ChiCTR2400087226 版本V1.0 版本创建时间2024/07/23 10:22:40 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：

 ChiCTR2400087226 

最近更新日期：

Date of Last Refreshed on：

 2024-07-23 10:22:36 

注册时间：

Date of Registration：

 2024-07-23 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

一项在可切除II期到IIIB期NSCLC中使用替雷利珠单抗联合化疗用于新辅助及术后辅助治疗的临床研究

Public title：

A clinical study of the use of Tirelizumab in combination with chemotherapy for neoadjuvant and postoperative adjuvant treatment in resectable stage II to IIIB NSCLC

注册题目简写：

English Acronym：

研究课题的正式科学名称：

一项在可切除II期到IIIB期NSCLC中使用替雷利珠单抗联合化疗用于新辅助及术后辅助治疗的临床研究

Scientific title：

A clinical study of the use of Tirelizumab in combination with chemotherapy for neoadjuvant and postoperative adjuvant treatment in resectable stage II to IIIB NSCLC

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：

何进喜 

研究负责人：

何进喜 

Applicant：

Jinxi He 

Study leader：

Jinxi He 

申请注册联系人电话：

Applicant telephone：

 +86 139 9511 9619

研究负责人电话：

Study leader's
telephone：

+86 139 9511 9619

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：

 13995119619@163.com

研究负责人电子邮件：

Study leader's E-mail：

 13995119619@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：

宁夏银川市兴庆区胜利南街804号

研究负责人通讯地址：

宁夏银川市兴庆区胜利南街804号

Applicant address：

No. 804 Shengli south street, Xingqing District, Yinchuan, Ningxia Province

Study leader's address：

No. 804 Shengli south street, Xingqing District, Yinchuan, Ningxia Province

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：

宁夏医科大学总医院

Applicant's institution：

General Hospital of Ningxia Medical University

研究负责人所在单位：

宁夏医科大学总医院

Affiliation of the Leader：

General Hospital of Ningxia Medical University

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：

 KYLL-2024-0907

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：

宁夏医科大学总医院医学科研伦理审查委员会

Name of the ethic committee：

Medical Research Ethics Review Committee of General Hospital of Ningxia Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-04-20 00:00:00

伦理委员会联系人：

贾乐川

Contact Name of the ethic committee：

Lechuan Jia

伦理委员会联系地址：

宁夏银川市兴庆区胜利南街804号

Contact Address of the ethic committee：

No. 804 Shengli south street, Xingqing District, Yinchuan, Ningxia Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 139 9511 9619

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：

宁夏医科大学总医院

Primary sponsor：

General Hospital of Ningxia Medical University

研究实施负责（组长）单位地址：

宁夏银川市兴庆区胜利南街804号

Primary sponsor's address：

No. 804 Shengli south street, Xingqing District, Yinchuan, Ningxia 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)：

宁夏

市(区县)：

银川

Country：

China

Province：

Ningxia

City：

Yinchuan

单位(医院)：

宁夏医科大学总医院

具体地址：

宁夏银川市兴庆区胜利南街804号

Institution
hospital：

General Hospital of Ningxia Medical University

Address：

No. 804 Shengli south street, Xingqing District, Yinchuan, Ningxia Province

经费或物资来源：

百济神州

Source(s) of funding：

BeiGene

研究疾病：

肺癌  

Target disease：

Lung cancer

研究疾病代码：

Target disease code：

研究类型：

观察性研究

Study type：

Observational study

研究所处阶段：

 II-III期临床试验 

Study phase：

2-3

研究设计：

队列研究 

Study design：

Cohort study 

研究目的：

主要研究目的 在接受替雷利珠单抗联合化疗作为新辅助治疗的患者中评估完全病理学缓解（pCR）率 次要研究目的 1.在接受替雷利珠单抗联合化疗作为新辅助治疗，随后未达pCR的治疗臂辅以替雷利珠单抗作为辅助治疗的无事件生存期（EFS） 2.在接受替雷利珠单抗联合化疗作为新辅助治疗，随后达到pCR的治疗臂评估的无事件生存期（EFS）。 3.评价替雷利珠单抗联合化疗用于肺癌围手术期患者的总生存期（OS） 4.在接受替雷利珠单抗联合化疗作为新辅助治疗的患者中评估主要病理学缓解（MPR）率 5.通过治疗期间的不良事件评估替雷利珠单抗联合化疗作为新辅助和辅助治疗人群的安全性和耐受性 6.评估接受替雷利珠单抗联合化疗作为新辅助治疗的手术结局 探索性研究目的 评价从组织和血液中提取的生物标记物与替雷利珠单抗临床有效性、作用和耐药机制以及患者预后的潜在关联。  

