ChiCTR2000032288 版本V1.4 版本创建时间2020/04/25 10:37:51 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：

 ChiCTR2000032288 

最近更新日期：

Date of Last Refreshed on：

 2020-04-25 10:37:04 

注册时间：

Date of Registration：

 2020-04-25 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

PD-1单抗联合化疗对比贝伐珠单抗联合化疗一线治疗PD-L1表达阴性且EGFR/ALK野生型晚期或转移性非鳞非小细胞肺癌患者的开放性、随机、多中心III期临床研究

Public title：

PD-1 antibody plus chemotherapy versus bevacizumab plus chemotherapy as first-line treatment for patients with PD-L1 negative and EGFR/ALK wild-type advanced or metastatic non-squamous non-small cell lung cancer : an open-label, randomised, multicentre phase 3 trial

注册题目简写：

English Acronym：

研究课题的正式科学名称：

PD-1单抗联合化疗对比贝伐珠单抗联合化疗一线治疗PD-L1表达阴性且EGFR/ALK野生型晚期或转移性非鳞非小细胞肺癌患者的开放性、随机、多中心III期临床研究

Scientific title：

PD-1 antibody plus chemotherapy versus bevacizumab plus chemotherapy as first-line treatment for patients with PD-L1 negative and EGFR/ALK wild-type advanced or metastatic non-squamous non-small cell lung cancer : an open-label, randomised, multicentre phase 3 trial

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：

任胜祥 

研究负责人：

周彩存 

Applicant：

Shengxiang Ren 

Study leader：

Caicun Zhou 

申请注册联系人电话：

Applicant telephone：

 +86 021-65115006-3056

研究负责人电话：

Study leader's
telephone：

+86 021-65115006-3049

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：

 harry_ren@126.com

研究负责人电子邮件：

Study leader's E-mail：

 caicunzhoudr@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号上海市肺科医院肿瘤科

研究负责人通讯地址：

上海市杨浦区政民路507号上海市肺科医院肿瘤科

Applicant address：

507 Zhengmin Road, Yangpu District, Shanghai, China

Study leader's address：

507 Zhengmin Road, Yangpu District, Shanghai, 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：

上海市肺科医院

Applicant's institution：

Shanghai Pulmonary Hospital

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：

 K20-232Y

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：

上海市肺科医院伦理审查委员会

Name of the ethic committee：

Shanghai Pulmonary Hospital Ethics Committee

伦理委员会批准日期：

Date of approved by ethic committee：

 2020-04-23 00:00:00

伦理委员会联系人：

张雷

Contact Name of the ethic committee：

Lei Zhang

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：

507 Zhengmin Road, Yangpu District, Shanghai, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

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：

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：

507 Zhengmin Road, Yangpu District, Shanghai, 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)：

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：

507 Zhengmin Road, Yangpu District

经费或物资来源：

上海市肺科医院临床研究基金

Source(s) of funding：

Clinical Research foundation of Shanghai Pulmonary Hospital

研究疾病：

肺癌  

Target disease：

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：

 III期临床试验 

Study phase：

3

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

对比PD-1单抗联合化疗和贝伐珠单抗联合化疗一线治疗PD-L1表达阴性且EGFR/ALK野生型晚期或转移性非鳞非小细胞肺癌患者的疗效和安全性。  

Objectives of Study：

The project aimed to compare the efficacy and safety of PD-1 antibody plus chemotherapy versus bevacizumab plus chemotherapy as first-line treatment for patients with PD-L1 negative and EGFR/ALK wild-type advanced or metastatic non-squamous non-small cell lung cancer

