American Association for Cancer Research
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Supplemental Table S1 from A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor–Resistant Lung Tumors

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journal contribution
posted on 2023-03-30, 23:21 authored by Sheri L. Moores, Mark L. Chiu, Barbara S. Bushey, Kristen Chevalier, Leopoldo Luistro, Keri Dorn, Randall J. Brezski, Peter Haytko, Thomas Kelly, Sheng-Jiun Wu, Pauline L. Martin, Joost Neijssen, Paul W.H.I. Parren, Janine Schuurman, Ricardo M. Attar, Sylvie Laquerre, Matthew V. Lorenzi, G. Mark Anderson

Origins and Genotypes of Lung Cancer Tumor Cell Lines



Non–small cell lung cancers (NSCLC) with activating EGFR mutations become resistant to tyrosine kinase inhibitors (TKI), often through second-site mutations in EGFR (T790M) and/or activation of the cMet pathway. We engineered a bispecific EGFR-cMet antibody (JNJ-61186372) with multiple mechanisms of action to inhibit primary/secondary EGFR mutations and the cMet pathway. JNJ-61186372 blocked ligand-induced phosphorylation of EGFR and cMet and inhibited phospho-ERK and phospho-AKT more potently than the combination of single receptor–binding antibodies. In NSCLC tumor models driven by EGFR and/or cMet, JNJ-61186372 treatment resulted in tumor regression through inhibition of signaling/receptor downmodulation and Fc-driven effector interactions. Complete and durable regression of human lung xenograft tumors was observed with the combination of JNJ-61186372 and a third-generation EGFR TKI. Interestingly, treatment of cynomolgus monkeys with JNJ-61186372 resulted in no major toxicities, including absence of skin rash observed with other EGFR-directed agents. These results highlight the differentiated potential of JNJ-61186372 to inhibit the spectrum of mutations driving EGFR TKI resistance in NSCLC. Cancer Res; 76(13); 3942–53. ©2016 AACR.

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