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：	ChiCTR2500101884
最近更新日期： Date of Last Refreshed on：	2025-04-30 16:39:13
注册时间： Date of Registration：	2025-04-30 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	斯鲁利单抗联合贝伐珠单抗联合奥沙利铂和氟尿嘧啶类为基础的化疗(CapeOX/mFOLFOX6)方案一线治疗RAS突变、MSS型晚期结直肠癌的有效性和安全性
Public title：	The efficacy and safety of the first-line treatment of Serplulimab combined with bevacizumab plus oxaliplatin and fluorouracil-based chemotherapy (CapeOX/ mFOLFOX6) with RAS-mutated and MSS metastatic colorectal cancer
注册题目简写：
English Acronym：
研究课题的正式科学名称：	斯鲁利单抗联合贝伐珠单抗联合奥沙利铂和氟尿嘧啶类为基础的化疗(CapeOX/mFOLFOX6)方案一线治疗RAS突变、MSS型晚期结直肠癌的有效性和安全性
Scientific title：	The efficacy and safety of the first-line treatment of Serplulimab combined with bevacizumab plus oxaliplatin and fluorouracil-based chemotherapy (CapeOX/ mFOLFOX6) with RAS-mutated and MSS metastatic colorectal cancer
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：	孟超	研究负责人：	孟超
Applicant：	Meng Chao	Study leader：	Meng Chao
申请注册联系人电话： Applicant telephone：	+86 136 0106 2791	研究负责人电话： Study leader's telephone：	+86 136 0106 2791
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：	mengchao@pkuih.edu.cn	研究负责人电子邮件： Study leader's E-mail：	mengchao@pkuih.edu.cn
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：	北京市昌平区生命科学园生命园路1号	研究负责人通讯地址：	北京市昌平区生命科学园生命园路1号
Applicant address：	Life Park Road No.1,Life Science Park of Zhong Guancun, Changping District, Beijing, China	Study leader's address：	Life Park Road No.1,Life Science Park of Zhong Guancun, Changping District, Beijing, 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：	北京大学国际医院
Applicant's institution：	Peking University International Hospital
研究负责人所在单位：	北京大学国际医院
Affiliation of the Leader：	Peking University International Hospital

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：	2025-KY-0020-01	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：	北京大学国际医院生物医学伦理委员会
Name of the ethic committee：	Biomedical Ethics Committee of Peking University International Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2025-04-12 00:00:00
伦理委员会联系人：	赵俊
Contact Name of the ethic committee：	Zhao Jun
伦理委员会联系地址：	北京市昌平区中关村生命科学园生命园路1号
Contact Address of the ethic committee：	Life Park Road No.1,Life Science Park of Zhong Guancun, Changping District, Beijing, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 10 6900 7608	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：

北京大学国际医院

Primary sponsor：

Peking University International Hospital

研究实施负责（组长）单位地址：

北京市昌平区中关村生命科学园生命园路1号

Primary sponsor's address：

Life Park Road No.1,Life Science Park of Zhong Guancun, Changping District, Beijing, 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)：	北京市	市(区县)：
Country：	China	Province：	Beijing	City：
单位(医院)：	北京大学国际医院	具体地址：	北京市昌平区中关村生命科学园生命园路1号
Institution hospital：	Peking University International Hospital	Address：	Life Park Road No.1,Life Science Park of Zhong Guancun, Changping District, Beijing, China

经费或物资来源：

吴阶平医学基金会

Source(s) of funding：

Wu Jieping Medical Foundation

研究疾病：

结直肠癌

Target disease：

Colorectal 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：

其它

Study phase：

N/A

研究设计：

单臂

Study design：

Single arm

研究目的：

评估斯鲁利单抗联合贝伐珠单抗联合奥沙利铂和氟尿嘧啶类为基础的化疗(CapeOX/ mFOLFOX6)方案一线治疗RAS突变、MSS型转移性结直肠癌的有效性和安全性研究，主要终点为无进展生存期（PFS），次要终点包括客观缓解率（ORR），总生存期（OS），疾病控制率（DCR）及治疗期间安全性。

Objectives of Study：

To evaluate the efficacy and safety of the first-line treatment of Serplulimab combined with bevacizumab plus oxaliplatin and fluorouracil-based chemotherapy (CapeOX/ mFOLFOX6) with RAS-mutated and MSS metastatic colorectal cancer.The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR),overall survival (OS), disease control rate (DCR) and adverse events.

