中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2600127077
最近更新日期： Date of Last Refreshed on：	2026-06-24 11:05:42
注册时间： Date of Registration：	2026-06-24 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	一项评估佐利替尼联合芦康沙妥珠单抗治疗第三代EGFR-TKIs一线耐药EGFR突变伴脑转移NSCLC患者有效性和安全性的前瞻性临床研究
Public title：	A Prospective Clinical Study Evaluating the Efficacy and Safety of Zorifertinib in Combination with Sacituzumab Tirumotecan in Patients with EGFR-mutated NSCLC and Brain Metastases after First-line Resistance to Third-generation EGFR-TKIs.
注册题目简写：
English Acronym：
研究课题的正式科学名称：	一项评估佐利替尼联合芦康沙妥珠单抗治疗第三代EGFR-TKIs一线耐药EGFR突变伴脑转移NSCLC患者有效性和安全性的前瞻性临床研究
Scientific title：	A Prospective Clinical Study Evaluating the Efficacy and Safety of Zorifertinib in Combination with Sacituzumab Tirumotecan in Patients with EGFR-mutated NSCLC and Brain Metastases after First-line Resistance to Third-generation EGFR-TKIs.
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：	王龑	研究负责人：	任胜祥; 陈晓霞
Applicant：	Wang Yan	Study leader：	Ren Shengxiang; Chen Xiaoxia
申请注册联系人电话： Applicant telephone：	+86 13918127364	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：	1259347283@qq.com	研究负责人电子邮件： Study leader's E-mail：	harry_ren@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：	中国上海市杨浦区政民路507号	研究负责人通讯地址：	中国上海市杨浦区政民路507号
Applicant address：	No. 507, Zhengmin Road, Yangpu District, Shanghai, China	Study leader's address：	No. 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：	L26-516	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：	Medical Ethics Committee of Shanghai Pulmonary Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2026-04-23 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：	中国上海市杨浦区政民路507号
Contact Address of the ethic committee：	No. 507, Zhengmin Road, Yangpu District, Shanghai, China
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：

中国上海市杨浦区政民路507号

Primary sponsor's address：

No. 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：	中国上海市杨浦区政民路507号
Institution hospital：	Shanghai Pulmonary Hospital	Address：	No. 507, Zhengmin Road, Yangpu District, Shanghai, China

经费或物资来源：

自选课题（自筹）

Source(s) of funding：

Self-selected topic (self-funded)

研究疾病：

第三代EGFR-TKIs一线治疗（单药或联合）出现疾病进展的，影像学确诊存在脑实质转移（可合并脑膜转移，单纯脑膜转移除外）的非小细胞肺癌

Target disease：

Non-small cell lung cancer patients with brain parenchymal metastasis (except meningeal metastasis) diagnosed by imaging after disease progression during first-line treatment with third-generation EGFR-TKIs (single agent or combination)

