Advancing MET-Aberrant NSCLC Therapy with Glumetinib: Pharmacokinetics, Efficacy, Safety, Drug Interactions, and Clinical Prospects

Targeting Mesenchymal-Epithelial Transition Factor (MET) gene aberrations has emerged as a pivotal strategy in the precision treatment of Non-Small Cell Lung Cancer (NSCLC). Among these, MET exon 14 (METex14) skipping mutation represents a well-established and significant therapeutic target. Glumetinib, a highly selective oral MET inhibitor developed in China, has been approved by the National Medical Products Administration (NMPA) and the Pharmaceuticals and Medical Devices Agency (PMDA) for the treatment of advanced or relapsed NSCLC with METex 14 skipping mutation. Glumetinib has not yet received approval from the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). However, a phase II clinical trial is ongoing in the United States, planning to enroll 78 patients with advanced c-MET-positive NSCLC, which may support future regulatory submissions. Preclinical investigations have shown that glumetinib effectively inhibits MET-driven tumors by specifically targeting c-Met kinase activity and its associated downstream signaling pathways. In the pivotal phase II GLORY trial, patients with METex14-positive NSCLC were administered glumetinib (300 mg/day) and demonstrated an Objective Response Rate (ORR) of 66% and a median Progression-Free Survival (PFS) of 8.5 months. Notably, patients with brain metastases exhibited an ORR of 85%. Treatment-Related Adverse Events (TRAEs) of grade≥3 severity were reported in 54% of patients, with only 8% discontinuing treatment due to TRAEs, suggesting a manageable safety profile. From the perspective of China's healthcare system, glumetinib is considered more cost-effective than savolitinib in treating NSCLC patients with METex14 skipping. The clinical applications of glumetinib are broadening to encompass strategies to overcome drug resistance and combination therapies. This manuscript seeks to provide a comprehensive overview of the essential characteristics, mechanism of action, pharmacokinetics, efficacy, safety, drug interactions, and cost-effectiveness of glumetinib while also exploring its future therapeutic potential.