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

Inclusion Criteria: * Signed informed consent; * ≥18 years of age; * Eastern Cooperative Oncology Group performance status of 0 to 2; * Life expectancy \>6 months; * Histological, pathological, and/or cytological confirmation of Prostate cancer (PCa); * Positive 64Cu-SAR-bisPSMA PET/CT scan, where 64Cu-SAR-bisPSMA uptake (standardized uptake value \[SUV\] max) of at least 1 known lesion is higher than that of the liver on the 1 hour positron emission tomography (PET)/computed tomography (CT) scan; * Castrate level of serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L); * Have 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 \[androgen receptor pathway inhibitorsARPIs\]). * Cohort Expansion Main Group: Participant has progressed once or twice on a prior second generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide). No concomitant ARPI on study. Note: First generation ARPI is allowed but not considered as prior ARPI. Second generation ARPI must be the most recent therapy received. * 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). Note: First generation ARPI is allowed but not considered as prior ARPI. Second generation ARPI must be the most recent therapy received. Documented progressive mCRPC will be based on at least 1 of the following criteria: 1. Serum/plasma prostate specific antigen (PSA) progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal value for study enrollment is 2.0 ng/mL; 2. Soft-tissue progression defined as a ≥20% increase in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since the last treatment directed at the metastatic cancer has started (not including hormonal therapy) or the appearance of 1 or more new lesions; 3. Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan. * ≥1 metastatic lesion that is present at screening CT, magnetic resonance imaging (MRI), or bone scan imaging obtained ≤28 days prior to enrollment into the study; * Participants must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (prior chemotherapy, radiation, immunotherapy, etc.); * Participants must have adequate organ function: * Bone marrow reserve: * White blood cell (WBC) count ≥2.5 x 109/L (2.5 x 109/L is equivalent to 2.5 x 103/μL and 2.5 x K/μL and 2.5 x 103/cc and 2500/μL) OR * Absolute neutrophil count (ANC) ≥1.5 x 109 /L (1.5 x 109 /L is equivalent to 1.5 x 103 /μL and 1.5 x K/μL and 1.5 x 103 /cc and 1500/μL); * Platelets ≥100 x 109 /L (100 x 109 /L is equivalent to 100 x 103 /μL and 100 x K/μL and 100 x 103 /cc and 100,000/μL); * Hemoglobin ≥9 g/dL (5.59 mmol/L); * Total bilirubin ≤1.5 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤3 x ULN is permitted; * Alanine aminotransferase or aspartate aminotransferase ≤3.0 x ULN OR ≤5.0 x ULN for participants with liver metastases; * Creatinine clearance or estimated glomerular filtration rate ≥50 mL/min * For participants who are human immunodeficiency virus infected: Participant must be healthy and have a low risk of Acquired Immune Deficiency Syndrome related outcomes in the opinion of the Investigator; * For participants who have partners of childbearing potential: Partner and/or participant must use a method of birth control with adequate barrier protection. Exclusion Criteria: * Major surgery within 12 weeks prior to enrollment into the study; * Brain metastasis; * Histologic diagnosis of small cell or neuroendocrine prostate cancer; * Prior history of leukemia or Myelodysplastic Syndrome; * Diagnosis of Deep Vein Thrombosis or Pulmonary Embolism within 4 weeks prior to enrollment into the study; * Unmanageable urinary tract obstruction; * Evidence of progressive lesion(s) on MRI and/or CT (according to Response Evaluation Criteria in Solid Tumors V1.1) that is prostate-specific membrane antigen (PSMA) negative on the 1 hour 64Cu-SAR-bisPSMA PET/CT scan as determined at screening. NOTE: THIS CRITERION IS NOT APPLICABLE TO PARTICIPANTS IN THE 64Cu-SAR-bisPSMA DOSIMETRY PHASE AND DOSE ESCALATION PHASE. * Previous treatment with a systemic radionuclide: * Dose Escalation: 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; * Cohort Expansion: Previous treatment with a systemic radionuclide, including Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, 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; Any previous PSMA targeted radionuclide therapy (including 177Lu and Actinium-225) is also excluded. * 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 Luteinizing Hormone Releasing Hormone (LHRH), any other androgen deprivation therapy (ADT) or low dose corticosteroids. * Dose Escalation: prior treatment with chemotherapy within 4 weeks of first administration of 67Cu-SAR-bisPSMA is also excluded. * Cohort Expansion: Prior treatment with cytotoxic chemotherapy for castration resistant PCa (e.g. taxanes, platinu