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：	ChiCTR2600123887
最近更新日期： Date of Last Refreshed on：	2026-04-30 15:55:53
注册时间： Date of Registration：	2026-04-30 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	YMN-M12 腺病毒肿瘤疫苗用于晚期实体瘤肺部转移患者的安全性、耐受性、免疫原性及初步有效性临床研究
Public title：	Safety, Tolerability, Immunogenicity and Preliminary Efficacy of YMN-M12 Adenoviral Tumor Vaccine in Patients with Advanced Lung Cancer
注册题目简写：
English Acronym：
研究课题的正式科学名称：	YMN-M12 腺病毒肿瘤疫苗用于晚期实体瘤肺部转移患者的安全性、耐受性、免疫原性及初步有效性
Scientific title：	Safety, Tolerability, Immunogenicity and Preliminary Efficacy of YMN-M12 Adenoviral Tumor Vaccine in Patients with Advanced Lung Cancer
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：	林楠	研究负责人：	马学磊
Applicant：	Nan Lin	Study leader：	Xuelei Ma
申请注册联系人电话： Applicant telephone：	+86 28 8542 2683	研究负责人电话： Study leader's telephone：	+86 28 8542 2683
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：	linnan@stu.scu.edu.cn	研究负责人电子邮件： Study leader's E-mail：	linnan@stu.scu.edu.cn
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：	中国四川省成都市武侯区国学巷37号	研究负责人通讯地址：	中国四川省成都市武侯区国学巷37号
Applicant address：	37, Guoxue Lane, Wuhou District, Chengdu, Sichuan,China	Study leader's address：	37, Guoxue Lane, Wuhou District, Chengdu, Sichuan,China
申请注册联系人邮政编码： Applicant postcode：	067513	研究负责人邮政编码： Study leader's postcode：	067513
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
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	2026年审(858)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：	Biomedical Ethics Committee of West China Hospital, Sichuan University
伦理委员会批准日期： Date of approved by ethic committee：	2026-04-22 00:00:00
伦理委员会联系人：	邓绍林
Contact Name of the ethic committee：	Shaolin Deng
伦理委员会联系地址：	中国四川省成都市武侯区国学巷37号
Contact Address of the ethic committee：	37 Guo Xue Lane, Wuhou District, Chengdu, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 28 8542 2654	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：

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：

中国四川省成都市武侯区国学巷37号

Primary sponsor's address：

37 Guo Xue Lane, Wuhou District, Chengdu, 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)：	四川	市(区县)：	成都
Country：	China	Province：	Sichuan	City：	Chengdu
单位(医院)：	四川大学华西医院	具体地址：	中国四川省成都市武侯区国学巷37号
Institution hospital：	West China Hospital, Sichuan University	Address：	37 Guo Xue Lane, Wuhou District, Chengdu, China

经费或物资来源：

SCI经费

Source(s) of funding：

SCI funding

研究疾病：

肺癌

Target disease：

lung cancer

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：

I期临床试验

Study phase：

1

研究设计：

单臂

Study design：

Single arm

研究目的：

1. 主要目的：本研究拟评价 YMN-M12 腺病毒滴鼻治疗联合二线标准抗肿瘤治疗用于晚期实体瘤肺转移患者的安全性、耐受性、免疫原性及初步有效性。 2. 次要目的：评价YMN-M12腺病毒滴鼻联合二线标准抗肿瘤治疗用于晚期实体瘤肺转移患者的免疫原性及初步有效性。

Objectives of Study：

1.Primary Objective: This study aims to evaluate the safety, tolerability, immunogenicity and preliminary efficacy of intranasal administration of YMN-M12 adenovirus in combination with standard second-line antineoplastic therapy in patients with pulmonary metastases from advanced solid tumors. 2. Secondary Objective: To evaluate the immunogenicity and preliminary efficacy of intranasal administration of YMN-M12 adenovirus combined with standard second-line antineoplastic therapy in patients with pulmonary metastases from advanced solid tumors.

