Multinational phase 2 trial of second-line tepotinib plus osimertinib for EGFR-mutated non-small cell lung cancer with MET amplification

Patients with EGFR-mutated non-small lung cancer and MET amplification as a mechanism of resistance to first-line osimertinib have few treatment options. The phase 2 INSIGHT 2 trial, at 179 centers in 17 countries, evaluated the combination of the MET inhibitor tepotinib and osimertinib in this population. Eligible patients were adults with an ECOG performance status 0 of 1 and advanced or metastatic EGFR-mutated NSCLC with MET amplification progressing on first-line osimertinib. The primary endpoint was independently assessed objective response to tepotinib plus osimertinib with at least 9 months of follow-up. The median follow-up was 12.7 months (IQR 9.9-20.3). The confirmed ORR was 50.0% (95% CI 39.7-60.3). The most common treatment-related grade 3 or worse adverse events were peripheral edema (5% of patients), decrease appetite (4%), prolonged QT interval (4%), and pneumonitis (3%). Serious TRAEs were reported in 13%. Death of 3% of patients was potentially related to either trial drug. The authors conclude that tepotinib plus osimertinib showed promising activity and acceptable safety in patients with EGFR-mutated aNSCLC with MET amplification as a mechanism of resistance to first-line osimertinib.