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：	ChiCTR2500113154
最近更新日期： Date of Last Refreshed on：	2025-11-25 15:43:46
注册时间： Date of Registration：	2025-11-25 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	SYS6010联合奥希替尼对照奥希替尼新辅助治疗可切除Ⅱ-ⅢB期伴EGFR敏感突变非鳞非小细胞肺癌的Ⅱ期临床研究
Public title：	A Study of SYS6010 Combined with Osimertinib versus Osimertinib alone as Neoadjuvant Therapy for Patients with EGFRm Resectable Non-squamous Non-small Cell Lung Cancer
注册题目简写：
English Acronym：
研究课题的正式科学名称：	一项评价SYS6010联合奥希替尼对照奥希替尼新辅助治疗可切除Ⅱ-ⅢB期伴EGFR敏感突变非鳞非小细胞肺癌参与者安全性和有效性的Ⅱ期临床研究
Scientific title：	A Phase II study to evaluate the safety and efficacy of SYS6010 combined with osimertinib versus osimertinib as neoadjuvant therapy in participants with resectable Stage II-IIIB non-squamous non-small cell lung cancer with EGFRm
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：	临床试验信息组	研究负责人：	李子明; 张鹏
Applicant：	Clinical Trials Information Group	Study leader：	Li Ziming; Zhang Peng
申请注册联系人电话： Applicant telephone：	+86 311 6908 5587	研究负责人电话： Study leader's telephone：	+86 21 2220 0000
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：	ctr-contact@cspc.cn	研究负责人电子邮件： Study leader's E-mail：	shunlu_shchest@sina.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：	中国河北省石家庄市高新区中山东路896号石药集团	研究负责人通讯地址：	中国上海市徐汇区淮海西路241号; 中国上海市杨浦区政民路507号
Applicant address：	896 Zhongshan East Road, Shijiazhuang, Hebei Province, China.	Study leader's address：	241 Huaihai West Road, Xuhui District, Shanghai, China; 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：	石药集团巨石生物制药有限公司
Applicant's institution：	CSPC Megalith Biopharmaceutical Co., Ltd
研究负责人所在单位：	上海市胸科医院; 上海市肺科医院
Affiliation of the Leader：	Shanghai Chest Hospital; 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：	LS25098	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：	上海市胸科医院伦理委员会
Name of the ethic committee：	Ethics Committee of Shanghai Chest Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2025-09-08 00:00:00
伦理委员会联系人：	陈仲林
Contact Name of the ethic committee：	Chen Zhonglin
伦理委员会联系地址：	中国上海市徐汇区淮海西路241号
Contact Address of the ethic committee：	241 Huaihai West Road, Xuhui District, Shanghai, China.
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 2220 0000	伦理委员会联系人邮箱： Contact email of the ethic committee：	chestgcp@126.com

研究实施负责（组长）单位：

上海市胸科医院; 上海市肺科医院

Primary sponsor：

Shanghai Chest Hospital; Shanghai Pulmonary Hospital

研究实施负责（组长）单位地址：

中国上海市徐汇区淮海西路241号; 中国上海市杨浦区政民路507号

Primary sponsor's address：

241 Huaihai West Road, Xuhui District, Shanghai, China; 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)：	河北	市(区县)：	石家庄
Country：	China	Province：	Hebei	City：	Shijiazhuang
单位(医院)：	石药集团巨石生物制药有限公司	具体地址：	河北省石家庄市高新区中山东路896号
Institution hospital：	CSPC Megalith Biopharmaceutical Co., Ltd	Address：	896 Zhongshan East Road, Shijiazhuang, Hebei Province, China.

