Recent clinical trials reveal significant advancements in therapies targeting non-small cell lung cancer (NSCLC) patients with EGFR mutations. The ACROSS 2 Phase III trial demonstrated that combining aumolertinib, a third-generation EGFR-TKI, with chemotherapy improves progression-free survival. Meanwhile, a bispecific antibody-drug conjugate, iza-bren, achieved a 100% objective response rate when combined with osimertinib, highlighting its potential as a breakthrough treatment. Additionally, the COMPEL study indicates that continuing osimertinib alongside chemotherapy post-progression enhances progression-free survival. These developments mark pivotal strides in personalized lung cancer therapy, offering new hope for patients with limited options.