Safety and efficacy of the oral bromodomain and extraterminal inhibitor GS-5829, both alone and in combination with enzalutamide, in patients with metastatic castration-resistant prostate cancer (mCRPC) were investigated in phase Ib research (1,604). Likewise, a phase I research (1,599) was carried out on solid tumors and lymphoma. In a 3 + 3 dose escalation paradigm, GS-5829 was administered at 2 mg once daily in combination with 160 mg once day enzalutamide to males with proven mCRPC who had disease progression on abiraterone and/or enzalutamide. The primary effectiveness outcome was the rate of progression-free survival at week 24; supplementary endpoints included the change in prostate-specific antigen from baseline, the rate of progression, and the pharmacokinetics of GS-5829 (PK). In addition to assessing pharmacokinetics and safety, Study 1,599 looked at the effects of 2 doses. There were 31 male participants in Research 1,604, and they had all received at least 1 dose of the study medicine. About 94% of patients reported treatment-emergent adverse events (TEAEs), and 16% stopped treatment due to TEAEs. The once-daily dosing of GS-5829 2–9 mg did not result in dose-dependent increases in AUCtau or Cmax, and the biomarkers CCR2 inhibition and HEXIM1 induction were only elevated at higher dosages when used alone. Interpatient variation in pharmacokinetic and pharmacodynamic parameters was substantial across all dosages. Among all treated patients, 25% had achieved nonprogression by week 24 (95% CI, 10-42) according to the Kaplan-Meier method. Patients with mCRPC were able to tolerate GS-5829, although the drug showed only modest effectiveness and no dose-related changes in plasma concentrations.