The COSMYC Trial (COmbined Suppression of MYC)

This research is being done to determine if receiving the combination of testosterone and ZEN-3694 followed by the combination of enzalutamide plus ZEN-3694 will decrease the size of tumors in patients with prostate cancer that has become resistant to castration and other therapies. The investigators also want to determine if dosing first with the combination of testosterone and ZEN-3694 may cause enzalutamide and ZEN-3694 to work more effectively.

Inclusion Criteria: 1. Eastern Cooperative Oncology Group (ECOG) Performance status ≤2. 2. Age ≥18 years. 3. Histologically-confirmed adenocarcinoma of the prostate. 4. Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist/antagonist). 5. Documented castrate level of serum testosterone (\4 weeks from last dose. 11. Prior treatment with BAT is allowed if the patient has progressed on an AR-axis inhibitor (i.e. abiraterone or antiandrogen) since BAT treatment. 12. Patients must be withdrawn from second-generation AR-axis inhibitor (Abiraterone, Enzalutamide, Darolutamide, or Apalutamide) for ≥ 2 weeks. 13. Attempts must be made to wean patients off prednisone prior to starting therapy. Patients who cannot be weaned due to symptoms may continue on lowest dose of prednisone achieved during weaning period. 14. Acceptable liver function: 1. Bilirubin \< 2.5 times institutional upper limit of normal (ULN) 2. Aspartate Transferase (AST) (SGOT) and Alanine Transaminase (ALT) (SGPT) \< 2.5 times ULN 15. Acceptable renal function: a. Serum creatinine \