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.	签署ICF时年龄在18-75岁（含）之间的男性或女性
2.	经组织病理学、影像学证实的RAS突变、MSS型不可切除的转移性结直肠腺癌
3.	预期寿命≥ 12 周
4.	既往未接受过任何针对转移性结直肠腺癌的全身抗肿瘤药物治疗
5.	对于之前接受过新辅助/辅助治疗的参与者，从最后一次治疗到复发或进展的时间必须超过6个月。
6.	本研究中既往中药治疗结束与首次给药之间的间隔应≥ 2 周
7.	既往治疗相关 AE恢复到美国国家癌症研究所不良事件通用术语标准 （NCI-CTCAE） ≤ 1 级（脱发除外）
8.	根据 RECIST 1.1版标准，经研究中心评估至少具有一个可测量病灶，可测量病灶应为未接受过放疗等局部治疗(位于既往放疗区域内的病灶，如果证实发生进展，也可作为符合要求的可测量病灶)
9.	同意提供足够的先前保存的肿瘤组织标本或同意进行活检以收集肿瘤组织进行 PD-L1表达水平测定、TMB 检测以及 KRAS、BRAF、NRAS 等的基因突变检测
10.	在接受研究药物第一剂前 7 天内的 ECOG PS 评分为 0 或 1
11.	乙型肝炎表面抗原(HBSAg)(-)并且乙肝核心抗体(HBcAb)(-)，且临床判定不存在活动性肝炎。如果HBSAg(+)或者 HBcAb(+)，则乙肝病毒脱氧核糖核酸(HBV-DNA)必须<2.5 × 103拷贝/mL或500 IU/mL(若研究单位检测下限>500 IU/m，则低于检测下限即可入组)方可入组
12.	丙型肝炎病毒(HCV)抗体(-);若HCV抗体(+)则必须 HCVRNA 检查呈阴性方可入组。存在乙肝及丙肝共同感染的受试者需排除(HBSAg 或 HBcAb检查呈阳性EHCV抗体检查呈阳性)
13.	以下标准表明具有足够的主要器官功能（在研究药物首次给药前 14 天内未接受输血、白蛋白、重组人促血小板生成素或集落刺激因子 [CSF] 治疗）
血液系统：嗜中性粒细胞（ANC）：≥1.5×10 9 /L;血小板 （PLT） ≥ 100×10 9 /L;血红蛋白 （Hb） ≥ 90g/L 
肝功能：总胆红素 （TBIL） ≤1.5×正常上限 （ULN）；谷氨酸转氨酶 （ALT） ： ≤ 2.5×ULN、对于肝转移患者≤ 5.0×ULN；天冬氨酸氨基转移酶 （AST） ≤ 2.5×ULN、对于肝转移患者≤ 5.0×ULN；碱性磷酸酶（ALP）：≤ 2.5×ULN、对于肝转移患者≤ 5.0×ULN;白蛋白≥ 30 g/L。
肾功能：肌酐 （Cr） ≤ 1.5×ULN，如果 Cr > 1.5 × ULN，肌酐清除率需≥ 50mL/min（通过 Cockcroft-Gault 公式计算）；
凝血：活化部分凝血活酶时间（APTT） ≤ 1.5×ULN；凝血酶原时间 （PT） ≤ 1.5×ULN；国际标准化比值 （INR） ≤ 1.5×ULN；
尿液分析/24小时尿蛋白：尿蛋白：尿蛋白定性检查 ≤ 1+;如果≥ 2+，则需要进行 24 小时尿蛋白测试，如果 24 小时尿蛋白为 <1g，则允许入组
14.	有生育能力的女性受试者（包括即使闭经 12 个月或更长时间也不能通过抗肿瘤药物治疗排除怀孕的受试者）必须在接受第一剂研究药物前 7 天内血清妊娠试验阴性。 对于有生育能力的女性受试者和有生育能力伴侣的男性受试者，在研究期间，直到最后一次施用斯鲁利单抗/安慰剂和贝伐珠单抗后至少 3 个月，以及最后一次化疗后至少 6 个月（以较晚者为准），他们必须同意使用至少一种医学上可接受的避孕措施（例如 宫内节育器、避孕药或避孕套）。
15.	提供签署的 ICF，并愿意遵守协议中规定的所有研究程序和规则。

