MET exon 14 mutation

Utilising a robust next-generation sequencing platform, we have identified this mutation in 5.3% of cases in our cohort. In the absence of information on MET exon 14 skipping from India, this case series will throw some light on this variation in our subcontinent and highlights the fact that the real-world effectiveness of MET inhibitors like Tepotinib and Capmantinib might be lower than expected.

The present study marks the initial discovery of MET exon 14 skipping and EGFR Del19 in a single patient, who achieved partial response through a treatment plan involving Osimertinib and Gumarontinib. These findings provide valuable perspectives on treatment approaches for individuals sharing similar genetic profiles.

P1/2, N=862, Recruiting, DualityBio Inc. | Trial completion date: Jan 2028 --> May 2028 | Trial primary completion date: Sep 2027 --> Dec 2027

SAC was an aggressive NSCLC subtype, with KRAS and METex14 as the most common driver mutations. Given the high prevalence of PD-L1 expression in SAC, further research on immunotherapy efficacy in this group is warranted.

P1/2, N=231, Recruiting, Regeneron Pharmaceuticals | Active, not recruiting --> Recruiting

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). 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.

All these molecular and biological effects were inhibited by trametinib, a MEK inhibitor, which was potentiated by combination with capmatinib, a MET inhibitor. Thus, we report an original and powerful strategy to uncover key regulators, including transcription factors that have not been widely described in METex14Del signaling, such as SMAD3. These factors are activated by specific signaling pathways and could provide a novel therapeutic strategy involving a combination of receptor and signaling inhibitors.

Driver mutations were detected in 70% of resected NSCLC, including stage I. The recurrence patterns observed support integrating NGS into early-stage management and exploring tailored adjuvant therapies, even for stage I tumors.

P2, N=75, Not yet recruiting, The First Affiliated Hospital, Zhejiang University School of Medicine; The First Affiliated Hospital, Zhejiang University School of Medicine

P=N/A, N=9, Not yet recruiting, Beijing Tiantan Hospital Affiliated to Capital Medical University; Beijing Tiantan Hospital Affiliated to Capital Medical University

Treatment-related adverse events leading to permanent discontinuation occurred in 8.3% (7/84) of patients. Gumarontinib showed promising efficacy and acceptable toxicities in East Asian population, with a rapid onset of action, substantial and durable response, which can be converted into a long-term survival benefit.