2023 Targeted Therapies of Lung Cancer Meeting (Poster)-P1.09. Activating MET Kinase Domain Mutations Define a Novel Targetable Molecular Subtype of Non-Small Cell Lung Cancer That is Clinically Sensitive to MET Inhibitor Elzovantinib (TPX-0022)

P1.09. Activating MET Kinase Domain Mutations Define a Novel Targetable Molecular Subtype of Non-Small Cell Lung Cancer That is Clinically Sensitive to MET Inhibitor Elzovantinib (TPX-0022)

Back to course

Pdf Summary

A study conducted by researchers from various institutions has identified a novel molecular subtype of non-small cell lung cancer (NSCLC) that is sensitive to a MET inhibitor called elzovantinib (TPX-0022). The subtype is characterized by activating mutations in the MET kinase domain (MET-TKD mutations), specifically without concurrent MET exon 14 skipping mutations. The study analyzed genomic data from multiple datasets and identified these mutations in 0.2% of NSCLC cases.<br /><br />The researchers found that MET-TKD mutations occur in NSCLC cases individually, without other known driver mutations. They conducted comprehensive genomic profiling and observed promising radiologic responses in two patients with lung adenocarcinoma carrying MET-TKD mutations when treated with elzovantinib.<br /><br />The study highlights the importance of detecting these MET-TKD mutations in NSCLC patients and using them to guide treatment selection and clinical trial enrollment. However, due to the rarity of these mutations, further research and clinical studies are needed to validate their significance as a targetable subtype of NSCLC.<br /><br />The identified MET-TKD mutation subtype was found to be present in various datasets, including GENIE, China Pan-Cancer, TCGA, DFCI, and MSKCC. The prevalence of MET-TKD mutations varied across the datasets but remained low overall. The study also provided additional information on the clinicopathologic characteristics of patients with NSCLC harboring de-novo oncogenic MET-TKD mutations.<br /><br />Overall, this study contributes to the understanding of molecular subtypes in NSCLC and emphasizes the need for comprehensive genomic profiling to identify targetable alterations and guide treatment decisions for patients with NSCLC.

Asset Subtitle

Federica Pecci, Lowe Center for Thoracic Oncology, Dana-farber Cancer Institute, United States

Meta Tag

Speaker Federica Pecci, Lowe Center for Thoracic Oncology, Dana-farber Cancer Institute, United States

Topic Poster Listing

Keywords

non-small cell lung cancer

NSCLC

molecular subtype

MET inhibitor

elzovantinib

MET-TKD mutations

MET kinase domain

MET exon 14 skipping mutations

genomic data

lung adenocarcinoma