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Vebreltinib reported to show antitumour activity in MET amplification-driven NSCLC with limited chemotherapy options

In patients ineligible for, unsuccessfully treated with, or refusing standard chemotherapy, researchers reported antitumour activity with the investigational agent vebreltinib; a phase 3 comparison with standard treatment is being initiated.

  • Yi-Long Wu, MD; Yu Yao, MD; Jin-Ji Yang, MD; Lin Wu, PhD; Wei Zhang, PhD; Ying Wang, MD; et al.

  • December 6, 2025

  • The Lancet Oncology
  • The Lancet Oncology, Volume 27, Issue 1, Pages 36–44
  • 10.1016/S1470-2045(25)00594-7

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Evidence before this study

We searched PubMed for studies published from database inception to June 17, 2025, using the keywords “MET” or “mesenchymal-epithelial transition” and “advanced” and “non-small cell lung cancer” or “non-small cell lung cancer”, and applied “clinical trial” as a filter, which yielded 250 results. We identified several single-arm trials investigating novel target therapies in MET amplification-driven non-small-cell lung cancer (NSCLC) with different MET amplification cutoffs. The GEOMETRY mono-1 study investigated capmatinib in pretreated patients with a gene copy number (GCN) of six to nine and ten or higher, and in treatment-naive patients with a GCN of ten or higher. The AcSé crizotinib phase 2 study assessed crizotinib in patients with NSCLC and a GCN of six or higher. However, these small-scale studies investigating the efficacy of MET inhibitors in patients with chemotherapy-treated MET amplification-driven NSCLC reported variable and unsatisfactory objective response rates, and prospective clinical studies are still needed to assess whether MET amplification could be a promising therapeutic target and to verify effective MET inhibitors.

Added value of this study

In this study, vebreltinib showed notable antitumour activity and a manageable safety profile in patients with MET amplification-driven NSCLC who were ineligible for, unsuccessfully treated with, or refused standard chemotherapy. A durable response was observed with promising progression-free survival, indicating that a substantial proportion of patients benefited from treatment, which translated into a potential long-term survival benefit. The adverse events associated with vebreltinib were predominantly mild to moderate.

Implications of all the available evidence

The findings of this study suggested that vebreltinib could be an effective treatment option for MET amplification-driven NSCLC, particularly in patients with few treatment options due to the unsuitability or ineffectiveness of chemotherapy. The phase III study comparing vebreltinib to standard treatment in MET amplification-driven advanced NSCLC is currently being initiated.

Source: The Lancet Oncology

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