Shukui, Qin, Stephen, Lam Chan, Wattana, Sukeepaisarnjaroen, Guohong, Han, Su Pin , Choo, Virote , Sriuranpong, Hongming, Pan, Thomas , Yau, Yabing , Guo, Minshan , Chen, Zhenggang, Ren, Jianming, Xu, Chia-Jui , Yen, Zhong-Zhe , Lin, Gu, Gary, Sun, Yongjian , Tiedt, Ralph, Hao, Lu, Song, Vicky, Tanwandee, Tawesak and Manenti, Luigi (2019) A Phase II Study of the Efficacy and Safety of the MET Inhibitor Capmatinib (INC280) in Patients with Advanced Hepatocellular Carcinoma. Therapeutic Advances in Medical Oncology, 11 (2019 D). ISSN 1758-83591758-8359

Abstract

Background: 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 assess the safety, pharmacokinetics, and correlation of biomarkers with response.
Study Design: This phase II, open-label, single-arm study evaluated twice-daily (BID) oral capmatinib in a dose-determining part, utilizing a Bayesian Logistic Regression Model (BLRM) subject to Escalation with Overdose Control criteria, safety, pharmacokinetic, and pharmacodynamic information to determine a recommended dose for expansion (RDE) evaluating efficacy in patients with MET-dysregulated HCC.
Results: Thirty-eight patients received treatment. In the dose-determining part, 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 qualifying (drug-related, dose-limiting) 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 part, in a subgroup of 10 patients with MET-high HCC, the overall response rate was 30%, including one durable complete response (>600 days) and two partial responses (one 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.

Item Type:	Article
Date Deposited:	21 Jan 2020 00:45
Last Modified:	21 Jan 2020 00:45
URI:	https://oak.novartis.com/id/eprint/41515