Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib after Failure of Epidermal Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients with EGFR-Mutated, MET Factor-Dysregulated Non-Small-Cell Lung Cancer

Yi Long Wu, Li Zhang, Dong Wan Kim, Xiaoqing Liu, Dae Ho Lee, James Chih Hsin Yang, Myung Ju Ahn, Johan F. Vansteenkiste, Wu Chou Su, Enriqueta Felip, Vincent Chia, Sabine Glaser, Philippe Pultar, Sylvia Zhao, Bin Peng, Mikhail Akimov, Daniel S.W. Tan

研究成果: Article同行評審

122 引文 斯高帕斯(Scopus)

摘要

Purpose Mesenchymal-epithelial transition factor (MET) dysregulation occurs in up to 26% of non-small-cell lung cancers (NSCLCs) after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. Capmatinib (INC280) is a potent and selective MET inhibitor with preclinical activity in combination with gefitinib in EGFR-mutant, MET-amplified/overexpressing models of acquired EGFR-TKI resistance. This phase Ib/II study investigated the safety and efficacy of capmatinib plus gefitinib in patients with EGFR-mutated, MET-dysregulated (amplified/overexpressing) NSCLC who experienced disease progression while receiving EGFR-TKI treatment. Methods Patients in phase Ib received capmatinib 100- to 800-mg capsules once per day or 200- to 600-mg capsules or tablets twice per day, plus gefitinib 250 mg once per day. Patients in phase II received the recommended phase II dose. The primary end point was the overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Results Sixty-one patients were treated in phase Ib, and 100 were treated in phase II. The recommended phase II dose was capmatinib 400 mg twice per day plus gefitinib 250 mg once per day. Preliminary clinical activity was observed, with an ORR across phase Ib/II of 27%. Increased activity was seen in patients with high MET-amplified tumors, with a phase II ORR of 47% in patients with a MET gene copy number ≥ 6. Across phases Ib and II, the most common drug-related adverse events were nausea (28%), peripheral edema (22%), decreased appetite (21%), and rash (20%); the most common drug-related grade 3/4 adverse events were increased amylase and lipase levels (both 6%). No significant drug-drug interactions between capmatinib and gefitinib were evident. Conclusion This study, focused on a predominant EGFR-TKI resistance mechanism in patients with EGFRmutated NSCLC, shows that the combination of capmatinib with gefitinib is a promising treatment for patients with EGFR-mutated, MET-dysregulated NSCLC, particularly MET-amplified disease.

原文English
頁(從 - 到)3101-3109
頁數9
期刊Journal of Clinical Oncology
36
發行號31
DOIs
出版狀態Published - 2018 十一月 1

All Science Journal Classification (ASJC) codes

  • 腫瘤科
  • 癌症研究

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