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Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study

Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study

Authors :
Kristopher K. Frese
Donna M. Graham
Nicholas Hickson
Alexandra Clipson
Crispin J. Miller
Sumitra Mohan
Saba Ferdous
Matthew G Krebs
Alexander J Vickers
Bedirhan Kilerci
Helen Eaton
Caroline Dive
Siobhan Southam
Roopa Kurup
Hannah Frost
Ciara O’Brien
Fiona C Thistlethwaite
Richard Marais
Allan M. Jordan
Mahmood Ayub
Robert Metcalf
Jaseela Chiramel
Louise Carter
Daniel J. White
Emma Dean
Matthew Howell
Sreeja Aruketty
Avinash Gupta
Joanne Dransfield
Ged Brady
Kamrun Nessa
Donal Landers
Claire L. S. Kelly
Shaun Villa
Julie Stevenson
Dominic G. Rothwell
Nigel K Smith
Andrew Hughes
Nadina Tinsley
Natalie Cook
Sakshi Gulati
Andrew L. Wallace
Source :
Rothwell, D, Ayub, M, Cook, N, Thistlethwaite, F, Carter, L, Dean, E, Smith, N, Villa, S, Dransfield, J, Clipson, A, White, D, Nessa, K, Ferdous, S, Howell, M, Gupta, A, Kilerci, B, Mohan, S, Frese, K, Gulati, S, Miller, C, Jordan, A, Eaton, H, Hickson, N, O'Brien, C, Graham, D, Kelly, C, Aruketty, S, Metcalf, R, Chiramel, J, Tinsley, N, Vickers, AJ, Kurup, R, Frost, H, Stevenson, J, Southam, S, Landers, D, Wallace, A, Marais, R, Hughes, AM, Brady, G, Dive, C & Krebs, M 2019, ' Utility of ctDNA to support patient selection for early phase clinical trials: The TARGET Study ', Nature Medicine, vol. 25, no. 5, pp. 738-743 . https://doi.org/10.1038/s41591-019-0380-z, https://doi.org/10.1038/s41591-019-0380-z
Publication Year :
2019
Publisher :
Springer Science and Business Media LLC, 2019.

Abstract

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) supports blood-based genomic profiling but is not yet routinely implemented in the setting of a phase I trials clinic. TARGET is a molecular profiling program with the primary aim to match patients with a broad range of advanced cancers to early phase clinical trials on the basis of 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 tumor and results were turned round within a clinically acceptable timeframe for Molecular Tumor Board (MTB) review. When a 2.5% variant allele frequency (VAF) threshold was applied, actionable mutations were identified in 41 of 100 patients, and 11 of these patients received a matched therapy. These data support the application of ctDNA in this early phase trial setting where broad genomic profiling of contemporaneous tumor material enhances patient stratification to novel therapies and provides a practical template for bringing routinely applied blood-based analyses to the clinic.

Details

ISSN :
1546170X and 10788956
Volume :
25
Database :
OpenAIRE
Journal :
Nature Medicine
Accession number :
edsair.doi.dedup.....6ab8deb506ba3c33e67a2a24472d46ac
Full Text :
https://doi.org/10.1038/s41591-019-0380-z