ChiCTR2500098420 版本V1.0 版本创建时间2025/03/07 11:58:15 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：

ChiCTR2500098420 

最近更新日期：

Date of Last Refreshed on：

2025-03-07 11:57:56 

注册时间：

Date of Registration：

2025-03-07 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

HRS-4642 联合尼妥珠单抗（基础用药）治疗携带 KRAS G12D 突变经系统治疗失败的复发 或转移性胰腺导管腺癌探索性临床研究

Public title：

HRS-4642 combined with Nimotuzumab in the treatment of recurrent or metastatic pancreatic ductal adenocarcinoma with KRAS G12D mutation that has failed systemic therapy

注册题目简写：

English Acronym：

研究课题的正式科学名称：

HRS-4642 联合尼妥珠单抗（基础用药）治疗携带 KRAS G12D 突变经系统治疗失败的复发或转移性胰腺导管腺癌探索性临床研究

Scientific title：

HRS-4642 combined with Nimotuzumab in the treatment of recurrent or metastatic pancreatic ductal adenocarcinoma with KRAS G12D mutation that has failed systemic 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：

曹丹 

研究负责人：

曹丹 

Applicant：

Dan Cao 

Study leader：

Dan Cao 

申请注册联系人电话：

Applicant telephone：

+86 18980605963

研究负责人电话：

Study leader's telephone：

+86 28 85423609

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：

caodan@scu.edu.cn

研究负责人电子邮件：

Study leader's E-mail：

caodan316@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：

四川大学华西医院腹部肿瘤科

研究负责人通讯地址：

四川省成都市武侯区国学巷37号

Applicant address：

Department of Abdominal Oncology, West China Hospital, Sichuan University

Study leader's address：

#37 Guoxue Lane, Wuhou District, Chengdu City, Sichuan 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：

四川大学华西医院

Applicant's institution：

West China Hospital,Sichuan University

研究负责人所在单位：

四川大学华西医院

Affiliation of the Leader：

West China Hospital,Sichuan University

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

2024年审(2239)号

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：

四川大学华西医院生物医学伦理审查委员会

Name of the ethic committee：

Ethics Committee on Biomedical Research West China Hospital of Sichuan University

伦理委员会批准日期：

Date of approved by ethic committee：

2025-01-16 00:00:00

伦理委员会联系人：

李娜

Contact Name of the ethic committee：

Li Na

伦理委员会联系地址：

四川省成都市武侯区国学巷37号

Contact Address of the ethic committee：

#37 Guoxue Lane, Wuhou District, Chengdu City, Sichuan Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 28 85422654

伦理委员会联系人邮箱：

Contact email of the ethic committee：

188974152@qq.com

研究实施负责（组长）单位：

四川大学华西医院

Primary sponsor：

West China Hospital,Sichuan University

研究实施负责（组长）单位地址：

四川省成都市武侯区国学巷37号

Primary sponsor's address：

#37 Guoxue Lane, Wuhou District, Chengdu City, Sichuan 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)：

四川

市(区县)：

Country：

China

Province：

Sichuan

City：

单位(医院)：

四川大学华西医院

具体地址：

四川省成都市武侯区国学巷37号

Institution
hospital：

West China Hospital,Sichuan University

Address：

#37 Guoxue Lane, Wuhou District, Chengdu City, Sichuan Province

经费或物资来源：

自选课题（自筹）

Source(s) of funding：

Optional project

Target disease：

pancreatic ductal adenocarcinoma

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 I期+II期 

Study phase：

1-2

研究设计：

单臂 

Study design：

Single arm 

研究目的：

本研究安全性导入阶段，以AE的发生率和严重程度、实验室检查等结果的改变、DLT和RP2D等为主要终点；疗效探索阶段以客观缓解率（ORR）为主要研究终点，即采用RECIST 1.1标准通过影像学（CT/MRI）评估最佳肿瘤应答达到完全缓解（CR）与局部缓解（PR）的受试者占所有治疗受试者的比例。此单臂II期研究以评价ORR为主要终点指标来评估HRS-4642联合尼妥珠单抗（基础用药）方案的有效性和安全性。  

