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ctDNA-Guided Immunotherapy for dMMR/MSI-H Colon Cancer

2026年9月24日 更新者：Junjie Peng、Fudan University

A Single-Arm Phase II Study of Circulating Tumor DNA-Guided Neoadjuvant Immunotherapy for dMMR/MSI-H Colon Cancer

This prospective, multicenter, single-arm phase II interventional study evaluates whether longitudinal circulating tumor DNA (ctDNA) monitoring can guide neoadjuvant immunotherapy and surgical decision-making in dMMR/MSI-H colon cancer. Participants with ctDNA clearance proceed to curative surgery, whereas those with persistent ctDNA positivity escalate to combined PD-1 and CTLA-4 inhibitor therapy.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

This prospective, multicenter, single-arm phase II study evaluates the clinical utility of longitudinal circulating tumor DNA (ctDNA) monitoring to guide neoadjuvant immunotherapy and surgical decision-making in patients with dMMR/MSI-H colon cancer.

Eligible participants will initially receive neoadjuvant PD-1 inhibitor monotherapy. Peripheral-blood ctDNA will be assessed at baseline and after 3 to 4 treatment cycles. Participants with ctDNA clearance will proceed to curative surgery. Participants with persistent ctDNA positivity will be considered to have potential resistance to PD-1 inhibitor monotherapy and will escalate to combined PD-1 and CTLA-4 inhibitor therapy. ctDNA will be reassessed every 2 cycles during combination therapy. Participants will undergo curative surgery after ctDNA clearance or after no more than 4 cycles of combination treatment, regardless of final ctDNA status.

All participants will undergo postoperative ctDNA/minimal residual disease (MRD) testing 1 month after surgery. The study will evaluate pathological response, survival outcomes, the concordance of ctDNA with pathological and imaging assessments, and treatment- and surgery-related safety.

研究类型

介入性

注册 (估计的)

23

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。

学习联系方式

研究联系人备份

学习地点

  • 中国
      • Shanghai、中国、200000
        • 招聘中
        • Fudan University Shanghai Cancer Center
        • 接触：

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 75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 informed consent obtained before any study-related procedures.
  • Age 18 to 75 years, inclusive.
  • Histologically confirmed colon adenocarcinoma, mucinous adenocarcinoma, or signet-ring cell carcinoma, with the tumor located at least 15 cm from the anal verge.
  • dMMR/MSI-H status confirmed by immunohistochemistry, polymerase chain reaction, or next-generation sequencing.
  • Eastern Cooperative Oncology Group performance status of 0 or 1 and an expected survival of at least 3 months.
  • Adequate hematologic, hepatic, renal, coagulation, thyroid, and cardiac function, as defined in the protocol.
  • Negative pregnancy test for women of childbearing potential; agreement to use highly effective contraception, when applicable.

Exclusion Criteria:

  • Prior treatment with a PD-1 inhibitor, CTLA-4 inhibitor, or other immunotherapy.
  • Symptomatic or high-risk bowel obstruction, bleeding, perforation, pneumonitis, or other conditions that may compromise safe study participation.
  • Another malignancy diagnosed within 5 years before the first study treatment, except for specified definitively treated low-risk malignancies.
  • Current participation in another interventional clinical study, or receipt of another investigational drug or investigational device within 4 weeks before the first study treatment.
  • Active autoimmune disease requiring systemic treatment within 2 years before the first study treatment, or recent systemic corticosteroid or other immunosuppressive therapy.
  • Uncontrolled pleural effusion or ascites, prior allogeneic organ transplantation (except corneal transplantation), or allogeneic hematopoietic stem cell transplantation.
  • Known hypersensitivity to any study drug component.
  • Toxicities or complications from prior treatment not recovered to Grade 1 or baseline, except for specified conditions.
  • HIV infection, untreated active hepatitis B infection, or active hepatitis C infection.
  • Receipt of a live vaccine within 30 days before the first study treatment.
  • Pregnancy or breastfeeding.
  • Any serious or uncontrolled systemic disease, active infection, clinically significant laboratory abnormality, or other condition that may interfere with study participation or place the participant at unacceptable risk, as judged by the investigator.

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：ctDNA-Guided Neoadjuvant Immunotherapy |

Participants receive PD-1 inhibitor monotherapy. ctDNA testing after 3-4 cycles determines whether they proceed to curative surgery or escalate to PD-1 plus CTLA-4 inhibitor therapy; all participants subsequently undergo curative surgery.
药品：PD-1 inhibitor

200 mg intravenously on Day 1 of each 3-week cycle. All participants receive initial monotherapy.

