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：	ChiCTR2500103982
最近更新日期： Date of Last Refreshed on：	2025-06-09 16:52:06
注册时间： Date of Registration：	2025-06-09 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	以mRNA-LNP（PMC2129G12）为基础的新型靶向技术治疗晚期恶性实体瘤患者的安全耐受性和初步疗效的单臂、探索性临床研究
Public title：	A single-arm, exploratory clinical study of the safety tolerability and preliminary efficacy of a novel mRNA-LNP(PMC2129G12-based targeted technology in the treatment of patients with advanced malignant solid tumors
注册题目简写：
English Acronym：
研究课题的正式科学名称：	以mRNA-LNP（PMC2129G12）为基础的新型靶向技术治疗晚期恶性实体瘤患者的安全耐受性和初步疗效的单臂、探索性临床研究
Scientific title：	A single-arm, exploratory clinical study of the safety tolerability and preliminary efficacy of a novel mRNA-LNP(PMC2129G12-based targeted technology in the treatment of patients with advanced malignant solid tumors
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：	王珊珊	研究负责人：	于淼
Applicant：	Shanshan Wang	Study leader：	Yu Miao
申请注册联系人电话： Applicant telephone：	+86 136 8737 5263	研究负责人电话： Study leader's telephone：	+86 173 9502 8667
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：	wangshanshan@promab.cn	研究负责人电子邮件： Study leader's E-mail：	travy@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：	湖南省长沙市高新技术开发区林语路239号顺畅产业园5楼	研究负责人通讯地址：	东岗西路204号
Applicant address：	5th Floor, Shunshun Industrial Park, No. 239, Linyu Road, High-tech Development Zone, Changsha City,	Study leader's address：	Donggang WestRoad 204
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：	湖南远泰生物技术有限公司
Applicant's institution：	Hunan Yuantai Biotechnology Co., Ltd
研究负责人所在单位：	甘肃省人民医院
Affiliation of the Leader：	Gansu Provincial 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：	(药/械)伦审(2025)第(33)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：	甘肃省人民医院药物/医疗器械临床试验伦理委员会
Name of the ethic committee：	Drug/Medical Device Clinical Trial Ethics Committee of Gansu Provincial Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2025-03-28 00:00:00
伦理委员会联系人：	马海忠
Contact Name of the ethic committee：	mahaizhong
伦理委员会联系地址：	东岗西路204号
Contact Address of the ethic committee：	Donggang WestRoad 204
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 931 828 2240	伦理委员会联系人邮箱： Contact email of the ethic committee：	mhzygb@163.com

研究实施负责（组长）单位：

甘肃省人民医院

Primary sponsor：

Gansu Provincial Hospital

研究实施负责（组长）单位地址：

东岗西路204号

Primary sponsor's address：

Donggang WestRoad 204

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	甘肃省	市(区县)：
Country：	China	Province：	Gansu	City：
单位(医院)：	甘肃省人民医院	具体地址：	东岗西路204号
Institution hospital：	Gansu Provincial Hospital	Address：	Donggang WestRoad 204

经费或物资来源：

湖南远泰生物技术有限公司

Source(s) of funding：

Hunan Yuantai Biotechnology Co., Ltd.

研究疾病：

EpCAM阳性的晚期恶性实体瘤（肝癌，结直肠癌，乳腺癌等）

Target disease：

EpCAM positive advanced malignant solid tumors (such as liver cancer, colorectal cancer, breast cancer, etc.)

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：

评价PMC2129G12治疗晚期恶性实体瘤患者的安全耐受性，观察剂量限制性毒性（DLT），确定最大耐受剂量（MTD）

Objectives of Study：

To evaluate the safety and tolerability of PMC2129G12 treatment in patients with advanced malignant solid tumors, to observe dose-limiting toxicities (DLTs), and to determine the maximum tolerated dose (MTD)

