2023 World Conference on Lung Cancer (Posters)-P1.22. Predictive Biomarkers of Response to REGN5093 to Guide Patient Selection in MET-Altered Advanced Non-small Cell Lung Cancer

P1.22. Predictive Biomarkers of Response to REGN5093 to Guide Patient Selection in MET-Altered Advanced Non-small Cell Lung Cancer - PDF(Slides)

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The poster presents a study conducted by Regeneron Pharmaceuticals to investigate the potential of REGN5093, a human bispecific antibody, in the treatment of MET-altered advanced non-small cell lung cancer (aNSCLC). MET alterations, such as MET exon 14 mutation and MET gene amplification, have been identified as oncogenic drivers in NSCLC. The study enrolled patients with MET-altered aNSCLC and evaluated their response to REGN5093 monotherapy.<br /><br />Baseline tumor profiling was performed to confirm MET alterations in ctDNA and tissue samples. The study found that response to REGN5093 was observed in MET exon 14 mutation and MET amplification and overexpression subgroups, regardless of EGFR mutation status. The response rates in these subgroups were higher compared to the overall population. The study also identified other somatic variants with known functional significance and observed clustering of these variants based on cohort assignment, centrally confirmed MET alterations, and EGFR status.<br /><br />The concentrations of REGN5093 and soluble MET (sMET) were measured during treatment. The study found that total concentrations of REGN5093 were higher than total sMET concentrations in serum, suggesting sufficient antibody saturation. While total sMET and hepatocyte growth factor (HGF) levels increased post-dose, no association was observed between baseline or post-treatment sMET or HGF concentrations and response.<br /><br />In conclusion, preliminary data from the study indicate that REGN5093 monotherapy can induce tumor responses in patients with MET-altered aNSCLC. Differences in response rates were observed between MET-altered subgroups, and certain baseline somatic mutations in non-responders may act as potential bypass resistance mechanisms. The study supports the selection of the 2,000 mg Q3W dose regimen of REGN5093. Further analysis of ctDNA is ongoing to assess the impact of MET alterations on outcomes.

Asset Subtitle

Mary Laughlin

Meta Tag

Speaker Mary Laughlin

Topic Pathology & Biomarkers: Genetic Biomarkers

Keywords

REGN5093

bispecific antibody

MET-altered

non-small cell lung cancer

MET exon 14 mutation

MET gene amplification

oncogenic drivers

response rates

somatic variants

EGFR mutation