NEOadjuvant PembRolizumab In Stratified Medicine - ColoRectal Cancer — NEOPRISM-CRC  

Adenocarcinoma of the Colon Clinical Trial

Official title: NEOPRISM-CRC : Neoadjuvant Pembrolizumab Stratified to Tumour Mutation Burden for High Risk Stage 2 or Stage 3 MMR-deficient Colorectal Cancer

Status Recruiting

Clinical Trial Summary

Colorectal cancer (CRC) is the 2nd to 3rd most common malignant disease in developed countries, with over 1 million new cases and 500,000 deaths worldwide each year. The primary treatment for early stage CRC is surgery to remove the tumour, which is possible in 80% of patients. Even after surgery up to half of patients will develop recurrence or spread of the disease (metastases) which is incurable. Survival after 5 years is approximately 14% for patients with metastatic disease. Clinical trials using immunotherapy drugs called 'immune checkpoint inhibitors' have shown excellent results in advanced colorectal cancer patients who have certain genetic characteristics called 'mismatch repair deficiency (MMR-d)' and 'high microsatellite instability (MSI-h)'. The benefits of immunotherapy as a treatment prior to surgery to remove the tumour (neoadjuvant treatment) has been observed in both melanoma and in glioblastoma with enhanced local and systemic anti-tumour responses.

Pembrolizumab is an immunotherapy drug and works by helping the body's own immune system to fight the cancer cells. The NEOPRISM-CRC trial will investigate whether giving pembrolizumab before surgery is safe, and whether it improves the chances of the tumour being removed completely, and whether this delays or prevents the cancer from coming back.

Pembrolizumab treatment lasts for a maximum of 9 weeks (maximum of 3 cycles of treatment, each cycle consisting of 3 weeks) and is given prior to surgery. Following surgery patients will be followed up for at least 3 years after their surgery and to a maximum of 5 years. Target recruitment is 32 patients and recruitment is expected to take place over a 24 month period.

Blood, tissue, mouth swabs and stool samples will be collected from patients throughout the trial to better understand the biology of immunotherapy as a treatment for CRC prior to surgery.

Clinical Trial Description

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 improves pathological complete response rate in advanced colorectal cancer patients with MSI-H or MMR-d. The trial will investigate whether the treatment is safe, and whether it improves the chances of the tumour being removed completely, and whether this delays or prevents the cancer from coming back. 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 consented to the NEOPRISM-CRC trial, a trial colonoscopy will be performed and tissue samples taken during the procedure will be shipped to the FoundationOne Medicine testing Laboratory and analysed to determine the TMB (tumour mutation burden) status assessed by the FOUNDATIONONE®CDx (FM1) test. In addition, a PCR (Polymerase Chain reaction) test or Microsatellite testing will be done 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 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 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 is 32 patients and recruitment is expected to take place over a 24 month period. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Colon
• Colorectal Neoplasms

• NCT number: NCT05197322
• Study type: Interventional
• Source: University College, London
• Contact: Reshma Bhat
• Phone: 02076799336
• Email: ctc.neoprism@ucl.ac.uk
• Status: Recruiting
• Phase: Phase 2
• Start date: July 20, 2022
• Completion date: September 2027