ChiCTR2500113360 版本V1.0 版本创建时间2025/11/27 11:22:52 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：

 ChiCTR2500113360 

最近更新日期：

Date of Last Refreshed on：

 2025-11-27 11:22:35 

注册时间：

Date of Registration：

 2025-11-27 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

依沃西单抗联合三代EGFR-TKIs治疗EGFR-TKIs中缓慢进展及潜在进展的晚期非小细胞肺癌的Ⅱ期临床研究

Public title：

A phase II clinical study of ivosimab combined with third-generation EGFR-TKIs in the treatment of advanced non-small cell lung cancer with slow progression and potential progression during EGFR-TKIs therapy

注册题目简写：

English Acronym：

研究课题的正式科学名称：

依沃西单抗联合三代EGFR-TKIs治疗EGFR-TKIs中缓慢进展及潜在进展的晚期非小细胞肺癌的Ⅱ期临床研究

Scientific title：

A phase II clinical study of ivosimab combined with third-generation EGFR-TKIs in the treatment of advanced non-small cell lung cancer with slow progression and potential progression during EGFR-TKIs 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：

孟祥姣 

研究负责人：

孟祥姣 

Applicant：

Meng Xiangjiao 

Study leader：

Meng Xiangjiao 

申请注册联系人电话：

Applicant telephone：

 +86 137 9315 0996

研究负责人电话：

Study leader's
telephone：

+86 137 9315 0996

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：

 mengxiangjiao@126.com

研究负责人电子邮件：

Study leader's E-mail：

 mengxiangjiao@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：

山东省济南市槐荫区济兖公路440号

研究负责人通讯地址：

山东省济南市槐荫区济兖公路440号

Applicant address：

No. 440, Jiyuan Road, Huaiyin District, Jinan City, Shandong Province

Study leader's address：

No. 440, Jiyuan Road, Huaiyin District, Jinan City, Shandong 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：

山东第一医科大学附属肿瘤医院(山东省肿瘤医院)

Applicant's institution：

Shandong First Medical University Affiliated Tumor Hospital (Shandong Provincial Tumor Hospital)

研究负责人所在单位：

山东第一医科大学附属肿瘤医院(山东省肿瘤医院)

Affiliation of the Leader：

Shandong First Medical University Affiliated Tumor Hospital (Shandong Provincial Tumor 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：

 SDZLEC2025-480-02

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 Shandong First Medical University Affiliated Tumor Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2025-11-10 00:00:00

伦理委员会联系人：

宋现让

Contact Name of the ethic committee：

Song Xianrang

伦理委员会联系地址：

山东省济南市槐荫区济兖公路440号

Contact Address of the ethic committee：

No. 440, Jiyan Highway, Huaiyin District, Jinan City, Shandong Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 531 6267 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：

山东第一医科大学附属肿瘤医院

Primary sponsor：

Shandong First Medical University Affiliated Tumor Hospital

研究实施负责（组长）单位地址：

山东省济南市槐荫区济兖公路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)：

山东

市(区县)：

济南

Country：

China

Province：

Shandong

City：

Jinan

单位(医院)：

山东第一医科大学附属肿瘤医院

具体地址：

山东省济南市槐荫区济兖公路440号

Institution
hospital：

Shandong First Medical University Affiliated Tumor Hospital

Address：

No. 440, Jiyuan Road, Huaiyin District, Jinan City, Shandong Province

经费或物资来源：

依沃西单抗（100mg,736/瓶）全免，由康方药业有限公司提供

Source(s) of funding：

Ivosimod (100mg, 736 tablets per bottle) is provided free of charge and is supplied by Kangfang Pharmaceutical Co., Ltd.

研究疾病：

非小细胞肺癌  

Target disease：

NSCLC

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-III期临床试验 

Study phase：

2-3

研究设计：

单臂 

Study design：

Single arm 

研究目的：

评价依沃西单抗联合三代EGFR-TKIs治疗EGFR-TKIs中缓慢进展及潜在进展的晚期非小细胞肺癌的疗效和安全性  

Objectives of Study：

Evaluation of the efficacy and safety of evolocumab combined with third-generation EGFR-TKIs in the treatment of advanced non-small cell lung cancer with slow progression and potential progression during EGFR-TKIs therapy by YI WO.

