Ivonescimab Plus Chemotherapy in Non–Small Cell Lung Cancer With EGFR Variant

• DOI: 10.1001/jama.2024.10613
• Publication Date: 2024-05-31T20:30:27Z
• Authors: 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 ...; Baiyong Li; Michelle Xia; Li Zhang
• Keywords: Pemetrexed; Carboplatin; Clinical endpoint; Interim analysis; Progression-free survival

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