NEOadjuvant PembRolizumab In Stratified Medicine - ColoRectal Cancer

The NEOPRISM-CRC study is a phase II clinical trial. The purpose of the trial is to evaluate the efficacy and safety of pembrolizumab (Study IMP) in patients with high risk Stage 2 or Stage 3 MMR-deficient colorectal cancer stratified with tumour mutation burden status. Pembrolizumab is a type of immunotherapy that has demonstrated excellent results in clinical trials for patients with advanced colorectal cancer who have certain genetic characteristics (mismatch repair deficiency (MMR-d) / high microsatellite instability (MSI-H)). There are previous studies providing evidence that checkpoint inhibitors when given before surgery have shown better local and systemic anti-tumour responses in melanoma and glioblastoma than surgery alone. The main question the researcher wants to investigate is whether pembrolizumab given prior to having surgery delays or prevents the cancer from coming back in advanced colorectal cancer patients with MSI-H or MMR-d. The trial will investigate whether the treatment is safe, whether it improves pathological complete response rate and whether it improves the chances of the tumour being removed completely. The trial will also investigate whether pembrolizumab causes any delay to surgery due to side effects. The trial will also measure post-surgery complications and impact of the treatment on patient's quality of life. Once patients have enrolled into the NEOPRISM-CRC trial, if patient has consented to a trial colonoscopy, tissue samples will be taken during the procedure and shipped to the FoundationOne Medicine testing Laboratory and analysed to determine the TMB (tumour mutation burden) status assessed by the FOUNDATIONONE®CDx (FM1 Solid CDx) test. If patient does not consent to Trial Colonoscopy, blood sample will be taken to test the TMB status assessed by the FOUNDATIONONE® Liquid CDx (FM1 Liquid CDx) test . In addition if a patient has consented to Trial Colonoscopy, a PCR (Polymerase Chain reaction) test or Microsatellite testing will be done on tissue sample to confirm the Microsatellite Instability (MSI) status. Patients will receive one of two pre-operative regimens depending upon their TMB status/MSI status All patients will have one cycle of pembrolizumab 200 mg IV (a cycle is 21 days). Prior to cycle 2 the FM1 result should be available and patients will continue their treatment as follows: * If results is TMB-high or medium (or MSI-h if FM1 Solid CDx/ Liquid CDx test is not evaluable): A further two cycles of pembrolizumab 200 mg IV every 21 days and then will proceed to surgery 4 - 6 weeks after last dose of pembrolizumab * If result is TMB-low (or if FM1 Solid CDx/ Liquid CDx test and MSI result are not evaluable): No further cycles of pembrolizumab; will proceed to surgery 4 - 6 weeks after last dose of pembrolizumab Following surgery, patients will receive standard of care adjuvant treatment which may include post-operative chemotherapy in accordance with investigators clinical decision. Patients will continue to be followed up according to routine standard of care for a maximum of 5 years after surgery. Target recruitment was 88 patients and recruitment took place over a 48 month period. As of September 2026, the trial has closed to recruitment after achieving its recruitment target. Final patient was enrolled on 02/09/2026.