近期的临床前研究发现了放疗和免疫检查点抑制剂之间的独特协同作用，在肺癌中已经带来了显著的生存益处。在局部晚期直肠癌（LARC）中，新辅助放疗加免疫检查点抑制剂甚至在能力匹配修复缺陷患者中也实现了令人惊讶的高病理完全缓解率（pathological complete response, pCR）。由于现有研究仅为二期单组的试验，我们旨在进行一项随机对照试验，以进一步阐明这种新型联合治疗的疗效和安全性。符合条件的LARC患者随机分配到三个组（两个实验组，一个对照组）。所有组的患者均接受长程放疗和同步的卡培他滨作为新辅助治疗，以及根治性手术。特别的是，第一组的患者在放疗的第8天开始接受抗PD-1（Programmed Death 1）治疗（同时方案），第二组的患者在放疗结束2周后开始接受抗PD-1治疗（顺序方案）。Tislelizumab（抗PD-1）每次计划给予200毫克，连续三次，间隔3周。随机分配按不同参与中心分层进行，块大小为6。主要终点是pCR率，次要终点包括新辅助治疗相关不良事件率，以及手术后2、3和5年的无病生存率和总生存率。数据将采用意向治疗分析方法进行分析。该方案已获得北京友谊医院（主要中心）的伦理委员会批准，批准编号为2022-P2-050-01。在向同行评审期刊发表之前，该研究的数据将存储在专门开发的临床试验数据库中。NCT05245474.©作者（或其雇主）2023。根据CC BY-NC许可进行再使用。未经授权，不得进行商业再利用。由BMJ出版。

Recent preclinical studies have discovered unique synergism between radiotherapy and immune checkpoint inhibitors, which has already brought significant survival benefit in lung cancer. In locally advanced rectal cancer (LARC), neoadjuvant radiotherapy plus immune checkpoint inhibitors have also achieved surprisingly high pathological complete response (pCR) rates even in proficient mismatch-repair patients. As existing researches are all phase 2, single-cohort trials, we aim to conduct a randomised, controlled trial to further clarify the efficacy and safety of this novel combination therapy.Eligible patients with LARC are randomised to three arms (two experiment arms, one control arm). Patients in all arms receive long-course radiotherapy plus concurrent capecitabine as neoadjuvant therapy, as well as radical surgery. Distinguishingly, patients in arm 1 also receive anti-PD-1 (Programmed Death 1) treatment starting at Day 8 of radiation (concurrent plan), and patients in arm 2 receive anti-PD-1 treatment starting 2 weeks after completion of radiation (sequential plan). Tislelizumab (anti-PD-1) is scheduled to be administered at 200 mg each time for three consecutive times, with 3-week intervals. Randomisation is stratified by different participating centres, with a block size of 6. The primary endpoint is pCR rate, and secondary endpoints include neoadjuvant-treatment-related adverse event rate, as well as disease-free and overall survival rates at 2, 3 and 5 years postoperation. Data will be analysed with an intention-to-treat approach.This protocol has been approved by the institutional ethical committee of Beijing Friendship Hospital (the primary centre) with an identifying serial number of 2022-P2-050-01. Before publication to peer-reviewed journals, data of this research will be stored in a specially developed clinical trial database.NCT05245474.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.