ChiCTR2400094816 版本V1.1 版本创建时间2024/12/29 18:16:13 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2400094816 

最近更新日期：

Date of Last Refreshed on：

 2024-12-27 16:18:15 

注册时间：

Date of Registration：

 2024-12-27 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

培美曲塞/卡铂/贝伐珠单抗联合或不联合信迪利单抗用于EGFR敏感突变、EGFR-TKI治疗失败的晚期非鳞非小细胞肺癌的疗效研究

Public title：

Efficacy study of pemetrexed/carboplatin/bevacizumab with or without combination of sincilumab in advanced non-squamous and non-small cell lung cancer with EGFR-sensitive mutations and failed EGFR-TKI therapy

注册题目简写：

化疗/贝伐珠单抗对比化疗/贝伐珠单抗联合信迪利单抗在EGFR-TKI治疗耐药的非小细胞肺癌的疗效研究

English Acronym：

Efficacy of chemotherapy/bevacizumab versus chemotherapy/bevacizumab combined with sincilumab in advanced non-small cell lung cancer with drug-resistant of EGFR-TKI treatment

研究课题的正式科学名称：

培美曲塞/卡铂/贝伐珠单抗联合或不联合信迪利单抗用于EGFR敏感突变、EGFR-TKI治疗失败的晚期非鳞非小细胞肺癌的疗效研究

Scientific title：

Efficacy study of pemetrexed/carboplatin/bevacizumab with or without combination of sincilumab in advanced non-squamous and non-small cell lung cancer with EGFR-sensitive mutations and failed EGFR-TKI therapy

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：

张洁 

研究负责人：

张洁 

Applicant：

Jie Zhang 

Study leader：

Jie Zhang 

申请注册联系人电话：

Applicant telephone：

 +86 13501878890

研究负责人电话：

Study leader's
telephone：

+86 21 65115006

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：

 zhangjie2172@163.com

研究负责人电子邮件：

Study leader's E-mail：

 zhangjie2172@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：

上海市杨浦区政民路507号

研究负责人通讯地址：

上海市杨浦区政民路507号

Applicant address：

No. 507, Zhengmin Road, Yangpu District, Shanghai City

Study leader's address：

No. 507 Zhengmin Road, Yangpu District, Shanghai

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：

同济大学附属上海市肺科医院

Applicant's institution：

Shanghai Pulmonary Hospital Affiliated to Tongji University

研究负责人所在单位：

上海市肺科医院

Affiliation of the Leader：

Shanghai Pulmonary 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：

 L24-672

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：

上海市肺科医院医学伦理委员会

Name of the ethic committee：

Instituional Review Board Shanghai Pulmonary Hospital Tongji University

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-12-02 00:00:00

伦理委员会联系人：

桂涛

Contact Name of the ethic committee：

Gui Tao

伦理委员会联系地址：

上海市杨浦区政民路507号

Contact Address of the ethic committee：

No. 507 Zhengmin Road, Yangpu District, Shanghai

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 21 65115006

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 fkyygcp@163.com

研究实施负责（组长）单位：

上海市肺科医院

Primary sponsor：

Shanghai Pulmonary Hospital

研究实施负责（组长）单位地址：

上海市杨浦区政民路507号

Primary sponsor's address：

No. 507 Zhengmin Road, Yangpu District, Shanghai

试验主办单位(项目批准或申办者)：

Secondary sponsor：

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

具体地址：

上海市杨浦区政民路507号

Institution
hospital：

Shanghai Pulmonary Hospital

Address：

No. 507 Zhengmin Road, Yangpu District, Shanghai

经费或物资来源：

自选课题（自筹）

Source(s) of funding：

self-raised

研究疾病：

非小细胞肺癌  

Target disease：

Non- Small Cell Lung 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：

 上市后药物 

Study phase：

4

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

1.根据RECIST1.1标准评估培美曲塞/铂类/贝伐珠单抗联合或不联合信迪利单抗在治疗EGFR突变阳性、EGFR-TKI治疗失败的晚期非鳞非小细胞肺癌患者的12个月无进展生存率(12-month PFS rate)。 2.根据RECIST1.1标准评估两组患者的无进展生存期(PFS)，总生存期(OS)，客观缓解率(ORR)，疾病控制率(DCR)，缓解持续时间(DOR)和18个月无进展生存率(18-month PFS rate)。 3.评价两组患者的安全性和耐受性。  

