PMID- 31853265 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220411 IS - 1758-8340 (Print) IS - 1758-8359 (Electronic) IS - 1758-8340 (Linking) VI - 11 DP - 2019 TI - A phase II study of the efficacy and safety of the MET inhibitor capmatinib (INC280) in patients with advanced hepatocellular carcinoma. PG - 1758835919889001 LID - 10.1177/1758835919889001 [doi] LID - 1758835919889001 AB - BACKGROUND: 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. CI - (c) The Author(s), 2019. FAU - Qin, Shukui AU - Qin S AD - PLA Cancer Center, Nanjing Bayi Hospital, Nanjing 210002, China. FAU - Chan, Stephen Lam AU - Chan SL AD - Department of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China. FAU - Sukeepaisarnjaroen, Wattana AU - Sukeepaisarnjaroen W AD - Department of Medicine, Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand. FAU - Han, Guohong AU - Han G AD - Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China. FAU - Choo, Su Pin AU - Choo SP AD - Division of Medical Oncology, National Cancer Center Singapore, Singapore. FAU - Sriuranpong, Virote AU - Sriuranpong V AD - Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. FAU - Pan, Hongming AU - Pan H AD - Department of Medical Oncology, Sir Run Shaw Hospital, Zhejiang University, Hangzhou, China. FAU - Yau, Thomas AU - Yau T AD - Department of Surgery, Queen Mary Hospital, University of Hong Kong, Hong Kong, China. FAU - Guo, Yabing AU - Guo Y AD - Nanfang Hospital, Guangzhou Southern Medical University, Guangzhou, China. FAU - Chen, Minshan AU - Chen M AD - Sun Yat-Sen University Cancer Center, Guangzhou, China. FAU - Ren, Zhenggang AU - Ren Z AD - Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Xu, Jianming AU - Xu J AD - Department of Gastrointestinal Oncology, 307 Hospital of People's Liberation Army, Beijing, China. FAU - Yen, Chia-Jui AU - Yen CJ AD - Department of Internal Medicine, National Cheng Kung University Hospital, Tainan City. FAU - Lin, Zhong-Zhe AU - Lin ZZ AD - Department of Oncology, National Taiwan University Hospital, Taipei City. FAU - Manenti, Luigi AU - Manenti L AD - Translational Clinical Oncology, Novartis Institutes for BioMedical Research, East Hanover, NJ, USA. FAU - Gu, Yi AU - Gu Y AD - PK Sciences, China Novartis Institutes for BioMedical Research, Shanghai, China. FAU - Sun, Yongjian AU - Sun Y AD - Translational Clinical Oncology, China Novartis Institutes for BioMedical Research, Shanghai, China. FAU - Tiedt, Ralph AU - Tiedt R AD - Novartis Institutes for BioMedical Research, Basel, Basel-Stadt, Switzerland. FAU - Hao, Lu AU - Hao L AD - Translational Clinical Oncology, China Novartis Institutes for BioMedical Research, Shanghai, China. FAU - Song, Wenjie AU - Song W AD - Translational Clinical Oncology, China Novartis Institutes for BioMedical Research, Shanghai, China. FAU - Tanwandee, Tawesak AU - Tanwandee T AD - Division of Gastroenterology, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. LA - eng SI - ClinicalTrials.gov/NCT01737827 PT - Journal Article DEP - 20191211 PL - England TA - Ther Adv Med Oncol JT - Therapeutic advances in medical oncology JID - 101510808 EIN - Ther Adv Med Oncol. 2020 Mar 12;12:1758835920913426. PMID: 32201507 PMC - PMC6906348 OTO - NOTNLM OT - HCC OT - INC280 OT - MET inhibitor OT - capmatinib OT - phase II COIS- Conflict of interest statement: Su Pin Choo received funding, nonfinancial support, and honoraria from BMS, nonfinancial support and honoraria from Bayer, and honoraria from Novartis, Shire, Sirtex, Eisai, and Celgene. Virote Sriuranpong has received research support from Novartis. Shukui Qin, Stephen Lam Chan, Wattana Sukeepaisarnjaroen, Guohong Han, Hongming Pan, Thomas Yau, Yabing Guo, Minshan Chen, Zhenggang Ren, Jianming Xu, Chia-Jui Yen, Zhong-Zhe Lin, and Tawesak Tanwandee have no competing financial interests. Yi Gu, Yongjian Sun, Lu Hao, and Wenjie Song are employees of Novartis. Luigi Manenti and Ralph Tiedt are employees of Novartis and hold stock with Novartis. EDAT- 2019/12/20 06:00 MHDA- 2019/12/20 06:01 PMCR- 2019/12/11 CRDT- 2019/12/20 06:00 PHST- 2019/05/23 00:00 [received] PHST- 2019/10/17 00:00 [accepted] PHST- 2019/12/20 06:00 [entrez] PHST- 2019/12/20 06:00 [pubmed] PHST- 2019/12/20 06:01 [medline] PHST- 2019/12/11 00:00 [pmc-release] AID - 10.1177_1758835919889001 [pii] AID - 10.1177/1758835919889001 [doi] PST - epublish SO - Ther Adv Med Oncol. 2019 Dec 11;11:1758835919889001. doi: 10.1177/1758835919889001. eCollection 2019.