中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2600123178
最近更新日期： Date of Last Refreshed on：	2026-04-22 11:57:08
注册时间： Date of Registration：	2026-04-22 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	替雷利珠单抗联合新辅助治疗pMMR/MSS直肠癌：长程与短程放疗策略的随机对照研究
Public title：	Tislelizumab in Neoadjuvant Therapy for pMMR/MSS Rectal Cancer: Long-course vs Short-course Radiotherapy—A Randomized Trial
注册题目简写：
English Acronym：
研究课题的正式科学名称：	长程放化疗联合替雷利珠单抗序贯化疗联合替雷利珠单抗对比短程放疗序贯化疗联合替雷利珠单抗全程新辅助治疗pMMR/MSS型局部进展期直肠癌的II期临床研究
Scientific title：	Long-course Chemoradiotherapy Plus Tislelizumab Followed by Chemotherapy Plus Tislelizumab Versus Short-course Radiotherapy Followed by Chemotherapy Plus Tislelizumab as Total Neoadjuvant Therapy for pMMR/MSS Locally Advanced Rectal Cancer: A Phase II Clinical Study
研究课题代号(代码)： Study subject ID：
在二级注册机构或其它机构的注册号： The registration number of the Partner Registry or other register：

申请注册联系人：	李金	研究负责人：	熊文俊
Applicant：	Jin Li	Study leader：	Wenjun Xiong
申请注册联系人电话： Applicant telephone：	+86 137 2676 6484	研究负责人电话： Study leader's telephone：	+86 159 2055 3177
申请注册联系人传真： Applicant Fax：		研究负责人传真： Study leader's fax：
申请注册联系人电子邮件： Applicant E-mail：	lj1990131@163.com	研究负责人电子邮件： Study leader's E-mail：	xiongwj1988@163.com
申请单位网址(自愿提供)： Applicant website(voluntary supply)：		研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：
申请注册联系人通讯地址：	中国广东省广州市白云区机场路16号	研究负责人通讯地址：	中国广东省广州市白云区机场路16号
Applicant address：	No. 16 Jichang Road, Baiyun District, Guangzhou, Guangdong, China	Study leader's address：	No. 16 Jichang Road, Baiyun District, Guangzhou, Guangdong, China
申请注册联系人邮政编码： Applicant postcode：		研究负责人邮政编码： Study leader's postcode：
申请人所在单位：	广州中医药大学第一附属医院
Applicant's institution：	The First Affiliated Hospital of Guangzhou University of Chinese Medicine
研究负责人所在单位：	广州中医药大学第一附属医院
Affiliation of the Leader：	The First Affiliated Hospital of Guangzhou University of Chinese Medicine

是否获伦理委员会批准：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	NO.K-2026-031	伦理委员会批件附件： Approved file of Ethical Committee：	查看附件View
批准本研究的伦理委员会名称：	广州中医药大学第一附属医院伦理委员会
Name of the ethic committee：	Medical Ethics Committee of The First Affiliated Hospital of Guangzhou University of Chinese Medicine
伦理委员会批准日期： Date of approved by ethic committee：	2026-03-16 00:00:00
伦理委员会联系人：	黎欣盈
Contact Name of the ethic committee：	Xinying Li
伦理委员会联系地址：	中国广东省广州市白云区机场路16号
Contact Address of the ethic committee：	No. 16 Jichang Road, Baiyun District, Guangzhou, Guangdong, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 20 3658 8667	伦理委员会联系人邮箱： Contact email of the ethic committee：

研究实施负责（组长）单位：

广州中医药大学第一附属医院

Primary sponsor：

The First Affiliated Hospital of Guangzhou University of Chinese Medicine

研究实施负责（组长）单位地址：

中国广东省广州市白云区机场路16号

Primary sponsor's address：

No. 16 Jichang Road, Baiyun District, Guangzhou, Guangdong, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	广东	市(区县)：
Country：	China	Province：	Guangdong	City：
单位(医院)：	广州中医药大学第一附属医院	具体地址：	中国广东省广州市白云区机场路16号
Institution hospital：	The First Affiliated Hospital of Guangzhou University of Chinese Medicine	Address：	No. 16 Jichang Road, Baiyun District, Guangzhou, Guangdong, China

