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

NCT03746431 | Terminated Phase 1 FDA Drug

• 1 other identifier: FPX-01-01
• Study Type: interventional
• Target: 78
• Locations: 3 countries
• Sites: 13

Brief 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).

Conditions

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

Keywords

225-Ac Labelled Humanized Monoclonal Antibody Against IGF-1R; [225Ac]-FPI-1434; IGF-IR Targeted Alpha Therapeutic; IGF-IR Radioligand Therapy; Radiopharmaceuticals

Outcome Measures

Primary Outcomes (9)

• Dose Escalation: Incidence of adverse events (AEs).

  Phase 1

  Approximately one year post final [225Ac]-FPI-1434 Injection.

• Single-Dose Escalation: Incidence of dose limiting toxicities (DLTs).

  Phase 1

  8 weeks.

• Multi-Dose Escalation: Incidence of DLTs.

  Phase 1

  6 weeks.

• Dose Escalation: Incidence of clinically significant clinical laboratory abnormalities.

  Phase 1

  Approximately one year post final [225Ac]-FPI-1434 Injection.

• Dose Escalation: Changes in electrocardiogram (ECG) parameters (PR, QRS, QT, and QTc intervals).

  Phase 1

  4 weeks post final [225Ac]-FPI-1434 Injection.

• Cold Antibody Sub-Study: Changes in uptake of [111In]-FPI-1547 Injection following FPI-1175 Infusion in selected regions of interest on SPECT/CT images.

  Phase 1

  Within two weeks of the first [111In]-FPI-1547 Injection.

• Cold Antibody Sub-Study: Changes in radiation dose estimates for selected tissues, organs and whole body both for [111In]-FPI-1547 and [225Ac]-FPI-1434 Injection at various dose levels following FPI-1175 Infusion.

  Phase 1

  Within two weeks of the first [111In]-FPI-1547 Injection.

• Evaluate anti-tumour activity of [225Ac]-FPI-1434 regimen

  Phase 2

  Approximately one year post final [225Ac]-FPI-1434 injection.

• Objective response rate (ORR) RECIST v1.1.

  Phase 2

  Approximately one year post final [225Ac]-FPI-1434 Injection.

Secondary Outcomes (21)

• Dose Escalation and Cold Antibody Sub-Study: Tumour uptake of [111In]-FPI-1547 in selected regions of interest on SPECT/CT images.

  Dose Escalation: Within one week of the [111In]-FPI-1547 Injection. Cold-Antibody Sub-Study: Within two weeks of the first [111In]-FPI-1547 Injection.

• Dose Escalation: Radiation doses for selected organs and whole body both for [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection.

  Within one week of the [111In]-FPI-1547 Injection.

• Dose Escalation and Cold-Antibody Sub-Study: Changes in radiation absorbed doses for tumour lesions for [225Ac]-FPI-1434.

  Dose Escalation: Within one week of the [111In]-FPI-1547 Injection. Cold-Antibody Sub-Study: Within two weeks of the first [111In]-FPI-1547 Injection.

• Dose Escalation and Cold-Antibody Sub-Study: Clearance for radioactivity and for the targeting antibody.

  4 weeks post final [225Ac]-FPI-1434 Injection.

• Dose Escalation and Cold-Antibody Sub-Study: Area under the curve (AUC) for radioactivity and for the targeting antibody.

  4 weeks post final [225Ac]-FPI-1434 Injection.

Study Arms (4)

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

EXPERIMENTAL

Drug: [111In]-FPI-1547 Injection; Drug: [225Ac]-FPI-1434 Injection single-dose

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

EXPERIMENTAL

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

Drug: [111In]-FPI-1547 Injection; Drug: [225Ac]-FPI-1434 Injection multi-dose; Biological: FPI-1175 Infusion

FPI-1175 Cold Antibody

EXPERIMENTAL

Drug: [111In]-FPI-1547 Injection; Drug: [225Ac]-FPI-1434 Injection multi-dose; Biological: FPI-1175 Infusion

[225Ac]-FPI-1434 Multi-Dose

EXPERIMENTAL

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).

Drug: [111In]-FPI-1547 Injection; Drug: [225Ac]-FPI-1434 Injection multi-dose; Biological: FPI-1175 Infusion

Interventions

[111In]-FPI-1547 Injection 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.

FPI-1175 Cold Antibody; [225Ac]-FPI-1434 Multi-Dose; [225Ac]-FPI-1434 Multi-Dose Escalation; [225Ac]-FPI-1434 Single-Dose Escalation

[225Ac]-FPI-1434 Injection multi-dose 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 Cold Antibody; [225Ac]-FPI-1434 Multi-Dose; [225Ac]-FPI-1434 Multi-Dose Escalation

FPI-1175 Infusion 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; [225Ac]-FPI-1434 Multi-Dose; [225Ac]-FPI-1434 Multi-Dose Escalation

[225Ac]-FPI-1434 Injection single-dose 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 Single-Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Measurable or evaluable disease in accordance with RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.
• Life expectancy of greater than 3 months as judged by the treating physician.
• Available tumour tissue (either archival or fresh biopsy) for IGF-1R immunohistochemistry. Submission of the tissue is not required prior to enrollment.
• Adequate heart, kidney, and liver function
• Adequate bone marrow reserves
• Ability to understand and the willingness to sign a written informed consent document.
• Phase 2 Specific
• 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.
• 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
• Prior to the initial \[225Ac\]-FPI-1434 cycle: Sufficient target expression in at least 1 lesion following \[111In\]-FPI-1547 and SPECT imaging.

You may not qualify if:

• Systemic therapeutic radiopharmaceutical within 6 months prior to enrollment into this study.
• Contraindications to or inability to perform the required imaging procedures in this study (e.g., inability to lay flat during scan time)
• Uncontrolled brain metastasis, including but not limited to the need for treatment with steroids, surgery or radiation therapy.
• Anticancer therapy (including investigational agents) or external beam radiation therapy within 14 days of the dosing of \[111In\]-FPI-1547
• 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.
• Residual CTCAE ≥ Grade 2 side effects of prior therapy, with the exception of residual grade 2 alopecia.
• Prior organ transplantation, including stem cell transplantation.
• Any prior treatment with nitrosoureas or actinomycin-D.
• Clinically relevant levels of protein in the urine
• Known or suspected allergies or contraindications to the Investigational Products or any component of the investigational drug formulation.
• 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.
• Received \> 20 Gy prior radiation to large areas of the bone marrow

Sponsors & Collaborators

• Fusion Pharmaceuticals Inc.: lead

Study Sites (13)

City of Hope

Duarte, California, 91010, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Juravinski Cancer Center - Hamilton Health

Hamilton, Ontario, L8V 5C2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2C1, Canada

Location

Centre Hospitalier De I'Universite de Montreal

Montreal, Quebec, H2X 0C1, Canada

Location

Quebec University Hospital- Laval

Québec, Quebec, G1R 2J6, Canada

Location

Related Publications (2)

• 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.

  PMID: 36457575 DERIVED

• 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.

  PMID: 36383907 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms; Uterine Cervical Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Triple Negative Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Adrenocortical Carcinoma; Uveal Melanoma

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Uterine Cervical Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Adenocarcinoma; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Study Officials

• Julia Kazakin, MD

  Fusion Pharmaceuticals Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2018
• First Posted: November 19, 2018
• Study Start: January 17, 2019
• Primary Completion: December 3, 2025
• Study Completion: December 3, 2025
• Last Updated: January 7, 2026

Record last verified: 2026-01

Locations

CA (4); AU (2); US (7)