FOR46 in Combination With Enzalutamide in Patients With Metastatic Castration Resistant Prostate Cancer

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.

Inclusion Criteria: 1. Histologically confirmed metastatic prostate adenocarcinoma. 2. Disease progression by PCWG3 criteria at study entry. 3. Prior progression by PCWG3 criteria on one or more androgen signaling inhibitors including abiraterone acetate, enzalutamide, apalutamide, and/or darolutamide. 4. No prior taxane-based chemotherapy for the treatment of mCRPC. Prior taxane use in the castration-sensitive prostate cancer (CSPC) setting allowed provided last dose \> 6 months prior to study entry. 5. Patients must be evaluable for the primary endpoint of composite response, and must have either serum PSA ≥ 2 ng/mL during Screening and/or measurable disease by RECIST 1.1 criteria. 6. Participants must be willing to undergo metastatic tumor biopsy during Screening. If there is no safely accessible metastatic lesion, this requirement will be waived. 7. Dose Expansion only: Participants must be willing to undergo CD46-directed Positron Emission Tomography (PET) imaging during Screening (Co-enrolling on NCT05245006, Groups B and C) 8. Castrate level of serum testosterone at study entry (\=18 years. 11. Eastern Cooperative Oncology Group (ECOG) performance status \= 70 percent (%)). 12. Demonstrates adequate organ function as defined below: 1. Absolute neutrophil count ≥ 1,500/microliter (mcL). 2. Platelets \>= 100,000/mcL and no platelet transfusions during the 14 days prior to first dose of FOR46. 3. Hemoglobin \>= 8.0 grams per deciliter (g/dL) without red blood cell transfusion during the 14 days prior to first dose of FOR46. 4. Total bilirubin \