经费或物资来源：

广州中医药大学第一附属医院

Source(s) of funding：

The First Affiliated Hospital of Guangzhou University of Chinese Medicine

研究疾病：

直肠癌

Target disease：

rectal cancer

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

I期临床试验

Study phase：

1

研究设计：

随机平行对照

Study design：

Parallel

研究目的：

主要目的：长程放化疗联合替雷利珠单抗序贯化疗联合替雷利珠单抗对比短程放疗序贯化疗联合替雷利珠单抗全程新辅助治疗pMMR/MSS型局部进展期直肠癌的完全缓解（CR）率（包括cCR及pCR）。次要目的：长程放化疗联合替雷利珠单抗序贯化疗联合替雷利珠单抗对比短程放疗序贯化疗联合替雷利珠单抗全程新辅助治疗pMMR/MSS型局部进展期直肠癌的肿瘤退缩分级（TRG）、肿瘤降期率、观察等待率、保肛率、R0切除率、3年无事件生存（EFS）率、3年远处转移率、3年局部复发率、3年总生存（OS）率。长程放化疗联合替雷利珠单抗序贯化疗联合替雷利珠单抗对比短程放疗序贯化疗联合替雷利珠单抗全程新辅助治疗pMMR/MSS型局部进展期直肠癌的安全性。探索性目的：探索受试者肿瘤组织和外周血中潜在的生物标志物，包括但不限于与研究药物的疗效响应、耐药机制和疾病状态等的关联。

Objectives of Study：

Primary Objective: To compare the complete response (CR) rate (including clinical CR [cCR] and pathological CR [pCR]) between long-course chemoradiotherapy plus tislelizumab followed by chemotherapy plus tislelizumab versus short-course radiotherapy followed by chemotherapy plus tislelizumab as total neoadjuvant therapy for pMMR/MSS locally advanced rectal cancer. Secondary Objectives: To compare tumor regression grade (TRG), tumor downstaging rate, watch-and-wait rate, sphincter-preservation rate, R0 resection rate, 3-year event-free survival (EFS) rate, 3-year distant metastasis rate, 3-year local recurrence rate, and 3-year overall survival (OS) rate between the two regimens as total neoadjuvant therapy for pMMR/MSS locally advanced rectal cancer. To evaluate the safety of long-course chemoradiotherapy plus tislelizumab followed by chemotherapy plus tislelizumab versus short-course radiotherapy followed by chemotherapy plus tislelizumab as total neoadjuvant therapy for pMMR/MSS locally advanced rectal cancer. Exploratory Objectives: To explore potential biomarkers in tumor tissues and peripheral blood of participants, including but not limited to associations with treatment response, resistance mechanisms, and disease status.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

