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First-in-Human Phase I Study of Fisogatinib (BLU-554) Validates Aberrant Fibroblast Growth Factor 19 Signaling as a Driver Event in Hepatocellular Carcinoma

Kim, RD; Sarker, D; Meyer, T; Yau, T; Macarulla, T; Park, J-W; Choo, SP; ... Kang, Y-K; + view all (2019) First-in-Human Phase I Study of Fisogatinib (BLU-554) Validates Aberrant Fibroblast Growth Factor 19 Signaling as a Driver Event in Hepatocellular Carcinoma. Cancer Discovery 10.1158/2159-8290.CD-19-0555. (In press).

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Abstract

Outcomes for patients with advanced hepatocellular carcinoma (HCC) remain poor despite recent progress in drug development. Emerging data implicate FGF19 as a potential HCC driver, suggesting its receptor, FGFR4, as a novel therapeutic target. We evaluated fisogatinib (BLU-554), a highly potent and selective oral FGFR4 inhibitor, in a phase I dose-escalation/dose-expansion study in advanced HCC using FGF19 expression by immunohistochemistry as a biomarker for pathway activation. For dose escalation, 25 patients received 140 to 900 mg fisogatinib once daily; the maximum-tolerated dose (600 mg once daily) was expanded in 81 patients. fisogatinib was well tolerated; most adverse events were manageable, grade 1/2 gastrointestinal events, primarily diarrhea, nausea, and vomiting. Across doses, the overall response rate was 17% in FGF19-positive patients (median duration of response: 5.3 months [95% CI, 3.7-not reached]) and 0% in FGF19-negative patients. These results validate FGFR4 as a targetable driver in FGF19-positive advanced HCC.

Type: Article
Title: First-in-Human Phase I Study of Fisogatinib (BLU-554) Validates Aberrant Fibroblast Growth Factor 19 Signaling as a Driver Event in Hepatocellular Carcinoma
Location: United States
DOI: 10.1158/2159-8290.CD-19-0555
Publisher version: https://doi.org/10.1158/2159-8290.CD-19-0555
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10083759
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