Imperial College London


Faculty of MedicineNational Heart & Lung Institute

Reader in Cancer Medicine



+44 (0)20 7808 2132s.popat Website




Royal Marsden HospitalThe Royal Marsden Hospital






BibTex format

author = {Middleton, G and Crack, LR and Popat, S and Swanton, C and Hollingsworth, SJ and Buller, R and Walker, I and Carr, TH and Wherton, D and Billingham, LJ},
doi = {annonc/mdv394},
journal = {Annals of Oncology},
pages = {2464--2469},
title = {The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer},
url = {},
volume = {26},
year = {2015}

RIS format (EndNote, RefMan)

AB - BACKGROUND: The management of NSCLC has been transformed by stratified medicine. The National Lung Matrix Trial (NLMT) is a UK-wide study exploring the activity of rationally selected biomarker/targeted therapy combinations. PATIENTS AND METHODS: The Cancer Research UK (CRUK) Stratified Medicine Programme 2 is undertaking the large volume national molecular pre-screening which integrates with the NLMT. At study initiation, there are eight drugs being used to target 18 molecular cohorts. The aim is to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation. A Bayesian adaptive design that gives a more realistic approach to decision making and flexibility to make conclusions without fixing the sample size was chosen. The screening platform is an adaptable 28-gene Nextera next-generation sequencing platform designed by Illumina, covering the range of molecular abnormalities being targeted. The adaptive design allows new biomarker-drug combination cohorts to be incorporated by substantial amendment. The pre-clinical justification for each biomarker-drug combination has been rigorously assessed creating molecular exclusion rules and a trumping strategy in patients harbouring concomitant actionable genetic abnormalities. Discrete routes of pathway activation or inactivation determined by cancer genome aberrations are treated as separate cohorts. Key translational analyses include the deep genomic analysis of pre- and post-treatment biopsies, the establishment of patient-derived xenograft models and longitudinal ctDNA collection, in order to define predictive biomarkers, mechanisms of resistance and early markers of response and relapse. CONCLUSION: The SMP2 platform will provide large scale genetic screening to inform entry into the NLMT, a trial explicitly aimed at discovering novel actionable cohorts in NSCLC. CLINICAL TRIAL ISRCTN: 38344105.
AU - Middleton,G
AU - Crack,LR
AU - Popat,S
AU - Swanton,C
AU - Hollingsworth,SJ
AU - Buller,R
AU - Walker,I
AU - Carr,TH
AU - Wherton,D
AU - Billingham,LJ
DO - annonc/mdv394
EP - 2469
PY - 2015///
SN - 1569-8041
SP - 2464
TI - The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer
T2 - Annals of Oncology
UR -
UR -
VL - 26
ER -