A Single-Arm Phase II Study of Circulating Tumor DNA-Guided Neoadjuvant Immunotherapy for dMMR/MSI-H Colon Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Pathological Complete Response Rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: PD-1 inhibitor (Drug)
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.
干预措施: CTLA-4 inhibitor (Drug)
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.
干预措施: ctDNA/MRD testing (Diagnostic Test)
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.
干预措施: Curative Surgery (Procedure)
结局指标
主要结局
Pathological Complete Response Rate
时间窗: 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).
次要结局
- Major Pathological Response Rate(At curative surgery, following completion of neoadjuvant therapy)
- 3-Year Event-Free Survival(From enrollment up to 3 years)
- 3-Year Overall Survival(From enrollment up to 3 years)
- Concordance of ctDNA Status With Pathological Complete Response(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(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(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(From first dose through 30 days after the last dose.)
- Number of Participants With Serious Adverse Events(From first dose through 90 days after the last dose.)
- Number of Participants With Treatment-Related Delay of Curative Surgery(From first dose through curative surgery up to 24 weeks)