MET-Inhibitor Combination Shows Activity in EGFR-Mutated, MET-Dysregulated NSCLC

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Combination therapy showed activity in epidermal growth factor receptor-mutated, mesenchymal-epithelial transition factor-dysregulated non–small-cell lung cancer.
Combination therapy showed activity in epidermal growth factor receptor-mutated, mesenchymal-epithelial transition factor-dysregulated non–small-cell lung cancer.

In a phase 1b/2 trial, capmatinib plus gefitinib showed acceptable safety and efficacy in patients with epidermal growth factor receptor (EGFR)-mutated, mesenchymal-epithelial transition factor (MET)-dysregulated non-small cell lung cancer (NSCLC).1 Capmatinib (INC280) is an MET inhibitor that has shown preclinical activity. The trial results were published in the Journal of Clinical Oncology.

Patients were enrolled on trial who had EGFR-mutated, MET-dysregulated NSCLC that progressed during prior EGFR-tyrosine kinase inhibitor (TKI) treatment. A total of 61 patients were treated in the phase 1b portion of the trial; 100 patients were treated in phase 2. Phase 1b patients received gefitinib 250 mg daily plus capmatinib capsules of either 100 to 800 mg per day or 200 to 600 twice per day. Phase 2 patients were treated with the recommended phase 2 dose of capmatinib 400 mg twice per day plus gefitinib 250 mg once per day. The primary endpoint during phase 2 was overall response rate (ORR).

In phase 2 patients, the ORR was 29%; for patients with MET-amplified tumors, ORR was 47%. The disease control rate was 73% and median duration of response was 5.6 months (95% CI, 3.8-7.2 months). Nausea (28%), peripheral edema (22%), decreased appetite (21%), and rash (20%) were the most common adverse events reported by phase 1b and 2 patients. Increased amylase and lipase levels were the most common grade 3 or 4 adverse events.

“The combination of capmatinib with gefitinib has been shown to be both feasible and rational, and the data from this study suggest that the combination of capmatinib with an EGFR-TKI may be a promising treatment option for patients with EGFR-mutated, MET-dysregulated NSCLC and particularly for patients with MET-amplified tumors,” the study authors concluded.

Disclosure: The study was funded by Novartis Pharma AG.

Reference

  1. Wu YL, Zhang L, Kim DW, et al. 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. J Clin Oncol. 2018;36:3101-3109. doi: 10.1200/JCO.2018.77.7326

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