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

April 2, 2026 updated by: Fusion Pharmaceuticals Inc.

A Phase 2, Randomized, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of FPI-2265 (225Ac-PSMA-I&T) in Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This is an open-label, randomized, multicenter study of FPI-2265 (225Ac-PSMA-I&T). Patient population is adult participants with PSMA positive mCRPC who have had previous treatment with with 177Lu-PSMA-617 or another 177Lu-PSMA radioconjugate (RC). The purpose of the study is to determine the safety and tolerability, and recommended dose and regiment of FPI-2265.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, randomized, multicenter study of FPI-2265 (225Ac-PSMA-I&T). The purpose of this dose optimization study is to determine the recommended FPI-2265 dose and regimen. Conclusions will be based on safety, tolerability, and anti-tumor activity.

Screening Period: At screening, participants will be assessed for eligibility and undergo a positron emission tomography (PET)/computed tomography (CT) scan to evaluate PSMA positivity. Only participants with PSMA positive cancer and confirmed eligibility criteria will be randomized.

Participants randomized will enter the treatment period and receive investigational doses of FPI2265 according to the dose level and schedule as specified per proposed dose arm.

Part A participants will enroll 1:1:1 at three dose level/schedules, to arms 1, 2 or 3

Part B participants will enroll after completion of part A, in a 1:1 randomization scheme to arms 6 or 7.

Once Part A is fully enrolled and participants have been followed for at least 12 weeks, data from Arm 1 and 2 will be analyzed to assess the feasibility of enrolling participants to arms 4 and 5.

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

Supportive care will be allowed in all arms at the discretion of the investigator and includes available care for the eligible participant according to best institutional practice for mCRPC treatment, including androgen deprivation therapy (ADT).

Follow-up after end of treatment visit will proceed for 5 years.

5 participants will be enrolled into a dosimetry substudy (open at select sites only). Dosimetry substudy participants will be administered one dose at of FPI2265 and proceed with dosimetric assessments will be taken at a number of timepoints after dose administration.

Study Type

Interventional

Enrollment (Actual)

110

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

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
      • Irvine, California, United States, 92618
        • Hoag Health Center Irvine
      • Los Angeles, California, United States, 90095
        • University of California Los Angeles
      • Los Angeles, California, United States, 90073
        • VA Greater Los Angeles Healthcare System
      • San Francisco, California, United States, 94143
        • UCSF School of Medicine
    • Florida
      • Miami, Florida, United States, 33165
        • Biogenix Molecular, LLC
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Maryland
      • Glen Burnie, Maryland, United States, 21061
        • United Theranostics
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • BAMF Health
    • Missouri
      • St Louis, Missouri, United States, 63104
        • SSM Health Saint Louis University Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • XCancer
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • New Mexico Oncology Hematology Consultants Ltd.
    • New York
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center - NYC
    • Oregon
      • Portland, Oregon, United States, 97239-3098
        • Oregon Health and Science University (OHSU, Knight Cancer Center)
    • Texas
      • Dallas, Texas, United States, 75390
        • The University of Texas Southwestern Medical Center
      • Dallas, Texas, United States, 75216
        • VA North Texas Health Care System, Nuclear Medicine Service
      • Houston, Texas, United States, 77030
        • U.T. MD Anderson 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

Key Inclusion Criteria:

  • 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 at time of study entry.
  • 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.
  • Participants who progress prior to administration of the 3rd cycle 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
  • 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.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A Arm 1
Drug: FPI-2265

Investigational treatment FPI2265 is a PSMA ligand radiolabelled with 225Ac.

Other Names:

225Ac-PSMA-I&T
Experimental: Part A Arm 2
Drug: FPI-2265

Investigational treatment FPI2265 is a PSMA ligand radiolabelled with 225Ac.

Other Names:

225Ac-PSMA-I&T
Experimental: Part A Arm 3
Drug: FPI-2265

Investigational treatment FPI2265 is a PSMA ligand radiolabelled with 225Ac.

Other Names:

225Ac-PSMA-I&T
Experimental: Part B Arm 4
to be utilized based on analysis of Part A
Drug: FPI-2265

Investigational treatment FPI2265 is a PSMA ligand radiolabelled with 225Ac.

Other Names:

225Ac-PSMA-I&T
Experimental: Part B Arm 5
to be utilized based on analysis of Part A
Drug: FPI-2265

Investigational treatment FPI2265 is a PSMA ligand radiolabelled with 225Ac.

Other Names:

225Ac-PSMA-I&T
Experimental: Part B Arm 6
Drug: FPI-2265

Investigational treatment FPI2265 is a PSMA ligand radiolabelled with 225Ac.

Other Names:

225Ac-PSMA-I&T
Experimental: Part B Arm 7
Drug: FPI-2265

Investigational treatment FPI2265 is a PSMA ligand radiolabelled with 225Ac.

Other Names:

225Ac-PSMA-I&T

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency and proportion of participants with PSA50 response
Time Frame: From first dose until 12 weeks after the first administered dose of FPI-2265.
PSA50 response is defined as a decline in PSA levels by at least 50% and is used to evaluate anti-tumor activity.
From first dose until 12 weeks after the first administered dose of FPI-2265.
Frequency, duration, and severity of treatment-emergent adverse events (TEAEs)
Time Frame: From first dose until end of long-term follow-up, 5 years from end of treatment visit.
Frequencies and percentages of participants with TEAEs will be summarized. Analysis will also be completed regarding duration of TEAEs and their severity.
From first dose until end of long-term follow-up, 5 years from end of treatment visit.

Collaborators and Investigators

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

Sponsor

Fusion Pharmaceuticals Inc.

Investigators

  • Study Director: Charlotte Hawkins, MPH, CCRP, PMP, 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)

March 5, 2024

Primary Completion (Estimated)

December 23, 2026

Study Completion (Estimated)

January 23, 2031

Study Registration Dates

First Submitted

April 26, 2024

First Submitted That Met QC Criteria

May 2, 2024

First Posted (Actual)

May 7, 2024

Study Record Updates

Last Update Posted (Actual)

April 8, 2026

Last Update Submitted That Met QC Criteria

April 2, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FPI-2265-202

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.

No

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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