ZEN003694 and Enzalutamide Versus Enzalutamide Monotherapy in Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria

• Males age ≥ 18 years
• Metastatic, castration-resistant, histologically confirmed prostate cancer
• Surgical castration or continuous medical castration for ≥ 8 weeks prior to screening; serum testosterone < 50 ng/dL confirmed within 4 weeks of first administration of study drug
• Have progressed on prior abiraterone treatment by PCWG3 criteria
• Patients who are not candidates for chemotherapy in the opinion of the investigator or patients who decline chemotherapy
• Cohort A only - Patient must meet definition of poor responder to abiraterone by one of the following:
• Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: < 12 months duration on abiraterone or failure to achieve PSA nadir of 0.2 ng/mL while taking abiraterone
• Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: < 6 months duration on abiraterone or failure to achieve a PSA50 response
• Cohort B only - Patient must meet definition of responder to abiraterone by one of the following:
• Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: ≥ 12 months duration on abiraterone and nadir PSA < 0.2 ng/mL
• Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: ≥ 6 months duration on abiraterone and PSA50 response
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria

• Any history of brain metastases, prior seizure, conditions predisposing to seizure activity
• Have previously received an investigational BET inhibitor (including previous participation in this study or a study of ZEN003694)
• Receipt of prior second-generation androgen receptor inhibitors (e.g. enzalutamide, apalutamide, darolutamide, proxalutamide). Receipt of first-generation AR antagonists (e.g. bicalutamide, nilutamide, flutamide) does not count towards this limit.
• Have received prior chemotherapy in the metastatic castration-resistant setting (prior chemotherapy in the hormone-sensitive setting is allowed provided last dose was at least 6 months prior to first dose of study drug)
• Have received prior systemic anti-cancer therapy within 2 weeks or five half-lives, whichever is shorter, prior to the first administration of study drug
• Have received exogenous administration of testosterone therapy since discontinuation of abiraterone.
• Failure to recover to Grade 1 or lower toxicity related to prior systemic therapy (excluding alopecia and neuropathy) prior to study entry
• Radiation therapy within 2 weeks of the first administration of study drug