NEOadjuvant PembRolizumab In Stratified Medicine - ColoRectal Cancer

NCT05197322 | Recruiting Phase 2

• 1 other identifier: UCL/127464
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 6

Brief 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, whether it improves the chances of the tumour being removed completely and whether it 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 88 patients and recruitment is expected to take place over a 48 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.

Conditions

Adenocarcinoma of the Colon

Outcome Measures

Primary Outcomes (1)

• Relapse-free survival

  Relapse-free Survival (RFS) is defined as time from start of treatment to time of any signs or symptoms of the cancer or time of death from any cause.

  From registration to any signs or symptoms of the cancer or death assessed up to a maximum of 3 years from surgery date

Secondary Outcomes (7)

• Pathological complete response rate (pCR)

  Pathological complete response rate (pCR) assessed at 3 months following surgery

• Overall survival

  From registration to death from any cause, assessed up to a maximum of 3 years from surgery date

• Frequency and severity of adverse events

  From informed consent to 3 months after surgery

• Rate of R0 resection and completed surgery

  Assessed from surgery to 28-35 days following surgery

• Frequency and severity of post-operative surgical complications

  Assessed from surgery up to last follow up visit (maximum of 5 years from date of surgery)

Study Arms (2)

Tumour Mutation Burden high or medium (or MSI-High)

OTHER

Patients will one cycle of pembrolizumab 200 mg IV (a cycle is 21 days). Prior to cycle 2 the result of the FOUNDATIONONE®CDx test or FOUNDATIONONE® Liquid CDx should be available and patients will continue their treatment as follows: TMB-high (defined as ≥20 mutations per Mb) or medium (defined as 6-19 mutations per Mb); FOUNDATIONONE®CDx or FOUNDATIONONE® Liquid CDx test (or MSI-H if FOUNDATIONONE®CDx or FOUNDATIONONE® Liquid CDx test is not evaluable): * A further two cycles of pembrolizumab 200 mg IV every 21 days * Planned surgery to remove the CRC 4 - 6 weeks after last dose of pembrolizumab

Drug: Pembrolizumab

Tumour Mutation Burden low or unevaluable

OTHER

Patients will one cycle of pembrolizumab 200 mg IV (a cycle is 21 days). Prior to cycle 2 the result of the FOUNDATIONONE®CDx or FOUNDATIONONE® Liquid CDx test should be available and patients will continue their treatment as follows: TMB-low (defined as ≤5 mutations per Mb); FOUNDATIONONE®CDx or FOUNDATIONONE® Liquid CDx OR if FOUNDATIONONE test and MSI result by PCR are both not evaluable): • Planned surgery to remove the CRC 4 - 6 weeks after last dose of pembrolizumab

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Dose: 200mg by IV infusion on Day 1 of each treatment cycle

Tumour Mutation Burden high or medium (or MSI-High)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven adenocarcinoma of the colon or rectum which is MMR-d by IHC or MSI-H by PCR (or microsatellite testing if routine practice).
• Patient is fit (ECOG 0-1) and eligible for planned curative surgery in keeping with NICE guidelines and considered fit/suitable for adjuvant chemotherapy as per local site investigator's discretion based on:
• Radiological node positive T1-4 CRC or
• Node negative high risk T3 defined as EITHER ≥ 5mm of extramural depth of invasion OR unequivocal EMVI on imaging (regardless of depth) or Node negative T4 disease
• Patients with rectal cancer are eligible if it is determined that neoadjuvant chemo-radiotherapy is not required to achieve a R0 resection.
• Patients presenting with acute colonic obstruction may enter the trial only after obstruction is relieved by a successful defunctioning stoma/stent, and when recovered to a fitness level consistent with the other eligibility criteria
• Adequate bone marrow function:
• White Blood Cell \>3.0 x 10\^9/L;
• Absolute neutrophil count ≥1.5 x 10\^9/L
• Platelets ≥100 x 10\^9/L.
• Haemoglobin ≥90 g/L
• Adequate renal function:
• GFR \>50 mL/min estimated using validated creatinine clearance calculation (e.g. Cockroft-Gault) NB If the calculated creatinine clearance is \< 50 mL/min, a formal 24 hour urine collection or isotope clearance must be carried out demonstrating GFR ≥ 50 mL/min as per institutional standards
• Adequate liver function:
• Total bilirubin \< 1.5 times Upper Limit of Normal (ULN) OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN

You may not qualify if:

• Any patient for whom radiotherapy is advised by the MDT
• Strong evidence of distant metastases or peritoneal nodules (M1)
• Prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137)
• Prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to registration.
• (NB: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline, with the exception of alopecia. Participants with ≤Grade 2 neuropathy may be eligible.) (NB: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.)
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to registration (seasonal flu vaccines that do not contain live virus are permitted). Administration of killed vaccines is allowed
• Any investigational agents or investigational devices within 4 weeks prior to registration Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10mg daily of prednisolone or equivalent), or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment Note: the use of physiologic doses of corticosteroids may be approved after consultation with UCL CTC.
• Patients with concurrent or previous malignancy that could compromise assessment of the primary or secondary endpoints of the trial
• Has known active CNS metastases and/or carcinomatous meningitis.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or to any of its excipients.
• Has previous severe or life-threatening skin adverse reaction with other immune-stimulatory anticancer agents
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• NB: Replacement therapy (e.g. levothyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is permitted.
• History of (non-infectious) pneumonitis/interstitial lung disease that required steroids, or current pneumonitis/interstitial lung disease

Sponsors & Collaborators

• University College, London: lead
• Merck Sharp & Dohme LLC: collaborator
• Sharp: collaborator
• Foundation Medicine: collaborator
• University College London (UCL) Cancer Institute: collaborator
• University of Leeds: collaborator
• University College London Hospitals: collaborator
• Personalis Inc.: collaborator

Study Sites (6)

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

RECRUITING

St James University Hospital (SJUH)

Leeds, LS9 7TF, United Kingdom

COMPLETED

University College Hospital

London, NW1 2BU, United Kingdom

RECRUITING

Christie Hospital NHS Trust, Wilmslow Road,

Manchester, M20 4BX, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

COMPLETED

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Kai-Keen Shiu

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Reshma Bhat

CONTACT

02076799336; ctc.neoprism@ucl.ac.uk

Rubina Begum

CONTACT

02076799514; ctc.neoprism@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label, 2 arm phase II trial

Study Record Dates

• First Submitted: December 14, 2021
• First Posted: January 19, 2022
• Study Start: July 20, 2022
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2029
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

GB (6)