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：	ChiCTR2400089410
最近更新日期： Date of Last Refreshed on：	2024-09-09 08:35:56
注册时间： Date of Registration：	2024-09-09 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	依沃西单抗（抗 PD-1 和 VEGF 双特异性抗体）联合化疗新辅助治疗可切除 EGFR 敏感突变的非小细胞肺癌：一项单臂、单中心、II 期临床研究
Public title：	A Single-Arm, Single-Center, Phase II Clinical Study of Neoadjuvant Treatment of Resectable EGFR-Sensitive Mutant Non-Small Cell Lung Cancer with Ivonescimab (Anti-PD-1 and VEGF Bispecific Antibody) Combination with Chemotherapy
注册题目简写：
English Acronym：
研究课题的正式科学名称：	依沃西单抗（抗 PD-1 和 VEGF 双特异性抗体）联合化疗新辅助治疗可切除 EGFR 敏感突变的非小细胞肺癌：一项单臂、单中心、II 期临床研究
Scientific title：	A Single-Arm, Single-Center, Phase II Clinical Study of Neoadjuvant Treatment of Resectable EGFR-Sensitive Mutant Non-Small Cell Lung Cancer with Ivonescimab (Anti-PD-1 and VEGF Bispecific Antibody) Combination with Chemotherapy
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：	王海永	研究负责人：	王海永
Applicant：	Haiyong Wang	Study leader：	Haiyong Wang
申请注册联系人电话： Applicant telephone：	+86 156 6587 8316	研究负责人电话： Study leader's telephone：	+86 156 6587 8316
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：	13818294401@126.com	研究负责人电子邮件： Study leader's E-mail：	13818294401@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：	山东省济南市济兖路440号	研究负责人通讯地址：	山东省济南市济兖路440号
Applicant address：	No. 440, Jiyan Road, Jinan City, Shandong Province, China	Study leader's address：	No. 440, Jiyan Road, Jinan City, Shandong Province, 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：	山东第一医科大学附属肿瘤医院
Applicant's institution：	Cancer Hospital Affiliated of Shandong First Medical University
研究负责人所在单位：	山东第一医科大学附属肿瘤医院
Affiliation of the Leader：	Cancer Hospital Affiliated of Shandong First 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：	SDZLEC2024-236-02	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 the Affiliated Cancer Hospital of Shandong First Medical University
伦理委员会批准日期： Date of approved by ethic committee：	2024-08-09 00:00:00
伦理委员会联系人：	宋现让
Contact Name of the ethic committee：	Xianrang Song
伦理委员会联系地址：	山东省济南市槐荫区济兖路440号山东省肿瘤医院
Contact Address of the ethic committee：	Shandong Cancer Hospital, No. 440, Jiyan Road, Huaiyin District, Jinan City, Shandong Province, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 531 6762 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：

Cancer Hospital Affiliated of Shandong First Medical University

研究实施负责（组长）单位地址：

山东省济南市槐荫区济兖路440号

Primary sponsor's address：

No. 440, Jiyan Road, Huaiyin District, Jinan City, Shandong Province, 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)：	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路440号
Institution hospital：	Cancer Hospital Affiliated of Shandong First Medical University	Address：	No. 440, Jiyan Road, Huaiyin District, Jinan City, Shandong Province, China

经费或物资来源：

研究药物由康方赛诺有限公司提供

Source(s) of funding：

Study drug provided by Kangfang Sainuo 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期临床试验

Study phase：

2

研究设计：

单臂

Study design：

Single arm

研究目的：

主要目的：评估依沃西单抗联合化疗新辅助治疗可切除 EGFR 敏感突变的非小细胞肺癌的初步的有效性；次要目的：评估依沃西单抗联合化疗新辅助治疗可切除 EGFR 敏感突变的非小细胞肺癌的安全性；

Objectives of Study：

Primary objective: To assess the preliminary efficacy of neoadjuvant treatment with ivonescimab in combination with chemotherapy for resectable non-small cell lung cancer with EGFR-sensitive mutations; Secondary Objective: To evaluate the safety of neoadjuvant treatment with ivonescimab in combination with chemotherapy for resectable non-small cell lung cancer with EGFR-sensitive mutations;

