A Study of [225Ac]-FPI-1966 in Participants With Advanced Solid Tumours

December 13, 2023 updated by: Fusion Pharmaceuticals Inc.

A Phase 1/2 Study of [225Ac]-FPI-1966, [111In]-FPI-1967, and Vofatamab in Participants With FGFR3-expressing Advanced, Inoperable, Metastatic and/or Recurrent Solid Tumours

This first-in-human study evaluates safety, tolerability and distribution of [225Ac] FPI-1966, [111In]-FPI-1967, and vofatamab in patients with FGFR3-expressing solid tumors.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

In phase 1, cohort 1, the potential impact of pre-dose administration of vofatamab on the dosimetry, PK, safety, and tolerability of [225Ac]-FPI-1966 and [111In]-FPI-1967 will be evaluated.

In later phase 1 cohorts, [225Ac]-FPI-1966 will be evaluated at ascending dose levels. Participants will receive [111In]-FPI-1967 during the imaging screening period to assess FGFR3 expression and to determine biodistribution and estimate radiation exposure to critical organs.

Once the recommended phase 2 dose (RP2D) or regimen is established and confirmed, three tumour-agnostic expansion cohorts may be initiated in parallel.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Contact

Study Locations

  • Australia
      • Melbourne, Australia
        • St Vincent's Hospital
    • Western Australia
      • Murdoch, Western Australia, Australia, 6150
        • GC Murdoch
  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering 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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Signed ICF prior to initiation of any study-specific procedures
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Histologically and/or cytologically documented diagnosis of locally advanced, inoperable, or metastatic solid tumours
  • Refractory to all standard treatments, or for whom standard treatment is not available, or tolerable, or is contraindicated, or the participant refuses standard therapy
  • Measurable disease per RECIST v. 1.1
  • Available tumour tissue (archival or fresh biopsy)
  • Adequate bone marrow, heart, liver, and kidney function

Key Exclusion Criteria:

  • Prior systemic radiopharmaceutical therapy within six months prior to the first dose of [111In]-FPI-1967
  • Prior radiation therapy (RT) to bone marrow > 20 Gy
  • RT within 30 days prior to the first dose of [111In]-FPI-1967
  • Prior anti-cancer treatment (chemotherapy, immunotherapy, hormonal therapy, targeted therapy, or investigational agents) within a certain amount of time prior to administration of the first dose of [111In]-FPI-1967
  • Concurrent serious co-morbidities that could limit participants' full participation and compliance

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: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1
Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered with or without pre-dosing with vofatamab.
Drug: [225Ac]-FPI-1966
[225Ac]-FPI-1966 is a targeted alpha therapeutic that consists of vofatamab, a bifunctional chelate, and actinium-225, an alpha particle emitting radionuclide. In Phase 1, the dose depends on cohort assignment. In Phase 2, the RP2D regimen will be administered.
Drug: [111In]-FPI-1967
[111In]-FPI-1967 is an imaging agent that consists of vofatamab, a bifunctional chelate and indium-111 radionuclide. Participants will receive [111In]-FPI-1967 Injection of 185 MBq for imaging.
Biological: vofatamab
Vofatamab is a Fibroblast Growth Factor Receptor 3 (FGFR3)-targeting human monoclonal antibody without a radioisotope. In Phase 1, the dose depends on cohort assignment. In Phase 2, if pre-dosing with vofatamab is indicated, the RP2D regimen will be administered.
Experimental: Phase 2
Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered either with or without pre-administration of vofatamab, depending on the RP2D/regimen as determined in the phase 1 portion of the study.
Drug: [225Ac]-FPI-1966
[225Ac]-FPI-1966 is a targeted alpha therapeutic that consists of vofatamab, a bifunctional chelate, and actinium-225, an alpha particle emitting radionuclide. In Phase 1, the dose depends on cohort assignment. In Phase 2, the RP2D regimen will be administered.
Drug: [111In]-FPI-1967
[111In]-FPI-1967 is an imaging agent that consists of vofatamab, a bifunctional chelate and indium-111 radionuclide. Participants will receive [111In]-FPI-1967 Injection of 185 MBq for imaging.
Biological: vofatamab
Vofatamab is a Fibroblast Growth Factor Receptor 3 (FGFR3)-targeting human monoclonal antibody without a radioisotope. In Phase 1, the dose depends on cohort assignment. In Phase 2, if pre-dosing with vofatamab is indicated, the RP2D regimen will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phase 1: Phase 1: Incidence of AEs to evaluate safety and tolerability of [225Ac]-FPI-1966, [111In]-FPI-1967, and vofatamab.
Time Frame: Approximately 2 years post final administration
Approximately 2 years post final administration
Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966
Time Frame: Approximately 42 days post administration.
Approximately 42 days post administration.
Phase 1: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)
Time Frame: Within one week of administration
Within one week of administration
Phase 1: Effect of pre-dose administration of vofatamab on the radiation dosimetry of [111In]-FPI-1967 and [225Ac]-FPI-1966.
Time Frame: Within one week of administration
Within one week of administration
Phase 2: Objective response rate (ORR) (sum of complete and partial response) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time Frame: Up to two years post final administration.
Up to two years post final administration.

