ChiCTR2600125232 版本V1.0 版本创建时间2026/05/22 15:47:37 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：

 ChiCTR2600125232 

最近更新日期：

Date of Last Refreshed on：

 2026-05-22 15:47:32 

注册时间：

Date of Registration：

 2026-05-22 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

艾帕洛利托沃瑞利单抗联合贝伐珠单抗及HAIC在一线治疗中晚期肝细胞癌的单臂干预临床研究

Public title：

A single-arm intervention clinical study of apalolitovolrelimab combined with bevacizumab and HAIC in the first-line treatment of advanced hepatocellular carcinoma

注册题目简写：

English Acronym：

研究课题的正式科学名称：

艾帕洛利托沃瑞利单抗联合贝伐珠单抗及HAIC在一线治疗中晚期肝细胞癌的单臂干预临床研究

Scientific title：

A single-arm intervention clinical study of apalolitovolrelimab combined with bevacizumab and HAIC in the first-line treatment of advanced hepatocellular carcinoma

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：

金仁安 

研究负责人：

蔡秀军 

Applicant：

Renan Jin 

Study leader：

Xiujun Cai 

申请注册联系人电话：

Applicant telephone：

 +86 150 0581 7586

研究负责人电话：

Study leader's
telephone：

+86 150 0581 7586

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：

 jason198508@126.com

研究负责人电子邮件：

Study leader's E-mail：

 jason198508@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：

浙江省杭州市庆春东路3号

研究负责人通讯地址：

浙江省杭州市庆春东路3号

Applicant address：

3 Qingchun Road East, Jianggan District, Hangzhou, Zhejiang, China

Study leader's address：

3 Qingchun Road East, Jianggan District, Hangzhou, Zhejiang, 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：

浙江大学医学院附属邵逸夫医院

Applicant's institution：

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

研究负责人所在单位：

浙江大学医学院附属邵逸夫医院

Affiliation of the Leader：

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang 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：

 邵逸夫医院伦审2025研第0669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：

浙江大学医学院附属邵逸夫医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine

伦理委员会批准日期：

Date of approved by ethic committee：

 2025-09-17 00:00:00

伦理委员会联系人：

金烨成

Contact Name of the ethic committee：

Jin Yecheng

伦理委员会联系地址：

浙江省杭州市庆春东路3号

Contact Address of the ethic committee：

3 Qingchun Road East, Jianggan District, Hangzhou, Zhejiang, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 571 8600 6811

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：

浙江大学医学院附属邵逸夫医院

Primary sponsor：

Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine

研究实施负责（组长）单位地址：

浙江省杭州市庆春东路3号

Primary sponsor's address：

3 Qingchun Road East, Jianggan District, Hangzhou, Zhejiang, 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)：

浙江

市(区县)：

杭州

Country：

China

Province：

Zhejiang

City：

Hangzhou

单位(医院)：

浙江大学医学院附属邵逸夫医院

具体地址：

浙江省杭州市庆春东路3号

Institution
hospital：

Run Run Shaw Hospital affiliated to Zhejiang University School of Medicine

Address：

3 Qingchun Road East, Jianggan District, Hangzhou, Zhejiang, China

经费或物资来源：

自选课题（自筹）

Source(s) of funding：

Self-selected topics and self-funded

研究疾病：

中晚期肝细胞癌  

Target disease：

Advanced hepatocellular carcinoma

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：

本研究拟探索艾帕洛利托沃瑞利单抗联合贝伐珠单抗及 HAIC 在中晚期肝细胞癌患者治疗的有效性与安全性。  

Objectives of Study：

This study aims to explore the efficacy and safety of apalolitovolrelimab in combination with bevacizumab and HAIC in the treatment of patients with advanced hepatocellular carcinoma.

