Clinical trial NCT05363605: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Fusion Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2022-05-06
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Phase 1: Phase 1: Incidence of AEs to evaluate safety and tolerability of [225Ac]-FPI-1966, [111In]-FPI-1967, and vofatamab.
timeFrame: Approximately 2 years post final administration
measure: Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966
timeFrame: Approximately 42 days post administration.
measure: Phase 1: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)
timeFrame: Within one week of administration
measure: Phase 1: Effect of pre-dose administration of vofatamab on the radiation dosimetry of [111In]-FPI-1967 and [225Ac]-FPI-1966.
timeFrame: Within one week of administration
measure: Phase 2: Objective response rate (ORR) (sum of complete and partial response) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
timeFrame: Up to two years post final administration.
Secondary outcomes:
measure: Phase 1 and 2: Anti-tumour activity of [225Ac]-FPI-1966 regimen measured by response per RECIST v1.1
timeFrame: Approximately 2 years post final administration
measure: Phase 1 and 2: Tumour uptake of [111In]-FPI-1967 by evaluating SPECT/CT and/or planar images
timeFrame: Within one week of administration
measure: Phase 2: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)
timeFrame: Within one week of administration
measure: Phase 1 and 2: Clearance for radioactivity and for the targeting antibody.
timeFrame: 28 days post final [225Ac]-FPI-1966administration
measure: Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody
timeFrame: 28 days post final [225Ac]-FPI-1966administration.
measure: Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody.
timeFrame: 28 days post final[225Ac]-FPI-1966 administration
measure: Phase 1 and 2: Half-life for radioactivity and targeting antibody.
timeFrame: 28 days post final [225Ac]-FPI-1966 administration
measure: Phase 1: Changes in clearance for radioactivity and targeting antibody following pre-dose administration of vofatamab
timeFrame: 28 days post final [225Ac]-FPI-1966 administration
measure: Phase 1: Changes in AUC for radioactivity and targeting antibody following pre-dose administration of vofatamab.
timeFrame: 28 days post final [225Ac]-FPI-1966 administration
measure: Phase 1: Changes in Cmax for radioactivity and targeting antibody following pre-dose administration of vofatamab.
timeFrame: 28 days post final [225Ac]-FPI-1966 administration
measure: Phase 1: Changes in half-life for radioactivity and targeting antibody following pre-dose administration of vofatamab
timeFrame: 28 days post final [225Ac]-FPI-1966 administration
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Murdoch
country: Australia
facility: GC Murdoch
state: Western Australia
city: Melbourne
country: Australia
facility: St Vincent's Hospital
Study officials:
affiliation: Fusion Pharmaceuticals Inc.
name: Julia Kazakin, MD
role: STUDY_DIRECTOR
References: