Phase 1/2A Study of TRC253, an Androgen Receptor Antagonist, in Metastatic Castration-resistant Prostate Cancer Patients

Inclusion Criteria

• •1. Must have received at least 2 prior therapies approved for CRPC; including a prior AR inhibitor (e.g., enzalutamide or apalutamide). (Part 1 only)
• •2. Must have received enzalutamide or apalutamide. (Note: additional therapies approved for CRPC prior to enzalutamide or apalutamide are allowed.) (Part 2 only)
• •3. Must have shown clinical characteristics of acquired resistance to enzalutamide or apalutamide defined as: decline in serum PSA ≥50% compared to baseline serum levels by week 12 (±4 weeks) of enzalutamide or apalutamide treatment and before disease progression by PCWG3 PSA criteria, OR disease progression by PCWG3 radiographic criteria. (Part 2 only)
• •Parts 1 and 2:
• •4. Histologically confirmed adenocarcinoma of the prostate with metastatic disease.
• •5. Male ≥18 years of age.
• •6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• •7. Prior orchiectomy or serum testosterone levels \<50 ng/dL determined within 4 weeks prior to start of study drug.
• •8. Adequate baseline organ function.
• •9. Ongoing androgen depletion therapy with a gonadotropin-releasing hormone (GnRH) analog or inhibitor, or orchiectomy (i.e., surgical or medical castration). Note: patients who have not undergone orchiectomy must continue GnRH analog therapy for the duration of this protocol.
• •10. For patients previously treated with first generation anti-androgens (i.e., flutamide, nilutamide, or bicalutamide), discontinuation of flutamide or nilutamide therapy must occur \>4 weeks (\>6 weeks for bicalutamide) prior to start of study drug with no evidence of an anti-androgen withdrawal response (i.e., no decline in serum PSA).
• •11. For patients previously treated with chemotherapy, targeted therapy, immunotherapy, or treatment with an investigational anticancer agent, discontinuation must have occurred ≥2 weeks, or after at least 4 half-lives, whichever is longer, prior to study drug administration. For enzalutamide and apalutamide, the washout period will be at least 3 weeks prior to start of study drug with no evidence of an anti-androgen withdrawal response (i.e., no decline in serum PSA).
• •12. For patients previously treated with other agents approved for the treatment of prostate cancer (5-α reductase inhibitors, estrogens, others), discontinuation of therapy must have occurred ≥4 weeks prior to start of study drug.
• •13. Palliative radiotherapy (to bone or soft tissue lesions) must be completed \>2 weeks prior to start of study drug.
• •14. For patients receiving bone-loss prevention treatment (e.g., bisphosphonates or denosumab), the patient must be on stable dose ≥4 weeks prior to start of study drug.
• •15. A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control during the study and for 4 weeks after receiving the last dose of study drug. All men must also not donate sperm during the study and for 90 days after receiving the last dose of study drug.
• •16. Patient must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
• •17. Each patient must sign an informed consent form (ICF) indicating that he understands the purpose of and procedures required for the study and is willing to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the patient's disease.