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.自愿参加本研究，并签署知情同意书。 2.年龄18至75周岁（包含边界值）。 3.经病理/临床诊断为原发性肝细胞癌、或原发性肝细胞癌根治性切除术后复发；根据中国肝癌分期（CNLC 分期）2-3期，或巴塞罗那临床肝癌（BCLC）分期分类为 B/C 期，且研究者评估为不适合进行手术者。 4.根据筛选期临床数据和实验室数据评估肝功能状态Child Pugh A 级，或Child Pugh B 级经护肝治疗后评估为Child Pugh A 级。 5.日本肝癌研究小组分型（Vp 分型）为 Vp1-Vp2 的患者。 6.既往未接受过系统抗肿瘤治疗和免疫检查点抑制剂单药或联合治疗方案。 7.至少有一个可测量病灶（根据 RECIST v1.1 或 mRECIST 要求）。 8.ECOG PS 评分：0～1。 9.良好的器官功能符合下列要求（不包括在筛选期间使用任何血液成分及细胞生长因子）：白细胞计数 >=3.0×10^9 /L；中性粒细胞绝对计数 >=1.5×10^9 /L；血小板 >=80×10^9 /L；血红蛋白>=9g/dL。2.血清白蛋白>=3g/dL。促甲状腺激素（TSH）<=1×ULN（如异常应同时考察 T3、T4 水平，如 T3、T4 水平正常，可以入组)。总胆红素<=2.0×ULN；ALT、AST 均<=5.0×ULN。5.血清肌酐<=1.5×ULN 或肌酐清除率>=60mL/min（应用标准的 Cockcroft-Gault 公式）；尿常规结果显示尿蛋白<2+；对基线时尿常规检测显示尿蛋白 2+的患者，应进行 24h 尿液采集且 24h 尿蛋白定量<1g；凝血功能检测：国际标准化比率（INR）<=2 或凝血酶原时间（PT）超过正常范围上限<=6 秒。 10.如果 HBsAg（+），要求 HBV DNA 必须＜2000 IU/mL 或 10^4拷贝/mL，并且在研究期间全程使用恩替卡韦、富马酸替诺福韦酯、富马酸丙酚替诺福韦或艾米替诺福韦有效抗 HBV 治疗。既往有 HCV感染史但 HCV RNA 的 PCR 结果为阴性的患者可认为未感染 HCV。 11.育龄妇女在入组前必须确认非妊娠状态。所有入组患者（不论男性或女性）均应在整个治疗期间及治疗结束后 4 周内采取充分的避孕措施。

Inclusion criteria

1. Willing to participate in this study and sign the informed consent form. 2. Age between 18 and 75 years (inclusive). 3. Pathologically or clinically diagnosed with primary hepatocellular carcinoma, or recurrence after curative resection for primary hepatocellular carcinoma; classified as stage 2–3 according to the Chinese Liver Cancer Staging System (CNLC), or B/C stage according to the Barcelona Clinic Liver Cancer (BCLC) staging system, and assessed by the investigator as unsuitable for surgery. 4. Liver function status evaluated as Child-Pugh A based on clinical and laboratory data during screening, or Child-Pugh B that has been downgraded to Child-Pugh A following liver-protective treatment. 5. Patients classified as Vp1–Vp2 according to the Japan Liver Cancer Research Group classification (Vp classification). 6. No prior systemic anti-tumor therapy, including monotherapy or combination therapy with immune checkpoint inhibitors. 7. At least one measurable lesion (according to RECIST v1.1 or mRECIST criteria). 8. ECOG performance status score of 0–1. 9. Adequate organ function meeting the following requirements (excluding use of blood components or growth factors during screening): (1) white blood cell count >=3.0×10^9/L; (2) absolute neutrophil count >=1.5×10^9/L; (3) platelet count >=80×10^9/L; (4) hemoglobin >=9 g/dL; (5) serum albumin >=3 g/dL; (6) thyroid-stimulating hormone (TSH) <=1×ULN (if abnormal, T3 and T4 levels should also be assessed; patients with normal T3 and T4 levels are eligible); (7) total bilirubin <=2.0×ULN; (8) ALT and AST both <=5.0×ULN; (9) serum creatinine <=1.5×ULN or creatinine clearance >=60 mL/min (calculated using the standard Cockcroft-Gault formula); (10) urinalysis showing urine protein <2+; for patients with urine protein 2+ at baseline, a 24-hour urine collection is required, with 24-hour urinary protein quantification <1 g; (11) coagulation function: international normalized ratio (INR) <=2 or prothrombin time (PT) within 6 seconds above the upper limit of normal. 10. For HBsAg-positive patients, HBV DNA must be <2000 IU/mL or <10^4 copies/mL, and effective antiviral therapy with entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide, or emtricitabine must be continued throughout the study period. Patients with a history of HCV infection but negative PCR results for HCV RNA may be considered non-infected. 11. Female participants of childbearing potential must confirm they are not pregnant before enrollment. All enrolled patients (male or female) must use adequate contraception throughout the treatment period and for 4 weeks after treatment completion.

