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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05363605




Registration number
NCT05363605
Ethics application status
Date submitted
26/04/2022
Date registered
6/05/2022
Date last updated
19/12/2023

Titles & IDs
Public title
A Study of [225Ac]-FPI-1966 in Participants With Advanced Solid Tumours
Scientific 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
Secondary ID [1] 0 0
FPI-1966-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
Head and Neck Squamous Cell Carcinoma 0 0
Bladder Carcinoma 0 0
Susceptible FGFR3 Genetic Alterations 0 0
FGFR3 0 0
FGFR3 Overexpression 0 0
FGFR3 Receptor 0 0
FGFR3 Protein Overexpression 0 0
Ovarian Cancer 0 0
Colorectal Cancer 0 0
Breast Cancer 0 0
Liver Cancer 0 0
Lung Cancer 0 0
Gastric Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - [225Ac]-FPI-1966
Treatment: Drugs - [111In]-FPI-1967
Other interventions - vofatamab

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

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.


Treatment: Drugs: [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.

Treatment: Drugs: [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.

Other interventions: 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.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: Phase 1: Incidence of AEs to evaluate safety and tolerability of [225Ac]-FPI-1966, [111In]-FPI-1967, and vofatamab.
Timepoint [1] 0 0
Approximately 2 years post final administration
Primary outcome [2] 0 0
Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966
Timepoint [2] 0 0
Approximately 42 days post administration.
Primary outcome [3] 0 0
Phase 1: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)
Timepoint [3] 0 0
Within one week of administration
Primary outcome [4] 0 0
Phase 1: Effect of pre-dose administration of vofatamab on the radiation dosimetry of [111In]-FPI-1967 and [225Ac]-FPI-1966.
Timepoint [4] 0 0
Within one week of administration
Primary outcome [5] 0 0
Phase 2: Objective response rate (ORR) (sum of complete and partial response) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Timepoint [5] 0 0
Up to two years post final administration.
Secondary outcome [1] 0 0
Phase 1 and 2: Anti-tumour activity of [225Ac]-FPI-1966 regimen measured by response per RECIST v1.1
Timepoint [1] 0 0
Approximately 2 years post final administration
Secondary outcome [2] 0 0
Phase 1 and 2: Tumour uptake of [111In]-FPI-1967 by evaluating SPECT/CT and/or planar images
Timepoint [2] 0 0
Within one week of administration
Secondary outcome [3] 0 0
Phase 2: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)
Timepoint [3] 0 0
Within one week of administration
Secondary outcome [4] 0 0
Phase 1 and 2: Clearance for radioactivity and for the targeting antibody.
Timepoint [4] 0 0
28 days post final [225Ac]-FPI-1966administration
Secondary outcome [5] 0 0
Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody
Timepoint [5] 0 0
28 days post final [225Ac]-FPI-1966administration.
Secondary outcome [6] 0 0
Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody.
Timepoint [6] 0 0
28 days post final[225Ac]-FPI-1966 administration
Secondary outcome [7] 0 0
Phase 1 and 2: Half-life for radioactivity and targeting antibody.
Timepoint [7] 0 0
28 days post final [225Ac]-FPI-1966 administration
Secondary outcome [8] 0 0
Phase 1: Changes in clearance for radioactivity and targeting antibody following pre-dose administration of vofatamab
Timepoint [8] 0 0
28 days post final [225Ac]-FPI-1966 administration
Secondary outcome [9] 0 0
Phase 1: Changes in AUC for radioactivity and targeting antibody following pre-dose administration of vofatamab.
Timepoint [9] 0 0
28 days post final [225Ac]-FPI-1966 administration
Secondary outcome [10] 0 0
Phase 1: Changes in Cmax for radioactivity and targeting antibody following pre-dose administration of vofatamab.
Timepoint [10] 0 0
28 days post final [225Ac]-FPI-1966 administration
Secondary outcome [11] 0 0
Phase 1: Changes in half-life for radioactivity and targeting antibody following pre-dose administration of vofatamab
Timepoint [11] 0 0
28 days post final [225Ac]-FPI-1966 administration

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/04/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/09/2023
Sample size
Target
Accrual to date
Final
6
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
GC Murdoch - Murdoch
Recruitment hospital [2] 0 0
St Vincent's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
6150 - Murdoch
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Iowa
Country [3] 0 0
United States of America
State/province [3] 0 0
New York

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Fusion Pharmaceuticals Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05363605
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Julia Kazakin, MD
Address 0 0
Fusion Pharmaceuticals Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05363605