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. Subjects voluntarily participate in the clinical study, understand the study procedures and are able to sign an informed consent form (ICF) in person.
2. Age at the time of signing ICF: 18~75 years old (including both ends), gender is not limited.
3. Patients with recurrent/metastatic advanced solid tumors confirmed by tissue or cytology, who have failed or are intolerant of standard clinical treatment or lack of standard treatment options.
4. EpCAM expression was confirmed by immunohistochemistry.
5. Measurable tumor lesions according to RECIST 1.1 criteria.
6. ECOG PS score: 0-1 points.
7. Expected survival time>=  3 months.
8. Have sufficient bone marrow, liver, kidney, metabolic and coagulation functions, and the functional level of organs within 7 days before dosing meets the following requirements (no blood transfusion, no use of hematopoietic stimulating factors, no use of albumin or blood products within 14 days before examination): Platelet count (PLT) >=  100×10^9/L, absolute neutrophil value (NEUT) >= 1.5×10^9/L, hemoglobin (Hb) >=  90 g/L or >= 5.6 mmol/L; Total bilirubin (TBIL) <=  2 × ULN (upper limit of normal) (TBIL <=  3× ULN for subjects with evidence confirmed/suspected of Gilbert's syndrome), alanine aminotransferase (ALT) <=  3 × ULN, aspartate aminotransferase (AST) <=  3 × ULN (AST is allowed if liver metastases are present, ALT <=  5 times the upper limit of normal);  Serum creatinine (Cr) <=  1.5 × ULN or creatinine clearance (Ccr) >=  50 ml/min (calculated using the Cockcroft-Gault formula); Albumin >=  28g/L (albumin infusion is not allowed within 14 days before the first dose) The international normalized ratio (INR), activated partial thromboplastin time (APTT) and prothrombin time (PT) were all <=  1.5 × ULN.
9. Female subjects of childbearing potential should agree to use contraception (such as intrauterine device, contraceptive pills, or condoms) during the study and for 6 months after the end of the study, have a negative serum pregnancy test within 7 days prior to dosing, and must be non-lactating subjects; Male subjects (female partners of childbearing potential) must use effective contraception during the study and for 6 months after the end of the study period.

排除标准：

1. 既往使用过针对EpCAM或者CD3靶点相关的治疗。
2. 首次使用本研究药物前5个半衰期内或21天内（以时间长者为准），接受过抗肿瘤治疗（包括化疗、放疗、靶向治疗、免疫治疗、服用抗肿瘤活性的中药等）；或参加其他临床试验且接受临床试验用药小于4周。
3. 研究治疗开始前2年内需要系统治疗的活动性自身免疫性疾病，或研究者判断存在可能复发或计划治疗的自身免疫性疾病，包括但不限于炎症性肠病、乳糜泻、韦格纳综合征、桥本甲状腺炎、系统性红斑狼疮、硬皮病、结节病或自身免疫性肝炎，以下除外： (1) 仅需要稳定剂量的激素替代治疗的 I 型糖尿病或甲状腺功能减退； (2) 由桥本甲状腺炎引起的甲状腺功能减退，仅需要稳定剂量的激素替代治疗； (3) 不需系统治疗的皮肤病（如：白癜风、脱发、银屑病或湿疹）； (4) 童年期哮喘已完全缓解，成人后无需任何干预； (5) 研究者判断所患疾病在无外部触发因素的情况下不会复发。
4. 在首次给药前14天内需要使用糖皮质激素（＞10mg/天泼尼松或等效剂量药物）或其他免疫抑制药物进行全身治疗的受试者，以下除外： (1) 如果没有活动性自身免疫性疾病，允许使用吸入性、眼科、关节内或局部使用糖皮质激素； (2) 生理剂量的系统性糖皮质激素的用量≤10 mg/天泼尼松或等效剂量的其他糖皮质激素； (3) 糖皮质激素作为输液反应或过敏反应预处理（如：CT检查前用药等）。
5. 已知的脑转移患者。
6. 合并有严重的恶性胸腹水（需要一个月内引流至少一次的）。
7. 既往抗肿瘤治疗未能缓解的毒性，定义为未消退至NCI CTCAE（v5.0）0级或1级，或入选/排除标准中规定的水平，但脱发/色素沉着除外。对于发生不可逆毒性且预期研究药物给药后不会加重的受试者（例如听力损失），在与申办方协商后，可能会被纳入研究。放疗引起的远期毒性，经研究者判断不能恢复的受试者，在与申办方协商后，可能会被纳入研究。
8. 筛选前5年内合并第二恶性肿瘤，但本研究中正在研究的癌症类型以及已经治愈的局部复发性癌症（例如已经切除的基底细胞或鳞状细胞皮肤癌、浅表性膀胱癌、局限型前列腺癌、宫颈原位癌或乳腺原位癌）除外。
9. 心脏功能和疾病符合下述情况之一： a) 长 QTc 综合征或 QTc 间期延长，男性>450 ms，女性>470 ms； b) 完全性左束支传导阻滞，II 度或 III 度房室传导阻滞； c) 需要药物治疗的严重、未控制的心律失常； d) 美国纽约心脏病学会（NYHA）＞ 2级的心力衰竭； e) 左心室射血分数（LVEF）低于 50%； f) 在入组前 6 个月内出现心肌梗死、不稳定心绞痛、严重不稳定室性心律失常病史或其他任何需要治疗的心律失常、临床严重的心包疾病或有急性缺血性或活动性传导系异常的心电图证据。
10. 拟注射部位有活动性出血。
11. 控制不佳的系统性疾病（如控制不佳的高血压、糖尿病等）。
12. 无法控制的活动性感染。
13. 人类免疫缺陷病毒（HIV）感染者（HIV抗体阳性）、乙肝活动期感染（乙肝病毒表面抗原阳性且乙肝病毒 DNA 超过 1×103 IU/mL）、丙肝活动期感染（丙肝病毒 RNA 超过 1×103 IU/mL）；
14. 对研究药物的同类药物或辅料成分有已知的即时或者延迟超敏反应史，或对其他单克隆抗体药物发生过严重过敏反应史。
15. 孕妇、哺乳期女性、研究期间拒绝采取有效避孕措施的患者。
16. 伴有严重的神经或精神病史；
17. 经研究者判断，受试者有其他可能影响研究结果，或增加研究给药风险，或导致研究被迫终止的因素，如酗酒、药物滥用、患有其他严重的急性或慢性身体或心理疾病、实验室检查严重异常、家庭社会会其他因素影响受试者安全的情况等，受试者不适宜参加本研究。