排除标准：

1.已知肉瘤样HCC、混合细胞癌及纤维板层细胞癌；5年内或同时患有除HCC外的其它活动性恶性肿瘤；HCC伴有三个及以上部位转移或合并脑转移患者。 2.既往接受过同种异体干细胞或实体器官移植。 3.研究治疗开始前6个月内有消化道出血病史；有门静脉高压患者，研究者认为出血风险高的患者（包括有出血风险的中重度食管胃底静脉曲张、局部活动性消化道溃疡及持续大便隐血阳性），需要进行胃镜检查，排除有“红色征”的患者。如果胃镜检查历史有“红色征”，需排除入组。 4.研究治疗开始前6个月内出现过腹部瘘管、胃肠道穿孔或腹腔脓肿。 5.已知存在的遗传性或获得性出血（如凝血功能障碍）或血栓症状。 6.研究治疗开始前6个月内发生过血栓形成及任何级别的动静脉血栓栓塞事件。 7.患有高血压，且经降压药物治疗无法获得良好控制（收缩压 >=160mmHg 或者舒张压 >=100mmHg）；既往曾出现高血压危象或高血压性脑病。 8.在研究治疗开始前6个月内出现重大血管疾病（包括但不限于冠状动脉粥样硬化性心脏病、急性心肌梗死、主动脉夹层、脑血栓、脑出血等）。 9.严重、未愈合或裂开的伤口以及活动期溃疡。 10.在研究治疗开始前4周内接受过手术治疗。 11.既往和目前有肺纤维化史、机化性肺炎（例如，闭塞性细支气管炎）、间质性肺炎、尘肺、药物相关肺炎、特发性肺炎。 12.存在任何活动性自身免疫病或有自身免疫病病史在治疗期间有复发。 13.存在HAIC治疗、贝伐珠单抗、PD-1抑制剂、CTLA-4抑制剂或FOLFOX方案的任何禁忌。 14.在开始研究治疗之前28天内接受过减毒活疫苗治疗，或预期于PD-1免疫抑制剂治疗期间或pD-1免疫抑制剂末次给药后 60 天内需要接种此类疫苗。 15.已知有人类免疫缺陷病毒（HIV）感染病史。 16.在开始研究治疗之前 28 天内接受过其他试验用药物治疗。 17.妊娠期、哺乳期或计划在研究期间妊娠的女性受试者。 18.存在研究者认为患者不适合参加本研究的其他情况等。

