Using preclinical NSCLC models and state-of-the-art techniques, we show that osimertinib combined with anti-HER3 mAbs offers superior tumor control, and this is not just a synergistic effect of targeting EGFR/HER3 signalling simultaneously, but that HER3 mAbs also engage TAMs (via STING activation in trans), redirecting them to execute FcγR-mediated tumor cytotoxicity. This evidence concerns the gene ERBB3 and neoplasm.