Clinical Trials

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 PCa.
• Positive 64Cu-SAR-bisPSMA PET/CT scan, where 64Cu-SARbisPSMA 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.
  • NOTE: ALL OTHER ELIGIBILITY CRITERIA MUST BE FULFILLED BEFORE THE 64Cu-SAR-bisPSMA ADMINISTRATION IS PERMITTED. THIS CRITERION IS NOT APPLICABLE TO PARTICIPANTS IN THE DOSIMETRY PHASE;
• Castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).
• Have progressive 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.

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 (> 1 cm in mean   diameter) 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 DOSIMETRY AND DOSE ESCALATION PHASE.
• Previous  treatment  with  any  systemic  radionuclide  (e.g.,  Lu, Strontium-89,   Samarium-153,    Rhenium-186,    Rhenium-188, Actinium-225,  Radium-223,  Iodine-131)  within  6 months  of treatment initiation;
• 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.
  • NOTE: THIS CRITERION IS NOT APPLICABLE TO PARTICIPANTS IN THE DOSIMETRY PHASE.
• 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 EBRT is scheduled after enrollment into the study.
  • NOTE: THIS CRITERION IS NOT APPLICABLE TO PARTICIPANTS IN THE DOSIMETRY PHASE.