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）签署知情同意书；
（2）研究者判断其能遵守研究方案；
（3）受试者签署知情同意书时年龄18－70周岁，男女均可；
（4）组织学或细胞学确诊为非鳞癌非小细胞肺癌（NSCLC）、并且为IV期肿瘤（按照第8版美国癌症联合委员会分期手册判断）的受试者；
（5）研究中心必须能够提供受试者EGFR突变和ALK融合基因状态的相关文件资料，且必须均为阴性。在研究中心源文件中记录的EGFR突变和ALK融合基因状态获得前受试者不能随机入组。研究中心必须能够提供受试者肿瘤组织PD-L1表达水平的文件资料，PD-L1表达水平必须由以下28-8/22C3/SP263抗体其中之一检测，受试者PD-L1肿瘤细胞TPS评分<1%。
（6）既往未接受针对晚期/转移性NSCLC的全身系统性化疗。允许化疗和/或放疗作为新辅助/辅助治疗的一部分使用，只要治疗在诊断出晚期或转移性疾病前已经结束至少12个月。
（7）必须提供诊断为晚期或转移性肿瘤时或之后的肿瘤组织标本，首次用药前6个月内存档的或新鲜获取的、经福尔马林固定、石蜡包埋（FFPE）后的肿瘤组织块能切出至少10张切片供染色、检测（如经申办方医学监查人员批准，可提供少于10张切片）。细针穿刺活检的标本、胸腔积液引流离心的细胞涂片、或者钻取活检不足以用于生物标志物检测。没有软组织成分或脱钙骨肿瘤标本的骨病变也不可接受。
（8）按照RECIST 1.1标准，受试者必须有通过CT或MRI检查的可测量靶病灶。肿瘤影像学评价在首次用药前的28天内进行。
（9）ECOG PS评分：0-1分。
（10）预期的生存期≥3个月。
（11）按照方案要求进行所有的筛选期实验室检查，而且需要在首次用药前的14天内进行。筛查所做的实验室检查的值必须符合下列标准：
①血常规检查：（筛查前14天内未输血、未使用G-CSF、未使用药物纠正）
a)血红蛋白（HB）≥90g/L；
b)中性粒细胞计数绝对值（ANC）≥1.5×109/L；
c)血小板计数（PLT）≥100×109/L；
d)白细胞计数（WBC）≥4.0×109/L并且≤15×109/L；
②生化检查：（筛查前14天内未输血或白蛋白）
e)AST和ALT≤1.5×ULN（如存在肿瘤肝转移，≤5×ULN）；
f)ALP≤2.5×ULN（如存在肿瘤骨转移，≤5×ULN）；
g)TBiL≤1.5×ULN；
h)ALB≥30 g/L；
i)Cr≤1.5×ULN，同时肌酐清除率(CrCL)≥60 mL/min（Cockcroft-Gault公式）；
j)APTT≤1.5×ULN，同时INR或PT≤1.5×ULN（未接受抗凝治疗）；
③筛选时HIC检测结果阴性；
④筛选时乙型肝炎表面抗原（HBsAg）检测结果阴性；筛选时乙型肝炎核心抗体（HBcAb）检测结果阴性，或筛选时乙型肝炎核心抗体（HBcAb）检测结果阳性但随后的乙型肝炎病毒（HBV）DNA检测为阴性；
⑤筛选时丙型肝炎（HCV）抗体检测结果阴性；或筛选时丙型肝炎（HCV）抗体检测结果阳性，但随后的丙型肝炎病毒（HCV）RNA检测为阴性
（12）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。
（13）育龄男性统一禁欲（不进行异性性交）或使用避孕套，同意不捐精子。
（14）自愿参加临床研究，并签署知情同意书。

