A phase II study of the efficacy and safety of the MET inhibitor capmatinib (INC280) in patients with advanced hepatocellular carcinoma.
HCC
INC280
MET inhibitor
capmatinib
phase II
Journal
Therapeutic advances in medical oncology
ISSN: 1758-8340
Titre abrégé: Ther Adv Med Oncol
Pays: England
ID NLM: 101510808
Informations de publication
Date de publication:
2019
2019
Historique:
received:
23
05
2019
accepted:
17
10
2019
entrez:
20
12
2019
pubmed:
20
12
2019
medline:
20
12
2019
Statut:
epublish
Résumé
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. 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. A total of 38 patients received treatment. In the dose-determining stage, patients received capmatinib 300 mg BID capsules ( 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. ClinicalTrials.gov: NCT01737827. https://clinicaltrials.gov/ct2/show/NCT01737827.
Sections du résumé
BACKGROUND
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
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
RESULTS
A total of 38 patients received treatment. In the dose-determining stage, patients received capmatinib 300 mg BID capsules (
CONCLUSIONS
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
BACKGROUND
ClinicalTrials.gov: NCT01737827. https://clinicaltrials.gov/ct2/show/NCT01737827.
Identifiants
pubmed: 31853265
doi: 10.1177/1758835919889001
pii: 10.1177_1758835919889001
pmc: PMC6906348
doi:
Banques de données
ClinicalTrials.gov
['NCT01737827']
Types de publication
Journal Article
Langues
eng
Pagination
1758835919889001Commentaires et corrections
Type : ErratumIn
Informations de copyright
© The Author(s), 2019.
Déclaration de conflit d'intérêts
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.
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