Capmatinib Plus Gefitinib May Be Effective in Some Forms of Resistant Non-Small Cell Lung Cancer

Capmatinib plus gefitinib may be an effective treatment for patients with epidermal growth factor receptor (EGFR)-mutated, mesenchymal-epithelial transition factor (MET)-dysregulated non-small cell lung cancer (NSCLC), according to a study published in the Journal of Clinical Oncology.¹

MET dysregulation is a common occurrence among patients treated with EGFR-tyrosine kinase inhibitors (TKI) such as gefitinib, and has been associated with the development of resistance among this patient population. Capmatinib, a MET inhibitor, has demonstrated preclinical activity in EGFR-mutant and MET-activated NSCLC, with concurrent EGFR-TKIs.

For this phase 1b/2 study, researchers treated 161 patients with capmatinib plus gefitinib; the 61 patients in phase 1b received capmatinib 100-800 mg once daily or 200-600 mg twice daily plus gefitinib 250 mg once daily. Patients in phase 2 received the recommended capmatinib 400 mg twice daily plus gefitinib 250 mg once daily. Eligible participants had EGFR mutations, developed drug resistance to gefitinib, erlotinib, or afatinib, underwent disease progression, and had MET dysregulation (defined as MET gene copy number ≥ 5 and/or MET/centromere ratio ≥ 2, or MET overexpression defined as ≥ 50% of tumor cells).

Results showed that the overall response rate (ORR) was 27% among patients across both study phases, and was 29% among patients in phase 2 treated with the recommended phase 2 dosing.

Patients with MET-amplified tumors had increased activity, with a phase 2 ORR of 47% among patients that had MET gene copy number 6 or higher.

The most frequently observed drug-related adverse events occurred in more than 20% of patients across both phases and included nausea, peripheral edema, decreased appetite, and rash. The most common grade 3 to 4 drug-related adverse events were amylase and lipase level elevations, which both occurred in 6% of patients.

The authors concluded that this regimen is “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.”

Reference

1. Wu YL, Zhang L, Kim DW, 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 [published online August 29, 2018]. J Clin Oncol. doi: 10.1200/JCO.2018.77.732.