Innv-13. Allele: a Consortium for Prospective Genomics and Functional Diagnostics to Guide Patient Care and Trial Analysis in Newly-diagnosed Glioblastoma
Year: 2018
Type: article
Abstract: Advances in genomic profiling, together with a better understanding of cancer genetic drivers have generated opportunities for precision medicine trials in newly diagnosed glioblastoma (GBM). ALLELE is a consortium to create independent infrastructure for prospective genomics and functional diagnostics to support biomarker-driven trials in GBM. Multi-center prospective study of molecular profiling in newly diagnosed GBM. Clinical (CLIA) tumor/normal whole exome sequencing (WES) and genome-wide copy number array (CNA) were performed. Primary objective: to evaluate the feasibility of genotyping tumors with a turnaround time allowing prospective data use in prospective trials. Secondary objectives included developing infrastructure for novel functional biomarker assays and investigating the clinical yield of tumor/normal WES and CNA in GBM. As of 5/1/18, 65 patients with GBM enrolled among 7 sites. Median age was 59. WES and CMA were completed in 60 patients, with a median time between tissue submission and reporting of 22 days (range 15–35). 33 patients were enrolled in INSIGhT, a randomized platform adaptive trial comparing standard of care versus adjuvant CC-115, neratinib or abemaciclib in MGMT unmethylated newly diagnosed GBM (NCT02977780). In each arm, pre-defined biomarkers (EGFR, PI3K and CDK) will be evaluated for their ability to predict outcome. Potentially actionable findings were identified in 30 patients, and included EGFR amplification, mutations of BRAF, FGFR1, IDH1/2 or FGFR3 or MET fusion. Four tumors were reclassified based on genomics. Functional biomarker assays were developed for real-time evaluation of pharmacodynamic responses in ex vivo models. Updated results of exploratory biomarker analyses will be presented at the conference. Real-time WES, copy number arrays and functional diagnostics are feasible in newly diagnosed glioblastoma, and can support a variety of biomarker-driven trials. Genomic analyses conducted in a prospective manner can inform subsequent clinical trial analysis aiming at matching outcome with tumor genotyping.
Source: Neuro-Oncology
Authors: Mehdi Touat, Adrian Dubuc, David Meredith, Junko Tsuji, Caitlin Mills, Sarah Gaffey, Jack Geduldig, Fiona Watkinson, Kristine Pelton, Seth Malinowski, Niall Lennon, Peter Sorger, Lorenzo Trippa, Shakti Ramkissoon, David Reardon, John de Groot, Evanthia Galanis, Mary Welch, L Burt Nabors, Isabel Arrillaga-Romany, E Antonio Chiocca, Sandro Santagata, David Schiff, Manmeet Ahluwalia, Howard Colman, Jan Drappatz, Brian Alexander, Patrick Wen, Keith Ligon
Institutions: Harvard University, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Broad Institute, Foundation Medicine (United States), The University of Texas MD Anderson Cancer Center, Mayo Clinic, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, University of Alabama at Birmingham, Massachusetts General Hospital, University of Virginia, Cleveland Clinic, University of Utah, Huntsman Cancer Institute
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,132
OpenAlex ID: W2900044394