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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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FGFR3, Advanced Solid Tumor, Head and Neck Squamous Cell Carcinoma, Bladder Carcinoma, Susceptible FGFR3 Genetic Alterations, FGFR3 Overexpression, FGFR3 Receptor, FGFR3 Protein Overexpression, Ovarian Cancer, Colorectal Cancer, Breast Cancer, Liver Cancer, Lung Cancer, Gastric Cancer

Intervention / Treatment
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* Drug: [225Ac]-FPI-1966
* Drug: [111In]-FPI-1967
* Biological: vofatamab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1<br>Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered with or without pre-dosing with vofatamab. | Drug: [225Ac]-FPI-1966<br>* [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.<br>Drug: [111In]-FPI-1967<br>* [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.<br>Biological: vofatamab<br>* 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.<br>|
| Experimental: Phase 2<br>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<br>* [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.<br>Drug: [111In]-FPI-1967<br>* [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.<br>Biological: vofatamab<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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: 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. | 
| 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: 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Actinium-225, Targeted Alpha Therapy, Radiopharmaceutical, Radioimmunoconjugate, Theranostic, Theragnostic, Radioligand, Antineoplastic agents, [225Ac]-FPI-1966