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