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. Voluntarily sign the written informed consent form, be able to understand and comply with the requirements of the study protocol, and complete all visits, examinations and treatment procedures on time.
2. Age 18-75 years, both genders.
3. Patients with histologically or cytologically confirmed malignant tumors at an advanced stage, with evidence of pulmonary metastasis confirmed by imaging and/or pathology; subjects must have at least one measurable or evaluable pulmonary metastatic lesion.
4. Positive IMP3 protein expression in tumor tissues confirmed by immunohistochemistry (IHC) testing (definition: proportion of IHC-positive tumor cells >=5%; for samples with unclear IHC results, borderline expression, or as prespecified in the study, further supplementary verification by FISH is allowed).
5. Failure, intolerance, or lack of available standard effective treatment as judged by the investigator after prior standard anti-tumor therapy. Specific requirements are as follows:
   (1) For malignant tumors with a clear standard treatment pathway, disease progression should have occurred after at least the corresponding standard systemic therapy;
   (2) For tumors with targetable driver genes or molecular markers, disease progression after completing the corresponding standard targeted therapy, or intolerance to standard targeted therapy;
   (3) For patients who have previously received immunotherapy, chemotherapy, targeted therapy, endocrine therapy, or other standard treatments, there must be clear evidence of treatment failure or disease progression;
   (4) For patients who, in the investigator's judgment, have no expected benefit from standard therapy or are unsuitable to continue receiving existing standard treatment, enrollment may be considered after thorough evaluation.
6. ECOG performance status score of 0-1, with an estimated survival time >=3 months.
7. Baseline laboratory tests meet the following organ function criteria (tests conducted within <=7 days prior to enrollment):
   (1) Blood routine: absolute neutrophil count (ANC) >=1.5×10^9/L, platelet count (PLT) >=100×10^9/L, hemoglobin (Hb) >=90 g/L;
   (2) Liver function: AST/ALT <=2.5×ULN (<=5×ULN for patients with liver metastases), total bilirubin <=1.5×ULN (<=3×ULN for patients with liver metastases);
   (3) Renal function: serum creatinine <=1.5×ULN, or creatinine clearance >=50 mL/min (calculated by the Cockcroft-Gault formula);
   (4) Coagulation function: INR <=1.5, APTT <=1.5×ULN.
8. Women of childbearing potential must have a negative serum pregnancy test before enrollment; all men and women of childbearing potential agree to use medically recognized effective contraceptive measures during the study period and for 6 months after study completion.
9. Ability to provide sufficient archived or fresh tumor tissue specimens for IMP3 expression detection and subsequent biomarker analysis; specimens may be derived from primary or metastatic lesions.

