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

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ClinicalTrials.gov Identifier: NCT05363605
Recruitment Status : Recruiting
First Posted : May 6, 2022
Last Update Posted : October 28, 2022
Sponsor:
Information provided by (Responsible Party):
Fusion Pharmaceuticals Inc.

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Head and Neck Squamous Cell Carcinoma Bladder Carcinoma Susceptible FGFR3 Genetic Alterations FGFR3 FGFR3 Overexpression FGFR3 Receptor FGFR3 Protein Overexpression Ovarian Cancer Colorectal Cancer Breast Cancer Liver Cancer Lung Cancer Gastric Cancer Drug: [225Ac]-FPI-1966 Drug: [111In]-FPI-1967 Biological: vofatamab Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : April 20, 2022
Estimated Primary Completion Date : June 2026
Estimated Study Completion Date : December 2026


Arm Intervention/treatment
Experimental: Phase 1
Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered with or without pre-dosing with vofatamab.
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
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
[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.




Primary Outcome Measures :
  1. 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 ]
  2. Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966 [ Time Frame: Approximately 42 days post administration. ]
  3. 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 ]
  4. 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 ]
  5. 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 Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. Phase 1 and 2: Clearance for radioactivity and for the targeting antibody. [ Time Frame: 28 days post final [225Ac]-FPI-1966administration ]
  5. Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody [ Time Frame: 28 days post final [225Ac]-FPI-1966administration. ]
  6. Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody. [ Time Frame: 28 days post final[225Ac]-FPI-1966 administration ]
  7. Phase 1 and 2: Half-life for radioactivity and targeting antibody. [ Time Frame: 28 days post final [225Ac]-FPI-1966 administration ]
  8. Phase 1: Changes in clearance for radioactivity and targeting antibody following pre-dose administration of vofatamab [ Time Frame: 28 days post final [225Ac]-FPI-1966 administration ]
  9. Phase 1: Changes in AUC for radioactivity and targeting antibody following pre-dose administration of vofatamab. [ Time Frame: 28 days post final [225Ac]-FPI-1966 administration ]
  10. Phase 1: Changes in Cmax for radioactivity and targeting antibody following pre-dose administration of vofatamab. [ Time Frame: 28 days post final [225Ac]-FPI-1966 administration ]
  11. Phase 1: Changes in half-life for radioactivity and targeting antibody following pre-dose administration of vofatamab [ Time Frame: 28 days post final [225Ac]-FPI-1966 administration ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05363605


Contacts
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Contact: Clinical Trials Fusion Pharmaceutical +1 (888) 506-4215 clinicaltrials@fusionpharma.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Australia, Western Australia
GC Murdoch Recruiting
Murdoch, Western Australia, Australia, 6150
Sponsors and Collaborators
Fusion Pharmaceuticals Inc.
Investigators
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Study Director: Julia Kazakin, MD Fusion Pharmaceuticals Inc.
Additional Information:
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Responsible Party: Fusion Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT05363605    
Other Study ID Numbers: FPI-1966-101
First Posted: May 6, 2022    Key Record Dates
Last Update Posted: October 28, 2022
Last Verified: October 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fusion Pharmaceuticals Inc.:
Actinium-225
Targeted Alpha Therapy
Radiopharmaceutical
Radioimmunoconjugate
Theranostic
Theragnostic
Radioligand
Antineoplastic agents
[225Ac]-FPI-1966
Additional relevant MeSH terms:
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Carcinoma
Squamous Cell Carcinoma of Head and Neck
Urinary Bladder Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Carcinoma, Squamous Cell
Urogenital Neoplasms
Head and Neck Neoplasms
Urologic Neoplasms
Urinary Bladder Diseases
Urologic Diseases