Inclusion criteria

1.Male or female aged 18-75 years (inclusive) when signing the ICF
2.Histopathologically or imaging confirmed RAS-mutated and MSS unresectable metastatic colorectal adenocarcinoma
3.Life expectancy >= 12 weeks
4.Have not received any previous systemic anti-tumor drug treatment for metastatic colorectal adenocarcinoma
5.For participants who have previously received neoadjuvant/adjuvant therapy, the time from the last treatment to recurrence or progression must exceed 12 months.
6.The interval between the end of previous traditional Chinese medicine treatment and the first dose in this study should be >= 2 weeks
7.Recovering of previous treatment-related AEs to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade <= 1 (except for alopecia)
8.With at least one measurable lesion as assessed by the IRRC per RECIST v1.1, and the measurable lesion should not have been treated locally such as with radiotherapy (a lesion located in an area subjected to previous radiotherapy can also be regarded as a measurable lesion if PD is confirmed)
9.Agree to provide sufficient previously preserved tumor tissue specimens or agree to undergo biopsy to collect tumor tissue for PD-L1 expression level determination, TMB testing, as well as gene mutation detection of KRAS, BRAF, NRAS, etc.
10.Have an ECOG PS score of 0 or 1 within 7 days prior to receiving the first dose of the study drugs
11.Hepatitis B surface antigen (HBsAg) (-) and hepatitis B core antibody (HBcAb) (-), with no clinically judged active hepatitis. If HBsAg (+) or HBcAb (+), then hepatitis B virus deoxyribonucleic acid (HBV-DNA) must be < 2.5 × 10^3copies/mL or 500 IU/mL (if the lower limit of detection of the study site is > 500 IU/mL, below the limit of detection is acceptable for inclusion)
12.Hepatitis C Virus (HCV) antibody (-); if HCV antibody is positive (+), HCV-RNA test must be negative for patients to be enrolled. Subjects with co-infection with hepatitis B and C should be excluded (positive for HBsAg or HBcAb test, and positive for HCV antibody test)
13.Adequate major organ functions indicated by the following criteria (no treatment with blood transfusions, albumin, recombinant human thrombopoietin, or colony-stimulating factor [CSF] within 14 days prior to the first dose of study drugs):
Hematological System:Neutrophils (ANC): >= 1.5×10^9 /L; Platelets (PLT) >= 100×10^9 /L;Hemoglobin (Hb) >= 90g/L Hepatic Function:Total bilirubin (TBIL) <= 1.5×upper limit of normal(ULN) Glutamate aminotransferase (ALT) : <= 2.5×ULN; <= 5.0×ULN for patients with liver metastases Aspartate aminotransferase (AST) <= 2.5×ULN; <= 5.0×ULN for patients with liver metastases Alkaline Phosphatase(ALP): <= 2.5×ULN; <= 5.0×ULN for patients with liver and/or bone metastases; Albumin >= 30 g/L Renal Function: Creatinine (Cr) <= 1.5×ULN; Creatinine clearance >= 50mL/min if Cr > 1.5 × ULN; (Calculated by Cockcroft-Gault formula) Coagulation Activated partial thromboplastin time(APTT) <= 1.5×ULN Prothrombin time (PT) <= 1.5×ULN International Normalized Ratio (INR) <= 1.5×ULN Urinalysis/24-hour urine protein Urine protein Qualitative examination on urine protein <= 1+; in case of >= 2+, a 24-hour urine protein test will be required, and if the 24-hour urine protein is <1g, the enrollment will be allowed
14.Female subjects of childbearing potential (including subjects whose pregnancy cannot be ruled out by treatment with antineoplastic agents even if they have had amenorrhea for 12 months or longer) must have a negative serum pregnancy test within 7 days prior to receiving the first dose of study drugs. For female subjects of childbearing potential, and male subjects with partners of childbearing potential, they must agree to use at least one medically acceptable contraceptive measure (e.g. intra-uterine device, contraceptives or condoms) during the study period, and until at least 3 months after the last administration of serplulimab/placebo and bevacizumab, and at least 6 months after the last chemotherapy session (whichever occurs later).
15.Provide signed ICF and is willing to comply with all study procedures and rules as specified in the protocol.

