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Perioperative Cadonilimab (AK104) in Locally Advanced MSI-H/dMMR Gastric or Gastroesophageal Junction and Colorectal Adenocarcinoma

2026年11月2日 更新者:Jiafu Ji、Peking University

A Multicenter, Open-Label, Phase II Study of Anti-PD-1/CTLA-4 Bispecific Antibody AK104 in the Perioperative Treatment of Locally Advanced Microsatellite Instability/Mismatch Repair Protein-Deficient Gastric and Colorectal Adenocarcinoma

The goal of this phase 2 clinical trial is to learn whether a medicine called cadonilimab (AK104) can safely and effectively treat certain stomach and colon cancers when it is given before and after surgery. Cadonilimab is a type of immunotherapy that targets PD-1 and CTLA-4. The study includes two groups of participants:

  • Cohort 1: people with locally advanced gastric or gastroesophageal junction adenocarcinoma
  • Cohort 2: people with locally advanced colorectal adenocarcinoma

All participants will have a tumor with a genetic change called MSI-H or dMMR and will be able to have surgery.The main question this study aims to answer is:• How many participants have no signs of cancer left in the tissue removed during surgery (pathologic complete response) after receiving cadonilimab?Other questions the study will look at include:

  • How long participants live overall and without the cancer coming back
  • How many participants have a major but not complete response in the removed tumor tissue
  • What side effects happen with cadonilimab before and after surgery

In this multicenter, single-arm trial, all participants will:

  • Receive cadonilimab by intravenous infusion every 3 weeks for 3 cycles before surgery
  • Have surgery to remove the tumor
  • May continue cadonilimab once a month for up to 6 months after surgery, or stop sooner if the cancer gets worse or side effects are not tolerable
  • Have regular clinic visits, blood tests, and scans so researchers can monitor their health and how the cancer responds to treatment

The study uses a two-stage design to decide whether cadonilimab shows enough benefit to justify further research.

研究概览

研究类型

介入性

注册 (估计的)

47

阶段

  • 阶段2

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

    • Beijing Municipality
      • Beijing、Beijing Municipality、中国、100142
        • Peking University Cancer Hospital & Institute

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

18年 至 80年 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Written and signed informed consent.
  • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.
  • The estimated life expectancy of ≥3 months.
  • Confirmed MSI-H/dMMR status by the central laboratory.
  • For cohort 1, histologically or cytologically documented locally advanced gastric carcinoma(cT3-T4a, Nx, M0). For cohort 2, histologically or cytologically documented locally advanced colorectal cancer(cT3-T4a, Nx, M0).
  • Haven't received any chemotherapy or radiotherapy.
  • Adequate organ function.
  • All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.

Exclusion Criteria:

  • Is currently participating in a study of an investigational agent or using an investigational device;
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2 years prior to the first dose of study treatment;
  • Has undergone major surgery within 30 days of Study Day 1;
  • Has a known additional malignancy that is progressing or requires systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has known active central nervous system (CNS) metastases;
  • Has carcinomatous meningitis;
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment NOTE: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study;
  • Has an active infection requiring systemic therapy;
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected);
  • History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 12 months prior to day 1 of study treatment;
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of this subject to participate, in the opinion of the treating investigator;
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study;
  • Has received a live virus vaccine within 30 days of the planned first dose of study therapy;
  • Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment;
  • Has any concurrent medical condition that, in the opinion of the Investigator, would complicate or compromise compliance with the study or the well-being of the subject.

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:不适用
  • 介入模型:单组作业
  • 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:AK104 for Gastric/GEJ and Colorectal Adenocarcinoma

Participants with locally advanced MSI-H or dMMR gastric/GEJ and colorectal adenocarcinoma will receive neoadjuvant AK104 10 mg/kg by intravenous infusion every 3 weeks for 3 cycles. Surgery will be performed 3-6 weeks after completion of neoadjuvant treatment. After surgery, participants will receive postoperative AK104 6 mg/kg by intravenous infusion once monthly for up to 6 months or until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met.

