WCLC 2025 - Posters & ePosters-P3.12.59 A Phase Ib/Ii Study of Vebreltinib Plus Tislelizumab in Patients With MET-Amplified and PD-L1-Positive Locally Advanced or Metastatic NSCLC

P3.12.59 A Phase Ib/Ii Study of Vebreltinib Plus Tislelizumab in Patients With MET-Amplified and PD-L1-Positive Locally Advanced or Metastatic NSCLC

Back to course

Pdf Summary

This phase Ib/II investigator-initiated study evaluated the combination of Vebreltinib, a selective MET tyrosine kinase inhibitor, with the PD-1 inhibitor Tislelizumab as first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring MET amplification and positive PD-L1 expression. MET amplification is an oncogenic driver associated with poor prognosis in NSCLC, and given its frequent co-occurrence with high PD-L1, combining MET inhibition with immune checkpoint blockade may yield enhanced benefits.<br /><br />Four male patients (ages 62-68) were enrolled, all with good performance status and varying MET amplification levels assessed by next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH). Tumor responses were evaluated every 6 weeks. Objective response rates (ORR) showed rapid and durable partial responses in all patients, with tumor shrinkage ranging from 42.6% to 71.8%. The treatment was ongoing in three patients, and one withdrew despite response. The results highlight the regimen’s promising antitumor activity.<br /><br />However, notable was the discrepancy in MET amplification quantification: some patients had low-level amplification by NGS but high gene copy number (GCN) by FISH, suggesting that optimal cut-offs for defining MET amplification need further clarification to refine patient selection.<br /><br />Safety monitoring emphasized vigilance for immune-related adverse events, consistent with checkpoint inhibitor therapy profiles. The authors conclude that while these preliminary findings support combining Vebreltinib with Tislelizumab for this molecular subset of NSCLC, larger, confirmatory studies are necessary to validate efficacy and safety.<br /><br />In summary, this combination therapy demonstrates potential as a first-line option for MET-amplified, PD-L1-positive advanced NSCLC, offering rapid, durable tumor responses, with a need for further research into MET amplification diagnostics and management of immune toxicity.

Asset Subtitle

Zhijie Wang

Meta Tag

Speaker Zhijie Wang

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

Vebreltinib

Tislelizumab

MET amplification

PD-L1 expression

non-small cell lung cancer

NSCLC

immune checkpoint blockade

tyrosine kinase inhibitor

objective response rate

immune-related adverse events