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

Phase 2TerminatedNCT05363605

Fusion Pharmaceuticals Inc.6 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumor Head and Neck Squamous Cell Carcinoma Bladder Carcinoma

Interventions

[225Ac]-FPI-1966DRUG

\[225Ac\]-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-1967DRUG

\[111In\]-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.

vofatamabBIOLOGICAL

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (6)

City of Hope

Duarte, California, United States

University of California, San Francisco

San Francisco, 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

GC Murdoch

Murdoch, Western Australia, Australia

St Vincent's Hospital

Melbourne, Australia

Outcomes

Primary Outcomes

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

Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966

Time frame: Approximately 42 days post administration.

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

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

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 Outcomes

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

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

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

Phase 1 and 2: Clearance for radioactivity and for the targeting antibody.

Time frame: 28 days post final [225Ac]-FPI-1966administration

Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody

Time frame: 28 days post final [225Ac]-FPI-1966administration.

Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody.

Time frame: 28 days post final[225Ac]-FPI-1966 administration

Phase 1 and 2: Half-life for radioactivity and targeting antibody.