Title |
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
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Published in |
Journal of Clinical Oncology, August 2018
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DOI | 10.1200/jco.2018.77.7326 |
Pubmed ID | |
Authors |
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 |
Abstract |
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 EGFR-mutated 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 11 | 39% |
France | 2 | 7% |
Spain | 2 | 7% |
Singapore | 1 | 4% |
Italy | 1 | 4% |
Hong Kong | 1 | 4% |
Japan | 1 | 4% |
Canada | 1 | 4% |
Switzerland | 1 | 4% |
Other | 0 | 0% |
Unknown | 7 | 25% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 14 | 50% |
Scientists | 8 | 29% |
Practitioners (doctors, other healthcare professionals) | 5 | 18% |
Science communicators (journalists, bloggers, editors) | 1 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 131 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 21 | 16% |
Student > Ph. D. Student | 17 | 13% |
Other | 14 | 11% |
Student > Bachelor | 10 | 8% |
Student > Postgraduate | 8 | 6% |
Other | 23 | 18% |
Unknown | 38 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 34 | 26% |
Biochemistry, Genetics and Molecular Biology | 19 | 15% |
Pharmacology, Toxicology and Pharmaceutical Science | 8 | 6% |
Agricultural and Biological Sciences | 7 | 5% |
Nursing and Health Professions | 5 | 4% |
Other | 17 | 13% |
Unknown | 41 | 31% |