64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for Identification and Treatment of PSMA-expressing Metastatic Castrate Resistant Prostate Cancer (SECuRE)

Required: FOLH1 imaging positive (64Cu-SAR-bisPSMA uptake (SUVmax) of at least 1 known lesion is higher than that of the liver)

Positive 64Cu-SAR-bisPSMA PET/CT scan, where 64Cu-SAR-bisPSMA uptake (SUV max) of at least 1 known lesion is higher than that of the liver

Excluded: FOLH1 imaging negative

Evidence of progressive lesion(s) on MRI and/or CT (according to RECIST V1.1) that is prostate-specific membrane antigen (PSMA) negative on the 1 hour 64Cu-SAR-bisPSMA PET/CT scan as determined at screening

Must have received: androgen receptor pathway inhibitor (enzalutamide, abiraterone, darolutamide, apalutamide) — castration-resistant

progressive metastatic castration-resistant prostate cancer (mCRPC) despite prior androgen deprivation therapy and: Dose Escalation: at least either enzalutamide and/or abiraterone (or other such androgen receptor pathway inhibitors [ARPIs]). Cohort Expansion Main Group: Participant has progressed once or twice on a prior second generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide). Cohort Expansion Concomitant Enzalutamide Group: Participant has progressed only once on prior second generation ARPI (prior abiraterone, darolutamide, or apalutamide is allowed, prior treatment with enzalutamide is not allowed).

Cannot have received: systemic radionuclide (177Lu, Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Actinium-225, Iodine-131, Radium-223)

Previous treatment with a systemic radionuclide, including 177Lu, Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Actinium-225, Iodine-131 within 6 months or in case of Radium-223 within 3 months of treatment initiation (Day 0) without prior approval of the medical monitor

Cannot have received: PSMA targeted radionuclide therapy (177Lu, Actinium-225)

Any previous PSMA targeted radionuclide therapy (including 177Lu and Actinium-225) is also excluded

Cannot have received: systemic anti-cancer therapy

Exception: LHRH, any other androgen deprivation therapy (ADT) or low dose corticosteroids allowed

Previous treatment with any systemic anti-cancer therapy (e.g. immunotherapy or biological therapy [including monoclonal antibodies]) within 4 weeks prior to treatment on study with the exception of LHRH, any other androgen deprivation therapy (ADT) or low dose corticosteroids

Cannot have received: chemotherapy

Exception: adjuvant or neoadjuvant taxane exposure (max 6 cycles) allowed if 12 months have elapsed since completion

Prior treatment with cytotoxic chemotherapy for castration resistant PCa (e.g. taxanes, platinum, estramustine, vincristine, methotrexate, etc) is also excluded. Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy

Cannot have received: PARP inhibitor

Prior treatment with any poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) is also excluded

Cannot have received: investigational agent

Previous treatment with any investigational agents within 4 weeks prior enrollment into the study