排除标准：

1. 研究药物首次给药前 5 年内的其他活动性恶性肿瘤。已治愈的局限性肿瘤，如皮肤基底细胞癌、皮肤鳞状细胞癌、浅表性膀胱癌、前列腺原位癌、宫颈原位癌、乳腺癌原位癌等，可纳入本研究 2. 已确认 RAS野生型或MSI-H的CRC 3. 无组织病理学或影像学证实的转移的受试者 4. 存在中枢神经系统（CNS）或软脑膜转移 5. 在开始研究治疗之前6个月内接受过放疗;在开始研究治疗之前14天以前对骨病症进行的姑息放疗除外;不允许首次给药前28天内接受覆盖30%以上骨髓区域的放疗 6. 既往接受过针对EGFR或VEGF/血管内皮生长因子受体(VEGFR)靶点的靶向药物的术后辅助治疗(包括贝伐珠单抗、西妥昔单抗、帕尼单抗、阿柏西普、瑞戈非尼、或上述药物的生物类似药等) 7. 既往接受过任何T细胞共刺激或免疫检查点治疗，包括但不限于CTLA-4抑制剂、PD-1抑制剂PD-L1/2抑制剂或其他靶向T细胞的药物 8. 已知对任何单克隆抗体或研究药物辅料有严重过敏史8. 9. 通过适当干预后无法控制的胸腔积液、心包积液或需经常引流的腹水 10. 6个月内发生过脑血管意外、心肌梗塞、不稳定型心绞痛、心律失常控制不佳（包括男性QTc间期≥450毫秒，女性≥470毫秒）（QTc间期按Fridericia公式计算） 11. 纽约心脏协会（NYHA）超声心动图显示 III 级或 IV 级心功能不全或左心室射血分数（LVEF） < 50% 12. 有免疫缺陷病史，包括人类免疫缺陷病毒（HIV）抗体检测呈阳性，或其他获得性、先天性免疫缺陷病，或器官移植和同种异体骨髓移植史 13. 患有活动性肺结核 14. 有间质性肺炎、尘肺病、放射性肺炎、药物相关性肺炎、严重肺功能障碍或任何可能干扰可疑的药物相关性肺毒性的检测和处理的患者 15. 有活动性或自身免疫性疾病病史（例如间质性肺炎、结肠炎、肝炎、垂体炎、血管炎、肾炎、甲状腺功能亢进症、甲状腺功能减退症，包括但不限于这些疾病或综合征）。允许以下受试者：白癜风或康复的儿童哮喘/过敏患者，成年后无需任何干预;接受稳定剂量甲状腺替代激素治疗的自身免疫介导的甲状腺功能减退症患者;I型糖尿病患者接受稳定剂量的胰岛素治疗 16. 在研究药物首次给药前 28 天内接受过减毒活疫苗治疗 17. 需要连续使用（> 7 天）皮质类固醇（> 10 毫克/天的泼尼松或等效剂量的类似药物）或其他免疫抑制剂在研究药物首次给药前 14 天内或研究期间进行全身治疗。在没有活动性自身免疫性疾病的情况下，允许使用吸入或局部类固醇，以及肾上腺激素替代疗法，治疗剂量为≤ 10 mg/天泼尼松 18. 