Objectives of Study：

In the safety introduction phase of this study, the incidence and severity of AE, changes in laboratory results, DLT and RP2D were the primary endpoint. Objective response rate (ORR) was used as the primary endpoint in the phase of efficacy exploration, that is, the proportion of all treated subjects who achieved complete response (CR) and local response (PR) by CT/MRI assessment of optimal tumor response using RECIST 1.1 criteria. This single-arm Phase II study evaluated ORR as the primary endpoint to evaluate the efficacy and safety of the HRS-4642 plus Nimotuzumab regimen.

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. 18-75 岁的男性和女性受试者（包括 18 岁和 75 岁）； 2. 病理学（组织学）或细胞学确诊的胰腺导管腺癌，确认携带 KRAS G12D 突变者； 3. 一线及以上系统治疗后进展或不耐受的转移性胰腺导管腺癌，在辅助治疗 6 个月内发生 复发或转移的患者也可以纳入研究； 4. 在研究入组时根据实体瘤疗效评价标准（RECIST1.1），影像学诊断至少有一个可测量 病灶（根据 CT 或 MRI 评价，病灶长径≥10 mm、淋巴结短径≥15 mm）； 5. 体力状况评分 ECOG 评分 0-2 分； 6. 预计生存期 ≥ 12 周； 7. 主要器官功能正常，即符合下列标准： ①血常规（14 天内未输血及血制品，未使用 G-CSF 及其他造血刺激因子纠正）： a. Hb≥90 g/L； b. ANC≥1.5×10^9/L； c. PLT≥75×10^9/L； d. WBC≥3.0×10^9/L； ②血生化： a. TBIL≤1.5×ULN（肝转移患者≤ 2×ULN）； b. ALT 和 AST≤2.5×ULN（肝转移患者≤ 5×ULN）； c.血清 Cr≤1.5×ULN 或肌酐清除率≥50 mL/min； d.血浆白蛋白≥30g/L； ③凝血常规：国际标准化比值（INR）≤1.5×ULN，活化部分凝血活酶时间（APTT）≤1.5×ULN； ④心功能：左室射血分数（LVEF）≥50%，QTcF ≤ 450 msec（男性）或 ≤ 470 msec（女性）； ⑤尿蛋白≤1+，若尿蛋白>1+，需收集 24 小时尿蛋白测定，其总量需≤1.0g； 8. 既往抗肿瘤治疗所致 AE 须恢复至≤ 1 级（CTCAE v5.0）或入排标准规定的水平，若研 究者判断 NCI-CTCAE≤ 2 级且对受试者无安全性风险则可以入组，如接受过免疫检查点抑 制剂治疗，经激素替代治疗后可稳定的 I 型糖尿病和甲状腺功能减退的受试者； 9. 有生育能力的女性受试者必须在首次用药前 7 天内进行血清妊娠试验，且结果为阴性； 且必须为非哺乳期。有生育能力的女性受试者和伴侣为育龄妇女的男性受试者必须同意从签 署知情同意书开始直到试验药物末次给药后 30 天（接受 HRS-4642 的受试者）内遵守避孕 要求； 10. 受试者自愿加入本研究，并签署知情同意书，依从性好，配合随访。

