ChiCTR2500109506 版本V1.1 版本创建时间2025/09/19 11:12:50 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：

 ChiCTR2500109506 

最近更新日期：

Date of Last Refreshed on：

 2025-09-19 11:12:05 

注册时间：

Date of Registration：

 2025-09-19 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

评价重组人IL-21溶瘤痘病毒注射液（hV01）联合通用型CAR-raNK细胞注射液（IBR854）治疗晚期恶性实体瘤的安全性和初步有效性的临床研究

Public title：

A study to evaluate the safety and primary efficacy of the combination therapy of recombinant human IL-21 oncolytic vaccinia virus injection (hV01) and ready-to-use CAR-raNK cells (IBR854) in 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：

评价重组人IL-21溶瘤痘病毒注射液（hV01）联合通用型CAR-raNK细胞注射液（IBR854）治疗晚期恶性实体瘤的安全性和初步有效性的临床研究

Scientific title：

A study to evaluate the safety and primary efficacy of the combination therapy of recombinant human IL-21 oncolytic vaccinia virus injection (hV01) and ready-to-use CAR-raNK cells (IBR854) in 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：

黄诚 

研究负责人：

黄诚 

Applicant：

Huang Cheng 

Study leader：

Huang Cheng 

申请注册联系人电话：

Applicant telephone：

 +86 13905010379

研究负责人电话：

Study leader's
telephone：

+86 13905010379

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：

 huangcheng@haxm.org

研究负责人电子邮件：

Study leader's E-mail：

 huangcheng@haxm.org

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：

福建省厦门市湖里区仙岳路3777号

研究负责人通讯地址：

福建省厦门市湖里区仙岳路3777号

Applicant address：

No. 3777,?Xianyue?Road,?Huli?District,?Xiamen, Fujian Province

Study leader's address：

No. 3777,?Xianyue?Road,?Huli?District,?Xiamen, Fujian 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：

厦门弘爱医院

Applicant's institution：

Xiamen Humanity Hospital

研究负责人所在单位：

厦门弘爱医院

Affiliation of the Leader：

Xiamen Humanity 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：

 HAXM-MEC-20240314-021-02; HAXM-MEC-20240314-021-04

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：

厦门弘爱医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Xiamen Hongai Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2025-08-01 00:00:00

伦理委员会联系人：

邱兰秀

Contact Name of the ethic committee：

Qiu Lanxiu

伦理委员会联系地址：

福建省厦门市湖里区仙岳路3777号

Contact Address of the ethic committee：

No. 3777,?Xianyue?Road,?Huli?District,?Xiamen, Fujian Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 592 5261060

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 292666745@qq.com

研究实施负责（组长）单位：

厦门弘爱医院

Primary sponsor：

Xiamen Humanity Hospital

研究实施负责（组长）单位地址：

福建省厦门市湖里区仙岳路3777号

Primary sponsor's address：

No. 3777,?Xianyue?Road,?Huli?District,?Xiamen, Fujian 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)：

福建省

市(区县)：

Country：

China

Province：

Fujian

City：

单位(医院)：

厦门弘爱医院

具体地址：

福建省厦门市湖里区仙岳路3777号

Institution
hospital：

Xiamen Humanity Hospital

Address：

No. 3777,?Xianyue?Road,?Huli?District,?Xiamen, Fujian Province

经费或物资来源：

杭州康万达医药科技有限公司

Source(s) of funding：

Hangzhou ConVerd Co., Ltd.