Objectives of Study：

1. To evaluate the 12-month progression-free survival rate (12-month PFS rate) of pemetrexed/platinum/bevacizumab with or without sinidimab in patients with EGFR mutation-positive patients with advanced non-squamous non-small cell lung cancer who have failed EGFR-TKI treatment based on the RECIST1.1 criteria. 2. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR) and 18-month PFS rate of patients in the two groups were evaluated according to the RECIST1.1 criteria. 3. The safety and tolerability of the two groups of patients were evaluated.

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.对本研究已充分了解并自愿签署知情同意书（ICF）；
2.年龄18岁-75岁，性别不限；
3.经组织学和/或细胞学确诊的晚期或复发III B-C或IV期非鳞非小细胞肺癌（根据AJCC第8版分期系统）伴敏感EGFR突变，且同时符合以下条件：1）既往一代或二代EGFR-TKI（包括吉非替尼、厄洛替尼、埃克替尼及阿法替尼等）治疗失败后无 20 外显子T790M突变；2）既往一代或二代EGFR-TKI单药（包括吉非替尼、厄洛替尼、埃克替尼及阿法替尼等）治疗失败后出现20外显子T790M突变，之后接受奥希替尼或其他三代EGFR-TKI治疗后再次出现疾病进展； 3）既往奥希替尼或其他三代EGFR-TKI治疗(作为一线治疗)失败的参与者均符合入组标准(无论其EGFR T790M突变状态如何)。4）允许前期接受新辅助/辅助化疗，且在最后一剂化疗完成后6个月以上出现疾病复发或转移。
4.至少有一个可测量病灶（根据 RECIST 1.1）；
5.同意提供既往储存的EGFR-TKI治疗失败后的肿瘤组织标本或者新鲜活检肿瘤病灶组织，必须提供上述标本的相关病理学报告。必须有再活检后组织的PD-L1检测结果；
6.根据东部肿瘤协作组（ECOG）标准，体能状态评分为0或1；
7.预期生存期≥3 月；
8.血液学功能充分（筛查前14天内未输血、未使用G-CSF、未使用药物纠正）：血红蛋白（HB）≥90g/L；中性粒细胞计数绝对值（ANC）≥1.5×109/L；血小板计数（PLT）≥100×109/L；白细胞计数（WBC）≥4.0×109/L 或本研究中心的正常值下限，并且≤15×109/L；
9.肝功能充分（筛查前14天内未输血或白蛋白）：AST 和 ALT≤1.5xULN（如存在肿瘤肝转移，≤5×ULN）；ALP≤2.5×ULN（如存在肿瘤骨转移，≤5×ULN）；TBiL≤1.5×ULN；ALB≥30g/L；
10.肾功能充分：Cr≤1.5×ULN，同时肌酐清除率(CrCL)≥60 mL/min（顺铂）或 CrCL≥50 mL/min（卡铂）（Cockcroft-Gault公式）；
11.凝血功能充分：APTT≤1.5×ULN，同时INR或PT≤1.5×ULN（未接受抗凝治疗）；
12.任何既往治疗、手术或放疗导致的不良事件必须已缓解至0或1级（根据美国国家癌症研究所-不良事件通用术语标准（NCI-CTCAE 5.0），任何等级的脱发除外；
13.愿意并能够遵守研究计划的访视、治疗计划、实验室检查和其他研究程序；
14.育龄妇女必须在首次用药前3天内进行血清妊娠试验，且结果为阴性。育龄妇女受试者和伴侣为育龄妇女的男性受试者必须同意在研究期间和末次给予研究药物后180天内采用高效方法避孕。