经费或物资来源：

完全自筹-申办方

Source(s) of funding：

Self-financing-sponsor

研究疾病：

可切除的Ⅱ-ⅢB期伴EGFR敏感突变（19Del和L858R）的非鳞非小细胞肺癌

Target disease：

Resectable Stage II-IIIB non-squamous non-small cell lung cancer with EGFRm

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期临床试验

Study phase：

2

研究设计：

随机平行对照

Study design：

Parallel

研究目的：

评估接受SYS6010联合奥希替尼对照奥希替尼单药新辅助治疗EGFR敏感突变非鳞非小细胞肺癌参与者的主要病理反应率（MPR）的差异。

Objectives of Study：

To evaluate the difference in major pathological response (MPR) rate, based on blinded independent pathological review (BIPR), in participants with non-squamous non-small cell lung cancer with EGFR m receiving SYS6010 combined with osimertinib versus osimertinib monotherapy as neoadjuvant therapy.

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. 能够理解并自愿签署书面知情同意书（ICF）；  
2. 年龄 18-75 岁，性别不限；  
3. 经组织学或细胞学（需提供病理报告）确诊的非鳞非小细胞肺癌，根据国际肺癌研究协会（IASLC）第 8 版 TNM 分期标准为可切除或潜在可切除的 II-IIIB 期疾病（淋巴结转移不超过 N2），并在筛选时具备接受肺叶切除术、袖状切除术或双肺叶切除术的条件；  
4. 在筛选时，经由多学科团队（至少包括行肺癌手术的胸外科医生）进行评估，必须具备对原发肿瘤手术完全切除的条件；T4 分期的肿瘤只有在仅根据其大小（>=7 cm）定义为 T4 的情况下才符合条件；任何其他导致 T4 的原因（例如与以下任何结构粘连：膈肌、纵隔、心脏、大血管、气管、喉返神经、食管、椎体、隆突）都不符合；  
5. 淋巴结状态应通过全身性 18F-氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）以及增强 CT 进行评估。如果检查显示纵膈淋巴结阳性，须进行组织学确认，首选的方法是超声内镜（支气管内超声/食管超声），也可进行纵隔镜检查或胸腔镜检查进行淋巴结活检；  
6. 经中心实验室或当地检测机构检测确认存在 EGFR 敏感突变（19 外显子缺失或 21 外显子 L858R 突变，允许与其他 EGFR 位点突变共存）；  
7. 既往未接受过系统性抗肿瘤治疗（包括化疗、生物疗法、靶向治疗、免疫治疗）；  
8. 基线至少存在一个符合 RECIST v1.1 标准定义的可测量病灶；  
9. ECOG PS 体能状态评分 0 分或 1 分；  
10. 预期生存时间 >= 6 个月；  
11. 主要器官和骨髓功能在首次给药前 7 天内，符合：  
    (1) 血常规：  
        1) 中性粒细胞绝对计数（ANC）>= 1.5×10^9/L （在血液学评估前 7 天内未接受过细胞生长因子治疗，14 天内未接受过长效粒细胞集落刺激因子（G-CSF）和聚乙二醇化重组人粒细胞刺激因子（PEG-CSF）治疗）；  
        2) 血小板 >= 100×10^9/L（在血液学评估前 7 天内未接受过血小板输注或重组人血小板生成素治疗）；  
        3) 血红蛋白 >= 100 g/L（在血液学评估前 14 天内无红细胞输注/输血治疗）；  
    (2) 肾功能：血清肌酐 <= 1.5×ULN，且肌酐清除率（CrCL) >= 50 mL/min（使用 Cockcroft-Gault 公式，附录：13.8）；  
    (3) 肝功能：  
        1) 总胆红素 <= 1.5×ULN（Gilbert 综合征 <= 3×ULN）；  
        2) 天冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）<= 2.5×ULN；  
    (4) 凝血功能：  
        1) 国际标准化比值（INR）<= 1.5×ULN；  
        2) 部分活化凝血活酶时间（APTT）<= 1.5×ULN；  
12. 有生育能力的女性必须使用高效的避孕措施。有生育能力的女性在随机前 7 天内的血妊娠试验为阴性；任何有生育能力的男性和女性参与者必须同意在整个试验期间以及末次给药后 7 个月内使用高效的避孕方法（具体请详见 13.1.2，其中男性参与者必须愿意使用屏障避孕方法），且男性参与者应在末次给药后 7 个月内避免捐献精子。参与者有生育能力是指：他/她生物学上有能力有孩子以及有正常的性生活。女性参与者满足至少下列标准之一证明没有妊娠风险：医学确认为绝经后状态（绝经后定义为 50 岁或 50 岁以上，并在停止所有外源激素治疗后闭经至少 12 个月;如果 50 岁以下的女性在停止外源性激素治疗后闭经 12 个月或更长时间，并且 LH 和 FSH 水平处于绝经后范围内，则视为绝经后状态）；曾经接受不可逆的绝育手术，包括子宫切除术或双侧卵巢切除术或双侧输卵管切除（除外双侧输卵管结扎）。