Objectives of Study：

Main Objective: Complete pathological response (pCR) rates were assessed in patients receiving tirellizumab in combination with chemotherapy as neoadjuvant therapy Secondary Objective: 1. Event-free survival (EFS) of patients who received Tirellizumab combined with chemotherapy as neoadjuvant therapy and subsequently failed to reach pCR with Tirellizumab as adjuvant therapy 2. Event-free survival (EFS) assessed by pCR was achieved after receiving Tirellizumab in combination with chemotherapy as neoadjuvant therapy. 3. Evaluation of overall survival (OS) in perioperative lung cancer patients treated with Tirellizumab combined with chemotherapy 4. The rate of major pathological response (MPR) was assessed in patients receiving tirellizumab in combination with chemotherapy as neoadjuvant therapy 5. To evaluate the safety and tolerability of tirellizumab combined with chemotherapy as a neoadjuvant and adjuvant therapy population by adverse events during treatment 6. To evaluate the surgical outcomes of patients receiving tirellizumab combined with chemotherapy as neoadjuvant therapy Exploratory Objective: To evaluate the potential association of tissue and blood biomarkers with clinical efficacy, action and resistance mechanisms of tirellizumab and patient outcomes.

药物成份或治疗方案详述：

注射用替雷利珠单抗（通用名“注射用替雷利珠单抗”）（生产厂家：百济神州）：200mg，每周期第1天静脉输注给药，每3周为1周期（Q3W） 化疗方案：白蛋白紫杉醇（鳞癌）(260mg/m2 iv d1)/紫杉醇（鳞癌）（175 mg/m2 iv d1）/培美曲塞（非鳞癌）（500 mg/m2 iv d1）+卡铂（AUC5 iv d1），每3周为1周期，在完成两个周期治疗后的4-6周，患者接受根治性切除手术治疗。 在辅助期间，每3周为一周期，每周期第1天，静脉输注给药，最多16个周期.  

Description for medicine or protocol of treatment in detail：

Tislelizumab Injection (generic name "Tislelizumab Injection") (Manufacturer: BeiGene) : 200mg, intravenous infusion on the first day of each cycle, every 3 weeks for 1 cycle (Q3W) Chemotherapy regimen: Albuminpaclitaxel (squamous cell carcinoma) (260mg/m2 iv d1)/ paclitaxel (squamous cell carcinoma) (175 mg/m2 iv d1)/ Pemetrexed (non-squamous cell carcinoma) (500 mg/m2 iv d1) + carboplatin (AUC5 iv d1), every 3 weeks, at 4 to 6 weeks after the completion of two cycles of treatment. The patient underwent radical resection. During the adjuvant period, the drug is administered intravenously every 3 weeks on the first day of each cycle for a maximum of 16 cycles. 

纳入标准：

1. 年龄≥18 岁，＜70 岁； 2. 既往未接受过肿瘤疾病相关治疗（包括放化疗、靶向、免疫或中医中药治疗）； 3. 经组织学证实的II期到IIIB期非小细胞肺癌，（根据AJCC第9版/国际抗癌联盟NSCLC分期系统定义） 4. 具有研究者根据RECIST 1.1版评估的可测量疾病 5. 经胸外科医生评估，确认符合出于根治性治疗的目的进行R0切除的要求 6. ECOG评分0~1分； 7. 要求患者提供存档肿瘤组织样本（FFPE组织块或大约15片[≥6]新切的未染色FFPE切片）以及该基线样本的病理报告，用于PD-L1和其它生物标记物分析（如患者需进行 EGFR检测，则要求额外提供至少 6张切片）。如果没有可用的存档样本或样本不可用，则要求在基线时取活检样本。 8. 主要器官功能正常，即符合下列标准：　　　　 (1) 患者在筛选期采血前≤14天内不得接受输血或生长因子支持 ;血常规随机化前7天内以下各项实验室指标达到以下结果检查须符合： 中性粒细胞绝对计数≥1.5 x 109/L 血小板≥75×109/L 血红蛋白≥90 g/L (2)国际标准化比率（INR）≤2.3 或凝血酶原时间（PT）超过正常对照的范围≤6 秒； (3)尿蛋白<2+（若尿蛋白≥2+，可以进行 24 小时（h）尿蛋白定量，24h 尿蛋白定量<1.0 g 可以入组）； 注：国际标准化比值(INR)或凝血酶原时间(PT)≤1.5×正常值上限(ULN);活化部分凝血活酶时间(aPTT)≤1.5×ULN ;血清总胆红素≤1.5×ULN(Gilbert综合征患者的总胆红素必须<3×ULN);天门冬氨酸和丙氨酸氨基转移酶(AST 和 ALT)≤2.5×ULN，或肝脏转移患者的 AST 和ALT≤5×ULN； 9. 自愿加入本研究，签署知情同意书； 10. 预期寿命≥3个月。