Inclusion criteria

1.Have fully understood this study and voluntarily signed the informed consent form (ICF);
2.Age 18 - 75 years old, regardless of gender;
3.Advanced or recurrent stage III B-C or IV non-squamous or non-small cell lung cancer confirmed by histology and/or cytology (According to the AJCC staging system, version 8) with sensitive EGFR mutations and meeting the following conditions: 1) After treatment failure with first or second-generation EGFR-TKI (Including gefitinib, erlotinib, icotinib, afatinib, etc), the patient's genetic test showed no T790M mutation in exon 20 after re-biopsy; 2) After treatment failure with first or second-generation EGFR-TKI single agent (Including gefitinib, erlotinib, icotinib, afatinib, etc), the patient's genetic test after re-biopsy developed a T790M mutation in exon 20, and then developed disease progression again after receiving osimertinib or other three-generation EGFR-TKIs; 3) Participants who had failed previous osimertinib or other three-generation EGFR-TKIs as first-line treatment met the inclusion criteria (regardless of their EGFR T790M mutation status). 4) Premature neoadjuvant/adjuvant chemotherapy is allowed, and disease recurrence or metastasis occurs more than 6 months after the last dose of chemotherapy is completed；
4.At least one measurable lesion (according to RECIST 1.1);
5.If you agree to provide previously stored tumor tissue specimens after failed EGFR-TKI treatment or freshly biopsied tumor lesion tissue, relevant pathology reports of the above specimens must be provided. PD-L1 test results must be available for tissue after re-biopsy;
6.Performance status score of 0 or 1 according to Eastern Cooperative Oncology Group (ECOG) criteria;
7.Expected survival time ≥3 months;
8.Adequate hematological function (no blood transfusion, no G-CSF use, no medication correction within 14 days before screening): Hemoglobin (HB) ≥90g/L; absolute neutrophil count (ANC) ≥1.5×109/L; platelet count (PLT) ≥100×109/L; white blood cell count (WBC) ≥4.0×109/L or the lower limit of normal for this study site, and ≤15×109/L;
9.Adequate liver function (no blood transfusion or albumin within 14 days prior to screening): AST and ALT≤1.5xULN (≤5×ULN if tumor liver metastases are present);ALP≤ 2.5xULN (≤5×ULN if tumor bone metastases are present);TBiL≤ 1.5xULN;ALB≥30g/L;
10.Adequate renal function: Cr≤1.5×ULN, while creatinine clearance (CrCL)≥60 mL/min (cisplatin) or CrCL≥50 mL/min (carboplatin)(Cockcroft-Gault formula);
11.Adequate coagulation function: APTT≤1.5×ULN, and INR or PT≤1.5×ULN (not receiving anticoagulant therapy);
12.Any adverse event caused by previous treatment, surgery, or radiotherapy must have resolved to Grade 0 or 1 (except for hair loss of any grade according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE 5.0);
13.Willing and able to comply with planned visits, treatment plans, laboratory tests and other study procedures;
14.Women of childbearing age must take a serum pregnancy test within 3 days before the first dose and the result is negative. Female subjects of childbearing potential and male subjects whose partner is a woman of childbearing potential must agree to use a highly effective method of contraception during the study and for 180 days after the last dose of study drug.

