Methodological issues in precision oncology trials


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Lucinda Billingham1
1Cancer Research UK Clinical Trials Unit, University of Birmingham

Abstract

In striving for precision oncology, master protocols provide an efficient framework in which to investigate the efficacy and safety of drugs for multiple biomarker-defined populations. Such protocols can take the form of an umbrella or basket design. Experience in the design and implementation of master protocols allows the challenges of such trials to become apparent. 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 a phase II umbrella-basket trial in patients with advanced non-small cell lung cancer testing 7 different drugs targeting 20 molecular markers. In addition, patients with no actionable genetic change (NA) are included and treated with a sequential pipeline of drugs. The trial opened to recruitment in March 2015 and is ongoing. Challenges include: screening patients within standard NHS practice and translating them into trial patients; choosing a statistical design that is flexible and fit-for-purpose; enabling conclusions from very rare molecularly-defined cohorts alongside the more prevalent ones; adding new drug-biomarker cohorts into the trial; reporting trial results from drug-biomarker cohorts with varying recruitment rates.