• HARMONi-A Study Investigators, Wenfeng Fang, Yuanyuan Zhao, Yongzhong Luo, Runxiang Yang, Yan Huang, Zhiyong He, Hui Zhao, Mingjun Li, Kai Li, Qibing Song, Xiaobo Du, Yulan Sun, Wei Li, Fei Xu, 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, Jifeng Feng, 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 Cheng, Likun Chen, Xue Hou, Yu Zhang, Jun Guo, Zhen Wang, Hong Lu, Di Wu, Weineng Feng, Wen Li, Jianan Huang, Yan Wang, Xia Song, Jiewen Peng, Laiyu Liu, Yubiao Guo, Wenting Li, Dongmei Lu, Mingxiu Hu, Zhongmin Maxwell Wang, Baiyong Li, Michelle Xia, and Li Zhang.
• Sun Yat-sen University Cancer Center, Guangzhou, China.
• JAMA. 2024 Aug 20; 332 (7): 561570561-570.

ImportanceFor patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited.ObjectiveTo compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant.Design, Setting, And ParticipantsDouble-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled.InterventionsParticipants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed.Main Outcomes And MeasuresThe primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported.ResultsAmong 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group.ConclusionsIvonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer.Trial RegistrationClinicalTrials.gov Identifier: NCT05184712.

53 keywords...

hide…