Targeted Alpha Therapy With 225Actinium-Prostate Specific Membrane Antigen (PSMA)-I&T of Castration-resISTant Prostate Cancer (TATCIST).

Inclusion Criteria

• •1. Participants aged ≥ 18 years.
• •2. Participants must have the ability to understand and sign an approved informed consent (ICF).
• •3. Participants must have the ability to understand and comply with all protocol requirements.
• •4. Adenocarcinoma of prostate proven by histopathology.
• •5. Life expectancy of 6 months or more.
• •6. Unresectable metastases.
• •7. Documented progressive disease (PD); progressive mCRPC will be based on at least 1 of the following criteria:
• •1. Serum PSA progression is defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal starting value is 1.0 ng/mL, if PSA is the only indication of progression.
• •2. Soft-tissue progression defined as an increase ≥ 20% 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 treatment started or the appearance of one or more new lesions.
• •3. Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 PCWG3 criteria).
• •8. If known Breast Cancer gene (BRCA) mutations are present, participants should have received FDA approved therapies such as poly-ADP ribose polymerase (PARP) inhibitors and progressed.
• •9. Castration resistant disease with confirmed testosterone level ≤ 50 ng/dL under prior androgen deprivation therapy (ADT). Must have a castrate level of serum testosterone (\< 50 ng/dL or \< 1.7 nmol/L).
• •10. Positive PSMA PET/CT scans, obtained with approved PSMA-ligands, defined as at least one PSMA-positive metastatic lesion and no PSMA-negative lesions.
• •11. ECOG-PS 0 to 1.
• •12. Hemoglobin (Hgb) concentration ≥ 9.0 g/dL.
• •13. Platelet counts ≥ 100 × 10\^9/L.
• •14. White blood cell (WBC) count ≥ 2.0 × 10\^9/L, absolute neutrophil count (ANC) \> 1.5 × 10\^9/L.
• •a. Hematological criteria cannot be met with ongoing or recent blood transfusions (within 7 days prior to the scheduled first dose of study treatment) or require growth factor support (within 21 days prior to the scheduled first dose of study treatment).
• •15. Alanine aminotransferase or aspartate aminotransferase ≤ 3.0 × upper limit of normal (ULN).
• •16. Serum total bilirubin ≤ 1.5 × ULN; in participants with Gilbert's syndrome, a total bilirubin ≤ 3 times ULN and direct bilirubin within normal limits are permitted.
• •17. Albumin ≥ 2.5 g/dL.
• •18. Serum/plasma creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min based on the Cockcroft-Gault formula.
• •19. Prothrombin time, international normalized ratio or prothrombin time test \< 1.5 × ULN.
• •20. Received ≥ 1 androgen receptor axis-targeted therapies (ARAT).
• •21. Participants on anti-androgen therapy are allowed to continue their treatment at the discretion of their treating physician.