A Phase 1, Dose-escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours

July 6, 2026 updated by: AstraZeneca

A Phase 1, First-in-human, Multicentre, Open-label, Dose Escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours

This is a first-in-human, Phase 1, non-randomized, multicenter, open-label clinical study designed to investigate the safety, tolerability, dosimetry, biodistribution, and pharmacokinetics (PK) of [225Ac]-FPI-2068, [111In]-FPI-2107, and FPI-2053 in metastatic and/or recurrent solid tumors (HNSCC, NSCLC, mCRC, PDAC, GC, RCC).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The study will be conducted in 2 parts:

Part A: optimization of the FPI-2053 dose (treatment with dose level 1 of [225Ac]-FPI-2068 - fixed dose).

Part B: dose escalation of [225Ac]-FPI-2068 with optimal FPI-2053. Part B will commence once the optimal dose of FPI-2053 is determined in Part A. The RP2D will be determined from Part B based on all available safety, efficacy, PK, and dosimetry information.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • 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 Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H2X 0A9
        • Research Site
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Research Site
  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Research Site
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Research Site
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Research Site
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Research Site
    • Washington
      • Seattle, Washington, United States, 98109
        • Research Site

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

Histologically and/or cytologically confirmed solid tumor that is metastatic, locally advanced, recurrent or inoperable.

Disease that has progressed despite prior treatment, and for which additional effective standard therapy is not available or is contraindicated, not tolerable, or the participant refuses standard therapy.

Measurable disease as defined by RECIST Version 1.1

ECOG Performance status of 0 or 1

Adequate organ function

Key Exclusion Criteria:

Previous treatment with any systemic radiopharmaceutical

Prior anti-cancer therapy unless adequate washout and recovery from toxicities

Contraindications to or inability to perform the imaging procedures required in this study

Radiation therapy (RT) within 28 days prior to the first dose of [111In]-FPI-2107

Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (≥ once per month)

Patients with known CNS metastatic disease unless treated and stable

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: Dose Exploration and Dose Escalation

The study conducted in two parts: Part A Dose Exploration and Part B Dose Escalation

FPI-2053 dose exploration to determine the optimal pre-dose administration of FPI-2053 with a fixed dose of [225Ac]-FPI-2068.

[225Ac]-FPI-2068 dose escalation with the optimal dose of FPI-2053 as determined in Part A.
Drug: FPI-2053
FPI-2053 is a bispecific antibody that targets EGFR and cMET
Drug: [111In]-FPI-2107

[111In]-FPI-2107 is an imaging agent in which indium-111 is conjugated to FPI-2053.

Participants will have a fixed dose of [111In]-FPI-2107 followed by imaging scans (with or without pre-administration of FPI-2053).

Drug: [225Ac]-FPI-2068

[225Ac]-FPI-2068 is a radiopharmaceutical therapy in which an alpha emitter, actinium-225, is conjugated to FPI-2053.

Participants will be dosed through IV administration every 56 days for up to 3 cycles of the Treatment Period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate safety and tolerability of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068
Time Frame: From informed consent up to approximately 5 years post last administration
Frequency, duration, and severity of AEs, DLTs, and changes in clinical, laboratory, and ECG parameters compared to baseline
From informed consent up to approximately 5 years post last administration
Determine radiation dose of [111In]-FPI-2107 and [225Ac]-FPI-2068 to whole body, organs, and selected regions of interest.
Time Frame: Within 56 days of administration
Changes in uptake of [111In]-FPI-2107 and projected RAD of [225Ac]-FPI-2068 by imaging following the administration of varying doses of FPI-2053
Within 56 days of administration
Determine the RP2D of [225Ac]-FPI-2068, given with or without FPI-2053
Time Frame: 56 days post administration
Estimates of residence time and absorbed radiation doses to the whole body, organs, and selected regions of interest for [111In]-FPI-2107 and [225Ac]-FPI-2068.
56 days post administration
Determine the effect of predose administration of varying doses of FPI-2053 on the radiation dosimetry of [111In]-FPI-2107 and [225Ac]-FPI-2068 to whole body, organs, and selected regions of interest.
Time Frame: 56 days post-administration
Changes in uptake of [111In]-FPI- 2107 and projected RAD of [225Ac]-FPI-2068 by imaging following the administration of varying doses of FPI-2053
56 days post-administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess preliminary anti-tumor activity of [225Ac]-FPI-2068
Time Frame: Approximately 5 years post final administration
  • Tumor assessments will be based on RECIST v1.1 (Eisenhauer et al, 2009) and will be performed every 8 weeks (± 1 weeks) after first [225Ac]-FPI-2068 dose. During Long term follow up will be every 3 months (± 2 weeks) for 2 years and then every 6 months for 3 years, or as clinically indicated or until disease progression.
  • Percentage changes in total ctDNA (VAF), compared to baseline
Approximately 5 years post final administration
Tumor uptake of [111In]-FPI-2107
Time Frame: Within 56 days of administration
• Tumor uptake of [111In]-FPI-2107 in selected regions of interest on SPECT/CT and/or planar images
Within 56 days of administration
Pharmacokinetics (PK) of [111In]-FPI-2107, and [225Ac]-FPI-2068, by measuring changes in clearance, AUC, Cmax, and half-life.
Time Frame: From first dose of investigation product until 56 days after the last dose of investigational product.
• Determine the plasma concentrations and PK parameters of [111In]-FPI-2107, and [225Ac]-FPI-2068 and the effect of pre-dose administration of FPI-2053 on the plasma concentrations and PK parameters of [111In]-FPI-2107.
From first dose of investigation product until 56 days after the last dose of investigational product.
To assess the immunogenicity of [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053
Time Frame: From first dose of investigation product until 56 days after the last dose of investigational product.
• Presence of ADA for [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053
From first dose of investigation product until 56 days after the last dose of investigational product.

Collaborators and Investigators

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

Sponsor

AstraZeneca

Collaborators

AstraZeneca

Investigators

  • Study Director: Lorraine Hughes, MS, 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)

July 31, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

November 20, 2023

First Submitted That Met QC Criteria

November 20, 2023

First Posted (Actual)

November 27, 2023

Study Record Updates

Last Update Posted (Actual)

July 7, 2026

Last Update Submitted That Met QC Criteria

July 6, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FPI-2068-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

Subscribe