1365TiP A phase I/II, open-label study of BBT-176, a triple mutation targeting EGFR TKI, in patients with NSCLC who progressed after prior EGFR TKI therapy

Abstract

First- and third-generation epidermal growth factor receptor (EGFR) inhibitors such as gefitinib and osimertinib, respectively, have improved survival outcomes for patients with advanced EGFR-mutant NSCLC. However, acquired resistance invariably emerges, leading to disease progression. The predominant mechanism of acquired resistance is a tertiary mutation at C797 position of EGFR gene added to T790M mutation which is the most well-known resistance mechanism to 1st generation EGFR inhibitors. BBT-176 specifically and non-covalently inhibits triple-mutant EGFR (exon19del/T790M/C797S and L858R/T790M/C797S).