Ivonescimab edged past pembrolizumab in a prespecified interim analysis of the HARMONi-2 phase 3 trial in PD-L1-positive advanced NSCLC, reporting median overall survival of 30.8 months versus 22.6 months with pembrolizumab. The finding adds another option to the crowded first-line landscape where PD-(L)1 selection and combination strategy drive patient outcomes. Elsewhere in lung cancer, new Phase 3 readouts continued to widen the pool of targeted and immunotherapy combinations. A separate report on zipalertinib plus platinum-pemetrexed in EGFR exon 20 insertion NSCLC (REZILIENT 3) extended median progression-free survival from 8.5 to 14.5 months, strengthening the rationale for earlier use of exon-20-directed therapy alongside chemotherapy. Taken together, the latest late-stage data underscore how increasingly stratified NSCLC treatment has become—where biomarkers and regimen sequencing can meaningfully shift survival and disease-control endpoints.