Dosing of FPI-1966 Starts in Patients with Advanced Solid Tumors Express FGFR3

The targeted alpha therapy, FPI-1966, has been dosed for the first time in a phase 1/2 study of patients with advanced solid tumors that express FGFR3.

The first patient with an advanced solid tumor expressing FGFR3 has been dosed with FPI-1966 in a phase 1/2 study (NCT05363605), according to an announcement by Fusion Pharmaceuticals, Inc.1

FPI-1966 is a targeted alpha therapy that delivers actinium-225 to cancer cells that express FGFR3, which can include bladder cancer, ovarian cancer, and head and neck cancer.

The phase 1/2 study of FPI-1966 in combination with vofatamab aims to enroll 155 patients with FGFR3-expressing advanced solid tumors. Phase 1 of the study will follow a 3 + 3 design. FPI-1966 will be administered in ascending doses that will repeat for 42-day cycles at 185 MBq ahead of imaging. The addition of vofatamab can be administered as a pre-dose over a fixed range of doses, depending on the cohort being treated.2

"This study will evaluate FPI-1966 in patients with solid tumors expressing FGFR3, a validated cancer target found in multiple tumor types with substantial unmet need, notably bladder, ovarian, and head and neck cancers. FPI-1966, and the growing number of TATs in our pipeline, are designed as next-generation antibody-drug conjugates (ADCs) in that they leverage the potency of actinium-225 and alpha particle radiation in place of chemical toxins to selectively eradicate cancer cells. Given the prevalence of the FGFR3 target, and the use of a precision medicine approach that employs an imaging analog to enable patient selection, we believe FPI-1966 has the potential to become an important new treatment paradigm for cancer patients, said," said John Valliant, PhD, chief executive officer of Fusion Pharmaceuticals Inc, in a press release.1

The phase 1 coprimary end points include the incidence of adverse events, dose-limiting toxicities, clinically significant clinical laboratory abnormalities compared to baseline, changes in electrocardiogram parameters, radiation doses for selected organs and whole body both for FPI-1966, changes in radiation, and changes in tumor uptake for FPI-1966. The phase 2 primary end point of objective response rate.2

In phase 1, ORR will be assessed as a secondary end point. In both phases, other key secondary end point include time to response, duration of response, progression-free survival, time to progression, disease control rate, and overall survival.

Patients eligible for the study are males or females aged 18 years or older with histologically or cytologically confirmed disease that is refractory to standard therapy. Patients are required to have measurable disease per RECIST v1.1, available tumor tissue for biopsy, and adequate bone marrow, cardiovascular, hepatic, and renal function.

The study excludes patients who received prior systemic radiopharmaceutical therapy within 6 months before to the first dose of FPI-1966, prior radiation therapy to bone marrow > 20 Gy, radiation therapy within 30 days prior to the first dose of FPI-1966, and prior anticancer therapy within 5 half-lives or 4 weeks.

"Dosing of the first patient in this phase 1/2 study of FPI-1966 demonstrates our continued ability to bring innovative targeted alpha therapies (TATs) into the clinic," said Valliant, in the press release.1

The phase 1/2 study is actively recruiting patients with FGFR3-expressing advanced solid tumors at locations in California, Iowa, and New York.2


1. Fusion Pharmaceuticals announces first patient dosed in phase 1/2 study of FPI-1966 in patients with advanced solid tumors expressing FGFR3. News release. Fusion Pharmaceuticals, Inc. August 29, 2022. Accessed August 30, 2022.

2. A study of [225Ac]-FPI-1966 in participants with advanced solid tumours. August 17, 2022.Accessed August 30, 2022.