Authors
HARMONi-A Study Investigators, Wenfeng Fang, Yuanyuan Zhao, Yongzhong Luo, Runxiang Yang, Yan Huang, Zhiyong He, Hui Zhao, Mingjun Li, Kai Li, Qibin Song, Xiaobo Du, Yulan Sun, Wei Li, Longhua Sun, Zhiyu Wang, Kunning Yang, Yun Fan, Baogang Liu, Hongyun Zhao, Ying Hu, Li Jia, Shen Xu, Tienan Yi, Dongqing Lv, Haitao Lan, Mengxia Li, Wenhua Liang, Yongsheng Wang, Hui Yang, Yuming Jia, Yuan Chen, Junguo Lu, Meiqi Shi, Chunling Liu, Ming Zhou, Jianya Zhou, Xianling Liu, Ningning Zhou, Ming He, Xiaorong Dong, Hualin Chen, Yongxing Chen, Haichuan Su, Xiaoling Li, Zhihong Zhang, Lei Yang, Ying Liu, Likun Chen, Xue Hou, Yu Zhang, Jun Guo, Ruiqiang Ma, Hong Lu, Di Wu, Weineng Feng, Wen Li, Jianan Huang, Yan Wang, Xia Song, Jiewen Peng, Laiyu Liu, Yubiao Guo, Wenting Li, Mengying Xia, Dongmei Lu, Mingxiu Hu, Zhongmin Maxwell Wang, Baiyong Li, Michelle Y Xia, Li Zhang
Published in
JAMA. Jun 17, 2026. Epub Jun 17, 2026.
Abstract
Patients with epidermal growth factor receptor (EGFR) gene variant nonsquamous non-small 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.
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.
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 EGFR-variant nonsquamous NSCLC who had received prior EGFR-TKI therapy were enrolled. The data cutoff date was April 12, 2025.
Patients were randomized 1:1 to receive ivonescimab (20 mg/kg; n = 161) or placebo (n = 161) plus chemotherapy with pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy.
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).
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; P = .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.
Ivonescimab plus chemotherapy provided a statistically significant and clinically meaningful improvement in overall survival with an acceptable safety profile in patients with EGFR-variant NSCLC after EGFR-TKI therapy.
ClinicalTrials.gov Identifier: NCT05184712.
PMID:
42307937
Bibliographic data and abstract were imported from PubMed on 17 Jun 2026.
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