排除标准：

1.排除肿瘤组织学或细胞学病理证实的鳞癌，腺鳞混合或合并小细胞肺癌成分;
2.合并其他有已知药物治疗的驱动基因突变，包括但不仅限于：ALK基因重排、ROS1突变、BRAF600E突变;
3.既往接受过针对晚期NSCLC的系统化疗;
4.排除无可测量病灶受试者;
5.排除有癌性脑膜炎、脊髓压迫等情况的受试者。未针对脊髓压迫进行明确的手术和/或放疗，或对于既往诊断和治疗的脊髓压迫，无证据表明随机化前疾病在临床上稳定≥2 周;
6.排除未经治疗的中枢神经系统（CNS）肿瘤转移的受试者。如果受试者的CNS肿瘤转移仅限于幕上和/或小脑，已经接受过充分治疗（放射治疗或CNS转移灶的手术），临床稳定（影像学检测，首选增强MRI或CT）已维持至少4周，并且受试者的神经系统等临床症状能够在首次用药前至少 2 周恢复至NCI-CTCAE≤1度，则可以参加研究。如果在筛选期扫描时发现患者出现新的无症状 CNS 转移者，必须接受放射治疗或者/和 CNS 转移灶的手术。 此外，受试者如果使用皮质类固醇类激素治疗相关临床症状，接受剂量稳定或逐渐降低的≤10 mg/天的泼尼松（或等价物）至少 2 周方可参加研究，否则不能入组;
7.既往接受过针对PD-1受体或其配体PD-L1或细胞毒性T淋巴细胞相关蛋白4（CTLA-4）受体的治疗;
8.肿瘤压迫周围重要脏器(如食管)且伴随相关症状，压迫上腔静脉或侵犯纵膈大血管、心脏等;
9.在入选治疗前6 个月内发生过任何动脉血栓、栓塞或缺血，如心肌梗死、不稳定型心绞痛、脑血管意外或一过性脑缺血发作等。在入组前 3个月内有深静脉血栓、肺栓塞或其它任何严重血栓栓塞的病史(植入式静脉输液港或导管源性血栓形成，或浅表静脉血栓形成不被视为“严重”血栓栓塞);
10.排除存在任何活动性、已知或可疑自身免疫疾病的受试者。自身免疫性疾病病史，包括但不限于重症肌无力、肌炎、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、与抗磷脂综合征有关的血管血栓形成、韦格纳肉芽肿病、干燥综合征、格林-巴利综合征、多发性硬化、血管炎或肾小球肾炎;
11.排除首次用药前14天内，需要使用皮质类固醇（>10 mg/天的泼尼松或等价物）或其他免疫抑制剂进行系统治疗的受试者。在没有活动性自身免疫疾病的情况下，允许吸入或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;
12.排除首次用药前1个月内用过抗肿瘤疫苗或其他具有免疫刺激作用的抗肿瘤药（干扰素、白介素、胸腺肽、免疫细胞疗法等）治疗的受试者;
13.排除正在参加其他临床研究或首次用药时间距离前一项临床研究结束（末次给药）时间少于4周（或该研究药物的5个半衰期）的受试者;
14.排除预期在研究中需要任何其它形式的抗肿瘤治疗（包括其它NSCLC药物的维持治疗、放疗和/或手术切除）的受试者;
15.入组前4周内进行过外科大手术或尚未从之前的手术中完全恢复的受试者;
16.首次用药前4周内>30 Gy的非胸部放射治疗者，首次用药前6个月内>30Gy 的胸部放射者，以及首次用药前2周内接受≤30Gy的姑息性放射者，且未能从这些干预措施的毒性和/或并发症恢复至NCI-CTCAE≤1度（脱发和疲劳除外）的受试者。允许为控制症状进行的姑息性放疗，必须在研究药物开始治疗前至少2周完成，并且没有计划对相同病灶进行额外放疗;
17.排除高度怀疑有间质性肺炎的受试者；或可能会干扰可疑的药物相关肺毒性的检测或处理的受试者；或其他严重影响肺功能的中重度肺部疾病;
18.排除需要同时治疗的其他活动性恶性肿瘤的受试者;
19.排除首次用药前5年内患有除非小细胞肺癌之外的其它恶性肿瘤。转移或死亡风险可忽略（例如，预期的5年OS>90%）且治疗后预期可获得根治性结果的恶性肿瘤（例如，充分治疗的宫颈原位癌、基底或鳞状细胞皮肤癌、根治性目的治疗的局限性前列腺癌、根治性目的手术治疗的原位导管癌、根治性目的手术治疗的甲状腺乳头状癌）可除外;
20.排除患有Ⅱ级以上心肌缺血或心肌梗塞、控制不良的心律失常的受试者。排除按照NYHA标准Ⅲ～Ⅳ级心功能不全或心脏彩超检查：LVEF（左室射血分数）＜50%的受试者;
21.患有活动性肺结核（TB）的患者，正在接受抗结核治疗或者筛选前1年内接受过抗结核治疗;
22.排除首次用药前4周内发生过严重感染的受试者，包括但不局限于需要住院治疗的感染并发症，菌血症，重症肺炎等。排除伴有任何活动性感染的受试者。不排除肺癌淋巴扩散的情况;
23.排除准备进行或者既往接受过组织/器官移植的受试者;
24.排除首次用药前30天内接种过或将接种活疫苗的受试者;
25.排除首次用药前伴有铂类药物治疗禁忌症的受试者：痛风（针对使用顺铂的受试者）、水痘、带状疱疹、≥2级外周神经病变;
26.未控制的胸腔积液、心包积液，或需要反复引流的腹水（一月一次或更频繁）；经过引流后症状稳定至少两周的受试者是可以入组的;
27.排除伴有未控制的肿瘤相关疼痛的受试者。需要止痛药治疗的受试者必须在随机分组前已有稳定的止痛治疗方案；适合姑息性放疗的症状性病灶（如骨转移或转移侵犯神经）应在入选至少2周前完成治疗；无症状的转移性病灶，如果其进一步生长可能会导致功能障碍或顽固性疼痛（如没有表现出脊髓压迫的硬膜外转移），若适合，应在随机前考虑局部-区域治疗;
28.已知有人类免疫缺陷病毒（HIV）检查阳性病史或已知有获得性免疫缺陷综合征（艾滋病）;
29.未经治疗的活动性肝炎。乙肝：乙型肝炎病毒表面抗原（HBsAg）阳性且HBV DNA检测值高于正常值上限； 丙肝：丙型肝炎病毒抗体（HCV Ab）阳性，HCV RNA阳性；合并乙肝和丙肝共同感染。 注：乙肝核心抗体（HBcAb）阳性者，也需检测HBV-DNA，HBV DNA检测值低于正常值上限才可入组;
30.对其他单克隆抗体发生过重度过敏反应;
31.对培美曲塞、铂类或其预防用药等有严重过敏史;
32.排除伴有精神疾病、酗酒、吸毒或药物滥用等情况的受试者;
33.根据研究者的判断，排除患有可能混淆研究结果、干扰受试者参与研究程序或不符合受试者参加研究最佳利益的任何疾病、治疗或实验室异常的病史或当前证据的受试者。

