Non-Small Cell Lung Cancer Clinical Trials in the UK (2026)
26 May 202613 min readTrialConnect Research Team
Non-small cell lung cancer (NSCLC) accounts for around 85% of all lung cancers, with approximately 40,000 new cases annually in the UK. It has become the poster child for precision oncology — molecular profiling at diagnosis now identifies actionable mutations in over 50% of patients, opening doors to targeted therapies, immunotherapy combinations, and novel approaches like antibody-drug conjugates. UK centres are leading many of these breakthrough trials.
UK lung cancer research is coordinated through the NCRI Lung Cancer Clinical Studies Group, with major trial centres at the Royal Marsden, the Christie, UCLH, and the Glasgow Beatson. The NHS Genomic Medicine Service provides routine molecular profiling at diagnosis for all advanced NSCLC patients, testing for EGFR, ALK, ROS1, BRAF, KRAS, MET, RET, NTRK, and PD-L1 status.
This comprehensive molecular profiling means that every patient diagnosed with advanced NSCLC in the UK should have their treatment guided by the genetic makeup of their tumour — and should be considered for mutation-specific clinical trials.
There are currently over 120 actively recruiting NSCLC trials in the UK, making it one of the most active trial areas in oncology.
Types of NSCLC Trials
Targeted Therapy
EGFR inhibitors (osimertinib and beyond), ALK/ROS1 inhibitors, KRAS G12C inhibitors, and other mutation-specific agents targeting the tumour's genetic drivers.
Immunotherapy
Anti-PD-1/PD-L1 checkpoint inhibitors, dual checkpoint blockade, and combinations with chemotherapy, targeted therapy, or novel immune modulators.
ADCs
Antibody-drug conjugates delivering potent chemotherapy directly to tumour cells via targets like TROP2, HER3, and MET — precision chemotherapy.
Early-Stage
Neoadjuvant and adjuvant treatment for resectable NSCLC, including immunotherapy before and after surgery, and ctDNA-guided treatment decisions.
EGFR-Targeted Therapy
EGFR mutations occur in 10–15% of UK NSCLC patients (higher in never-smokers and those of Asian ethnicity):
Osimertinib (Tagrisso) — third-generation EGFR TKI, now standard first-line for EGFR-mutant NSCLC. UK trials exploring: osimertinib + chemotherapy combinations (FLAURA2 regimen showing PFS benefit), osimertinib + anti-VEGF (ramucirumab), and osimertinib + immunotherapy (managing overlapping toxicity concerns)
Fourth-generation EGFR inhibitors — targeting the C797S resistance mutation that develops on osimertinib treatment. UK Phase 1/2 trials with BLU-945, BPI-361175, and other next-generation compounds for patients who have progressed on osimertinib
EGFR exon 20 insertion mutations — amivantamab (Rybrevant, bispecific EGFR/MET antibody) and mobocertinib for this historically treatment-resistant EGFR variant. UK trials testing: amivantamab + lazertinib combinations, and newer agents with improved selectivity
Combination approaches after progression — UK trials testing: osimertinib rechallenge after treatment holiday, osimertinib + MET inhibitors for MET-amplified resistance, and triplet combinations with chemotherapy + anti-VEGF
ALK, ROS1 & RET Targeted Therapy
Rearrangement-driven NSCLC has multiple highly effective targeted options:
ALK inhibitors — alectinib is standard first-line, but UK trials are testing next-generation ALK inhibitors (lorlatinib, ensartinib) for greater brain penetration and activity against resistance mutations. Lorlatinib is now approved after alectinib, and UK trials exploring: lorlatinib first-line vs alectinib, and sequencing strategies
ROS1 rearrangements — entrectinib and crizotinib are established, but UK trials testing repotrectinib and taletrectinib — next-generation ROS1 inhibitors designed to overcome resistance mutations, with improved CNS activity
