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一项评估新辅助免疫治疗组合在可手术切除的肝细胞癌患者中的疗效和安全性的研究

2026年8月19日 更新者：Hoffmann-La Roche

一项 Ib/II 期、开放标签、多中心、随机平台研究，评估新辅助免疫治疗组合在可手术切除的肝细胞癌 (MORPHEUS-NEO HCC) 患者中的疗效和安全性

这是一项 Ib/II 期、开放标签、多中心、随机平台研究，旨在评估可切除 HCC 参与者的新辅助免疫治疗组合。 该研究的设计具有灵活性，可以在新药物可用时开放新的治疗组，关闭表现出最小临床活性或不可接受毒性的现有治疗组，或修改参与者人群。

研究概览

地位

终止

条件

干预/治疗

研究类型

介入性

注册 (实际的)

62

阶段

  • 阶段2
  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 奥地利
      • Klagenfurt、奥地利、9020
        • Klinikum Klagenfurt Am Worthersee
      • Vienna、奥地利、1090
        • Department of Internal Medicine III AKH and Medical University of Vienna
  • 德国
      • Essen、德国、45147
        • University Essen
      • Frankfurt、德国、60596
        • Universitaets Klinikum Frankfurt - Zentrum der Inneren Medizin
  • 法国
      • Dijon、法国、21079
        • Centre Georges Francois Leclerc (CGFL)
      • Villejuif、法国、94800
        • Gustave Roussy
  • 美国
    • California
      • Los Angeles、California、美国、90033
        • University of Southern California (USC)
      • Santa Monica、California、美国、90404-2023
        • University of California Los Angeles (UCLA) - Cancer Care - Santa Monica
    • District of Columbia
      • Washington D.C.、District of Columbia、美国、20007
        • Georgetown University Medical Center
    • New York
      • New York、New York、美国、10032
        • Columbia University Medical Center
    • Texas
      • Dallas、Texas、美国、75390-8813
        • UT Southwestern Medical Center
  • 英国
      • London、英国
        • Imperial College London - Imperial Centre for Translational and Experimental Medicine (ICTEM)
  • 西班牙
      • Madrid、西班牙、28040
        • Hospital Universitario Fundacion Jimenez Diaz.
    • Cantabria
      • Santander、Cantabria、西班牙、39008
        • Hospital Universitario Marqués de Valdecilla

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

纳入标准：

  • 根据肝硬化患者的 AASLD 标准，经组织学或临床证实 HCC 的诊断。 对于没有肝硬化的参与者，必须进行组织学确认。
  • 参与治疗的外科医生和肿瘤学家或肝病学家认为适合进行 R0 手术切除并具有治愈目的的 HCC。 符合或超出米兰标准（无肝外扩散或大血管浸润）的可切除 HCC 患者符合条件。
  • 由研究者根据 RECIST v1.1 确定的可测量疾病（至少一个目标病变）
  • 随机分组前 7 天内东部肿瘤合作组 (ECOG) 体能状态为 0 或 1
  • 随机化前 7 天内的 Child-Pugh A 级
  • 筛查时 HIV 检测呈阴性
  • 既往无 HCC 局部或全身治疗
  • 足够的血液学和终末器官功能
  • 记录的肝炎病毒学状况
  • 对于有生育能力的女性：同意保持禁欲（避免异性性交）或采取避孕措施
  • 对于男性：同意保持禁欲（避免异性性交）或使用避孕措施，并同意不捐献精子

一般排除标准：

  • 存在肝外疾病或大血管侵犯
  • 已知的纤维板层 HCC、肉瘤样 HCC、混合性胆管癌和 HCC，或其他罕见的 HCC 变体
  • 研究治疗开始前一年内有肝性脑病病史（如果有临床意义）
  • 中度或重度腹水
  • 活动性 HBV 和 HCV 合并感染
  • 活动性合并感染 HBV 和 D 型肝炎病毒感染
  • 既往接受过 CD137 激动剂或免疫检查点抑制剂治疗，包括抗 CTLA-4、抗 PD-1 和抗 PD-L1 治疗性抗体
  • 研究治疗开始前 28 天内接受研究性治疗
  • 未经治疗或未完全治疗的食管和/或胃静脉曲张出血或出血风险高
  • 研究治疗开始前 6 个月内因食管和/或胃静脉曲张引起的既往出血事件
  • 高血压控制不当
  • 高血压危象或高血压脑病史
  • 研究治疗开始前 6 个月内发生重大血管疾病
  • 研究治疗开始前 1 个月内有咯血史
  • 出血素质或严重凝血障碍的证据
  • 当前或最近（<= 研究治疗开始前 10 天）为治疗目的使用全剂量口服或肠胃外抗凝剂或溶栓剂
  • 开始研究治疗前 6 个月内有腹部或气管食管瘘、胃肠道穿孔或腹内脓肿病史
  • 肠梗阻史和/或胃肠道梗阻的临床体征或症状
  • 严重、未愈合或裂开的伤口、活动性溃疡或未经治疗的骨折
  • 等级 >= 蛋白尿
  • 重大外科手术、开放式活组织检查或重大外伤、腹部手术、干预或外伤，或预期需要除潜在治愈性肝切除术以外的重大外科手术
  • 使用非甾体类抗炎药 (NSAID) 进行长期日常治疗
  • 需要口服或静脉注射抗生素和/或住院治疗的严重感染

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Atezo + Bev
Atezolizumab 加贝伐单抗（Atezo + Bev）组的参与者将接受最多三个周期的治疗，直到手术或不可接受的毒性，以先发生者为准。
药品：阿替珠单抗
Atezolizumab 将在第 1 天通过静脉输注以 1200 mg 的剂量给药。
其他名称：
  • 技术中心
药品：贝伐单抗
贝伐珠单抗将在第 1 天通过静脉输注以 15 mg/kg 的剂量给药。
其他名称：
  • 阿瓦斯汀
实验性的：Atezo + Bev + Tira
Atezolizumab 加贝伐珠单抗加 tiragolumab（Atezo + Bev + Tira）组的参与者将接受最多三个周期的治疗，直到手术或出现不可接受的毒性，以先发生者为准。
药品：阿替珠单抗
Atezolizumab 将在第 1 天通过静脉输注以 1200 mg 的剂量给药。
其他名称：
  • 技术中心
药品：贝伐单抗
贝伐珠单抗将在第 1 天通过静脉输注以 15 mg/kg 的剂量给药。
其他名称：
  • 阿瓦斯汀
药品：替拉戈单抗
Tiragolumab 将在第 1 天通过静脉输注以 600 mg 的剂量给药。
实验性的：Tobe + bev

Tobemstomig + Bev ARM的参与者将在手术或不可接受的毒性之前获得多达三个周期的治疗。

入学率关闭。
药品：贝伐单抗
贝伐珠单抗将在第 1 天通过静脉输注以 15 mg/kg 的剂量给药。
其他名称：
  • 阿瓦斯汀
药品：托贝斯特米格
Tobemstomig 将在第 1 天通过静脉输注以 600 mg 的剂量给药
其他名称：
  • RO7247669

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Major Pathologic Response (MPR) Rate
大体时间：At the time of surgery (up to 15 weeks)
MPR rate was defined as the percentage of participants who had achieved MPR and was estimated for each treatment cohort in the efficacy-evaluable population. MPR was defined as ≤ 10% residual viable tumor in the tumor bed at the time of surgical resection in the primary tumor, as assessed by the central pathology laboratory. Participants who did not proceed to surgery were considered as non-responders for MPR. Percentages have been rounded off.
At the time of surgery (up to 15 weeks)

