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Cited by 12Lung Cancer Treatments and MutationsLung Cancer Research StudiesLung Cancer Diagnosis and Treatment

The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.

Bispecific Antibody Ivonescimab Added to Chemotherapy in EGFR -Variant Non–Small Cell Lung Cancer: The HARMONi-A Randomized Clinical Trial

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HARMONi-A Study Investigators, Fang, Wenfeng, Zhao, Yuanyuan, Luo, Yongzhong, Yang, Runxiang, Huang, Yan, He, Zhiyong, Zhao, Hui, Li, Mingjun, Li, Kai, Song, Qibin, Du, Xiaobo, Sun, Yulan, Li, Wei, Sun, Longhua, Wang, Zhiyu, Yang, Kunning, Fan, Yun, Liu, Baogang, Zhao, Hongyun, Hu, Ying, Jia, Li, Xu, Shen, Yi, Tienan, Lv, Dongqing, Lan, Haitao, Li, Mengxia, Liang, Wenhua, Wang, Yongsheng, Yang, Hui, Jia, Yuming, Chen, Yuan, Lu, Junguo, Shi, Meiqi, Liu, Chunling, Zhou, Ming, Zhou, Jianya, Liu, Xianling, Zhou, Ningning, He, Ming, Dong, Xiaorong, Chen, Hualin, Chen, Yongxing, Su, Haichuan, Li, Xiaoling, Zhang, Zhihong, Yang, Lei, Liu, Ying, Chen, Likun, Hou, Xue, Zhang, Yu, Guo, Jun, Ma, Ruiqiang, Lu, Hong, Wu, Di, Feng, Weineng, Li, Wen, Huang, Jianan, Wang, Yan, Song, Xia, Peng, Jiewen, Liu, Laiyu, Guo, Yubiao, Li, Wenting, Xia, Mengying, Lu, Dongmei, Hu, Mingxiu, Wang, Zhongmin Maxwell, Li, Baiyong, Xia, Michelle Y., Zhang, Li·2026·JAMA
DOI 10.1001/jama.2026.7745
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Abstract

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Interventions: 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. Main Outcomes and Measures: 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). Results: 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT05184712

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  1. Wang, 2025, Osimertinib acquired resistance among patients with EGFR-mutated NSCLC: from molecular mechanisms to clinical therapeutic strategies., Cancer Drug Resist, 8, 61

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Authors
HARMONi-A Study Investigators, Fang, W., Zhao, Y., Luo, Y., Yang, R., Huang, Y., He, Z., Zhao, H., Li, M., Li, K., Song, Q., Du, X., Sun, Y., Li, W., Sun, L., Wang, Z., Yang, K., Fan, Y., Liu, B., Zhao, H., Hu, Y., Jia, L., Xu, S., Yi, T., Lv, D., Lan, H., Li, M., Liang, W., Wang, Y., Yang, H., Jia, Y., Chen, Y., Lu, J., Shi, M., Liu, C., Zhou, M., Zhou, J., Liu, X., Zhou, N., He, M., Dong, X., Chen, H., Chen, Y., Su, H., Li, X., Zhang, Z., Yang, L., Liu, Y., Chen, L., Hou, X., Zhang, Y., Guo, J., Ma, R., Lu, H., Wu, D., Feng, W., Li, W., Huang, J., Wang, Y., Song, X., Peng, J., Liu, L., Guo, Y., Li, W., Xia, M., Lu, D., Hu, M., Wang, Z. M., Li, B., Xia, M. Y., & Zhang, L.
Affiliations
  • Sun Yat-sen University Cancer Center (CN)
  • Hunan Cancer Hospital (CN)
  • Kunming Medical University (CN)
  • Fujian Provincial Cancer Hospital (CN)
  • The Second Hospital of Anhui Medical University, Hefei, China
  • The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  • Tianjin Medical University Cancer Institute and Hospital (CN)
  • Renmin Hospital of Wuhan University (CN)
  • Mianyang Central Hospital (CN)
  • Shandong Tumor Hospital (CN)
  • First Affiliated Hospital of Bengbu Medical College (CN)
  • First Affiliated Hospital of Nanchang University (CN)
  • Fourth Hospital of Hebei Medical University (CN)
  • Weifang People's Hospital (CN)
  • Zhejiang Cancer Hospital (CN)
  • Third Affiliated Hospital of Harbin Medical University (CN)
  • Sun Yat-sen University Cancer Center, Guangzhou, China
  • Capital Medical University (CN)
  • Yuncheng Central Hospital (CN)
  • Zhangzhou Municipal Hospital of Fujian Province, Zhangzhou, China
  • Xiangyang Central Hospital (CN)
  • Taizhou Municipal Hospital (CN)
  • Sichuan Provincial People’s Hospital, Chengdu, China
  • Army Medical Center of the Chinese People’s Liberation Army, Chongqing, China
  • First Affiliated Hospital of Guangzhou Medical University (CN)
  • West China Hospital of Sichuan University (CN)
  • The Second Affiliated Hospital of Xiamen Medical College (CN)
  • Second People’s Hospital of Yibin (CN)
  • Hainan General Hospital (CN)
  • Nantong Tumor Hospital (CN)
  • Jiangsu Cancer Hospital (CN)
  • Xinjiang Medical University (CN)
  • Guangzhou Medical University Cancer Hospital (CN)
  • First Affiliated Hospital Zhejiang University (CN)
  • The Second Xiangya Hospital of Central South University, Changsha, China
  • Wuhan Union Hospital (CN)
  • Guangdong Medical College (CN)
  • Tang Du Hospital (CN)
  • Liaoning Cancer Hospital & Institute (CN)
  • Anhui Provincial Cancer Hospital, Hefei, China
  • Gansu Provincial Cancer Hospital, Lanzhou, China
  • Jilin Province Tumor Hospital (CN)
  • Nanjing Chest Hospital (CN)
  • Xingtai People's Hospital (CN)
  • Linyi Cancer Hospital, Linyi, China
  • Henan University (CN)
  • Jinan University (CN)
  • The First People’s Hospital of Foshan, Foshan, China
  • First Affiliated Hospital of Soochow University (CN)
  • Shanxi Provincial Cancer Hospital (CN)
  • Zhongshan People's Hospital (CN)
  • Nanfang Hospital, Nanfang Medical University, Guangzhou, China
  • The First Affiliated Hospital, Sun Yat-sen University (CN)
  • Akeso Biopharma Inc, Zhongshan, China
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2026-07-28
Volume
336
Issue
4
Pages
306
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2026.7745
OpenAlex
W7165007685
Cited by
8
References
15
Citations by year
2026: 8
FWCI
37.20
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords
ivonescimab, bispecific antibodies, EGFR variants, non-squamous non-small cell lung cancer, EGFR tyrosine kinase inhibitor resistance, pemetrexed, carboplatin, chemotherapy, overall survival, progression-free survival, maintenance therapy, treatment-emergent adverse events, Chinese patients, real-world data
MeSH terms
Pemetrexed, Progression-Free Survival, Tyrosine Kinase Inhibitors, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, China, Double-Blind Method, Female, Humans, Infusions, Intravenous, Lung Neoplasms, Male, Middle Aged, Carboplatin, Antibodies, Bispecific, Vascular Endothelial Growth Factor A, Programmed Cell Death 1 Receptor, ErbB Receptors

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