criterion.
The trial can be stopped if any one of three criteria is met:
1. The posterior probability of targeted toxicity exceeds 70% and at least 6 subjects have been 
allocated at a dose level
2. Maximum number of subjects (N=12) has been treated at a dose level 
3. Maximum number of subjects (N=30) has been reached

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1. Planned Dose Levels
The provisional dose levels for GS-5829 are 3 mg, 4 mg, 6 mg and 9 mg once daily. 
2. Prior Specification
The prior distribution for (log(α), log(β)) is assumed to be a bivariate normal distribution. The 
following non-informative prior is used first:

The median DLT rate at 3 mg is assumed to be 15%, i.e. mean(log(α))= -1.73.

A doubling in dose is assumed to double the odds of DLT, i.e. mean(log(β)) = 0 

The StD of log(α) is set to 2 and the StD of log(β) to 1.

The correlation between log(α) and log(β) is set to be 0.  
Then the posterior is calculated based on the data collected from other on-going studies 
(GS-US-350-1599 and GS-US-350-1604) and will be updated as more data in these studies are 
collected. The prior for the current study will be based on the posterior calculated based on the 
data from GS-US-350-1599 and GS-US-350-1604 with inflated variance to discount the 
information from GS-US-350-1599 and GS-US-350-1604 considering between-trial variations.
Appendix Table 1.
DLT data collected in GS-US-350-1599 and GS-US-350-1604 as of 
22 July 2016*
QD Dose (mg)
Total number of evaluable subjects
Number of subjects with DLT
0.6
2
0
1.4
1
0
2
5
0
3
10**
1
4
2
1
*
Current data were collected only for subjects with GS-5829 monotherapy
**    A total of 13 subjects dosed, but 10 were evaluable
Appendix Table 2.
Prior for and Posterior from current data collected in 
GS-US-350-1599 and GS-US-350-1604
Parameter
Means
Variances
Correlation
Prior for (log(α), log(β))
(-1.73, 0)
(4, 1)
0
Posterior for (log(α), log(β)) from data in 
Appendix Table 1
(-2.13, 0.52)
(0.56, 1.02)
-0.01
Prior for (log(α), log(β)) used to assess operating 
characteristics by simulation  
(-2.13, 0.52)
(1.12, 2.04)
-0.01

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Appendix Table 3 shows the posterior probabilities of DLT rate based on current data from 
GS-US-1599 and GS-1604. Because there is a high chance of under dosing for 2 mg and low 
chance of overdosing for 3 mg, 3 mg once daily of GS-5829 is planned as the starting dose in the 
Phase 1b Dose Escalation portion of this study. The starting dose level may be either higher or
lower than 3 mg once daily, if either a higher or lower dose has been demonstrated to be both 
safe and tolerable in Studies GS-US-350-1599 and GS-US-250-1604. The new dose level will be 
selected prior to initiating dosing in this study.
Appendix Table 3.
Summary of posterior probabilities of DLT based on data from 
GS-US-350-1599 and GS-US-350-1604 as of 22 July 2016
QD Dose (mg)
Pr(DLT)
Posterior Probability of
Median
Under
[0%, 16.7%)
Target
[16.7% 33.3%]
Excessive
(33.3%, 100%)
2 
0.05
0.95
0.05
0.001
3 
0.10
0.68
0.30
0.02
4 
0.2
0.43
0.35
0.23
6 
0.34
0.24
0.26
0.50
9 
0.51
0.15
0.20
0.65
3. Operating Characteristics
In order to assess operating characteristics, simulation was performed under 2 hypothetical 
scenarios using East software {Cytel Inc 2016}. A total of 1000 trials were simulated under each 
scenario.
Scenario 1: Only the lowest dose level (2 mg) is safe
Scenario 2: The dose level of 4 mg or below are safe
Appendix Table 4.
True underlying DLT rates in hypothetical scenarios 
QD Dose (mg)
True DLT rate
Scenario 1
Scenario 2
2 
0.30
0.10
3 
0.40
0.20
4 
0.50
0.30
6 
0.60
0.40
9 
0.70
0.50

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As shown in Appendix Table 5, the simulations illustrate that the model has reasonable operating 
characteristics. The probabilities of recommending a correct dose level and stopping the study 
with declaring all dose levels to be toxic are 27.9% and 53.1%, respectively, in Scenario 1. The 
probability of recommending a correct dose level in Scenario 2 is 73.8%. The design is not 
aggressive to assign subjects to high toxic dose levels even with strong prior information based 
on the safety data from 20 evaluable subjects from other studies as of July 22, 2016.
Appendix Table 5.
Simulation results for operating characteristics in hypothetical 
scenarios
Operating Characteristics
Scenario 1
Scenario 2
Proportion of trials that recommend dose levels with true 
Pr(DLT) in [0.167, 0.333] (Correct decision)
27.9%
73.8%
Proportion of trials that recommend dose levels with true 
Pr(DLT)>0.333 (Patient risk)
19.0%
13.7%
Proportion of trials that recommend dose levels with true 
Pr(DLT)<0.167 
0
3.6%
Proportion of trials which stops early because all dose levels are 
too toxic
53.1%
8.9%
Average number of subjects evaluated
15
20