次要结果测量

结果测量
措施说明
大体时间
Pathologic Complete Response (pCR) Rate
大体时间：At the time of surgery (up to 15 weeks)
pCR rate was defined as the percentage of participants who had achieved pCR. pCR was defined as the absence of any viable tumor cells in both the primary tumor and all sampled lymph nodes at the time of surgical resection, as assessed by central pathological review. Percentages have been rounded off.
At the time of surgery (up to 15 weeks)
Relapse-free Survival (RFS), as Assessed by the Investigator According to European Association for the Study of the Liver (EASL) and/or Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
大体时间：From surgery to the first documented recurrence of disease (up to 20.5 months)
RFS was defined as the time from surgery to the first documented recurrence of disease (intrahepatic or extrahepatic), as assessed by the investigator according to EASL and/or RECIST v1.1, or death from any cause. Intrahepatic recurrence was defined by the appearance of one or more intrahepatic lesions with a longest diameter of > 1 cm and a typical vascular pattern of HCC on dynamic imaging (i.e., hypervascularization in the arterial phase with washout in the portal venous or late venous phase). Extrahepatic recurrence was assessed by RECIST v1.1 as the appearance of new, measurable malignant lesions outside the liver. Data for participants who did not have documented recurrence of disease or death were censored at the day of the last tumor assessment for participants. Kaplan-Meier (K-M) method was used to estimate median RFS.
From surgery to the first documented recurrence of disease (up to 20.5 months)
Event-free Survival (EFS), as Assessed by the Investigator According to EASL and RECIST v1.1
大体时间：From randomization to PD that precluded surgery or disease recurrence or death from any cause, whichever occurred first (up to 20.5 months)
EFS was defined as the time from randomization to any of the following events, whichever occurred first: PD that precluded surgery, as assessed by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline); local, regional, or distant disease recurrence as measured by EASL and/or RECIST v1.1; or death from any cause. Data for participants who had not experienced EFS events were censored at the time of their last post-surgical tumor assessment. K-M method was used to estimate median RFS.
From randomization to PD that precluded surgery or disease recurrence or death from any cause, whichever occurred first (up to 20.5 months)
Overall Survival (OS)
大体时间：From randomization to death from any cause (up to 20.5 months)
OS was defined as the time from randomization to death from any cause. Data for participants who had not died were censored at the last date they were known to be alive. K-M method was used to estimate median OS.
From randomization to death from any cause (up to 20.5 months)
OS Rate at 6 Months, 12 Months, and 18 Months
大体时间：At Months 6, 12, and 18
OS rate at 6, 12, and 18 months was defined as the percentage of participants who had not experienced death from any cause at 6 months, 12 months, and 18 months after randomization, respectively. OS was defined as the time from randomization to death from any cause. K-M method was used to estimate OS rate. Percentages have been rounded off. Due to the low number of events the results need to be interpreted with caution.
At Months 6, 12, and 18
Objective Response Rate (ORR), as Assessed by the Investigator According to RECIST v1.1
大体时间：Prior to surgery (at approximately Week 11)
ORR was defined as the percentage of participants with a radiographic objective response (OR), characterized by a complete response (CR) or a partial response (PR) prior to surgery, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions. Additionally, any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.
Prior to surgery (at approximately Week 11)
ORR, as Assessed by the Investigator According to Hepatocellular Carcinoma-Specific Modified Response Evaluation Criteria in Solid Tumors (HCC mRECIST)
大体时间：Prior to surgery (at approximately Week 11)
ORR was defined as the percentage of participants with a radiographic OR, characterized by a CR or a PR prior to surgery, as determined by the investigator according to HCC mRECIST. CR was defined as the disappearance of any intratumoral arterial enhancement in all target and non-target lesions. PR was defined as an increase of at least 30% in the sum of the longest diameters of viable (contrast enhancement in the arterial phase) target lesions, taking as reference the baseline SOD of target lesions. Percentages have been rounded off.
Prior to surgery (at approximately Week 11)
Percentage of Participants Downstaged to Within Milan Criteria (for Participants Beyond Criteria at Randomization)
大体时间：At the time of surgery (up to 15 weeks)
Percentage of participants downstaged to within Milan Criteria was defined as the number of participants who were beyond Milan criteria at enrollment and staged as within Milan criteria (single tumor ≤ 5 or 2 to 3 nodules all ≤ 3 centimeters [cm]) during the study. Milan criteria=single tumor > 5 cm or 2 to 3 nodules > 3 cm, or ≥ 4 nodules. Percentages have been rounded off.