1.自愿签署书面知情同意书。
2.入组时年龄 ≥ 18岁且≤ 75岁。
3.东部肿瘤协作组织（ECOG）体能状况评分为0或 1。
4.预期寿命大于2年。
5.组织学证实的直肠腺癌。
6.肿瘤活检免疫组化提示pMMR, 即MSH1、MSH2、MSH6和PMS2四种蛋白均阳性，或者基因检测提示为MSS。
7.根据美国癌症分类联合委员会第8版TNM分期，采用高分辨率MRI±超声肠镜/经直肠彩超评估临床分期为cT3-4NanyM0或cTxN+M0的II-III期直肠癌，MRI检查明确肿瘤下极距离肛缘小于等于12cm。
8.在研究入组前，受试者需由1名负责手术的外科主治医生根据病史进行评估，以确认其是否符合以根治为目的进行R0切除的研究要求。
9.研究治疗前未接受过针对直肠癌的系统性或局部抗肿瘤治疗，包括放疗、化疗、免疫治疗、生物制剂、小分子靶向治疗等。
10.受试者同意采集筛选期及研究过程中需要的肿瘤组织及外周血标本并应用于相关研究。
11.具有良好的器官功能：
a)	血液学（开始研究治疗前7天内未使用任何血液成分及细胞生长因子支持治疗）：
i.	中性粒细胞绝对值ANC ≥ 1.5 ×10^9/L (1,500/mm^3) ； 
ii.	血小板计数 ≥ 100 × 10^9/L (100,000/mm^3) ； 
iii.	血红蛋白 ≥ 90 g/L。
b)	肾脏：
i.	肌酐清除率* (CrCl) 计算值 ≥ 50 mL/min
   * 将采用 Cockcroft-Gault 公式计算CrCl (Cockcroft-Gault 公式)
          CrCl (mL/min) = {(140 - 年龄) × 体重 (kg) × 0.85}/ (血清肌酐. (mg/dL) × 72)
ii. 尿蛋白 < 2+ 或24小时（h）尿蛋白定量 < 1.0 g。
c)	肝脏：
i.	血清总胆红素（TBil）≤ 1.5 × ULN
ii.	AST和ALT ≤ 2.5× ULN
iii. 血清白蛋白（ALB）≥ 28 g/L
d)	凝血功能：
i.	国际标准化比率（INR）和活化部分凝血活酶时间（APTT）≤ 1.5 × ULN。
e)	心功能：
i.	左室射血分数（LVEF）≥ 50%。
12.具有生育能力的女性受试者必须在研究治疗前3天内进行尿液或血清妊娠检查（如尿液妊娠检查结果不能确认为阴性，需进行血清妊娠检查，以血清妊娠结果为准），且结果为阴性。如具有生育能力的女性受试者与未绝育的男性伴侣发生性行为，该受试者必须自筛选开始采取可接受的避孕方法，且必须同意在研究药物末次用药后的120天内持续使用采用避孕方法；关于在此时间点后是否停止避孕，应与研究者讨论。周期性禁欲、安全期避孕是不可接受的避孕方法。：
a)有生育能力的女性是指未经手术绝育（即双侧输卵管结扎术、双侧卵巢切除术或全子宫切除术）或未绝经的女性（绝经的定义为无替代医学原因的前提下至少连续12个月停经，血清促卵泡激素水平在绝经后女性的实验室参考范围之内）；
b) 高效的避孕方法是指在持续正确使用情况下避孕失败率很低（如每年低于 1%）的避孕方法。并非所有避孕方法均是高效的。除屏障避孕法之外，有生育能力的女性受试者还必须单独使用激素避孕法（如避孕药），以确保不发生妊娠。
13.受试者愿意而且能够遵守日程表规定的访视、治疗方案、实验室检查，及遵守研究的其他要求。