Inclusion criteria

1. sign the informed consent;
2. the researcher judges that they can comply with the research plan;
3. Aged 18-70 years old at the time of signing the informed consent, both male or female;
4. subjects with histologically or cytologically confirmed non-squamous cell carcinoma of non-small cell lung cancer (NSCLC) and stage IV tumor (as determined by the eighth edition of the American joint committee on cancer staging manual);
5. the research center must be able to provide relevant documentation of the subjects' EGFR mutation and ALK fusion gene status, and all of them must be negative. Subjects were not randomized prior to the acquisition of EGFR mutation and ALK fusion gene status as documented in the study center source files. The research center must be able to provide documents on the expression level of pd-L1 in subjects' tumor tissues. The expression level of pd-L1 must be detected by one of the following 28-8/22c3 /SP263 antibodies. TPS score of subjects' pd-L1 tumor cells is <1%.
6. subjects have not received systemic chemotherapy for advanced/metastatic NSCLC. Chemotherapy and/or radiotherapy are permitted as part of neoadjuvant/adjuvant therapy as long as the treatment has been terminated at least 12 months prior to diagnosis of advanced or metastatic disease;
7. Specimens of tumor tissue at or after diagnosis of advanced or metastatic tumor must be provided, at least 10 sections can be cut out for staining and detection of tumor tissue blocks which are archived or freshly obtained within 6 months before the first application, fixed by formalin and embedded in paraffin (FFPE) (If approved by the sponsor's medical inspectors, less than 10 slices can be provided). Fine needle biopsy specimens, cell smears centrifuged by pleural effusion drainage, or drillage biopsy are not sufficient for biomarker detection. Bone lesions without soft tissue components or decalcified bone tumor specimens are also unacceptable;
8. Subjects must have a measurable target lesion that has passed CT or MRI according to RECIST 1.1. The tumor imaging evaluation was carried out within 28 days before the first application;
9. ECOG PS score 0-1;
10. expected survival >=3 months;
11. all screening period laboratory tests are performed in accordance with protocol requirements and within 14 days prior to initial administration. The values of the laboratory tests performed for screening must meet the following criteria:
(1) Blood routine examination: (No blood transfusion, no use of G-CSF, no medication correction within 14 days before screening)
hemoglobin (HB) >=90g/L; absolute value of neutrophil count (ANC) >=1.5x10^9/L; platelet count (PLT) >=100x10^9/L; white blood cell count (WBC) 4.0 to 15x109/L;
(2) biochemical examination: (no blood transfusion or albumin within 14 days before screening)
AST and ALT<=1.5 ULN (if there is tumor liver metastasis <=5 ULN); ALP<=2.5 ULN (if there is tumor bone metastasis, <=5 ULN); TBiL 1.5 ULN or less; propagated acuity 30 g/L; Cr<=1.5 ULN, and creatinine clearance rate (CrCL)>=60 mL/min (Cockcroft-Gault formula); APTT<=1.5 ULN, and INR or PT<=1.5 ULN (no anticoagulation treatment);
(3) The HIC test result was negative during screening;
(4) when screening hepatitis b surface antigen (HBsAg) test results negative; At the time of screening, the hepatitis b core antibody (HBcAb) test results were negative, or at the time of screening, the hepatitis b core antibody (HBcAb) test results were positive but the subsequent hepatitis b virus (HBV) DNA test was negative;
(5) negative antibody test results of hepatitis c (HCV) during screening; Or hepatitis c (HCV) antibody test results at the time of screening were positive, but the subsequent hepatitis c virus (HCV) RNA test was negative;
12. women of child-bearing age must undergo a serum pregnancy test with negative results within 3 days before the first medication. Subjects of women of childbearing age and male subjects whose partners are women of childbearing age must agree to use a highly effective method of contraception during the study period and 180 days after the last dose of the study drug;
13. all men of childbearing age abstain from sex (no heterosexual intercourse) or use condoms, and agree not to donate sperm;
14. voluntarily participate in clinical research and sign informed consent.

