Fusion Pharmaceuticals has dosed the first subject in the Phase I/II clinical trial of [225Ac]-FPI-1966 (FPI-1966) in advanced solid tumours expressing fibroblast growth factor receptor three (FGFR3) patients. 

The multicentre, open-label trial will analyse the safety, tolerability, dosimetry, biodistribution, and pharmacokinetics of FPI-1966 in FGFR3-expressing advanced, inoperable, metastatic, and/or recurrent solid tumour patients. 

It has a three + three dose escalation design to assess various ascending doses of FPI-1966. 

To determine the effect of pre-dosing on tumour uptake and pharmacokinetics, the first cohort will have sub-groups in which several dosages of non-radiolabeled vofatamab (cold antibody) will be assessed. 

Subjects will receive FPI-1967, an imaging analogue of FPI-1966, and people whose imaging meet the predefined tumour uptake will be given FPI-1966. 

The Phase II segment will have two tumour-specific cohorts and one basket cohort.

After initial experience with subject screening through FPI-1967 imaging for predicting the pace of participant enrolment, the company intends to offer guidance on timing for the initial pharmacokinetic, imaging and safety data.

FPI-1966 is a targeted alpha therapy and can act on and offer an alpha-emitting medical isotope, actinium-225, to cancer cells that express FGFR3.

Leveraging the Fast-Clear linker of the company, FPI-1966 connects to a human monoclonal antibody targeting FGFR3, vofatamab, with actinium-225.

Fusion Pharmaceuticals CEO John Valliant said: “This study will evaluate FPI-1966 in patients with solid tumours expressing FGFR3, a validated cancer target found in multiple tumour 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.”

The company nominated the first targeted alpha therapy (TAT) candidate under a partnership agreement with AstraZeneca to begin Phase I trials.