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；
 受试者必须按照主管部门和研究机构的指南签署IRB/IEC批准的知情同意书并署上日期。知情同意书必须在进行任何方案相关程序（不属于受试者常规医疗的部分内容）之前签署。
 受试者必须愿意而且能够遵守日程表规定的访视、治疗方案、实验室检查，及遵守研究的其他要求。
2.入组时年龄≥18周岁且≤75周岁，男女均可；
3.东部肿瘤协作组织（ECOG）体能状况评分为0或1；
4.预期生存期≥3个月；
5.经病理组织学或细胞学确诊的非小细胞肺癌患者，且可切除的临床分期为II-IIIB (T3N2) 期（根据第8版肺癌TNM分期）；
6.经病理组织学或细胞学检测明确EGFR敏感突变阳性（19del或L858R）；
7.既往未接受过任何形式的抗肿瘤治疗。
8.根据 RECIST v1.1，至少有一个可测量病灶，（根据RECIST 1.1标准，肿瘤病灶CT扫描长径≥10mm，淋巴结病灶CT扫描短径≥15mm），且适合反复准确测量；
9.受试者必须具有足够的心肺功能，用于预期的根治性肺切除手术。
10.通过以下要求确定良好的器官功能：
1)	肺通气功能检查，FEV1≥1.5L，或预计肺叶/全肺切除术后FEV1≥800ml；
2)	血液学（开始研究治疗前7天内未使用任何血液成分及细胞生长因子支持治疗）：
i.	中性粒细胞绝对值ANC≥1.5×10^9/L； 
ii.	血小板计数≥100×10^9/L； 
iii.	血红蛋白≥90 g/L
3)	肾脏：
i.	血清肌酐（Cr）≤1.5×正常值上限（ULN），或肌酐清除率* (CrCl) 计算值≥50 mL/min；
*将采用 Cockcroft-Gault公式计算CrCl；
CrCl (mL/min) = {(140-年龄) ×体重(kg)×F}/(SCr (mg/dL) × 72)；
其中男性F=1，女性F=0.85；SCr=血清肌酐
ii. 尿蛋白＜2+，或24小时（h）尿蛋白定量＜1.0 g
4)	肝脏：
i.	血清总胆红素（TBIL）≤1.5×ULN；对于肝转移或确诊/疑似Gilbert综合征的受试者，TBIL≤3×ULN；
ii.	AST和ALT≤2.5×ULN；对于肝转移的受试者，AST和ALT≤5×ULN；
iii. 血清白蛋白（ALB）≥28 g/L；
5)	凝血功能：国际标准化比率（INR），且部分促凝血酶原时间（PTT）或活化部分凝血活酶时间（APTT）≤ 1.5×ULN； 
11.同意接受根治性手术治疗的患者；
12.专科医师判断无手术禁忌的患者
13.育龄期女性受试者在首次用药前3天内的尿液或血清妊娠检查结果为阴性（如尿液妊娠检查结果不能确认为阴性，需进行血清妊娠检查，以血清妊娠结果为准）；
14.如具有生育能力的女性受试者与未绝育的男性伴侣发生性行为，该受试者必须自筛选开始采取高效的避孕方法，且必须同意持续使用这些防范措施直至研究药物末次给药后的120天；周期性禁欲、安全期避孕和体外射精是不可接受的避孕方法。
1)有生育能力的女性是指未经手术绝育（即双侧输卵管结扎术、双侧卵巢切除术或全子宫切除术）或未绝经的女性（绝经的定义为无替代医学原因的前提下至少连续12个月停经，血清促卵泡激素水平在绝经后女性的实验室参考范围之内）。
2)高效的避孕方法是指在持续正确使用情况下避孕失败率很低（如每年低于1%）的避孕方法。可接受的有效避孕方法（下表）包括双侧输卵管结扎、男性绝育、抑制排卵的激素类避孕药、激素释放型宫内节育器和铜环宫内节育器。并非所有避孕方法均是高效的。除屏障避孕法（如男用避孕套加杀精剂）之外，有生育能力的女性受试者还必须单独使用激素避孕法（如避孕药），以确保不发生妊娠。
15.如未绝育的男性受试者与具有生育能力的女性伴侣发生性行为，该受试者必须自筛选开始至末次给药后的第120天采取有效的避孕方法（下表）；关于在此时间点后是否停止避孕，应与研究者讨论。

