Abstract 72: Comprehensive liquid biopsy profiling enabled by PGDx elio plasmacomplete to facilitate precision oncology through decentralized access to testing

Abstract Despite the growing body of clinical evidence to support the utility of comprehensive genomic profiling (CGP) for advanced cancer patients, only a small fraction of individuals receive precision oncology guided treatment strategies. To facilitate globally available CGP solutions, we have developed and validated the PGDx elio plasma complete cell-free DNA (cfDNA) kitted assay, which employs a hybrid capture-based 521-gene, 2.1 Mb targeted panel, combined with automated bioinformatics and reporting. PGDx elio plasma complete detects single nucleotide variants (SNVs), insertions and deletions (indels), amplifications, translocations, microsatellite instability (MSI), blood tumor mutation burden (bTMB), and loss of heterozygosity (LOH). Targets include clinically relevant alterations, such as those contained within ALK, BRAF, BRCA1/2, EGFR, ERBB2, FGFR1/2/3, KIT, KRAS, MET, NRAS, NTRK1/2/3, PIK3CA, RET, and ROS1. With as little as 10 ng of sample input of cfDNA, and sequenced on the NovaSeq 6000, PGDx elio plasma complete achieves deep coverage across the target region combined with automated bioinformatics and reporting algorithms. We assessed the analytical performance of this assay. Analytical specificity in a cohort of 20 non-cancerous donors was 100% for all clinically actionable variants and 99.9% panel-wide. The reportable range of the assay is ≥ 0.10% variant allele frequency (VAF) for SNVs and indels, ≥ 3 fusion reads for translocations, and ≥ 1.15-fold for amplifications. Furthermore, analytical sensitivity studies using dilution series with known positive alterations demonstrated a limit of detection ranging from 0.32-0.78% VAF for actionable mutations, 0.34-1.75% VAF for panel-wide mutations, 0.33% VAF for translocations, and 1.32-fold for amplifications. The assay produces highly reproducible results, with 100% average positive agreement (APA) for clinically actionable alterations and 92.5% APA for panel-wide alterations across operators, days, and runs. Compared to a CGP assay of a similar size, PGDx elio plasma complete achieved a 94.7% positive predictive value and >99.9% negative predictive value across all variant types assessed. The PGDx elio plasma complete assay can be processed manually or through automated liquid handling systems with high concordance, with an overall success rate of 97.8%. Taken together, these data demonstrate that the PGDx elio plasma complete assay is a sensitive, specific, accurate, reproducible, and robust approach to enable CGP to guide both translational biomarker discovery and CGP-informed precision oncology strategies. Citation Format: Kenneth C. Valkenburg, Vito Caropreso, Jesse Fox, Christopher Gault, Andrew Georgiadis, Kelly M. Gerding, Aanavi Karandikar, Cynthia Maddox, Paul McGregor, David Riley, Vuna Fa. Comprehensive liquid biopsy profiling enabled by PGDx elio plasmacomplete to facilitate precision oncology through decentralized access to testing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 72.