BIEGi-1 is a potent and selective binary inhibitor of EGFR that effectively blocks EGFR-catalyzed nucleotide exchange and disrupts the EGFR–Rheb interaction. It robustly inhibits both EGFR kinase activity and mTORC1 signaling in EGFR-mutant cancer cells. BIEGi-1 exhibits significant anti-proliferative effects with an IC50 of 17 nM for PC9 and 20 nM for HCC827.