For a study, researchers sought to see if emibetuzumab + erlotinib could overcome acquired resistance to erlotinib in MET protein-positive NSCLC patients enriched for EGFRmt. Patients with Stage IV NSCLC with MET diagnostic (+) (≥10% of cells expressing MET at ≥2+ IHC staining intensity at any time) were randomized (3:1) to receive emibetuzumab 750 mg every two weeks or erlotinib 150 mg once daily. The primary goal was to compare the overall response rate (ORR) to historical control, with a secondary goal of determining ORR in patients with MET expression in more than or equal to 60% of cells of more than or equal to 2+ (MET ≥60%). Emibetuzumab plus erlotinib (N=83) or emibetuzumab monotherapy (N=28) were given to 111 MET+ patients. After erlotinib, 89 of the 111 MET+ tests were positive. In patients with post-erlotinib progression biopsies available (n=89), ORR was 3.0% for emibetuzumab plus erlotinib (95% CI: 0.4, 10.5) and 4.3% for emibetuzumab (95% CI: 0.1, 21.9). Patients with MET expression of more than or equal to 60% (n=74) had similar outcomes. Emibetuzumab + erlotinib had a greater disease control rate and progression-free survival rate (50% /3.3 months) than emibetuzumab alone (26% /1.6 months). There were no unexpected warning signs. Patients with and without EGFRmt or MET amplification showed partial responses. In 84.2% of patients with available tissue (85/101), EGFR sensitizing mutations were discovered retrospectively. Emibetuzumab plus erlotinib or emibetuzumab monotherapy did not reverse acquired resistance to erlotinib in MET diagnostic (+) patients, while a subset of patients saw the clinical benefit.

Source:www.clinical-lung-cancer.com/article/S1525-7304(22)00039-0/fulltext