研究疾病：

晚期肉瘤、胰腺癌、原发性肝癌、头颈部肿瘤、妇科肿瘤  

Target disease：

Advanced sarcoma, pancreatic cancer, primary hepatic cancer, head and neck tumors, and gynecological tumors

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：

主要目的： 1.评价hV01和IBR854联合治疗晚期恶性实体瘤的安全性和耐受性； 次要目的： 1.初步评价hV01和IBR854联合治疗晚期恶性实体瘤的疗效（根据RECIST v1.1和iRECIST标准进行评估）； 探索性目的： 1.探索外周血细胞因子水平的变化； 2.探索外周血淋巴细胞亚群水平的变化； 3.探索基线外周血中肿瘤基因组特征与疗效的相关性； 4.探索给药后外周血免疫组库特征变化。  

Objectives of Study：

Primary objectives: 1. To evaluate the safety and tolerance of the combination therapy of hV01 and IBR854 in patients with advanced malignant solid tumors; Secondary objectives: 1. To preliminarily assess the efficacy of the combination therapy of hV01 and IBR854 in patients with advanced malignant solid tumors (evaluated according to RECIST v1.1 and iRECIST standards); Exploratory objectives: 1. To explore the changes in cytokine levels in peripheral blood; 2. To explore the changes in lymphocyte subset levels in peripheral blood; 3. To explore the correlation between baseline tumor genomic characteristics in peripheral blood and efficacy; 4. To explore the changes in immune repertoire characteristics in peripheral blood after administration.

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.受试者自愿参加本临床试验并签署知情同意书； 2.年龄18 ~75周岁（含18周岁和75周岁），性别不限； 3.经组织学和/或细胞学确证的，现阶段已无标准治疗或经标准治疗失败的晚期肉瘤、胰腺癌、原发性肝癌、头颈部肿瘤或妇科肿瘤患者； 4.根据 RECIST v1.1标准至少有一个或多个可测量病灶，并可直接目视下瘤内注射或通过医学影像仪器（B超/CT）和/或内窥镜辅助瘤内注射给药，注射病灶基线最长径>1.5 cm； 注：既往接受过放疗的肿瘤病灶不应视为靶病灶，除非放疗后病灶发生明确进展； 5.美国东部肿瘤协作组体力状态评分（ECOG）0~1分； 6.预计生存期>=3个月； 7.主要器官功能基本正常： (1)血液学：绝对中性粒细胞计数（ANC）>= 1.5×10^9/L，血小板（PLT）>= 75×10^9/L，血红蛋白（Hb）>=90 g/L（实验室检查前14天内未接受过支持治疗）； (2)肝功能：血清总胆红素（TBIL）<=1.5×ULN（Gilbert’s 综合征或肝转移患者<=3×ULN）；丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）<=3×ULN（原发性肝癌或肝转移患者AST及ALT＜5×ULN）； (3)肾功能：血清肌酐（Cr）<=1.5×ULN，且肌酐清除率（Cockcroft-Gault 法）>=45 mL/min：男性肌酐清除率=[(140-年龄)×体重(kg)]/[0.818×肌酐(μmol/L)]；女性肌酐清除率=[(140-年龄)×体重(kg)×0.85]/[0.818×肌酐(μmol/L)]； (4)凝血功能：活化的部分凝血活酶时间（APTT）<=1.5×ULN；国际标准化比值（INR）<=1.5×ULN; 8.育龄女性受试者血清妊娠试验必须为阴性；育龄女性受试者，以及伴侣为育龄女性的男性受试者须同意在整个治疗期间和末次用药后3个月内采用经医学认可的避孕措施（激素或屏障法或禁欲），男性受试者还须避免精子捐献；注：非育龄期女性包括永久绝育（子宫切除术、双侧卵巢切除术或双侧输卵管切除术）和已绝经妇女。对于>=50岁女性，如果在计划随机入组日期前12个月已停经且无其他医学病因，则认为该女性已绝经。对于＜50岁的女性，如果停止外源性激素治疗后已停经12个月或以上、且促卵泡生成激素（FSH）水平在绝经后范围内，则认为该女性已绝经。

