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

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    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
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    Affiliation
    Clinical Experimental Pharmacology Group, CRUK Manchester Institute, Manchester, UKClinical Experimental Pharmacology Group, CRUK Manchester Institute, Manchester, UK
    Issue Date
    2019
    
    Metadata
    Show full item record
    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.
    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.
    Journal
    Nature Medicine
    URI
    http://hdl.handle.net/10541/621823
    DOI
    10.1038/s41591-019-0380-z
    PubMed ID
    31011204
    Additional Links
    https://dx.doi.org/10.1038/s41591-019-0380-z
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41591-019-0380-z
    Scopus Count
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