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

Sponsor
Fusion Pharmaceuticals Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05363605
Collaborator
(none)
155
3
2
55.4
51.7
0.9

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.

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

Study Type:
Interventional
Anticipated Enrollment :
155 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 :
Apr 20, 2022
Anticipated Primary Completion Date :
Jun 1, 2026
Anticipated Study Completion Date :
Dec 1, 2026

Arms and Interventions

Arm Intervention/Treatment
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.

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.

Outcome Measures

Primary Outcome Measures

  1. Phase 1: Incidence of Adverse Events (AEs) [Approximately two years post final [225Ac]-FPI-1966 administration.]

  2. Phase 1: Incidence of dose limiting toxicities (DLTs). [42 days post first [225Ac]-FPI-1966 administration.]

  3. Phase 1: Incidence of clinically significant clinical laboratory abnormalities compared to baseline. [Approximately 28 post final [225Ac]-FPI-1966 administration.]

  4. 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.]

  5. 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.]

  6. 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.]

  7. 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.]

  8. 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.]

  9. 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.]

  10. 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

  1. Phase 1: ORR (sum of complete and partial response) per RECIST v1.1. [Up to two years post final [225Ac]-FPI-1966 administration.]

  2. 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.]

  3. Phase 1 and 2: Time to response (TTR). [Up to two years post final [225Ac]-FPI-1966 administration.]

  4. Phase 1 and 2: Duration of response (DoR). [Up to two years post final [225Ac]-FPI-1966 administration.]

  5. Phase 1 and 2: Progression free survival (PFS). [Up to two years post final [225Ac]-FPI-1966 administration.]

  6. Phase 1 and 2: Time to progression (TTP). [Up to two years post final [225Ac]-FPI-1966 administration.]

  7. Phase 1 and 2: Disease control rate (DCR). [Up to two years post final [225Ac]-FPI-1966 administration.]

  8. Phase 1 and 2: Overall survival (OS). [Up to two years post final [225Ac]-FPI-1966 administration.]

  9. 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.]

  10. Phase 1 and 2: Clearance for radioactivity and for the targeting antibody. [28 days post final [225Ac]-FPI-1966 administration.]

  11. Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody. [28 days post final [225Ac]-FPI-1966 administration.]

  12. Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody. [28 days post final [225Ac]-FPI-1966 administration.]

  13. Phase 1 and 2: Half-life for radioactivity and targeting antibody. [28 days post final [225Ac]-FPI-1966 administration.]

  14. Phase 1: Changes in clearance for radioactivity and targeting antibody following pre-dose administration of vofatamab. [28 days post final [225Ac]-FPI-1966 administration.]

  15. Phase 1: Changes in AUC for radioactivity and targeting antibody following pre-dose administration of vofatamab. [28 days post final [225Ac]-FPI-1966 administration.]

  16. Phase 1: Changes in Cmax for radioactivity and targeting antibody following pre-dose administration of vofatamab. [28 days post final [225Ac]-FPI-1966 administration.]

  17. 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.]

  18. Phase 2: Incidence of Adverse Events (AEs) [Approximately two years post final [225Ac]-FPI-1966 administration.]

  19. Phase 2: Incidence of clinically significant clinical laboratory abnormalities compared to baseline. [Approximately 28 post final [225Ac]-FPI-1966 administration.]

  20. 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.]

  21. 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.]

  22. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
  • Signed ICF prior to initiation of any study-specific procedures

  • Male and female participants, ≥ 18 years of age, with 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 with at least one non-nodal lesion of ≥ 20 mm in the longest diameter

  • 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)

  • Adequate bone marrow, cardiovascular, hepatic, and renal 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 five half-lives or four weeks, whichever is shorter, 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

Site City State Country Postal Code
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.
Responsible Party:
Fusion Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT05363605
Other Study ID Numbers:
  • FPI-1966-101
First Posted:
May 6, 2022
Last Update Posted:
Aug 17, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Fusion Pharmaceuticals Inc.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 17, 2022