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

September 2, 2026 updated by: Fusion Pharmaceuticals Inc.

A Phase 2, Open-label, Multi-centre Study of FPI-2265 (225Ac-PSMA-I&T) and Olaparib in Participants With Metastatic Castration Resistant Prostate Cancer (mCRPC)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

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 study will be conducted in two parts, with Part A enrolling participants who have been previously treated with lutetium-177 (177Lu) vipivotide tetraxetan or other 177Lu-PSMA radioligand therapy (RLT) and Part B enrolling participants who have not been previously treated with lutetium-177 (177Lu) vipivotide tetraxetan or other 177Lu-PSMA radioligand therapy. For each part of the study, a Simon 2-stage design will be used to evaluate two dosing regimens. The purpose of this investigation is to determine the recommended FPI-2265 dose and regimen. Conclusions from this Phase 2 study will be based on safety, tolerability, and anti-tumor activity data. Participants with PSMA-positive mCRPC will be allocated to Arm 1 and Arm 2 in a singular, alternating fashion, until all Stage 1 participants are enrolled into each of the two regimens:

Arm 1: Will consist of up to six doses of FPI-2265 every six weeks at Dose A and olaparib twice a day on days 1 to 14 of each cycle.

Arm 2: Will consist of up to nine doses of FPI-2265 every four weeks at Dose B and olaparib twice a day on days 1 to 14 of each cycle Participants will be monitored and assessed for efficacy response, disease progression, and adverse events.

Study Type

Interventional

Enrollment (Estimated)

85

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Macquarie Park, New South Wales, Australia, 2113
        • Macquarie University Hospital
    • Queensland
      • Woolloongabba, Queensland, Australia, 4102
        • Princess Alexandra Hospital
    • South Australia
      • Kurralta Park, South Australia, Australia, 5037
        • Icon Cancer Centre Kurralta Park
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adult male participants with mCRPC that is progressing at the time of study entry
  2. ECOG performance status 0-1 and life expectancy of at least three months
  3. Must have received at least one novel anti-androgen deprivation therapy
  4. Participants with known BRCA mutations should have received approved therapies such as PARP inhibitors, per Investigator discretion.
  5. All prior treatment-related AEs must have resolved to CTCAE Grade ≤1 (except alopecia).
  6. 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)
  7. Positive PSMA PET/CT scans .

  8. 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

Exclusion Criteria:

  1. Previous treatment with any of the following within 6 months of first dose: Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation.
  2. Participants who received more than two (2) prior lines of cytotoxic chemotherapy for CRPC.
  3. Participants with known unresolved urinary tract obstruction.
  4. Transfusion- or growth factor-dependent participants.
  5. 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.
  6. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
  7. Participants with any liver metastases.
  8. Participants with skeletal metastases presenting as a superscan .
  9. Previous history of interstitial lung disease or non-infectious pneumonitis.
  10. Participants with a history or clinical and/or laboratory features suggestive of MDS/AML.
  11. Major surgery ≤28 days prior to the first dose of study treatment.
  12. Planning to conceive a pregnancy during the treatment and up to six months after the last treatment.
  13. Participants unable to swallow orally administered medications or with malabsorptive gastrointestinal disorders.
  14. Concomitant use of known strong or moderate CYP3A inhibitors or inducers

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A

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
PSMA ligand radiolabeled with Ac225
Drug: Olaparib
Poly (ADP-ribose) polymerase (PARP) inhibitor
Experimental: Part B

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
PSMA ligand radiolabeled with Ac225
Drug: Olaparib
Poly (ADP-ribose) polymerase (PARP) inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate anti-tumour activity of FPI-2265 administered in combination with olaparib
Time Frame: From first dose until approximately 12 weeks after the first administered dose of FPI-2265
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
Time Frame: From first dose until end of long-term follow-up, 5 years from the last administered dose of FPI-2265
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fusion Pharmaceuticals Inc.

Investigators

  • Study Director: Dipti Shoop, Fusion Pharmaceuticals Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 26, 2025

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

May 1, 2027

Study Registration Dates

First Submitted

March 21, 2025

First Submitted That Met QC Criteria

March 27, 2025

First Posted (Actual)

April 4, 2025

Study Record Updates

Last Update Posted (Actual)

September 3, 2026

Last Update Submitted That Met QC Criteria

September 2, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FPI-2265-203
  • CT-2024-CTN-00137-1 (Other Identifier: TGA Clinical Trial Notification (CTN))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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