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Conference Paper: A Phase I/II study of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2 and VEGFR in advanced hepatocellular carcinoma (HCC)

TitleA Phase I/II study of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2 and VEGFR in advanced hepatocellular carcinoma (HCC)
Authors
KeywordsMedical sciences
Gastroenterology
Issue Date2011
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
The 46th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress 2011), Berlin, Germany, 30 March-3 April 2011. In Journal of Hepatology, 2011, v. 54 suppl. 1, p. S268, abstract no. 665 How to Cite?
AbstractBACKGROUND AND AIMS: Foretinib is an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2 and VEGFR. HGF/MET signaling plays a pivotal role in tumour cell proliferation, migration and invasion, and circulating levels of HGF correlate with poor prognosis in HCC. This phase I/II trial (MET111645) is evaluating oral foretinib as first line therapy in advanced Asian HCC patients. METHODS: Patients with measurable unresectable/metastatic HCC, no prior sorafenib or other multi-kinase inhibitors, ECOG PS 0–1, adequate organ function and Child–Pugh grade A are eligible for enrolment. Phase I is a standard 3+3 design using increasing doses of oral foretinib to evaluate safety and determine the maximum tolerated dose (MTD). Secondary objectives include antitumour activity and pharmacokinetics. RESULTS: As of November 16, 2010, 13 patients have been enrolled: median age 57 years (range 31–78 years), M/F = 9/4. BCLC stage 0/A/B/C at screening: 0/0/3/10. Prior lines of therapy including local treatment: unknown/1/2/3/4: 1/3/5/2/1. Drug-related adverse events (AE) were reported in 10 patients (77%). The most common AEs were hypertension (54%), diarrhoea (31%), thrombocytopenia (23%), and peripheral oedema (23%). Serious treatment-emergent toxicities were reported in 54% of patients. Two dose-limiting toxicities (renal failure, proteinuria) were observed in 2/6 patients at 45mg OD but no DLTs were observed in 6 patients at 30mg OD. Nine patients were evaluable for response according to RECIST 1.0; 2 patients had a best response of partial response (PR); objective response rate (ORR) 22%. When tumour response was assessed according to modified RECIST criteria for HCC, 1 patient showed a complete response and 3 patients had a PR; ORR 44%. Exposure of 30- and 45-mg OD foretinib was overlapping and similar to higher doses in other tumour types. CONCLUSION: The foretinib MTD was determined to be 30mg OD. The early promising signal of activity observed in this phase I trial needs to be confirmed in phase II.
DescriptionThis journal suppl. is Abstract Book of The International Liver Congress™ 2011
Poster Session
Persistent Identifierhttp://hdl.handle.net/10722/137893
ISSN
2015 Impact Factor: 10.59
2015 SCImago Journal Rankings: 4.570

 

DC FieldValueLanguage
dc.contributor.authorYau, Ten_US
dc.contributor.authorYen, CJen_US
dc.contributor.authorChen, PJen_US
dc.contributor.authorChau, Yen_US
dc.contributor.authorLencioni, Ren_US
dc.contributor.authorKallender, Hen_US
dc.contributor.authorOttesen, LHen_US
dc.contributor.authorPoon, RTPen_US
dc.date.accessioned2011-08-26T14:36:30Z-
dc.date.available2011-08-26T14:36:30Z-
dc.date.issued2011en_US
dc.identifier.citationThe 46th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress 2011), Berlin, Germany, 30 March-3 April 2011. In Journal of Hepatology, 2011, v. 54 suppl. 1, p. S268, abstract no. 665en_US
dc.identifier.issn0168-8278-
dc.identifier.urihttp://hdl.handle.net/10722/137893-
dc.descriptionThis journal suppl. is Abstract Book of The International Liver Congress™ 2011-
dc.descriptionPoster Session-
dc.description.abstractBACKGROUND AND AIMS: Foretinib is an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2 and VEGFR. HGF/MET signaling plays a pivotal role in tumour cell proliferation, migration and invasion, and circulating levels of HGF correlate with poor prognosis in HCC. This phase I/II trial (MET111645) is evaluating oral foretinib as first line therapy in advanced Asian HCC patients. METHODS: Patients with measurable unresectable/metastatic HCC, no prior sorafenib or other multi-kinase inhibitors, ECOG PS 0–1, adequate organ function and Child–Pugh grade A are eligible for enrolment. Phase I is a standard 3+3 design using increasing doses of oral foretinib to evaluate safety and determine the maximum tolerated dose (MTD). Secondary objectives include antitumour activity and pharmacokinetics. RESULTS: As of November 16, 2010, 13 patients have been enrolled: median age 57 years (range 31–78 years), M/F = 9/4. BCLC stage 0/A/B/C at screening: 0/0/3/10. Prior lines of therapy including local treatment: unknown/1/2/3/4: 1/3/5/2/1. Drug-related adverse events (AE) were reported in 10 patients (77%). The most common AEs were hypertension (54%), diarrhoea (31%), thrombocytopenia (23%), and peripheral oedema (23%). Serious treatment-emergent toxicities were reported in 54% of patients. Two dose-limiting toxicities (renal failure, proteinuria) were observed in 2/6 patients at 45mg OD but no DLTs were observed in 6 patients at 30mg OD. Nine patients were evaluable for response according to RECIST 1.0; 2 patients had a best response of partial response (PR); objective response rate (ORR) 22%. When tumour response was assessed according to modified RECIST criteria for HCC, 1 patient showed a complete response and 3 patients had a PR; ORR 44%. Exposure of 30- and 45-mg OD foretinib was overlapping and similar to higher doses in other tumour types. CONCLUSION: The foretinib MTD was determined to be 30mg OD. The early promising signal of activity observed in this phase I trial needs to be confirmed in phase II.-
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep-
dc.relation.ispartofJournal of Hepatologyen_US
dc.subjectMedical sciences-
dc.subjectGastroenterology-
dc.titleA Phase I/II study of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2 and VEGFR in advanced hepatocellular carcinoma (HCC)en_US
dc.typeConference_Paperen_US
dc.identifier.emailYau, T: tyaucc@hku.hken_US
dc.identifier.emailPoon, RTP: poontp@hku.hken_US
dc.identifier.authorityYau, T=rp01466en_US
dc.identifier.authorityPoon, RTP=rp00446en_US
dc.identifier.hkuros189738en_US
dc.identifier.volume54en_US
dc.identifier.issuesuppl. 1en_US
dc.identifier.spageS268, abstract no. 665-
dc.identifier.epageS268, abstract no. 665-
dc.publisher.placeNetherlands-
dc.description.otherThe 46th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress 2011), Berlin, Germany, 30 March-3 April 2011. In Journal of Hepatology, 2011, v. 54 suppl. 1, p. S268, abstract no. 665-

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