Perioperative tislelizumab plus chemotherapy for locally advanced gastric cancer: A randomized, prospective phase 2 trial.

IF 56.1 1区医学 Q1 CELL BIOLOGY

Cancer Cell Pub Date : 2026-08-10 Epub Date: 2026-07-15 DOI:10.1016/j.ccell.2026.06.015

Zhiyuan Xu, Can Hu, Litao Yang, Pengfei Yu, Yanqiang Zhang, Jiahui Chen, Guoliang Zheng, Xiaodong Chen, Tao Zhang, Weiyang He, Xiangyu Meng, Panpan Yu, Yian Du, Xiaowen Liu, Youdong Liu, Yongxiang Wang, Xiaoxiao Wu, Siwei Pan, Ruolan Zhang, Shengjie Zhang, Zhirong Xiong, Wei Sun, Chuanxin Dong, Jiajun Liu, Yuexian Wu, Xiangdong Cheng

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引用次数: 0

Abstract

Perioperative immunotherapy improves outcomes in locally advanced gastric or gastroesophageal junction cancer (GC/GEJC), but reliable predictive biomarkers remain elusive. In this biomarker-stratified, randomized, multicenter phase 2 Mountain-02 trail (NCT06374901), 136 patients with operable cT3-4aN + M0 GC/GEJC were enrolled and stratified by tumor-specific MHC class II (tsMHC-II) expression status and then randomized (1:1) to receive perioperative tislelizumab plus chemotherapy or chemotherapy alone. Among tsMHC-II-positive patients, adding tislelizumab to chemotherapy significantly increased the major pathological response (mPR) rate compared with chemotherapy alone (61.8% vs. 26.5%, p = 0.003), meeting the pre-specified primary endpoint. In contrast, no significant benefit was observed in the tsMHC-II-negative subgroup. Within the combination therapy arm, tsMHC-II-positive patients also achieved numerically higher mPR (61.8% vs. 23.5%, p = 0.001) and higher pathological complete response (pCR) rate (32.4% vs. 5.9%, p = 0.006) than tsMHC-II-negative patients. These findings support tsMHC-II as a promising predictive biomarker for perioperative immunotherapy and warrant further validation in larger studies.

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局部晚期胃癌围手术期tislelizumab联合化疗：一项随机前瞻性2期试验

围手术期免疫治疗可改善局部晚期胃癌或胃食管结癌（GC/GEJC）的预后，但可靠的预测性生物标志物仍然难以捉摸。在这项生物标志物分层、随机、多中心的2期临床试验（NCT06374901）中，136例可手术的cT3-4aN + M0 GC/GEJC患者入组，并根据肿瘤特异性MHC II类（tsMHC-II）表达状态进行分层，然后随机（1:1）接受围手术期tislelizumab联合化疗或单独化疗。在tsmhc - ii阳性患者中，与单独化疗相比，联合tislelizumab化疗显著提高了主要病理反应（mPR）率（61.8% vs. 26.5%, p = 0.003），达到了预先设定的主要终点。相比之下，在tsmhc - ii阴性亚组中没有观察到明显的益处。在联合治疗组中，tsmhc - ii阳性患者的mPR （61.8% vs. 23.5%, p = 0.001）和病理完全缓解（pCR）率（32.4% vs. 5.9%, p = 0.006）也高于tsmhc - ii阴性患者。这些发现支持tsMHC-II作为围手术期免疫治疗的一种有前景的预测性生物标志物，并需要在更大规模的研究中进一步验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell 医学-肿瘤学

CiteScore

55.20

自引率

1.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.