Renal Cell Carcinoma Clinical Trials in the UK (2026)
26 May 202612 min readTrialConnect Research Team
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, with around 13,000 new cases annually in the UK. The treatment landscape has been transformed by immunotherapy — combination checkpoint blockade is now standard first-line treatment for advanced disease. The next frontier includes HIF-2α inhibitors targeting the fundamental biology of kidney cancer, CAR-T therapy, and adjuvant treatment to prevent recurrence after surgery.
UK kidney cancer research is coordinated through the NCRI Renal Cancer Clinical Studies Group, with leading trial centres at the Royal Marsden, the Christie, UCLH, and Cambridge. The UK played a central role in the CheckMate and KEYNOTE trials that established nivolumab + ipilimumab and pembrolizumab + axitinib as first-line standards. Now, UK centres are driving the next wave of innovation.
Most clear cell RCC (the most common subtype, ~75%) is driven by loss of the VHL tumour suppressor gene, leading to HIF-2α overexpression. This molecular understanding has opened entirely new treatment targets beyond immunotherapy and angiogenesis inhibition.
There are currently over 60 actively recruiting RCC trials in the UK, spanning adjuvant, metastatic, and biomarker-driven settings.
Types of Kidney Cancer Trials
Immunotherapy
Dual checkpoint blockade (nivolumab + ipilimumab), anti-PD-1 + VEGF-TKI combinations, and novel checkpoint targets including LAG-3 and TIM-3.
CAR-T cells targeting carbonic anhydrase IX (CAIX) and other kidney cancer antigens. TIL therapy for advanced RCC.
Adjuvant Therapy
Post-surgery treatment to prevent recurrence — the biggest unresolved question in kidney cancer management.
Immunotherapy Combinations
Immunotherapy is the backbone of modern RCC treatment, and UK trials are refining it further:
Nivolumab + ipilimumab (CheckMate) — the established first-line standard for intermediate/poor-risk metastatic RCC. UK trials now exploring: 2-year vs indefinite treatment duration, biomarker-guided de-escalation (can patients with complete response stop treatment?), and rechallenge strategies after progression
Pembrolizumab + axitinib (KEYNOTE) — standard first-line for favourable-risk disease. UK trials testing: pembrolizumab + newer VEGF inhibitors (tivozanib, cabozantinib), and triplet combinations adding a third agent
Nivolumab + cabozantinib (CheckMate 9ER) — increasingly popular first-line combination. UK trials comparing head-to-head with nivolumab + ipilimumab, and testing in non-clear cell RCC subtypes
Triple therapy — nivolumab + ipilimumab + cabozantinib in UK Phase 2/3 trials for high-risk disease, balancing efficacy against increased toxicity
Novel checkpoint combinations — anti-LAG-3 (relatlimab) + anti-PD-1, anti-TIM-3 + anti-PD-1, and CD70-targeted therapies in UK early-phase trials
HIF-2α Inhibitors & Novel Targets
Targeting the HIF-2α pathway represents the first mechanism-driven therapy for RCC:
Belzutifan (WELIREG) — first-in-class HIF-2α inhibitor, already approved for VHL disease. UK Phase 3 trials now testing in sporadic clear cell RCC: as monotherapy, in combination with pembrolizumab, and as adjuvant treatment after surgery. This targets the fundamental driver of most clear cell RCC
Next-generation HIF-2α inhibitors — newer compounds with improved potency and pharmacokinetics entering UK Phase 1 trials, designed to overcome resistance to belzutifan
VEGF tyrosine kinase inhibitors — cabozantinib, lenvatinib, and tivozanib in UK combination trials with immunotherapy. Exploring optimal sequencing: which TKI after immunotherapy failure?
