注册号：
Registration number：
ChiCTR2600117863 最近更新日期：
Date of Last Refreshed on：
2026-01-29 14:49:54 注册时间：
Date of Registration：
2026-01-29 00:00:00 注册号状态：
预注册Registration Status：
Prospective registration注册题目：
SHR-4849注射液联合其他抗肿瘤药物在恶性实体瘤患者中的多中心、开放II期临床研究Public title：
Multicenter, open-access Phase II clinical study of SHR-4849 injection combined with other anti-tumor drugs in patients with malignant solid tumors注册题目简写：English Acronym：研究课题的正式科学名称：
SHR-4849注射液联合其他抗肿瘤药物在恶性实体瘤患者中的多中心、开放II期临床研究Scientific title：
Multicenter, open-access Phase II clinical study of SHR-4849 injection combined with other anti-tumor drugs in patients with malignant solid tumors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：
侯未
研究负责人：
于金明 Applicant：
Hou Wei
Study leader：
Yu Jinming 申请注册联系人电话：
Applicant telephone：
+86 180 3661 8327
研究负责人电话：
Study leader's telephone：
+86 531 6762 6971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：
wei.hou@hengrui.com
研究负责人电子邮件：
Study leader's E-mail：
sdyujinming@126.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(江苏)自由贸易试验区苏州片区苏州工业园区凤里街350号
研究负责人通讯地址：
山东省济南市槐荫区济兖路440号山东省肿瘤医院Applicant address：
No. 350, Fengli Street, Suzhou Industrial Park, Suzhou Area, China (Jiangsu) Pilot Free Trade Zone
Study leader's address：
No. 440, Jiyuan Road, Huaiyin District, Jinan City, Shandong Province, Shandong Cancer Hospital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：
江苏恒瑞医药股份有限公司Applicant's institution：
Jiangsu Hengrui Medicine Co., LTD研究负责人所在单位：
山东省肿瘤医院Affiliation of the Leader：
Shandong Cancer 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：
SDZLEC2025-246-03
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：
山东第一医科大学附属肿瘤医院伦理委员会Name of the ethic committee：
Ethics Committee of the Affiliated Cancer Hospital of Shandong First Medical University伦理委员会批准日期：
Date of approved by ethic committee：
2025-08-12 00:00:00伦理委员会联系人：
于金明Contact Name of the ethic committee：
Yu Jinming伦理委员会联系地址：
山东省济南市槐荫区济兖路440号Contact Address of the ethic committee：
No. 440, Jiyuan Road, Huaiyin District, Jinan City, Shandong Province伦理委员会联系人电话：
Contact phone of the ethic committee：
+86 531 6762 6929
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：
山东省肿瘤医院Primary sponsor：
Shandong Cancer Hospital研究实施负责（组长）单位地址：
山东省济南市槐荫区济兖路440号Primary sponsor's address：
No. 440, Jiyuan Road, Huaiyin District, Jinan City, Shandong Province试验主办单位(项目批准或申办者)：
Secondary sponsor：
国家：
中国
省(直辖市)：
江苏
市(区县)：
Country：
China
Province：
Jiangsu
City：
单位(医院)：
苏州盛迪亚生物医药有限公司
具体地址：
中国(江苏)自由贸易试验区苏州片区苏州工业园区凤里街350号
Institution
hospital：
Suzhou Shengdiya Biomedical Co., LTD
Address：
No. 350, Fengli Street, Suzhou Industrial Park, Suzhou Area, China (Jiangsu) Pilot Free Trade Zone经费或物资来源：
申办者Source(s) of funding：
sponsor研究疾病：
经组织学或细胞学证实的恶性实体瘤患者 Target disease：
Patients with malignant solid tumors confirmed by histology or cytology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：
II期临床试验 Study phase：
2研究设计：
单臂 Study design：
Single arm 研究目的：
第一阶段：剂量探索阶段
主要研究目的：
• 评估 SHR-4849 联合抗肿瘤药物在恶性实体瘤受试者中的安全性和耐受性，确定联合治疗的 II 期推荐剂量（RP2D）。
次要研究目的：
• 评估 SHR-4849 联合抗肿瘤药物在恶性实体瘤受试者中的初步有效性。
第二阶段：疗效拓展阶段
主要研究目的
• 评估 SHR-4849 联合抗肿瘤药物在恶性实体瘤受试者中的客观缓解率。
次要研究目的
• 评估 SHR-4849 联合抗肿瘤药物在恶性实体瘤受试者中的其他有效性终点；
• 评估SHR-4849 联合抗肿瘤药物在恶性实体瘤受试者中的安全性。 Objectives of Study：
Phase One: Dose Exploration Phase
Main research objectives:
To evaluate the safety and tolerability of SHR-4849 in combination with anti-tumor drugs in patients with malignant solid tumors, and to determine the recommended Phase II dose (RP2D) for the combination therapy.
Secondary research objectives:
To evaluate the preliminary efficacy of SHR-4849 in combination with anti-tumor drugs in subjects with malignant solid tumors.
Phase Two: The stage of expanding therapeutic effects
Main research purpose
To evaluate the objective response rate of SHR-4849 in combination with anti-tumor drugs in patients with malignant solid tumors.
