Mobocertinib, a targeted EGFR exon 20 inhibitor, shows clinical activity, yet the genomic resistance mechanisms remain poorly characterized, particularly through circulating tumor DNA (ctDNA) analysis.<h4>Methods</h4>In this single-center prospective observational study, 22 patients with EGFR exon 20 insertion-positive NSCLC treated with mobocertinib were analyzed. The gene discussed is EGFR; the disease is neoplasm.