Participants will receive AK104 10 mg/kg by intravenous infusion every 3 weeks for 3 cycles before surgery. Surgery will be performed 3-6 weeks after completion of neoadjuvant treatment. After surgery, participants will receive AK104 6 mg/kg by intravenous infusion once monthly for up to 6 months or until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria are met.

For participants with gastric or gastroesophageal junction adenocarcinoma, radical gastrectomy or gastroesophageal junction resection with appropriate lymphadenectomy will be performed according to tumor location and institutional standards. For participants with colorectal adenocarcinoma, radical colorectal resection with regional lymphadenectomy, will be performed according to tumor location and institutional standards.

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
The rate of pathologic complete response
大体时间:After surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).

Proportion of patients with locally advanced dMMR/MSI-H gastric or colorectal adenocarcinoma who receive neoadjuvant AK104 monotherapy and undergo surgery, who achieve a pathologic complete response based on blinded pathologic assessment by two pathologists with an associate senior professional title or higher.

After surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).

次要结果测量

结果测量
措施说明
大体时间
Major Pathologic Response (MPR) rate
大体时间:After surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).

Proportion of participants who achieve a major pathologic response, defined as residual viable tumor (RVT) ≤10% in the resected primary tumor specimen.

After surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
R0 resection rate
大体时间:At surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).

Proportion of participants who achieve an R0 resection, defined as microscopically margin-negative resection with no residual tumor at the resection margins.

At surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
Event-free survival (EFS)
大体时间:From the first dose of study treatment to the first EFS event or censoring, up to 5 years; EFS rates assessed at 12, 24, and 36 months.
From the first dose of study treatment to the first EFS event or censoring, up to 5 years; EFS rates assessed at 12, 24, and 36 months.
Disease-Free Survival (DFS)
大体时间:From the first dose of study treatment to the first DFS event or censoring, up to 5 years; DFS rates assessed at 12, 24, and 36 months.
From the first dose of study treatment to the first DFS event or censoring, up to 5 years; DFS rates assessed at 12, 24, and 36 months.
Overall survival (OS)
大体时间:From the first dose of study treatment to the first OS event or censoring, up to 5 years; OS rates assessed at 12, 24, and 36 months.
From the first dose of study treatment to the first OS event or censoring, up to 5 years; OS rates assessed at 12, 24, and 36 months.
Postoperative Complication Within 30 Days
大体时间:From the date of surgery through 30 days after surgery.
From the date of surgery through 30 days after surgery.
Adverse Events (AEs)
大体时间:From first dose to 30 days after the last study-treatment dose or start of other anticancer therapy, whichever occurs first; immune-related AEs through 90 days after the last AK104 dose, regardless of subsequent anticancer therapy.
From first dose to 30 days after the last study-treatment dose or start of other anticancer therapy, whichever occurs first; immune-related AEs through 90 days after the last AK104 dose, regardless of subsequent anticancer therapy.
Completion Rate of Postoperative Adjuvant Therapy
大体时间:From the first postoperative adjuvant dose to completion or discontinuation of the 6 planned cycles (each cycle is 28 days; planned duration is 24 weeks).
From the first postoperative adjuvant dose to completion or discontinuation of the 6 planned cycles (each cycle is 28 days; planned duration is 24 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。

调查人员

  • 首席研究员:Jiafu Ji、Peking University Cancer Hospital & Institute

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)

2024年2月1日

初级完成 (估计的)

2026年12月1日

研究完成 (估计的)

2028年12月1日

研究注册日期

首次提交

2020年9月14日

首先提交符合 QC 标准的

2020年9月14日

首次发布 (实际的)

2020年9月21日

研究记录更新

最后更新发布 (实际的)

2026年11月5日

上次提交的符合 QC 标准的更新

2026年11月2日

最后验证

2026年6月1日

更多信息

与本研究相关的术语

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

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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