Inclusion criteria

1. Voluntary signed written informed consent;
 Subjects must sign and date the IRB/IEC-approved informed consent form in accordance with the guidelines of the competent authority and the research organization. The informed consent must be signed prior to performing any protocol-related procedures that are not part of the subject's routine medical care.
 Subjects must be willing and able to comply with the visits, treatment regimens, laboratory tests, and comply with other requirements of the study as specified in the schedule.
2. age ≥18 years and ≤75 years at enrollment, both sexes;
3. Eastern Cooperative Oncology Group (ECOG) physical status score of 0 or 1;
4. expected survival ≥ 3 months;
5. patients with non-small cell lung cancer diagnosed by histologic or cytologic pathology and resectable clinical stage II-IIIB (T3N2) (according to the 8th edition of TNM staging of lung cancer);
6. Clearly EGFR-sensitive mutation-positive (19del or L858R) by pathohistologic or cytologic testing;
7. No previous antitumor therapy of any kind.
8. have at least one measurable lesion according to RECIST v1.1, (≥10mm long diameter on CT scan for tumor lesions and ≥15mm short diameter on CT scan for lymph node lesions according to RECIST 1.1 criteria) that is suitable for repeated accurate measurements;
9. subjects must have adequate cardiopulmonary function for the intended radical lung resection.
10. good organ function is determined by the following requirements:
1) Lung ventilation function test with FEV1 ≥ 1.5L or expected FEV1 ≥ 800ml after lobectomy/total lung resection;
2) Hematology (no supportive therapy with any blood component or cell growth factor within 7 days prior to initiation of study treatment):
i. Absolute neutrophil ANC ≥ 1.5 x 10^9/L; 
ii. platelet count ≥ 100 x 10^9/L; 
iii. hemoglobin ≥ 90 g/L
3) Renal:
i. Serum creatinine (Cr) ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance* (CrCl) calculated value ≥ 50 mL/min;
*CrCl will be calculated using the Cockcroft-Gault formula;
CrCl (mL/min) = {(140 - age) × body weight (kg) × F}/(SCr (mg/dL) × 72);
where F = 1 for men and F = 0.85 for women; SCr = serum creatinine
ii. urine protein <2+, or 24-hour (h) urine protein quantification <1.0 g
4) Liver:
i. serum total bilirubin (TBIL) ≤ 1.5 x ULN; TBIL ≤ 3 x ULN for subjects with liver metastases or confirmed/suspected Gilbert's Syndrome;
ii. AST and ALT ≤ 2.5 x ULN; for subjects with liver metastases, AST and ALT ≤ 5 x ULN;
iii. serum albumin (ALB) ≥ 28 g/L;
5) Coagulation: International Normalized Ratio (INR) with Partial Thromboplastin Time (PTT) or Activated Partial Thromboplastin Time (APTT) ≤ 1.5 x ULN; 
11. Patients who agree to undergo radical surgical treatment;
12. Patients with no contraindications to surgery as judged by a specialist physician
13. Female subjects of childbearing age with negative urine or serum pregnancy test results within 3 days prior to the first dose (if the urine pregnancy test results cannot be confirmed as negative, serum pregnancy test is required, and the serum pregnancy results shall prevail);
14.If a female subject of childbearing potential engages in sexual intercourse with a male partner who is not sterilized, that subject must be using a highly effective method of contraception from the start of screening and must agree to the continued use of these precautions up to 120 days after the last dose of study drug; cyclic abstinence, safe period contraception, and extracorporeal ejaculation are unacceptable methods of contraception.
1)Females of childbearing potential are those who have not been surgically sterilized (i.e., bilateral tubal ligation, bilateral salpingo-oophorectomy, or total hysterectomy) or who are not menopausal (menopause is defined as the cessation of menstruation for at least 12 consecutive months in the absence of an alternative medical cause, and serum follicle-stimulating hormone levels that are within the laboratory reference ranges for postmenopausal women).
2) Highly effective contraceptive methods are those that have a very low contraceptive failure rate (e.g., less than 1% per year) when used consistently and correctly. Acceptable highly effective contraceptive methods (table below) include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper-ring IUDs. Not all contraceptive methods are highly effective. In addition to barrier contraceptive methods (e.g., male condom with spermicide), hormonal contraceptive methods (e.g., birth control pills) must be used alone in fertile female subjects to ensure that pregnancy does not occur.
15. If a non-sterilized male subject engages in sexual intercourse with a female partner of childbearing potential, the subject must use an effective method of contraception from the start of screening until Day 120 after the last dose (Table below); the decision to discontinue contraception after this time point should be discussed with the Investigator.

