GB263T dose-dependently inhibited the proliferation of cells containing EGFR exon 20 insertion mutations and C797S mutations. In addition, potent ADCC function against NSCLC cell lines was observed. Significant in vivo anti-tumor efficacy was demonstrated by multiple tumor models of EGFR exon 20 insertion, EGFR C797S mutation, cMET amplification, and cMET exon 14 skipping mutation....GB263T is a novel tri-specific antibody that exhibited robust anti-tumor activity. The preclinical data indicate that GB263T has great potential to become an effective therapeutics in the treatment of NSCLC.