Exclusion criteria：

1. Previous use of EpCAM or CD3 target-related therapy. 2. Received anti-tumor therapy (including chemotherapy, radiotherapy, targeted therapy, immunotherapy, taking anti-tumor active Chinese medicine, etc.) within 5 half-lives or within 21 days (whichever is longer) before the first use of the investigational drug; or participate in other clinical trials and have received clinical trial drugs for less than 4 weeks. 3. Active autoimmune disease requiring systemic therapy within 2 years prior to initiation of study treatment, or in the judgment of the investigator with an autoimmune disease that may relapse or is planned for treatment, including but not limited to inflammatory bowel disease, celiac disease, Wegener syndrome, Hashimoto's thyroiditis, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis, except for the following: (1) Type I diabetes mellitus or hypothyroidism requiring only a stable dose of hormone replacement therapy; (2) hypothyroidism caused by Hashimoto's thyroiditis requiring only stable doses of hormone replacement therapy; (3) Skin diseases that do not require systemic treatment (e.g. vitiligo, alopecia, psoriasis or eczema); (4) Childhood asthma has been completely relieved and no intervention is required in adulthood; (5) The investigator judges that the disease will not recur in the absence of external triggers. 4. Subjects requiring systemic treatment with glucocorticoids (>10mg/day prednisone or equivalent) or other immunosuppressive drugs within 14 days prior to the first dose, with the following exceptions: (1) If there is no active autoimmune disease, inhaled, ophthalmic, intra-articular or topical glucocorticoids are allowed; (2) Physiological doses of systemic glucocorticoids<= 10 mg/day prednisone or equivalent doses of other glucocorticoids; (3) Glucocorticoids as pretreatment for infusion reactions or allergic reactions (e.g., premedication before CT examination, etc.). 5. Patients with known brain metastases. 6. Combined with severe malignant thoracic ascites (need to be drained at least once within a month). 7. Toxicity that has not been resolved by prior antineoplastic therapy, defined as not regressing to NCI CTCAE (v5.0) Grade 0 or 1, or the level specified in the inclusion/exclusion criteria, with the exception of alopecia/pigmentation. Subjects who develop irreversible toxicity and are not expected to worsen after study drug administration (e.g., hearing loss) may be included in the study in consultation with the sponsor. Subjects with long-term toxicity caused by radiotherapy, which cannot be recovered in the judgment of the investigator, may be included in the study after consultation with the sponsor. 8. Concomitant second malignancy within 5 years prior to screening, except for the type of cancer being studied in this study and locally recurrent cancer that has been cured (such as basal cell or squamous cell skin cancer that has been resected, superficial bladder cancer, localized prostate cancer, cervical carcinoma in situ, or breast carcinoma in situ). 9. Cardiac function and disease consistent with one of the following: a) long QTc syndrome or prolonged QTc interval, > 450 ms for males and 470 ms for females>; b) Complete left bundle branch block, second- or third-degree atrioventricular block; c) severe, uncontrolled cardiac arrhythmias requiring medication; d) New York College of Cardiology (NYHA) > Class 2 heart failure; e) Left ventricular ejection fraction (LVEF) less than 50%; f) Myocardial infarction, unstable angina, history of severe unstable ventricular arrhythmia, or any other cardiac arrhythmia requiring treatment, clinically significant pericardial disease, or ECG evidence of acute ischemic or active conduction system abnormalities within 6 months prior to enrollment. 10. Active bleeding at the proposed injection site. 11. Poorly controlled systemic diseases (e.g., poorly controlled hypertension, diabetes, etc.). 12. Uncontrollable active infection. 13. Human immunodeficiency virus (HIV) infection (HIV antibody positive), active hepatitis B infection (hepatitis B virus surface antigen positive and hepatitis B virus DNA greater than 1×103 IU/mL), active hepatitis C infection (hepatitis C virus RNA exceeding 1×103 IU/mL); 14. Known history of immediate or delayed hypersensitivity reaction to the same drug or excipient component of the study drug, or history of severe allergic reaction to other monoclonal antibody drugs. 15. Pregnant women, lactating females, patients who refuse to use effective contraception during the study. 16. Concomitant history of severe neurological or psychiatric illness; 17. In the judgment of the investigator, the subject has other factors that may affect the results of the study, or increase the risk of study administration, or cause the study to be terminated, such as alcoholism, drug abuse, other serious acute or chronic physical or psychological diseases, serious abnormalities in laboratory tests, family and social factors affecting the safety of the subject, etc., and the subject is not suitable to participate in this study.

