Neoadjuvant Immunotherapy and Organ-sparing Treatment in Patients With Stage I-III dMMR Colon Cancer

NCT07409844 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: p-2025-19412
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

The RESET C2 trial aims to introduce organ sparing treatment or watch-and-wait (WW) to patients with localized deficient mismatch repair (dMMR) colon cancer through use of neoadjuvant pembrolizumab. Patients will be divided into four treatment arms based on their surgical and oncologic risks. Each arm provides different intensity neoadjuvant immunotherapy regimens. Patients with complete response at disease restaging procedures will be offered non-operative management, whereas those with non-complete response will proceed to surgery ± adjuvant chemotherapy as standard of care. A WW protocol with regular disease surveillance continues over survivorship. If there is recurrence, surgery and/or appropriate oncologic therapy will be offered determined by multi-disciplinary teams. This is a national, non-randomised, investigator-initiated trial including patients from 13 hospitals across Denmark. The rationale, design, and clinical response metrics are derived from the RESET C study (NCT05662527) showing efficacy, safety and feasibility of neoadjuvant pembrolizumab in this cohort.

Conditions

DMMR Colorectal Cancer; Colon Cancer Stage I; Colon Cancer Stage II/III; Pembrolizumab; Immunotherapy

Keywords

Pembrolizumab; dMMR; colon cancer; watch-and-wait; organ sparing; neoadjuvant immunotherapy

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with clinical complete response (cCR)

  The proportion of patients achieving a clinical complete response defined as 1) the absence of residual local tumour based on predefined endoscopic criteria and 2) absence of metastatic disease on cross-sectional CT imaging. Pathological examination may be performed to support the local tumour response assessment when endoscopic findings are equivocal. These tissue specimens will be reported as per the Mandard Tumour Regression Grading system with pathologic Complete Response (pCR) defined as Mandard Tumour Regression Grade 1.

  Periprocedural

Secondary Outcomes (21)

• Overall Survival (OS)

  Up to 3 years

• Disease-free survival (DFS)

  Up to 3 years

• Major patholological response (MPR) in patients undergoing surgery as per Mandard TRG

  Perioperative

• Adverse events related to pembrolizumab as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  1 year

• Adverse events related to surgery as per Clavien-Dindo (CD) classification

  Up to 12 weeks

Study Arms (4)

Low and medium surgical risk participants with stage I-II CRC

EXPERIMENTAL

These participants receive 1 cycle of up-front pembrolizumab before disease re-assessment. An additional cycle may given in the case of non-complete response

Drug: 1 Cycle of Pembrolizumab; Drug: Additional Cycle of Pembrolizumab

Low and medium surgical risk participants with stage III CRC

EXPERIMENTAL

These participants receive 2 cycles of up-front pembrolizumab before disease re-assessment (no additional cycles are offered if non-complete response)

Drug: 2 Cycles of Pembrolizumab

High surgical risk participants with stage I-II CRC

ACTIVE COMPARATOR

These participants receive 2 cycles of up-front pembrolizumab before disease re-assessment. An additional cycle may given in the case of non-complete response

Drug: 2 Cycles of Pembrolizumab; Drug: Additional Cycle of Pembrolizumab

High surgical risk participants with stage III CRC

ACTIVE COMPARATOR

These participants receive 3 cycles of up-front pembrolizumab before disease re-assessment. An additional cycle may given in the case of non-complete response

Drug: 3 Cycles of Pembrolizumab; Drug: Additional Cycle of Pembrolizumab

Interventions

2 Cycles of Pembrolizumab DRUG

2 Cycles of Pembrolizumab 4mg/kg (maximum of 400mg) every 6 weeks

Also known as: Keytruda

High surgical risk participants with stage I-II CRC; Low and medium surgical risk participants with stage III CRC

3 Cycles of Pembrolizumab DRUG

3 Cycles of Pembrolizumab 4mg/kg (maximum of 400mg) every 6 weeks

Also known as: Keytruda

High surgical risk participants with stage III CRC

1 Cycle of Pembrolizumab DRUG

1 cycle of 4mg/kg (maximum of 400mg) every 6 weeks

Also known as: Keytruda

Low and medium surgical risk participants with stage I-II CRC

Additional Cycle of Pembrolizumab DRUG

An additional 4mg/kg (maximum of 400mg) cycle of pembrolizumab in the case of non-complete response

High surgical risk participants with stage I-II CRC; High surgical risk participants with stage III CRC; Low and medium surgical risk participants with stage I-II CRC

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Written informed consent
• Clinical UICC stage I-III dMMR colon carcinoma
• Indication for elective curative-intent surgery
• ECOG status 0-2

You may not qualify if:

• Patients deemed to be non-surgical candidates by MDT
• Patients with a need for emergent surgery due to tumour obstruction
• Contraindications to pembrolizumab, including allergy and hypersensitivity reactions, assessed by the study investigator(s)
• Any serious or uncontrolled medical disorder, including other malignant disease, that may increase the risk associated with participation or drug administration.
• Patients with colonic stents
• Additional Circumstances:
• In the following circumstances, eligibility will be individually verified:
• Synchronous colonic tumours (may be included if other lesions are biopsy-verified with dMMR status)
• Concurrent tumours (e.g., patients with prostate cancer may be included if this does not hinder their other cancer treatment or assessments of efficacy)
• In the following circumstance patients may be excluded from the PROMs outcomes:
• Danish language skills insufficient to answer PROMs
• Unable to use eBoks

Sponsors & Collaborators

• Herlev and Gentofte Hospital: collaborator
• Gødstrup Hospital: collaborator
• Horsens Hospital: collaborator
• Hvidovre University Hospital: collaborator
• Odense University Hospital: collaborator
• Randers Regional Hospital: collaborator
• Slagelse Hospital: collaborator
• Vejle Hospital: collaborator
• Aalborg University Hospital: collaborator
• Aarhus University Hospital: collaborator
• Zealand University Hospital: collaborator
• Ismail Gögenur: lead
• Rigshospitalet, Denmark: collaborator
• Bispebjerg Hospital: collaborator
• University of Copenhagen: collaborator

Study Sites (1)

Zealand University Hospital

Køge, 4600, Denmark

Location

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

pembrolizumab

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

Central Study Contacts

Ismail Gögenur, Professor

CONTACT

+4526336426; igo@regionsjaelland.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD, DMSc, Consultant

Study Record Dates

• First Submitted: January 15, 2026
• First Posted: February 13, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): January 1, 2031
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

DK (1)