Secondary research purpose
• Evaluate other efficacy endpoints of SHR-4849 in combination with anti-tumor drugs in subjects with malignant solid tumors;
To evaluate the safety of SHR-4849 in combination with anti-tumor drugs in patients with malignant solid tumors.药物成份或治疗方案详述：
Description for medicine or protocol of treatment in
detail：
纳入标准：
受试者必须符合以下所有标准才能进入本研究：
1. 自愿参加本临床研究，理解研究程序且能够书面签署知情同意书；
2. 年龄 18 周岁至75 周岁（含两端值），性别不限；
3. 经组织学或细胞学证实不可手术的实体瘤患者（具体如下）：
第一阶段：剂量探索阶段：
1）Part A/B/C/D/E：既往至少经过标准治疗后进展的复发或转移性小细胞肺癌、肺大细胞神经内分泌癌、其他神经内分泌癌患者。既往系统性化疗不超过 2 线。
2）Part F/G/H：既往仅经过 1 线标准治疗后进展的复发或转移性广泛期小细胞肺癌、肺大细胞神经内分泌癌、其他神经内分泌癌患者。接受过铂类化疗的患者要求末次铂类化疗至疾病出现进展的时间超过 90 天。
第二阶段：疗效拓展阶段
1) 小细胞肺癌（SCLC），队列 A1/B1/C1/D1/E1：既往经过≤2 线标准治疗后进展的复发或转移性小细胞肺癌患者。队列F1/G1/H1：既往经过≤1 线标准治疗后进展的复发或转移性广泛期小细胞肺癌，接受过铂类化疗的患者要求末次铂类化疗至疾病出现进展的时间超过 90 天。标准治疗中至少包括含铂和PD-1/PD-L1 抑制剂治疗（除外患者拒绝或者研究者判断不适合接受免疫治疗）。
2) 肺大细胞神经内分泌癌（LCNEC），队列 A2/B2/C2/D2/E2 要求既往经过≤2 线标准治疗后进展的复发或转移性肺 LCNEC 患者。队列 F2/G2/H2 既往经过≤1 线标准治疗后进展的复发或转移性肺 LCNEC 患者，接受过铂类化疗的患者要求末次铂类化疗至疾病出现进展的时间超过 90 天。标准治疗中至少包括含铂治疗方案。
3) 除外 SCLC 和肺 LCNEC 外其他神经内分泌癌：队列A3/B3/C3/D3/E3 要求既往经过≤2 线标准治疗后进展的复发或转移性其他神经内分泌癌患者；队列 F3/G3/H3 要求既往经过≤1 线标准治疗后进展的复发或转移性其他神经内分泌癌患者，接受过铂类化疗的患者要求末次铂类化疗至疾病出现进展的时间超过90 天。标准治疗中至少包括含铂治疗方案。
4) 其他晚期或转移性实体瘤：要求既往经过≤2 线标准治疗失败（仅适用队列 A4/B4/C4/D4/E4）。
4. 受试者需提供肿瘤组织样本进行 DLL3 表达检测。肿瘤组织样本要求为：中性福尔马林固定、石蜡包埋的 FFPE 组织块或至少 5 张未染色肿瘤组织切片，新鲜或存档样本均可，新鲜样本为优。对于无法提供满足上述要求肿瘤组织样本的受试者，需与申办方讨论后确认是否入组。
5. 根据实体瘤疗效评价标准（RECIST 1.1），具有至少一个靶病灶；
6. ECOG 体能状况评分 0 分或 1 分；
7. 预计生存时间 3 个月以上；
8. 有充足的骨髓及器官功能（开始研究治疗前 14 天内未使用任何血液成分和/或细胞生长因子）：
• 中性粒细胞计数（ANC）≥1.5×10^9/L（1,500/mm^3）；
• 血小板≥100×10^9/L（100,000/mm^3）；
• 血红蛋白（Hgb）≥9.0 g/dL（90 g/L）；
• 白蛋白≥3.0 g/dl（30 g/l）；
• 丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）≤ 3×ULN；
• 总胆红素≤1.5×ULN（确诊 Gilbert 综合征受试者，总胆红素≤ 3×ULN）；
• 脂肪酶≤1.5×ULN，淀粉酶≤1.5×ULN（若脂肪酶、淀粉酶> 1.5×ULN 但无临床或影像学证实胰腺炎的情况可以入组）；
• 肌酐清除率≥60 mL/min（根据 Cockcroft-Gault 公式计算）；
• 国际标准化比值（INR）和活化部分凝血活酶（APTT）时间≤1.5×ULN；
9. 有生育能力的女性受试者必须同意从签署知情同意书开始直到试验用药品末次给药后 8 个月内高效避孕且避免捐献卵子，首次给药前 7 天内血清妊娠检测须为阴性，且不在哺乳期；伴侣为有生育能力女性的男性受试者须同意从签署知情同意书开始直到试验
用药品末次给药后6 个月内高效避孕且避免捐献精子（详见第13.1节）。Inclusion criteria
Subjects must meet all of the following criteria to enter this study:
1. Voluntarily participate in this clinical study, understand the research procedures and be able to sign the informed consent form in person;
2. Age: 18 to 75 years old (inclusive), gender not limited.
3. Patients with solid tumors that have been histologically or cytologically confirmed as inoperable (as detailed below) :
Phase One: Dose Exploration Phase
Part A/B/C/D/E: Patients with recurrent or metastatic small cell lung cancer, large cell neuroendocrine carcinoma of the lung, or other neuroendocrine carcinomas who have progressed after at least standard treatment in the past. The previous systemic chemotherapy has not exceeded two lines.
2) Part F/G/H: Patients with relapsed or metastatic extensive-stage small cell lung cancer, large cell neuroendocrine carcinoma of the lung, and other neuroendocrine carcinomas who have progressed after only one line of standard treatment in the past. Patients who have received platinum-based chemotherapy are required to have more than 90 days from the last platinum-based chemotherapy to the onset of disease progression.
Phase Two: The stage of expanding therapeutic effects
Small cell lung cancer (SCLC), cohort A1/B1/C1/D1/E1: Patients with recurrent or metastatic small cell lung cancer who have progressed after <=2 lines of standard treatment. Cohort F1/G1/H1: Patients with relapsed or metastatic extensious-stage small cell lung cancer who have progressed after <=1 line of standard treatment and have received platinum-based chemotherapy are required to have a time from the last platinum-based chemotherapy to disease progression exceeding 90 days. The standard treatment should at least include platinum-containing and PD-1/PD-L1 inhibitor therapy (except when the patient refuses or the researcher determines that they are not suitable for immunotherapy).