排除标准：

1.目标疾病排除标准：
1）排除其他病理组织学类型的非小细胞肺癌受试者，包括鳞腺混合癌受试者、含小细胞肺癌、神经内分泌癌成份的NSCLC受试者。
2）排除EGFR突变或ALK融合阳性受试者。
3）排除无可测量病灶受试者。
4）排除有癌性脑膜炎、脊髓压迫等情况的受试者。
5）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，如临床稳定（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-CTC AE ≤1度，则可以参加研究。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。
6）可以手术切除或根治性放射治疗的受试者。
7）曾接受过抗PD-1(L1)或CTLA4单抗治疗的受试者。
2.病史和合并症排除标准
1）排除存在任何活动性、已知或可疑自身免疫疾病的受试者。允许入组处于稳定状态，不需要全身免疫抑制剂治疗的受试者，如患有I型糖尿病、只需接受激素替代治疗的甲状腺功能减退症、无需进行全身治疗的皮肤疾病（例如，白癜风、银屑病或脱发），或预计在无外部触发因素的状态下情况不会再现的受试者可以入选。
2）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。
3）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。
4）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。
5）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。
6）排除首次用药前4周内接受重大外科手术者，首次用药前4周内>30 Gy的非胸部放射治疗者，首次用药前24周内>30 Gy的胸部放射者，以及首次用药前2周内接受≤30 Gy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-CTC AE ≤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。
7）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。
8）排除需要同时治疗的其他活动性恶性肿瘤的受试者。
9）排除以前有恶性肿瘤病史的受试者，除非是在筛选前至少5年达到完全缓解且在研究期间不需要或预计不需要其他治疗的皮肤基底细胞癌、表浅膀胱癌、皮肤鳞状细胞癌或原位宫颈癌。
10）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。
11）排除随机前1个月内存在明显的咳鲜血、或日咯血量达半茶勺（2.5ml）或以上者。
12）排除随机前1个月内出现过显著临床意义的出血症状或具有明确的出血倾向，如消化道出血、出血性胃溃疡，或患有脉管炎等。
13）排除随机前3个月内发生的动/静脉血栓事件，如脑血管意外（包括暂时性缺血性发作、脑出血、脑梗塞）、深静脉血栓及肺栓塞等。
14）排除伴有活动性肺结核（TB）的受试者。
15）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。
16）排除准备进行或者既往接受过组织/器官移植的受试者。
17）排除首次用药前30天内接种过或将接种活疫苗的受试者。
18）排除首次用药前伴有铂类药物治疗禁忌症的受试者：痛风、水痘、带状疱疹、≥2级外周神经病变。
19）不建议入选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治疗。
3.查体和实验室检查所见排除标准
1）排除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）。
2）排除未经治疗的活动性肝炎。乙肝：乙型肝炎病毒表面抗原（HBV sAg）阳性且HBV DNA检测值高于正常值上限；丙肝：丙型肝炎病毒（HCV）抗体阳性，HCV RNA阳性，且肝功能异常；合并乙肝和丙肝共同感染。
3）排除伴有未控制的需要反复引流的胸腔积液、心包积液，或腹水的受试者。
4.过敏反应和药物不良反应排除标准
1）对其他单克隆抗体发生过重度过敏反应。
2）对输液发生过过敏或不耐受。
3）对培美曲塞、卡铂或其预防用药等有严重过敏史。
5.排除伴有精神疾病、酗酒、无法戒烟、吸毒或药物滥用等情况的受试者。
6.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. Exclusion criteria for target disease:
1) subjects with other histopathological types of non-small cell lung cancer were excluded, including subjects with mixed squamous adenocarcinoma and NSCLC subjects with small cell lung cancer and neuroendocrine carcinoma.
2) exclude EGFR mutation or ALK fusion positive subjects.
3) excluded subjects with unmeasured lesions.
4) subjects with cancerous meningitis and spinal cord compression were excluded.
5) subjects with untreated central nervous system (CNS) metastases were excluded. If subjects with CNS metastasis limited to supratentorial and / or cerebellum have received adequate treatment and maintained clinical stability (enhanced MRI or CT imaging detection, preferred) for at least 4 weeks, and the clinical symptoms such as nervous system of subjects can recover to NCI-CTC AE ≤ 1 degree at least 2 weeks before the first medication, they can participate in research. In addition, subjects who were treated with corticosteroids for related clinical symptoms were excluded from the study unless they received at least 2 weeks of prednisone (or its equivalent) with a steady or gradual decrease in dose <=10 mg/day;
6) subjects who can be removed surgically or treated with radical radiotherapy;
7) subjects who had received anti-pd-1 (L1) or CTLA4 monoclonal antibody therapy;
2. Exclusion criteria for medical history and complications:
1) exclude subjects with any active, known or suspected autoimmune diseases. Allowed to enroll subjects in a stable state who do not need treatment of systemic immune inhibitors.Subjects with type 1 diabetes, hypothyroidism requiring only hormone replacement therapy, skin conditions that require no systemic treatment (e.g., vitiligo, psoriasis, or hair loss), or conditions that are not expected to recur in the absence of external triggers can be selected;
2) subjects requiring systemic treatment with corticosteroids (>10 mg/ day prednisone or equivalent) or other immunosuppressive agents within 14 days prior to initial administration were excluded. In the absence of active autoimmune disease, inhaled or topical administration of corticosteroids and adrenal hormone replacement therapy with a dose of > 10 mg/ day prednisone is permitted;
3) subjects who had been treated with anti-tumor vaccine or other immunostimulant anti-tumor drugs (interferon, interleukin, thymosin, immunocell therapy, etc.) within 1 month before the first medication were excluded;
4) subjects who were enrolled in other clinical studies or whose first use of the drug was less than 4 weeks (or 5 half-lives of the drug in the study) from the end of the previous study (last administration);
