Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5829 as a Single Agent and In Combination With Enzalutamide in Participants With Metastatic Castrate-Resistant Prostate Cancer

Key Inclusion Criteria:

- Histologically or cytologically confirmed prostate cancer (individuals with primary
neuroendocrine carcinoma of prostate are excluded)

- Must have documented progressive disease by meeting at least one of the Prostate
Cancer Working Group 2 Criteria

- Castration resistant disease defined as ongoing androgen deprivation therapy with
gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy and serum
testosterone level ≤ 1.73 nmol/l (50 ng/dL) at screening visit. Individuals who have
not had a bilateral orchiectomy must have a plan to maintain effective GnRH-analogue
therapy for the duration of the trial.

- Metastatic disease documented by bone lesions on bone scan or by measurable soft
tissue disease by CT/MRI. Patients whose disease spread is limited to regional pelvic
lymph nodes are not eligible

- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1

- Adequate organ function defined as follows:

- Hematologic: Platelets ≥ 100 x 10^9/L; Hemoglobin ≥ 9.0 g/dL; absolute neutrophil
count (ANC) ≥ 1.5 x 10^9/L (without platelet transfusion or any growth factors
within previous 7 days of the hematologic laboratory values obtained at screening
visit)

- Hepatic: Aspartate transaminase (AST) / Alanine transaminase (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

- Renal: Serum Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min as
calculated by the Cockroft-Gault method

- Coagulation: International Normalized Ratio (INR) ≤ 1.2

Key Exclusion Criteria:

- Known brain metastasis or leptomeningeal disease

- Myocardial infarction, symptomatic congestive heart failure (New York Heart
Association Classification > Class II), unstable angina, or serious uncontrolled
cardiac arrhythmia within the last 6 months of Cycle 1 Day 1

- 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) Grade > 1

- Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy) within
21 days or 5 half-lives, whichever is longer, of study drug dosing (6 weeks for
nitrosoureas, mitomycin C, or molecular agents with t1/2 > 10 days); concurrent use of
an luteinizing hormone releasing hormone (LHRH) agonist is permitted for all
individuals and ongoing enzalutamide is required in Group 3.

- History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia
method) at screening is prolonged (> 450 ms).

- Prior exposure to bromodomain (BET) inhibitors

- Clinically significant bleeding within 28 days of Cycle 1 Day 1

- Known human immunodeficiency virus (HIV) infection

- HBsAg positive

- Hepatitis C virus (HCV) antibody positive

- Use of moderate/strong cytochrome P450 (CYP)3A4 inhibitors or moderate/strong CYP3A4
inducers within 2 weeks prior to the first dose of study drug (with the exception of
enzalutamide in the combination arms)

- Evidence of bleeding diathesis

- History of hemoptysis of ≥ 2.5 mL/1 teaspoon within 6 months of Cycle 1 Day 1

- History of high grade esophageal or gastric varices

- Anticoagulation/antiplatelet therapy within 7 days of Cycle 1 Day 1, including low
molecular weight heparin, or warfarin.

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.