Exclusion criteria：

1.Patients are diagnosed with squamous cell carcinoma, mixed adeno-scale or combined small cell lung cancer components confirmed by tumor histology or cytology;
2.Genetic testing of the patient's pathological tissue combined with other driver gene mutations with known drug treatments, including but not limited to: ALK gene rearrangement, ROS1 mutation, and BRAF600E mutation;
3.The patient had previously received systemic chemotherapy for advanced NSCLC;
4.Excluding subjects with no measurable lesions;
5.Subjects with cancerous meningitis, spinal cord compression, etc. No clear surgery and/or radiotherapy was performed for spinal cord compression, or for previously diagnosed and treated spinal cord compression, there was no evidence that the disease was clinically stable for ≥2 weeks prior to randomization;
6.Subjects with untreated central nervous system (CNS) tumors that have metastasized. Subjects may participate in the study if their CNS tumor metastases are limited to the supratentorial and/or cerebellum, have received adequate treatment (radiotherapy or surgery for CNS metastases) and maintained clinical stability (imaging detection, preferred enhanced MRI or CT) for at least 4 weeks, and the subjects 'nervous system and other clinical symptoms can recover to NCI-CTCAE≤1 at least 2 weeks before the first dose. If a patient is found to have new asymptomatic CNS metastases during the screening scan, he must undergo radiotherapy or/and surgery for the CNS metastases. In addition, subjects who use corticosteroids to treat relevant clinical symptoms cannot participate in the study if they receive a stable or gradually decreasing dose of prednisone (or equivalent) ≤10 mg/day for at least 2 weeks, otherwise they cannot be enrolled;
7.Previous treatment against the PD-1 receptor or its ligand PD-L1 or the cytotoxic T lymphocyte associated protein 4 (CTLA-4) receptor;
8.The patient's tumor compresses important surrounding organs (such as esophagus) and is accompanied by related symptoms, compresses the superior vena cava or invades the mediastinal great vessels, heart, etc.;
9.The patient had any arterial thrombosis, embolism or ischemia within 6 months before being enrolled in treatment, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack. History of deep vein thrombosis, pulmonary embolism, or any other serious thromboembolism within 3 months prior to enrollment (thrombosis from implanted venous access port or catheter origin, or superficial venous thrombosis is not considered "serious" thromboembolism);
10.Subjects with any active, known or suspected autoimmune disease were excluded. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis;
11.Subjects who required systemic treatment with corticosteroids (10 mg/day prednisone or equivalent) or other immunosuppressants within 14 days before the first dose were excluded. In the absence of active autoimmune disease, inhaled or topical corticosteroids, as well as adrenal hormone replacement therapy at doses ≤10 mg/day, effective doses of prednisone are allowed;
12.Excluding subjects who have been treated with anti-tumor vaccines or other anti-tumor drugs with immunostimulating effects (interferons, interleukins, thymosin, immune cell therapy, etc.) within 1 month before the first dose;
13.Excluding subjects who are participating in other clinical studies or whose first dose has been less than 4 weeks (or 5 half-lives of the study drug) since the end of the previous clinical study (last dose);
14.Excluding subjects expected to require any other form of antitumor treatment in the study (including maintenance treatment with other NSCLC drugs, radiotherapy and/or surgical resection);
15.Subjects who had undergone major surgical surgery within 4 weeks prior to enrollment or have not fully recovered from previous surgery;
16.Subjects who received non-thoracic radiation therapy 30 Gy within 4 weeks before the first dose, those who received thoracic radiation 30Gy within 6 months before the first dose, and those who received palliative radiation ≤30Gy within 2 weeks before the first dose, and failed to recover to NCI-CTCAE≤1 (excluding hair loss and fatigue) from the toxicities and/or complications of these interventions. Palliative radiotherapy allowed to control symptoms must be completed at least 2 weeks before the start of study drug treatment, and no additional radiotherapy to the same lesion is planned;
