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

24 settembre 2026 aggiornato da: 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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Stimato)

23

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

      • Shanghai, Cina, 200000
        • Reclutamento
        • Fudan University Shanghai Cancer Center
        • Contatto:

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 75 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.

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.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Pathological Complete Response Rate
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Major Pathological Response Rate
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

14 settembre 2026

Completamento primario (Stimato)

31 dicembre 2027

Completamento dello studio (Stimato)

31 dicembre 2030

Date di iscrizione allo studio

Primo inviato

12 settembre 2026

Primo inviato che soddisfa i criteri di controllo qualità

24 settembre 2026

Primo Inserito (Effettivo)

25 settembre 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

25 settembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

24 settembre 2026

Ultimo verificato

1 settembre 2026

Maggiori informazioni

Termini relativi a questo studio

Altri numeri di identificazione dello studio

  • Neo-ctDNA-Colon

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Descrizione del piano IPD

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.

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .