American Association for Cancer Research
ccr-22-2180_supplementary_table_1_suppts1.xlsx (17.43 kB)

Supplementary Table 1 from Preclinical Study of a Biparatopic METxMET Antibody–Drug Conjugate, REGN5093-M114, Overcomes MET-driven Acquired Resistance to EGFR TKIs in EGFR-mutant NSCLC

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posted on 2023-04-01, 00:05 authored by Seung Yeon Oh, You Won Lee, Eun Ji Lee, Jae Hwan Kim, YoungJoon Park, Seong Gu Heo, Mi Ra Yu, Min Hee Hong, John DaSilva, Christopher Daly, Byoung Chul Cho, Sun Min Lim, Mi Ran Yun

Whole Exom Sequencing_Somatic Mutation


National Research Foundation of Korea (NRF)



MET amplification is a frequent mechanism of resistance to EGFR tyrosine kinase inhibitors (TKI) in patients with EGFR-mutated non–small cell lung cancer (NSCLC), and combined treatment with EGFR TKIs and MET TKIs has been explored as a strategy to overcome resistance. However, durable response is invariably limited by the emergence of acquired resistance. Here, we investigated the preclinical activity of REGN5093-M114, a novel antibody–drug conjugate targeting MET in MET-driven patient-derived models. Patient-derived organoids, patient-derived cells, or ATCC cell lines were used to investigate the in vitro/in vivo activity of REGN5093-M114. REGN5093-M114 exhibited significant antitumor efficacy compared with MET TKI or unconjugated METxMET biparatopic antibody (REGN5093). Regardless of MET gene copy number, MET-overexpressed TKI-naïve EGFR-mutant NSCLC cells responded to REGN5093-M114 treatment. Cell surface MET expression had the most predictive power in determining the efficacy of REGN5093-M114. REGN5093-M114 potently reduced tumor growth of EGFR-mutant NSCLC with PTEN loss or MET Y1230C mutation after progression on prior osimertinib and savolitinib treatment. Altogether, REGN5093-M114 is a promising candidate to overcome the challenges facing functional MET pathway blockade.

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