Colorectal Cancer Clinical Trials in the UK (2026)
26 May 202612 min readTrialConnect Research Team
Colorectal cancer (bowel cancer) is the fourth most common cancer in the UK, with around 44,000 new diagnoses each year. While early-stage disease has a good prognosis, advanced and metastatic colorectal cancer remains a major therapeutic challenge. UK researchers are leading trials in immunotherapy for mismatch repair-deficient tumours, KRAS-targeted drugs, CAR-T cell therapy, and AI-powered screening — opening new avenues for patients at every stage.
The UK has one of the most active colorectal cancer trial portfolios in the world, anchored by the National Cancer Research Institute (NCRI) colorectal subgroup and the bowel cancer research networks across all four nations. The NHS Genomic Medicine Service provides routine molecular profiling (MSI status, RAS/BRAF mutations, HER2 expression, and consensus molecular subtyping) that directly matches patients to trials.
There are currently over 120 actively recruiting colorectal cancer trials in the UK, spanning Phase 1 first-in-human studies through to Phase 3 practice-changing trials. Many are run through the National Institute for Health Research (NIHR) Clinical Research Network.
Types of Colorectal Cancer Trials
Immunotherapy
Checkpoint inhibitors for MSI-H/dMMR tumours, and combination immunotherapy strategies for MSS/pMMR disease that traditionally resists immunotherapy.
Targeted Therapy
KRAS G12C inhibitors, BRAF/MEK combinations, HER2-directed therapy, and anti-angiogenic agents in later-line settings.
Cell & Gene Therapy
CAR-T cells targeting GCC and CEA, tumour-infiltrating lymphocyte (TIL) therapy, and mRNA cancer vaccines personalised to tumour neoantigens.
Surgical & Radiological
Organ-preserving approaches (watch-and-wait after complete clinical response), robotic surgery trials, and SBRT for oligometastatic disease.
Immunotherapy & Checkpoint Inhibitors
Immunotherapy has transformed the outlook for a subset of colorectal cancer patients and UK trials are pushing to expand its reach:
MSI-H/dMMR disease — Around 5% of metastatic colorectal cancers are microsatellite instability-high. UK trials are exploring adjuvant immunotherapy for stage II/III MSI-H disease (avoiding chemotherapy), neoadjuvant pembrolizumab and nivolumab, and the optimal duration of treatment in the metastatic setting
Overcoming MSS resistance — The vast majority of colorectal cancers are microsatellite stable and resistant to single-agent checkpoint inhibition. UK trials are testing combination strategies: anti-PD-1 plus anti-VEGF (bevacizumab), dual checkpoint blockade (PD-1 + LAG-3 or TIGIT), and immunotherapy combined with radiotherapy
Adjuvant immunotherapy — trials investigating whether immunotherapy can replace or reduce chemotherapy after surgery for high-risk early-stage disease
Peritoneal immunotherapy — intraperitoneal delivery of checkpoint inhibitors combined with pressurised intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal metastases
Targeted Therapy
Molecular profiling is now standard in UK colorectal cancer care, enabling precise matching to targeted therapy trials:
KRAS G12C inhibitors — adagrasib and sotorasib, initially approved in lung cancer, are now in dedicated colorectal cancer trials combining KRAS inhibition with anti-EGFR antibodies (cetuximab) to overcome feedback reactivation
BRAF V600E — encorafenib plus cetuximab (BEACON regimen) is established, but UK trials are exploring triplet combinations adding immunotherapy, and next-generation BRAF degraders
HER2-positive colorectal cancer — trastuzumab deruxtecan (T-DXd), pertuzumab combinations, and tucatinib-based regimens in HER2-amplified metastatic disease
Anti-angiogenic strategies — fruquintinib (VEGFR inhibitor) now approved, with UK trials testing it in earlier lines and in combination with immunotherapy
NTRK fusions — larotrectinib and entrectinib for the rare but targetable NTRK fusion-positive subset
Cell Therapy & Cancer Vaccines
UK centres are at the forefront of personalised cell therapy in solid tumours:
CAR-T for colorectal cancer — trials targeting guanylyl cyclase C (GCC), a protein expressed on most colorectal cancers but not healthy tissue. Also CEA-directed CAR-T and CAR-NK approaches
Tumour-infiltrating lymphocyte (TIL) therapy — extracting and expanding the patient's own tumour-resident T cells, then reinfusing them after lymphodepletion. UK trials at the Christie and Royal Marsden
mRNA cancer vaccines — personalised neoantigen vaccines manufactured from each patient's tumour sequencing data, delivered alongside checkpoint inhibition
Oncolytic virus therapy — modified viruses that selectively infect and kill cancer cells while stimulating anti-tumour immunity, in UK Phase 1/2 trials
Early-Stage & Neoadjuvant Approaches
Treating colorectal cancer before or instead of major surgery is a growing research area:
Total neoadjuvant therapy (TNT) — giving all chemotherapy and radiotherapy before surgery for rectal cancer, with UK trials comparing different TNT sequencing strategies
Watch-and-wait — for rectal cancer patients achieving a complete clinical response after neoadjuvant therapy, avoiding surgery entirely. UK trials are refining patient selection and surveillance protocols
Organ preservation — trials of local excision (TAMIS/TEM) versus radical surgery for early rectal cancer, with quality-of-life endpoints
Circulating tumour DNA (ctDNA) — using post-surgery blood tests to detect minimal residual disease and guide adjuvant treatment decisions, reducing overtreatment
Screening & AI Diagnostics
The UK's bowel cancer screening programme is evolving with technology trials:
AI-assisted colonoscopy — computer vision systems that highlight polyps and early cancers in real-time during endoscopy, improving detection rates
Blood-based screening — cell-free DNA and protein biomarker panels that could complement or replace FIT (faecal immunochemical test) for colorectal cancer screening
Earlier screening age — trials evaluating the impact of lowering the screening age from 50 to 40, given rising incidence in younger adults
Risk-stratified screening — using polygenic risk scores and lifestyle factors to personalise screening intervals
Who Can Participate?
Eligibility varies by trial type and disease stage:
Immunotherapy trials — typically require confirmed MSI-H/dMMR status (for monotherapy trials) or MSS disease with measurable metastases (for combination trials). Prior treatment lines vary by study
Targeted therapy trials — require molecular profiling showing the relevant target (KRAS G12C, BRAF V600E, HER2 amplification, NTRK fusion). Your oncologist can arrange testing through the NHS Genomic Medicine Service
Cell therapy trials — usually require metastatic disease after multiple prior lines, adequate organ function, and no active autoimmune disease
Neoadjuvant trials — require resectable or borderline resectable disease, often stage II/III, with adequate performance status
General criteria — ECOG performance status 0–2, adequate blood counts and organ function, no uncontrolled infections, and no concurrent pregnancy
💡 Tip: Request Molecular Profiling Early
If you have metastatic or high-risk colorectal cancer, ask your oncologist about comprehensive molecular profiling. Tests for MSI status, RAS/BRAF mutations, HER2, and NTRK fusions are now available through the NHS and are essential for matching to the right clinical trial. Having these results ready speeds up the trial eligibility process significantly.
UK Colorectal Cancer Trial Locations
Major UK centres running colorectal cancer trials include:
London — Royal Marsden Hospital, UCLH, Guy's and St Thomas', Imperial College Healthcare
Manchester — The Christie NHS Foundation Trust, Manchester Royal Infirmary
Leeds — St James's University Hospital (Leeds Cancer Centre)
Birmingham — Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham
Glasgow — Beatson West of Scotland Cancer Centre
Edinburgh — Western General Hospital (Edinburgh Cancer Centre)
Cardiff — Velindre Cancer Centre, University Hospital of Wales
Cambridge — Addenbrooke's Hospital, Cambridge University Hospitals
How to Find Your Match
Use our Smart Matcher to find colorectal cancer trials tailored to your tumour molecular profile, stage, and treatment history. Whether you are exploring immunotherapy for MSI-H disease, targeted therapy for a specific mutation, or novel cell therapy approaches, we can match you to actively recruiting studies.