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

• ClinicalTrials.gov Identifier: NCT05363605
• Recruitment Status: Active, not recruiting
• First Posted: May 6, 2022
• Last Update Posted: May 12, 2023
• Sponsor: Fusion Pharmaceuticals Inc.
• Information provided by (Responsible Party): Fusion Pharmaceuticals Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor; Head and Neck Squamous Cell Carcinoma; Bladder Carcinoma; Susceptible FGFR3 Genetic Alterations; FGFR3; FGFR3 Overexpression; FGFR3 Receptor; FGFR3 Protein Overexpression; Ovarian Cancer; Colorectal Cancer; Breast Cancer; Liver Cancer; Lung Cancer; Gastric Cancer	Drug: [225Ac]-FPI-1966; Drug: [111In]-FPI-1967; Biological: vofatamab	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 20, 2022
• Estimated Primary Completion Date: June 2026
• Estimated Study Completion Date: December 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase 1; Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered with or without pre-dosing with vofatamab.	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.; Drug: [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.
Experimental: Phase 2; 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.	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.; Drug: [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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

City of Hope

Duarte, California, United States, 91010

University of California, San Francisco

San Francisco, California, United States, 94143

United States, Iowa

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Australia, Western Australia

GC Murdoch

Murdoch, Western Australia, Australia, 6150

Australia

St Vincent's Hospital

Melbourne, Australia

Sponsors and Collaborators

Fusion Pharmaceuticals Inc.

Investigators

• Study Director: Julia Kazakin, MD; Fusion Pharmaceuticals Inc.

More Information

Additional Information:

Sponsor website 

• Responsible Party: Fusion Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT05363605
• Other Study ID Numbers: FPI-1966-101
• First Posted: May 6, 2022
• Last Update Posted: May 12, 2023
• Last Verified: May 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Fusion Pharmaceuticals Inc.:

Actinium-225; Targeted Alpha Therapy; Radiopharmaceutical; Radioimmunoconjugate; Theranostic; Theragnostic; Radioligand; Antineoplastic agents; [225Ac]-FPI-1966

Additional relevant MeSH terms:

Carcinoma; Squamous Cell Carcinoma of Head and Neck; Urinary Bladder Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma, Squamous Cell; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urogenital Neoplasms; Head and Neck Neoplasms; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases