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

Last updated: March 27, 2025
Sponsor: Fusion Pharmaceuticals Inc.
Overall Status: Active - Recruiting

Phase

2

Condition

Prostate Disorders

Urologic Cancer

Prostate Cancer

Treatment

FPI-2265

Olaparib

Clinical Study ID

NCT06909825
FPI-2265-203
CT-2024-CTN-00137-1
  • Ages > 18
  • Male

Study 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.

Eligibility Criteria

Inclusion

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 suchas PARP inhibitors, per Investigator discretion.

  5. All prior treatment-related AEs must have resolved to CTCAE Grade ≤1 (exceptalopecia).

  6. Participants must have had prior orchiectomy and/or ongoing androgen deprivationtherapy 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

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 chemotherapyfor 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 havereceived therapy (and are neurologically stable, asymptomatic, and not receivingcorticosteroids for the purposes of maintaining neurologic integrity.

  6. Symptomatic cord compression, or clinical or radiologic findings indicative ofimpending 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 ofMDS/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 thelast treatment.

  13. Participants unable to swallow orally administered medications or with malabsorptivegastrointestinal disorders.

  14. Concomitant use of known strong or moderate CYP3A inhibitors or inducers

Study Design

Total Participants: 85
Treatment Group(s): 2
Primary Treatment: FPI-2265
Phase: 2
Study Start date:
February 26, 2025
Estimated Completion Date:
August 12, 2030

Study 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.

Connect with a study center

  • St Vincent's Hospital Sydney

    Darlinghurst, New South Wales 2010
    Australia

    Site Not Available

  • Macquarie University Hospital

    Macquarie Park, New South Wales 2113
    Australia

    Active - Recruiting

  • Icon Cancer Centre North Lakes

    North Lakes, Queensland 4509
    Australia

    Active - Recruiting

  • Princess Alexandra Hospital

    Woolloongabba, Queensland 4102
    Australia

    Site Not Available

  • Royal Adelaide Hospital

    Adelaide, South Australia 5000
    Australia

    Site Not Available

  • Icon Cancer Centre Kurralta Park

    Kurralta Park, South Australia 5037
    Australia

    Active - Recruiting

  • Austin Hospital

    Heidelberg, Victoria 3084
    Australia

    Site Not Available

  • Peter MacCallum Cancer Center

    Melbourne, Victoria 3000
    Australia

    Active - Recruiting

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