Abstract LB095: ASPYRE-Lung addresses critical gaps in NGS-based biomarker testing: Robust variant calling from NGS QC fails
Authors: Ryan T. Evans, Elyse Shapiro, Elizabeth Gillon-Zhang, Julia N. Brown, Candace King, Cory Kiser, Mary Beth Rossi, Darren Davis, Michelle L. Taylor, Jennifer Clower, Jian Yang, Cullen A. Taylor, Robert W. Snyder, Wendy J. Levin
Journal: Cancer Research (2024)

Abstract Advanced NSCLC treatment guidelines recommend testing patients for genomic biomarkers to utilize over 30 FDA-approved targeted therapies. A major challenge with current NGS-based testing methods is that ~45% of patient samples fail NGS quality control (QC), leading to inadequate patient care. The ASPYRE® technology addresses the urgent need for rapid, accessible and affordable diagnostics informing actionable genomic target variants. The ASPYRE-Lung® panel covers 114 variants in 11 genes (ALK, BRAF, EGFR, ERBB2, KRAS, RET, ROS1, MET &amp; NTRK1/2/3) to robustly inform clinical management, based on clinical practice guidelines. The assay concurrently detects single nucleotide variants, insertions, deletions, and gene fusions from NSCLC tissue-derived DNA and RNA. In this study, we investigated an NSCLC patient sample set from Precision for Medicine, including biobanked clinical specimens that had previously failed NGS QC, and for which genomic biomarker data were unavailable. 120 matched DNA and RNA biobanked NSCLC FFPE patient samples previously analyzed by Illumina TSO 500 were tested using ASPYRE-Lung in Biofidelity’s CLIA laboratory, including 94 samples which failed NGS QC parameters for DNA, RNA, or both, and 26 control samples which passed NGS QC. Samples were tested by ASPYRE-Lung using an input of 20 ng DNA and 6 ng RNA, except for 5 patient samples that were run at lower inputs, ranging from 4.25 to 14 ng DNA. Key findings:•Of the 94 patient samples that failed NGS QC, 98% of samples (92/94) passed ASPYRE-Lung QC and could inform patient care.•In the 92 patient samples that passed ASPYRE-Lung QC, 47% (43/92) had a detectable variant identified by ASPYRE-Lung.•All 26 control samples that passed NGS QC also passed ASPYRE-Lung QC.•Of the 5 samples with 4.25 to 14 ng DNA inputs to ASPYRE-Lung, data were generated on 4/5 samples and 2/4 had a detectable variant.•ASPYRE-Lung has the potential to provide actionable clinical information on patient samples deemed to be of insufficient quantity for NGS testing.ASPYRE-Lung has a high success rate, is easily adoptable and cost effective making it suitable as a first-line testing option, or for samples that are either QNS or fail NGS QC, and can provide a large fraction of NSCLC patients with actionable biomarker information, with potentially smaller tissue requirements. ASPYRE-Lung genomic testing is transformative for cancer care management, and allows more patients with NSCLC to benefit from effective and better tolerated therapies. Citation Format: Ryan T. Evans, Elyse Shapiro, Elizabeth Gillon-Zhang, Julia N. Brown, Candace King, Cory Kiser, Mary Beth Rossi, Darren Davis, Michelle L. Taylor, Jennifer Clower, Jian Yang, Cullen A. Taylor, Robert W. Snyder, Wendy J. Levin. ASPYRE-Lung addresses critical gaps in NGS-based biomarker testing: Robust variant calling from NGS QC fails [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB095.