FPI-2265 (225Ac-PSMA-I&T) for Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This is an open-label, randomized, multicenter study of FPI-2265 (225Ac-PSMA-I\&T). The purpose of this dose optimization study is to determine the recommended FPI-2265 dose and regimen. Conclusions will be based on safety, tolerability, and anti-tumor activity. Screening Period: At screening, participants will be assessed for eligibility and undergo a positron emission tomography (PET)/computed tomography (CT) scan to evaluate PSMA positivity. Only participants with PSMA positive cancer and confirmed eligibility criteria will be randomized. Participants randomized will enter the treatment period and receive investigational doses of FPI2265 according to the dose level and schedule as specified per proposed dose arm. Part A participants will enroll 1:1:1 at three dose level/schedules, to arms 1, 2 or 3 Part B participants will enroll after completion of part A, in a 1:1 randomization scheme to arms 6 or 7. Once Part A is fully enrolled and participants have been followed for at least 12 weeks, data from Arm 1 and 2 will be analyzed to assess the feasibility of enrolling participants to arms 4 and 5. All participants will be monitored and assessed for efficacy response, disease progression and adverse events. Supportive care will be allowed in all arms at the discretion of the investigator and includes available care for the eligible participant according to best institutional practice for mCRPC treatment, including androgen deprivation therapy (ADT). Follow-up after end of treatment visit will proceed for 5 years. 5 participants will be enrolled into a dosimetry substudy (open at select sites only). Dosimetry substudy participants will be administered one dose at of FPI2265 and proceed with dosimetric assessments will be taken at a number of timepoints after dose administration.