National Lung Matrix Trial: successful implementation of a phase II umbrella trial testing multiple genetic-marker-directed drugs in advanced non-small cell lung cancer


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Lucinda Billingham1,Dee Wherton1,Laura Llewellyn1,Susannah Brown1,Sarah Johnson1,Peter Fletcher1,Clive Mulatero2,Timothy Yap3,Yvonne Summers4,James Spicer5,Rowena Sharpe6,Sanjay Popat7,Gary Middleton8
1Cancer Research UK Clinical Trials Unit, University of Birmingham,2Leeds Teaching Hospitals NHS Trust, Leeds,3Royal Marsden Hospital and Institute of Cancer Research, London,4The Christie NHS Foundation Trust, Manchester,5King's College London, and Guy's and St Thomas’ NHS Foundation Trust, London,6Cancer Research UK, London,7Royal Marsden Hospital and Imperial College, London,8Institute of Immunology and Immunotherapy, University of Birmingham

Abstract

Background

The National Lung Matrix Trial (NLMT) is a flagship trial in the United Kingdom being the first to combine the development of a technology platform that screens for multiple genetic aberrations in tumours (provided by the Cancer Research UK Stratified Medicine Programme 2) with testing of multiple novel genetic-marker-directed drugs. The trial is focused on patients with advanced non-small cell lung cancer (NSCLC) and currently includes 7 different drugs targeting 20 molecular markers. In addition, patients with no actionable genetic change (NA) are included and will be treated with a sequential pipeline of drugs. This paper summarises the progress with the implementation of this umbrella trial.

Method

Eligible patients are recruited to treatment arms depending on molecular targets identified by SMP2. The protocol currently includes targeted drugs that inhibit FGFR (AZD4547), MTORC-1/2 (vistusertib), CDK-4/6 (palbociclib), ALK (crizotinib), MEK (selumetinib) combined with docetaxel, AKT (AZD5363) and EGFR mutation positive T790M+ (osimertinib). Current treatment for NA is a PD-L1 Inhibitor (durvalumab). The trial aims to recruit from the 18 Experimental Cancer Medicine Centres (ECMCs) with each treating additional patients referred from feeder sites. Target recruitment for each drug-biomarker cohort is 30 patients to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation with interim analyses after 15 patients.

Results

The first participating centre opened to recruitment in March 2015 and by June 2016, 12 ECMC sites were open. At that time, 61 patients had been recruited covering all treatment arms (range 1 to 16 with 18 on the NA arm) and only 3 drug-biomarker cohorts with no patients.

Conclusion

NLMT has been successfully implemented with two further treatment arms in the pipeline. Continued recruitment will ensure the trial produces important results in the stratified treatment of advanced NSCLC.