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

This study is designed to evaluate the safety, tolerability and antitumor activity of FOR46 in patients with metastatic castration-resistant prostate cancer. This study will be conducted in two parts:

Dose escalation:

This part will evaluate increasing doses of FOR46 to identify the maximum tolerated dose (MTD). The first patient enrolled on the study will receive the lowest dose of FOR46. Once this dose is shown to be safe, a second patient will be enrolled at the next higher dose. Patients will continue to be enrolled into either single or multiple patient groups receiving increasing doses until the MTD is reached.

Dose expansion:

This part of the study will further evaluate the safety, tolerability and antitumor activity of FOR46 at a dose shown to be safe in the dose escalation part of the study. Patients will be enrolled into 1 of 2 groups, based on histology.

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)