药品：CTLA-4 inhibitor

1 mg/kg intravenously on Day 1 of each 3-week cycle. Administered with the PD-1 inhibitor only to participants with persistent ctDNA positivity after 3-4 cycles of monotherapy.

诊断测试：ctDNA/MRD testing

Peripheral-blood ctDNA testing at baseline and after 3-4 cycles of monotherapy; every 2 cycles during combination therapy, when applicable; and 1 month after surgery.

程序：Curative Surgery

Curative surgery after ctDNA clearance or after no more than 4 cycles of combination treatment.

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
Pathological Complete Response Rate
大体时间：At curative surgery, following completion of neoadjuvant therapy

Pathological assessment of the surgical resection specimen; pCR is defined as no residual viable cancer cells after treatment (ypT0N0M0).
At curative surgery, following completion of neoadjuvant therapy

次要结果测量

结果测量
措施说明
大体时间
Major Pathological Response Rate
大体时间：At curative surgery, following completion of neoadjuvant therapy

Pathological assessment of the surgical resection specimen; MPR is defined as residual viable tumor cells ≤10%.
At curative surgery, following completion of neoadjuvant therapy
3-Year Event-Free Survival
大体时间：From enrollment up to 3 years

Time from enrollment to first radiographic disease progression or death, whichever occurs first.
From enrollment up to 3 years
3-Year Overall Survival
大体时间：From enrollment up to 3 years

Time from enrollment to death from any cause.
From enrollment up to 3 years
Concordance of ctDNA Status With Pathological Complete Response
大体时间：After 3-4 cycles of PD-1 inhibitor monotherapy (21-day cycles) and at curative surgery; for persistent ctDNA positivity, every 2 cycles of PD-1 plus CTLA-4 inhibitor therapy (21-day cycles; up to 4 cycles).

Preoperative ctDNA status will be compared with postoperative pathological complete response results.
After 3-4 cycles of PD-1 inhibitor monotherapy (21-day cycles) and at curative surgery; for persistent ctDNA positivity, every 2 cycles of PD-1 plus CTLA-4 inhibitor therapy (21-day cycles; up to 4 cycles).
Concordance Between ctDNA Dynamics and Imaging Assessment
大体时间：Baseline through curative surgery, up to 24 weeks (each cycle is 21 days).

ctDNA positivity, clearance, and dynamic changes will be compared with RECIST version 1.1 imaging response assessments.
Baseline through curative surgery, up to 24 weeks (each cycle is 21 days).
Number of Participants With Treatment-Emergent Adverse Events, as Assessed by CTCAE v5.0
大体时间：From first dose through 30 days after the last dose.

Number and proportion of participants with at least one treatment-emergent adverse event, including treatment-related and immune-related adverse events.
From first dose through 30 days after the last dose.
Number of Participants With Grade 3 or Higher Treatment-Related Adverse Events, as Assessed by CTCAE v5.0
大体时间：From first dose through 30 days after the last dose.

Number and proportion of participants with at least one Grade 3 or higher treatment-related adverse event.
From first dose through 30 days after the last dose.
Number of Participants With Serious Adverse Events
大体时间：From first dose through 90 days after the last dose.

Number and proportion of participants with at least one serious adverse event.
From first dose through 90 days after the last dose.
Number of Participants With Treatment-Related Delay of Curative Surgery
大体时间：From first dose through curative surgery up to 24 weeks

Number and proportion of participants whose curative surgery is delayed because of treatment-related toxicity, as determined by the investigator.
From first dose through curative surgery up to 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。

赞助

Fudan University

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

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 (估计的)

2026年9月14日

初级完成 (估计的)

2027年12月31日

研究完成 (估计的)

2030年12月31日

研究注册日期

首次提交

2026年9月12日

首先提交符合 QC 标准的

2026年9月24日

首次发布 (实际的)

2026年9月25日

研究记录更新

最后更新发布 (实际的)

2026年9月25日

上次提交的符合 QC 标准的更新

2026年9月24日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • Neo-ctDNA-Colon

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

IPD 计划说明

Individual participant data, including de-identified data, will not be made available to external researchers. Study data will be processed and stored within China. Aggregate results may be published without identifiable participant information.

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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