排除标准：

1. 对Ad5腺病毒载体、疫苗辅料、IL-12类药物存在明确过敏史，或既往对同类生物制剂发生过严重过敏反应的患者。 2. 存在影响经鼻给药安全性、耐受性或药物黏膜吸收的鼻腔/鼻窦疾病或解剖异常者，包括但不限于：重度鼻炎（含重度过敏性鼻炎）、活动性鼻窦炎、鼻息肉、严重萎缩性鼻炎、反复鼻出血、鼻腔恶性肿瘤、明显鼻腔结构异常（如明显鼻中隔偏曲等）、筛查前3个月内接受过鼻腔或鼻窦手术，或其他研究者判断不适合接受滴鼻给药的情况。 3. 既往接受过靶向IMP3的抗肿瘤治疗、Ad5载体疫苗治疗或重组IL-12类药物治疗的患者。 4. 存在活动性自身免疫性疾病病史（如系统性红斑狼疮、类风湿关节炎、多发性硬化、自身免疫性肺炎/肝炎/肠炎等），或过去2年内需要全身性免疫抑制剂/糖皮质激素治疗的自身免疫性疾病患者；吸入/局部用糖皮质激素、甲状腺素替代治疗除外。 5. 经胸部影像学证实存在活动性间质性肺病、肺纤维化，或有非感染性肺炎病史且既往需要全身性激素治疗的患者。 6. 存在有症状的中枢神经系统（CNS）转移、癌性脑膜炎，或需要激素/脱水治疗控制颅内症状的CNS转移患者；无症状、稳定的CNS转移（完成局部治疗后>=4周，影像学无进展，无需激素治疗）除外。 7. 存在活动性感染，包括：（1）需要静脉抗感染治疗的细菌、真菌、病毒感染；（2）活动性结核病；（3）HBsAg阳性且HBV DNA高于检测下限（未接受规范抗病毒治疗）；（4）HCV RNA阳性；（5）HIV抗体阳性。 8. 存在严重的基础器质性疾病，包括：（1）纽约心脏病协会（NYHA）III-IV级充血性心力衰竭、不稳定型心绞痛、入组前6个月内发生过心肌梗死/脑卒中、严重控制不佳的心律失常；（2）肝硬化失代偿期、慢性肾功能衰竭需要规律透析；（3）未控制的重度高血压、糖尿病（经规范治疗后仍不达标）。 9. 入组前2周内使用过全身性糖皮质激素（剂量>=10 mg/天泼尼松等效剂量）或其他免疫抑制剂治疗的患者；吸入/局部用糖皮质激素、激素止吐治疗除外。 10. 存在明显影响安全性评估或研究执行的肺部情况，包括：（1）未控制的肺部感染；（2）明显低氧血症或需要持续吸氧支持；（3）广泛肺部转移导致严重呼吸功能受损；（4）无法控制的胸腔积液，或入组前4周内需反复穿刺引流（>=2次）；（5）研究者判断存在显著气道压迫、肺不张或其他可能增加滴鼻给药风险的情况。 11. 存在无法控制的腹水、心包积液，或需反复穿刺引流的患者。 12. 存在肿瘤负荷极高且病情进展迅速，研究者判断短期内难以完成首周期安全性观察或可能显著影响研究评价的患者。 13. 妊娠或哺乳期女性。 14. 入组前3个月内参与过其他临床试验并接受过其他试验药物/器械治疗的患者。 15. 存在已知的先天性或获得性严重免疫缺陷疾病，或既往接受过器官移植、异基因造血干细胞移植的患者。 16. 存在精神疾病、认知障碍，无法理解知情同意内容、无法配合完成研究流程的患者。 17. 研究者判断存在其他可能危及受试者安全、干扰研究结果评价，或导致受试者无法完成研究的情况。