排除标准：

肿瘤相关特征及治疗： 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.存在局部晚期不可切除的或转移性疾病； 3.所有携带其他类型EGFR敏感突变的患者； 4.针对 NSCLC 进行过任何全身性或局部抗肿瘤治疗，包括细胞毒性药物治疗、免疫药物治疗、放疗、试验性治疗、生物制剂、小分子靶向治疗等； 5.同时入组另一项临床研究，除非其为一项非干预性的临床研究或干预性研究的随访期（定义为首次用药时间距离前一项临床研究末次用药时间达4周以上或该研究药物的5个半衰期以上，以较短者为准）； 6.首次给药前2周内针对非靶病灶进行了姑息性局部治疗；首次给药前2周内接受过非特异性免疫调节治疗（如白介素、干扰素、胸腺肽、肿瘤坏死因子等，不包括用于治疗血小板减少的IL-11）；首次给药前1周内曾接受具有抗肿瘤适应症的中草药或中成药；既往病史及合并疾病： 7.首次用药前3年内患有除NSCLC以外的其他恶性肿瘤；允许纳入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； 8.首次用药前2年内患有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）（不包括使用PD-1/L1抑制剂导致的irAE）。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； 9.首次用药前1年内存在重大疾病病史，具体为：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），或可能影响研究药物安全性评价的其他心脏损害（如控制不佳的心律失常，心肌缺血等）；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；首次给药前6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；首次给药前4周内发生慢性阻塞性肺病急性加重； 10.首次给药前6个月内有胃肠道穿孔和/或瘘管病史，胃肠梗阻病史（包括需要肠外营养的不完全肠梗阻），广泛肠切除（部分结肠切除或广泛小肠切除，并发慢性腹泻）； 11.在首次给药前4周内接种了活疫苗或减毒活疫苗，或计划在研究期间接种活疫苗或减毒活疫苗，允许使用灭活疫苗； 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；在首次给药前2周内接受过全身抗感染治疗的活动性感染（不包括乙型肝炎或丙型肝炎的抗病毒治疗）； 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.有严重出血倾向或凝血功能障碍病史；首次给药前4周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）；首次用药前10天内接受过持续的抗血小板或抗凝治疗； 15.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； 16.经治疗未能控制的高血糖（空腹血糖＞10 mmol/L）； 17.既往存在需要系统性糖皮质激素治疗的非感染性肺炎病史或当前存在间质性肺疾病； 18.活动性或既往有明确的炎症性肠病（如克罗恩病、溃疡性结肠炎或慢性腹泻）病史； 19.存在免疫缺陷病史；HIV抗体检测阳性者；当前正在长期使用系统性皮质类固醇激素或其他免疫抑制剂； 20.已知异体器官移植史和异体造血干细胞移植史； 21.未经治疗的活动性乙型肝炎受试者（HBsAg阳性且HBV-DNA超过1000拷贝/mL（200 IU/mL）或高于检测下限，以高者为准），对于患有乙型肝炎的受试者，要求在研究治疗期间接受抗乙肝病毒治疗；活动性的丙型肝炎受试者（HCV抗体阳性且HCV-RNA水平高于检测下限）； 22.已知存在活动性肺结核（TB）：怀疑有活动性TB的受试者，需进行临床检查排除； 23.已知的活动性梅毒感染； 24.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； 25.已知有精神疾病、药物滥用、酗酒或吸毒史； 26.既往或当前存在任何疾病、治疗、实验室检查异常，可能会混淆研究结果，影响受试者全程参与研究，或参与研究可能不符合受试者的最佳利益； 27.不受控制的代谢紊乱，或非恶性肿瘤导致的局部或全身性疾病，或肿瘤继发的疾病或症状，并可导致较高医学风险和/或生存期评价的不确定性，如肿瘤类白血病反应（白细胞计数>20×10^9/L）、恶液质表现（如已知的筛选前3个月体重减轻超过10%）等；其他情况： 28.处于妊娠期或哺乳期，或计划在研究期间哺乳； 29.其他研究者认为不适合入组的情况。