2) Large cell neuroendocrine carcinoma of the lung (LCNEC), cohort A2/B2/C2/D2/E2 requires patients with recurrent or metastatic LCNEC of the lung who have progressed after ≤2 lines of standard treatment. Cohort F2/G2/H2 patients with recurrent or metastatic lung LCNEC who had progressed after <=1 line of standard treatment were required to have a time from the last platinum-based chemotherapy to disease progression exceeding 90 days. Standard treatment should at least include platinum-based treatment regimens.
3) Excluding SCLC and lung LCNEC, other neuroendocrine carcinomas: Cohort A3/B3/C3/D3/E3 requires patients with recurrent or metastatic other neuroendocrine carcinomas who have progressed after <=2 lines of standard treatment in the past; Cohort F3/G3/H3 requires patients with recurrent or metastatic other neuroendocrine carcinomas who have progressed after <=1 line of standard treatment in the past. For patients who have received platinum-based chemotherapy, the time from the last platinum-based chemotherapy to disease progression should exceed 90 days. Standard treatment should at least include platinum-based treatment regimens.
4) Other advanced or metastatic solid tumors: Previous failure of <=2 lines of standard treatment is required (only applicable to cohort A4/B4/C4/D4/E4).
4. The subjects are required to provide tumor tissue samples for DLL3 expression detection. The requirements for tumor tissue samples are as follows: neutral formalin-fixed and paraffin-embedded FFPE tissue blocks or at least 5 unstained tumor tissue sections. Both fresh and archived samples are acceptable, with fresh samples being preferred. For subjects who are unable to provide tumor tissue samples that meet the above requirements, it is necessary to discuss with the sponsor to confirm whether they can be enrolled.
5. According to the efficacy evaluation criteria for solid tumors (RECIST 1.1), there is at least one target lesion;
6. ECOG physical condition score: 0 or 1 point;
7. The expected survival time is more than three months;
8. Have adequate bone marrow and organ function (no blood components and/or cell growth factors have been used within 14 days prior to the start of the study treatment) :
• Neutrophil count (ANC) >=1.5×109/L (1,500/mm^3);
Platelet count >=100×10^9/L (100,000/mm^3);
Hemoglobin (Hgb) >=9.0 g/dL (90 g/L);
Albumin >=3.0 g/dl (30 g/l);
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3×ULN;
• Total bilirubin <=1.5×ULN (for subjects diagnosed with Gilbert syndrome, total bilirubin <= 3×ULN);
• Lipase <=1.5×ULN, amylase <=1.5×ULN (if lipase and amylase > 1.5×ULN but there is no clinical or imaging confirmation of pancreatitis, they can be enrolled);
• Creatinine clearance rate >=60 mL/min (calculated according to the Cockcroft-Gault formula);
• International normalized ratio (INR) and activated partial thromboplastin (APTT) time <=1.5×ULN;
9. Fertile female subjects must agree to achieve efficient contraception and avoid egg donation from the date of signing the informed consent form until 8 months after the last administration of the investigational drug. The serum pregnancy test must be negative within 7 days before the first administration, and they must not be in the lactation period. Male subjects whose partners are fertile women must agree from the signing of the informed consent form until the trial
Use highly effective contraception within 6 months after the last administration of the drug and avoid sperm donation (see Section 13.1 for details).排除标准：
受试者若符合下列标准中的任意一条，将不能进入本研究：
1. 混合性的神经内分泌癌、复合性小细胞肺癌（除外小细胞肺癌复合大细胞神经内分泌癌）
2. 伴有未经局部治疗（放疗或手术）或活动性中枢神经系统（CNS）肿瘤转移。有脑膜转移病史或当前有脑膜转移的受试者。
- 对于 CNS 转移受试者，如果 CNS 肿瘤已接受过充分的局部治疗（手术或放疗）；局部治疗结束至筛选期影像学检查未发现进展；受试者的神经系统症状能够在首次用药前至少稳定 2 周，且不需要糖皮质激素治疗或者接受≤10 mg/天的泼尼松（或等价激素）；则可以参加研究；
