Melanoma is the fifth most common cancer in the UK, with around 16,000 new cases and 2,300 deaths annually. It is also one of the greatest success stories in modern oncology — immunotherapy and targeted therapy have transformed advanced melanoma from a near-fatal diagnosis to one where long-term survival is achievable. UK centres have been at the centre of this revolution, and the next wave of trials is pushing cure rates even higher.
UK melanoma research is coordinated through the NCRI Skin Cancer Clinical Studies Group, with major trial centres at the Royal Marsden, the Christie, and Scottish cancer centres. The UK was a pivotal contributor to the CheckMate and KEYNOTE trials that established immunotherapy for melanoma. NICE has approved multiple immunotherapy and targeted therapy combinations, and the NHS Genomic Medicine Service provides routine BRAF testing at diagnosis.
There are currently over 80 actively recruiting melanoma trials in the UK, spanning adjuvant, neoadjuvant, and metastatic settings.
Types of Melanoma Trials
Immunotherapy
Anti-PD-1, anti-CTLA-4, and novel checkpoint combinations, plus intratumoural immunotherapy injecting agents directly into melanoma lesions.
Targeted Therapy
BRAF/MEK inhibitor combinations for BRAF-mutant melanoma (~50% of cases), and emerging targets like NRAS and c-KIT.
Cell Therapy
Tumour-infiltrating lymphocyte (TIL) therapy — extracting and expanding the patient's own immune cells that have already recognised the tumour.
Vaccines & Viruses
Personalised mRNA vaccines and oncolytic virus therapy stimulating immune responses against melanoma-specific antigens.
Immunotherapy Combinations
Immunotherapy is the backbone of modern melanoma treatment, and UK trials are optimising it further:
Anti-PD-1 monotherapy — nivolumab and pembrolizumab are standard first-line. UK trials testing: 1-year vs 2-year treatment duration, biomarker-guided stopping (using ctDNA and tumour mutational burden), and rechallenge after progression
Dual checkpoint blockade — nivolumab + ipilimumab (anti-PD-1 + anti-CTLA-4) for higher response rates. UK trials exploring: lower-dose ipilimumab to reduce toxicity, shorter induction courses, and biomarkers predicting who needs dual vs single-agent
Next-generation checkpoints — anti-LAG-3 (relatlimab + nivolumab, now approved), anti-TIGIT, and anti-TIM-3 in UK Phase 2/3 trials
Intratumoural immunotherapy — injecting immune-stimulating agents (T-VEC oncolytic virus, mRNA, STING agonists, IL-2) directly into melanoma deposits to activate local and systemic immune responses, with lower toxicity than systemic treatment
Immunotherapy + targeted therapy — trials combining anti-PD-1 with BRAF/MEK inhibitors (spatially combining two effective approaches), managing overlapping toxicities
BRAF/MEK Targeted Therapy
About half of melanomas carry a BRAF V600 mutation, making them targets for BRAF/MEK inhibitor combinations:
Dabrafenib + trametinib — standard first-line for BRAF-mutant melanoma. UK trials exploring: triplet combinations adding immunotherapy, intermittent dosing to delay resistance, and as neoadjuvant before surgery
Encorafenib + binimetinib — alternative BRAF/MEK combination with once-daily dosing convenience, in UK comparative trials
Vemurafenib + cobimetinib — established combination, now being tested in adjuvant settings in UK trials
Next-generation BRAF inhibitors — paradox-breaking BRAF inhibitors that don't cause the secondary skin cancers seen with current BRAF inhibitors, in UK Phase 1 trials
NRAS-mutant melanoma — MEK inhibitors, binimetinib, and novel combination approaches for NRAS-mutant disease (20–25% of melanomas), which currently has fewer targeted options
Neoadjuvant & Adjuvant Approaches
Giving systemic therapy before (neoadjuvant) or after (adjuvant) surgery is a rapidly growing area:
Neoadjuvant immunotherapy — UK trials (SWOG S1801, PRADO) showing that giving anti-PD-1 before surgery improves event-free survival compared to adjuvant-only treatment. Pathological complete response is emerging as a powerful surrogate endpoint
Neoadjuvant targeted therapy — BRAF/MEK inhibitors before surgery for resectable stage III BRAF-mutant melanoma, with pathological response guiding adjuvant treatment decisions