17.Excluding subjects with high suspicion of having interstitial pneumonia; or subjects who may interfere with the detection or management of suspected drug-related pulmonary toxicity; or other moderate to severe pulmonary diseases that seriously affect lung function;
18.Exclusion of subjects with other active malignancies requiring concurrent treatment;
19.Exclusion of having other malignant tumors other than small cell lung cancer within 5 years before the first dose. Excluding malignancies with negligible risk of metastasis or death (e.g., expected 5-year OS>90%) and expected to achieve radical results after treatment (e.g., adequately treated cervical carcinoma in situ, basal or squamous cell skin carcinoma, localized prostate cancer treated for radical purposes, ductal carcinoma in situ treated surgically for radical purposes, papillary thyroid carcinoma treated surgically for radical purposes);
20.Subjects with myocardial ischemia or myocardial infarction of grade II or above, and poorly controlled arrhythmia were excluded. Subjects with cardiac dysfunction of Class III ~ IV according to NYHA standards or cardiac ultrasound examination: LVEF (left ventricular ejection fraction)<50% were excluded;
21.Patients with active pulmonary tuberculosis (TB) who are receiving anti-TB treatment or who have received anti-TB treatment within 1 year prior to screening;
22.Subjects who had a serious infection within 4 weeks before the first dose were excluded, including but not limited to infectious complications requiring hospitalization, bacteremia, severe pneumonia, etc. Subjects with any active infections were excluded. Lymphatic spread of lung cancer cannot be ruled out;
23.Exclusion of subjects who are preparing for or who have previously received tissue/organ transplants;
24.Excluding subjects who have received or will receive a live vaccine within 30 days before the first dose;
25.Excluding subjects with contraindications to platinum treatment before the first dose: gout (for subjects using cisplatin), chickenpox, herpes zoster, grade ≥2 peripheral neuropathy;
26.Patients with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once a month or more frequently) can be enrolled with stable symptoms for at least two weeks after drainage；
27.Subjects with uncontrolled tumor-related pain were excluded. Subjects requiring painkillers must have a stable analgesic treatment regimen before randomization; symptomatic lesions suitable for palliative radiotherapy (such as bone metastases or metastases that invade nerves) should be completed at least 2 weeks before enrollment; asymptomatic metastatic lesions, if their further growth may lead to dysfunction or refractory pain (such as epidural metastases that do not show spinal cord compression), if appropriate, local-regional treatment should be considered before randomization;
28.Subject has a history of positive human immunodeficiency virus (HIV) testing or is known to have acquired immunodeficiency syndrome (AIDS);
29.Untreated active hepatitis. Hepatitis B: Hepatitis B virus surface antigen (HBsAg) is positive and the HBV DNA test value is higher than the upper limit of normal; hepatitis C: Hepatitis C virus antibody (HCV Ab) is positive and HCV RNA is positive; concurrent hepatitis B and hepatitis C co-infection. Note: Those who are positive for hepatitis B core antibody (HBcAb) must also be tested for HBV-DNA. Only when the HBV DNA test value is lower than the upper limit of normal can they be enrolled;
30.Severe allergic reactions to other monoclonal antibodies;
31.A history of severe allergies to pemetrexed, platinum or their prophylactic medications;
32.Exclusion of subjects with mental illness, alcohol abuse, drug abuse, etc.;
33.Subjects with medical history or current evidence of any disease, treatment, or laboratory abnormality that may confound the results of the study, interfere with the subject's participation in study procedures, or are not in the subject's best interest in participating in the study will be excluded at the discretion of the investigator.

