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

TitleFirst-in-Human Phase I Study of Fisogatinib (BLU-554) Validates Aberrant FGF19 Signaling as a Driver Event in Hepatocellular Carcinoma
Authors
Issue Date2019
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerdiscovery.aacrjournals.org/
Citation
Cancer Discovery, 2019, v. 9 n. 12, p. 1696-1707 How to Cite?
AbstractOutcomes 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.
DescriptionLink to Free access
Persistent Identifierhttp://hdl.handle.net/10722/279572
ISSN
2019 Impact Factor: 29.497
2015 SCImago Journal Rankings: 5.326

 

DC FieldValueLanguage
dc.contributor.authorKim, RD-
dc.contributor.authorSarker, D-
dc.contributor.authorMeyer, T-
dc.contributor.authorYau, T-
dc.contributor.authorMacarulla, T-
dc.contributor.authorPark, JW-
dc.contributor.authorChoo, SP-
dc.contributor.authorHollebecque, A-
dc.contributor.authorSung, MW-
dc.contributor.authorLim, HY-
dc.contributor.authorMazzaferro, V-
dc.contributor.authorTrojan, J-
dc.contributor.authorZhu, AX-
dc.contributor.authorYoon, JH-
dc.contributor.authorSharma, S-
dc.contributor.authorLin, ZZ-
dc.contributor.authorChan, SL-
dc.contributor.authorFaivre, S-
dc.contributor.authorFeun, LG-
dc.contributor.authorYen, C-J-
dc.contributor.authorDufour, J-F-
dc.contributor.authorPalmer, DH-
dc.contributor.authorLlovet, JM-
dc.contributor.authorManoogian, M-
dc.contributor.authorTugnait, M-
dc.contributor.authorStransky, N-
dc.contributor.authorHagel, M-
dc.contributor.authorKohl, NE-
dc.contributor.authorLengauer, C-
dc.contributor.authorSherwin, CA-
dc.contributor.authorSchmidt-Kittler, O-
dc.contributor.authorHoeflich, KP-
dc.contributor.authorShi, H-
dc.contributor.authorWolf, BB-
dc.contributor.authorKang, Y-K-
dc.date.accessioned2019-11-01T07:19:55Z-
dc.date.available2019-11-01T07:19:55Z-
dc.date.issued2019-
dc.identifier.citationCancer Discovery, 2019, v. 9 n. 12, p. 1696-1707-
dc.identifier.issn2159-8274-
dc.identifier.urihttp://hdl.handle.net/10722/279572-
dc.descriptionLink to Free access-
dc.description.abstractOutcomes 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.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerdiscovery.aacrjournals.org/-
dc.relation.ispartofCancer Discovery-
dc.titleFirst-in-Human Phase I Study of Fisogatinib (BLU-554) Validates Aberrant FGF19 Signaling as a Driver Event in Hepatocellular Carcinoma-
dc.typeArticle-
dc.identifier.emailYau, T: tyaucc@hku.hk-
dc.identifier.authorityYau, T=rp01466-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/2159-8290.CD-19-0555-
dc.identifier.hkuros308505-
dc.identifier.volume9-
dc.identifier.issue12-
dc.identifier.spage1696-
dc.identifier.epage1707-
dc.publisher.placeUnited States-

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