Adjuvant immunotherapy duration — trials testing whether 6 months of adjuvant anti-PD-1 is non-inferior to 12 months, reducing toxicity and cost
ctDNA-guided adjuvant therapy — using circulating tumour DNA to identify high-risk patients who need adjuvant treatment, and low-risk patients who can safely avoid it
TIL Therapy & Cell Therapy
Tumour-infiltrating lymphocyte (TIL) therapy harnesses the patient's own immune cells:
Lifileucel (Amtagvi) — the first FDA-approved TIL therapy for advanced melanoma, now in UK trials at the Christie and Royal Marsden. Involves surgically removing a tumour, extracting and expanding the T cells that have infiltrated it, then reinfusing them after lymphodepletion
UK TIL manufacturing — the UK is developing domestic TIL manufacturing capability, reducing costs and enabling broader access. Clinical trials are testing simplified, shorter manufacturing processes
Genetically enhanced TIL — engineering TIL cells to express cytokines or checkpoint-resistant receptors before reinfusion, enhancing their anti-tumour activity
TIL + checkpoint inhibition — UK trials combining TIL infusion with anti-PD-1 therapy to maintain the immune response after TIL administration
Vaccines & Oncolytic Viruses
Personalised cancer vaccines are entering late-stage development:
mRNA-4157 (individualised neoantigen therapy) — personalised mRNA vaccine encoding up to 34 tumour-specific neoantigens, combined with pembrolizumab. UK Phase 3 trials showing significant reduction in recurrence for resected melanoma
Talimogene laherparepvec (T-VEC) — oncolytic HSV virus injected directly into melanoma lesions. UK trials combining with checkpoint inhibitors and testing in earlier-stage disease
RP1 oncolytic virus — enhanced oncolytic herpes virus expressing GM-CSF and a GalT-knockout, in UK Phase 2 trials with nivolumab
Peptide vaccines — melanoma-associated antigen peptides (MART-1, gp100, tyrosinase) combined with immune adjuvants, in UK trials for adjuvant and maintenance settings
Who Can Participate?
Melanoma trial eligibility depends on stage, mutation status, and prior treatment:
Immunotherapy trials — unresectable stage III or stage IV melanoma, treatment-naïve or after specific prior therapy. Autoimmune disease may exclude. PD-L1 expression may be required for some studies
Targeted therapy trials — require confirmed BRAF V600E or V600K mutation (for BRAF/MEK trials), or NRAS mutation (for NRAS-directed trials)
Neoadjuvant trials — resectable stage III or oligometastatic stage IV disease, adequate performance status for surgery, and no prior systemic therapy (for most trials)
TIL therapy trials — resectable tumour deposit for TIL extraction, adequate organ function for lymphodepletion chemotherapy, and no active brain metastases
General criteria — ECOG 0–1, adequate organ function, treated brain metastases may be allowed (stable for ≥4 weeks), no active autoimmune disease requiring immunosuppression
💡 Tip: Get BRAF Tested at Diagnosis
All melanoma patients should have BRAF mutation testing at diagnosis — this is now standard NHS care. Knowing your BRAF status immediately opens (or closes) the door to targeted therapy trials. Also ask about NRAS and c-KIT testing. These molecular results, combined with your stage and disease burden, determine which trials you can access. Keep copies of your pathology and molecular reports.
UK Melanoma Trial Locations
Major UK centres running melanoma trials include:
London — Royal Marsden Hospital, UCLH, Guy's and St Thomas', Imperial College Healthcare
Manchester — The Christie NHS Foundation Trust (major melanoma and TIL centre)
Glasgow — Beatson West of Scotland Cancer Centre
Edinburgh — Western General Hospital (Edinburgh Cancer Centre)
Leeds — St James's University Hospital (Leeds Cancer Centre)
Cambridge — Addenbrooke's Hospital
Southampton — University Hospital Southampton (experimental cancer medicine centre)
Newcastle — Northern Centre for Cancer Care, Freeman Hospital
How to Find Your Match
Use our Smart Matcher to find melanoma trials tailored to your stage, mutation status, and treatment history. Whether you are exploring adjuvant therapy after surgery, neoadjuvant treatment before resection, immunotherapy combinations, TIL therapy, or novel vaccines, we can match you to actively recruiting studies.