First In Human Phase 1 Study Of Fisogatinib (BLU-554) Validates Aberrant FGF 19 Signaling As A Driver Event In Hepatocellular Carcinoma

In a recent publication from the American Association of cancer research, in the Journal Cancer Discovery, investigators reported on the outcome of fisogatinib (BLU-554), a highly potent and selective small molecule inhibitor of FGFR4.  

The study was a phase 1 dose escalation/dose expansion study in patients with advanced hepatocellular carcinoma.  Immunohistochemistry was utilized to determine FGF19 expression levels.  For the dose escalation component, 25 patients were treated with doses of fisogatinib (BLU-554) between 140 and 900 mg once daily.  The maximum tolerated dose was 600 mg once a day.  The final expansion cohort included 81 patients.

Fisogatinib (BLU-554) was well-tolerated, and most adverse events were described as “manageable”.  Grade 1 and 2 gastrointestinal events were predominantly diarrhea, nausea and vomiting.  The overall response rate across all the doses was 17% in patients who expressed FGF19.  The median duration of response was 5.3 months.  The overall response rate was 0% in patients who were negative for FGF19 expression. 

The authors concluded that these results validate FGFR4 as a targetable driver in FGF19 positive hepatocellular carcinoma.