Advanced Solid Tumor, Bladder Carcinoma, Breast Cancer, Colorectal Cancer, FGFR3, FGFR3 Overexpression, FGFR3 Protein Overexpression, FGFR3 Receptor, Gastric Cancer, Head and Neck Squamous Cell Carcinoma, Liver Cancer, Lung Cancer, Ovarian Cancer, Susceptible FGFR3 Genetic Alterations
Conditions
Keywords
Actinium-225, Targeted Alpha Therapy, Radiopharmaceutical, Radioimmunoconjugate, Theranostic, Theragnostic, Radioligand, Antineoplastic agents, [225Ac]-FPI-1966
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.
Interventions
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.
BIOLOGICALvofatamab
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.
Sponsors
Fusion Pharmaceuticals Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 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 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
| Measure | Time frame |
|---|---|
| Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody. | 28 days post final[225Ac]-FPI-1966 administration |
| Phase 1 and 2: Half-life for radioactivity and targeting antibody. | 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 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: Changes in Cmax for radioactivity and targeting antibody following pre-dose administration of vofatamab. | 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 AUC for radioactivity and targeting antibody following pre-dose administration of vofatamab. | 28 days post final [225Ac]-FPI-1966 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 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: Clearance for radioactivity and for the targeting antibody. | 28 days post final [225Ac]-FPI-1966administration |
| Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody | 28 days post final [225Ac]-FPI-1966administration. |
Countries
Australia, United States
Outcome results
None listed