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：

其它

Study phase：

N/A

研究设计：

单臂

Study design：

Single arm

研究目的：

评估佐利替尼联合芦康沙妥珠单抗治疗第三代EGFR-TKIs一线耐药EGFR突变伴脑转移NSCLC患者的初步有效性和安全性特征。

Objectives of Study：

To evaluate the preliminary efficacy and safety profiles of zorifertinib in combination with sacituzumab tirumotecan in EGFR-mutated NSCLC patients with brain metastases who have developed resistance to first-line third-generation EGFR-TKIs.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1.The subject has fully understood the study and voluntarily signed the Written Informed Consent Form (ICF).
2.Aged 18 to 75 years (inclusive) at the time of signing the ICF.
3.Histologically or cytologically confirmed NSCLC with documented EGFR-sensitive mutations (including L858R and/or Exon 19 Del).
4.Radiographically confirmed brain parenchymal metastases. Patients may have concurrent leptomeningeal metastases (LM); however, those with LM only, spinal cord compression, or extensive LM are excluded.
5.Disease progression following first-line treatment with a third-generation EGFR-TKI (either as monotherapy or in combination), including patients who failed adjuvant therapy (progression during adjuvant therapy or within 6 months after treatment discontinuation).
6.Must have at least one reproducible and evaluable target lesion (intracranial and/or extracranial) according to RECIST v1.1. Previously irradiated lesions cannot be considered target lesions unless radiographic evidence shows clear progression of the lesion.
7.For subjects with neurological symptoms, the symptoms must be stable, requiring no increase in corticosteroid dosage for at least 1 week prior to the start of study treatment to maintain CNS symptom control.
8.All toxicities related to prior anti-tumor therapies (including radiotherapy) must have recovered to CTCAE v5.0 grade <=1 (except for platinum-related neurotoxicity, which must recover to grade <= 2; and alopecia of any grade, which is permitted).
9. During the screening period for the subjects, the following conditions must be met: (1) Neutrophil count >= 1.5 x 10^9/L (2) Platelet count >= 100 x 10^9/L (3) Hemoglobin >=90 g/L (4) Serum creatinine <= 1.5 x ULN, or creatinine clearance rate (Cockcroft-Gault formula) >= 50 mL/min (5) Total bilirubin <= 1.5 x ULN (for subjects with Gilbert syndrome or liver metastasis, <= 3 x ULN is allowed) (6) Aspartate aminotransferase <=2.5 x ULN (for subjects with liver metastasis, <= 5 x ULN is allowed) (7) Alanine aminotransferase <= 2.5 x ULN (for subjects with liver metastasis, <= 5 x ULN is allowed);
10.The subject's estimated survival period is >= 3 months.
11. ECOG performance status <= 1.

排除标准：

1.研究药物用药前28天内有放疗史，或发生在研究用药前14天内的骨骼姑息性放疗。
2.在研究治疗首次给药前4周内，接受过重大外科手术（如胸腔内、腹腔内或盆腔内手术）或尚未从上述手术相关副作用中恢复的受试者。
3.除NSCLC，还合并有其他的目前需要治疗的恶性肿瘤。
4.患有有临床意义、不可控的心脏疾病和/或6个月内有心脏相关事件，如：（1）筛选期前6个月内有心肌梗死或有记录的心衰病史（NYHA分级III-IV）；（2）难以控制的高血压：收缩压≥160 mmHg和/或舒张压≥100 mmHg，伴或不伴有降压药物治疗，筛选期前调整降压药是允许的；（3）药物不能控制的心律失常；（4）筛选期QTcF＞470 ms；（5）左心室射血分数(LVEF)<50%。
5.患有胃肠道疾病或胃肠道功能严重损伤，可能明显影响药物吸收（如溃疡性疾病，不能控制的恶心，或呕吐、腹泻，或吸收不良综合征）。
6.有记录的重度干眼综合征，重度睑板腺疾病和/或睑缘炎，或存在妨碍/延迟角膜愈合的严重的角膜疾病病史。
7.肺部并发疾病导致的临床严重肺损害，包括但不限于任何基础肺部疾病（如首次给药前 3 个月内的严重哮喘、重度慢性阻塞性肺疾病、限制性肺疾病等）或任何可能累及肺部的自身免疫、结缔组织或炎性疾病（即类风湿关节炎、干燥综合征、结节病等），或既往全肺切除术。
8.首次给药前 4 周内发生严重感染，包括但不限于伴有需要住院治疗的并发症、败血症或严重肺炎；首次给药前 2 周内存在需要接受全身系统性抗感染治疗的活动性感染。
9.给药前 2 周内接受过非特异性免疫调节治疗（包括但不限于干扰素、 IL-2）。
10.研究药物用药前1周内及在研究期间不能停用如下药物：CYP3A4的强诱导剂或强抑制剂、可能导致QT间期延长或尖端扭转型室速的药物。
11.已知的既往有或目前合并有HIV感染患者；已知活动性梅毒感染患者；HCV抗体阳性的患者，如检测不到HCV-RNA（HCV-RNA检测正常下限以研究中心的检测值为准），且没有合并乙型肝炎病毒（HBV）感染，则可以入组。HBV感染者如满足以下条件则允许入组： 1) 活动性乙肝患者须满足如下条件：开始研究治疗前至少抗病毒6周，HBV DNA须＜100 IU/mL，ALT和AST水平须＜ULN； 2) 乙肝已缓解或慢性乙肝患者须满足以下：研究治疗开始前患者已接受预防性抗病毒治疗至少2周，转氨酶低于ULN，HBV DNA低于100IU/ml 。
12.已检测出怀孕或哺乳期妇女；育龄期妇女和可生育男性要求在佐利替尼给药期间和末次给药后3个月内、芦康沙妥珠单抗给药期间和末次给药后6个月内能够采用高效的避孕方法。
13.伴有其他严重的、急性或慢性医学疾病如不可控制的糖尿病或心理疾病或实验室检查异常，研究者判断参与研究给药可能给受试者带来更多风险或使研究结果难以解释。
14.存在需要类固醇治疗的（非感染性）间质性肺病（ILD）或非感染性肺炎病史，目前有ILD或非感染性肺炎，或筛选时存在无法经影像学检查排除的可疑ILD或非感染性肺炎。
15.既往曾接受过佐利替尼或原料药治疗的受试者。
16.既往接受过 TROP2 靶向治疗，或任何靶向拓扑异构酶 I 的药物治疗，包括抗体偶联药物（ADC）治疗（包括在辅助、新辅助治疗背景下）。
17.研究药物首次给药前30天内接种过活疫苗，或计划在研究期间接种活疫苗的受试者。
18.明确已知的对研究药物的活性或辅料或与研究药物化学结构或类别相似的药物过敏史。
19.合并其他的疾病或其他因素，研究者认为参加临床试验可能对受试者带来的风险较大。

