Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study
Rothwell, Dominic G Ayub, Mahmood Carter, Louise Smith, Nigel K Villa, Shaun Dransfield, Joanne Clipson, Alexandra
Rothwell, Dominic G
Ayub, Mahmood
Carter, Louise
Smith, Nigel K
Villa, Shaun
Dransfield, Joanne
Clipson, Alexandra
Citations
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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.
Authors
Rothwell, Dominic G
Ayub, Mahmood
Cook, Natalie
Thistlethwaite, Fiona C
Carter, Louise
Dean, Emma J
Smith, Nigel K
Villa, Shaun
Dransfield, Joanne
Clipson, Alexandra
White, Daniel J
Nessa, Kamrun
Ferdous, Saba
Howell, Matthew
Gupta, Avinash
Kilerci, Bedirhan
Mohan, Sumitra
Frese, Kristopher K
Gulati, Sakshi
Miller, Crispin J
Jordan, Allan M
Eaton, H
Hickson, N
O'Brien, Ciara S
Graham, Donna
Kelly, Claire
Aruketty, Sreeja
Metcalf, Robert
Chiramel, Jaseela
Tinsley, Nadina
Vickers, Alexander J
Kurup, Roopa
Frost, Hannah
Stevenson, Julie
Southam, Siobhan
Landers, Donal
Wallace, A
Marais, Richard
Hughes, Andrew M
Brady, Ged
Dive, Caroline
Krebs, Matthew G
Ayub, Mahmood
Cook, Natalie
Thistlethwaite, Fiona C
Carter, Louise
Dean, Emma J
Smith, Nigel K
Villa, Shaun
Dransfield, Joanne
Clipson, Alexandra
White, Daniel J
Nessa, Kamrun
Ferdous, Saba
Howell, Matthew
Gupta, Avinash
Kilerci, Bedirhan
Mohan, Sumitra
Frese, Kristopher K
Gulati, Sakshi
Miller, Crispin J
Jordan, Allan M
Eaton, H
Hickson, N
O'Brien, Ciara S
Graham, Donna
Kelly, Claire
Aruketty, Sreeja
Metcalf, Robert
Chiramel, Jaseela
Tinsley, Nadina
Vickers, Alexander J
Kurup, Roopa
Frost, Hannah
Stevenson, Julie
Southam, Siobhan
Landers, Donal
Wallace, A
Marais, Richard
Hughes, Andrew M
Brady, Ged
Dive, Caroline
Krebs, Matthew G
Description
Date
2019
Publisher
Collections
Keywords
Type
Article
Citation
Rothwell DG, Ayub M, Cook N, Thistlethwaite F, Carter L, Dean E, et al. Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study. Nat Med. 2019; 25(5):738-43.