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Article: A phase II study of the efficacy and safety of the MET inhibitor capmatinib (INC280) in patients with advanced hepatocellular carcinoma

TitleA phase II study of the efficacy and safety of the MET inhibitor capmatinib (INC280) in patients with advanced hepatocellular carcinoma
Authors
KeywordsCapmatinib
INC280
HCC
MET inhibitor
Phase II
Issue Date2019
PublisherSAGE Publications (UK and US): Open Access Titles. The Journal's web site is located at https://journals.sagepub.com/home/tama
Citation
Therapeutic Advances in Medical Oncology, 2019, v. 11, p. 1-12 How to Cite?
AbstractBackground: The objectives of this phase II study were to determine the clinical activity of the MET tyrosine kinase inhibitor capmatinib (INC280) in patients with MET-dysregulated advanced hepatocellular carcinoma (HCC) and to assess the safety, pharmacokinetics, and correlation of biomarkers with the response. Methods: This phase II, open-label, single-arm study evaluated twice daily (BID) oral capmatinib in a dose-determining stage, utilizing a Bayesian Logistic Regression Model (BLRM) subject to Escalation with Overdose Control criteria, safety, pharmacokinetics, and pharmacodynamic information to determine a recommended dose for expansion (RDE) evaluating efficacy in patients with MET-dysregulated HCC. Results: A total of 38 patients received treatment. In the dose-determining stage, patients received capmatinib 300 mg BID capsules (n = 8), and in the expansion, patients received 600 mg BID capsules (n = 28) or 400 mg BID tablets (n = 2) based on the BLRM and other relevant clinical data. No predefined qualifying adverse events (AEs) were observed during the first 28 days of treatment, and the RDE was 600 mg BID capsules (equivalent pharmacokinetics to 400 mg BID tablets). The most common any causality AEs were nausea (42%), vomiting (37%), and diarrhea (34%). In the expansion stage, in a subgroup of 10 patients with MET-high HCC, the overall response rate was 30%, including 1 durable complete response (>600 days) and 2 partial responses [1 durable (>600 days)]. Conclusions: Single agent capmatinib at the RDE is tolerable with a manageable safety profile. Antitumor activity was seen in a subset of patients with MET-dysregulated (MET-high) HCC. Trial registration: ClinicalTrials.gov: NCT01737827. https://clinicaltrials.gov/ct2/show/NCT01737827
Persistent Identifierhttp://hdl.handle.net/10722/279463
ISSN
2017 Impact Factor: 6.238
2015 SCImago Journal Rankings: 1.407
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorQin, S-
dc.contributor.authorChan, SL-
dc.contributor.authorSukeepaisarnjaroen, W-
dc.contributor.authorHan, G-
dc.contributor.authorChoo, SP-
dc.contributor.authorSriuranpong, V-
dc.contributor.authorPan, H-
dc.contributor.authorYau, T-
dc.contributor.authorGuo, Y-
dc.contributor.authorChen, M-
dc.contributor.authorRen, Z-
dc.contributor.authorXu, J-
dc.contributor.authorYen, CJ-
dc.contributor.authorLin, ZZ-
dc.contributor.authorManenti, L-
dc.contributor.authorGu, Y-
dc.contributor.authorSun, Y-
dc.contributor.authorTiedt, R-
dc.contributor.authorHao, L-
dc.contributor.authorSong, W-
dc.contributor.authorTanwandee, T-
dc.date.accessioned2019-11-01T07:17:51Z-
dc.date.available2019-11-01T07:17:51Z-
dc.date.issued2019-
dc.identifier.citationTherapeutic Advances in Medical Oncology, 2019, v. 11, p. 1-12-
dc.identifier.issn1758-8340-
dc.identifier.urihttp://hdl.handle.net/10722/279463-
dc.description.abstractBackground: The objectives of this phase II study were to determine the clinical activity of the MET tyrosine kinase inhibitor capmatinib (INC280) in patients with MET-dysregulated advanced hepatocellular carcinoma (HCC) and to assess the safety, pharmacokinetics, and correlation of biomarkers with the response. Methods: This phase II, open-label, single-arm study evaluated twice daily (BID) oral capmatinib in a dose-determining stage, utilizing a Bayesian Logistic Regression Model (BLRM) subject to Escalation with Overdose Control criteria, safety, pharmacokinetics, and pharmacodynamic information to determine a recommended dose for expansion (RDE) evaluating efficacy in patients with MET-dysregulated HCC. Results: A total of 38 patients received treatment. In the dose-determining stage, patients received capmatinib 300 mg BID capsules (n = 8), and in the expansion, patients received 600 mg BID capsules (n = 28) or 400 mg BID tablets (n = 2) based on the BLRM and other relevant clinical data. No predefined qualifying adverse events (AEs) were observed during the first 28 days of treatment, and the RDE was 600 mg BID capsules (equivalent pharmacokinetics to 400 mg BID tablets). The most common any causality AEs were nausea (42%), vomiting (37%), and diarrhea (34%). In the expansion stage, in a subgroup of 10 patients with MET-high HCC, the overall response rate was 30%, including 1 durable complete response (>600 days) and 2 partial responses [1 durable (>600 days)]. Conclusions: Single agent capmatinib at the RDE is tolerable with a manageable safety profile. Antitumor activity was seen in a subset of patients with MET-dysregulated (MET-high) HCC. Trial registration: ClinicalTrials.gov: NCT01737827. https://clinicaltrials.gov/ct2/show/NCT01737827-
dc.languageeng-
dc.publisherSAGE Publications (UK and US): Open Access Titles. The Journal's web site is located at https://journals.sagepub.com/home/tama-
dc.relation.ispartofTherapeutic Advances in Medical Oncology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCapmatinib-
dc.subjectINC280-
dc.subjectHCC-
dc.subjectMET inhibitor-
dc.subjectPhase II-
dc.titleA phase II study of the efficacy and safety of the MET inhibitor capmatinib (INC280) in patients with advanced hepatocellular carcinoma-
dc.typeArticle-
dc.identifier.emailYau, T: tyaucc@hku.hk-
dc.identifier.authorityYau, T=rp01466-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1177/1758835919889001-
dc.identifier.pmid31853265-
dc.identifier.pmcidPMC6906348-
dc.identifier.scopuseid_2-s2.0-85076565560-
dc.identifier.hkuros308506-
dc.identifier.volume11-
dc.identifier.spage1-
dc.identifier.epage12-
dc.identifier.isiWOS:000502363000001-
dc.publisher.placeUnited Kingdom-

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