Inclusion criteria

1. Voluntarily provide written informed consent.
2. Age >= 18 years and <= 75 years at the time of enrollment.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Life expectancy greater than 2 years.
5. Histologically confirmed rectal adenocarcinoma.
6. Tumor biopsy immunohistochemistry indicating pMMR (i.e., all four proteins MSH1, MSH2, MSH6, and PMS2 positive) or genetic testing indicating MSS.
7. According to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system, clinical stage assessed by high-resolution MRI +/- endorectal ultrasound/transrectal color Doppler ultrasound as cT3-4NanyM0 or cTxN+M0 Stage II-III rectal cancer, with MRI confirming the lower margin of the tumor <= 12 cm from the anal verge.
8. Prior to study enrollment, the subject must be evaluated by one attending surgeon responsible for surgery based on medical history to confirm eligibility for R0 resection with curative intent.
9. No prior systemic or local anti-tumor treatment for rectal cancer before study treatment, including radiotherapy, chemotherapy, immunotherapy, biological agents, small molecule targeted therapy, etc.
10. Subjects agree to provide tumor tissue and peripheral blood samples required during screening and throughout the study for relevant research.
11. Adequate organ function:  
a) Hematology (no blood products or hematopoietic growth factors within 7 days prior to starting study treatment):  
i. Absolute neutrophil count (ANC) >= 1.5 × 10⁹/L (1,500/mm³);  
ii. Platelet count >= 100 × 10⁹/L (100,000/mm³);  
iii. Hemoglobin >= 90 g/L.  
b) Renal:  
i. Estimated creatinine clearance (CrCl) >= 50 mL/min.            * CrCl will be calculated using the Cockcroft-Gault formula:  CrCl (mL/min) = {(140 - Age) × Weight (kg) × 0.85} / (Serum Creatinine (mg/dL) × 72)  
ii. Urine protein < 2+ or 24-hour urine protein < 1.0 g.  
c) Hepatic:  
i. Total bilirubin (TBil) <= 1.5 × upper limit of normal (ULN);  
ii. AST and ALT <= 2.5 × ULN;  
iii. Serum albumin (ALB) >= 28 g/L.  
d) Coagulation:  
i. International normalized ratio (INR) and activated partial thromboplastin time (APTT) <= 1.5 × ULN.  
e) Cardiac:  
i. Left ventricular ejection fraction (LVEF) >= 50%.
12. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to study treatment (if urine pregnancy test results cannot be confirmed as negative, a serum pregnancy test is required, with serum pregnancy test results taking precedence). If a female subject of childbearing potential is sexually active with a non-sterilized male partner, the subject must use an acceptable method of contraception starting from screening and must agree to continue using contraception for 120 days after the last dose of study drug; whether to discontinue contraception after this time point should be discussed with the investigator. Periodic abstinence and calendar methods are not acceptable methods of contraception.  
a) A female of childbearing potential is a female who has not undergone surgical sterilization (i.e., bilateral tubal ligation, bilateral oophorectomy, or total hysterectomy) or is not postmenopausal (postmenopausal is defined as at least 12 consecutive months of amenorrhea without alternative medical causes, with serum follicle-stimulating hormone levels within the laboratory reference range for postmenopausal women);  
b) Highly effective contraception refers to methods with low failure rates (i.e., less than 1% per year) when used consistently and correctly. Not all contraceptive methods are highly effective. In addition to barrier methods, female subjects of childbearing potential must also use hormonal contraception (e.g., contraceptive pills) alone to ensure no pregnancy occurs.
13. Subjects are willing and able to comply with scheduled visits, treatment regimen, laboratory examinations, and other study requirements.