Exclusion criteria：

1.Have a history of radiotherapy within 28 days prior to study drug administration, or palliative radiotherapy to bone occurring within 14 days prior to study drug administration. 2.Have undergone major surgery (e.g., intrathoracic, intra-abdominal, or intrapelvic surgery) within 4 weeks prior to the first dose of study treatment, or have not recovered from the side effects of such surgery. 3.Have other active malignancies currently requiring treatment, besides NSCLC. 4.Have clinically significant, uncontrolled heart disease and/or a cardiac-related event within the past 6 months, such as: (1) Myocardial infarction or documented history of heart failure (NYHA Class III‑IV) within 6 months prior to screening; (2) Uncontrolled hypertension: systolic blood pressure >=160 mmHg and/or diastolic blood pressure >=100 mmHg, with or without antihypertensive medication; adjustment of antihypertensive medication before screening is permitted; (3) Arrhythmias not controlled by medication; (4) QTcF >470 ms at screening; (5) Left ventricular ejection fraction (LVEF) <50%. 5.Have gastrointestinal diseases or severely impaired gastrointestinal function that may significantly affect drug absorption (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome). 6.Have a documented history of severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or severe corneal disease that impedes/delays corneal healing. 7.Have clinically severe pulmonary impairment due to concomitant lung diseases, including but not limited to any underlying lung disease (e.g., severe asthma within 3 months prior to the first dose, severe COPD, restrictive lung disease, etc.) or any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.), or previous pneumonectomy. 8.Have a serious infection within 4 weeks prior to the first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; or have an active infection requiring systemic anti-infective therapy within 2 weeks prior to the first dose. 9.Have received non‑specific immunomodulatory therapy (including but not limited to interferon, IL‑2) within 2 weeks prior to dosing. 10.Cannot discontinue the following drugs within 1 week prior to study drug administration and during the study period: strong inducers or strong inhibitors of CYP3A4, or drugs that may prolong the QT interval or cause torsade de pointes. 11.Known previous or current HIV infection; known active syphilis infection; patients who are HCV antibody positive may be enrolled if HCV‑RNA is undetectable (lower limit of normal based on the study site's assay) and there is no concurrent hepatitis B virus (HBV) infection. HBV‑infected patients may be enrolled if the following criteria are met: For active hepatitis B: at least 6 weeks of antiviral therapy before starting study treatment, HBV DNA <100 IU/mL, and ALT and AST levels

