AzTrials
AzTrials

Advanced Solid TumoursPhase 1NCT03746431

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

A Phase 1 study testing [111In]-FPI-1547 Injection, [225Ac]-FPI-1434 Injection multi-dose and FPI-1175 Infusion in people with Advanced Solid Tumours and Endometrial Cancer, run by Fusion Pharmaceuticals Inc. at 13 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
[111In]-FPI-1547 Injection, [225Ac]-FPI-1434 Injection multi-dose and FPI-1175 Infusion
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
13 sitesin 3 countries
Study dates
17 Jan 2019to 3 Dec 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 13Show fewer
  • 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.

Who cannot join

  • 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.
Show all 12Show fewer
  • 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

Trial locations and contacts

13 sites in 3 countries.

13 sites in 3 countries

United States7 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14203

  • City of Hope

    Duarte, California, 91010

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

Canada4 sites

  • Juravinski Cancer Center - Hamilton Health

    Hamilton, Ontario, L8V 5C2

  • Centre Hospitalier De I'Universite de Montreal

    Montreal, Quebec, H2X 0C1

  • Quebec University Hospital- Laval

    Québec, Quebec, G1R 2J6

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2C1

Other trials in Canada

Australia2 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Austin Hospital

    Heidelberg, Victoria, 3084

Other trials in Australia

About this study

Official title: A Phase 1 Study of [225Ac]-FPI-1434 Injection in Patients With Locally Advanced or Metastatic Solid Tumours

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).

Read the detailed 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.

Being tested
[111In]-FPI-1547 Injection, [225Ac]-FPI-1434 Injection multi-dose, FPI-1175 Infusion, [225Ac]-FPI-1434 Injection single-dose
Keywords
225-Ac Labelled Humanized Monoclonal Antibody Against IGF-1R, [225Ac]-FPI-1434, IGF-IR Targeted Alpha Therapeutic, IGF-IR Radioligand Therapy, Radiopharmaceuticals
Medical subject headings
Endometrial Neoplasms, Uterine Cervical Neoplasms, Ovarian Neoplasms, Breast Neoplasms, Triple Negative Breast Neoplasms, Squamous Cell Carcinoma of Head and Neck, Adrenocortical Carcinoma, Uveal Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • [111In]-FPI-1547 InjectionDrug

    [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-doseDrug

    [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 InfusionBiological

    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 Injection single-doseDrug

    [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.

Study groups in NCT03746431
Study groupRoleWhat they receive
[225Ac]-FPI-1434 Single-Dose EscalationExperimentalNot described
Receives: Drug: [111In]-FPI-1547 Injection; Drug: [225Ac]-FPI-1434 Injection single-dose
[225Ac]-FPI-1434 Multi-Dose EscalationExperimental[225Ac]-FPI-1434 treatment with or without pre-administration of FPI-1175 (cold antibody).
Receives: Drug: [111In]-FPI-1547 Injection; Drug: [225Ac]-FPI-1434 Injection multi-dose; Biological: FPI-1175 Infusion
FPI-1175 Cold AntibodyExperimentalNot described
Receives: Drug: [111In]-FPI-1547 Injection; Drug: [225Ac]-FPI-1434 Injection multi-dose; Biological: FPI-1175 Infusion
[225Ac]-FPI-1434 Multi-DoseExperimentalPhase 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).
Receives: Drug: [111In]-FPI-1547 Injection; Drug: [225Ac]-FPI-1434 Injection multi-dose; Biological: FPI-1175 Infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Phase 1

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

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

    Phase 1

    Measured: 8 weeks.

  3. Multi-Dose Escalation: Incidence of DLTs.

    Phase 1

    Measured: 6 weeks.

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

    Phase 1

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

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

    Phase 1

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

  6. 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

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

  7. 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

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

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

    Phase 2

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

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

    Phase 2

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

Secondary outcomes (21)

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

    Phase 1 and 2

    Measured: 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.

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

    Phase 1 and 2

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

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

    Phase 1 and 2

    Measured: 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.

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

    Phase 1 and 2

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

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

    Phase 1 and 2

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

  6. Dose Escalation and Cold-Antibody Sub-Study: Cmax for radioactivity and for the targeting antibody.

    Phase 1 and 2

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

  7. Dose Escalation and Cold-Antibody Sub-Study: Half-life for radioactivity and for the targeting antibody.

    Phase 1 and 2

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

  8. Dose Escalation and Cold-Antibody Sub-Study: Objective response rate (ORR) (sum of complete and partial response) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Prostate Cancer Working Group 3 (PCWG3) guidelines.

    Phase 1

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

  9. Dose Escalation: Changes in the corrected QT (QTc) interval in milliseconds after [225Ac]-FPI-1434 treatment, compared to baseline.

    Phase 1 and 2

    Measured: Approximately 24 hours from the time of [225Ac]-FPI-1434 Injection administration.

  10. Dose Escalation and Cold-Antibody Sub-Study: Changes in human growth hormone (hGh) following [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection.

    Phase 1 and 2

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

  11. Dose Escalation and Cold-Antibody Sub-Study: Changes in insulin-like growth factor 1 (IGF-1) following [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection.

    Phase 1 and 2

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

  12. Dose Escalation and Cold-Antibody Sub-Study: Changes in insulin-like growth factor binding protein 3 (IGFBP-3) following [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection.

    Phase 1 and 2

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

  13. Cold Antibody Sub-Study: Incidence of AEs.

    Phase 1 and 2

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

  14. Cold Antibody Sub-Study: Incidence of clinically significant clinical laboratory abnormalities.

    Phase 1 and 2

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

  15. Cold Antibody Sub-Study: Changes in ECG parameters (PR, QRS, QT, and QTc intervals).

    Phase 1 and 2

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

  16. Dose Escalation and Cold-Antibody Sub-Study: Time to response (TTR).

    Phase 1 and 2

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

  17. Dose Escalation and Cold-Antibody Sub-Study: Duration of response (DoR).

    Phase 1 and 2

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

  18. Dose Escalation and Cold-Antibody Sub-Study: Progression free survival (PFS).

    Phase 1 and 2

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

  19. Dose Escalation and Cold-Antibody Sub-Study: Time to Progression (TTP).

    Phase 1 and 2

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

  20. Dose Escalation and Cold-Antibody Sub-Study: Disease control rate (DCR).

    Phase 1 and 2

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

  21. Dose Escalation and Cold-Antibody Sub-Study: Overall survival (OS).

    Phase 1 and 2

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2018
  2. Study start17 Jan 2019
  3. Primary completion3 Dec 2025
  4. Study completion3 Dec 2025

Why it stopped: A strategic decision was made to discontinue the study and prioritize other programs within the portfolio. The study was not discontinued due to safety issues or adverse events related to FPI-1434, FPE-1547, or FPI-1175.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03746431
Sponsor's protocol ID
FPX-01-01
Status last verified
Jan 2026
First submitted
9 Nov 2018
Last updated
7 Jan 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 36457575

  • 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.

    PubMed 36383907

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing [111In]-FPI-1547 Injection, [225Ac]-FPI-1434 Injection multi-dose and FPI-1175 Infusion in people with Advanced Solid Tumours and Endometrial Cancer, run by Fusion Pharmaceuticals Inc. at 13 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States, Canada, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: A strategic decision was made to discontinue the study and prioritize other programs within the portfolio. The study was not discontinued due to safety issues or adverse events related to FPI-1434, FPE-1547, or FPI-1175.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Escalation: Incidence of adverse events (AEs). (time frame: Approximately one year post final [225Ac]-FPI-1434 Injection.). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03746431, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in