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.自愿签署书面知情同意书； 2.≥18周岁； 3.东部肿瘤协作组（ECOG）体能状况评分为0或1； 4.预期生存期 ≥3个月； 5.组织学或细胞学证实的，不能行手术完全切除且不能接受根治性同步/序贯放化疗的局部晚期（IIIB/IIIC期）或转移性（IV期）非鳞状NSCLC（根据国际抗癌联盟和美国癌症联合委员会第8版肺癌TNM分期）； 6.入组前经肿瘤组织学或细胞学或血液学证实EGFR敏感突变阳性，19外显子缺失（19Del）和21外显子点突变（L858R），EGFR-T790M突变者也可入组。 7.接受EGFR-TKIs治疗中发生缓慢进展或潜在进展： 缓慢进展定义：EGFR TKIs治疗疗效达完全缓解（CR）或部分缓解（PR），患者6个月肿瘤负荷增加不超过20%（靶病灶增加不超过20%；和/或出现不超过3个新发病灶, 和/或非靶病灶个数增加不超过20%），无临床症状恶化。 潜在进展定义：血液CEA <10.0ng/mL，连续2次检测值≥10ng/mL（检测时间间隔不少于1个月）；或血液CEA≥10.0ng/mL，连续两次检测逐渐增加（间隔时间不少于1个月）。 8.至少有一个可测量病灶； 9.主要器官功能正常，即符合下列标准： 1) 血常规检查须符合（14天内未输血、未使用造血因子和未使用药物纠正）： a.中性粒细胞绝对值（ANC）≥1.5×10^9/L（1,500/mm^3）；b.血小板计数（PLT）≥90×10^9/L（100,000/mm^3）；c.血红蛋白（HB）≥90g/L； 2) 生化检查须符合以下标准： a.丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）≤2.5×ULN；b. 血清白蛋白（ALB）≥28g/L ；c.血清肌酐sCr ≤1.5×ULN，(Cockcroft-Gault公式，尿蛋白＜2+或24小时尿蛋白定量＜1.0g； 3) 凝血功能须符合：国际标准化比率INR≤1.5×ULN且活化部分凝血活酶时间APTT≤1.5×ULN；

Inclusion criteria

1. Voluntary signing of a written informed consent form; 2. >= 18 years old; 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 4. Expected survival period >= 3 months; 5. Histological or cytological confirmed, locally advanced (IIIB/IIIC stage) or metastatic (IV stage) non-squamous NSCLC (according to the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer 8th edition lung cancer TNM staging); 6. Before enrollment, confirmed by tumor histology or cytology or hematology that EGFR sensitive mutations are positive, including 19 exon deletion (19Del) and 21 exon point mutation (L858R), and patients with EGFR-T790M mutation can also be enrolled. 7. Occurrence of slow progression or potential progression during EGFR-TKIs treatment: Slow progression definition: EGFR TKIs treatment efficacy reaches complete response (CR) or partial response (PR), and the patient's tumor burden increases by no more than 20% within 6 months (target lesion increase by no more than 20%; and/or no more than 3 new lesions, and/or non-target lesion number increase by no more than 20%), without clinical symptom deterioration. Potential progression definition: Blood CEA < 10.0 ng/mL, and two consecutive test values >= 10 ng/mL (time interval of detection not less than 1 month); or blood CEA >= 10.0 ng/mL, and two consecutive tests gradually increase (time interval not less than 1 month). 8. At least one measurable lesion; 9. Normal major organ function, that is, meeting the following criteria: 1) Blood routine examination must meet (within 14 days, no blood transfusion, no use of hematopoietic factors and no use of drugs to correct): a. Absolute neutrophil count (ANC) >= 1.5 × 10^9/L (1,500/mm^3); b. Platelet count (PLT) >= 90 × 10^9/L (100,000/mm^3); c. Hemoglobin (HB) >= 90 g/L; 2) Biochemical examination must meet the following criteria: a. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) <= 2.5 × ULN; b. Serum albumin (ALB) >= 28 g/L; c. Serum creatinine sCr <= 1.5 × ULN, (Cockcroft-Gault formula, urine protein < 2+ or 24-hour urine protein quantification < 1.0 g; 3) Coagulation function must meet: international normalized ratio INR <= 1.5 × ULN and activated partial thromboplastin time APTT <= 1.5 × ULN

