Abstract CT014: Perioperative adebrelimab (A) plus chemotherapy (chemo) in resectable stage II-III NSCLC: Phase 3 EFS interim analysis (IA) and molecular residual disease (MRD) analysis

Abstract Background: Perioperative A (IgG4 anti-PD-L1 antibody) + chemo showed promising efficacy and favorable safety in resectable NSCLC in the phase 1 part of a phase 1b/3 study (NCT04316364). We now report EFS IA and exploratory MRD results from the double-blind, randomized, phase 3 part. Methods: Patients (pts) with untreated, resectable stage II-III (IIIA/T3N2M0 IIIB) NSCLC per AJCC v8 and without EGFR/ALK alterations were randomized 1:1 to receive 3 cycles of A 20 mg/kg or placebo (PBO) with histology-based platinum-doublet chemo (Q3W), followed by surgery (Sx) and 16 cycles of adjuvant A 20 mg/kg or PBO (Q3W). Primary endpoints were EFS per BICR and MPR per BIPR. MRD was based on tumor-informed assays. A prespecified IA was done at 158 (69.0% of total expected) EFS events. Results: 501 pts were randomized and treated. At data cutoff, median follow-up was 23.6 mo. Perioperative A + chemo significantly improved EFS and MPR vs PBO + chemo (Table 1). Definitive surgery (88.8% vs 83.2%) and pCR (31.1% vs 7.6%) rates also favored A arm. Grade ≥3 AEs related to any study agent occurred in 52.6% in A arm vs 53.6% in PBO arm; of these, all reported in ≥2% with A were hematologic. Among 316 MRD+ pts at baseline (detectable ctDNA), those with pre-Sx ctDNA clearance (CL) in A arm were more likely to achieve MPR (PPV 83.1% vs 48.5%) and pCR (PPV 57.6% vs 21.2%) vs PBO arm. Pre-Sx ctDNA CL was associated with improved EFS in both arms, with a trend toward longer EFS with A vs PBO irrespective of CL (CL: HR 0.85 [95% CI 0.28-2.59]; no CL: HR 0.64 [0.40-1.02]). Pts without post-Sx ctDNA CL (adjuvant C1D1) had poor EFS, with a trend favoring A vs PBO (HR 0.25 [0.08-0.82]). Conclusions: Perioperative A + chemo significantly improved EFS and MPR with manageable safety in resectable stage II-III NSCLC. ctDNA dynamics were prognostic of clinical outcomes, providing a potential tool for refined perioperative risk stratification. Citation Format: Yi-Long Wu, Wen-Zhao Zhong, Li-Xu Yan, Keneng Chen, Wanpu Yan, Yongzhong Luo, Wenxiang Wang, Wenqun Xing, Xiaolong Yan, Lin Wu, Feng Yao, Dongsheng Yue, Naiquan Mao, Yu Qi, Bentong Yu, Jianji Guo, Jindan Kai, Yuejun Chen, Hui Wang, Qin Zhang, Lunxu Liu, Honghai Wang, Yuanyuan Ji, Yongtao Han, Yongxiang Song, Jianjun Xu, Wei Guo, Hongxu Liu, Di Ge, Hecheng Li, XiuJuan Qu, Jifang Yao, Junfeng Liu, Tingyan Zhong, Yanhua Huang, Li Song, Wei Shi. Perioperative adebrelimab (A) plus chemotherapy (chemo) in resectable stage II-III NSCLC: Phase 3 EFS interim analysis (IA) and molecular residual disease (MRD) analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT014.