Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104)
Chao Zhang, Yuxuan Sun, Dingcheng Yi, Ben‐Yuan Jiang, Li‐Xu Yan, Ze-Dao Liu, Lishan Peng, Wenjie Zhang, Hao Sun, Zhiyong Chen, Danhua Wang, Di Peng, Songan Chen, Siqi Li, Ze Zhang, Xiaoyue Tan, Jie Yang, Zhang-Yi Zhao, Wanting Zhang, Jian Su, Yang-Si Li, Ri-Qiang Liao, Song Dong, Chong‐Rui Xu, Qing Zhou, Xue-Ning Yang, Yi‐Long Wu, Zemin Zhang, Wen‐Zhao Zhong
Abstract
The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro . Infiltration and T cell receptor (TCR) clonal expansion of CCR8 + regulatory T (Treg) hi /CXCL13 + exhausted T (Tex) lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC.