Kim RD, Sarker D, Meyer T, et al. - Since the FGFR4, a receptor of FGF19 has been suggested as a new therapeutic target in hepatocellular carcinoma (HCC), researchers undertook a phase I dose-escalation/dose-expansion study to assess a highly potent and selective oral FGFR4 inhibitor, fisogatinib (BLU-554), in advanced HCC, utilizing FGF19 expression by immunohistochemistry as a biomarker for pathway activation. For dose escalation, they administered 140 to 900 mg fisogatinib once daily to 25 patients; the maximum-tolerated dose (600 mg once daily) was expanded in 81 patients. Findings revealed the good tolerability of fisogatinib as well as its manageable profile for most adverse events, grade 1/2 gastrointestinal events, primarily diarrhea, nausea, and vomiting. In FGF19-positive patients and in FGF19-negative patients, the overall response rate was estimated to be 17% (median duration of response: 5.3 months [95% CI, 3.7-not reached]) and 0%, respectively, across doses. Overall, FGFR4 was validated as a targetable driver in FGF19-positive advanced HCC.