Inclusion criteria

1. Patients must meet all of the following criteria to be enrolled in this study. 1) Male and female subjects aged 18-75 years (including 18 and 75 years); 2. Pancreatic ductal adenocarcinoma confirmed by pathology (histology) or cytology, identified as a carrier of KRAS G12D mutation; 3. Metastatic pancreatic ductal adenocarcinoma that progresses or is intolerant after first-line and above system therapy, occurring within 6 months of adjuvant therapy Patients with recurrence or metastasis may also be included in the study; 4. At the time of study enrollment, at least one radiographic diagnosis was measurable according to the solid tumor efficacy evaluation criteria (RECIST1.1) Lesions (lesion diameter >=10 mm and lymph node diameter >=15 mm according to CT or MRI evaluation); 5. Physical condition score ECOG score 0-2 points; 6. Expected survival >= 12 weeks; 7. Major organ function is normal, that is, meet the following criteria: (1) blood routine (no blood transfusion and blood products within 14 days, no G-CSF and other hematopoietic stimulating factors correction) : a. Hb >=90 g/L; b. ANC >=1.5×10^9/L; c. PLT>=75×10^9/L; d. WBC>=3.0×10^9/L; (2) Blood biochemistry: a. TBIL <=1.5×ULN (patients with liver metastasis <= 2×ULN);b. ALT and AST <=2.5×ULN (<= 5×ULN for patients with liver metastasis);c. Serum Cr<=1.5×ULN or creatinine clearance >=50 mL/min;d. Plasma albumin >=30g/L; (3) Coagulation routine: International standardized ratio (INR) <=1.5×ULN, activated partial thromboplastin time (APTT) <=1.5×ULN; (4) Cardiac function: left ventricular ejection fraction (LVEF) >=50%, QTcF >= 450 msec (male) or <= 470 msec (female); (5) Urine protein <=1+, if urine protein >1+, urine protein measurement should be collected for 24 hours, and the total amount should be <=1.0g; 8. The AE caused by previous antitumor therapy must be restored to a level of <= Grade 1 (CTCAE v5.0) or the level specified in the exclusion criteria If the investigator judged that NCI-CTCAE≤ grade 2 and there was no safety risk to the subjects, they could be enrolled, such as receiving immune checkpoint suppression Formulation-treated subjects with type 1 diabetes and hypothyroidism who are stable after hormone replacement therapy; 9. Fertile female subjects must undergo a serum pregnancy test within 7 days before the first dose, and the result is negative; And must be non-lactating. A fertile female subject and a male subject whose partner is a woman of childbearing age must consent to the sign-off Adherence to contraception began with informed consent until 30 days after the last administration of the trial drug (subjects receiving HRS-4642) Require; 10. The subjects voluntarily joined the study and signed the informed consent, with good compliance and follow-up.

