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

Condition(s) studied

Investigational drug(s) / intervention(s)

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

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

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

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

Study 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.

Eligibility

Primary outcome measure(s)

• Proportion of patients with clinical complete response (cCR) — Periprocedural
  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.

Trial sites (1)