Inclusion criteria

1.Signing an informed consent form; 2.Men or women aged 18 to 75 years; 3.Histologically and/or cytologically confirmed advanced sarcoma, pancreatic cancer, primary hepatic cancer, head and neck tumor, and gynecological tumors refractory or failed to respond to standard therapies; 4.At least one measurable lesion according to RECIST v1.1 criteria, which can be injected intratumorally either directly or with the assistance of medical imaging equipment such as B-ultrasound, CT, or EUS fine-needle aspiration device. The baseline longest diameter of the lesion targeted for injection should be more than 1.5 cm. Note: Lesions that received radiotherapy should not be selected as target lesions unless unequivocal progression is demonstrated; 5.Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; 6.Life expectancy of at least 3 months; 7. Major organ functions are basically normal: (1) Hematology: Absolute Neutrophil Count (ANC) >= 1.5×10^9/L, Platelets (PLT) >= 75×10^9/L, Hemoglobin (Hb) >= 90 g/L (no supportive treatment received in the 14 days prior to laboratory testing); (2) Liver function: Serum Total Bilirubin (TBIL) <= 1.5×ULN (for patients with Gilbert’s syndrome or liver metastasis <= 3×ULN); Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) <= 3×ULN (for primary liver cancer or liver metastasis patients, AST and ALT < 5×ULN); (3) Kidney function: Serum Creatinine (Cr) <= 1.5×ULN, and Creatinine Clearance (Cockcroft-Gault method) >= 45 mL/min: Male creatinine clearance = [(140-age) × weight (kg)] / [0.818 × creatinine (μmol/L)]; Female creatinine clearance = [(140-age) × weight (kg) × 0.85] / [0.818 × creatinine (μmol/L)]; (4) Coagulation function: Activated Partial Thromboplastin Time (APTT) <= 1.5×ULN; International Normalized Ratio (INR) <= 1.5×ULN; 8. Pregnant test for women of childbearing age must be negative; female participants of childbearing age, as well as male participants with partners of childbearing age, must agree to use medically approved contraceptive measures (hormonal or barrier methods or abstinence) throughout the treatment period and for 3 months after the last dose, and male participants must also avoid sperm donation; Note: Non-childbearing women include those who are permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) and postmenopausal women. For women aged >= 50, if they have been menopause for 12 months or more before the planned randomization date with no other medical causes, they are considered to be postmenopausal. For women aged < 50, if menopause has occurred for 12 months or more after discontinuing exogenous hormone therapy, and their Follicle Stimulating Hormone (FSH) levels are within menopause range, they are considered to be postmenopausal.

