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)