A Study of [225Ac]-FPI-1966 in Participants With Advanced Solid Tumours

Phase 1

Terminated

• Conditions: Bladder Carcinoma; Head and Neck Squamous Cell Carcinoma; Susceptible FGFR3 Genetic Alterations; Breast Cancer; FGFR3 Receptor; FGFR3 Protein Overexpression; Colorectal Cancer; Liver Cancer; Advanced Solid Tumor; FGFR3
• Interventions: Drug: [225Ac]-FPI-1966; Drug: [111In]-FPI-1967; Biological: vofatamab

• Registration Number: NCT05363605
• Lead Sponsor: Fusion Pharmaceuticals Inc.

Brief Summary

This first-in-human study evaluates safety, tolerability and distribution of \[225Ac\] FPI-1966, \[111In\]-FPI-1967, and vofatamab in patients with FGFR3-expressing solid tumors.

Detailed Description

In phase 1, cohort 1, the potential impact of pre-dose administration of vofatamab on the dosimetry, PK, safety, and tolerability of \[225Ac\]-FPI-1966 and \[111In\]-FPI-1967 will be evaluated.

In later phase 1 cohorts, \[225Ac\]-FPI-1966 will be evaluated at ascending dose levels. Participants will receive \[111In\]-FPI-1967 during the imaging screening period to assess FGFR3 expression and to determine biodistribution and estimate radiation exposure to critical organs.

Once the recommended phase 2 dose (RP2D) or regimen is established and confirmed, three tumour-agnostic expansion cohorts may be initiated in parallel.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2022-04-20
• Study First Submitted: 2022-04-26
• Study First Submitted QC: 2022-05-03
• Study First Posted: 2022-05-06
• Primary Completion: 2023-09-08
• Study Completion: 2023-09-08
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-13
• Last Update Posted: 2023-12-19

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• Signed ICF prior to initiation of any study-specific procedures
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histologically and/or cytologically documented diagnosis of locally advanced, inoperable, or metastatic solid tumours
• Refractory to all standard treatments, or for whom standard treatment is not available, or tolerable, or is contraindicated, or the participant refuses standard therapy
• Measurable disease per RECIST v. 1.1
• Available tumour tissue (archival or fresh biopsy)
• Adequate bone marrow, heart, liver, and kidney function

Key

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Exclusion Criteria

• Prior systemic radiopharmaceutical therapy within six months prior to the first dose of [111In]-FPI-1967
• Prior radiation therapy (RT) to bone marrow > 20 Gy
• RT within 30 days prior to the first dose of [111In]-FPI-1967
• Prior anti-cancer treatment (chemotherapy, immunotherapy, hormonal therapy, targeted therapy, or investigational agents) within a certain amount of time prior to administration of the first dose of [111In]-FPI-1967
• Concurrent serious co-morbidities that could limit participants' full participation and compliance

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1	[225Ac]-FPI-1966	Depending on assigned cohort, \[In111\]-FPI-1967/\[225Ac\]-FPI-1966 will be administered with or without pre-dosing with vofatamab.
Phase 1	[111In]-FPI-1967	Depending on assigned cohort, \[In111\]-FPI-1967/\[225Ac\]-FPI-1966 will be administered with or without pre-dosing with vofatamab.
Phase 2	[111In]-FPI-1967	Depending on assigned cohort, \[In111\]-FPI-1967/\[225Ac\]-FPI-1966 will be administered either with or without pre-administration of vofatamab, depending on the RP2D/regimen as determined in the phase 1 portion of the study.
Phase 2	vofatamab	Depending on assigned cohort, \[In111\]-FPI-1967/\[225Ac\]-FPI-1966 will be administered either with or without pre-administration of vofatamab, depending on the RP2D/regimen as determined in the phase 1 portion of the study.
Phase 1	vofatamab	Depending on assigned cohort, \[In111\]-FPI-1967/\[225Ac\]-FPI-1966 will be administered with or without pre-dosing with vofatamab.
Phase 2	[225Ac]-FPI-1966	Depending on assigned cohort, \[In111\]-FPI-1967/\[225Ac\]-FPI-1966 will be administered either with or without pre-administration of vofatamab, depending on the RP2D/regimen as determined in the phase 1 portion of the study.

Primary Outcome Measures

Name	Time	Method
Phase 1: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)	Within one week of administration
Phase 1: Effect of pre-dose administration of vofatamab on the radiation dosimetry of [111In]-FPI-1967 and [225Ac]-FPI-1966.	Within one week of administration
Phase 1: Phase 1: Incidence of AEs to evaluate safety and tolerability of [225Ac]-FPI-1966, [111In]-FPI-1967, and vofatamab.	Approximately 2 years post final administration
Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966	Approximately 42 days post administration.
Phase 2: Objective response rate (ORR) (sum of complete and partial response) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Up to two years post final administration.

Secondary Outcome Measures

Name	Time	Method
Phase 1 and 2: Clearance for radioactivity and for the targeting antibody.	28 days post final [225Ac]-FPI-1966administration
Phase 1 and 2: Half-life for radioactivity and targeting antibody.	28 days post final [225Ac]-FPI-1966 administration
Phase 2: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)	Within one week of administration
Phase 1 and 2: Tumour uptake of [111In]-FPI-1967 by evaluating SPECT/CT and/or planar images	Within one week of administration
Phase 1 and 2: Anti-tumour activity of [225Ac]-FPI-1966 regimen measured by response per RECIST v1.1	Approximately 2 years post final administration
Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody	28 days post final [225Ac]-FPI-1966administration.
Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody.	28 days post final[225Ac]-FPI-1966 administration
Phase 1: Changes in half-life for radioactivity and targeting antibody following pre-dose administration of vofatamab	28 days post final [225Ac]-FPI-1966 administration
Phase 1: Changes in clearance for radioactivity and targeting antibody following pre-dose administration of vofatamab	28 days post final [225Ac]-FPI-1966 administration
Phase 1: Changes in AUC for radioactivity and targeting antibody following pre-dose administration of vofatamab.	28 days post final [225Ac]-FPI-1966 administration
Phase 1: Changes in Cmax for radioactivity and targeting antibody following pre-dose administration of vofatamab.	28 days post final [225Ac]-FPI-1966 administration

Trial Locations

Locations (6)

St Vincent's Hospital; 🇦🇺 Melbourne, Australia

City of Hope; 🇺🇸 Duarte, California, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

GC Murdoch; 🇦🇺 Murdoch, Western Australia, Australia