研究实施时间：

Study execute time：

从 From 2026-06-30 00:00:00至 To 2028-12-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2026-07-01 00:00:00 至 To 2027-06-30 00:00:00

干预措施：

Interventions：

组别：	干预组	样本量：	40
Group：	Intervention group	Sample size：	40
干预措施：	佐利替尼联合芦康沙妥珠单抗	干预措施代码：
Intervention：	Zorifertinib combination with Sacituzumab Tirumotecan	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

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：	三级甲等
Institution hospital：	Jiangsu Provincial Cancer 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)：	东阳市人民医院	单位级别：	三级甲等
Institution hospital：	Dongyang People's Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

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：	治疗开始后每8周±14天进行影像学检查	测量方法：	基于RECIST1.1标准/评估，定义为完全缓解（CR）及部分缓解（PR）的受试者占总受试者的比例
Measure time point of outcome：	Imaging examinations will be performed every 8 weeks (±14 days) after the start of treatment.	Measure method：	Based on RECIST 1.1 criteria, defined as the proportion of subjects who achieve Complete Response (CR) or Partial Response (PR) among all subjects.

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：	治疗开始后每8周±14天进行影像学检查	测量方法：	首次使用研究治疗至基于RECIST1.1标准评估受试者整体客观疾病进展或死亡（非疾病进展导致的死亡）的时间。
Measure time point of outcome：	Imaging examinations will be performed every 8 weeks (±14 days) after the start of treatment.	Measure method：	The time from the first use of study treatment to the overall objective disease progression as assessed by RECIST 1.1 criteria, or death (death not due to disease progression).

指标中文名：	颅内客观缓解率	指标类型：	次要指标
Outcome：	Intracranial Objective Response Rate	Type：	Secondary indicator
测量时间点：	治疗开始后每8周±14天进行影像学检查	测量方法：	基于mRECIST1.1/RANO-BM标准评估，定义为颅内完全缓解（CR）及部分缓解（PR）的受试者占总受试者的比例。
Measure time point of outcome：	Imaging examinations will be performed every 8 weeks (±14 days) after the start of treatment.	Measure method：	Based on mRECIST 1.1 / RANO?BM criteria, defined as the proportion of subjects who achieve intracranial Complete Response (CR) or Partial Response (PR) among all subjects.

指标中文名：	颅内无进展生存期	指标类型：	次要指标
Outcome：	Intracranial Progression-Free Survival	Type：	Secondary indicator
测量时间点：	治疗开始后每8周±14天进行影像学检查	测量方法：	首次使用研究治疗至基于mRECIST1.1标准/RANO-BM标准评估颅内疾病进展或死亡（非疾病进展导致的死亡）的时间。
Measure time point of outcome：	Imaging examinations will be performed every 8 weeks (±14 days) after the start of treatment.	Measure method：	The time from the first use of study treatment to intracranial disease progression assessed according to mRECIST 1.1 criteria / RANO?BM criteria, or death (death not due to disease progression).

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：	2.5年	测量方法：	从首次服用研究用药至（因任何原因）死亡的时间。
Measure time point of outcome：	2.5 years	Measure method：	The time from the first dose of study treatment to death from any cause.

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	无	组织：
Sample Name：	N/A	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）：

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:

不公开/Private

盲法：	无
Blinding：	None

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)：	N/A
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：	无/No
注册人： Name of Registration：	2026-06-24 11:03:56