Therapeutics: c-Met receptor tyrosine kinase (c-MET; MET; HGFR; c-Met proto-oncogene); epidermal growth factor receptor (EGFR); EGFR1 (HER1; ErbB1)

Cell culture and mouse studies suggest combined inhibition of c-MET and EGFR could help treat NSCLC. In co-cultures of human lung cancer cell lines and NK cells, a bispecific antibody against c-MET and EGFR (JNJ-61186372) increased NK-mediated antibody-dependent cellular cytotoxicity (ADCC) of cancer cells compared with the anti-EGFR antibody Erbitux cetuximab or an IgG1 isotype control. In patient-derived xenograft mouse models of EGFR-mutant and EGFR-mutant/c-MET-expressing lung cancers, JNJ-61186372 decreased tumor growth compared with the EGFR1 inhibitor Tarceva erlotinib. In xenograft mouse models of EGFR-mutant and EGFR-mutant/c-MET-expressing lung cancers, JNJ-61186372 plus Tagrisso osimertinib decreased tumor growth compared with either agent alone. The Janssen R&D LLC unit of Johnson & Johnson and Genmab A/S have JNJ-61186372 in a Phase I trial to treat NSCLC.

Eli Lilly and Co. and Merck KGaA market Erbitux to treat colorectal and head and neck cancers, and have the compound in Phase III testing for gastric cancer and Phase II testing for biliary and breast cancers. ...