Recent Phase III clinical trials reveal promising new therapeutic combinations for EGFR-mutated non-small cell lung cancer (NSCLC). The FLAURA2 trial showed improved overall survival when osimertinib was combined with chemotherapy as first-line treatment. The ACROSS 2 study demonstrated enhanced progression-free survival with aumolertinib plus chemotherapy. Summit Therapeutics’ ivonescimab, a bispecific antibody targeting PD-1 and VEGF, showed regional variability with significant benefits in Chinese patients but not statistically significant in Western cohorts, potentially complicating regulatory approvals. Additionally, novel bispecific antibody-drug conjugate iza-bren (BL-B01D1), combined with osimertinib, achieved a 100% response rate in early studies, marking a significant step forward for targeted therapies in this subset.