The National Lung Matrix Trial : translating the biology of stratification in advanced non-small-cell lung cancer

G Middleton; L R Crack; S Popat; C Swanton; S J Hollingsworth; R Buller; I Walker; T H Carr; D Wherton; L J Billingham

doi:10.1093/annonc/mdv394

The National Lung Matrix Trial : translating the biology of stratification in advanced non-small-cell lung cancer

G Middleton, L R Crack, S Popat, C Swanton, S J Hollingsworth, R Buller, I Walker, T H Carr, D Wherton, L J Billingham

Research output: Contribution to journal › Article › peer-review

44 Citations (Scopus)

277 Downloads (Pure)

Abstract

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.

Original language	English
Pages (from-to)	2464-2469
Journal	Annals of Oncology
Volume	26
Issue number	12
Early online date	25 Sept 2015
DOIs	https://doi.org/10.1093/annonc/mdv394
Publication status	Published - 12 Dec 2015

Bibliographical note

Keywords

National Lung Matrix Trial
non-small-cell lung cancer
stratified medicine
adaptive trial design
Umbrella Trial

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/annonc/mdv394

Middleton_et_al_2015_National_Lung_Matrix_Trial_Annals_Oncology
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658545/Licence: Creative Commons: Attribution (CC BY)

44 Citations
1 Article

The National Lung Matrix Trial of personalized therapy in lung cancer
Middleton, G., Fletcher, P., Popat, S., Savage, J., Summers, Y., Greystoke, A., Gilligan, D., Cave, J., O’rourke, N., Brewster, A., Toy, E., Spicer, J., Jain, P., Dangoor, A., Mackean, M., Forster, M., Farley, A., Wherton, D., Mehmi, M., Sharpe, R., & 7 othersMills, T. C., Cerone, M. A., Yap, T. A., Watkins, T. B. K., Lim, E., Swanton, C. & Billingham, L., 30 Jul 2020, In: Nature. 583, 7818, p. 807-812 6 p.
Research output: Contribution to journal › Article › peer-review

Open Access
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14 Citations (Scopus)

463 Downloads (Pure)

1 Finished

Tracking Cancer Evolution through Therapy (Tracer X)
Middleton, G. & Naidu, B.
Cancer Research UK
1/01/14 → 31/12/22
Project: Research

Cite this

Middleton, G., Crack, L. R., Popat, S., Swanton, C., Hollingsworth, S. J., Buller, R., Walker, I., Carr, T. H., Wherton, D., & Billingham, L. J. (2015). The National Lung Matrix Trial : translating the biology of stratification in advanced non-small-cell lung cancer. Annals of Oncology, 26(12), 2464-2469. Advance online publication. https://doi.org/10.1093/annonc/mdv394

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The National Lung Matrix Trial : translating the biology of stratification in advanced non-small-cell lung cancer

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Fingerprint

Research output

The National Lung Matrix Trial of personalized therapy in lung cancer

Projects

Tracking Cancer Evolution through Therapy (Tracer X)

Cite this