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

Primary Purpose

Advanced Solid Tumor, Head and Neck Squamous Cell Carcinoma, Bladder Carcinoma

Status

Active

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

[225Ac]-FPI-1966

[111In]-FPI-1967

vofatamab

About this trial

This is an interventional treatment trial for Advanced Solid Tumor focused on measuring Actinium-225, Targeted Alpha Therapy, Radiopharmaceutical, Radioimmunoconjugate, Theranostic, Theragnostic, Radioligand, Antineoplastic agents, [225Ac]-FPI-1966

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

City of Hope
University of California, San Francisco
University of Iowa Hospitals and Clinics
Memorial Sloan Kettering Cancer Center
GC Murdoch
St Vincent's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Phase 1

Phase 2

Arm Description

Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered with or without pre-dosing with vofatamab.

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.

Outcomes

Primary Outcome Measures

Phase 1: Phase 1: Incidence of AEs to evaluate safety and tolerability of [225Ac]-FPI-1966, [111In]-FPI-1967, and vofatamab.

Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966

Phase 1: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)

Phase 1: Effect of pre-dose administration of vofatamab on the radiation dosimetry of [111In]-FPI-1967 and [225Ac]-FPI-1966.

Phase 2: Objective response rate (ORR) (sum of complete and partial response) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Secondary Outcome Measures

Phase 1 and 2: Anti-tumour activity of [225Ac]-FPI-1966 regimen measured by response per RECIST v1.1

Phase 1 and 2: Tumour uptake of [111In]-FPI-1967 by evaluating SPECT/CT and/or planar images

Phase 2: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)

Phase 1 and 2: Clearance for radioactivity and for the targeting antibody.

Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody

Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody.

Phase 1 and 2: Half-life for radioactivity and targeting antibody.

Phase 1: Changes in clearance for radioactivity and targeting antibody following pre-dose administration of vofatamab

Phase 1: Changes in AUC for radioactivity and targeting antibody following pre-dose administration of vofatamab.

Phase 1: Changes in Cmax for radioactivity and targeting antibody following pre-dose administration of vofatamab.

Phase 1: Changes in half-life for radioactivity and targeting antibody following pre-dose administration of vofatamab

Full Information

NCT ID

NCT05363605

First Posted

April 26, 2022

Last Updated

May 11, 2023

Sponsor

Fusion Pharmaceuticals Inc.

1. Study Identification

Unique Protocol Identification Number

NCT05363605

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

April 20, 2022 (Actual)

Primary Completion Date

June 2026 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fusion Pharmaceuticals Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Actinium-225, Targeted Alpha Therapy, Radiopharmaceutical, Radioimmunoconjugate, Theranostic, Theragnostic, Radioligand, Antineoplastic agents, [225Ac]-FPI-1966

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase 1

Arm Type

Experimental

Arm Description

Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered with or without pre-dosing with vofatamab.

Arm Title

Phase 2

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

[225Ac]-FPI-1966

Intervention Description

[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.

Intervention Type

Drug

Intervention Name(s)

[111In]-FPI-1967

Intervention Description

[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.

Intervention Type

Biological

Intervention Name(s)

vofatamab

Intervention Description

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 Measure Information:

Title

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

Title

Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966

Time Frame

Approximately 42 days post administration.

Title

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

Title

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

Title

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 Measure Information:

Title

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

Title

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

Title

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

Title

Phase 1 and 2: Clearance for radioactivity and for the targeting antibody.

Time Frame

28 days post final [225Ac]-FPI-1966administration

Title

Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody

Time Frame

28 days post final [225Ac]-FPI-1966administration.

Title

Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody.

Time Frame

28 days post final[225Ac]-FPI-1966 administration

Title

Phase 1 and 2: Half-life for radioactivity and targeting antibody.

Time Frame