Capmatinib plus gefitinib had a 27% to 29% response rate in patients who progressed on prior EGFR TKI therapy.

  • Major finding: Capmatinib plus gefitinib had a 27% to 29% response rate in patients who progressed on prior EGFR TKI therapy.

  • Approach: A phase Ib/II trial assessed capmatinib plus gefitinib in patients with EGFR-mutant MET-dysregulated NSCLC.

  • Impact: Combination therapy with capmatinib and gefitinib may be effective after resistance to prior EGFR TKIs.

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MET dysregulation occurs frequently in patients with non–small-cell lung cancer (NSCLC) and can confer resistance to tyrosine kinase inhibitors (TKI) targeting EGFR. Preclinical studies have suggested that the potent specific MET inhibitor capmatinib may be combined with the EGFR inhibitor gefitinib to suppress acquired EGFR inhibitor resistance. Thus, Wu and colleagues evaluated the safety and efficacy of capmatinib plus gefitinib in a phase Ib/II study of patients with EGFR-mutant NSCLC with MET amplification or overexpression who progressed while receiving EGFR TKI treatment. A total of 61 patients were treated in the phase I part of the study and 100 patients were treated in phase II. The primary end point was the overall response rate. Across phases Ib and II the overall response rate was 27%. The treatment combination achieved greater activity in the 36 patients with MET-amplified tumors (with at least 6 copies of MET), with 47% experiencing an overall response. Combination therapy had an acceptable safety profile, with treatment-related grade 3–4 adverse events occurring in 46 of 161 (29%) patients. Adverse events led to treatment discontinuation in 27 of 161 (17%) patients. No significant drug–drug interactions were observed between capmatinib and gefitinib. Taken together, these findings indicate that combination therapy with capmatinib and gefitinib is safe and exhibits antitumor activity in patients with EGFR-mutant, MET-dysregulated tumors. Further, this combination may overcome resistance to other EGFR TKIs.

Wu YL, Zhang L, Kim DW, Liu X, Lee DH, Yang JC, et al. Phase Ib/II study of capmatinib (INC280) plus gefitinib after failure of endothelial growth factor receptor (EGFR) inhibitor therapy in patients with EGFR-mutated, MET factor-dysregulated non-small-cell lung cancer. J Clin Oncol 2018 Aug 29 [Epub ahead of print].

Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.

©2018 American Association for Cancer Research.
2018
American Association for Cancer Research.