First-in-Human Phase I Study of Fisogatinib (BLU-554) Validates Aberrant FGF19 Signaling as a Driver Event in Hepatocellular Carcinoma.

Kim, Richard D; Sarker, Debashis; Meyer, Tim; Yau, Thomas; Macarulla, Teresa; Park, Joong-Won; Choo, Su Pin; Hollebecque, Antoine; Sung, Max W; Lim, Ho-Yeong; Mazzaferro, Vincenzo; Trojan, Joerg; Zhu, Andrew X; Yoon, Jung-Hwan; Sharma, Sunil; Lin, Zhong-Zhe; Chan, Stephen L; Faivre, Sandrine; Feun, Lynn G; Yen, Chia-Jui; ... (2019). First-in-Human Phase I Study of Fisogatinib (BLU-554) Validates Aberrant FGF19 Signaling as a Driver Event in Hepatocellular Carcinoma. Cancer discovery, 9(12), pp. 1696-1707. American Association for Cancer Research 10.1158/2159-8290.CD-19-0555

Text 1696.full.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (14MB)

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 measured by IHC 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. SIGNIFICANCE: Fisogatinib elicited clinical responses in patients with tumor FGF19 overexpression in advanced HCC. These results validate the oncogenic driver role of the FGFR4 pathway in HCC and the use of FGF19 as a biomarker for patient selection.See related commentary by Subbiah and Pal, p. 1646.This article is highlighted in the In This Issue feature, p. 1631.

Interest & Impact

Downloads

1 since deposited on 14 Jan 2020
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item