3. 首次使用研究药物前五年内患有其他恶性肿瘤，除外充分治疗的宫颈原位癌、基底细胞或鳞状上皮细胞皮肤癌、根治术后的局部前列腺癌、根治术后的导管原位癌、根治术后的甲状腺乳头状癌；
4. 由研究者判断的伴有无法控制的肿瘤相关疼痛者。需要止痛药物治疗的受试者必须在进入研究时已经有稳定的止痛治疗方案；适合姑息放疗的症状性病灶应该在进入研究前完成治疗；
5. 有严重的心脑血管疾病，包括但不限于：
• 首次使用研究药物前6 个月内严重的心脏节律或传导异常，如需要临床干预的室性心律失常、II-III 度房室传导阻滞等；
• 首次使用研究药物前6 个月内发生过急性冠脉综合征、充血性心力衰竭（美国纽约心脏病协会（NYHA）心功能分级≥II 级）、主动脉夹层；
• 首次使用研究药物前6 个月发生过动静脉血栓事件，如脑血管意外（短暂性脑缺血发作，脑出血，脑卒中），深静脉血栓及肺栓塞等；
• 首次使用研究药物前28 天内左室射血分数（LVEF）< 50％；
• 静息状态下，基线 12 导联心电图检查得出的平均 QTcF> 470 ms（女性）或者 QTcF> 450 ms（男性）；
6. 首次研究用药前 3 个月内出现过显著临床意义的出血症状，首次研究用药前 1 个月内存在明显的咯鲜血，每次咯血量≥2.5ml；
7. 首次研究用药 2 周内存在无法控制的胸腔积液、腹腔积液或心包积液，需要反复引流；
8. 既往治疗期间发生过间质性肺炎；患有特发性肺纤维化病史、机化性肺炎（如闭塞性细支气管炎）、药物诱导的肺炎、放射性肺炎（除外放射区仅存在放射性纤维化且无需类固醇治疗的受试者）等间质性肺炎病史；目前需要类固醇治疗的非感染性肺部炎症；筛选期影像显示已知或可疑有间质性肺炎的患者；首次给药前三个月内合并其他严重影响呼吸功能的中重度肺部疾病（包括但不限于呼吸衰竭、严重慢性阻塞性肺疾病、肺功能严重通气功能/弥散功能异常）。
9. 在开始研究治疗之前 4 周内有重度感染，包括但不限于菌血症、重症肺炎或其他需要住院治疗的严重感染并发症等；在首次给药前 2 周内存在需要使用系统抗生素治疗的 CTCAE ≥ 2 级的活动性感染；
10. 有免疫缺陷病史，包括 HIV 检测阳性；存在活动性乙型肝炎（HBsAg 阳性者HBV DNA 高于所在研究中心正常值上限，若该中心无正常值上限，则 HBV-DNA 定量须小于 1000 拷贝数/ml 或500 IU/ml）或丙型肝炎（抗-HCV 阳性且 HCV RNA 高于分析方法检测下限）；
11. 通过病史或影像检查发现入组前 1 年内有活动性肺结核感染者，或者超过 1 年以前有活动性肺结核感染病史但未经正规治疗者；
12. 既往针对肿瘤治疗的不良反应尚未恢复到 CTCAE ≤ 1 级（脱发、2 级外周神经毒性，达到入组标准中的数值要求或其他经研究者判定不影响研究药物治疗的情况除外）；
13. 既往接受免疫检查点抑制剂治疗，符合以下任一条件者：1）受试者出现过导致免疫治疗永久停药的免疫相关不良反应；2)受试者出现过任何严重或危及生命的免疫相关不良反应； 3)受试者出现过 2 级及以上级别免疫性肺炎、肌炎、心肌炎、或神经免疫相关不良反应；
14. 既往治疗洗脱未满足如下要求：首次使用研究药物前 4 周内接受过化疗、生物治疗、靶向治疗、免疫治疗、或其他未上市的临床研究药物治疗等抗肿瘤治疗（不包括需要接受激素剥夺疗法的激素难治性前列腺癌或者乳腺癌）；除外
-小分子靶向药物为首次使用研究药物前2 周或药物的5 个半衰期内（以时间短的为准）；
-首次使用研究药物前 2 周内接受过有抗肿瘤适应症的中药
15. 既往使用过 DLL3 抗体偶联药物（ADC）、或使用过成分中含拓扑异构酶 I 抑制剂的 ADC 治疗。
16. 既往使用过 CTLA-4 抑制剂药物治疗（仅限 Part B/D/G）；
17. 首次使用研究药物前 24 周内接受>30 Gy 的胸部放射治疗者，首次用药前 4 周内接受>30 Gy 的非胸部放射治疗者（在首次用药前14 天已完成脑转移放射治疗的受试者可以入组），以及首次用药前 14 天内接受≤30 Gy 的姑息性放射的受试者。
18. 在首次使用研究药物前 4 周内接受过重要脏器的外科手术（不包括穿刺活检）、出现过显著外伤或需要在试验期间接受择期手术；
19. 活动性、已知或怀疑自身免疫性疾病及自身免疫性疾病病史，包括但不仅限于重症肌无力、自身免疫性肝炎、系统性红斑狼疮类风湿性关节炎、炎性肠病等。允许 I 型糖尿病（通过胰岛素治疗血糖得以控制）、仅需要激素替代疗法治疗的因自身免疫性甲状腺炎导致的残留甲状腺功能减退，或缺乏外因刺激的情况下预期不会复发的情况可以入组；患有湿疹、牛皮癣、慢性单纯性苔藓或仅有白癜风皮肤病表现的患者（需排除银屑病性关节炎）如果皮疹覆盖面积小于体表面积 10%，基线时疾病已充分控制且仅需要低效价的局部类固醇治疗，过去 12 个月内基础疾病未出现急性加重（不需要补骨脂素加紫外线辐射[PUVA]、氨甲喋呤、类视黄醇、生物制剂、口服钙调磷酸酶抑制剂、高效价或口服类固醇）则可以进入研究；
20. 首次研究用药前 14 天内接受过系统性免疫抑制剂治疗（包括但不局限于糖皮质激素、环磷酰胺、硫唑嘌呤、甲氨蝶呤、沙利度胺和抗肿瘤坏死因子[抗-TNF]药物等）者；
- 对于接受短期使用皮质类固醇针对恶心、呕吐或过敏反应管理或预防用药），可以参与本项研究。
- 允许使用吸入或者局部使用皮质类固醇，以及剂量≤10 mg/天泼尼松疗效剂量的肾上腺激素替代疗法。
21. 首次使用研究药物前 28 天内使用减毒活疫苗，或预计研究治疗期间需要使用减毒活疫苗
22. 妊娠期、哺乳期女性或计划在研究期间至末次使用试验用药品后 8个月内生育的受试者；
23. 已知对 SHR-4849、SHR-1316、卡铂、顺铂、SHR-8068、BP102 产品的任何成分或辅料过敏者；或对其他单克隆抗体/融合蛋白类药物发生过重度过敏反应史；
24. 经研究者判断，受试者有其他可能影响研究结果或导致本研究被迫中途终止的因素，如酗酒、药物滥用、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、家庭或社会因素及其他可能影响到受试者安全或试验资料收集的情况等。 对于参加 Part C/D/E/H 受试者需要同时不符合下列补充标准：
25. 有高血压，且经降压药物治疗无法获得良好控制（收缩压≥140 mmHg 或者舒张压≥ 90 mmHg ）；既往曾出现高血压危象或高血压性脑病。
26. 首次用药前7 天内的24h 蛋白尿定量≥1g(筛选期的尿常规如显示尿白蛋白≥2+，需额外检测 24 小时尿蛋白定量);
27. 存在出血风险、凝血功能障碍、或血栓倾向。
首次用药前7 天内使用过或者需要长期使用阿司匹林、氯吡格雷、替格瑞洛、双嘧达莫、噻氯匹定、西洛他唑等抑制血小板功能的药物治疗；
首次用药前 7 天内出于治疗目的使用抗凝治疗或者溶栓治疗 [允许针对开放的静脉输液系统进行预防性抗凝治疗，允许预防性使用低分子量肝素（ 如依诺肝素钠 40 mg/d））]。
CT/MRI 提示肿瘤包绕或侵犯大血管或经研究者判断患者肿瘤在治疗期间有极高可能侵袭重要血管而引起大出血的情况。
在首次用药前 6 个月内出现过胃肠道出血（包括呕血、黑便、血便等，如确认为痔疮出血或仅表现为大便潜血阳性可以入组）、气管-食管瘘、胃肠穿孔、胃肠瘘及腹腔脓肿；处于活动期的消化性溃疡；筛选时临床症状或体征提示患有肠梗阻。
在首次用药前 6 个月内出现过 CTCAE ≥ 3 级或 3 个月内曾出现 CTCAE ≥ 2 级的胃肠道以外的出血（如异常阴道出血等）；
首次用药前 6 个月内患有重要血管疾病(包括但不限于需要手术干预的血管瘤等) 、血栓性疾病史。
首次用药前 7 天内接受过穿刺活检或其他小手术(不包括血管通路装置的置入); 具有严重、未愈合的伤口，活动性溃疡或未经治疗的骨折。
28. 既往使用过 VEGF/VEGFR 抑制剂等抗血管生成药物治疗，包括但不限于贝伐珠单抗、重组人血管内皮抑制素、阿帕替尼、安罗替尼、呋喹替尼等。Exclusion criteria：
Subjects who meet any of the following criteria will not be allowed to enter this study:
1. Mixed neuroendocrine carcinoma and complex small cell lung cancer (excluding small cell lung cancer combined with large cell neuroendocrine carcinoma)
2. Accompanied by metastasis of tumors in the central nervous system (CNS) that have not received local treatment (radiotherapy or surgery) or are active. Subjects with a history of meningeal metastasis or those currently having meningeal metastasis.