mTOR and PI3K pathway — everolimus and temsirolimus in UK trials for non-clear cell RCC subtypes (papillary, chromophobe) where VEGF/HIF-targeted therapy is less effective
MET inhibitors — savolitinib and crizotinib for papillary RCC driven by MET alterations. UK trials for this less common but aggressive subtype
Adjuvant & Neoadjuvant Treatment
One of the biggest debates in kidney cancer is whether to give treatment after surgery to prevent recurrence:
Pembrolizumab adjuvant (KEYNOTE-564) — the first positive adjuvant RCC trial, showing disease-free survival benefit for high-risk patients after nephrectomy. UK trials now exploring: optimal patient selection (who actually benefits?), duration of treatment, and long-term overall survival data
Belzutifan adjuvant — UK trials testing HIF-2α inhibition after surgery for clear cell RCC patients with high recurrence risk, offering a targeted alternative to immunotherapy
Nivolumab adjuvant — UK centres participating in trials of adjuvant nivolumab after nephrectomy, with biomarker-guided patient selection
Neoadjuvant approaches — giving immunotherapy or targeted therapy before surgery for large or locally advanced tumours to shrink the tumour and reduce recurrence risk. UK trials exploring downsizing before partial nephrectomy
Active surveillance vs treatment — UK trials comparing close monitoring after surgery against immediate adjuvant treatment, using ctDNA and other biomarkers to guide decision-making
CAR-T & Cell Therapy
Cell therapy is entering the RCC space with novel targets:
CAIX-targeted CAR-T — carbonic anhydrase IX is highly expressed on clear cell RCC cells but minimally on normal tissue, making it an ideal target. UK Phase 1 trials testing CAR-T cells engineered to target CAIX, with safety and efficacy endpoints
TIL therapy for RCC — extracting and expanding tumour-infiltrating lymphocytes from kidney cancer resections. UK trials at the Royal Marsden testing whether expanded TIL cells can target residual disease
TCR-engineered T cells — T cells engineered with T-cell receptors targeting RCC-specific antigens including HLA-restricted peptides from VHL-mutated proteins
Bispecific antibodies — dual-targeting antibodies engaging T cells to RCC cells, similar to the blinatumomab approach in leukaemia. UK early-phase trials for metastatic RCC
Biomarker-Guided Treatment
Precision medicine is reshaping how kidney cancer is treated:
IMDC risk scoring — the International Metastatic RCC Database Consortium risk model (based on haemoglobin, calcium, performance status, time from diagnosis, neutrophils, platelets) guides first-line treatment selection. UK trials refining and validating updated risk models
ctDNA monitoring — circulating tumour DNA to detect recurrence after surgery earlier than imaging. UK trials using ctDNA to guide adjuvant treatment decisions — treat only ctDNA-positive patients, avoid overtreatment in ctDNA-negative patients
Gene expression profiling — transcriptomic signatures (angiogenesis, immune, proliferative) predicting response to immunotherapy vs VEGF-TKI. UK trials using molecular subtyping to guide first-line treatment choice
Tumour mutation burden and immune signatures — identifying patients most likely to benefit from dual checkpoint blockade vs single-agent anti-PD-1 combinations
💡 Tip: Know Your Subtype and Risk
RCC treatment decisions depend on three critical pieces of information: (1) the histological subtype (clear cell vs non-clear cell), (2) the IMDC risk score, and (3) whether your tumour has VHL loss or other molecular features. Ask your oncologist about your subtype and risk category — this directly determines which first-line treatment and which clinical trials are appropriate for you.
Who Can Participate?
RCC trial eligibility depends on stage, subtype, risk category, and prior treatment:
First-line immunotherapy trials — metastatic or unresectable RCC, treatment-naïve for advanced disease (prior adjuvant therapy may be allowed depending on timing), ECOG 0–1, measurable disease by RECIST criteria
Adjuvant trials — post-nephrectomy with high-risk features (pT2 grade 4, pT3-4, or N+), no evidence of metastatic disease, adequate organ function
HIF-2α inhibitor trials — clear cell RCC subtype with confirmed VHL alteration (for some studies), specific prior treatment requirements vary by trial
CAR-T/cell therapy trials — metastatic RCC progressed on standard immunotherapy and VEGF-TKI, adequate organ function for lymphodepletion, accessible tumour tissue for TIL extraction
Non-clear cell trials — papillary, chromophobe, or other non-clear cell subtypes. These patients are often under-represented in trials, making dedicated studies especially important
UK RCC Trial Locations
Major UK centres running kidney cancer trials include:
London — Royal Marsden Hospital, UCLH, Guy's and St Thomas', Imperial College Healthcare
Manchester — The Christie NHS Foundation Trust
Cambridge — Addenbrooke's Hospital (major kidney cancer genomics centre)
Glasgow — Beatson West of Scotland Cancer Centre
Edinburgh — Western General Hospital (Edinburgh Cancer Centre)
Leeds — St James's University Hospital (Leeds Cancer Centre)
Southampton — University Hospital Southampton
Newcastle — Northern Centre for Cancer Care, Freeman Hospital
Oxford — Oxford University Hospitals
How to Find Your Match
Use our Smart Matcher to find kidney cancer trials tailored to your subtype, stage, and treatment history. Whether you have newly diagnosed metastatic disease, are considering adjuvant treatment after surgery, or have progressed after first-line therapy, we can match you to actively recruiting studies.