Inclusion criteria

1. Able to understand and voluntarily sign the written Informed Consent Form (ICF);  
2. Age 18–75 years, either sex;  
3. Histologically or cytologically confirmed (with pathology report) non-squamous non-small cell lung cancer (NSCLC), staged as resectable or potentially resectable Stage II–IIIB disease according to the IASLC 8th Edition TNM Staging System (lymph node involvement limited to N2), and eligible for lobectomy, sleeve resection, or bilobectomy at the time of screening;  
4. At screening, the participant must be evaluated by a multidisciplinary team (including at least a thoracic surgeon performing lung cancer surgery) and deemed eligible for complete surgical resection of the primary tumor; T4 tumors are eligible only if T4 status is defined solely by tumor size (>=7 cm); any other cause of T4 classification (e.g., invasion or adhesion to diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebrae, or carina) is excluded;  
5. Lymph node status must be assessed by whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contrast-enhanced CT. If mediastinal lymph nodes are suspected positive on imaging, histological confirmation is required, preferably via endobronchial ultrasound (EBUS) or endoscopic ultrasound (EUS); mediastinoscopy or thoracoscopy may be used as alternatives for lymph node biopsy;  
6. Confirmed by central or local laboratory testing the presence of an EGFR sensitizing mutation (exon 19 deletion or exon 21 L858R mutation; coexistence with other EGFR mutations is permitted);  
7. No prior systemic anti-tumor therapy (including chemotherapy, biologic therapy, targeted therapy, or immunotherapy);  
8. At least one measurable lesion according to RECIST v1.1 criteria at baseline;  
9. ECOG Performance Status (PS) score of 0 or 1;  
10. Expected survival time >= 6 months;  
11. Major organ and bone marrow function must meet the following criteria within 7 days prior to first dose:  
    (1) Hematological parameters:  
        1) Absolute neutrophil count (ANC) >= 1.5×10^9/L (without administration of hematopoietic growth factors within 7 days prior to hematological assessment, and no long-acting granulocyte colony-stimulating factor (G-CSF) or pegylated recombinant human G-CSF (PEG-CSF) within 14 days prior);  
        2) Platelet count >= 100×10^9/L (without platelet transfusion or recombinant human thrombopoietin within 7 days prior to hematological assessment);  
        3) Hemoglobin >= 100 g/L (without red blood cell transfusion within 14 days prior to hematological assessment);  
    (2) Renal function: serum creatinine <= 1.5×ULN, and creatinine clearance (CrCL) >= 50 mL/min (calculated using the Cockcroft-Gault formula; see Appendix 13.8);  
    (3) Hepatic function:  
        1) Total bilirubin <= 1.5×ULN (<= 3×ULN for Gilbert’s syndrome);  
        2) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5×ULN;  
    (4) Coagulation function:  
        1) International normalized ratio (INR) <= 1.5×ULN;  
        2) Activated partial thromboplastin time (APTT) <= 1.5×ULN;  
12. Women of childbearing potential must use highly effective contraception. A negative pregnancy test must be confirmed in women of childbearing potential within 7 days prior to randomization. All participants of childbearing potential—both male and female—must agree to use highly effective contraceptive methods throughout the trial and for 7 months after the last dose (details in Section 13.1.2); male participants must consent to use barrier contraception and must refrain from donating sperm for 7 months after the last dose. A participant is considered of childbearing potential if biologically capable of having children and having normal sexual activity. A female participant may be considered not at risk of pregnancy if she meets at least one of the following criteria: medically confirmed postmenopausal status (defined as age >=50 years with amenorrhea for at least 12 months following cessation of all exogenous hormone therapy; if under age 50, amenorrhea for 12 months or longer following cessation of exogenous hormone therapy, with LH and FSH levels in the postmenopausal range, is considered postmenopausal); or prior irreversible sterilization procedure, including hysterectomy, bilateral oophorectomy, or bilateral salpingectomy (excluding bilateral tubal ligation).