For subjects with CNS metastases, if the CNS tumor has received adequate local treatment (surgery or radiotherapy); No progression was found in imaging examinations from the end of local treatment to the screening period. The neurological symptoms of the subjects could stabilize for at least 2 weeks before the first administration, and no glucocorticoid treatment or prednisone (or equivalent hormone) of <=10 mg/ day was required. Then one can participate in the research;
3. Having suffered from other malignant tumors within five years prior to the first use of the study drug, excluding fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical resection, ductal carcinoma in situ after radical resection, and papillary thyroid carcinoma after radical resection;
4. Those with uncontrollable tumor-related pain as determined by the researcher. Subjects who need pain-relieving drug treatment must have a stable pain-relieving treatment plan at the time of entering the study. Symptomatic lesions suitable for palliative radiotherapy should be treated before entering the study.
5. Have severe cardiovascular and cerebrovascular diseases, including but not limited to:
• Severe cardiac rhythm or conduction abnormalities within 6 months prior to the first use of the study drug, such as ventricular arrhythmias requiring clinical intervention, II-III degree atrioventricular block, etc.
• Acute coronary syndrome, congestive heart failure (New York Heart Association (NYHA) cardiac function classification ≥ grade II), and aortic dissection occurred within 6 months prior to the first use of the study drug;
• There have been arteriovenous thrombotic events such as cerebrovascular accidents (transient ischemic attack, cerebral hemorrhage, stroke), deep vein thrombosis and pulmonary embolism, etc. within 6 months before the first use of the study drug;
• Left ventricular ejection fraction (LVEF) < 50% within 28 days prior to the first use of the study drug;
At rest, the average QTcF obtained from baseline 12-lead electrocardiogram examination is > 470 ms (for females) or > 450 ms (for males);
6. Significant clinically significant bleeding symptoms occurred within 3 months before the first study of medication, and there was obvious hemoptysis within 1 month before the first study of medication, with each hemoptysis volume >=2.5ml.
7. In the first study, there was uncontrollable pleural effusion, peritoneal effusion or pericardial effusion within 2 weeks of medication, and repeated drainage was required;
8. Interstitial pneumonia occurred during previous treatment; A history of interstitial pneumonia such as idiopathic pulmonary fibrosis, organized pneumonia (such as oblusive bronchiolitis), drug-induced pneumonia, and radiation pneumonitis (excluding subjects with only radiation fibrosis in the radiation area and without steroid treatment); Non-infectious pulmonary inflammation that currently requires steroid treatment; Screening period imaging shows patients with known or suspected interstitial pneumonia; Within three months prior to the first administration, there are other moderate to severe pulmonary diseases that seriously affect respiratory function (including but not limited to respiratory failure, severe chronic obstructive pulmonary disease, and severe pulmonary function with abnormal ventilation function/diffusion function).
9. There was a severe infection within 4 weeks before the start of the study treatment, including but not limited to bacteremia, severe pneumonia or other serious infectious complications that require hospitalization, etc. There is an active infection of CTCAE grade >= 2 that requires systemic antibiotic treatment within 2 weeks before the first administration.
