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

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 (\<50 ng/dL). Patients without prior bilateral orchiectomy are required to remain on Luteinizing hormone-releasing hormone (LHRH) analogue treatment for duration of study.
• •9. No other systemic anti-cancer therapies administered other than LHRH analogue within 14 days or, 5 half-lives, whichever is shorter, prior to initiation of study treatment. Adverse events related to prior anti-cancer treatment related to therapies other than LHRH analogue must have recovered to Grade ≤ 1 with the exception of any grade alopecia. a. Patients receiving enzalutamide prior to study entry may continue treatment at their current enzalutamide dose level without requirement for wash-out period.
• •10. Age \>=18 years.
• •11. Eastern Cooperative Oncology Group (ECOG) performance status \<= 1 (Karnofsky 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 \<=1.5 x institutional upper limit of normal (ULN), unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
• •5. Aspartate aminotransferase (AST) /serum glutamic-oxaloacetic transaminase (SGOT) \<=3 x institutional institutional upper limit of normal (ULN).
• •6. Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) =3 x ULN.
• •7. Serum creatinine \<= 1.5 x institutional upper limit of normal OR Calculated creatinine clearance glomerular filtration rate (GFR) \>= 60 mL/min, calculated using the Cockcroft-Gault equation.
• •8. Serum sodium level \>=130 mmol/L.
• •13. Ability to understand a written informed consent document, and the willingness to sign it.
• •14. Individuals with concurrent second malignancy requiring active treatment at study entry. Nonmelanoma skin cancer, non-muscle invasive bladder cancer, and other carcinomas-in-situ are allowable exceptions.
• •15. Patients must agree to use adequate contraception prior to the study, for the duration of study participation, and 60 days after last administration of study treatment. Adequate contraception includes:
• •1. Patients who are sexually active should consider their female partner to be of childbearing potential if she has experienced menarche and is not postmenopausal (defined as amenorrhea \> 24 consecutive months) or has not undergone successful surgical sterilization. Even women who use contraceptive hormones (oral, implanted, or injected), an intrauterine device, or barrier methods (diaphragms, condoms, spermicide) should be considered to be of childbearing potential.
• •2. Acceptable methods of contraception include continuous total abstinence, or double-barrier method of birth control (e.g. condoms used with spermicide, or condoms used with oral contraceptives). Periodic abstinence and withdrawal are not acceptable methods of contraception.