Secondary Outcome Measures

Outcome Measure
Time Frame
Phase 1 and 2: Anti-tumour activity of [225Ac]-FPI-1966 regimen measured by response per RECIST v1.1
Time Frame: Approximately 2 years post final administration
Approximately 2 years post final administration
Phase 1 and 2: Tumour uptake of [111In]-FPI-1967 by evaluating SPECT/CT and/or planar images
Time Frame: Within one week of administration
Within one week of administration
Phase 2: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)
Time Frame: Within one week of administration
Within one week of administration
Phase 1 and 2: Clearance for radioactivity and for the targeting antibody.
Time Frame: 28 days post final [225Ac]-FPI-1966administration
28 days post final [225Ac]-FPI-1966administration
Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody
Time Frame: 28 days post final [225Ac]-FPI-1966administration.
28 days post final [225Ac]-FPI-1966administration.
Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody.
Time Frame: 28 days post final[225Ac]-FPI-1966 administration
28 days post final[225Ac]-FPI-1966 administration
Phase 1 and 2: Half-life for radioactivity and targeting antibody.
Time Frame: 28 days post final [225Ac]-FPI-1966 administration
28 days post final [225Ac]-FPI-1966 administration
Phase 1: Changes in clearance for radioactivity and targeting antibody following pre-dose administration of vofatamab
Time Frame: 28 days post final [225Ac]-FPI-1966 administration
28 days post final [225Ac]-FPI-1966 administration
Phase 1: Changes in AUC for radioactivity and targeting antibody following pre-dose administration of vofatamab.
Time Frame: 28 days post final [225Ac]-FPI-1966 administration
28 days post final [225Ac]-FPI-1966 administration
Phase 1: Changes in Cmax for radioactivity and targeting antibody following pre-dose administration of vofatamab.
Time Frame: 28 days post final [225Ac]-FPI-1966 administration
28 days post final [225Ac]-FPI-1966 administration
Phase 1: Changes in half-life for radioactivity and targeting antibody following pre-dose administration of vofatamab
Time Frame: 28 days post final [225Ac]-FPI-1966 administration
28 days post final [225Ac]-FPI-1966 administration

Collaborators and Investigators

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

Sponsor

Fusion Pharmaceuticals Inc.

Investigators

  • Study Director: Julia Kazakin, MD, Fusion Pharmaceuticals Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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)

April 20, 2022

Primary Completion (Actual)

September 8, 2023

Study Completion (Actual)

September 8, 2023

Study Registration Dates

First Submitted

April 26, 2022

First Submitted That Met QC Criteria

May 3, 2022

First Posted (Actual)

May 6, 2022

Study Record Updates

Last Update Posted (Estimated)

December 19, 2023

Last Update Submitted That Met QC Criteria

December 13, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FPI-1966-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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