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

Key Inclusion Criteria:

• Ability to understand and sign an approved informed consent form (ICF) and complywith all protocol requirements.

• Phase 2: Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

• Diagnosis of adenocarcinoma of prostate proven by histopathology.

• Must have had prior orchiectomy and/or ongoing androgen-deprivation therapy and acastrate level of serum/plasma testosterone

• Progressive mCRPC.

• Must have been previously treated with lutetium-PSMA therapy (lutetium-177vipivotide tetraxetan or other lutetium-177-PSMA RLT). Treatment must have beencompleted >6 weeks prior to the first dose of study drug.

• Participants with known BRCA mutations should have received FDA-approved therapiessuch as PARP inhibitors, per Investigator discretion.

• Positive PSMA PET/CT scan

• Adequate organ function

• For participants who have partners of childbearing potential: Partner and/orparticipant must not be planning to conceive and must use a method of birth controlwith adequate barrier protection deemed acceptable by the Principal Investigatorduring the study treatment and for six months after last study drug administration.

Key Exclusion Criteria:

• Participants who received more than two prior lines of cytotoxic chemotherapy forCRPC.

• Phase 2: participants who progress within two cycles of prior treatment with 177Lu-PSMA therapy

• All prior treatment-related adverse events must have resolved to Grade ≤1 (CTCAEv5.0). Alopecia and stable persistent Grade 2 peripheral neuropathy may be allowedat the discretion of the Investigator.

• Participants with known, unresolved, urinary tract obstruction are excluded.

• Administration of any systemic cytotoxic or investigational therapy ≤30 days of thefirst dose of study treatment or five half-lives, whichever is shorter. Completionof large-field external beam radiotherapy ≤four weeks of the first dose of studytreatment.

• Participants with a history of central nervous system (CNS) metastases are excludedexcept those who have received therapy

• Participants with any liver metastases will be excluded from the Phase 2 segment ofthe study.

• Participants with skeletal metastases presented as a superscan on a ⁹⁹ᵐTc bone scan.

• Previous or concurrent cancer that is distinct from the cancer under investigationin primary site or histology, except treated cutaneous basal cell carcinoma orsquamous cell carcinoma and superficial bladder tumors. Any cancer curativelytreated >two years prior to the first dose of treatment is permitted.

• Concurrent serious (as determined by the investigator) medical conditions

• Major surgery ≤30 days prior to the first dose of study treatment.