研究实施时间：

Study execute time：

从 From 2025-01-01 00:00:00至 To 2027-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-02-01 00:00:00 至 To 2026-12-31 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 82

Group：

A

Sample size：

干预措施：

信迪利单抗注射液

干预措施代码：

Intervention：

Sintilimab Injection

Intervention code：

组别：

对照组

样本量：

 82

Group：

B

Sample size：

干预措施：

无

干预措施代码：

Intervention：

NO

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

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：

 三级甲等 

Institution
hospital：

Shanghai Pulmonary Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

12个月无进展生存率

指标类型：

主要指标

Outcome：

12-month progression-free survival rate

Type：

Primary indicator

测量时间点：

受试者从首次使用研究药物到疾病进展或任何原因死亡的时间。

测量方法：

指患者从治疗开始之日至任何有客观记录的肿瘤进展或患者死亡时间大于等于12个月的病人比例。

Measure time point of outcome：

Time from the subject's first use of study drug to disease progression or death from any cause.

Measure method：

Proportion of patients with a time greater than or equal to 12 months from the start of treatment to any objectively documented tumor progression or patient death.

指标中文名：

无进展生存期

指标类型：

次要指标

Outcome：

progression-free survival, PFS

Type：

Secondary indicator

测量时间点：

受试者从首次使用研究药物到疾病进展或任何原因死亡的时间。

测量方法：

疾病进展或任何原因死亡的时间和首次使用研究药物的时间间隔（月）。

Measure time point of outcome：

Time from the subject's first use of study drug to disease progression or death from any cause.

Measure method：

Time to disease progression or death from any cause and time between first use of study drug（months）.

指标中文名：

总生存期

指标类型：

次要指标

Outcome：

overall survival, OS

Type：

Secondary indicator

测量时间点：

患者从随机化分组开始到因各种原因导致死亡之间的时间。

测量方法：

患者开始被随机的时间到受试者因任何原因死亡的时间的间隔。

Measure time point of outcome：

Time between randomization and death due to various causes.