10. Have a history of immune deficiency, including a positive HIV test; There is active hepatitis B (HBV DNA in HBsag-positive individuals is higher than the upper limit of the normal value at the research center where they are located. If there is no upper limit of the normal value at the center, Then the quantification of HBV-DNA must be less than 1000 copies /ml or 500 IU/ml) or hepatitis C (anti-HCV positive and HCV RNA higher than the detection limit of the analytical method);
11. Those who were found to have had active pulmonary tuberculosis infection within one year before enrollment through medical history or imaging examination, or those who had a history of active pulmonary tuberculosis infection more than one year ago but have not received regular treatment;
12. Previous adverse reactions to tumor treatment have not yet recovered to CTCAE <= grade 1 (except for alopecia, grade 2 peripheral neurotoxicity, meeting the numerical requirements in the inclusion criteria or other situations determined by the investigator that do not affect the treatment of the study drug);
13. Those who have previously received treatment with immune checkpoint inhibitors and meet any of the following conditions: 1) The subject has experienced immune-related adverse reactions that led to permanent discontinuation of immunotherapy; 2) The subject has experienced any serious or life-threatening immune-related adverse reactions; 3) The subject has experienced grade 2 or above immune pneumonia, myositis, myocarditis, or neuroimmune-related adverse reactions;
14. Previous treatment elution did not meet the following requirements: having received anti-tumor treatments such as chemotherapy, biological therapy, targeted therapy, immunotherapy, or other unmarketed clinical research drugs within 4 weeks before the first use of the study drug (excluding hormone-refractory prostate cancer or breast cancer that requires hormone deprivation therapy); Except
For small molecule targeted drugs, it is within two weeks before the first use of the study drug or within five half-lives of the drug (whichever is shorter).
- Had received traditional Chinese medicine with anti-tumor indications within two weeks before the first use of the study drug
15. Previous use of DLL3 antibody-drug conjugates (ADCs), or treatment with ADCs containing topoisomerase I inhibitors.
16. Previously treated with CTLA-4 inhibitor drugs (only Part B/D/G);
17. Those who received thoracic radiotherapy with a dose of >30 Gy within 24 weeks before the first use of the study drug, and those who received non-thoracic radiotherapy with a dose of >30 Gy within 4 weeks before the first use of the study drug (subjects who had completed radiotherapy for brain metastases 14 days before the first use of the study drug could be enrolled) And subjects who received palliative radiation of <=30 Gy within 14 days before the first administration.
18. Having undergone surgery on important organs (excluding biopsy), experienced significant trauma or required elective surgery during the trial period within 4 weeks prior to the first use of the study drug;
19. Active, known or suspected autoimmune diseases and a history of autoimmune diseases, including but not limited to myasthenia gravis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, etc. Type 1 diabetes (with blood sugar controlled through insulin treatment), residual hypothyroidism caused by autoimmune thyroiditis treated only with hormone replacement therapy, or those expected not to recur in the absence of external stimuli can be enrolled. Patients with eczema, psoriasis, chronic lichenoid simplex or only vitiligo skin disease manifestations (excluding psoriatic arthritis), if the rash covers an area less than 10% of the body surface area, the disease is well controlled at baseline and only low-potency local steroid treatment is required, If there has been no acute exacerbation of underlying diseases within the past 12 months (without the need for psoralen plus ultraviolet radiation [PUVA], methotrexate, retinoids, biological agents, oral calcineurin inhibitors, high-titer or oral steroids), the study can be conducted.
20. Those who received systemic immunosuppressant therapy (including but not limited to glucocorticoids, cyclophosphamide, azathioprine, methotrexate, thalidomide and anti-tumor necrosis factor [anti-TNF] drugs, etc.) within 14 days before the first study administration;
Those who have received short-term use of corticosteroids for the management or prevention of nausea, vomiting or allergic reactions can participate in this study.
The use of inhaled or topical corticosteroids, as well as adrenal hormone replacement therapy with a dose of no more than 10 mg/ day at the therapeutic dose of prednisone, is permitted.
21. Live attenuated vaccine was used within 28 days before the first use of the study drug, or it is expected that live attenuated vaccine will be needed during the study treatment period
22. Pregnant or lactating women, or subjects who plan to give birth within 8 months after the last use of the investigational drug during the study period;
23. Those who are known to be allergic to any component or excipient of products such as SHR-4849, SHR-1316, carboplatin, cisplatin, SHR-8068, and BP102; Or a history of severe allergic reactions to other monoclonal antibody/fusion protein drugs;
24. As determined by the researchers, the subjects have other factors that may affect the research results or lead to the forced termination of this study, such as alcohol abuse, drug abuse, suffering from other serious diseases (including mental disorders) requiring concurrent treatment, severely abnormal laboratory test values, family or social factors, and other circumstances that may affect the safety of the subjects or the collection of experimental data, etc. For the subjects participating in Part C/D/E/H, the following supplementary criteria must not be met simultaneously:
25. Have hypertension that cannot be well controlled after antihypertensive drug treatment (systolic blood pressure ≥140 mmHg or diastolic blood pressure >= 90 mmHg); There has been a history of hypertensive crisis or hypertensive encephalopathy.
26. The 24-hour proteinuria quantification within 7 days before the first administration is >=1g(if the urine routine during the screening period shows urine albumin >=2+, an additional 24-hour urine protein quantification test is required).
27. There is a risk of bleeding, coagulation dysfunction, or a tendency towards thrombosis.
Youdaoplaceholder0 Has been used within 7 days before the first administration or requires long-term use of drugs that inhibit platelet function, such as aspirin, clopidogrel, ticagrelor, dipyridamole, ticlopidine, cilostazole, etc.
Use of anticoagulant therapy or thrombolytic therapy for therapeutic purposes within 7 days prior to the first administration [prophylactic anticoagulant therapy for open intravenous infusion systems is permitted, and prophylactic use of low molecular weight heparin (such as enoxaparin sodium 40 mg/d) is permitted)].