排除标准：

1. 诊断为 I 期、N3 的 IIIB 期以及 IIIC、IVA 和 IVB 期非小细胞肺癌； 2. 双源发或多源发肿瘤（如为肺癌双源发，参考排除标准第 8 条），以及小细胞肺癌和其他非小细胞肺癌的混合型病理组织类型； 3. 因侵犯大血管、隆突、气管、食管、心脏和/或椎体诊断为 T4 期的肺癌；以及/或任何较大的 N2 期肺癌； 4. 仅适合进行段切除术或楔形切除术； 5. 随机前 1 周内接受过以治疗肺癌为适应症的中成药制剂； 6. 首次研究治疗前 4 周内接受过外科大手术或有严重的外伤性损伤，或预期在研究期间接受大手术。一些临床操作如血管通路置管、穿刺活检是允许的； 7. 同时入组另一项临床研究，除非该研究是一项观察性（非干预性）临床研究，或处于一项干预性研究的随访期； 8. 其他原发性恶性肿瘤的病史（包括任何已知或疑似同时发生的原发性肺癌），以下情况除外： (1) 根治性治疗的恶性肿瘤，且在首次使用试验药物前至少 2 年内无明显活动性疾病，且潜在复发风险低； (2) 经过充分治疗的皮肤癌（不包括恶性黑色素瘤），且无疾病进展迹象； (3) 经过充分治疗的原位癌，且无疾病进展迹象； (4) 如为同时发生的 IA 期原发性肺癌，其大小不超过 2 cm，并且计划在针对参加本研究的 II 至 IIIB 期肺部肿瘤手术中进行切除； 9. 目前正在接受或首次研究治疗前 14 天内无法停止使用 CYP3A4 的强效抑制剂或诱导剂、OATP1B1 和 OATP1B3 抑制剂，或研究期间不能避免使用为 CYP3A4 强效抑制剂或诱导剂、OATP1B1 和 OATP1B3 抑制剂的药物、中药制剂和/或食物； 10. 有自身免疫性疾病史（包括干燥综合征、系统性红斑狼疮、银屑病、皮肌炎等）、免疫缺陷病史（包括 HIV 检测阳性，或患有其他获得性、先天性免疫缺陷疾病）或有器官移植史（角膜移植者除外）； 11. 存在活动性感染（包括因感染而接受静脉治疗的患者），包括无法控制的活动性乙型肝炎（HBV-DNA 高于当地检测值上限）、活动性丙型肝炎（HCV-RNA 阳性）、活动性梅毒、活动性结核病等：有人类乙型肝炎病毒（HBV）感染病史患者符合下列所有标准可以考虑入组： (1) 没有合并感染丙型肝炎病毒（HCV）且没有丙型肝炎病毒感染病史； (2) 活动性 HBV 感染（HBV DNA > 100 IU/mL）开始研究治疗前接受至少 6 周抗病毒治疗，HBV DNA < 100 IU/mL 且转氨酶 < 1 ULN； (3) 既往 HBV 感染或慢性 HBV 感染符合以下条件： 1) HBsAg（-）且抗 HBc Ig G 或总抗 HBc Ab 阳性，此外，患者应就诊至当地肝病专家，并按照当地指南进行治疗； 2) 或 HBs Ag（+），但是转氨酶已经持续 6 个月及以上在正常范围内，且 HBV DNA < 100 IU/mL（病毒携带者，非活跃状态）。