Phase I Study of 225Ac-J591 Plus 177Lu-PSMA Small Molecule for Progressive Metastatic Castration Resistant Prostate Cancer

Inclusion Criteria: * Histologically or cytologically confirmed adenocarcinoma of prostate * Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria: PSA progression, Objective radiographic progression in soft tissue, New bone lesions * ECOG performance status of 0-2 * Have serum testosterone \< 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone bilateral orchiectomy * Have previously been treated with at least one of the following: Androgen receptor signaling inhibitor (such as enzalutamide), CYP 17 inhibitor (such as abiraterone acetate) * Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician or refused taxane chemotherapy * Age \> 18 years * Patients must have normal organ and marrow function as defined below: Absolute neutrophil count: \>2,000 cells/mm3, Hemoglobin: ≥9 g/dL, Platelet count: \>150,000 x 109/uL, Serum creatinine: \<1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault, Serum total bilirubin: \<1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin must be normal), Serum AST and ALT: \<1.5 x ULN in the absence of liver metastases; \<3 x ULN if due to liver metastases (in both circumstances bilirubin must meet entry criteria) * Ability to u…