First-in-human study of BLU-554, a potent, highly-selective FGFR4 inhibitor designed for hepatocellular carcinoma (HCC) with FGFR4 pathway activation

An abstract of the study of Kim et al. about BLU-554, a potent, highly-selective FGFR4 inhibitor designed for hepatocellular carcinoma (HCC) with FGFR4 pathway activation is presented. Among other things FGFR4 and its ligand, FGF19, normally promote hepatocyte proliferation and regulate bile acid homeostasis; however, emerging data show FGF19 overexpression in up to 30% of HCC and implicate FGF19-dependent FGFR4 activation as a driver of hepatocarcinogenesis. A phase 1 study (NCT02508467) was initiated to assess the safety, PK, PD and preliminary clinical activity of BLU-554, a potent, highly-selective, oral FGFR4 inhibitor. BLU-554, a potent, highly-selective FGFR4 inhibitor has acceptable tolerability in pts with advanced HCC and demonstrates objective clinical activity in FGF19 IHC-positive disease. These data further implicate the FGFR4 pathway as a driver in HCC and provide the first proof of principle for targeting FGFR4 in HCC. Expanded clinical testing of BLU-554 with prospective selection of FGF19 IHC-positive HCC pts is underway.