A Study of [225Ac]-FPI-1966 in Participants With Advanced Solid Tumours
Study Details
Study Description
Brief Summary
This is a first-in-human, Phase 1/2, non-randomized, multi-centre, open-label clinical study designed to investigate safety, tolerability, dosimetry, biodistribution, and PK of [225Ac] FPI-1966, [111In]-FPI-1967, and vofatamab and the preliminary anti-tumour activity of [225Ac]-FPI-1966 in participants with FGFR3-expressing advanced, inoperable, metastatic, and/or recurrent solid tumours. Phase 1 consists of five multiple dose escalation cohorts. Phase 2 consists of two tumour-specific cohorts and one basket cohort.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
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 Phase 1, Cohort 1 of the study. [225Ac]-FPI-1966 will be evaluated in Phase 1 across 5 planned, ascending dose cohorts using a 3 + 3 dose escalation design. Participants will receive 185 MBq of [111In]-FPI-1967 during the imaging screening period to determine biodistribution and estimate radiation exposure to critical organs.
Once the recommended phase 2 dose (RP2D) regimen is established and confirmed, three expansion cohorts may be initiated in parallel.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Phase 1 Ascending doses of [225Ac]-FPI-1966 will be administered in repeating, 42-day cycles. [In111]-FPI-1967 will be administered at 185 MBq prior to imaging sessions. Vofatamab may be administered pre-dose over a fixed range of doses, depending on sub-cohort assignment. |
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.
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Experimental: Phase 2 [225Ac]-FPI-1966 will be administered as multiple cycles at the recommended phase 2 dose. [In111]-FPI-1967 will be administered at 185 MBq prior to imaging sessions. Vofatamab may be administered pre-dose. |
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.
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Outcome Measures
Primary Outcome Measures
- Phase 1: Incidence of Adverse Events (AEs) [Approximately two years post final [225Ac]-FPI-1966 administration.]
- Phase 1: Incidence of dose limiting toxicities (DLTs). [42 days post first [225Ac]-FPI-1966 administration.]
- Phase 1: Incidence of clinically significant clinical laboratory abnormalities compared to baseline. [Approximately 28 post final [225Ac]-FPI-1966 administration.]
- Phase 1: Changes in electrocardiogram (ECG) parameters (PR, QRS, QT, and QTcF intervals) compared to baseline. [Approximately 28 days post final [225Ac]-FPI-1966 administration.]
- Phase 1: Radiation doses for selected organs and whole body both for [111In]-FPI-1967 and [225Ac]-FPI-1966. [Within one week of the [111In]-FPI-1967 administration.]
- Phase 1: Radiation doses for tumors for both for [111In]-FPI-1967 and [225Ac]-FPI-1966. [Within one week of the [111In]-FPI-1967 administration.]
- Phase 1: Changes in radiation doses for selected organs and whole body both for [111In]-FPI-1967 and [225Ac]-FPI-1966 following pre-dose administration of vofatamab. [Within one week of the [111In]-FPI-1967 administration.]
- Phase 1: Changes in radiation doses for tumors for [111In]-FPI-1967 and [225Ac]-FPI-1966 following pre-dose administration of vofatamab. [Within one week of the [111In]-FPI-1967 administration.]
- Phase 1: Changes in tumor uptake of [111In]-FPI-1967 Injection in selected regions of interest on SPECT/CT and/or planar images following pre-dose administration of vofatamab. [Within one week of the [111In]-FPI-1967 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 [225Ac]-FPI-1966 administration.]
Secondary Outcome Measures
- Phase 1: ORR (sum of complete and partial response) per RECIST v1.1. [Up to two years post final [225Ac]-FPI-1966 administration.]
- Phase 1: ORR (sum of complete and partial response) per Positron Emission Tomography Response Criteria (PERCIST) v1.0. [Up to two years post final [225Ac]-FPI-1966 administration.]
- Phase 1 and 2: Time to response (TTR). [Up to two years post final [225Ac]-FPI-1966 administration.]
- Phase 1 and 2: Duration of response (DoR). [Up to two years post final [225Ac]-FPI-1966 administration.]
- Phase 1 and 2: Progression free survival (PFS). [Up to two years post final [225Ac]-FPI-1966 administration.]
- Phase 1 and 2: Time to progression (TTP). [Up to two years post final [225Ac]-FPI-1966 administration.]
- Phase 1 and 2: Disease control rate (DCR). [Up to two years post final [225Ac]-FPI-1966 administration.]
- Phase 1 and 2: Overall survival (OS). [Up to two years post final [225Ac]-FPI-1966 administration.]
- Phase 1 and 2: Tumor uptake of [111In]-FPI-1967 Injection in selected regions of interest on SPECT/CT images and/or planar images. [Within one week of the [111In]-FPI-1967 administration.]
- Phase 1 and 2: Clearance for radioactivity and for the targeting antibody. [28 days post final [225Ac]-FPI-1966 administration.]
- Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody. [28 days post final [225Ac]-FPI-1966 administration.]
- 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.]
- Phase 2: Incidence of Adverse Events (AEs) [Approximately two years post final [225Ac]-FPI-1966 administration.]
- Phase 2: Incidence of clinically significant clinical laboratory abnormalities compared to baseline. [Approximately 28 post final [225Ac]-FPI-1966 administration.]
- Phase 2: Changes in electrocardiogram (ECG) parameters (PR, QRS, QT, and QTcF intervals) compared to baseline. [Approximately 28 days post final [225Ac]-FPI-1966 administration.]
- Phase 2: Radiation doses for selected organs and whole body both for [111In]-FPI-1967 and [225Ac]-FPI-1966. [Within one week of the [111In]-FPI-1967 administration.]
- Phase 2: Radiation doses for tumors for both for [111In]-FPI-1967 and [225Ac]-FPI-1966. [Within one week of the [111In]-FPI-1967 administration.]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Signed ICF prior to initiation of any study-specific procedures
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Male and female participants, ≥ 18 years of age, with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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Histologically and/or cytologically documented diagnosis of locally advanced, inoperable, or metastatic solid tumours
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Refractory to all standard treatments, or for whom standard treatment is not available, or tolerable, or is contraindicated, or the participant refuses standard therapy
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Measurable disease per RECIST v. 1.1 with at least one non-nodal lesion of ≥ 20 mm in the longest diameter
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Available tumour tissue (either archival within the last two years or fresh biopsy) for FGFR3 immunohistochemistry and biomarker analysis (submission of tissue not required prior to enrolment)
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Adequate bone marrow, cardiovascular, hepatic, and renal function
Key Exclusion Criteria:
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Prior systemic radiopharmaceutical therapy within six months prior to the first dose of [111In]-FPI-1967
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Prior radiation therapy (RT) to bone marrow > 20 Gy
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RT within 30 days prior to the first dose of [111In]-FPI-1967
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Prior anti-cancer treatment (chemotherapy, immunotherapy, hormonal therapy, targeted therapy, or investigational agents) within five half-lives or four weeks, whichever is shorter, prior to administration of the first dose of [111In]-FPI-1967
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Concurrent serious co-morbidities that could limit participants' full participation and compliance
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | City of Hope | Duarte | California | United States | 91010 |
2 | University of Iowa Hospitals and Clinics | Iowa City | Iowa | United States | 52242 |
3 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Fusion Pharmaceuticals Inc.
Investigators
- Study Director: Julia Kazakin, MD, Fusion Pharmaceuticals Inc.
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- FPI-1966-101