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

Fusion Pharmaceuticals

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Metastatic Castration-resistant Prostate Cancer

Treatments: Drug: FPI-2265

Study type: Interventional

Funder types: Industry

Identifiers

NCT06402331

FPI-2265-202

Details and patient eligibility

About

This is an open-label, randomized, multicenter study of FPI-2265 (225Ac-PSMA-I&T). The dose optimization Phase 2 part will be investigating the safety, tolerability, and anti-tumor activity of novel dosing regimens of FPI-2265 in participants with PSMA-positive mCRPC who have been previously treated with 177Lu-PSMA-617 or another 177Lu-PSMA radioligand therapy (RLT).

Full description

The purpose of the dose optimization segment (Phase 2) is to determine the recommended FPI-2265 dose and regimen. Conclusions from Phase 2 will be based on safety, tolerability, and anti-tumor activity.

Participants with PSMA positive scans will be randomized (1:1:1) to one of three different dosing arms:

Arm 1: Will consist of nine doses of FPI-2265, administered every four weeks at 50 kBq/kg.

Arm 2: Will consist of six doses of FPI-2265, administered every six weeks at 75 kBq/kg.

Arm 3: Will consist of four doses of FPI-2265, administered every eight weeks at 100 kBq/kg.

Participants will be monitored and assessed for efficacy response, disease progression and adverse events.

Enrollment: 60 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Ability to understand and sign an approved informed consent form (ICF) and comply with 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 a castrate level of serum/plasma testosterone
• Progressive mCRPC.
• Must have been previously treated with lutetium-PSMA therapy (lutetium-177 vipivotide tetraxetan or other lutetium-177-PSMA RLT). Treatment must have been completed >6 weeks prior to the first dose of study drug.
• Participants with known BRCA mutations should have received FDA-approved therapies such as PARP inhibitors, per Investigator discretion.
• Positive PSMA PET/CT scan
• Adequate organ function
• For participants who have partners of childbearing potential: Partner and/or participant must not be planning to conceive and must use a method of birth control with adequate barrier protection deemed acceptable by the Principal Investigator during 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 for CRPC.
• 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 (CTCAE v5.0). Alopecia and stable persistent Grade 2 peripheral neuropathy may be allowed at 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 the first dose of study treatment or five half-lives, whichever is shorter. Completion of large-field external beam radiotherapy ≤four weeks of the first dose of study treatment.
• Participants with a history of central nervous system (CNS) metastases are excluded except those who have received therapy
• Participants with any liver metastases will be excluded from the Phase 2 segment of the 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 investigation in primary site or histology, except treated cutaneous basal cell carcinoma or squamous cell carcinoma and superficial bladder tumors. Any cancer curatively treated >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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 3 patient groups

FPI-2265 50 kBq/kg

Experimental group

Description:

Arm 1: FPI-2265 administered by IV injection every four weeks; up to 9 doses.

Treatment:

Drug: FPI-2265

FPI-2265 75 kBq/kg

Experimental group

Description:

Arm 2: FPI-2265 administered by IV injection every six weeks; up to 6 doses.

Treatment:

Drug: FPI-2265

FPI-2265 100 kBq/kg

Experimental group

Description:

Arm 3: FPI-2265 administered by IV injection every eight weeks; up to 4 doses.

Treatment:

Drug: FPI-2265