5) subjects who are expected to require any other form of antitumor therapy (including maintenance therapy of other NSCLC medications, radiotherapy, and/or surgical resection) in the study;
6) subjects who received major surgery within 4 weeks before the first administration, non-chest radiotherapy of >30 Gy within 4 weeks before the first administration, chest radiotherapy of >30 Gy within 24 weeks before the first administration, and palliative radiation <=30 Gy within 2 weeks before the first administration and subjects who failed to recover from the toxicity and/or complications of these interventions to nci-ctc AE <=1 degree (except hair loss and fatigue);
7) subjects with highly suspected interstitial pneumonia; Or subjects who may interfere with the detection or management of suspected drug-related pulmonary toxicity; Or other severe lung diseases that seriously affect lung function;
8) subjects with other active malignancies that require concurrent treatment;
9) subjects with a previous history of malignancy were excluded, except for basal cell carcinoma of the skin, superficial bladder carcinoma, squamous cell carcinoma of the skin, or cervical cancer in situ, which achieved complete remission at least 5 years prior to screening and did not require or are expected to require additional treatment during the study period;
10) Subjects with myocardial ischemia or myocardial infarction above grade II and poor control of arrhythmia were excluded. Subjects with grade III-IV cardiac insufficiency or color Doppler echocardiography according to NYHA standard: LVEF < 50% were excluded;
11) subjects with obvious hemoptysis or daily hemoptysis volume up to half teaspoon (2.5ml) or above within the first month of randomization;
12) excluding subjects with the occurrence of clinically significant bleeding symptoms or clear bleeding tendency within the first month before the randomization, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, or vasculitis;
13) to exclude subjects with arteriovenous thrombotic events (such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism) that occurred in the first 3 months of the study;
14) subjects with active tuberculosis (TB);
15) subjects with severe infection within 4 weeks prior to the first administration were excluded, including but not limited to infectious complications requiring hospitalization, bacteremia, severe pneumonia, etc. Exclude subjects with any active infection. Lymphatic spread of lung cancer is not excluded;
16) subjects who are about to undergo or have previously received tissue/organ transplants;
17) subjects who had received or would receive live vaccine within 30 days prior to the first dose;
18) subjects with contraindications of platinum drugs before the first administration were excluded: gout, chickenpox, herpes zoster, >=grade 2 peripheral neuropathy;
19) subjects with uncontrolled tumor-related pain are not recommended for inclusion. Subjects requiring analgesic treatment must have a stable analgesic regimen prior to randomization; Symptomatic lesions suitable for palliative radiotherapy (such as bone metastases or nerve invasion by metastases) should be treated at least 2 weeks before inclusion. Asymptomatic metastatic foci, where further growth may lead to dysfunction or intractable pain (such as epidural metastasis without showing spinal cord compression), should be considered before randomization if appropriate;
3. Exclusion criteria for physical and laboratory examination
1) subjects with a known history of positive testing for human immunodeficiency virus (HIV) or a known history of acquired immunodeficiency syndrome (AIDS);
2) subjects with untreated active hepatitis were excluded. Hepatitis b: hepatitis b virus surface antigen (HBV sAg) positive and HBV DNA detection value is higher than the upper limit of normal value; Hepatitis C: hepatitis C virus (HCV) antibody positive, HCV RNA positive, and liver function is abnormal; Co-infection with hepatitis B and C;
3) exclude subjects with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
4. Exclusion criteria for allergic reactions and adverse drug reactions:
1) severe allergic reactions to other monoclonal antibodies;
2) allergy or intolerance to infusion;
3) have a history of severe allergy to pemetrexed, carboplatin or its prophylactic drugs;
5. Subjects with mental illness, alcoholism, inability to quit smoking, drug use or substance abuse were excluded.
6. In the investigator's judgment, exclude subjects with a history or current evidence of any disease, treatment, or laboratory abnormality that may confuse the results of the study, interfere with the subject's participation in the study program, or that is not in the subject's best interest to participate in the study.