The situation where a CT/MRI indicates that the tumor surrounds or invades major blood vessels, or where the researcher determines that the patient's tumor has a very high possibility of invading important blood vessels during treatment and causing massive hemorrhage.
The patient has experienced gastrointestinal bleeding (including hematemesis, melena, bloody stool, etc. If it is confirmed to be hemorrhoid bleeding or only shows positive fecal occult blood, they can be included in the group), tracheoesophageal fistula, gastrointestinal perforation, gastrointestinal fistula and abdominal abscess within 6 months before the first administration of the drug. Peptic ulcer in the active stage; Clinical symptoms or signs during screening suggest intestinal obstruction.
Youdaoplaceholder0 Has had CTCAE grade >= 3 or CTCAE grade >= 2 bleeding outside the gastrointestinal tract (such as abnormal vaginal bleeding, etc.) within 6 months prior to the first administration of the drug;
If the patient has a history of significant vascular diseases (including but not limited to hemangiomas requiring surgical intervention) or thrombotic diseases within 6 months prior to the first administration of the drug.
Has undergone a puncture biopsy or other minor surgery (excluding the implantation of vascular access devices) within 7 days prior to the first administration of the drug; Having severe, unhealed wounds, active ulcers or untreated fractures.
28. Previously treated with anti-angiogenic drugs such as VEGF/VEGFR inhibitors, including but not limited to bevacizumab, recombinant human endostatin, apatinib, anlotinib, fruquintinib, etc.研究实施时间：
Study execute time：
从
From
2026-01-20 00:00:00至
To
2030-01-20 00:00:00
征募观察对象时间：
Recruiting time：
从
From
2026-02-01 00:00:00
至
To
2028-02-01 00:00:00干预措施：
Interventions：
组别：
Part A
样本量：
15
Group：
Part A
Sample size：
干预措施：
SHR-4849 联合SHR-1316
干预措施代码：
Part A
Intervention：
SHR-4849 combined with SHR-1316
Intervention code：
组别：
Part B
样本量：
15
Group：
Part B
Sample size：
干预措施：
SHR-4849 联合SHR-1316 和 SHR-8068
干预措施代码：
Part B
Intervention：
SHR-4849 combined with SHR-1316 and SHR-8068
Intervention code：
组别：
Part C
样本量：
15
Group：
Part C
Sample size：
干预措施：
SHR-4849 联合 SHR-1316 和 BP102
干预措施代码：
Part C
Intervention：
SHR-4849 in combination with SHR-1316 and BP102
Intervention code：
组别：
Part D
样本量：
15
Group：
Part D
Sample size：
干预措施：
SHR-4849 联合 SHR-1316、BP102 和 SHR-8068
干预措施代码：
Part D
Intervention：
SHR-4849 in combination with SHR-1316, BP102 and SHR-8068
Intervention code：
组别：
Part E
样本量：
15
Group：
Part E
Sample size：
干预措施：
SHR-4849 联合 BP102
干预措施代码：
Part E
Intervention：
SHR-4849 combined with BP102
Intervention code：
组别：
Part F
样本量：
15
Group：
Part F
Sample size：
干预措施：
SHR-4849 联合SHR-1316 和卡铂或顺铂
干预措施代码：
Part F
Intervention：
SHR-4849 combined with SHR-1316 and carboplatin or cisplatin
Intervention code：
组别：
Part G
样本量：
15
Group：
Part G
Sample size：
干预措施：
SHR-4849 联合 SHR-1316、卡铂或顺铂和 SHR-8068
干预措施代码：
Part G
Intervention：
SHR-4849 combined with SHR-1316, carboplatin or cisplatin and SHR-8068
Intervention code：
组别：
Part H
样本量：
15
Group：
Part H
Sample size：
干预措施：
SHR-4849 联合 SHR-1316、卡铂或顺铂和 BP102
干预措施代码：
Part H
Intervention：
SHR-4849 combined with SHR-1316, carboplatin or cisplatin and BP102
Intervention code：研究实施地点：
Countries of recruitment and research settings：
国家：
中国
省(直辖市)：
山东
市(区县)：
Country：
China
Province：
Shandong
City：
单位(医院)：
山东第一医科大学附属肿瘤医院（山东省肿瘤防治研究院、山东省肿瘤医院）
单位级别：
三甲
Institution
hospital：
Shandong First Medical University Affiliated Cancer Hospital (Shandong Provincial Institute of Cancer Prevention and Treatment, Shandong Provincial Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
上海
市(区县)：
Country：
China
Province：
Shanghai
City：
单位(医院)：
上海市东方医院
单位级别：
三甲
Institution
hospital：
Shanghai East Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
上海市
市(区县)：
Country：
China
Province：
Shanghai
City：
单位(医院)：
上海交通大学医学院附属仁济医院
单位级别：
三甲
Institution
hospital：
Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
上海
市(区县)：
Country：
China
Province：
Shanghai
City：
单位(医院)：
上海市胸科医院
单位级别：
三甲
Institution
hospital：
Shanghai Chest Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
浙江
市(区县)：
Country：
China
Province：
Zhejiang
City：
单位(医院)：
浙江省肿瘤医院
单位级别：
三甲
Institution
hospital：
Zhejiang Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
河南
市(区县)：
Country：
China
Province：
Henan
City：
单位(医院)：
河南省肿瘤医院
单位级别：
三甲
Institution
hospital：
Henan Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
山西
市(区县)：
Country：
China
Province：
Shanxi
City：
单位(医院)：
山西省肿瘤医院
单位级别：
三甲
Institution
hospital：
Shanxi Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
黑龙江
市(区县)：
Country：
China
Province：
Heilongjiang
City：
单位(医院)：
哈尔滨医科大学附属肿瘤医院
单位级别：
三甲
Institution
hospital：
Harbin Medical University Affiliated Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
湖南
市(区县)：
Country：
China
Province：
Hunan
City：
单位(医院)：
湖南省肿瘤医院
单位级别：
三甲
Institution
hospital：
Hunan Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
