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

NCT ID: NCT03746431

Last Updated: 2026-01-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-17

Study Completion Date

2025-12-03

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Advanced Solid Tumours Endometrial Cancer Cervical Cancer Ovarian Cancer Breast Cancer Triple Negative Breast Cancer (TNBC) HER2-negative Breast Cancer Head and Neck Squamous Cell Carcinoma (HNSCC) Adrenocortical Carcinoma Uveal Melanoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

[225Ac]-FPI-1434 Single-Dose Escalation

Group Type EXPERIMENTAL

[111In]-FPI-1547 Injection

Intervention Type DRUG

\[111In\]-FPI-1547 is a targeted radioimmuno-imaging agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Indium-111, a radionuclide. Patients will receive \[111In\]-FPI-1547 Injection of 185 MBq (5 mCi) for imaging.

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

Intervention Type DRUG

\[225Ac\]-FPI-1434 is a targeted alpha radioimmuno-therapeutic agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Actinium-225, an alpha-emitting radionuclide. Patients will receive a single dose of \[225\]-FPI-1434 Injection. Dose is per cohort assignment.

[225Ac]-FPI-1434 Multi-Dose Escalation

\[225Ac\]-FPI-1434 treatment with or without pre-administration of FPI-1175 (cold antibody).

Group Type EXPERIMENTAL

[111In]-FPI-1547 Injection

Intervention Type DRUG

\[111In\]-FPI-1547 is a targeted radioimmuno-imaging agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Indium-111, a radionuclide. Patients will receive \[111In\]-FPI-1547 Injection of 185 MBq (5 mCi) for imaging.

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

Intervention Type DRUG

\[225Ac\]-FPI-1434 is a targeted alpha radioimmuno-therapeutic agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Actinium-225, an alpha-emitting radionuclide. Patients will receive multiple doses of \[225Ac\]-FPI-1434 Injection. Dose is per cohort assignment.

FPI-1175 Infusion

Intervention Type BIOLOGICAL

FPI-1175 is an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody without a radioisotope. Patients will receive FPI-1175 Infusion at a dose per cohort assignment.

FPI-1175 Cold Antibody

Group Type EXPERIMENTAL

[111In]-FPI-1547 Injection

Intervention Type DRUG

\[111In\]-FPI-1547 is a targeted radioimmuno-imaging agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Indium-111, a radionuclide. Patients will receive \[111In\]-FPI-1547 Injection of 185 MBq (5 mCi) for imaging.

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

Intervention Type DRUG

\[225Ac\]-FPI-1434 is a targeted alpha radioimmuno-therapeutic agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Actinium-225, an alpha-emitting radionuclide. Patients will receive multiple doses of \[225Ac\]-FPI-1434 Injection. Dose is per cohort assignment.

FPI-1175 Infusion

Intervention Type BIOLOGICAL

FPI-1175 is an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody without a radioisotope. Patients will receive FPI-1175 Infusion at a dose per cohort assignment.

[225Ac]-FPI-1434 Multi-Dose

Phase 2 Tumour Cohort - Head \& Neck Squamous Cell Carcinoma (HNSCC), Endometrial Cancer, Cervical Cancer, Ovarian Cancer, Triple Negative Breast Cancer (TNBC), HER2-negative, Adrenocortical Carcinoma (ACC), Uveal Melanoma, \[225Ac\]-FPI-1434 treatment with or without pre-administration of FPI-1175 (cold antibody).

Group Type EXPERIMENTAL

[111In]-FPI-1547 Injection

Intervention Type DRUG

\[111In\]-FPI-1547 is a targeted radioimmuno-imaging agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Indium-111, a radionuclide. Patients will receive \[111In\]-FPI-1547 Injection of 185 MBq (5 mCi) for imaging.

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

Intervention Type DRUG

\[225Ac\]-FPI-1434 is a targeted alpha radioimmuno-therapeutic agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Actinium-225, an alpha-emitting radionuclide. Patients will receive multiple doses of \[225Ac\]-FPI-1434 Injection. Dose is per cohort assignment.