Inclusion criteria

1. Age ≥18 years old, < 70 years old; 2. No previous treatment related to tumor disease (including radiotherapy and chemotherapy, targeting, immunization or traditional Chinese medicine treatment); 3. Histologically proven stage II to IIIB non-small cell lung cancer (as defined by AJCC 9th Edition/International Union against Cancer NSCLC Staging System) 4. Have a measurable disease assessed by the investigator according to RECIST version 1.1 5. After evaluation by the thoracic surgeon, it is confirmed that the requirements for R0 excision for the purpose of radical treatment are met 6. ECOG score 0~1; 7. Patients are asked to provide archived tumor tissue samples (FFPE tissue blocks or approximately 15 [≥6] newly cut unstained FFPE slices) and pathology reports of this baseline sample for PD-L1 and other biomarkers analysis (at least 6 additional slices if the patient requires EGFR testing). If no archived samples are available or samples are not available, a biopsy sample is required at baseline. 8. If the major organs function normally, the following criteria are met: (1) Patients should not receive blood transfusion or growth factor support within ≤14 days before blood collection during the screening period; Within 7 days before blood routine randomization, the following laboratory indicators must meet the following results: Absolute neutrophil count ≥1.5 x 109/L Platelet ≥75×109/L Hemoglobin ≥90 g/L (2) The International standardized ratio (INR) ≤2.3 or the prothrombin time (PT) exceeds the normal control range ≤6 seconds; (3) Urine protein <2+ (if urine protein ≥2+, 24 hours (h) urine protein quantification can be performed, 24 hours (h) urine protein quantification <1.0 g can be included in the group); Note: International Standardized ratio (INR) or prothrombin time (PT)≤1.5× upper limit of normal (ULN); Activated partial thromboplastin time (aPTT)≤1.5×ULN; Serum total bilirubin ≤1.5×ULN(Gilbert syndrome patients must have total bilirubin <3×ULN); Aspartate and alanine aminotransferase (AST and ALT)≤2.5×ULN, or AST and ALT≤5×ULN in patients with liver metastasis; 9. Voluntarily join the study and sign the informed consent; 10. Life expectancy ≥3 months.

排除标准：

1. 研究治疗开始前 6 个月内出现过肺炎、上消化道出血、食管瘘管、食道穿孔或胸腔脓肿； 2. 活动性自身免疫性疾病或可能复发的自身免疫性疾病病史。（如间质性肺炎、葡萄膜炎、肠炎、肝炎、垂体炎、血管炎、心肌炎、肾炎、甲状腺功能亢进、甲状腺功能降低（激素替代治疗后可纳入））；注：不排除以下疾病患者，可进一步筛查： ? 甲状腺功能减退症（只要单纯采用激素替代疗法进行治疗） ? 控制良好的I型糖尿病 ? 控制良好的乳糜泻 ? 不需要全身性治疗的皮肤疾病（例如白癜风、银屑病、脱发） ? 没有外部触发因素的情况下预期不会复发的任何其他疾病； 3. 入组前≤2 年的任何活动性恶性肿瘤，除外本研究中考察的特定癌症和任何已经根治的局部复发的癌症(例如已切除的基底细胞或鳞状细胞皮肤癌、浅表性膀胱癌、宫颈或乳腺原位癌) ； 4. 患有先天或后天免疫功能缺陷，如人类免疫缺陷病毒（HIV）感染者，活动性乙型肝炎（HBV DNA ≥ 500 IU/ml），丙型肝炎（丙肝抗体阳性，且HCV-RNA高于分析方法的检测下限）或合并乙肝和丙肝共同感染； 5. 之前曾针对当前所患肺癌进行过任何治疗，包括化疗或放疗 6. 随机化前≤4 周内接种活疫苗，注：季节性流感疫苗通常为灭活疫苗，允许接种此类疫苗的患者入组。鼻内流感疫苗为活疫苗，不允许接种此类疫苗的患者入组； 7. 临床上未经控制、在随机化前 2 周内需要胸腔穿刺或腹腔穿刺引流的胸腔积液或腹水,或既往3个月内接受过胸腹腔积液引流者,医学影像学显示少量胸腔积液或腹腔积液但不伴有临床症状者除外； 8. 具有临床意义的心包积液； 9. 严重慢性或活动性感染，需要全身抗菌、抗真菌或抗病毒治疗，包括结核感染等。 10. 在随机化前 4 周内或药物的 5 个半衰期内(以较长者为准)，使用全身免疫刺激剂(包括但不限于干扰素、白介素2、肿瘤坏死因子)治疗(允许既往治疗中使用癌症疫苗) ； 11. 同时参与另一项治疗性临床研究。注：允许同时参与观察性或非干预性研究； 12. 妊娠或哺乳女性； 13. 研究者认为存在可能损害受试者或者导致受试者无法满足或执行研究要求的任何状况； 14．携带EGFR/ALK敏感突变的患者； 15. 已知对免疫抑制剂或其辅料会产生变态反应、超敏反应或不耐受；