研究药物首次给药前 4 周内发生严重感染（CTCAE > 2 级），例如需要住院治疗的严重肺炎、菌血症和感染并发症;基线胸部影像学检查提示存在活动性肺部炎症伴相关临床症状或体征;研究药物首次给药前 2 周内的感染症状和体征，或需要口服或静脉注射抗生素治疗，预防性使用抗生素的情况除外 19. 在研究药物首次给药前 28 天内接受过大手术。本研究中的大手术被定义为需要至少 3 周恢复才能接受本研究治疗的手术 20. 之前接受过肠支架植入术，且至筛选期肠道支架仍未取出 21. 临床治疗后高血压仍未得到控制（定义为收缩压≥ 150 mmHg 和/或舒张压≥ 100 mmHg） 22. 有高血压危象或高血压性脑病病史 23. CT/MRI 图像显示肿瘤包裹或侵犯大血管腔（例如肺动脉或上腔静脉） 24. 随机分组前 1 个月内有严重/严重出血史，或在随机分组前 2 周内接受过输血。 25. 目前正在接受或已经接受过阿司匹林（> 325 毫克/天）或双嘧达莫、噻氯匹定、氯吡格雷和西洛他唑在研究药物首次给药前 7 天内。 26. 目前正在使用或研究药物首次用药之前7天内曾出于治疗目的使用全剂量口服或注射抗凝药物或溶栓药物。允许针对开放的静脉输液系统进行预防性抗凝治疗，只要在研究药物首次用药之前14天内药物活性使国际标准化比值(INR)<1.5x正常值上限ULN和部分凝血活酶时间(APTT)在正常范围内即可。允许预防性使用低分子量肝素(即，依诺肝素40mg/天) 27. 需要非甾体类抗炎药(NSAID)每日给药长期治疗。允许偶尔使用非甾体抗炎药来缓解医学症状，例如头痛或发热等 28. 有证据表明存在无法通过穿刺或近期外科手术解释的腹内积气 29. 存在严重、未愈合或裂开的伤口以及活动期溃疡或未经治疗的骨折 30. 研究药物首次给药前 6 个月内存在以下任何一种医疗状况： 1) 腹腔或气管食管瘘、胃肠道穿孔或腹腔内脓肿、研究者判断的大量腹水（定义为两周内需要引流或治疗的患者） 2) 肠梗阳和/或曾有胃肠道梗阴临床体征或症状，包括与原有疾病有关或需要常规肠外水化、肠外营养或管饲的不完全梗阻。既往如果有不完全梗阻/梗阻综合征/肠梗阻体征/症状的患者接受了治疗后症状改善，经研究者评估患者可入组研究 3) 根据研究者的判断，需要临床干预的严重、无法控制的腹腔内炎症 4) 主要血管疾病（例如，需要手术修复的主动脉瘤或与近期外周动脉血栓形成相关） 31. 已知有精神药物滥用或吸毒史 32. 正在参加其他临床研究，或计划开始本研究治疗距离前一项临床研究药物治疗结束时间不足14天 33. 妊娠期或哺乳期妇女(包括妊娠试验阴性但通过询问病史等发现有可能怀孕的受试者) 34. 经研究者判断，受试者有其他可能导致其被迫中途终止研究的因素，如患有其他严重疾病(含精神疾病)需要合并治疗，实验室检查值严重异常，家庭或社会因素，可能影响到受试者安全或试验资料收集的情况。

