The study schedule for each patient consists of a screening phase, a treatment phase, safety and long-term follow up phase, for an overall individual duration of approximately 32 months.~A minimum of 3 patients will be treated in each patient group at each dose level and evaluated for the occurrence of dose-limiting toxicity (DLT) during the first 6 weeks of treatment before consideration will be given to enrolling patients into the next dose level. Dose modifications for toxicity are allowed beyond the first 6 weeks of therapy and defined per protocol.~No more than 6 cycles of 225Ac-PSMA-617 will be administered. Patients may receive less than 6 cycles if they have disease progression, intolerable toxicity, started other anticancer therapy, or have withdrawn from treatment per subject or physician decision.~Subjects may also receive supportive care therapy, as determined by the investigative physician, however, subjects cannot receive concurrent investigational agents, cytotoxic chemotherapy, biological agents, targeted therapy, immunotherapy, other systemic radioisotopes, and hemi-body radiotherapy or novel androgen axis drugs [ARPIs] until completion of treatment with 225Ac-PSMA-617.
This is a Phase 1, open-label, international, dose escalation study to evaluate the safety of [225Ac]Ac-PSMA-617 (225Ac-PSMA-617) in men with PSMA-positive prostate cancer who have and have not had prior exposure to [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) or [177Lu]Lu-PSMA I&T (177Lu-PSMA I&T).