RET fusions — selpercatinib and pralsetinib have transformed RET-positive NSCLC treatment. UK trials testing: first-line vs chemotherapy + immunotherapy, resistance mechanisms and next-generation RET inhibitors, and combination approaches
NTRK fusions — larotrectinib and entrectinib for NTRK-positive tumours (rare in NSCLC but highly responsive). UK trials for second-generation TRK inhibitors (repotrectinib) overcoming acquired resistance
MET exon 14 skipping — tepotinib and capmatinib for this distinct molecular subtype. UK trials testing combinations and resistance management
KRAS G12C Inhibitors
KRAS G12C is the most common actionable mutation in NSCLC (~13% of patients), and finally has targeted treatments:
Sotorasib (Lumakras) — first FDA-approved KRAS G12C inhibitor. UK trials testing: sotorasib + anti-PD-1 (codeBreaK 200+), sotorasib + SHP2 inhibitors, and sotorasib + chemotherapy combinations
Adagrasib (Krazati) — second KRAS G12C inhibitor with longer half-life and CNS penetration. UK trials testing: adagrasib + cetuximab (anti-EGFR), adagrasib + anti-PD-1, and as neoadjuvant treatment before surgery
Novel KRAS G12C inhibitors — divarasib and other next-generation compounds with improved potency in UK Phase 1/2 trials
KRAS G12D and pan-KRAS — for non-G12C KRAS mutations (G12D, G12V, G13D). UK early-phase trials testing broader KRAS targeting for the majority of KRAS-mutant NSCLC patients who currently don't have targeted options
Resistance management — UK trials specifically studying mechanisms of acquired resistance to KRAS G12C inhibitors and testing combination strategies to prevent or overcome resistance
Immunotherapy Combinations
For patients without actionable mutations, immunotherapy-based combinations are the standard of care:
Anti-PD-1 + chemotherapy — pembrolizumab + platinum-doublet chemotherapy is standard first-line for PD-L1-negative and low-expressing NSCLC. UK trials optimising: chemotherapy backbone (carboplatin vs cisplatin), pembrolizumab + switched chemotherapy on progression, and 4 vs 6 cycles of induction
Dual checkpoint blockade — nivolumab + ipilimumab for PD-L1-high NSCLC (CheckMate 227), and nivolumab + relatlimab (anti-LAG-3) in UK Phase 2/3 trials
Anti-PD-1 + anti-VEGF + chemotherapy — atezolizumab + bevacizumab + chemotherapy (IMpower150 regimen) for non-squamous NSCLC. UK trials testing in EGFR/ALK-positive NSCLC after TKI progression
Novel immune targets — anti-TIGIT (tiragolumab), anti-TIM-3, CD73/A2AR pathway inhibitors, and STING agonists in UK trials combining with anti-PD-1 to overcome primary and acquired resistance
Immunotherapy in early-stage disease — durvalumab after chemoradiation for stage III (PACIFIC), and atezolizumab adjuvant after surgery (IMpower010). UK trials now testing neoadjuvant + adjuvant immunotherapy ("sandwich" approach)
Antibody-Drug Conjugates
ADCs deliver highly potent chemotherapy directly to tumour cells, sparing normal tissue:
TROP2-targeted ADCs — datopotamab deruxtecan (Dato-DXd) in UK Phase 3 trials for both squamous and non-squamous NSCLC. Showing impressive response rates as second-line treatment, with manageable toxicity profile
HER3-targeted ADCs — patritumab deruxtecan for EGFR-mutant NSCLC after osimertinib progression. UK trials testing: ADC as a bridge treatment before or after other targeted therapy, and combination with osimertinib
MET-targeted ADCs — telisotuzumab vedotin for MET-overexpressing NSCLC, in UK trials for patients with MET amplification or overexpression
CEACAM5-targeted ADCs — tusamitamab ravtansine for CEACAM5-expressing NSCLC (expressed in ~25% of squamous and non-squamous NSCLC)
