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 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:

      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;

   - 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;

   - Previous treatment with any systemic anti-cancer therapy (e.g. chemotherapy,
   immunotherapy or biological therapy [including monoclonal antibodies]) within 4 weeks
   prior to treatment on study with the exception of Luteinizing Hormone Releasing
   Hormone, any other androgen deprivation therapy (ADT) (if ADT is discontinued prior to
   enrolment, 14 days must elapse after abiraterone discontinuation and 28 days after
   enzalutamide before participant can be enrolled) or low dose corticosteroids;

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

   - Known hypersensitivity to the components of the investigational products or its
   analogues;

   - Transfusion for the sole purpose of making a participant eligible for study inclusion;

   - Spinal metastasis with symptomatic cord compression, or clinical or radiologic
   findings indicative of impending cord compression;

   - Concurrent serious medical conditions, including, but not limited to, New York Heart
   Association class III or IV congestive heart failure, history of congenital prolonged
   QT syndrome, uncontrolled infection, known active hepatitis B or C, or other
   significant co-morbid conditions that in the opinion of the Investigator would impair
   study participation or cooperation;

   - Diagnosed with other malignancies that are expected to alter life expectancy or may
   interfere with disease assessment. However, participants with a prior history of
   malignancy that has been adequately treated and who have been disease free for more
   than 3 years are eligible, as are participants with adequately treated non-melanoma
   skin cancer, superficial bladder cancer;

   - Any condition or personal situation that would pose an unacceptable radiation safety
   risk (as per institution guidelines, state and/or national regulations) to the
   participant or carer at the time of release following the completion of therapy (e.g.
   uncontrolled urinary incontinence, high dependency care);

   - Participants in whom it is known that external beam radiation therapy is scheduled
   after enrollment into the study.