Utility of ctDNA to support patient selection for early phase clinical trials: The TARGET Study

Dominic Rothwell, Mahmood Ayub, Natalie Cook, Fiona Thistlethwaite, L Carter, Emma Dean, N Smith, S Villa, J Dransfield, A Clipson, D White, K Nessa, Saba Ferdous, Matthew Howell, A Gupta, B Kilerci, S Mohan, K Frese, S Gulati, C MillerA Jordan, H Eaton, N Hickson, C O'Brien, D Graham, C Kelly, S Aruketty, R Metcalf, J Chiramel, Nadina Tinsley, AJ Vickers, Roopa Kurup, H Frost, J Stevenson, S Southam, Dónal Landers, A Wallace, Richard Marais, AM Hughes, G Brady, Caroline Dive, Matthew Krebs

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Abstract

Next generation sequencing (NGS) of circulating tumour DNA (ctDNA) supports blood-based genomic profiling but is not routinely implemented in the clinic. TARGET is a molecular profiling programme with the primary aim to match patients to early phase clinical trials based on analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumour and results were turned round within a clinically acceptable timeframe for Molecular Tumour Board (MTB) review. When applying a 2.5% Variant Allele Frequency (VAF) threshold actionable mutations were identified in 41/100 patients, with 11 of these patients going onto a matched therapy. These data support the application of ctDNA in an early phase trial setting where broad genomic profiling of contemporaneous tumour material enhances patient stratification to novel therapies and provides a practical template for bringing blood-based analyses to the clinic.
Original languageEnglish
Pages (from-to)738-743
Number of pages6
JournalNature Medicine
Volume25
Issue number5
Early online date22 Apr 2019
DOIs
Publication statusPublished - 22 Apr 2019

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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