Exclusion criteria：

1. Pneumonia, upper gastrointestinal bleeding, esophageal fistula, esophageal perforation, or chest abscess occurred within 6 months before the start of study treatment; 2. A history of active autoimmune disease or autoimmune disease that may recur. (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitaritis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (can be included after hormone replacement therapy); Note: Patients with the following diseases are not excluded and may be further screened: ? Hypothyroidism (as long as it is treated with hormone replacement therapy alone) ? Well-controlled type 1 diabetes ? Well-controlled celiac disease ? Skin conditions that do not require systemic treatment (e.g. Vitiligo, psoriasis, hair loss) Any other medical condition that is not expected to recur in the absence of external triggers; 3. Any active malignant tumor ≤2 years prior to entry, except for the specific cancer examined in this study and any locally recurrent cancer that has been eradicated (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ); 4. Have congenital or acquired immunodeficiency, such as human immunodeficiency virus (HIV) infection, active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (HCV antibody positive, and HCV-RNA above the lower detection limit of analytical methods) or co-infection with hepatitis B and hepatitis C; 5. Any previous treatment for your current lung cancer, including chemotherapy or radiation 6. Live vaccines were administered within ≤4 weeks before randomization. Note: Seasonal influenza vaccines are usually inactivated vaccines, and patients receiving such vaccines are allowed to be enrolled. Intranasal influenza vaccine is live vaccine, and patients receiving such vaccine are not allowed to enroll; 7. Patients with clinically uncontrolled pleural effusion or ascites requiring pleural puncture or peritoneal puncture drainage within 2 weeks prior to randomization, or those who had received pleural and peritoneal fluid drainage within 3 months prior, except those who showed a small amount of pleural effusion or peritoneal fluid without clinical symptoms on medical imaging; 8. Pericardial effusion with clinical significance; 9. Severe chronic or active infections that require systemic antimicrobial, antifungal or antiviral treatment, including tuberculosis infections. 10. Treatment with systemic immune stimulants (including, but not limited to, interferon, interleukin 2, tumor necrosis factor) within 4 weeks prior to randomization or within 5 half-lives of the drug, whichever is older (cancer vaccines allowed in previous treatment); 11. Participate in another therapeutic clinical study. Note: Simultaneous participation in observational or non-interventional studies is permitted; 12. Pregnant or breastfeeding women; 13. Any condition which, in the opinion of the investigator, is likely to harm the subject or cause the subject to be unable to meet or perform the study requirements; 14. Patients with EGFR/ALK sensitive mutations; 15. Known allergic reactions, hypersensitivities or intolerances to immunosuppressants or their excipients;

研究实施时间：

Study execute time：

从 From 2024-08-01 00:00:00至 To 2028-08-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-08-01 00:00:00 至 To 2025-08-01 00:00:00

干预措施：

Interventions：

组别：

A组（未达到pCR患者）

样本量：

 15

Group：

A group (Patients who have not reached pCR)

Sample size：

干预措施：

无

干预措施代码：

Intervention：

None

Intervention code：

组别：

B组（达到pCR患者）

样本量：

 15

Group：

B group (Patients who have reached pCR)

Sample size：

干预措施：

无

干预措施代码：

Intervention：

None

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 宁夏回族自治区 

市(区县)：

 银川 

Country：

China

Province：

Ningxia Hui Autonomous Region

City：

Yinchuan

单位(医院)：

 宁夏医科大学总医院 

单位级别：

 三甲 

Institution
hospital：

General Hospital of Ningxia Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

无事件生存期

指标类型：

次要指标

Outcome：

EFS

Type：

Secondary indicator

测量时间点：

首次用药至首次影像学疾病进展或死亡（以先发生者为准）。

测量方法：

Measure time point of outcome：

First medication to first radiographic disease progression or death (whichever occurs first).

Measure method：

指标中文名：

总生存期

指标类型：

次要指标

Outcome：

OS

Type：

Secondary indicator

测量时间点：

首次用药至受试者因任何原因死亡的时间。

测量方法：

Measure time point of outcome：

The time between the first dose and the subject's death from any cause.

Measure method：

指标中文名：

主要病理缓解率

指标类型：

次要指标

Outcome：

MPR

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

病理完全缓解率

指标类型：

主要指标

Outcome：

pCR

Type：

Primary 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 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）：

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）：

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）：

2025.06

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

2025.06

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

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

Case Record Form

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2024-07-23 10:22:36