A novel bispecific antibody-drug conjugate (ADC) named iza-bren (BL-B01D1) has demonstrated remarkable efficacy when combined with osimertinib, a third-generation EGFR tyrosine kinase inhibitor, achieving a 100% objective response rate in EGFR-mutated non-small cell lung cancer (NSCLC) patients. Presented at the IASLC 2025 WCLC conference, this first-in-class ADC targets EGFR-mutated tumors, marking a significant advance in targeted oncology. Complementing this, clinical data from the COMPEL study suggests that adding chemotherapy after disease progression on osimertinib improves progression-free survival, emphasizing the value of continued osimertinib beyond CNS progression. Additionally, the CheckMate 77T trial established that perioperative nivolumab preserves quality of life in resectable NSCLC. Together, these findings highlight multifaceted advances in managing EGFR-driven NSCLC by optimizing combination therapies and sequencing strategies.