Neoadjuvant treatment of IBI310 plus sintilimab in locally advanced MSI-H/dMMR colon cancer: A randomized phase 1b study
Rui Wang, Gong Chen, Meng Qiu, Jinfeng Ma, Xianwei Mo, Haiyi Liu, Yongqiang Li, Peirong Ding, Xiangbin Wan, Yingbin Hu, Xiwen Huang, Weiqin Jiang, Xiaojun Wu, Jia Luo, Yanbing Zhou, Leping Li, Yanlai Sun, Quan Wang, Nanya Wang, Jiang Wu, Weitang Yuan, Li Li, Linlin Liu, Xianglin Yuan, Guihua Wang, Zhangfa Song, Heli Liu, Jie Ge, Yaxu Wang, Peng Zhao, Taiyuan Li, Jun You, Jianqiang Tang, Xiaobo Du, Junzhong Lin, Rongxin Zhang, Zan Fu, Jianmin Xu, Haijun Zhong, Liang Kang, Yanhong Deng, Xiaoxiao Lu, Qun Guo, Hui Zhou, Rui‐Hua Xu
Abstract
Although neoadjuvant immunotherapy showed promising efficacy in locally advanced microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) colon cancer, whether dual immune checkpoint inhibition provides additional benefit over anti-PD-1 monotherapy remains unclear. This randomized phase 1b trial ( NCT05890742 ) evaluated a neoadjuvant regimen of IBI310 (anti-cytotoxic T lymphocyte-associated antigen 4 [CTLA-4]) plus sintilimab ( n = 52) versus sintilimab monotherapy ( n = 49). Surgery was performed in 51 and 45 patients, respectively. The primary endpoint, pathological complete response (pCR) rate, was significantly higher in the combination compared to the monotherapy arm within the modified intent-to-treat (mITT) population (78.4% versus 46.7%, p = 0.0015), with consistent results in the intent-to-treat (ITT) population (76.9% versus 42.9%). Safety in both arms was comparable and manageable without new safety signals. After a median follow-up of 21.4 months, no disease recurrences occurred. One death occurred in each arm due to postoperative complication and adverse events. These findings demonstrate the added benefit of neoadjuvant IBI310 plus sintilimab over sintilimab monotherapy for locally advanced MSI-H/dMMR colon cancer. • Neoadjuvant IBI310 plus sintilimab improves pCR rate in MSI-H/dMMR colon cancer • In both arms, pCR rates are consistently high in the Lynch syndrome subgroup • In patients without Lynch syndrome mutations, combination arm shows higher pCR rate • Safety profiles are comparable and manageable in both arms without new safety signals In a phase 1b randomized clinical trial, Wang et al. demonstrate the additional benefit of dual immune checkpoint inhibition as neoadjuvant treatment for locally advanced MSI-H/dMMR colon cancer. Compared with sintilimab monotherapy, IBI310 (anti-CLTA-4) plus sintilimab significantly improved pathological complete response rate, without new safety signals.