Abstract CT053: Aumolertinib with or without chemotherapy as first line treatment in locally advanced or metastatic NSCLC with sensitizing EGFR mutations (AENEAS2)

Abstract Introduction: Aumolertinib, a third generation selective EGFR-TKI, is standard of care for the first-line treatment in advanced or metastatic NSCLC with sensitizing EGFR mutations in China. Evidence has shown that combining EGFR-TKIs with chemotherapy can improve outcomes compared to EGFR-TKIs monotherapy. AENEAS2 (NCT04923906) is a randomized, open-label, multicenter, phase 3 study assessing the efficacy and safety of aumolertinib plus chemotherapy versus aumolertinib alone as first-line treatment in locally advanced or metastatic NSCLC with sensitizing EGFR mutations. Methods: Patients who were naïve to treatment with locally advanced or metastatic NSCLC harboring EGFR mutations (exon 19 deletion or L858R mutation) were randomly assigned in a 1:1 ratio to receive aumolertinib 110 mg QD in combination with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5), versus to receive aumolertinib 110 mg QD monotherapy. The primary endpoint is progression free survival (PFS) assessed by IRC (Independent Review Committee) per RECIST v1.1. Data cutoff date: 2024/06/18. Results: A total of 624 patients were randomized to aumolertinib plus chemotherapy (n=310) or aumolertinib monotherapy (n=314) and stratified according to EGFR mutation status (Ex19del verse L858R) and CNS metastases at baseline (yes versus no). Baseline characteristics were balanced between treatment arms (aumolertinib plus chemotherapy versus aumolertinib): median age (range), 58.0 (30-84)/59.0 (31-81) years; 55.5/52.5 % female; 49.0/49.0% Ex19del; 51.0/51.0% L858R; 30.0/30.9% CNS metastases. Median follow-up was 23.4 months. Median PFS assessed by IRC was 28.9 months (95% CI, 26.3 to NA) in combination arm versus 18.9 months (95% CI, 17.8 to 21.1) in monotherapy arm; hazard ratio (HR) 0.471 (95% CI, 0.371 to 0.598; p<0.0001). The PFS benefit was consistent across pre-defined subgroups. The overall survival (OS) was immature with event-patient rate 21.6%; HR 0.442 (95% CI, 0.308 to 0.636; p<0.0001). Median cycles of pemetrexed exposure (range) were 20.0 (1-42) cycles, 88.8% of patients completed 4∼6 cycles of platinum therapy. All causality grade ≥3 AEs (aumolertinib plus chemotherapy versus aumolertinib): 75.7%/23.7%; AEs leading to discontinuation of aumolertinib: 3.0%/1.3%. The safety profile of aumolertinib plus pemetrexed and platinum was consistent with the established profiles of the individual agent. Conclusion: Aumolertinib plus chemotherapy as a first-line treatment in advanced EGFR-mutant NSCLC demonstrated a statistically significant and clinically meaningful PFS improvement over aumoletinib monotherapy, with a manageable safety profile. Citation Format: Shun Lu, Jie Hu, Jianhua Chen, Yan Yu, Xiangjiao Meng, Xiaorong Dong, Yanping Hu, Yinghua Ji, Ying Cheng, Weibo Wang, Fangling Ning, Zhihong Zhang, Zhiye Zhang, Chunling Liu, Qiming Wang, Wei Zheng, Xiujuan Qu, Honghai Wang, Runxiang Yang, Renhua Guo, Jianhua Shi, Feng Wu, Dongqing Lv, Jian Fang, Zhi Xu, Huaqiu Shi, Haichuan Su, Yongxing Chen, Cheng zhi Zhou, Junhong Zhang, Xuewen Liu, Zhaoxia Dai, Wen Li, Zili Meng, Guojun Zhang, Biyong Ren, Lin Wu, Yalun Li, Xinmin Yu, Ziping Wang, Jian Feng, Yueyin Pan, Juan Li, Xiangdong Zhou, Suxian Hu, Tongmei Zhang, Laiyu Liu, Jiming Shen, Shaonan Fan, Zhenming Chen. Aumolertinib with or without chemotherapy as first line treatment in locally advanced or metastatic NSCLC with sensitizing EGFR mutations (AENEAS2) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT053.