研究实施时间：

Study execute time：

从 From 2020-05-01 00:00:00至 To 2023-05-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2020-05-01 00:00:00 至 To 2023-05-01 00:00:00

干预措施：

Interventions：

组别：

Group 2

样本量：

 255

Group：

Group 2

Sample size：

干预措施：

卡瑞利珠单抗+培美曲塞+卡铂/顺铂

干预措施代码：

Intervention：

Camrelizumab + pemetrexed + carboplatin / cisplatin

Intervention code：

组别：

Group 1

样本量：

 255

Group：

Group 1

Sample size：

干预措施：

贝伐珠单抗+培美曲塞+卡铂/顺铂

干预措施代码：

Intervention：

Bevacizumab + pemetrexed + carboplatin / cisplatin

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：

 三级甲等医院 

Institution
hospital：

Shanghai Pulmonary Hospital

Level of the institution：

Tertiary A Hospital

国家：

 中国

省(直辖市)：

 上海 

市(区县)：

  

Country：

China

Province：

Shanghai

City：

单位(医院)：

 上海交通大学医学院附属瑞金医院 

单位级别：

 三级甲等医院 

Institution
hospital：

Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine

Level of the institution：

Tertiary A Hospital

国家：

 中国

省(直辖市)：

 上海 

市(区县)：

  

Country：

China

Province：

Shanghai

City：

单位(医院)：

 上海市第十人民医院 

单位级别：

 三级甲等医院 

Institution
hospital：

Shanghai Tenth People’s Hospital

Level of the institution：

Tertiary A Hospital

国家：

 中国

省(直辖市)：

 上海 

市(区县)：

  

Country：

China

Province：

Shanghai

City：

单位(医院)：

 上海市第一人民医院 

单位级别：

 三级甲等医院 

Institution
hospital：

Shanghai General Hospital

Level of the institution：

Tertiary A Hospital

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：

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：

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：

不良反应

指标类型：

次要指标

Outcome：

Adverse event

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

 使用后保存  

说明

Fate of sample：

Preservation after use  

Note：

标本中文名：

血液

组织：

Sample Name：

Blood

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation 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 70 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）：

研究员将采用置换区组随机化方法按照1:1的比例进行随机分组，同时要考虑如下因素使两组间基线数据平衡：性别（男；女），吸烟史（≥400支/年；<400支/年或无），以确保治疗组间的分配平衡。

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

Block randomization according to the ratio of 1:1 by following factors: gender (male; Female), smoking history (≥400 cigarettes/year; <400 cigarettes/year or 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）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

是Yes

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）：

中国临床试验注册中心

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

Chinese clinical trial registry

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：

通过EDC系统采用电子病例报告表(eCRF)进行研究数据的采集与管理。

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

Electronic case report form (eCRF) was used to collect and manage research data through EDC system.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2020-04-25 10:21:23