研究实施时间：

Study execute time：

从 From 2025-03-10 00:00:00至 To 2028-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-06-10 00:00:00 至 To 2026-12-31 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	38
Group：	Test group	Sample size：	38
干预措施：	PMC2129G12	干预措施代码：
Intervention：	PMC2129G12 mRNA-LNP Injection	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	甘肃省	市(区县)：
Country：	China	Province：	Gansu	City：
单位(医院)：	甘肃省人民医院	单位级别：	三级甲等
Institution hospital：	Gansu Provincial Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	安全性指标	指标类型：	主要指标
Outcome：	Safety	Type：	Primary indicator
测量时间点：	签署知情同意书后	测量方法：	采用NCI-CTCAE v.5.0对研究过程中的不良事件及严重程度进行判断，重点观察药物的不良反应类型、发生率和严重程度，观察剂量限制性毒性和确定最大耐受剂量。
Measure time point of outcome：	After signing the ICF	Measure method：	NCI-CTCAE v.5.0 will be used to judge the adverse events and severity during the research process. Focus on observing the types, incidence rates and severity of drug adverse reactions, observing dose-limiting toxicity and determining the maximum tolerated dose.

指标中文名：	抗体浓度	指标类型：	次要指标
Outcome：	Antibody concentration	Type：	Secondary indicator
测量时间点：	治疗前后D1,D2,D4,D8,D10,D15,D28	测量方法：	PK样本将在中心实验室进行检测，对其中的研究药物浓度进行定量检测。
Measure time point of outcome：	Before and after treatment, D1, D2, D4, D8, D10, D15, D28	Measure method：	PK samples will be tested in the central laboratory, where the concentration of the investigational drug is quantitatively measured.

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：	首次评估在给药后D28天，之后每8周评估1次	测量方法：	根据RECIST v1.1进行评价，增强 CT 或 MRI扫描。
Measure time point of outcome：	The first assessment is conducted 28 days after administration, then once every 8 weeks thereafter	Measure method：	Evaluation will be conducted according to RECIST v1.1, using enhanced CT or MRI scans.

指标中文名：	疾病控制率	指标类型：	次要指标
Outcome：	Disease control 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：	缓解持续时间	指标类型：	次要指标
Outcome：	Duration of response	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：	外周血	组织：
Sample Name：	Peripheral 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）：

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）：	原始数据不共享
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	The raw data is not shared
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：	电子病例报告表和EDC
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	eCRF and EDC
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2025-06-09 16:51:59