Exclusion criteria：

Tumor-related features and treatment: 1. patients with large-cell and mixed-cell lung cancer, mixed with small-cell lung cancer components; 2. presence of locally advanced unresectable or metastatic disease; 3. all patients harboring other types of EGFR-sensitive mutations; 4. Any systemic or local antitumor therapy for NSCLC, including cytotoxic drug therapy, immunotherapy, radiotherapy, experimental therapy, biologics, and small molecule targeted therapy; 5. concurrent enrollment in another clinical study, unless it is a non-interventional clinical study or a follow-up period of an interventional study (defined as the time of the first dose being 4 weeks or more from the time of the last dose in the previous clinical study or 5 or more half-lives of the study drug, whichever is shorter); 6. Palliative local therapy for non-target lesions within 2 weeks prior to the first dose; non-specific immunomodulatory therapy (e.g., interleukin, interferon, thymic peptide, tumor necrosis factor, etc., excluding IL-11 used to treat thrombocytopenia) within 2 weeks prior to the first dose; and herbal or proprietary Chinese medicine with an antitumor indication within 1 week prior to the first dose; Past medical history and co-morbidities: 7. malignancy other than NSCLC within 3 years prior to first dose; allows for the inclusion of subjects with other malignancies that have been cured by local therapy, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, and carcinoma in situ of the cervix or breast; 8. active autoimmune disease (e.g., treatment with disease-modifying drugs, corticosteroids, immunosuppressants) requiring systemic therapy within 2 years prior to the first dose (excluding irAE resulting from the use of PD-1/L1 inhibitors). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a systemic therapy; 9. history of major medical illness within 1 year prior to first dose, specifically: Unstable angina pectoris, myocardial infarction, congestive heart failure (New York Heart Association NYHA classification ≥ grade 2) or vascular disease (e.g., aortic aneurysm with risk of rupture) requiring hospitalization, or other cardiac impairment (e.g., poorly controlled cardiac arrhythmia, myocardial ischemia, etc.) that may interfere with the evaluation of the safety of the investigational drug, within the 12 months prior to the first dose of study drug; History of esophagogastric fundal varices, severe ulcers, unhealed wounds, abdominal fistulas, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months prior to first dose; Any arterial thromboembolic event, venous thromboembolic event of grade 3 or greater as defined by NCI CTCAE 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to first dose;  Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks prior to first dose; 10. history of gastrointestinal perforation and/or fistula within 6 months prior to the first dose, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection complicated by chronic diarrhea); 11. live or live attenuated vaccine administered within 4 weeks prior to the first dose or planned to be administered during the study period; inactivated vaccines are permitted; 12. Serious infection within 4 weeks prior to the first dose, including, but not limited to, concomitant comorbidities requiring hospitalization, sepsis, or severe pneumonia; active infection for which systemic anti-infective therapy has been received within 2 weeks prior to the first dose (excluding antiviral therapy for hepatitis B or hepatitis C); 13. major surgery or serious trauma within 4 weeks prior to the first dose of the drug, or if major surgery is planned within 4 weeks of the first dose of the drug (at the discretion of the investigator); minor localized surgery within 3 days prior to the first dose of the drug (excluding transperipheral venous puncture central venous catheterization and intravenous infusion port implantation); 14. history of severe bleeding tendency or coagulopathy; clinically significant bleeding symptoms within 4 weeks prior to the first dose of the drug, including, but not limited to, gastrointestinal bleeding, coughing up blood (defined as coughing up or hemoptysis of ≥ 1 teaspoon of fresh blood or small clots or coughing up only blood without sputum, allowing for enrollment of those with blood in their sputum), bleeding from the nasal passages (excluding epistaxis bleedings and retracted slugs of blood); and receipt of continuous antiplatelet or anticoagulant therapy; 15. Current hypertension with systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after treatment with oral antihypertensive medications; 16. Uncontrolled hyperglycemia (fasting blood glucose >10 mmol/L) after treatment; 17. past history of non-infectious pneumonia requiring systemic glucocorticoid therapy or current interstitial lung disease; 18. active or previous history of defined inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea) 19. the presence of a history of immunodeficiency; those who have tested positive for HIV antibodies; and those who are currently on long-term use of systemic corticosteroids or other immunosuppressive agents; 20. a known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation 21. untreated subjects with active hepatitis B (HBsAg positive and HBV-DNA greater than 1000 copies/mL (200 IU/mL) or above the lower limit of detection, whichever is higher), and for subjects with hepatitis B, anti-hepatitis B virus treatment is required during study treatment; subjects with active hepatitis C (HCV antibody positive and HCV-RNA levels above the lower limit of detection); 22. Known active tuberculosis (TB): subjects suspected of having active TB require clinical examination for exclusion; 23. known active syphilis infection; 24. known hypersensitivity to any component of any investigational drug; known history of severe hypersensitivity reactions to other monoclonal antibodies; 25. known history of mental illness, substance abuse, alcoholism or drug addiction; 26. any previous or current medical condition, treatment, or laboratory test abnormality that may confound the results of the study, interfere with the subject's full participation in the study, or participation in the study may not be in the subject's best interest; 27. uncontrolled metabolic disorders, or local or systemic diseases due to non-malignant tumors, or diseases or conditions secondary to tumors, and which can lead to higher medical risk and/or uncertainty in the evaluation of survival, such as tumor-like leukemic reactions (white blood cell count >20 x 10^9/L), malignant manifestations (e.g., known weight loss of more than 10% in the 3 months prior to screening); Other circumstances: 28. in pregnancy or breastfeeding, or planning to breastfeed during the study; 29. other conditions that the investigator considers inappropriate for enrollment.