Exclusion criteria：

1. Patients with a clear history of allergy to Ad5 adenovirus vector, vaccine excipients, or IL-12-related drugs, or those who have previously experienced severe hypersensitivity reactions to similar biological agents. 2. Patients with nasal/sinus diseases or anatomical abnormalities that may affect the safety, tolerability, or mucosal absorption of intranasal administration, including but not limited to: severe rhinitis (including severe allergic rhinitis), active sinusitis, nasal polyps, severe atrophic rhinitis, recurrent epistaxis, nasal malignant tumors, obvious nasal structural abnormalities (e.g., significant deviation of the nasal septum), those who have undergone nasal or sinus surgery within 3 months before screening, or other conditions deemed unsuitable for intranasal administration by the investigator. 3. Patients with prior receipt of IMP3-targeted anti-tumor therapy, Ad5 vector vaccine treatment, or recombinant IL-12-related drug therapy. 4. Patients with a history of active autoimmune disease (such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, autoimmune pneumonia/hepatitis/enteritis, etc.), or autoimmune disease requiring systemic immunosuppressants/glucocorticoids within the past 2 years; patients using inhaled/topical glucocorticoids or thyroid hormone replacement therapy are excluded. 5. Patients with active interstitial lung disease or pulmonary fibrosis confirmed by chest imaging, or a history of non-infectious pneumonia that previously required systemic hormone therapy. 6. Patients with symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or CNS metastases requiring hormone/dehydration therapy to control intracranial symptoms; patients with asymptomatic, stable CNS metastases (>=4 weeks after local treatment, no radiological progression, and no need for hormone therapy) are excluded. 7. Patients with active infections, including: (1) Bacterial, fungal, or viral infections requiring intravenous anti-infective treatment; (2) Active tuberculosis; (3) HBsAg positive with HBV DNA above the lower limit of detection (without standardized antiviral treatment); (4) HCV RNA positive; (5) HIV antibody positive. 8. Patients with severe underlying organic diseases, including: (1) New York Heart Association (NYHA) class III-IV congestive heart failure, unstable angina, myocardial infarction/stroke within 6 months before enrollment, or severe uncontrolled arrhythmia; (2) Decompensated liver cirrhosis or chronic renal failure requiring regular dialysis; (3) Uncontrolled severe hypertension or diabetes mellitus (failing to achieve target despite standardized treatment). 9. Patients who have received systemic glucocorticoids (prednisone equivalent dose >=10 mg/day) or other immunosuppressants within 2 weeks before enrollment; patients using inhaled/topical glucocorticoids or hormone antiemetic therapy are excluded. 10. Patients with pulmonary conditions that significantly affect safety evaluation or study execution, including: (1) Uncontrolled pulmonary infection; (2) Significant hypoxemia or requirement for continuous oxygen support; (3) Extensive pulmonary metastases resulting in severe respiratory impairment; (4) Uncontrolled pleural effusion, or requiring repeated puncture and drainage (>=2 times within 4 weeks before enrollment); (5) Significant airway compression, atelectasis, or other conditions judged by the investigator to potentially increase the risk of intranasal administration. 11. Patients with uncontrolled ascites or pericardial effusion, or requiring repeated puncture and drainage. 12. Patients with extremely high tumor burden and rapidly progressive disease, who in the investigator's judgment are unlikely to complete the first-cycle safety observation in the short term or may significantly affect study evaluation. 13. Pregnant or lactating women. 14. Patients who have participated in other clinical trials and received other investigational drugs/devices within 3 months before enrollment. 15. Patients with known congenital or acquired severe immunodeficiency diseases, or a history of organ transplantation or allogeneic hematopoietic stem cell transplantation. 16. Patients with mental disorders or cognitive impairment who are unable to understand the informed consent content or cooperate with the study procedures. 17. Any other conditions judged by the investigator that may endanger the subject's safety, interfere with the evaluation of study results, or prevent the subject from completing the study.

研究实施时间：

Study execute time：

从 From 2026-05-01 00:00:00至 To 2028-05-01 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2026-05-01 00:00:00 至 To 2028-05-01 00:00:00

干预措施：

Interventions：

组别：	治疗组	样本量：	9
Group：	Treatment group	Sample size：	9
干预措施：	本研究采用“3+3”剂量递增设计，设置3个剂量水平。剂量水平1（DL1）：2×10^10 /次剂量水平2（DL2）：4×10^10 /次剂量水平3（DL3）：8×10^10 /次本研究以 21天为1个治疗周期。YMN-M12采用呼吸道黏膜给药方式，于每周期第1天（Day 1）给药1次。	干预措施代码：
Intervention：	This study adopts a 3+3 dose-escalation design with 3 dose levels established: Dose Level 1 (DL1): 2 × 10^1? viral particles per dose Dose Level 2 (DL2): 4 × 10^1? viral particles per dose Dose Level 3 (DL3): 8 × 10^1? viral particles per dose The treatment cycle is 21 days in duration. YMN-M12 is administered via the respiratory mucosal route, once on Day 1 of each cycle.	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	四川省	市(区县)：	成都
Country：	China	Province：	Sichuan	City：	Chengdu
单位(医院)：	四川大学华西医院	单位级别：	三甲
Institution hospital：	West China Hospital, Sichuan University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	安全性	指标类型：	主要指标
Outcome：	Safety	Type：	Primary indicator
测量时间点：	治疗期间及随访时	测量方法：
Measure time point of outcome：	During the treatment period and follow-up	Measure method：

