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

NCT06909825 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: FPI-2265-203CT-2024-CTN-00137-1
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 4

Brief Summary

This study is an open-label, multicenter study designed to investigate the efficacy, safety and tolerability of FPI-2265 (225Ac-PSMA-I\&T) in combination with Olaparib in participants with mCRPC. The dose optimization Phase 2 part will be investigating the safety, tolerability, and anti-tumor activity of novel dosing regimens of FPI-2265 and Olaparib in participants with metastatic castration-resistant prostate cancer.

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

mCRPC; 225Ac-PSMA-I&T; RLT; Radioligand Therapy; FPI-2265; Olaparib; Radioconjugate

Outcome Measures

Primary Outcomes (2)

• Evaluate anti-tumour activity of FPI-2265 administered in combination with olaparib

  The frequency and proportion of participants with PSA50 response will be summarized, where PSA50 is defined as ≥50% decline in PSA level from pre-treatment.

  From first dose until approximately 12 weeks after the first administered dose of FPI-2265

• Evaluate the safety and tolerability of FPI-2265 administered in combination with olaparib

  Safety will be assessed by percentage of patient with treatment emergent adverse events and serious adverse events; percentage of patients with SAEs during the first year of the long term follow up and the number of AESIs during the 5 year follow up period. Percentage of patients with interruption of FPI-2265; percentage of patients who discontinue treatment; number and grade for AEs related to study treatment.

  From first dose until end of long-term follow-up, 5 years from the last administered dose of FPI-2265

Study Arms (2)

Part A

EXPERIMENTAL

Regimen 1: FPI-2265 (Dose A intravenously \[IV\] every six weeks) plus olaparib (twice daily \[BID\], on Days 1 to 14 of each cycle). Regimen 2: . FPI-2265 (Dose B intravenously \[IV\] every 4 weeks) plus olaparib (twice daily \[BID\], on Days 1 to 14 of each cycle)

Drug: FPI-2265; Drug: Olaparib

Part B

EXPERIMENTAL

Regimen 1: FPI-2265 (Dose A intravenously \[IV\] every six weeks) plus olaparib (g twice daily \[BID\], on Days 1 to 14 of each cycle). Regimen 2: . FPI-2265 (Dose B intravenously \[IV\] every 4 weeks) plus olaparib (twice daily \[BID\], on Days 1 to 14 of each cycle)

Drug: FPI-2265; Drug: Olaparib

Interventions

FPI-2265 DRUG

PSMA ligand radiolabeled with Ac225

Part A; Part B

Olaparib DRUG

Poly (ADP-ribose) polymerase (PARP) inhibitor

Part A; Part B

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male participants with mCRPC that is progressing at the time of study entry
• ECOG performance status 0-1 and life expectancy of at least three months
• Must have received at least one novel anti-androgen deprivation therapy
• Participants with known BRCA mutations should have received approved therapies such as PARP inhibitors, per Investigator discretion.
• All prior treatment-related AEs must have resolved to CTCAE Grade ≤1 (except alopecia).
• Participants must have had prior orchiectomy and/or ongoing androgen deprivation therapy and a castrate level of serum testosterone (\<50 ng/dL or \<1.7 nmol/L)
• Positive PSMA PET/CT scans .
• Participants must have adequate organ and bone marrow function:
• Hgb \>/= 9g/dL
• Platelets \>/= 100 x 10\^9/L
• ANC \</= 1.5 x 10\^9/L
• CrCL \>/= 50 mL/min

You may not qualify if:

• Previous treatment with any of the following within 6 months of first dose: Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation.
• Participants who received more than two (2) prior lines of cytotoxic chemotherapy for CRPC.
• Participants with known unresolved urinary tract obstruction.
• Transfusion- or growth factor-dependent participants.
• Participants with a history of CNS metastases are excluded, except those who have received therapy (and are neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity.
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
• Participants with any liver metastases.
• Participants with skeletal metastases presenting as a superscan .
• Previous history of interstitial lung disease or non-infectious pneumonitis.
• Participants with a history or clinical and/or laboratory features suggestive of MDS/AML.
• Major surgery ≤28 days prior to the first dose of study treatment.
• Planning to conceive a pregnancy during the treatment and up to six months after the last treatment.
• Participants unable to swallow orally administered medications or with malabsorptive gastrointestinal disorders.
• Concomitant use of known strong or moderate CYP3A inhibitors or inducers

Sponsors & Collaborators

• Fusion Pharmaceuticals Inc.: lead

Study Sites (4)

Macquarie University Hospital

Macquarie Park, New South Wales, 2113, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Icon Cancer Centre Kurralta Park

Kurralta Park, South Australia, 5037, Australia

Location

Peter MacCallum Cancer Center

Melbourne, Victoria, 3000, Australia

Location

MeSH Terms

Interventions

olaparib

Study Officials

• Dipti Shoop

  Fusion Pharmaceuticals Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2025
• First Posted: April 4, 2025
• Study Start: February 26, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

AU (4)