Exclusion criteria：

1. Patients with sarcomatoid HCC, mixed cell carcinoma, or fibrolamellar cell carcinoma; those with other active malignant tumors other than HCC within 5 years or concurrently; and those with HCC with three or more metastatic sites or with brain metastases. 2. Those who have previously received allogeneic stem cell or solid organ transplantation. 3. Those with a history of gastrointestinal bleeding within 6 months before the start of the study treatment; those with portal hypertension and patients with a high risk of bleeding as determined by the investigator (including those with moderate to severe esophageal and gastric varices with a risk of bleeding, active local gastrointestinal ulcers, and persistent positive fecal occult blood), who need to undergo gastroscopy to rule out patients with "red signs". If there is a history of "red signs" in gastroscopy, they should be excluded from the study. 4. Those who have experienced abdominal fistula, gastrointestinal perforation, or abdominal abscess within 6 months before the start of the study treatment. 5. Those with known hereditary or acquired bleeding disorders (such as coagulation disorders) or thrombotic symptoms. 6. Those who have experienced thrombosis or any grade of arterial or venous thromboembolic events within 6 months before the start of the study treatment. 7. Those with hypertension that cannot be well controlled with antihypertensive drugs (systolic blood pressure>= 160 mmHg or diastolic blood pressure >= 100 mmHg); those with a history of hypertensive crisis or hypertensive encephalopathy. 8. Those with major vascular diseases within 6 months before the start of the study treatment (including but not limited to coronary atherosclerotic heart disease, acute myocardial infarction, aortic dissection, cerebral thrombosis, cerebral hemorrhage, etc.). 9. Those with severe, unhealed or open wounds and active ulcers. 10. Those who have undergone surgery within 4 weeks before the start of the study treatment. 11. Those with a history of or current pulmonary fibrosis, organizing pneumonia (such as obliterative bronchiolitis), interstitial pneumonia, pneumoconiosis, drug-related pneumonia, or idiopathic pneumonia. 12. Those with any active autoimmune disease or a history of autoimmune disease with recurrence during the treatment period. 13. Those with any contraindications to HAIC treatment, bevacizumab, PD-1 inhibitors, CTLA-4 inhibitors, or FOLFOX regimens. 14. Those who have received live attenuated vaccines within 28 days before the start of the study treatment, or those who are expected to receive such vaccines during the treatment period with PD-1 immune inhibitors or within 60 days after the last dose of PD-1 immune inhibitors. 15. Those with a known history of human immunodeficiency virus (HIV) infection. 16. Those who have received other investigational drugs within 28 days before the start of the study treatment. 17. Pregnant, lactating, or women planning to become pregnant during the study period. 18. Those with other conditions that the investigator deems unsuitable for participation in this study.

研究实施时间：

Study execute time：

从 From 2025-09-17 00:00:00至 To 2028-09-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2026-05-25 00:00:00 至 To 2028-09-01 00:00:00

干预措施：

Interventions：

组别：

实验组

样本量：

 46

Group：

Experimental Group

Sample size：

干预措施：

艾帕洛利托沃瑞利单抗联合贝伐珠单抗及HAIC

干预措施代码：

Intervention：

Apalolithovolrelimab combined with bevacizumab and HAIC

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 浙江省 

市(区县)：

 杭州市 

Country：

China

Province：

Zhejiang

City：

Hangzhou

单位(医院)：

 浙江大学医学院附属邵逸夫医院 

单位级别：

 三甲 

Institution
hospital：

Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine

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 remission rate

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

中位无进展生存期

指标类型：

次要指标

Outcome：

Median progression-free survival period

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

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：

中位总生存期

指标类型：

次要指标

Outcome：

Median overall survival period

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

不良事件发生率

指标类型：

次要指标

Outcome：

Incidence rate of adverse events

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

 使用后保存  

说明

Fate of sample：

Preservation 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 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）：

临床试验公共管理平台 IPD（http://www.medresman.org.cn）

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

The way of sharing IPD: ResMan IPD (http://www.medresman.org.cn).

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：

数据采集利用病例记录表，同时上传原始数据至第三方原始数据存放平台，临床试验公共管理平台 IPD（http://www.medresman.org.cn）

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

Data collection and Management:Data collection utilizes case record forms, at the same time, upload the original data to the third-party raw data storage platform, ResMan IPD (http://www.medresman.org.cn).

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：

  2026-05-22 15:47:32