并且参与者在首次给药前预防性接受 2-4 周抗病毒治疗； 12. 有需要治疗的重度或不可控制的心血管疾病，包括但不限于： (1) 心功能不全：随机前 6 个月内纽约心脏协会（NYHA）分级 >= II 级或因心功能不全住院； (2) 静息心电图节律、传导或形态的任何具有临床意义的重要异常，如完全性左束支传导阻滞、三度传导阻滞和二度传导阻滞； (3) 在随机前 6 个月内出现以下情况：心肌梗塞、严重或不稳定型心绞痛、充血性心力衰竭、主动脉夹层、冠脉或外周动脉搭桥术、血管成形术、脑血管意外、短暂性脑缺血发作或其他 3 级及以上心脑血管事件者； (4) 从 3 次 ECG 获得的使用 Fridericia 公式矫正的平均静息 QT 间期（QTcF）> 470 msec，患者有任何增加 QTc 延长风险或心律失常事件(如电解质异常)风险的因素，包括：低钾血症 >= CTCAE 2 级（首次给药前应记录电解质异常的纠正情况）； (5) 心力衰竭，先天性长 QT 综合征，长 QT 综合征家族史，或 40 岁以下一级亲属不明原因的猝死； (6) 严重心律失常，如频发室性早搏、心室颤动、严重快速性心律失常，以及 >= 2 级的室性心律失常； (7) 筛选期超声心动图（ECHO）或多门控采集（MUGA）技术显示左室射血分数（LVEF）<= 50%； (8) 未能有效控制的高血压（定义为经规范化降压药治疗后收缩压 >= 150 mmHg 和/或舒张压 >= 95 mmHg）； (9) 既往或当前患有心肌病，且经研究者判断对本试验可能有影响的； (10) 随机前 1 个月内有深静脉血栓形成或肺栓塞病史，允许无显著临床意义的血栓纳入（如非阻塞性导管相关血栓）； 13. 罹患全身性剥脱性皮炎、中毒性表皮坏死松解症和史蒂文斯-约翰逊综合征者； 14. 顽固性恶心、呕吐、慢性胃肠道疾病、无法口服吞咽药物、或既往接受小肠大部切除手术等存在经研究者判断严重影响胃肠道吸收的状况； 15. 存在病情严重或无法控制疾病的证据，包括但不限于无法控制的高血压、糖尿病和活动性出血倾向等； 16. 活动性或既往间质性肺病（ILD）/间质性肺炎病史，包括药物或放射诱发的间质性肺病/间质性肺炎病史； 17. 预计将在随机后 30 天内接受活疫苗治疗； 18. 既往有明确的神经或精神障碍史，包括癫痫或痴呆；已知对研究方案药物或任何研究药物辅料过敏或发生超敏反应或不可耐受的情况； 19. 妊娠期或哺乳期女性； 20. 不愿意或不能遵守研究程序和研究要求，经研究者判断对本试验依从性可能有影响，不适合参加本临床研究。

