Abstract CT126: Aumolertinib as adjuvant therapy in patients with stage II-IIIB EGFR-mutated NSCLC after complete tumor resection: A randomized, double-blind, placebo-controlled, phase 3 trial (ARTS)

Abstract Background: Lung cancer is the primary cause of cancer-related morbidity and mortality globally. Approximately 30% of patients with EGFR mutation (EGFRm) in NSCLC are diagnosed at an early stage and are candidates for curative-intent surgical resection; however, disease recurrence remains a substantial clinical challenge. Aumolertinib is a third-generation EGFR TKI that potently inhibits both sensitizing EGFR mutations (ex19del/L858R) and the resistance mutation T790M. ARTS (NCT04687241) is a randomized, double-blind, placebo-controlled, multicenter, phase 3 trial designed to evaluate the efficacy and safety of adjuvant aumolertinib versus placebo in patients with stage II-IIIB EGFRm NSCLC after complete resection, with or without adjuvant chemotherapy. Methods: Inclusion criteria included patients aged ≥18 years, ECOG PS 0-1, primary non-squamous stage II/IIIA/IIIB (T3N2M0) NSCLC, confirmed EGFRm (ex19del or L858R), complete resection with full postsurgical recovery, with or without postoperative adjuvant chemotherapy. Patients were randomized in a 1:1 ratio to receive aumolertinib (110 mg orally, once daily) or matched placebo for a planned treatment duration of 3 years. Stratification was based on stage (II, IIIA N2-, IIIA/B N2+) and mutation type (ex19del, L858R). The primary endpoint was disease-free survival (DFS), assessed by blinded independent central review (BICR). Secondary endpoints included investigator-assessed DFS, overall survival (OS), and safety profile. Data cutoff (DCO): April 15, 2024. Results: A total of 214 patients from China were randomized to treatment (Aumolertinib n=107, Placebo n=107). Baseline characteristics were balanced across treatment arms (aumolertinib/placebo): female 55.1%/57.0%, ever-smokers 28.0%/29.9%, stage II 44.9%/44.9%, stage III 54.2%/52.3%, ex19del 47.7%/50.5%, L858R 52.3%/49.5%, ECOG PS 0 36.4%/41.1%, ECOG PS 1 63.6%/58.9%. Median follow-up for DFS was 27.6 months. The mDFS assessed by BICR was not reached (95% CI, 29.1 to NA) in the aumolertinib arm versus 19.4 months (95% CI, 11.2 to 26.2) in the placebo arm; hazard ratio (HR) 0.166 (95% CI, 0.094 to 0.294); p<0.0001. The 2-year DFS rate was 88.2% in the aumolertinib arm versus 40.6% in the placebo arm. Investigator-assessed DFS was concordant with BICR assessment. OS data were immature at DCO (aumolertinib/placebo OS maturity: 2.8%/3.8%). The incidence of AEs leading to dose interruptions, dose reductions, and discontinuation in the aumolertinib/ placebo arm was 12.3%/ 17.8%, 9.4%/ 1.9%, and 0.9%/ 0, respectively. No new safety risks were observed. Conclusions: Adjuvant aumolertinib demonstrates a statistically significant and clinically meaningful improvement in DFS in patients with stage II-IIIB EGFRm NSCLC following complete tumor resection and adjuvant chemotherapy, when indicated. This DFS benefit underscores the promise of aumolertinib in fulfilling an unmet need for effective adjuvant EGFR-targeted therapy in early-stage NSCLC. Citation Format: Ying Cheng, Xiqin Zhang, Lin Wu, Wenxiang Wang, Wenqun Xing, Chunling Liu, Caigang Liu, Kai Chen, Jianhua Shi, Peng Zhang, Shidong Xu, Xiaodong Zhang, Xiaorong Dong, Haohui Fang, Xinmin Yu, Yang Gao, Gaofeng Li, Liang Chen, Huiyuan Gong, Renhua Guo, Zhenyuan Gao, Yinghua Ji, Lunxu Liu, Xianling Liu, Hui Tian, Fei Xiong, Xin Zhao, Lejie Cao, Qing Geng, Hongxu Liu, Jixian Liu, Li Yang, Zhenfa Zhang, Di Ge, Xingya Li, Minghui Wang, Yan Xu, Zhi Xu, Jun Chen, Zhaoxia Dai, Jian Hu, Juan Li, Shujun Li, Min Ye, Aimin Zang, Chanjuan Xie, Zhenzhong Su, Zhenmin Chen, Shaonan Fan. Aumolertinib as adjuvant therapy in patients with stage II-IIIB EGFR-mutated NSCLC after complete tumor resection: A randomized, double-blind, placebo-controlled, phase 3 trial (ARTS) [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 CT126.