Measure method：

The interval between the time a patient was initially randomized and the time the subject died from any cause.

指标中文名：

客观缓解率

指标类型：

次要指标

Outcome：

objective response rate, ORR

Type：

Secondary indicator

测量时间点：

在接受治疗前，以及每2个疗程后21天均进行1次recist 评估。

测量方法：

肿瘤体积缩小达到30%（通常）并能维持最低时限要求的受试者比例，是完全缓解（CR）和部分缓解（PR）比例之和。

Measure time point of outcome：

Recist assessments were performed before treatment and 21 days after every 2 cycles.

Measure method：

The proportion of subjects whose tumor volume shrinks by 30%(usually) and who can maintain the minimum time limit is the sum of the proportion of complete responses (CR) and partial responses.

指标中文名：

缓解持续时间duration of response, DOR

指标类型：

次要指标

Outcome：

duration of response, DOR

Type：

Secondary indicator

测量时间点：

在接受治疗前，以及每2个疗程后21天均进行1次recist 评估。

测量方法：

患者从首次记录确认缓解(CR或PR)到首次记录疾病进展(PD)或因任何原因导致死亡的持续时间(以先发生者为准)。

Measure time point of outcome：

Recist assessments were performed before treatment and 21 days after every 2 cycles.

Measure method：

The duration from the first record of a confirmed response (CR or PR) to the first record of disease progression (PD) or death from any cause (taking the first event as the criterion).

指标中文名：

疾病控制率

指标类型：

主要指标

Outcome：

disease control rate, DCR

Type：

Primary indicator

测量时间点：

在接受治疗前，以及每2个疗程后21天均进行1次recist 评估。

测量方法：

肿瘤缩小达到一定量并且保持一定时间的病人的比例，包含完全缓解(CR)、部分缓解(PR)和稳定(SD)的病例。

Measure time point of outcome：

Recist assessments were performed before treatment and 21 days after every 2 cycles.

Measure method：

The proportion of patients whose tumors shrink by a certain amount and remain for a certain period of time, including cases with complete response (CR), partial response (PR), and stable (SD).

指标中文名：

18个月无进展生存率

指标类型：

次要指标

Outcome：

18-month progression-free survival rate

Type：

Secondary indicator

测量时间点：

受试者从首次使用研究药物到疾病进展或任何原因死亡的时间。

测量方法：

指患者从治疗开始之日至任何有客观记录的肿瘤进展或患者死亡时间大于等于18个月的病人比例。

Measure time point of outcome：

Time from the subject's first use of study drug to disease progression or death from any cause.

Measure method：

Proportion of patients with a time greater than or equal to 18 months from the start of treatment to any objectively documented tumor progression or patient death.

指标中文名：

安全性

指标类型：

次要指标

Outcome：

safety

Type：

Secondary indicator

测量时间点：

每次治疗和随访期间。

测量方法：

根据CTCAE 5.0版对实验室检测结果和毒性等级进行总结分级。

Measure time point of outcome：

During each treatment and follow-up period.

Measure method：

Laboratory test results and toxicity grade were summarized and graded according to CTCAE version 5.0.

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

无

组织：

Sample Name：

NA

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）：

本研究将采用区组随机化的方法，区组长度为4，共有41个区组，组合方案为AABB、ABAB、ABBA、BABA、BAAB和BBAA，经筛选合格的受试者将按 1:1 的比例随机分配至试验组或对照组。

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

This study will adopt a block randomization method. The block length is 4 and there are 41 blocks in total. The combination scheme is AABB, ABAB, ABBA, BABA, BAAB and BBAA. Subjects who have passed the screening will be randomly assigned to the test group or the control group in a 1:1 ratio.

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：

开放标签，对评估者隐藏分组

Blinding：

Open-label study with blinded-evaluators

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）：

数据不共享

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

Data not shared.

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：

病例记录表（CRF)

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

Case Record Form (CRF)

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2024-12-27 16:18:04