Exclusion criteria：

1. Diagnosis of Stage I, N3 Stage IIIB, Stage IIIC, Stage IVA, or Stage IVB non-small cell lung cancer (NSCLC); 2. Dual or multiple primary tumors (if dual primary lung cancers, refer to exclusion criterion 8), or mixed histological subtypes including small cell lung cancer and other types of NSCLC; 3. NSCLC diagnosed as T4 due to invasion of major vessels, carina, trachea, esophagus, heart, and/or vertebrae; and/or any large N2-stage NSCLC; 4. Eligible only for segmentectomy or wedge resection; 5. Received traditional Chinese medicine formulations indicated for lung cancer treatment within 1 week prior to randomization; 6. Underwent major surgery or suffered severe traumatic injury within 4 weeks prior to first study treatment, or is anticipated to undergo major surgery during the study period. Minor procedures such as vascular access placement or biopsy are permitted; 7. Simultaneously enrolled in another clinical trial, unless the other trial is an observational (non-interventional) study or the participant is in the follow-up phase of an interventional trial; 8. History of other primary malignancies (including any known or suspected concurrent primary lung cancer), except for the following: (1) Malignancies treated with curative intent and with no evidence of active disease for at least 2 years prior to first study drug administration, and with low risk of recurrence; (2) Adequately treated skin cancer (excluding malignant melanoma) with no evidence of disease progression; (3) Adequately treated carcinoma in situ with no evidence of disease progression; (4) Concurrent IA-stage primary lung cancer measuring <= 2 cm in diameter, planned for resection during the surgical procedure for the Stage II–IIIB lung tumor enrolled in this study; 9. Currently receiving, or unable to discontinue within 14 days prior to first study treatment, strong CYP3A4 inhibitors or inducers, or OATP1B1 and OATP1B3 inhibitors; or inability to avoid use of such drugs, traditional Chinese medicine formulations, and/or foods during the study period that are strong CYP3A4 inhibitors or inducers or OATP1B1/OATP1B3 inhibitors; 10. History of autoimmune disease (including Sjögren’s syndrome, systemic lupus erythematosus, psoriasis, dermatomyositis, etc.), immunodeficiency disorders (including HIV positivity or other acquired or congenital immunodeficiencies), or organ transplantation history (except corneal transplantation); 11. Active infection, including patients receiving intravenous therapy for infection, such as uncontrolled active hepatitis B (HBV-DNA above the local upper limit of detection), active hepatitis C (HCV-RNA positive), active syphilis, or active tuberculosis: Patients with a history of human hepatitis B virus (HBV) infection may be considered eligible if they meet all of the following criteria: (1) No concurrent or prior infection with hepatitis C virus (HCV); (2) For active HBV infection (HBV DNA > 100 IU/mL), at least 6 weeks of antiviral therapy must be initiated prior to study treatment, with HBV DNA < 100 IU/mL and transaminases < 1 ULN; (3) For prior or chronic HBV infection, eligibility requires meeting one of the following: 1) HBsAg negative and anti-HBc IgG or total anti-HBc antibody positive; patients must be evaluated by a local hepatology specialist and managed according to local guidelines; 2) Or HBsAg positive, with transaminases persistently normal for at least 6 months and HBV DNA < 100 IU/mL (viral carrier, non-active state); participants must receive prophylactic antiviral therapy for 2–4 weeks prior to first dose; 12. Severe or uncontrolled cardiovascular disease requiring treatment, including but not limited to: (1) Cardiac insufficiency: NYHA class >= II within 6 months prior to randomization or hospitalization due to heart failure; (2) Any clinically significant abnormality in resting ECG rhythm, conduction, or morphology, such as complete left bundle branch block, third-degree heart block, or second-degree heart block; (3) Myocardial infarction, severe or unstable angina, congestive heart failure, aortic dissection, coronary or peripheral artery bypass grafting, angioplasty, cerebrovascular accident, transient ischemic attack, or other grade 3 or higher cardiovascular events within 6 months prior to randomization; (4) Average resting QTcF interval (corrected by Fridericia formula) from three ECGs > 470 msec; presence of any factor increasing risk of QTc prolongation or arrhythmia (e.g., electrolyte abnormalities), including hypokalemia >= CTCAE Grade 2 (electrolyte abnormalities must be corrected and documented prior to first dose); (5) Heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in a first-degree relative under age 40; (6) Severe arrhythmias, including frequent ventricular premature contractions, ventricular fibrillation, severe tachyarrhythmias, or grade >= 2 ventricular arrhythmias; (7) Left ventricular ejection fraction (LVEF) <= 50% as determined by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan during screening; (8) Poorly controlled hypertension (defined as systolic blood pressure >= 150 mmHg and/or diastolic blood pressure >= 95 mmHg despite adequate antihypertensive therapy); (9) History of or current cardiomyopathy, as judged by the investigator to potentially impact this trial; (10) History of deep vein thrombosis or pulmonary embolism within 1 month prior to randomization; non-clinically significant thrombosis (e.g., non-obstructive catheter-related thrombosis) is permitted; 13. History of generalized exfoliative dermatitis, toxic epidermal necrolysis, or Stevens-Johnson syndrome; 14. Intractable nausea/vomiting, chronic gastrointestinal disorders, inability to orally swallow medications, or prior extensive small bowel resection, as judged by the investigator to significantly impair gastrointestinal absorption; 15. Evidence of severe or uncontrolled conditions, including but not limited to uncontrolled hypertension, diabetes, or active bleeding diathesis; 16. History of active or prior interstitial lung disease (ILD)/interstitial pneumonia, including drug- or radiation-induced ILD/pneumonia; 17. Anticipated receipt of live vaccine within 30 days after randomization; 18. History of significant neurological or psychiatric disorders, including epilepsy or dementia; known hypersensitivity, allergic reaction, or intolerance to study drugs or any excipients in the study formulation; 19. Pregnant or lactating females; 20. Unwillingness or inability to comply with study procedures and requirements, as judged by the investigator to potentially compromise adherence to the trial and thus render the participant unsuitable for participation.