排除标准：

1) 患者既往使用过 KRAS 抑制剂或靶向 EGFR 治疗； 2) 已知对研究药物或其任何组分过敏； 3) 首次给药前 28 天内接受过化疗、靶向治疗和免疫治疗等系统性抗肿瘤治疗（包括未上 市的临床研究药物或治疗），除外以下几项：口服氟尿嘧啶类和小分子靶向药物为首次使用 研究药物前 14 天或药物的 5 个半衰期内（以时间较长者为准）。有抗肿瘤适应症的中药为 首次使用研究药物前 14 天内；首次给药前 28 天内接受过手术治疗（诊断性手术除外）；首 次给药前 14 天内接受放疗、介入、消融等局部治疗者； 4) 既往或同时患有其它恶性肿瘤，除非是在筛选前至少 2 年达到完全缓解且在研究期间不 需要或预计不需要其他治疗的皮肤基底细胞癌、表浅膀胱癌、皮肤鳞状细胞癌、原位宫颈癌、 局部前列腺癌、根治术后的乳腺导管原位癌、甲状腺乳头状癌（允许非转移性前列腺癌或乳 腺癌的激素治疗）等； 5) 伴有未经治疗或活动性中枢神经系统（CNS）肿瘤转移。有脑膜转移病史或当前有脑膜 15 转移的受试者。至首次用药前至少 2 周，若受试者的 CNS 肿瘤转移已经接受过充分局部治 疗（手术或放疗）且不需要接受激素治疗，同时神经学上恢复至基线（与 CNS 治疗相关的 遗留体征或症状除外），则可入组； 6) 进入研究前的 6 个月内，发生严重的心脑血管动脉血栓栓塞患者（例如，心肌梗死、不 稳定心绞痛、中风）、NYHA 2 级以上心功能不全以及有临床意义的室上性或室性心律失常 而需要临床干预的患者； 7) 研究治疗开始前 6 个月内存在消化道梗阻或存在消化道梗阻的症状和体征，但如果已行 手术治疗且梗阻完全解除可以进行筛选； 8） 首次给药前 3 个月内出现过门静脉高压导致的食管胃底静脉曲张出血事件； 9） 首次给药前 3 个月内接受过胃镜检查提示重度（G3）静脉曲张且未经治疗或经治后未 恢复；当前存在门静脉高压（包括影像学提示脾肿大）且研究者判定进入研究会引起较大的 出血风险； 10) 具有症状的、已播散到内脏的、短期内有出现危及生命的并发症风险的晚期患者（包括 有无法控制的大量渗出液[胸腔、心包、腹腔]的患者）；如进行积液引流，在引流后至少稳 定 2 周者可入组（签署知情前允许根据诊疗常规给予浆膜腔内局部治疗）； 11) 已知或疑似有间质性肺病、非感染性肺炎、慢阻肺、肺栓塞等肺部疾病或其他严重且未 控制的内科疾病、急性感染、近期重大手术史（28 天内或尚未从副作用中恢复）者； 12) 入组前 1 年内有活动性肺结核感染者，或超过 1 年以前有活动性肺结核感染病史但未经 正规治疗者； 13) 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 （筛选期乙肝病毒表面抗原[HBsAg]检测结果呈阳性同时检测到 HBV-DNA 检测值≥10000 拷贝/ml [2000 IU/ml]），活动性丙型肝炎（筛选期丙肝病毒抗体[HCV-Ab]检测结果呈阳性， 同时 HCV-RNA 阳性）或合并乙肝和丙肝共同感染； 14) 存在显著性临床意义的急性或慢性胰腺炎；有胰腺炎高风险的患者，如血清淀粉酶和/ 或脂肪酶浓度≥3 倍 ULN 的患者； 15) 首次研究用药前 28 天内使用减毒活疫苗，或预计研究治疗期间需要使用减毒活疫苗； 16) 在首次给药前 4 周内参加了任何药物或医疗器械的临床试验； 17) 存在无法控制的精神疾病以及已知酗酒、吸毒或药物滥用、刑拘等其他影响研究程序完 成的情况； 18) 研究者认为不应纳入的其他情况；

