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

NCT07841236 | Recruiting Phase 2

• 1 other identifier: Neo-ctDNA-Colon
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colon Cancer; Deficient Mismatch Repair; Microsatellite Instability-High (MSI-H)

Keywords

Circulating Tumor DNA; dMMR/MSI-H Colon Cancer; Neoadjuvant Immunotherapy; Pathological Complete Response; Minimal Residual Disease

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response Rate

  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

Secondary Outcomes (9)

• 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).

Study Arms (1)

ctDNA-Guided Neoadjuvant Immunotherapy |

EXPERIMENTAL

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

Interventions

PD-1 inhibitor DRUG

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

ctDNA-Guided Neoadjuvant Immunotherapy |

CTLA-4 inhibitor DRUG

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.

ctDNA-Guided Neoadjuvant Immunotherapy |

ctDNA/MRD testing DIAGNOSTIC_TEST

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.

ctDNA-Guided Neoadjuvant Immunotherapy |

Curative Surgery PROCEDURE

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

ctDNA-Guided Neoadjuvant Immunotherapy |

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, 200000, China

RECRUITING

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MeSH Terms

Conditions

Colonic Neoplasms; Neoplasm, Residual

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Junjie Peng, MD, PhD

CONTACT

86-18017317122; pengjj@shca.org.cn

Yaqi Li, MD, PhD

CONTACT

yaqili702@shca.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: All participants initially receive PD-1 inhibitor monotherapy. ctDNA status after 3-4 cycles guides subsequent treatment: participants with ctDNA clearance undergo curative surgery, whereas those with persistent ctDNA positivity escalate to PD-1 plus CTLA-4 inhibitor therapy before surgery.

Study Record Dates

• First Submitted: September 12, 2026
• First Posted: September 25, 2026
• Study Start: September 14, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)