排除标准：

1.存在可疑的转移病灶或存在局部晚期无法切除的疾病，无论疾病分期如何。 2.除直肠癌外，受试者在入组前5年内患有其他恶性肿瘤。不排除患有其他恶性肿瘤通过局部治疗已治愈的受试者，例如基底或皮肤鳞状细胞癌、浅表膀胱癌、乳腺原位癌等。 3.同时入组另一项临床研究，除非其为一项观察性、非干预性的临床研究或干预性研究的随访期。 4.存在有需要急诊手术处理的肠梗阻、肠穿孔、肠出血等。 5.多原发直肠癌。 6.有盆腔和腹部放疗史。 7.不能吞咽药片、吸收不良综合症、或任何影响胃肠吸收的状况。 8.既往接受过任何针对局晚期直肠癌的全身性或局部抗肿瘤治疗，包括根治性手术、化疗、放疗、免疫治疗（包括免疫检查点抑制剂、免疫检查点激动剂、免疫细胞治疗等任何针对肿瘤免疫作用机制的治疗）、生物制剂、小分子靶向治疗等 9.研究治疗前2周内接受过非特异性免疫调节治疗（如白介素、干扰素、胸腺肽、肿瘤坏死因子等，不包括用于治疗血小板减少的IL-11）；研究治疗前1周内曾接受具有抗肿瘤适应症的中草药或中成药。 10.患有在过去两年内需要系统性治疗的活动性自身免疫性疾病（如使用改善病情药物，皮质类固醇，免疫抑制剂治疗），替代治疗（如甲状腺素、胰岛素、或针对肾上腺或垂体功能不全的生理性皮质类固醇替代治疗）不认为是一种系统性治疗。 11.存在需要系统性糖皮质激素治疗的非感染性肺炎或肺炎病史或当前存在间质性肺疾病病史。 12.有严重出血倾向或凝血功能障碍病史；既往或当前需长期接受抗凝治疗的患者（例如房颤患者满足CHADS2评分≥2分）。 13.当前存在未得到控制的合并疾病，包括但不限于失代偿性肝硬化、肾病综合征、未控制的代谢紊乱、重度活动性消化性溃疡病或胃炎，或会限制受试者依从研究要求或影响受试者提供书面知情同意能力的精神疾病/社会状况。 14.既往存在心肌炎、心肌病、恶性心律失常病史。研究治疗前12个月内存在需住院治疗的不稳定性心绞痛、充血性心力衰竭或血管疾病（如需手术修复的主动脉瘤或外周静脉血栓），或可能影响研究药物安全性评价的其他心脏损害（如控制不佳的心律失常，心肌梗塞或缺血）；研究治疗前6个月内存在食管胃底静脉曲张，严重溃疡，伤口未愈，胃肠穿孔，腹瘘，胃肠梗阻，腹腔内脓肿或急性胃肠道出血病史；研究治疗前6个月内发生过任何动脉血栓栓塞事件，NCI CTCAE 5.0版3级及以上的静脉血栓栓塞，短暂性脑缺血发作，脑血管意外，高血压危象或高血压脑病；研究治疗前1个月内发生慢性阻塞性肺病急性加重；当前存在高血压且经口服降压药物治疗后收缩压≥160mmHg或舒张压≥100mmHg。 15.活动性或既往有明确的炎症性肠病（如克罗恩病、溃疡性结肠炎或慢性腹泻）病史。 16.研究治疗前4周内发生严重感染，包括但不局限于伴有需要住院治疗的合并症、败血症或严重肺炎；在研究治疗前10天内接受过全身抗感染治疗的活动性感染（不包括乙型肝炎或丙型肝炎的抗病毒治疗）。 17.在研究治疗前30天内进行过重大外科手术或发生严重外伤；在研究治疗前3天内进行过较小的局部手术（不包括经外周静脉穿刺中心静脉置管术）。 18.存在免疫缺陷病史；HIV抗体检测阳性者；当前正在长期使用系统性皮质类固醇激素或其他免疫抑制剂。 19.已知存在活动性肺结核（TB），怀疑有活动性TB的受试者，需进行临床检查排除（如痰结核菌检查、胸片等）；已知的活动性梅毒感染。 20.已知异体器官移植史和异体造血干细胞移植史。 21.未经治疗的活动性乙型肝炎受试者（HBsAg阳性且HBV-DNA超过1000拷贝/ml（200 IU/ml）或高于检测下限），对于患有乙型肝炎的受试者，要求在研究治疗期间接受抗乙肝病毒治疗；活动性的丙型肝炎受试者（HCV抗体阳性且HCV-RNA水平高于检测下限）。 22.在研究治疗前的30天内接种了活疫苗，或计划在研究期间接种活疫苗。 23.已知对任何研究药物的任何成分过敏；已知对其他单克隆抗体产生严重超敏反应的病史。 24.已知有精神疾病、药物滥用、酗酒或吸毒史。 25.妊娠期或哺乳期女性。 26.既往或当前存在任何疾病、治疗、实验室检查异常，可能会混淆研究结果，影响受试者全程参与研究，或参与研究可能不符合受试者的最佳利益。 27.非恶性肿瘤导致的局部或全身性疾病；或肿瘤继发的疾病或症状，并可导致较高医学风险和/或生存期评价的不确定性，如肿瘤类白血病反应（白细胞计数＞20×10^9/L）、恶液质表现（如已知的筛选前3个月体重减轻超过10%）、BMI小于等于18（BMI为体重（Kg）/身高（m）^2）等。

Exclusion criteria：

1. Presence of suspected metastatic lesions or locally advanced unresectable disease, regardless of disease stage. 2. Subjects with other malignancies within 5 years prior to enrollment, excluding rectal cancer. Subjects with other malignancies cured by local treatment are not excluded, such as basal or squamous cell skin cancer, superficial bladder cancer, ductal carcinoma in situ of the breast, etc. 3. Concurrent enrollment in another clinical study, unless it is an observational, non-interventional clinical study or the follow-up period of an interventional study. 4. Presence of intestinal obstruction, intestinal perforation, or intestinal bleeding requiring emergency surgical intervention. 5. Multiple primary rectal cancers. 6. History of pelvic and abdominal radiotherapy. 7. Inability to swallow tablets, malabsorption syndrome, or any condition affecting gastrointestinal absorption. 8. Prior receipt of any systemic or local anti-tumor treatment for locally advanced rectal cancer, including radical surgery, chemotherapy, radiotherapy, immunotherapy (including immune checkpoint inhibitors, immune checkpoint agonists, cellular immunotherapy, or any treatment targeting tumor immune mechanisms), biological agents, small molecule targeted therapy, etc. 9. Receipt of non-specific immunomodulatory therapy (such as interleukins, interferons, thymosin, tumor necrosis factor, etc., excluding IL-11 for treatment of thrombocytopenia) within 2 weeks prior to study treatment; receipt of Chinese herbal medicine or proprietary Chinese medicine with anti-tumor indications within 1 week prior to study treatment. 10. Active autoimmune disease requiring systemic treatment within the past two years (such as use of disease-modifying agents, corticosteroids, or immunosuppressants). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. 11. History of non-infectious pneumonia requiring systemic corticosteroid therapy, or current history of interstitial lung disease. 12. History of severe bleeding tendency or coagulation dysfunction; subjects with prior or current requirement for long-term anticoagulant therapy (e.g., atrial fibrillation patients with CHADS₂ score >= 2). 13. Currently uncontrolled comorbid conditions, including but not limited to decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements or affect the subject's ability to provide written informed consent. 14. Prior history of myocarditis, cardiomyopathy, or malignant arrhythmia. Within 12 months prior to study treatment, history of unstable angina requiring hospitalization, congestive heart failure, or vascular disease (e.g., aortic aneurysm requiring surgical repair or peripheral venous thrombosis), or other cardiac impairment that may affect safety evaluation of study drug (e.g., poorly controlled arrhythmia, myocardial infarction or ischemia); within 6 months prior to study treatment, history of esophageal and gastric varices, severe ulceration, unhealed wounds, gastrointestinal perforation, abdominal fistula, intestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding; within 6 months prior to study treatment, occurrence of any arterial thromboembolic event, venous thromboembolism of Grade 3 or higher per NCI CTCAE Version 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy; acute exacerbation of chronic obstructive pulmonary disease within 1 month prior to study treatment; current hypertension with systolic blood pressure ≥ 160 mmHg or diastolic blood pressure >= 100 mmHg despite oral antihypertensive medication. 15. Active or documented history of inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic diarrhea). 16. Severe infection occurring within 4 weeks prior to study treatment, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infection receiving systemic anti-infective treatment within 10 days prior to study treatment (excluding antiviral treatment for hepatitis B or hepatitis C). 17. Major surgical procedure or serious trauma within 30 days prior to study treatment; minor local surgery within 3 days prior to study treatment (excluding peripherally inserted central catheter placement). 18. History of immunodeficiency; subjects with positive HIV antibody test; current long-term use of systemic corticosteroids or other immunosuppressants. 19. Known active tuberculosis (TB); subjects suspected of active TB require clinical examination to exclude (e.g., sputum acid-fast bacilli smear, chest X-ray, etc.); known active syphilis infection. 20. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. 21. Untreated active hepatitis B (HBsAg positive with HBV-DNA > 1000 copies/mL [200 IU/mL] or above the lower limit of detection); for subjects with hepatitis B, anti-HBV treatment is required during study treatment; active hepatitis C (HCV antibody positive with HCV-RNA level above the lower limit of detection). 22. Receipt of live vaccine within 30 days prior to study treatment, or planned live vaccination during the study. 23. Known hypersensitivity to any component of any study drug; known history of severe hypersensitivity reaction to other monoclonal antibodies. 24. Known psychiatric illness, drug abuse, alcoholism, or history of drug addiction. 25. Pregnant or lactating females. 26. Any disease, treatment, or laboratory abnormality that may confound study results, affect the subject's participation throughout the study, or make participation not in the best interest of the subject. 27. Local or systemic diseases not caused by malignancy; or diseases or symptoms secondary to tumor that may result in higher medical risk and/or uncertainty in survival evaluation, such as tumor-related leukemoid reaction (white blood cell count > 20 × 10⁹/L), cachexia manifestations (e.g., known weight loss > 10% within 3 months prior to screening), BMI <= 18 (BMI = weight [kg] / height [m]²), etc.

研究实施时间：

Study execute time：

从 From 2026-03-30 00:00:00至 To 2031-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2026-05-01 00:00:00 至 To 2029-03-31 00:00:00

干预措施：

Interventions：

组别：	长程放疗组	样本量：	60
Group：	Long-course Chemoradiotherapy Group	Sample size：	60
干预措施：	长程放疗+同期替雷利珠单抗+CAPOX方案化疗2周期→替雷利珠单抗+CAPOX方案化疗4周期→末次卡培他滨给药后4-8周内接受手术或观察等待	干预措施代码：
Intervention：	Long-course radiotherapy + concurrent tislelizumab + CAPOX chemotherapy for 2 cycles → tislelizumab + CAPOX chemotherapy for 4 cycles → surgery or watch-and-wait within 4-8 weeks after the last dose of capecitabine	Intervention code：

组别：	短程放疗组	样本量：	60
Group：	Short-course Radiotherapy Group	Sample size：	60
干预措施：	短程放疗→替雷利珠单抗+CAPOX方案化疗6周期→末次卡培他滨给药后4-8周内接受手术或观察等待	干预措施代码：
Intervention：	Short-course radiotherapy → tislelizumab + CAPOX chemotherapy for 6 cycles → surgery or watch-and-wait within 4-8 weeks after the last dose of capecitabine	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	广东	市(区县)：
Country：	China	Province：	Guangdong	City：
单位(医院)：	广州中医药大学第一附属医院	单位级别：	三级甲等
Institution hospital：	The First Affiliated Hospital of Guangzhou University of Chinese Medicine	Level of the institution：	Tertiary, Tertiary A

国家：	中国	省(直辖市)：	广东	市(区县)：
Country：	China	Province：	Guangdong	City：
单位(医院)：	广州中医药大学第一附属医院深汕医院	单位级别：	三级甲等
Institution hospital：	The First Affiliated Hospital Shenshan Hospital of Guangzhou University of Chinese Medicine	Level of the institution：	Tertiary, Tertiary A

测量指标：

Outcomes：

指标中文名：	完全缓解率	指标类型：	主要指标
Outcome：	Complete Response Rate	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	3年无事件生存（EFS）率	指标类型：	次要指标
Outcome：	3-year event-free survival (EFS) rate	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	3年总生存（OS）率	指标类型：	次要指标
Outcome：	3-year overall survival (OS) rate	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	肿瘤组织	组织：
Sample Name：	Tumor Tissue	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age		岁 years
最大 Max age		岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

本研究采用中央随机化系统（Interactive Web Response System, IWRS）进行分层、动态区组随机。具体方法如下： 1.分层因素：基于以下两个因素进行分层： a)高危因素：T4、N2、MRF+、EMVI+、侧方淋巴结阳性任一因素即为高危（是/否） b)肿瘤下极距离肛缘位置：≤5cm vs. >5cm 上述因素组合形成4个分层（高危/低危 × ≤5cm/>5cm）。 2.动态区组随机：在每个分层内，采用动态可变区组长度的区组随机方法。区组长度将在{4, 6, 8}中随机选择，以保证分组过程的不可预测性，有效维持分配隐匿性。 3.随机执行：符合随机化条件的受试者由授权研究人员通过IWRS系统进行随机。系统根据受试者的分层因素，自动从相应的分层随机列表中分配下一个可用的治疗组别（A组或B组）。随机分配结果实时返回给研究人员，整个过程不可预测且无法回溯。 4.分配隐匿：随机序列的生成、区组长度的选择以及治疗分配均由IWRS系统独立完成，研究人员和申办方均无法提前预知分配结果，从而保证分组隐匿性。

Randomization Procedure (please state who generates the random number sequence and by what method)：

This study will employ a central randomization system (Interactive Web Response System, IWRS) for stratified, dynamic block randomization. The specific methodology is as follows: 1. Stratification Factors: Stratification will be based on the following two factors: a) High-risk factors: Presence of any of the following factors is defined as high-risk (Yes/No): T4, N2, MRF+, EMVI+, or positive lateral lymph nodes b) Distance of tumor lower margin from anal verge: ≤5 cm vs. >5 cm These factors combine to form 4 strata (High-risk/Low-risk × ≤5 cm/>5 cm). 2. Dynamic Block Randomization: Within each stratum, a dynamic variable block randomization method will be used. Block sizes will be randomly selected from {4, 6, 8} to ensure unpredictability of the allocation process and effectively maintain allocation concealment. 3. Randomization Execution: Eligible subjects will be randomized by authorized study personnel through the IWRS system. Based on the subject's stratification factors, the system will automatically assign the next available treatment group (Group A or Group B) from the corresponding stratum-specific randomization list. The randomization result will be returned to the investigator in real-time. The entire process is unpredictable and cannot be backtracked. 4. Allocation Concealment: The generation of randomization sequences, selection of block sizes, and treatment allocation will be performed independently by the IWRS system. Neither investigators nor the sponsor can foresee the allocation results in advance, thereby ensuring allocation concealment.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：	本研究采用开放标签设计
Blinding：	this study will be conducted as an open-label trial.
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

是否共享原始数据： IPD sharing	否No
共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：	本研究不公开共享原始数据，以保护参与者隐私并遵守数据保护法规。汇总结果及统计分析数据集将按照期刊要求发表。出于学术合作目的，经正式申请及机构审查委员会批准，并核实研究目的及符合《个人信息保护法》合规要求后，可考虑共享去标识化数据。
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Raw data will not be publicly shared to protect participant privacy and comply with data protection regulations. Aggregated results and statistical analysis datasets will be published in accordance with journal requirements. For academic collaboration purposes, de-identified data may be shared upon formal request and institutional review board approval, pending verification of research purpose and compliance with the Personal Information Protection Law.
数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：	本研究采用纸质病例记录表（Case Record Form, CRF）进行数据采集。各中心授权研究者根据源文件填写纸质CRF，经监查员（Monitor）现场核查源数据与CRF一致性后，由中心数据管理员将纸质CRF快递至牵头单位（广州中医药大学第一附属医院）。牵头单位数据管理员采用双人双份录入法将数据录入中心化Excel数据库，经逻辑核查、数据清理、质疑解决后锁定数据库。数据库设置访问权限控制及修改留痕，确保数据可追溯。纸质CRF及数据库备份保存至研究结束后至少5年。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	This study will utilize paper Case Record Forms (CRF) for data collection. Authorized investigators at each site will complete paper CRFs based on source documents. After monitoring by clinical research associates (CRA/Monitor) to verify consistency between source data and CRF entries, site data managers will courier the paper CRFs to the coordinating center (The First Affiliated Hospital of Guangzhou University of Chinese Medicine). Data managers at the coordinating center will perform double data entry into a centralized Excel database. The database will undergo logic verification, data cleaning, and query resolution before database lock. The database will be configured with access controls and audit trails for all modifications to ensure data traceability. Paper CRFs and database backups will be retained for at least 5 years after study completion.
数据与安全监察委员会： Data and Safety Monitoring Committee：	暂未确定/Not yet
注册人： Name of Registration：	2026-04-22 11:56:50