A Phase I/IIa Theranostic Study of 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for Identification and Treatment of PSMA-expressing Metastatic Castrate Resistant Prostate Cancer

• 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 at least either enzalutamide and/or abiraterone (or other such androgen receptor pathway inhibitors). Documented progressive mCRPC will be based on at least 1 of the following criteria:

• 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;

• 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;

• 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.