指标中文名：	剂量限制性毒性(DLT)	指标类型：	主要指标
Outcome：	Dose-limiting toxicity (DLT)	Type：	Primary indicator
测量时间点：	首次给药后28天内	测量方法：	CTCAE v5.0
Measure time point of outcome：	Within 28 days after the first administration	Measure method：

指标中文名：	初步有效性检测	指标类型：	次要指标
Outcome：	Preliminary effectiveness testing	Type：	Secondary indicator
测量时间点：	基线影像应在首次给药前28天内完成；此后于第6周、第12周进行首次和第二次疗效评估；之后每9周至第48周复查一次；第48周后改为每12周复查一次，直至影像学进展、开始新的抗肿瘤治疗、撤回知情同意、失访	测量方法：	影像学检查以胸部及上腹部增强CT为基础，必要时结合脑MRI、骨扫描、PET/CT或其他部位影像。
Measure time point of outcome：	Baseline imaging should be completed within 28 days before the first administration. The first and second efficacy evaluations were conducted at the 6th and 12th weeks respectively thereafter. Then, have a re-examination every 9 weeks to the 48th week. After the 48th week, the follow-up was changed to once every 12 weeks until the imaging progressed, a new anti-tumor treatment was initiated, informed consent was withdrawn, and the patient was lost to follow-up	Measure method：	Imaging examinations are based on enhanced CT of the chest and upper abdomen. When necessary, brain MRI, bone scan, PET/CT or images of other parts are combined.

指标中文名：	特异性免疫反应	指标类型：	次要指标
Outcome：	Specific immune response	Type：	Secondary indicator
测量时间点：	基线、第6周、第12周、EOT	测量方法：	采用 ELISpot、流式细胞术胞内细胞因子染色（ICS）或其他经验证的方法，检测 IMP3 特异性 T 细胞反应
Measure time point of outcome：	Baseline, week 6, week 12, EOT	Measure method：	ELISpot, flow cytometry intracellular cytokine staining (ICS) , or other validated methods were used to detect IMP3-specific T cell responses

指标中文名：	载体脱落/排出监测	指标类型：	次要指标
Outcome：	Vehicle shedding/discharge monitoring	Type：	Secondary indicator
测量时间点：	治疗期间及随访时	测量方法：	通过鼻拭子、咽拭子/唾液，必要时尿液或血液，采用核酸检测方法观察载体脱落情况。
Measure time point of outcome：	During the treatment period and follow-up	Measure method：	The shedding of the carrier can be observed through nasal swabs, throat swabs/saliva, and if necessary, urine or blood, using nucleic acid testing methods.

指标中文名：	免疫原性检测	指标类型：	次要指标
Outcome：	Immunogenicity tests	Type：	Secondary indicator
测量时间点：	基线、第6周、第12周、EOT	测量方法：	检测外周血淋巴细胞亚群（CD3、CD4、CD8、NK、B细胞）、Treg 比例等，用于描述全身免疫状态变化。
Measure time point of outcome：	Baseline, week 6, week 12, EOT	Measure method：	The detection of peripheral blood lymphocyte subsets (CD3, CD4, CD8, NK, B cells), Treg ratios, etc., is used to describe the changes in the systemic immune status.

指标中文名：	不良事件与严重不良事件	指标类型：	主要指标
Outcome：	Adverse events and serious adverse events	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	生命体征、体格检查和局部耐受性	指标类型：	主要指标
Outcome：	Vital signs, physical examination and local tolerance	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	细胞因子/药效学指标	指标类型：	次要指标
Outcome：	Cytokines/pharmacodynamic indicators	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	黏膜免疫指标	指标类型：	主要指标
Outcome：	Mucosal immune indicators	Type：	Primary 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：

标本中文名：	鼻拭子	组织：
Sample Name：	Nasal swab	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：
Blinding：

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）：	不共享
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：	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
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2026-04-30 15:55:14