研究实施时间：

Study execute time：

从 From 2025-11-30 00:00:00至 To 2032-12-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-11-30 00:00:00 至 To 2026-11-30 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	60
Group：	Trial group	Sample size：	60
干预措施：	SYS6010 4.5 mg/kg，静脉滴注，每 3 周一次（Q3W），联合奥希替尼 80 mg，口服，每日一次（QD），每 3 周为 1 个治疗周期	干预措施代码：
Intervention：	SYS6010 4.5 mg/kg via intravenous infusion every 3 weeks (Q3W), in combination with osimertinib 80 mg orally once daily (QD), with one treatment cycle lasting 3 weeks.	Intervention code：

组别：	对照组	样本量：	60
Group：	Control group	Sample size：	60
干预措施：	奥希替尼 80 mg，口服，QD，每 3 周为 1 个治疗周期	干预措施代码：
Intervention：	Osimertinib 80 mg orally once daily (QD), with one treatment cycle lasting 3 weeks.	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)：	上海市胸科医院	单位级别：	三甲
Institution hospital：	Shanghai Chest Hospital	Level of the institution：	Tertiary A

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：	三甲
Institution hospital：	Shanghai Pulmonary Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	基于盲态独立病理评审（BIPR）评估接受SYS6010联合奥希替尼对照奥希替尼单药新辅助治疗EGFR敏感突变非鳞非小细胞肺癌参与者的主要病理反应率（MPR）的差异	指标类型：	主要指标
Outcome：	To evaluate the difference in major pathological response (MPR) rate, based on blinded independent pathological review (BIPR), in participants with non-squamous non-small cell lung cancer with EGFR m receiving SYS6010 combined with osimertinib versus osimertinib monotherapy as neoadjuvant therapy	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	基于BIPR评估接受SYS6010联合奥希替尼对照奥希替尼单药新辅助治疗EGFR敏感突变非鳞非小细胞肺癌参与者的病理完全缓解率（pCR）的差异	指标类型：	次要指标
Outcome：	To evaluate the difference in pathological complete response (pCR) rate, based on BIPR, in participants with non-squamous non-small cell lung cancer with EGFR-sensitizing mutations receiving SYS6010 combined with osimertinib versus osimertinib monotherapy as neoadjuvant therapy	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	接受SYS6010联合奥希替尼对照奥希替尼单药新辅助治疗EGFR敏感突变非鳞非小细胞肺癌参与者的TNM分期降期的差异	指标类型：	次要指标
Outcome：	To evaluate the difference in TNM downstaging in participants with non-squamous non-small cell lung cancer with EGFR-sensitizing mutations receiving SYS6010 combined with osimertinib versus osimertinib monotherapy as neoadjuvant therapy	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	基于研究者评估接受SYS6010联合奥希替尼对照奥希替尼围手术期治疗EGFR敏感突变非鳞非小细胞肺癌参与者的客观缓解率（ORR）、无事件生存期（EFS）、无病生存期（DFS）的差异	指标类型：	次要指标
Outcome：	To evaluate the differences in objective response rate (ORR), event-free survival (EFS), and disease-free survival (DFS), based on investigator assessment, in participants with non-squamous non-small cell lung cancer with EGFR-sensitizing mutations receiving SYS6010 combined with osimertinib versus osimertinib monotherapy as perioperative therapy	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	评估接受SYS6010联合奥希替尼对照奥希替尼围手术期治疗EGFR敏感突变非鳞非小细胞肺癌参与者总生存期（OS）的差异	指标类型：	次要指标
