Advanced Solid TumorPhase 1/2NCT05363605
A Study of [225Ac]-FPI-1966 in Participants With Advanced Solid Tumours
A Phase 1/2 study testing [225Ac]-FPI-1966, [111In]-FPI-1967 and vofatamab in people with Advanced Solid Tumor and Head and Neck Squamous Cell Carcinoma, run by Fusion Pharmaceuticals Inc. at 6 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Head and Neck Squamous Cell Carcinoma, Bladder Carcinoma
- What is being tested?
- [225Ac]-FPI-1966, [111In]-FPI-1967 and vofatamab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 20 Apr 2022to 8 Sep 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States4 sites
City of Hope
Duarte, California, 91010
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of California, San Francisco
San Francisco, California, 94143
Australia2 sites
St Vincent's Hospital
Melbourne
GC Murdoch
Murdoch, Western Australia, 6150
About this study
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
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.
Read the 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.
- Conditions
- Advanced Solid Tumor, Head and Neck Squamous Cell Carcinoma, Bladder Carcinoma, Susceptible FGFR3 Genetic Alterations, FGFR3, FGFR3 Overexpression
- Being tested
- [225Ac]-FPI-1966, [111In]-FPI-1967, vofatamab
- Keywords
- Actinium-225, Targeted Alpha Therapy, Radiopharmaceutical, Radioimmunoconjugate, Theranostic, Theragnostic, Radioligand, Antineoplastic agents, [225Ac]-FPI-1966
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Urinary Bladder Neoplasms, Ovarian Neoplasms, Colorectal Neoplasms, Breast Neoplasms, Liver Neoplasms, Lung Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[225Ac]-FPI-1966Drug
[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.
[111In]-FPI-1967Drug
[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.
vofatamabBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 | Experimental | Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered with or without pre-dosing with vofatamab. Receives: Drug: [225Ac]-FPI-1966; Drug: [111In]-FPI-1967; Biological: vofatamab |
| Phase 2 | Experimental | 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. Receives: Drug: [225Ac]-FPI-1966; Drug: [111In]-FPI-1967; Biological: vofatamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Phase 1: Incidence of AEs to evaluate safety and tolerability of [225Ac]-FPI-1966, [111In]-FPI-1967, and vofatamab.
Measured: Approximately 2 years post final administration
Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966
Measured: Approximately 42 days post administration.
Phase 1: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)
Measured: Within one week of administration
Phase 1: Effect of pre-dose administration of vofatamab on the radiation dosimetry of [111In]-FPI-1967 and [225Ac]-FPI-1966.
Measured: Within one week of administration
Phase 2: Objective response rate (ORR) (sum of complete and partial response) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Measured: Up to two years post final administration.
Secondary outcomes (11)
Phase 1 and 2: Anti-tumour activity of [225Ac]-FPI-1966 regimen measured by response per RECIST v1.1
Measured: Approximately 2 years post final administration
Phase 1 and 2: Tumour uptake of [111In]-FPI-1967 by evaluating SPECT/CT and/or planar images
Measured: Within one week of administration
Phase 2: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)
Measured: Within one week of administration
Phase 1 and 2: Clearance for radioactivity and for the targeting antibody.
Measured: 28 days post final [225Ac]-FPI-1966administration
Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody
Measured: 28 days post final [225Ac]-FPI-1966administration.
Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody.
Measured: 28 days post final[225Ac]-FPI-1966 administration
Phase 1 and 2: Half-life for radioactivity and targeting antibody.
Measured: 28 days post final [225Ac]-FPI-1966 administration
Phase 1: Changes in clearance for radioactivity and targeting antibody following pre-dose administration of vofatamab
Measured: 28 days post final [225Ac]-FPI-1966 administration
Phase 1: Changes in AUC for radioactivity and targeting antibody following pre-dose administration of vofatamab.
Measured: 28 days post final [225Ac]-FPI-1966 administration
Phase 1: Changes in Cmax for radioactivity and targeting antibody following pre-dose administration of vofatamab.
Measured: 28 days post final [225Ac]-FPI-1966 administration
Phase 1: Changes in half-life for radioactivity and targeting antibody following pre-dose administration of vofatamab
Measured: 28 days post final [225Ac]-FPI-1966 administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2022
- Study start20 Apr 2022
- Primary completion8 Sep 2023
- Study completion8 Sep 2023
Why it stopped: Fusion announced that it is discontinuing this study as part of a portfolio prioritization and assessment; Fusion no longer plans to pursue development of FPI-1966.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fusion Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Julia Kazakin, MD, Study director, Fusion Pharmaceuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05363605
- Sponsor's protocol ID
- FPI-1966-101
- Status last verified
- Dec 2023
- First submitted
- 26 Apr 2022
- Last updated
- 19 Dec 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05363605
- Acronym / sponsor ID
- FPI-1966-101
- Conditions
- Advanced Solid Tumor, Head and Neck Squamous Cell Carcinoma, Bladder Carcinoma, Susceptible FGFR3 Genetic Alterations, FGFR3, FGFR3 Overexpression
- Keywords
- Actinium-225, Targeted Alpha Therapy, Radiopharmaceutical, Radioimmunoconjugate, Theranostic, Theragnostic, Radioligand, Antineoplastic agents
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Fusion announced that it is discontinuing this study as part of a portfolio prioritization and assessment; Fusion no longer plans to pursue development of FPI-1966.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Fusion Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Apr 2022 (actual)
- Primary completion
- 8 Sep 2023 (actual)
- Study completion
- 8 Sep 2023 (actual)
- First posted
- 6 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 | Experimental | Drug: [225Ac]-FPI-1966, Drug: [111In]-FPI-1967, Biological: vofatamabDepending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered with or without pre-dosing with vofatamab. |
| Phase 2 | Experimental | Drug: [225Ac]-FPI-1966, Drug: [111In]-FPI-1967, Biological: vofatamabDepending 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [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 | Phase 1, Phase 2 |
| [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. | Drug | Phase 1, Phase 2 |
| vofatamabVofatamab 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. | Biological | Phase 1, Phase 2 |
Primary outcome
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
Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966
Time frame: Approximately 42 days post administration.
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
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
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.
11 secondary outcomes
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
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
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
Phase 1 and 2: Clearance for radioactivity and for the targeting antibody.
Time frame: 28 days post final [225Ac]-FPI-1966administration
Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody
Time frame: 28 days post final [225Ac]-FPI-1966administration.
Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody.
Time frame: 28 days post final[225Ac]-FPI-1966 administration
Phase 1 and 2: Half-life for radioactivity and targeting antibody.
Time frame: 28 days post final [225Ac]-FPI-1966 administration
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
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
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
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
Results and safety
The study was stopped early (reason given: Fusion announced that it is discontinuing this study as part of a portfolio prioritization and assessment; Fusion no longer plans to pursue development of FPI-1966.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2023.
- Sponsor websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julia Kazakin, MD study director
Fusion Pharmaceuticals Inc.
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing [225Ac]-FPI-1966, [111In]-FPI-1967 and vofatamab in people with Advanced Solid Tumor and Head and Neck Squamous Cell Carcinoma, run by Fusion Pharmaceuticals Inc. at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Fusion announced that it is discontinuing this study as part of a portfolio prioritization and assessment; Fusion no longer plans to pursue development of FPI-1966.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2023.