Neoadjuvant & Adjuvant Approaches
Treating lung cancer earlier — before or after surgery — is a major paradigm shift:
Neoadjuvant immunotherapy + chemotherapy — the CheckMate 816 and KEYNOTE-671 trials established nivolumab/pembrolizumab + chemotherapy before surgery. UK trials now testing: pathological complete response as a guide for adjuvant treatment duration, and whether all patients need adjuvant treatment after neoadjuvant response
Perioperative immunotherapy ("sandwich") — neoadjuvant + adjuvant immunotherapy (AEGEAN, IMpower010, KEYNOTE-091). UK trials comparing: neoadjuvant-only vs neoadjuvant + adjuvant, and biomarkers identifying patients who benefit from adjuvant treatment
Neoadjuvant targeted therapy — osimertinib before surgery for EGFR-mutant resectable NSCLC. UK trials (NeoADAURA) testing whether neoadjuvant EGFR inhibition improves surgical outcomes and reduces recurrence
ctDNA-guided adjuvant treatment — using circulating tumour DNA after surgery to identify patients at highest risk of recurrence and guide adjuvant treatment decisions. UK MERMAID and related trials
Stereotactic ablative radiotherapy (SABR) — for patients who can't have surgery. UK trials combining SABR with immunotherapy for early-stage NSCLC
💡 Tip: Get Comprehensive Molecular Profiling at Diagnosis
If you're diagnosed with advanced NSCLC, ensure your oncologist orders comprehensive molecular profiling (not just PD-L1). You need testing for EGFR, ALK, ROS1, BRAF, KRAS, MET, RET, NTRK, and PD-L1 at minimum. This is standard NHS care but doesn't always happen promptly. Your mutation status determines which targeted therapy or clinical trial is right for you. Ask for your results and keep copies — these reports open doors to specific trials.
Who Can Participate?
NSCLC trial eligibility depends on molecular profile, stage, and prior treatment:
ALK/ROS1/RET trials — confirmed rearrangement by FISH or NGS. Treatment-naïve vs progressed on prior targeted therapy depends on the specific trial
KRAS G12C trials — confirmed KRAS G12C mutation. Most require prior treatment (chemotherapy + immunotherapy). Some accept treatment-naïve patients
Immunotherapy trials — no actionable mutation (or progressed on targeted therapy), PD-L1 expression level may be required, no active autoimmune disease, ECOG 0–1
Neoadjuvant/adjuvant trials — resectable stage IB–IIIA NSCLC, adequate surgical fitness, no prior systemic therapy (for most neoadjuvant trials)
General criteria — measurable disease by RECIST, adequate organ function, treated brain metastases may be allowed (stable ≥4 weeks), no active infection
UK NSCLC Trial Locations
Major UK centres running NSCLC trials include:
London — Royal Marsden Hospital, UCLH, Guy's and St Thomas', Imperial College Healthcare, Barts Health
Manchester — The Christie NHS Foundation Trust (one of Europe's largest lung cancer trial centres)
Glasgow — Beatson West of Scotland Cancer Centre
Edinburgh — Western General Hospital (Edinburgh Cancer Centre)
Leeds — St James's University Hospital (Leeds Cancer Centre)
Cambridge — Royal Papworth Hospital and Addenbrooke's (major thoracic surgery and lung cancer centre)
Southampton — University Hospital Southampton
Newcastle — Northern Centre for Cancer Care, Freeman Hospital
Leicester — University Hospitals of Leicester
Birmingham — Queen Elizabeth Hospital Birmingham
How to Find Your Match
Use our Smart Matcher to find NSCLC trials tailored to your molecular profile, stage, and treatment history. Whether you have an EGFR mutation and are exploring next-generation TKIs, KRAS G12C and considering targeted therapy, or non-driver-mutant disease suitable for immunotherapy combinations, we can match you to actively recruiting studies.