研究实施时间：

Study execute time：

从 From 2024-09-10 00:00:00至 To 2027-09-10 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-09-10 00:00:00 至 To 2026-09-10 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	25
Group：	Test group	Sample size：	25
干预措施：	依沃西单抗(AK112)+含铂双药化疗新辅助治疗	干预措施代码：
Intervention：	Neoadjuvant treatment with ivonescimab (AK112) + platinum-containing two-drug chemotherapy	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	单位级别：	三甲
Institution hospital：	Cancer Hospital Affiliated of Shandong First Medical University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	主要病理学缓解率	指标类型：	主要指标
Outcome：	Major Pathological response	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	病理学完全缓解率	指标类型：	次要指标
Outcome：	Pathological complete response	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	24 个月无事件生存率	指标类型：	次要指标
Outcome：	24m Event-free 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：	无事件生存期	指标类型：	次要指标
Outcome：	Event-free 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：	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：	手术 R0 切除率	指标类型：	次要指标
Outcome：	Surgery R0 Excision 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：	肿瘤降期率	指标类型：	次要指标
Outcome：	Tumor downstaging 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：	安全性	指标类型：	次要指标
Outcome：	security	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：

正在进行

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）：

NA

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

NA

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）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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）：	http://www.medresman.org.cn/login.aspx
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	http://www.medresman.org.cn/login.aspx
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：	电子采集和管理系统
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Electronic Data Capture, EDC
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：	2024-09-09 08:35:30