Outcome：	To evaluate the difference in overall survival (OS) in participants with non-squamous non-small cell lung cancer with EGFR-sensitizing mutations receiving SYS6010 combined with osimertinib versus osimertinib monotherapy as perioperative therapy	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	基于治疗后出现的不良事件（TEAE）评估接受SYS6010联合奥希替尼对照奥希替尼单药的安全性和耐受性的差异	指标类型：	次要指标
Outcome：	To evaluate the differences in safety and tolerability based on treatment-emergent adverse events (TEAEs) in participants receiving SYS6010 combined with osimertinib versus osimertinib monotherapy	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	评价SYS6010的药代动力学特征	指标类型：	次要指标
Outcome：	To evaluate the pharmacokinetic (PK) characteristics of SYS6010	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	评价SYS6010的免疫原性评估筛选期、术前、术后 12 周（±2周）、24 周（±2周）以及之后每 24 周，最长持续至术后3年，不同时间点循环肿瘤 DNA（ctDNA）及EGFR等相关基因变异的清除与否与临床疗效之间的相关性	指标类型：	次要指标
Outcome：	To evaluate the immunogenicity of SYS6010 To assess the correlation between clinical efficacy and the clearance of circulating tumor DNA (ctDNA) and EGFR-related gene variations at different time points (screening, pre-surgery, 12 weeks [±2 weeks], 24 weeks [±2 weeks] post-surgery, and every 24 weeks thereafter for up to 3 years post-surgery)	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：	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：

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）：

本试验将使用 IRT 完成参与者和试验干预的随机分配。本试验在新辅助阶段有 2 个治疗组。IRT 将以 1:1 的比例随机分配参与者到不同的治疗组。如果参与者完成所有筛选程序并符合所有筛选标准的要求，将通过 IRT 随机分配随机号。在新辅助阶段，筛选合格的参与者将按照（Ⅱ期和Ⅲ期）、突变类型（19Del 和 L858R）作为分层因素，按照 1:1 随机分配到不同的治疗组。参与者随机号是唯一编号，一旦分配，当参与者首次接受试验干预时，它将成为该参与者在试验中的永久识别码，1 例参与者仅能有 1 个随机号。如果参与者参加了试验但未接受干预，该参与者的随机号将不会被重新分配。筛选不符合的参与者将不会被分配到随机

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

This trial will use an Interactive Response Technology (IRT) system to randomize participants and assign trial interventions. There are two treatment arms during the neoadjuvant phase. IRT will randomly assign participants to the two treatment groups in a 1:1 ratio. Once a participant completes all screening procedures and meets all inclusion criteria, a randomization number will be assigned via IRT. During the neoadjuvant phase, eligible participants will be stratified by stage (II and III) and mutation type (19Del and L858R), and then randomly assigned in a 1:1 ratio to the respective treatment groups. The randomization number is a unique identifier; once assigned, it becomes the participant’s permanent trial identifier upon first administration of the investigational intervention. Each participant is assigned only one randomization number. If a participant enrolls in the trial but does not receive any intervention, their randomization number will not be reassigned. Participants who do not meet screening criteria will not be randomized.

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：	开放标签
Blinding：	Open-label
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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：	子采集和管理系统
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Electronic Data Capture
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2025-11-25 15:43:46