A Phase 1 Study of FOR46 in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Inclusion Criteria

• Male ≥ 18 years of age
• Has histologically confirmed prostate cancer that is metastatic and has progressed as defined by PCWG3 criteria during or after treatment with at least 1 ASI (eg, abiraterone, enzalutamide, apalutamide), or another second-generation anti-androgen or cytochrome P450 (CYP)17A1 inhibitor, with the most recent ASI administered in the castration-resistant setting
• Has serum testosterone levels < 50 ng/dL during screening. Patients without a history of bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analog during the course of protocol therapy
• ECOG performance status of 0 or 1
• Adequate hematologic, renal and hepatic function
• Males with female partners of childbearing potential must agree to use 2 effective methods of contraception
• Patients must provide signed informed consent
• Patients enrolled into the dose expansion phase must have prostate carcinoma without histologic evidence of small-cell/neuroendocrine carcinoma features on prior biopsy or must have unequivocal histologic evidence of small-cell/neuroendocrine prostate carcinoma (pure or mixed). Patients with treatment-emergent small-cell neuroendocrine cancer (pure or mixed) may have received no more than on prior chemotherapy regimen for mCRPC
• Patients enrolled into the dose expansion phase must be willing to undergo a metastatic tumor biopsy or has tissue available from a prior post-castration resistant tumor biopsy

Exclusion Criteria

• Persistent clinically significant toxicities from previous anticancer therapy
• Has NCI CTCAE Grade ≥ 2 peripheral neuropathy from any etiology or has a genetic disorder that is associated with peripheral neuropathy even without current neuropathic manifestations
• Prior treatment with cytotoxic chemotherapy for mCRPC (chemotherapy in the hormone-sensitive setting is allowed if > 6 months before study entry)
• Has received external-beam radiation or systemic anticancer therapy within 14 days before first dose of FOR46
• Has received treatment with an investigational drug within 28 days before first dose of FOR46
• Has had a major surgical procedure within 28 days before administration of FOR46 dose
• Clinically significant cardiovascular disease
• Uncontrolled, clinically significant pulmonary disease
• Has a history of brain or leptomeningeal metastases.
• Uncontrolled intercurrent illness
• Has a known positive status for HIV or either active/chronic hepatitis B/C
• Requires medications that are strong inhibitors or strong inducers of CYP3A4
• [Dose escalation only] Has a history of episodic atrial fibrillation or flutter (patients with chronic atrial fibrillation are not excluded)