Acquired Resistance to Osimertinib Plus Savolitinib Is Mediated by MET-D1228 and MET-Y1230 Mutations in EGFR-Mutated MET-Amplified Lung Cancer

Abstract

MET gene amplification is an established mechanism of acquired resistance to all classes of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated lung cancer. Novel strategies to target EGFR-mutated MET-amplified tumors in clinical trials have reported promising results, with a clear activity of the combination of osimertinib and savolitinib reported from the TATTON trial (NCT02143466) in 2020.1 Savolitinib is a type IB–selective MET kinase inhibitor in the same class as capmatinib and tepotinib (Table 1).