A Concise Review of the Approved MET TKIs (Savolitinib, Gumarontinib, Vebreltinib, Tepotinib, Capmatinib) in China for MET Exon 14 Splice Site Mutated (METex14+) NSCLC Circa 2025

Yanyan Hu,1 Sai-Hong Ignatius Ou2,3 1Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 2University of California Irvine School of Medicine, Orange, CA, 92868, USA; 3Chao Family Comprehensive Cancer Center, Orange, CA, 92868, USACorrespondence: Sai-Hong Ignatius Ou, Email [email protected]: Splice site mutations around or within exon 14 of MET (METex14+) are rare, but are one of the common actionable driver mutations in elderly patients with non-small cell lung cancer (NSCLC). Globally, only two MET tyrosine kinase inhibitors (TKIs), both Type Ib (capmatinib and tepotinib), have been approved in a single Phase 2 trial. In China, three additional Type Ib MET TKIs (savolitinib, gumarontinib, and vebreltinib), in addition to capmatinib, and tepotinib, have been approved. Here, we report the timeline for MET TKIs approval in China. We summarized the Chinese METex14+ NSCLC demographic and molecular characteristics and reviewed pivotal phase 2 data (clinical efficacy and adverse events). All five MET TKIs seem to have similar efficacy and adverse events with vebreltinib reported numerically the highest BIRC-ORR. Notably, the gumarontinib (GLORY) trial conducted in both China and Japan also led to the approval of gumarontinib in Japan for METex14+ NSCLC. On June 30, 2025, vebreltinib has been approved for NSCLC with MET amplification while combination of savoltinib and osimertinib has been approved for EGFR+ post EGFR TKINSCLC with MET amplification post EGFR TKI based on the SACHI trial (NCT05015608). We discuss the current unmet clinical need (need to develop Type II MET TKI to overcome acquired resistance MET mutations at D1228 and Y1230) and future optimal treatment approaches.Keywords: Type Ib MET TKI, Type II MET TKI, MET exon 14 mutation, savolitinib, gumarontinib, vebreltinib, tepotinib, capmatinib, amivantamab