Exclusion criteria：

1.Other active malignancies within 5 years prior to the first dose of study drugs.Localized tumors that have been cured, such as basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, prostate carcinoma in situ, cervix carcinoma in situ, breast carcinoma in situ, etc., may be enrolled in this study 2.Have confirmed RAS-wild type or MSI-H CRC 3.Subjects without metastasis confirmed by histopathology or imaging 4.Presence of central nervous system (CNS) or leptomeningeal metastases 5.Have received radiotherapy within 6 months prior to the initiation of study treatment, except for palliative radiotherapy for bone disorders at least 14 days prior to initiation of study treatment; radiotherapy covering more than 30% of the bone marrow area within 28 days prior to the first dose is not allowed 6.Have received postoperative adjuvant therapy with targeted drugs targeting EGFR or VEGF/vascular endothelial growth factor receptor (VEGFR) (including bevacizumab, cetuximab,panitumumab, aflibercept, regorafenib, or biosimilars of the above drugs) 7,Have received treatment with any T-cell co-stimulation or immune checkpoint therapy, including but not limited to CTLA4 inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors, or other drugs targeting T cells 8.With a known history of severe allergy to any monoclonal antibody or excipients of the study drugs. 9.With uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage after appropriate intervention 10.Cerebrovascular accident, myocardial infarction, unstable angina, poorly controlled arrhythmia (including QTc interval >= 450 ms in males and >= 470 ms in females) within 6 months (QTc interval is calculated by Fridericia's formula) 11.New York Heart Association (NYHA) Class III or IV cardiac insufficiency, or left ventricular ejection fraction (LVEF) < 50% by echocardiography 12.With history of immunodeficiency, including positive human immunodeficiency virus (HIV) antibody test, or other acquired, congenital immunodeficiency disorders, or history of organ transplantation and allogeneic bone marrow transplantation 13.With active pulmonary tuberculosis 14.With a history of or current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, severe pulmonary dysfunction, or any condition that may interfere with the detection and management of suspected drug-related pulmonary toxicity 15.With active or a history of autoimmune diseases (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes). The following subjects are allowed: patients with vitiligo or recovered childhood asthma/allergy without need of any intervention in adulthood; patients with autoimmune-mediated hypothyroidism treated with a stable dose of thyroid replacement hormone; patients with type I diabetes mellitus on a stable dose of insulin 16.Have received treatment with live attenuated vaccine within 28 days prior to the first dose of study drugs 17.Requiring continuous use (> 7 days) of corticosteroids (> 10 mg/day of prednisone or an equivalent dose of a similar drug) or other immunosuppressive agents for systemic treatment within 14 days prior to the first dose of study drugs or during the study period. In the absence of active autoimmune diseases, the use of inhaled or topical steroids is permitted, as is adrenal hormone replacement therapy with a therapeutic dose of <= 10 mg/day prednisone 18.Severe infection (CTCAE Grade > 2) occurred within 4 weeks prior to the first dose of study drugs, such as severe pneumonia, bacteremia and infection complications requiring hospitalization; baseline chest imaging indicates the presence of active pulmonary inflammation with associated clinical symptoms or signs; symptoms and signs of infection within 2 weeks prior to the first dose of study drugs, or the need for treatment with oral or intravenous antibiotics, except in cases of prophylactic use of antibiotics 19.Have received major surgery within 28 days prior to the first dose of study drugs. A major surgery in this study is defined as a surgery requiring at least 3 weeks of recovery to be able to receive the treatment in this study 20.Previously received intestinal stent implantation, with the stent remaining in place at the screening period 21.Uncontrolled hypertension despite clinical treatment (defined as systolic blood pressure >= 150 mmHg and/or diastolic blood pressure >= 100 mmHg) 22.With a history of hypertensive crisis or hypertensive encephalopathy 23.CT/MRI images showing tumor encapsulating or invading a large vascular lumen (e.g., pulmonary artery or superior vena cava) 24.With a history of significant/severe hemorrhage within 1 month prior to randomization, or have received blood transfusion within 2 weeks prior to randomization. 25.Currently receiving or have received aspirin (> 325 mg/day) or dipyridamole, ticlopidine, clopidogrel, and cilostazol within 7 days prior to the first dose of study drugs. 26.Currently receiving or have received full-dose of anticoagulants or thrombolytic agents via oral or injection for therapeutic purposes within 7 days prior to the first dose of the study drugs. Prophylactic anticoagulation therapy for an open intravenous infusion system is permitted, provided that the drug activity keeps the international normalized ratio (INR) < 1.5 × ULN and activated partial thromboplastin time (APTT) is within normal range within 14 days prior to the first dose of study drugs. Prophylactic use of low molecular weight heparin (i.e., enoxaparin at 40 mg/day) is allowed 27. Requiring long-term treatment with daily administration of nonsteroidal anti-inflammatory drugs (NSAIDs). Occasional use of NSAIDs to relieve medical symptoms such as headache or pyrexia is allowed 28.With evidence showing the presence of meteorism that cannot be attributed to puncture or recent surgery 29.Presence of severe, unhealed or split wounds and active ulcers or untreated fractures 30.Presence of any of the following medical conditions within 6 months prior to the first dose of study drugs:Abdominal or tracheoesophageal fistula, gastrointestinal perforation or intra-abdominal abscess, massive ascites as judged by the investigator (defined as patients requiring drainage or treatment within two weeks);Intestinal obstruction and/or previous clinical signs or symptoms of gastrointestinal obstruction, including incomplete obstruction associated with a preexisting disease or requiring routine parenteral hydration, parenteral nutrition, or tube feeding. Patients with previous symptoms of incomplete obstruction/obstructive syndrome/signs/symptoms of intestinal obstruction that have improved after treatment may be enrolled in the study as assessed by the investigator;Severe, uncontrollable intra-abdominal inflammation requiring clinical intervention as judged by the investigator;Major vascular disease (e.g., aortic aneurysm requiring surgical repair or associated with recent peripheral artery thrombosis) 31.With a known history of psychotropic substance abuse or drug use 32.Participating in another clinical study, or have completed the treatment of another clinical study within 14 days before the planned study treatment in thisstudy 33.Pregnant or lactating women (including subjects with negative pregnancy test results who are found to be potentially pregnant through medical interview) 34.Any other factors that may lead to study discontinuation as assessed by the investigator, such as other severe diseases (including mental diseases) that require concomitant therapy, significant laboratory abnormalities, family or social factors, and other conditions possibly affecting the safety or study data collection of the subject.

