Actively Recruiting
NEOPRISM-CRC Neoadjuvant Pembrolizumab Stratified by Tumor Mutation Burden for High Risk Stage 2 or Stage 3 MMR-deficient Colorectal Cancer
Led by University College, London · Updated on 2026-04-17
88
Participants Needed
6
Research Sites
156 weeks
Total Duration
On this page
Sponsors
U
University College, London
Lead Sponsor
M
Merck Sharp & Dohme LLC
Collaborating Sponsor
AI-Summary
What this Trial Is About
Colorectal cancer is a common and serious disease, with surgery as the main treatment for early stages. However, many patients still experience cancer recurrence or spread after surgery. This trial focuses on patients with high-risk Stage 2 or Stage 3 colorectal cancer that has specific genetic features called mismatch repair deficiency or high microsatellite instability. Researchers are studying if giving the immunotherapy drug pembrolizumab before surgery can improve outcomes by helping the immune system fight cancer and by reducing the chance of the cancer returning. Participants will receive pembrolizumab through intravenous infusion in cycles of 21 days. All patients get one cycle initially, then depending on genetic test results from tumor or blood samples, they may receive up to two additional cycles before surgery. Surgery to remove the tumor will take place 4 to 6 weeks after the last pembrolizumab dose. After surgery, patients may have standard chemotherapy based on their doctor's decision and will be followed for up to five years. During the study, blood, tissue, mouth swabs, and stool samples will be collected to understand how immunotherapy works for colorectal cancer. Researchers will monitor safety, tumor response, quality of life, and long-term outcomes including relapse-free survival. Follow-up visits and assessments will continue for at least three years after surgery, with some outcomes tracked for up to five years.
CONDITIONS
Brief Title
NEOadjuvant PembRolizumab In Stratified Medicine - ColoRectal Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically confirmed mismatch repair-deficient or high microsatellite instability adenocarcinoma of the colon or rectum
- Fit for planned curative surgery and eligible for adjuvant chemotherapy as per investigator's assessment
- Radiological node positive T1-4 colorectal cancer, or node negative high risk T3 with specific imaging features, or node negative T4 disease
- Rectal cancer patients not requiring neoadjuvant chemo-radiotherapy for complete tumor removal
- Patients with acute colonic obstruction may participate after relief by stoma or stent and recovery
- Adequate bone marrow function with specific blood count thresholds
- Adequate renal function (GFR >50 mL/min) confirmed by creatinine clearance or urine/isotope test
- Adequate liver function within defined bilirubin and enzyme limits
- Adequate coagulation parameters within specified ranges unless on anticoagulants within therapeutic range
- Age 18 years or older
- Able and willing to provide written informed consent
- Female patients of childbearing potential must use effective contraception during treatment and 120 days after last dose
You will not qualify if you...
- Radiotherapy advised by multidisciplinary team
- Evidence of distant metastases or peritoneal nodules
- Prior treatment with any anti-PD-1, anti-PD-L1, anti-PD-L2, or similar immune checkpoint agents
- Prior systemic anti-cancer therapy, including investigational agents, within 4 weeks before registration
- Receipt of live or live-attenuated vaccine within 30 days before registration
- Investigational agents or devices within 4 weeks prior to registration
- Immunodeficiency or chronic systemic steroid or immunosuppressive therapy within 7 days before first dose
- Concurrent or previous malignancy affecting trial assessments
- Known active central nervous system metastases or carcinomatous meningitis
- Severe hypersensitivity to pembrolizumab or its components
- Previous severe skin reactions to immune-stimulatory anticancer agents
- Active autoimmune disease requiring systemic treatment in past 2 years
- History or current pneumonitis or interstitial lung disease requiring steroids
- Active infection requiring systemic therapy
- Known HIV infection
- Known active hepatitis B or hepatitis C infection
- History of active tuberculosis
- Past allogenic tissue or solid organ transplant
- Peritonitis due to tumor perforation
- Unrelieved colonic obstruction
- Any condition or abnormality that could interfere with study participation or results
- Psychiatric or substance abuse disorders interfering with cooperation
- Female patients pregnant, breastfeeding, or planning pregnancy during trial and 120 days after last dose of pembrolizumab
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 9 weeks (3 cycles of 21 days each)
Participants receive pembrolizumab immunotherapy prior to surgery. All participants receive one cycle (21 days) of pembrolizumab 200 mg IV. Depending on tumor mutation burden or microsatellite instability test results, some participants receive two additional cycles every 21 days before proceeding to surgery.
3 visits (in-person, each 21 days apart)
Duration - 4 to 6 weeks
Participants undergo planned surgery to remove colorectal cancer 4 to 6 weeks after the last pembrolizumab dose, followed by immediate post-operative care.
1 surgery visit plus immediate post-operative visits
Duration - Up to 5 years
Participants receive standard of care adjuvant treatment as decided by their doctor, including possible chemotherapy, and are followed up with routine care for up to 5 years after surgery.
Visits according to routine standard of care
Trial Site Locations
Total: 6 locations
1
Addenbrookes Hospital
Cambridge, United Kingdom, CB2 0QQ
Actively Recruiting
2
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom, G12 0YN
Actively Recruiting
3
St James University Hospital (SJUH)
Leeds, United Kingdom, LS9 7TF
Completed
4
University College Hospital
London, United Kingdom, NW1 2BU
Actively Recruiting
5
Christie Hospital NHS Trust, Wilmslow Road,
Manchester, United Kingdom, M20 4BX
Actively Recruiting
6
Southampton General Hospital
Southampton, United Kingdom, SO16 6YD
Completed
Research Team
R
Reshma Bhat
R
Rubina Begum
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here