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

Inclusion Criteria:

1. Males age ≥ 18 years

2. Metastatic, castration-resistant, histologically confirmed prostate cancer

3. Surgical castration or continuous medical castration for ≥ 8 weeks prior toscreening; serum testosterone < 50 ng/dL confirmed within 4 weeks of firstadministration of study drug

4. Have progressed on prior abiraterone treatment by PCWG3 criteria

5. Patients who are not candidates for chemotherapy in the opinion of the investigatoror patients who decline chemotherapy

6. Cohort A only - Patient must meet definition of poor responder to abiraterone by oneof the following:

7. Abiraterone started in hormone-sensitive prostate cancer (HSPC) diseasesetting: < 12 months duration on abiraterone or failure to achieve PSA nadir of 0.2 ng/mL while taking abiraterone

8. Abiraterone started in castrate-resistant prostate cancer (CRPC) diseasesetting: < 6 months duration on abiraterone or failure to achieve a PSA50response

9. Cohort B only - Patient must meet definition of responder to abiraterone by one ofthe following:

10. Abiraterone started in hormone-sensitive prostate cancer (HSPC) diseasesetting: ≥ 12 months duration on abiraterone and nadir PSA < 0.2 ng/mL

11. Abiraterone started in castrate-resistant prostate cancer (CRPC) diseasesetting: ≥ 6 months duration on abiraterone and PSA50 response

12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

1. Any history of brain metastases, prior seizure, conditions predisposing to seizureactivity

2. Have previously received an investigational BET inhibitor (including previousparticipation in this study or a study of ZEN003694)

3. Receipt of prior second-generation androgen receptor inhibitors (e.g. enzalutamide,apalutamide, darolutamide, proxalutamide). Receipt of first-generation ARantagonists (e.g. bicalutamide, nilutamide, flutamide) does not count towards thislimit.

4. Have received prior chemotherapy in the metastatic castration-resistant setting (prior chemotherapy in the hormone-sensitive setting is allowed provided last dosewas at least 6 months prior to first dose of study drug)

5. 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

6. Have received exogenous administration of testosterone therapy since discontinuationof abiraterone.

7. Failure to recover to Grade 1 or lower toxicity related to prior systemic therapy (excluding alopecia and neuropathy) prior to study entry

8. Radiation therapy within 2 weeks of the first administration of study drug