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

Rothwell, D. G. et al. (2019) Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study. Nature Medicine, 25(5), pp. 738-743. (doi: 10.1038/s41591-019-0380-z) (PMID:31011204)

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.

• Item Type: Articles
• Additional Information: This research was co-funded by The Christie Charitable Fund, by Cancer Research UK (CRUK) via core-funding to the CRUK Manchester Institute (grant no. A27412, R.M.), the CRUK Manchester Centre (grant no. A25254, R.M.), the CRUK Manchester Experimental Cancer Medicines Centre (grant no. A25146, R.M.) and the NIHR Manchester Biomedical Research Centre (C.D. and M.K.). This research was supported by the NIHR Manchester Clinical Research Facility, the Manchester Academic Health Science Centre, the AstraZeneca iDECIDE Programme (grant no. 119106, C.D.) awarded to Manchester Cancer Research Centre, PCRF 2012 Project Grant (C.D.), CRUK Precision Panc grant (no. C480/A25235, C.D.), the EU IMI consortium CANCER-ID (grant no. 115749-Cancer-ID, C.D.) and Roche Products, Ltd. through the provision of the Foundation Medicine tumor profiling service.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Miller, Professor Crispin
• Authors: Rothwell, D. G., 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, A. J., Kurup, R., Frost, H., Stevenson, J., Southam, S., Landers, D., Wallace, A., Marais, R., Hughes, A. M., Brady, G., Dive, C., and Krebs, M. G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Medicine
• Publisher: Nature Research
• ISSN: 1078-8956
• ISSN (Online): 1546-170X
• Published Online: 22 April 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Nature Medicine 25(5): 738-743
• Publisher Policy: Reproduced in accordance with the publisher copyright policy