Multinational phase 1b study of telisotuzumab vedotin plus osimertinib for EGFR-mutated, c-Met overexpressing aNSCLC after progression on osimertinib

Osimertinib is the standard first-line treatment for advanced EGFR-mutated NSCLC, but treatment resistance is inevitable, and increased c-Met protein expression correlates with resistance. Telisotuzumab vedotin (teliso-V) is an antibody-drug conjugate targeting c-Met protein overexpression. A multinational phase 1b trial evaluated the combination of teliso-V and osimertinib for EGFR-mutated, c-Met protein-overexpressing locally advanced or metastatic non-squamous NSCLC after progession on osimertinib. The safety profile of the combination was manageable. The objective response rate per independent central review was 50.0%, the duration of response was not reached during median follow-up of 7.4 months, and the median progression-free survival was 7.4 months (95% CI 5.4-NR). The authors conclude that the combination of telisotuzumab vedotin and osimertinib had promising activity and a manageable safety profile in patients with c-Met protein overexpressing, EGFR-mutated non-squamous aNSCLC after progression on osimertinib.