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

INTRODUCTION

  • Org Study ID: FPI-1966-101
  • Secondary ID: N/A
  • NTC ID: NCT05363605
  • Sponsor: Fusion Pharmaceuticals Inc.
Sponsor website

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.

  • Overall Status
    Recruiting
  • Start Date
    May 2022
  • Phase
    Phase 1, Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Phase 1: Incidence of Adverse Events (AEs)

Primary Outcome 1 - Timeframe: Approximately two years post final [225Ac]-FPI-1966 administration.

Primary Outcome 2 - Measure: Phase 1: Incidence of dose limiting toxicities (DLTs).

Primary Outcome 2 - Timeframe: 42 days post first [225Ac]-FPI-1966 administration.

Primary Outcome 3 - Measure: Phase 1: Incidence of clinically significant clinical laboratory abnormalities compared to baseline.

Primary Outcome 3 - Timeframe: Approximately 28 post final [225Ac]-FPI-1966 administration.

Primary Outcome 4 - Measure: Phase 1: Changes in electrocardiogram (ECG) parameters (PR, QRS, QT, and QTcF intervals) compared to baseline.

Primary Outcome 4 - Timeframe: Approximately 28 days post final [225Ac]-FPI-1966 administration.

Primary Outcome 5 - Measure: Phase 1: Radiation doses for selected organs and whole body both for [111In]-FPI-1967 and [225Ac]-FPI-1966.

Primary Outcome 5 - Timeframe: Within one week of the [111In]-FPI-1967 administration.

Primary Outcome 6 - Measure: Phase 1: Radiation doses for tumors for both for [111In]-FPI-1967 and [225Ac]-FPI-1966.

Primary Outcome 6 - Timeframe: Within one week of the [111In]-FPI-1967 administration.

Primary Outcome 7 - Measure: 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.

Primary Outcome 7 - Timeframe: Within one week of the [111In]-FPI-1967 administration.

Primary Outcome 8 - Measure: Phase 1: Changes in radiation doses for tumors for [111In]-FPI-1967 and [225Ac]-FPI-1966 following pre-dose administration of vofatamab.

Primary Outcome 8 - Timeframe: Within one week of the [111In]-FPI-1967 administration.

Primary Outcome 9 - Measure: 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.

Primary Outcome 9 - Timeframe: Within one week of the [111In]-FPI-1967 administration.

Primary Outcome 10 - Measure: Phase 2: Objective response rate (ORR) (sum of complete and partial response) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Primary Outcome 10 - Timeframe: Up to two years post final [225Ac]-FPI-1966 administration.

CONDITION

  • 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

ELIGIBILITY

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Julia Kazakin, MD

Role: Study Director

Affiliation: Fusion Pharmaceuticals Inc.

Overall Contact

Name: Julia Kazakin, MD

Phone: +1 (888) 506-4215, +1 (888) 506-4215

Email: clinicaltrials@fusionpharma.com, clinicaltrials@fusionpharma.com

LOCATION

Facility Status Contact
Facility: City of Hope
Duarte, California 91010
United States
Status: Recruiting Contact: N/A