PRIMARY OBJECTIVES:~Phase 1b:~I. To determine the maximally tolerated dose (MTD) and recommended phase 2 dose (RP2D) of FOR46 in combination with enzalutamide in patients with mCRPC.~Phase 2:~I. To determine the composite response rate of FOR46 plus enzalutamide, defined as:~Decline in serum PSA >= 50% (PSA50) from baseline, confirmed by repeat measurement at least 4 weeks later, and/or~Objective response by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.~SECONDARY OBJECTIVES:~Phase 1b and Phase 2:~I. To determine the PSA50 response rate.~II. To determine the objective response rate by RECIST 1.1 criteria among patients with measurable soft tissue by RECIST 1.1 criteria at baseline.~III. To determine the median duration of objective response.~IIII. To determine the median time to prostate-specific antigen (PSA) progression by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria.~V. To determine the median radiographic progression-free survival by PCWG3 criteria.~VI. To determine the median overall survival.~VII. To determine the safety of the combination.~Participants may continue study treatment from the time of treatment initiation until confirmed radiographic disease progression per PCWG3 / RECIST 1.1 criteria, unequivocal clinical progression, unacceptable toxicity, or patient withdrawal, whichever occurs first. Patients will be followed for overall survival every 90 days (+/- 30 days) from last dose of study treatment, until death, withdrawal of consent, or the end of the study, whichever occurs first.
This is a Phase 1b/2 study evaluating FOR46 in combination with enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC) after prior progression on abiraterone. FOR46 is designed to target and bind to CD46, a transmembrane cellular protein expressed at moderate or high levels in numerous cancer types. The investigators hypothesize that the combination of FOR46 plus enzalutamide will achieve a clinically significant composite response rate with sufficient durability of response in mCRPC patients.