A Phase 1/2 Study of [225Ac]-FPI-1434 Injection

Last updated: April 14, 2025
Sponsor: Fusion Pharmaceuticals Inc.
Overall Status: Active - Recruiting

Phase

1/2

Condition

Carcinoma

Ovarian Cancer

Endometrial Cancer

Treatment

[225Ac]-FPI-1434 Injection single-dose

FPI-1175 Infusion

[111In]-FPI-1547 Injection

Clinical Study ID

NCT03746431
FPX-01-01
  • Ages > 18
  • All Genders

Study Summary

This is a first-in-human Phase 1/2, non-randomized, multi-centre, open-label clinical study designed to investigate safety, tolerability, PK, and preliminary anti-tumour activity of [225Ac]-FPI-1434 (radioimmuno-therapeutic agent) in patients with solid tumours that demonstrate uptake of [111In]-FPI-1547 (radioimmuno-imaging agent), and to establish the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of repeat doses of [225Ac]-FPI-1434 Injection in patients with solid tumours that demonstrate uptake of [111In]-FPI-1547 (radioimmuno-imaging agent).

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Pathologically documented, definitively diagnosed, advanced solid tumour that isrefractory to all standard treatment, for which no standard treatment is available,or it is contraindicated, or the patient refuses standard therapy.

  2. Measurable or evaluable disease in accordance with RECIST 1.1.

  3. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.

  4. Life expectancy of greater than 3 months as judged by the treating physician.

  5. Available tumour tissue (either archival or fresh biopsy) for IGF-1Rimmunohistochemistry. Submission of the tissue is not required prior to enrollment.

  6. Adequate heart, kidney, and liver function

  7. Adequate bone marrow reserves

  8. Ability to understand and the willingness to sign a written informed consentdocument. Phase 2 Specific

  9. Histologically and/or cytologically documented diagnosis of locally advanced,inoperable, metastatic, or recurrent solid tumour types: endometrial, cervical,ovarian, TNBC, HER 2-negative breast, HNSCC, ACC, or uveal melanoma.

  10. Have measurable disease per RECIST 1.1 Failure to respond to standard systemictherapy, or for whom standard or curative systemic therapy does not exist or is nottolerable. Imaging Eligibility

  11. Prior to the initial [225Ac]-FPI-1434 cycle: Sufficient target expression in atleast 1 lesion following [111In]-FPI-1547 and SPECT imaging.

Exclusion

Exclusion Criteria:

  1. Systemic therapeutic radiopharmaceutical within 6 months prior to enrollment intothis study.

  2. Contraindications to or inability to perform the required imaging procedures in thisstudy (e.g., inability to lay flat during scan time)

  3. Uncontrolled brain metastasis, including but not limited to the need for treatmentwith steroids, surgery or radiation therapy.

  4. Anticancer therapy (including investigational agents) or external beam radiationtherapy within 14 days of the dosing of [111In]-FPI-1547

  5. Has known additional malignancy that is progressing or has required active treatmentwithin the past 3 years. Patients with basal cell carcinoma of the skin, squamouscell carcinoma of the skin or carcinoma in situ (e.g., breast cancer, cervicalcancer, prostate) that have undergone potentially curative therapy are not excluded.

  6. Residual CTCAE ≥ Grade 2 side effects of prior therapy, with the exception ofresidual grade 2 alopecia.

  7. Prior organ transplantation, including stem cell transplantation.

  8. Any prior treatment with nitrosoureas or actinomycin-D.

  9. Clinically relevant levels of protein in the urine

  10. Known or suspected allergies or contraindications to the Investigational Products orany component of the investigational drug formulation.

  11. Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, diabetes, or psychiatric illness/social situations that would limitcompliance with study requirements.

  12. Received > 20 Gy prior radiation to large areas of the bone marrow

Study Design

Total Participants: 253
Treatment Group(s): 4
Primary Treatment: [225Ac]-FPI-1434 Injection single-dose
Phase: 1/2
Study Start date:
January 17, 2019
Estimated Completion Date:
June 30, 2026

Study Description

This study consists of a Phase 1 portion and a Phase 2 portion.

Phase 1 includes the following cohorts: Single dose-ascending cohorts and Multi- dose ascending cohorts of [225Ac]-FPI-1434 and Multi- dose ascending cohorts evaluating administration of FPI-1175 (cold antibody), followed by, [225Ac]-FPI-1434 (cold + hot), with cycles repeating every 42 days. And Cold Antibody Sub-study evaluating administration of ascending doses of FPI-1175 followed by [111In]-FPI-1547.

The Phase 2 will evaluate [111In]-FPI-1547 and [225Ac]-FPI-1434 with or without FPI-1175 in tumour-specific cohorts. The decision to utilize FPI-1175 in the Phase 2 portion of the study will be determined based on Phase 1 data, including safety, tolerability, pharmacokinetic and dosimetry results.

Connect with a study center

  • Royal Adelaide Hospital

    Adelaide, South Australia 5000
    Australia

    Completed

  • Austin Hospital

    Heidelberg, Victoria 3084
    Australia

    Active - Recruiting

  • Juravinski Cancer Center - Hamilton Health

    Hamilton, Ontario L8V 5C2
    Canada

    Completed

  • Princess Margaret Cancer Centre

    Toronto, Ontario M5G 2C1
    Canada

    Completed

  • Centre Hospitalier De I'Universite de Montreal

    Montréal, Quebec H2X 0C1
    Canada

    Active - Recruiting

  • Quebec University Hospital- Laval

    Québec City, Quebec G1R 2J6
    Canada

    Completed

  • Juravinski Cancer Center - Hamilton Health

    Hamilton, Ontario, L8V 5C2
    Canada

    Site Not Available

  • Centre Hospitalier De I'Universite de Montreal

    Montréal, Quebec, H2X 0C1
    Canada

    Site Not Available

  • City of Hope

    Duarte, California 91010
    United States

    Completed

  • Dana-Farber Cancer Institute

    Boston, Massachusetts 02215
    United States

    Active - Recruiting

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota 55455
    United States

    Active - Recruiting

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York 14203
    United States

    Completed

  • Memorial Sloan Kettering Cancer Center

    New York, New York 10065
    United States

    Site Not Available

  • Memorial Sloan Kettering Cancer Center

    New York City, New York 10065
    United States

    Completed

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania 19104
    United States

    Completed

  • University of Texas MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Completed

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