FPI-1175 Infusion

Intervention Type BIOLOGICAL

FPI-1175 is an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody without a radioisotope. Patients will receive FPI-1175 Infusion at a dose per cohort assignment.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

[111In]-FPI-1547 Injection

\[111In\]-FPI-1547 is a targeted radioimmuno-imaging agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Indium-111, a radionuclide. Patients will receive \[111In\]-FPI-1547 Injection of 185 MBq (5 mCi) for imaging.

Intervention Type DRUG

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

\[225Ac\]-FPI-1434 is a targeted alpha radioimmuno-therapeutic agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Actinium-225, an alpha-emitting radionuclide. Patients will receive multiple doses of \[225Ac\]-FPI-1434 Injection. Dose is per cohort assignment.

Intervention Type DRUG

FPI-1175 Infusion

FPI-1175 is an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody without a radioisotope. Patients will receive FPI-1175 Infusion at a dose per cohort assignment.

Intervention Type BIOLOGICAL

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

\[225Ac\]-FPI-1434 is a targeted alpha radioimmuno-therapeutic agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Actinium-225, an alpha-emitting radionuclide. Patients will receive a single dose of \[225\]-FPI-1434 Injection. Dose is per cohort assignment.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Pathologically documented, definitively diagnosed, advanced solid tumour that is refractory 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-1R immunohistochemistry. 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 consent document.

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 systemic therapy, or for whom standard or curative systemic therapy does not exist or is not tolerable.

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

Exclusion Criteria

1. Systemic therapeutic radiopharmaceutical within 6 months prior to enrollment into this study.
2. Contraindications to or inability to perform the required imaging procedures in this study (e.g., inability to lay flat during scan time)
3. Uncontrolled brain metastasis, including but not limited to the need for treatment with steroids, surgery or radiation therapy.
4. Anticancer therapy (including investigational agents) or external beam radiation therapy within 14 days of the dosing of \[111In\]-FPI-1547
5. Has known additional malignancy that is progressing or has required active treatment within the past 3 years. Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g., breast cancer, cervical cancer, prostate) that have undergone potentially curative therapy are not excluded.
6. Residual CTCAE ≥ Grade 2 side effects of prior therapy, with the exception of residual 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 or any component of the investigational drug formulation.
11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, or psychiatric illness/social situations that would limit compliance with study requirements.
12. Received \> 20 Gy prior radiation to large areas of the bone marrow
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Fusion Pharmaceuticals Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Julia Kazakin, MD

Role: STUDY_DIRECTOR

Fusion Pharmaceuticals Inc.

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

City of Hope

Duarte, California, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Austin Hospital

Heidelberg, Victoria, Australia

Site Status

Juravinski Cancer Center - Hamilton Health

Hamilton, Ontario, Canada

Site Status

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Centre Hospitalier De I'Universite de Montreal

Montreal, Quebec, Canada

Site Status

Quebec University Hospital- Laval

Québec, Quebec, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Australia Canada

References

Explore related publications, articles, or registry entries linked to this study.

Anderson PM, Subbiah V, Trucco MM. Current and future targeted alpha particle therapies for osteosarcoma: Radium-223, actinium-225, and thorium-227. Front Med (Lausanne). 2022 Nov 15;9:1030094. doi: 10.3389/fmed.2022.1030094. eCollection 2022.

Reference Type DERIVED
PMID: 36457575 (View on PubMed)

Martiniova L, Zielinski RJ, Lin M, DePalatis L, Ravizzini GC. The Role of Radiolabeled Monoclonal Antibodies in Cancer Imaging and ADC Treatment. Cancer J. 2022 Nov-Dec 01;28(6):446-453. doi: 10.1097/PPO.0000000000000625.

Reference Type DERIVED
PMID: 36383907 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

FPX-01-01

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.