At the time of surgery (up to 15 weeks)
Negative Surgical Margins (R0) Resection Rate
大体时间：At the time of surgery (up to 15 weeks)
R0 resection rate was defined as the percentage of resected participants who achieved complete resection (R0 resection), confirmed by pathology. R0 resection was defined as a microscopically margin-negative resection, in which no tumor (gross or microscopic) remains in the primary tumor bed. Percentages have been rounded off.
At the time of surgery (up to 15 weeks)
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Immune-related AEs
大体时间：From initiation of study treatment up to 135 days (Serious AEs and AESI) or 30 days (all other AEs) after the final dose of study treatment or until initiation of new systemic anti-cancer therapy (up to 7.7 moths)
An AE was defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any AE that meets any of the following criteria: Is fatal; Is life threatening; Requires or prolongs inpatient hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study treatment; Is a significant medical event in the investigator's judgment. Participants with immune-mediated Hepatitis (Diagnosis and Lab Abnormalities) have been reported as immune-related AEs.
From initiation of study treatment up to 135 days (Serious AEs and AESI) or 30 days (all other AEs) after the final dose of study treatment or until initiation of new systemic anti-cancer therapy (up to 7.7 moths)
Percentage of Participants With Delayed or Cancelled Surgery Due to Treatment-related Adverse Events (TRAEs)
大体时间：Assessed at pre-surgery (scheduled at Week 11)
Delayed Surgery was defined as delay in surgery by > 28 days from the surgical restaging or pre-surgery visit. Percentages have been rounded off.
Assessed at pre-surgery (scheduled at Week 11)
Length of Surgical Delays
大体时间：Assessed at pre-surgery (scheduled at Week 11) up to 20 weeks
Delayed Surgery was defined as a delay in surgery by > 28 days from the surgical restaging or pre-surgery visit.
Assessed at pre-surgery (scheduled at Week 11) up to 20 weeks
Duration of Surgery
大体时间：At the time of surgery (up to 15 weeks)
At the time of surgery (up to 15 weeks)
Duration of Hospital Stay Post-surgery
大体时间：From time of surgery (15 weeks) up to 6 weeks (± 2 weeks) post-surgery (up to 23 weeks)
From time of surgery (15 weeks) up to 6 weeks (± 2 weeks) post-surgery (up to 23 weeks)
Number of Participants With Specific Surgical Approach
大体时间：At the time of surgery (up to 15 weeks)
The surgical approach was categorized as: Hemihepatectomy; Sectionectomy; Segmentectomy; Other.
At the time of surgery (up to 15 weeks)
Intraoperative Blood Loss
大体时间：At the time of surgery (up to 15 weeks)
At the time of surgery (up to 15 weeks)
Number of Participants Needing Intraoperative Blood Transfusion
大体时间：At the time of surgery (up to 15 weeks)
At the time of surgery (up to 15 weeks)
Post-operative Surgical Complication Rates Assessed According to the Clavien-dindo Surgical Classification
大体时间：From time of surgery (15 weeks) up to neo-adjuvant treatment completion/discontinuation (6 weeks [± 2 weeks]) (up to 23 weeks)
Clavien-dindo Surgical Classification graded surgical complications as: Grade I- Any complication that does not need pharmacological treatment or surgical, endoscopic, & radiological interventions; Grade II- Complications requiring pharmacological treatment with drugs other than such allowed for Grade I complications or complications requiring blood transfusions & total parenteral nutrition; Grade III- Complications requiring surgical, endoscopic, or radiological intervention with (Grade IIIb) or without (Grade IIIa) general anesthesia; Grade IV- Life-threatening complications requiring intensive care unit (ICU) management, which may be single organ (Grade IVa) or multiorgan (Grade IVb) dysfunction; Grade V- Complications causing death. The percentage of participants with any post-surgical complications specifically related to the HCC resection was reported. Percentages have been rounded off.
From time of surgery (15 weeks) up to neo-adjuvant treatment completion/discontinuation (6 weeks [± 2 weeks]) (up to 23 weeks)
Number of Participants With Post-operative Mortality
大体时间：From surgery (15 weeks) up to 90 days post-surgery (up to 27.8 weeks)
From surgery (15 weeks) up to 90 days post-surgery (up to 27.8 weeks)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Hoffmann-La Roche

调查人员

  • 研究主任：Clinical Trials、Hoffmann-La Roche

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2023年12月5日

初级完成 (实际的)

2025年8月27日

研究完成 (实际的)

2025年11月13日

研究注册日期

首次提交

2023年6月7日

首先提交符合 QC 标准的

2023年6月15日

首次发布 (实际的)

2023年6月18日

研究记录更新

最后更新发布 (实际的)

2026年9月15日

上次提交的符合 QC 标准的更新

2026年8月19日

最后验证

2026年8月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • GO44457

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

合格的研究人员可以通过临床研究数据请求平台 (www.vivli.org) 请求访问个体患者水平的数据。 有关罗氏合格研究标准的更多详细信息，请参见此处 ( https://vivli.org/ourmember/roche/)。 有关罗氏临床信息共享全球政策的更多详细信息以及如何请求访问相关临床研究文件，请参见此处 (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm)。

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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