MET exon 14 mutation

P3, N=131, Recruiting, Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci

P2, N=52, Not yet recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

P1/2, N=120, Recruiting, Shanghai East Hospital; Novatim Immune Therapeutics (Zhejiang) Co., Ltd.

P1, N=500, Not yet recruiting, Sun Yat-sen University Cancer Center; Sichuan Baili Pharmaceutical Co., Ltd.

MET-TKIs are effective for NSCLC with the METex14 skipping mutation; however, their efficacy for patients with a poor PS is limited.

Encouragingly, several MET TKIs such as capmatinib, tepotinib, and savolitinib have been approved for the treatment of MET exon 14 skipping mutations. On 14 May 2025, the U.S. Food and Drug Administration granted accelerated approval to telisotuzumab vedotin-tllv for adult patients with locally advanced or metastatic non-squamous NSCLC whose tumors exhibit high c-Met protein overexpression and who have already received prior systemic therapy. In this review, we summarize the structure and physiological role of the MET receptor, the molecular mechanisms underlying aberrant MET activation, its contribution to acquired resistance against targeted therapies, and emerging strategies for effectively targeting MET alterations in NSCLC.

The MET exon 14 skipping mutation is an important target for the precision treatment of NSCLC, and MET-TKIs have remarkable efficacy but a prominent problem with drug resistance. The construction of a precision medicine system encompassing diagnosis, treatment, and drug resistance management through multi-omics research, technological innovation, and international collaboration is a key direction for improving prognosis.

P2, N=60, Active, not recruiting, Duke University | Trial completion date: Jan 2027 --> Mar 2026 | Trial primary completion date: Jan 2026 --> Sep 2025

P2, N=56, Recruiting, SWOG Cancer Research Network | Trial completion date: May 2029 --> May 2028

He received capmatinib (800 mg/day) and denosumab, with SBRT to vertebral metastases and later to the primary lung tumor. Temporary suspension of capmatinib during SBRT, along with careful monitoring, optimized tolerability, and outcomes. This case supports the feasibility and potential synergy of precision multimodal therapy in MET-driven oligometastatic NSCLC, highlighting the need for further prospective studies.

P2, N=47, Active, not recruiting, AstraZeneca | Trial completion date: Aug 2025 --> Jan 2027 | Trial primary completion date: Aug 2025 --> Jan 2027

Crizotinib demonstrated clinical activity across tumors with METamp and METex14.Subprotocol C1, but not C2, met its primary endpoint. In METex14 disease, a read count cutoff >50,000 may help distinguish true pathogenic variants from low-level splice transcripts and enable more accurate classification.