排除标准：

1.大细胞癌及混合细胞肺癌，混有小细胞肺癌成份的患者； 2.对EGFR-TKIs原发耐药的患者（EGFR-TKIs治疗时间< 3个月）； 3.经放疗后再次进展的脑转移及瘤内出血的患者； 4.筛选期影像学显示肿瘤包绕重要血管或存在明显坏死、空洞，且研究者判定进入研究会引起出血风险； 5.当前存在高血压且经口服降压药物治疗后收缩压≥150 mmHg或舒张压≥100 mmHg； 6.经治疗未能控制的高血糖（空腹血糖＞15 mmol/L）； 7.存在严重间质性肺炎； 8.有严重出血倾向或凝血功能障碍病史；首次给药前1个月内存在具有显著临床意义的出血症状，包括但不限于消化道出血、咳血（定义为咳出或咯出≥1茶匙鲜血或小血块或只咳血无痰液，允许痰中带血者入组）、鼻腔出血（不包括鼻衄出血及回缩性涕血）； 9.除非小细胞肺癌以外，受试者在入组前3年内患有其他恶性肿瘤。不排除患有其他恶性肿瘤通过局部治疗已治愈的受试者，例如基底或皮肤鳞状细胞癌、浅表膀胱癌、宫颈或乳腺原位癌。 10.患有在过去两年内需要系统性治疗的活动性自身免疫性疾病（如使用改善病情药物、皮质类固醇、免疫抑制剂治疗）。替代治疗（如甲状腺素、胰岛素、或针对肾上腺或垂体功能不全的生理性皮质类固醇替代治疗）不认为是一种系统性治疗； 11.首次用药前1年内存在重大疾病病史，具体为： 1) 首次给药前12个月内存在需住院治疗的不稳定性心绞痛、心肌梗塞、充血性心力衰竭（纽约心脏病协会NYHA分类≥2级）或血管疾病（如存在破裂风险的主动脉瘤）；有发生高血压危象，高血压脑病的病史。 2) 首次给药前6个月内存在食管胃底静脉曲张，严重溃疡，伤口未愈，腹瘘，腹腔内脓肿或急性胃肠道出血病史； 3) 首次给药前1个月内发生过任何动脉血栓栓塞事件，NCI CTCAE 5.0规定的3级及以上的静脉血栓栓塞事件，短暂性脑缺血发作，脑血管意外，高血压危象或高血压脑病； 4) 首次给药前4周内发生慢性阻塞性肺病急性加重； 12.首次给药前4周内发生严重感染，包括但不局限于伴有需要住院治疗的合并症、败血症或严重肺炎； 13.在首次给药前4周内进行过重大外科手术或发生严重外伤，或在首次给药后的4周内有重大外科手术计划者（由研究者决定）；在首次给药前3天内进行过较小的局部手术（不包括经外周静脉穿刺中心静脉置管术和静脉输液港植入术）； 14.存在有临床症状或需要引流的胸腔积液、心包积液或腹水的受试者； 15.已知异体器官移植史（排除角膜移植）或异体造血干细胞移植史； 16.已知对任何研究药物的任何成分过敏；已知对其他单克隆抗体产生严重超敏反应的病史； 17.同时入组另一项临床研究，除非其为一项观察性、非干预性的临床研究或干预性研究的随访期； 18.已知有精神疾病、药物滥用、酗酒或吸毒史； 19.怀孕或哺乳期妇女；有生育能力的受试者不愿或无法采取有效的避孕措施者。

