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

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

Interventions

DRUG

1 Cycle of Pembrolizumab

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

DRUG

2 Cycles of Pembrolizumab

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

DRUG

3 Cycles of Pembrolizumab

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

DRUG

Additional Cycle of Pembrolizumab

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

Sponsors & Collaborators

• Rigshospitalet, Denmark

  collaborator OTHER

• Bispebjerg Hospital

  collaborator OTHER

• Herlev and Gentofte Hospital

  collaborator OTHER

• Gødstrup Hospital

  collaborator OTHER

• Horsens Hospital

  collaborator OTHER

• Hvidovre University Hospital

  collaborator OTHER

• Odense University Hospital

  collaborator OTHER

• Randers Regional Hospital

  collaborator OTHER

• Slagelse Hospital

  collaborator OTHER

• Vejle Hospital

  collaborator OTHER

• Aalborg University Hospital

  collaborator OTHER

• Aarhus University Hospital

  collaborator OTHER

• Zealand University Hospital

  collaborator OTHER

• University of Copenhagen

  collaborator OTHER

• Ismail Gögenur

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-03-01

Primary Completion

2028-03-01

Completion

2031-01-01

Countries

• Denmark

Study Locations