排除标准：

1.既定时间内接受过以下抗肿瘤治疗： (1) 首次给药前4周内接受过系统性抗肿瘤治疗，包括化疗、大分子靶向、免疫治疗、内分泌治疗等（亚硝基脲或丝裂霉素C为首次给药前6周内）； (2) 首次给药前2周内或药物的5个半衰期内（以时间长的为准）接受过小分子靶向药治疗； (3) 首次给药前2周内接受过有抗肿瘤适应症的中/草药全身抗肿瘤治疗； (4) 首次给药前2周内接受过放疗（姑息性放疗除外）。 2.既往治疗引起的急性毒副反应未缓解至CTCAE v5.0等级评价1级或以下（脱发等研究者判断无安全风险的毒性除外）； 3.首次给药前4周内使用过任何其他临床试验药物； 4.首次给药前4周内进行过除诊断或活检外的其他治疗性手术，或预期需要在研究期间进行重大手术； 5.具有临床症状的中枢神经系统转移或脑膜转移，或有其他证据表明患者中枢神经系统转移或脑膜转移灶尚未控制，经研究者判断不适合入组； 6.已知或疑似活动性自身免疫性疾病（包括但不限于系统性红斑狼疮、干燥综合征、类风湿关节炎、牛皮癣、多发性硬化症、炎症性肠病、桥本甲状腺炎等）； 7.严重的心脑血管疾病史，包括： (1) 首次给药前12个月内患有急性冠脉综合征（包括心肌梗死、严重或不稳定心绞痛）、心肌炎、充血性心力衰竭、脑血管意外或其他CTCAE v5.0等级评价3级及以上心血管事件； (2) 需要临床干预的严重心律失常（如室性心动过速、室性纤维性颤动或尖端扭转型室性心动过速）； (3) 纽约心脏病协会（NYHA）分类>= II级，或静息状态下左室射血分数（LVEF）<50%； (4) 标准治疗无法控制的高血压（由研究者判断）或低血压; 8.具有临床意义和/或快速积聚的心包积液和/或胸腔积液； 9.首次给药前6个月内出现过显著临床意义的出血症状或具有明确的出血倾向； 10.需要药物治疗的重度炎症性皮肤疾病（如湿疹或牛皮癣需要全身治疗等）； 11.任何不可控的或需要全身抗感染治疗的活动性感染（CTCAE v5.0等级评价2级及以上），包括但不限于活动性结核、败血症、菌血症、真菌血症、病毒血症等； 12.已知人类免疫缺陷（HIV）或已知获得性免疫缺陷（AIDS）检测阳性史、梅毒螺旋体抗体（TP）阳性；活动性丙型肝炎（检测到HCV RNA 阳性）； 13.首次给药前2周内使用过治疗剂量的皮质类固醇（泼尼松或等效物>10 mg/天），或经研究者判断存在需要在试验期间使用系统性皮质类固醇治疗或其他免疫抑制药物治疗的合并症（除外以下情况：使用局部、眼部、关节腔内、鼻内和吸入型糖皮质激素治疗，短期使用糖皮质激素进行预防治疗[例如预防造影剂过敏]）； 14.首次给药前2周内使用过免疫调节药物，包括但不限于胸腺素、白介素、干扰素等； 15.首次给药前1周内使用过可能具有抗痘病毒作用的药物（如利巴韦林等，但除外符合条件的乙肝患者使用的抗乙肝病毒治疗药物）； 16.首次给药前4周内接种过活疫苗；注：活疫苗包括但不限于：麻疹、腮腺炎、风疹、水痘/带状疱疹、黄热病、狂犬病、卡介苗和伤寒疫苗。季节性流感疫苗一般为灭活疫苗，允许接种。鼻内流感疫苗是减毒活疫苗，不允许接种。 17.患有已知的可能影响试验依从性的精神障碍性疾病； 18.妊娠或哺乳期妇女； 19.其他研究者认为不适合入组的情况，包括但不限于肿瘤与重要神经血管结构、气道相邻或肿瘤位于具有不良事件高风险或不适合瘤内注射位置。

Exclusion criteria：

1.Receiving any of the following anti-tumor treatments within a specified time period: (1) Systemic anti-tumor treatment, including chemotherapy, large-molecule targeted therapy, immunotherapy, and endocrine therapy within 4 weeks before first dose (within 6 weeks of dosing for nitrosourea or mitomycin C); (2) Small-molecule targeted therapy within 2 weeks before first dose or within 5 half-lives of the small-molecule targeted drug (whichever is longer); (3) Traditional Chinese medicine or Chinese herbal medicine used as anti-tumor agent within 2 weeks before first dose; (4) Radiotherapy (excluding palliative radiotherapy) within 2 weeks before first dose; 2.Acute toxic effects from prior treatments not resolved to Common Terminology Criteria for Adverse Events (CTCAE, v5.0) grade 1 or below, except for toxicities deemed safe by the investigator, such as alopecia; 3.Receiving any investigational drug for clinical trials within 4 weeks prior to the first dose; 4.Undergoing any therapeutic surgeries (excluding diagnostic surgery or biopsy) within 4 weeks before the first dose, or there is a scheduled surgery while the patient is participating in the study; 5.Patients with clinical symptoms of central nervous system (CNS) metastasis or meningeal metastasis, or other evidence indicating that CNS or meningeal metastases are not controlled; 6.Known or suspected active autoimmune diseases (including but not limited to systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, and Hashimoto's thyroiditis); 7.History of severe cardiovascular and cerebrovascular diseases, including: (1) Acute coronary syndrome (including myocardial infarction, severe or unstable angina), myocarditis, congestive heart failure, cerebrovascular accidents, or other cardiovascular events of CTCAE (v5.0) grade 3 or higher within 12 months of dosing; (2) Severe arrhythmia requiring clinical intervention (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes); (3) New York Heart Association (NYHA) classification of class II or above, or left ventricular ejection fraction (LVEF) <50%; (4) Uncontrolled hypertension (as judged by the investigator) or hypotension despite standard treatment; 8.Rapidly progressing pericardial effusion and/or pleural effusion (and/or of clinical significance); 9.Bleeding symptoms of great clinical significance or clear bleeding tendency within six months prior to the initial dose; 10.Severe inflammatory skin diseases which require treatment with medicines (e.g. eczema or psoriasis requiring systematic treatment); 11.Any uncontrolled active infection requiring systemic anti-infective therapy (graded 2 or higher according to CTCAE v5.0), including but not limited to active tuberculosis, sepsis, bacteremia, fungemia, and viremia; 12.Any of the following infections: human immunodeficiency virus (HIV), syphilis spirochete(TP), active hepatitis C (positive HCV RNA test) or active hepatitis B (positive HBsAg and HBV DNA >= 2000 IU/mL or >=10^4 copies/mL); 13.Receiving therapeutic dosages of corticosteroids such as prednisone or its equivalent >10 mg daily within two weeks prior to the first dose, or having any coexisting diseases that might require systemic corticosteroids or any other immune suppressors during the study (assessed by the investigators) with the following exceptions: local administration of glucocorticoid (e.g. topical routes such as for eyes, intra-articular, intranasal, or inhaled); or usage of glucocorticoids for a short period of time for preventive purposes such as for the prevention of contrast media hypersensitivity); 14.Use of immunomodulatory drugs within 2 weeks of dosing, including but not limited to thymosin, interleukin, and interferon; 15.Use of antiviral drugs that might have anti-poxvirus properties within one week of the initial dose, such as ribavirin, except for anti-HBV drugs taken by patients with hepatitis B who are eligible for the study; 16.Receiving any of the live vaccines within four weeks of the first dose. Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and Typhoid vaccine. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed; 17.Mental disorders that could potentially impact the participant's ability to comply with the study requirements; 18.Pregnancy or lactation; 19.Other situations that, in the opinion of the investigators, are not suitable for the study. These include, but are not limited to, tumors to be injected lying too close to critical nerves, major blood vessels, or an airway; and tumors that are not suitable for intratumor injection or that are likely to result in high adverse events.

研究实施时间：

Study execute time：

从 From 2024-05-16 00:00:00至 To 2026-05-15 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-07-16 00:00:00 至 To 2024-11-07 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 5

Group：

Experimental group

Sample size：

干预措施：

重组人IL-21溶瘤痘病毒注射液（hV01）

干预措施代码：

Intervention：

Recombinant human IL-21 oncolytic vaccinia virus injection (hV01)

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 福建省 

市(区县)：

  

Country：

China

Province：

Fujian

City：

单位(医院)：

 厦门弘爱医院 

单位级别：

 三级医院 

Institution
hospital：

Xiamen Humanity Hospital

Level of the institution：

Tertiary

测量指标：

Outcomes：

指标中文名：

总生存期（OS）

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：

总体不良事件和耐受性

指标类型：

主要指标

Outcome：

Adverse events (AEs) and tolerability

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

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 toxicities (DLTs)

Type：

Primary 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（PFS）

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：

疾病控制率（DCR）

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：

缓解持续时间（DOR）

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：

总缓解率（ORR）

指标类型：

次要指标

Outcome：

Overall Response Rate (ORR)

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：

结束

/Completed

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

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）：

邮件联系研究者

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

Contact the researcher via email

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：

使用EDC系统和eCRF

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

EDC system and eCRF

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2025-09-19 11:11:53