研究实施时间：

Study execute time：

从 From 2025-04-01 00:00:00至 To 2026-10-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-05-01 00:00:00 至 To 2026-04-30 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	37
Group：	Experimental group	Sample size：	37
干预措施：	斯鲁利单抗联合贝伐珠单抗联合奥沙利铂和氟尿嘧啶类为基础的化疗(CapeOX/mFOLFOX6)	干预措施代码：
Intervention：	Serplulimab combined with bevacizumab plus oxaliplatin and fluorouracil-based chemotherapy (CapeOX/ mFOLFOX6).	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	北京市	市(区县)：
Country：	China	Province：	Beijing	City：
单位(医院)：	北京大学国际医院	单位级别：	三级
Institution hospital：	Peking University International Hospital	Level of the institution：	Tertiary

测量指标：

Outcomes：

指标中文名：	无进展生存期	指标类型：	主要指标
Outcome：	Progression free survival	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	客观缓解率	指标类型：	次要指标
Outcome：	Objective response 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：	总生存期	指标类型：	次要指标
Outcome：	Overall Survival	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	疾病控制率	指标类型：	次要指标
Outcome：	Disease Control 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：	不良事件	指标类型：	次要指标
Outcome：	Adverse Events	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：	无	组织：
Sample Name：	None	Tissue：
人体标本去向	其它	说明
Fate of sample：	0thers	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	18	岁 years
最大 Max age	75	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）：

无

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

None

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：
Blinding：
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）：	无
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	None
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：	CRF
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	CRF
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：	2025-04-30 16:36:01