A Phase 2 interventional study of PD-1 inhibitor and CTLA-4 inhibitor in Colon Cancer, Deficient Mismatch Repair and Microsatellite Instability-High (MSI-H), sponsored by Fudan University. Recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-09-25.
Sponsored by Fudan University · Phase 2, Interventional, and Treatment
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.
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.
Exclusion Criteria:
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.
Drug: PD-1 inhibitor · Drug: CTLA-4 inhibitor · Diagnostic Test: ctDNA/MRD testing · Procedure: Curative Surgery
200 mg intravenously on Day 1 of each 3-week cycle. All participants receive initial monotherapy.
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.
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.
Curative surgery after ctDNA clearance or after no more than 4 cycles of combination treatment.
Pathological Complete Response Rate
Pathological assessment of the surgical resection specimen; pCR is defined as no residual viable cancer cells after treatment (ypT0N0M0).
Time frame: At curative surgery, following completion of neoadjuvant therapy
Major Pathological Response Rate
Pathological assessment of the surgical resection specimen; MPR is defined as residual viable tumor cells ≤10%.
Time frame: At curative surgery, following completion of neoadjuvant therapy
3-Year Event-Free Survival
Time from enrollment to first radiographic disease progression or death, whichever occurs first.
Time frame: From enrollment up to 3 years
3-Year Overall Survival
Time from enrollment to death from any cause.
Time frame: From enrollment up to 3 years
Concordance of ctDNA Status With Pathological Complete Response
Preoperative ctDNA status will be compared with postoperative pathological complete response results.
Time frame: 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
ctDNA positivity, clearance, and dynamic changes will be compared with RECIST version 1.1 imaging response assessments.
Time frame: 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
Number and proportion of participants with at least one treatment-emergent adverse event, including treatment-related and immune-related adverse events.
Time frame: 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
Number and proportion of participants with at least one Grade 3 or higher treatment-related adverse event.
Time frame: From first dose through 30 days after the last dose.
Number of Participants With Serious Adverse Events
Number and proportion of participants with at least one serious adverse event.
Time frame: From first dose through 90 days after the last dose.
Number of Participants With Treatment-Related Delay of Curative Surgery
Number and proportion of participants whose curative surgery is delayed because of treatment-related toxicity, as determined by the investigator.
Time frame: From first dose through curative surgery up to 24 weeks
Plan to share: No — 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.
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