Neoadjuvant treatment of IBI310 plus sintilimab in locally advanced MSI-H/dMMR colon cancer: A randomized phase 1b study
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.
Authors
- Weitang Yuan (ORCID: https://orcid.org/0000-0003-2866-6261)
- Jiang Wu (ORCID: https://orcid.org/0000-0002-8603-7642)
- Xiaobo Du (ORCID: https://orcid.org/0000-0001-6348-0636)
- Qun Guo (ORCID: https://orcid.org/0000-0003-3015-6121)
- Nanya Wang
- Peirong Ding (ORCID: https://orcid.org/0000-0002-0796-8175)
- Weiqin Jiang (ORCID: https://orcid.org/0000-0003-3200-8835)
- Yingbin Hu (ORCID: https://orcid.org/0000-0003-3645-7339)
- Zhangfa Song (ORCID: https://orcid.org/0000-0001-6301-1813)
- Xiaojun Wu (ORCID: https://orcid.org/0000-0001-8737-6286)
- Rongxin Zhang (ORCID: https://orcid.org/0000-0001-5498-0428)
- Leping Li (ORCID: https://orcid.org/0000-0003-2329-6791)
- Xianwei Mo (ORCID: https://orcid.org/0000-0002-4245-2836)
- Xiaoxiao Lu (ORCID: https://orcid.org/0000-0001-8972-431X)
- Junzhong Lin (ORCID: https://orcid.org/0000-0003-4038-1939)
- Zan Fu (ORCID: https://orcid.org/0000-0002-3397-0770)
- Yanbing Zhou (ORCID: https://orcid.org/0000-0002-4196-5947)
- Jie Ge (ORCID: https://orcid.org/0000-0002-4186-4740)
- Meng Qiu (ORCID: https://orcid.org/0000-0002-5556-2313)
- Yaxu Wang (ORCID: https://orcid.org/0000-0002-4466-5675)
- Haijun Zhong
- Liang Kang (ORCID: https://orcid.org/0000-0001-7062-8280)
- Peng Zhao
- Gong Chen (ORCID: https://orcid.org/0000-0002-1857-3670)
- Linlin Liu
- Quan Wang (ORCID: https://orcid.org/0000-0003-4997-7173)
- Rui Wang (ORCID: https://orcid.org/0000-0003-1723-4746)
- Yongqiang Li (ORCID: https://orcid.org/0000-0002-8110-8835)
- Guihua Wang (ORCID: https://orcid.org/0000-0002-3624-6390)
- Jia Luo
- Jun You (ORCID: https://orcid.org/0000-0002-4646-1422)
- Xianglin Yuan (ORCID: https://orcid.org/0000-0001-5708-6368)
- Rui‐Hua Xu (ORCID: https://orcid.org/0000-0001-9771-8534)
- Heli Liu (ORCID: https://orcid.org/0000-0002-3443-6174)
- Taiyuan Li (ORCID: https://orcid.org/0000-0003-2623-4211)
- Li Li (ORCID: https://orcid.org/0009-0003-4636-9487)
- Jinfeng Ma (ORCID: https://orcid.org/0000-0003-2754-5193)
- Haiyi Liu (ORCID: https://orcid.org/0000-0003-4289-8480)
- Yanhong Deng (ORCID: https://orcid.org/0000-0002-4333-468X)
- Hui Zhou (ORCID: https://orcid.org/0000-0003-0562-4974)
- Jianqiang Tang
- Xiwen Huang (ORCID: https://orcid.org/0000-0002-6874-2241)
- Xiangbin Wan
- Yanlai Sun
- Jianmin Xu
Institutions
- Qingdao University (CN)
- Central South University (CN)
- Nanchang University (CN)
- Sun Yat-sen University (CN)
- Guangxi Medical University (CN)
- Dalian Medical University (CN)
- Jilin University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Sichuan University (CN)
- Fudan University (CN)
- Sir Run Run Shaw Hospital (CN)
- Tianjin Medical University Cancer Institute and Hospital (CN)
- Zhengzhou University (CN)
- Meizhou City People's Hospital (CN)
- First Affiliated Hospital of Xiamen University (CN)
- West China Hospital of Sichuan University (CN)
- Sixth Affiliated Hospital of Sun Yat-sen University (CN)
- Mianyang Central Hospital (CN)
- Second Affiliated Hospital of Chongqing Medical University (CN)
- Zhejiang Cancer Hospital (CN)
- Shandong Tumor Hospital (CN)
- Shanxi Provincial Cancer Hospital (CN)
- Second Affiliated Hospital of Nanchang University (CN)
- Hunan Cancer Hospital (CN)
- Shandong Provincial Hospital (CN)
- Affiliated Hospital of Qingdao University (CN)
- First Hospital of Jilin University (CN)
- Zhongshan Hospital (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- Henan Cancer Hospital (CN)
- First Bethune Hospital of Jilin University (CN)
- Sun Yat-sen University Cancer Center (CN)
- Jiangsu Province Hospital (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
- Xiangya Hospital Central South University (CN)
- Tongji Hospital (CN)
- Shandong First Medical University (CN)
- First Affiliated Hospital of Nanchang University (CN)
- First Affiliated Hospital Zhejiang University (CN)
- State Key Laboratory of Oncology in South China
- Huazhong University of Science and Technology (CN)
- Zhejiang University (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- Cancer Cell
- Published
- 2025-10-01
- DOI
- https://doi.org/10.1016/j.ccell.2025.09.004
- Citations
- 7
- Primary Topic
- Colorectal Cancer Surgical Treatments
- Type
- article
- Field-Weighted Citation Impact
- 7.32