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

Breast Cancer Clinical Trial

Official title:

A Phase 1/2 Study of [225Ac]-FPI-1966, [111In]-FPI-1967, and Vofatamab in Participants With FGFR3-expressing Advanced, Inoperable, Metastatic and/or Recurrent Solid Tumours

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05363605
• Other study ID #: FPI-1966-101
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 20, 2022
• Est. completion date: September 8, 2023

Study information

• Verified date: December 2023
• Source: Fusion Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: September 8, 2023
• Est. primary completion date: September 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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 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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Bladder Carcinoma
• Breast Cancer
• Carcinoma
• Colorectal Cancer
• Gastric Cancer
• Head and Neck Squamous Cell Carcinoma
• Liver Cancer
• Lung Cancer
• Ovarian Cancer
• Squamous Cell Carcinoma of Head and Neck
• Urinary Bladder Neoplasms

Intervention

Drug:
• [225Ac]-FPI-1966
[225Ac]-FPI-1966 is a targeted alpha therapeutic that consists of vofatamab, a bifunctional chelate, and actinium-225, an alpha particle emitting radionuclide. In Phase 1, the dose depends on cohort assignment. In Phase 2, the RP2D regimen will be administered.
• [111In]-FPI-1967
[111In]-FPI-1967 is an imaging agent that consists of vofatamab, a bifunctional chelate and indium-111 radionuclide. Participants will receive [111In]-FPI-1967 Injection of 185 MBq for imaging.

Biological:
• vofatamab
Vofatamab is a Fibroblast Growth Factor Receptor 3 (FGFR3)-targeting human monoclonal antibody without a radioisotope. In Phase 1, the dose depends on cohort assignment. In Phase 2, if pre-dosing with vofatamab is indicated, the RP2D regimen will be administered.

Locations

Country	Name	City	State
Australia	St Vincent's Hospital	Melbourne
Australia	GC Murdoch	Murdoch	Western Australia
United States	City of Hope	Duarte	California
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Fusion Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966		Approximately 42 days post administration.
Primary	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
Primary	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
Primary	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	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
Secondary	Phase 1 and 2: Tumour uptake of [111In]-FPI-1967 by evaluating SPECT/CT and/or planar images		Within one week of administration
Secondary	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
Secondary	Phase 1 and 2: Clearance for radioactivity and for the targeting antibody.		28 days post final [225Ac]-FPI-1966administration
Secondary	Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody		28 days post final [225Ac]-FPI-1966administration.
Secondary	Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody.		28 days post final[225Ac]-FPI-1966 administration
Secondary	Phase 1 and 2: Half-life for radioactivity and targeting antibody.		28 days post final [225Ac]-FPI-1966 administration
Secondary	Phase 1: Changes in clearance for radioactivity and targeting antibody following pre-dose administration of vofatamab		28 days post final [225Ac]-FPI-1966 administration
Secondary	Phase 1: Changes in AUC for radioactivity and targeting antibody following pre-dose administration of vofatamab.		28 days post final [225Ac]-FPI-1966 administration
Secondary	Phase 1: Changes in Cmax for radioactivity and targeting antibody following pre-dose administration of vofatamab.		28 days post final [225Ac]-FPI-1966 administration
Secondary	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

External Links

•   Sponsor website