Exclusion criteria：

1. Patients will not be admitted to the study if they meet any of the following criteria: 1) The patient had previously used KRAS inhibitors or targeted EGFR therapy; 2. known allergy to the investigational drug or any of its components; 3. Systemic antitumor therapy, including chemotherapy, targeted therapy and immunotherapy, has been received within 28 days before the first dose (including no treatment) City of clinical investigational drugs or treatments), except for the following: oral fluorouracil and small molecule targeted drugs for first use The first 14 days of the study of the drug or the five half-lives of the drug (whichever is longer). Chinese medicines with anti-tumor indications are Within 14 days before the first use of the investigational drug; Surgical treatment (except diagnostic surgery) within 28 days prior to initial dosing; The first Patients who received local treatment such as radiotherapy, intervention or ablation within 14 days before secondary administration; 4. Prior or co-existing other malignancies, unless complete remission was achieved at least 2 years prior to screening and not during the study period Basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, cervical cancer in situ, cancer of the skin that requires or is not expected to require other treatment Local prostate cancer, breast ductal carcinoma in situ after radical surgery, papillary thyroid cancer (non-metastatic prostate cancer or breast cancer allowed) Hormone therapy for adenocarcinoma); 5. accompanied by untreated or active central nervous system (CNS) tumor metastasis. Have a history of meningeal metastasis or current meninges 15 Transfer the subject. At least 2 weeks before the first dose, if the subject has received adequate local treatment for CNS metastasis Treatment (surgery or radiation) without the need for hormone therapy and neurological return to baseline (associated with CNS treatment) Except for remaining signs or symptoms), can be included in the group; 6. Patients with severe cardiovascular thromboembolism (e.g., myocardial infarction, no.) within 6 months prior to study entry Stable angina pectoris, stroke), NYHA grade 2 or above cardiac dysfunction, and clinically significant supraventricular or ventricular arrhythmias Patients who require clinical intervention; 7. Study the presence of digestive tract obstruction or the presence of signs and symptoms of digestive tract obstruction within 6 months before the start of treatment, but if it has been done Screening can be performed with surgical treatment and complete removal of obstruction. 8) Bleeding events of esophageal and gastric varices caused by portal hypertension occurred within 3 months before the first administration; 9. Had undergone a gastroscopy within 3 months prior to the first dose indicating severe (G3) varicose veins without treatment or without treatment Recover; Portal hypertension was present (including radiographic evidence of splenomegaly) and the investigators determined that admission to the study caused a larger risk Bleeding risk; 10. Advanced patients who are symptomatic, have spread to the internal organs, and are at risk of developing life-threatening complications in the short term (including Patients with uncontrolled exudation [chest, pericardium, abdominal cavity]; If effusion drainage is performed, at least stable after drainage Patients who have been diagnosed for 2 weeks can be enrolled in the group (local treatment within the serous cavity is allowed according to the diagnosis and treatment routine before signing the information); 11. Known or suspected pulmonary diseases such as interstitial lung disease, non-infectious pneumonia, COPD, pulmonary embolism, or other serious and undiagnosed pulmonary diseases Controlled medical disease, acute infection, recent history of major surgery (within 28 days or not recovered from side effects); 12. Had an active tuberculosis infection within 1 year before enrollment, or had a history of active tuberculosis infection more than 1 year ago but had not Regular healer; 13. People with congenital or acquired immune deficiency, such as human immunodeficiency virus (HIV) infection, active hepatitis B (During the screening period, HBV surface antigen [HBsAg] test results were positive and HBV-DNA test values ≥10000 were detected Copy /ml [2000 IU/ml]), active hepatitis C (positive for HCV antibody [HCV-AB] during screening, HCV RNA positive) or co-infection with hepatitis B and hepatitis C; 14. Acute or chronic pancreatitis with significant clinical significance; 6.Patients with high risk of pancreatitis, such as serum amylase and/or Or lipase concentration ≥3 times ULN; 15. Use of live attenuated vaccine within 28 days prior to the initial study administration, or anticipated use of live attenuated vaccine during the study treatment; 16. Participated in a clinical trial of any drug or medical device within 4 weeks prior to initial dosing; 17. The presence of uncontrolled mental illness and known effects of alcohol, drug or substance abuse, criminal detention, etc A case of success; 18. Other situations that the researchers believe should not be included;

研究实施时间：

Study execute time：

从 From 2024-10-01 00:00:00至 To 2027-01-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2025-02-08 00:00:00 至 To 2026-01-31 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

10

Group：

Test group

Sample size：

干预措施：

HRS-4642+Nimotuzumab

干预措施代码：

Intervention：

HRS-4642+Nimotuzumab

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 四川 

市(区县)：

  

Country：

China 

Province：

Sichuan 

City：

 

单位(医院)：

四川大学华西医院 

单位级别：

三级甲等 

Institution
hospital：

West China Hospital of Sichuan University

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：

主要指标

Outcome：

Objective Response Rate, ORR

Type：

Primary indicator

测量时间点：

Approximately 12 months

测量方法：

RECIST 1.1 criteria

Measure time point of outcome：

Approximately 12 months

Measure method：

RECIST 1.1 criteria

指标中文名：

疾病控制率

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：

客观缓解持续时间

指标类型：

次要指标

Outcome：

Duration of Response, DoR

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

无进展生存期

指标类型：

次要指标

Outcome：

Progression Free Survival, PFS

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

指标类型：

次要指标

Outcome：

Overall Survival, 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：

肿瘤标志物（CA19-9，CA125，CEA）

指标类型：

次要指标

Outcome：

Tumor markers (CA19-9, CA125, CEA)

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）：

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：

Blinding：

是否共享原始数据：

IPD sharing

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）：

研究公开发表后邮件联系研究负责人获取。

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

After the research is publicly published, contact the research leader by email to obtain it.

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 sheet

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2025-03-07 11:57:56