Exclusion criteria：

1. Patients with large cell carcinoma and mixed cell lung cancer, which contain small cell lung cancer components; 2. Patients who have primary resistance to EGFR-TKIs (the duration of EGFR-TKI treatment is less than 3 months); 3. Patients with brain metastasis and intratumoral hemorrhage who have experienced recurrence after radiotherapy; 4. Patients whose imaging results during the screening period show that the tumor surrounds important blood vessels or has obvious necrosis and cavities, and the investigator determines that participating in the study will cause bleeding risks; 5. Patients currently have hypertension and their systolic blood pressure is >= 150 mmHg or diastolic blood pressure is >= 100 mmHg after oral antihypertensive drug treatment; 6. Patients with uncontrolled hyperglycemia (fasting blood glucose > 15 mmol/L); 7. Patients with severe interstitial pneumonia; 8. Patients with a history of severe bleeding tendency or coagulation dysfunction; if there are significant clinical symptoms of bleeding within 1 month before the first administration, including but not limited to gastrointestinal bleeding, hemoptysis (defined as coughing or expectoration of >= 1 teaspoon of blood or small blood clots or only hemoptysis without sputum, allowing those with blood in sputum to be enrolled), nasal bleeding (excluding epistaxis bleeding and retrograde nasal bleeding); 9. Unless it is small cell lung cancer, the subjects had other malignant tumors within 3 years before enrollment. Patients with other malignant tumors that have been cured by local treatment, such as basal or skin squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ, are not excluded; 10. Patients with active autoimmune diseases that require systemic treatment in the past two years (such as treatment with disease-modifying drugs, corticosteroids, immunosuppressants). Alternative treatments (such as thyroid hormone, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) are not considered as systemic treatment; 11. Patients had a significant medical history within 1 year before the first administration, specifically: 1) Within 12 months before the first administration, there was the need for hospitalization for unstable angina pectoris, myocardial infarction, congestive heart failure (NYHA classification >= 2), or vascular diseases (such as aortic aneurysm with rupture risk); there was a history of hypertension crisis or hypertensive encephalopathy. 2) Within 6 months before the first administration, there was a history of esophageal and gastric varices, severe ulcers, wounds not healed, abdominal fistula, abdominal abscess or acute gastrointestinal bleeding; 3) Within 1 month before the first administration, there was any arterial thromboembolic event, grade 3 or above venous thromboembolic events, transient cerebral ischemic attack, cerebral vascular accident, hypertension crisis or hypertensive encephalopathy; 4) Within 4 weeks before the first administration, there was an acute exacerbation of chronic obstructive pulmonary disease; 12. Within 4 weeks before the first administration, patients had a severe infection, including but not limited to those requiring hospitalization for complications, sepsis or severe pneumonia; 13. Within 4 weeks before the first administration, patients had undergone major surgery or suffered from severe trauma, or had a major surgical plan within 4 weeks after the first administration (determined by the investigator); within 3 days before the first administration, patients had undergone minor local surgery (excluding peripheral venous puncture central venous catheterization and venous port implantation); 14. Patients with clinical symptoms or need for drainage of pleural effusion, pericardial effusion or ascites; 15. Patients with a known history of allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 16. Patients with a known history of any allergic reaction to any component of the study drug; patients with a known history of severe hypersensitivity reaction to other monoclonal antibodies; 17. Patients are simultaneously enrolled in another clinical study, unless it is an observational, non-interventional clinical study or the follow-up period of an intervention study; 18. Patients have a history of mental illness, drug abuse, alcoholism or drug addiction; Pregnant or lactating women; Those with reproductive capacity who are unwilling or unable to take effective contraceptive measures.

研究实施时间：

Study execute time：

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

征募观察对象时间：

Recruiting time：

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

干预措施：

Interventions：

组别：

干预组

样本量：

 36

Group：

intervention group

Sample size：

干预措施：

安全导入期：入组6例受试者，依沃西单抗20mg/kg Q3W+三代EGFR TKI QD 扩展入组期：入组30例受试者，依沃西单抗20mg/kg Q3W+三代EGFR TKI QD

干预措施代码：

Intervention：

Safe introduction period: 6 subjects were enrolled, with ivermectin at 20mg/kg every 3 weeks + third-generation EGFR TKI every day Expansion enrollment period: 30 subjects were enrolled, with ivermectin at 20mg/kg every 3 weeks + third-generation EGFR TKI every day

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)：

 济南 

Country：

China

Province：

Shandong

City：

Jinan

单位(医院)：

 山东第一医科大学附属肿瘤医院(山东省肿瘤医院) 

单位级别：

 三甲 

Institution
hospital：

Shandong First Medical University Affiliated Tumor Hospital (Shandong Provincial Tumor Hospital)

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

无进展生存期（PFS）

指标类型：

主要指标

Outcome：

Progression-free survival (PFS)

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（ORR）

指标类型：

次要指标

Outcome：

Objective response rate (ORR)

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（DCR）

指标类型：

次要指标

Outcome：

Disease control rate (DCR)

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（OS）

指标类型：

次要指标

Outcome：

Overall survival period (OS)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

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：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

收集血液及组织样本检测分子标志物表达、肿瘤突变负荷、免疫细胞浸润等，以识别治疗获益人群。

指标类型：

附加指标

Outcome：

Collect blood and tissue samples to detect the expression of molecular markers, tumor mutational burden, and immune cell infiltration, etc., in order to identify the population that will benefit from the treatment.

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：

标本中文名：

肺肿瘤组织

组织：

Sample Name：

Lung tumor tissue

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 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：

无

Blinding：

None

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

否No

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

无

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

None

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

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：

暂未确定/Not yet

注册人：

Name of Registration：

  2025-11-27 11:22:35