福建
市(区县)：
Country：
China
Province：
Fujian
City：
单位(医院)：
福建省肿瘤医院
单位级别：
三甲
Institution
hospital：
Fujian Provincial Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
江西
市(区县)：
Country：
China
Province：
Jiangxi
City：
单位(医院)：
南昌大学第一附属医院
单位级别：
三甲
Institution
hospital：
The First Affiliated Hospital of Nanchang University
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
上海
市(区县)：
Country：
China
Province：
Shanghai
City：
单位(医院)：
上海市肺科医院
单位级别：
三甲
Institution
hospital：
Shanghai Pulmonary Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
陕西
市(区县)：
Country：
China
Province：
Shanxi
City：
单位(医院)：
西安交通大学第一附属医院
单位级别：
三甲
Institution
hospital：
The First Affiliated Hospital of Xi 'an Jiaotong University
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
云南
市(区县)：
Country：
China
Province：
Yunnan
City：
单位(医院)：
云南省肿瘤医院
单位级别：
三甲
Institution
hospital：
Yunnan Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
江苏
市(区县)：
Country：
China
Province：
Jiangsu
City：
单位(医院)：
江苏省人民医院
单位级别：
三甲
Institution
hospital：
Jiangsu Province Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
安徽
市(区县)：
Country：
China
Province：
Anhui
City：
单位(医院)：
中国科学技术大学附属第一医院
单位级别：
三甲
Institution
hospital：
The First Affiliated Hospital of University of Science and Technology of China
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
安徽
市(区县)：
Country：
China
Province：
Anhui
City：
单位(医院)：
安徽省胸科医院
单位级别：
三甲
Institution
hospital：
Anhui Provincial Chest Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
河南
市(区县)：
Country：
China
Province：
Henan
City：
单位(医院)：
郑州大学第一附属医院
单位级别：
三甲
Institution
hospital：
First Affiliated Hospital of Zhengzhou University
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
江苏
市(区县)：
Country：
China
Province：
Jiangsu
City：
单位(医院)：
江苏省肿瘤医院
单位级别：
三甲
Institution
hospital：
Jiangsu Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
辽宁
市(区县)：
Country：
China
Province：
Liaoning
City：
单位(医院)：
辽宁省肿瘤医院
单位级别：
三甲
Institution
hospital：
Liaoning Cancer Hospital and Institute
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
天津
市(区县)：
Country：
China
Province：
Tianjin
City：
单位(医院)：
天津市肿瘤医院
单位级别：
三甲
Institution
hospital：
Tianjin Medical University Cancer Institute and Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
广东
市(区县)：
Country：
China
Province：
Guangdong
City：
单位(医院)：
中山大学附属第一医院
单位级别：
三甲
Institution
hospital：
Sun Yat-sen University First Affiliated Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
上海
市(区县)：
Country：
China
Province：
Shanghai
City：
单位(医院)：
复旦大学附属肿瘤医院
单位级别：
三甲
Institution
hospital：
Shanghai Cancer Center
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
吉林
市(区县)：
Country：
China
Province：
Jilin
City：
单位(医院)：
吉林省肿瘤医院
单位级别：
三甲
Institution
hospital：
Jilin Provincial Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
湖北
市(区县)：
Country：
China
Province：
Hubei
City：
单位(医院)：
华中科技大学同济医学院附属同济医院
单位级别：
三甲
Institution
hospital：
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
吉林
市(区县)：
Country：
China
Province：
Jilin
City：
单位(医院)：
吉林大学第一医院
单位级别：
三甲
Institution
hospital：
The First Hospital of Jilin University
Level of the institution：
Tertiary A测量指标：
Outcomes：
指标中文名：
剂量限制性毒性（DLT）发生率，不良事件（AE）/严重不良事件 （SAE）的发生率及严重程度（基于 CTCAE v5.0 进行评级）
指标类型：
主要指标
Outcome：
Incidence of dose-limiting toxicity (DLT), incidence and severity of adverse events (AE)/serious adverse events (SAE) (rated based on CTCAE v5.0)
Type：
Primary indicator
测量时间点：
测量方法：
Measure time point of outcome：
Measure method：
指标中文名：
研究者评估的客观缓解率
指标类型：
次要指标
Outcome：
The objective response rate evaluated by the researchers
Type：
Secondary indicator
测量时间点：
测量方法：
Measure time point of outcome：
Measure method：
指标中文名：
客观肿瘤响应持续时间
指标类型：
次要指标
Outcome：
Objective duration of tumor response
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：
无进展生存期
指标类型：
次要指标
Outcome：
progression free 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：
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：
PK 指标：SHR-4849 毒素结合抗体和游离毒素的浓度
指标类型：
附加指标
Outcome：
PK index: The concentration of SHR-4849 toxin-binding antibody and free toxin
Type：
Additional indicator
测量时间点：
测量方法：
Measure time point of outcome：
Measure method：
指标中文名：
免疫原性指标：抗 SHR-4849 抗体
指标类型：
附加指标
Outcome：
Immunogenicity index: Anti-SHR-4849 antibody
Type：
Additional 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：
血液
组织：
Sample Name：
Blood
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
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)：
NA是否公开试验完成后的统计结果:
Calculated Results after the Study Completed public access:
不公开/Private盲法：Blinding：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）：
NAThe way of sharing IPD”(include metadata and
protocol,
If use web-based public database, please provide
the
url)：
NA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：
NAData collection and Management (A
standard data collection and management system
include a CRF and an electronic data capture：
NA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：
2026-01-29 14:48:53
