{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:50:36Z","timestamp":1792601436359,"version":"4.5.0"},"reference-count":17,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2026,7,28]]},"abstract":"\n Importance<\/jats:title>\n \n Patients with epidermal growth factor receptor (\n EGFR<\/jats:italic>\n ) gene variant nonsquamous non\u2013small cell lung cancer (NSCLC) who have disease progression after prior EGFR tyrosine kinase inhibitor (TKI) therapy have limited treatment options, creating a need for more effective subsequent therapies.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To provide final overall results of a trial assessing whether adding ivonescimab (a bispecific antibody targeting programmed cell death protein 1 and vascular endothelial growth factor) to chemotherapy improves overall survival in this population.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n Randomized, double-blind, placebo-controlled phase 3 trial conducted at 55 sites in China. From January 25 to November 2, 2022, a total of 322 adult patients with locally advanced or metastatic\n EGFR<\/jats:italic>\n -variant nonsquamous NSCLC who had received prior EGFR-TKI therapy were enrolled. The data cutoff date was April 12, 2025.\n <\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Patients were randomized 1:1 to receive ivonescimab (20 mg\/kg; n\u2009=\u2009161) or placebo (n\u2009=\u2009161) plus chemotherapy with pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n This final results report focuses on overall survival, the key secondary end point, tested in a hierarchical manner (the primary end point was progression-free survival assessed by an independent radiology review committee).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The 322 enrolled patients had a median age of 59.4 years, and 51.6% were female. During a median follow-up of 32.5 months, ivonescimab plus chemotherapy improved overall survival compared with chemotherapy alone (median survival, 16.8 months vs 14.1 months; stratified hazard ratio, 0.74; 95% CI, 0.58-0.95;\n P<\/jats:italic>\n \u2009=\u2009.02). The absolute difference in median overall survival was 2.7 months. Estimated 30-month survival rates were 29.1% (95% CI, 22.1%-36.4%) with ivonescimab and 18.4% (95% CI, 12.8%-24.8%) with placebo. Grade 3 or higher treatment-emergent adverse events occurred in 67.1% and 54.7% of patients receiving ivonescimab and placebo, respectively.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n Ivonescimab plus chemotherapy provided a statistically significant and clinically meaningful improvement in overall survival with an acceptable safety profile in patients with\n EGFR<\/jats:italic>\n -variant NSCLC after EGFR-TKI therapy.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT05184712<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jama.2026.7745","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:30:28Z","timestamp":1781710228000},"page":"306","source":"Crossref","is-referenced-by-count":5,"title":["Bispecific Antibody Ivonescimab Added to Chemotherapy in\n EGFR<\/i>\n -Variant Non\u2013Small Cell Lung 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