Abstract 4105: External user testing of Biofidelity’s ASPYRE-Lung assay demonstrates breakthrough capabilities and ease of use

Abstract

Introduction: While the FDA has approved over 20 targeted therapies for non-small cell lung cancer (NSCLC), less than half of patients in the US undergo comprehensive biomarker testing to determine if they would benefit from these agents. This gap in testing is compounded in ex-US and minority populations. There are multiple barriers to access for biomarker testing, many of which stem from the complexity and high costs of current solutions, which limit testing to large, centralized laboratories. Alongside this, tissue requirements are high, turnaround times (TAT) for results typically take weeks, and reimbursement is uncertain. We demonstrate how ASPYRE can address these limitations by enabling ultra-sensitive biomarker testing using existing staff and widely available instrumentation. The technology is based on four enzyme steps (Silva et al 2020), the last of which is monitored on a real-time PCR instrument. ASPYRE-Lung targets 111 markers in 11 genes, including 77 DNA variants (substitutions and indels), and 34 RNA variants (fusions and exon skipping) across 24 wells, with a TAT of less than <4 hours from extracted nucleic acids to result. Experimental procedures: Four test sites were provided with ASPYRE reagents and contrived samples including Seracare ctDNA Mutation Mix v2 and a panel consisting of synthetic RNA oligonucleotides diluted in a background of normal lung RNA. The Seracare sample included variants in BRAF, EGFR, ERBB2, and KRAS at 0.25% variant allele fraction. The RNA sample included fusions in RET, ROS1 and NTRK1, with each fusion present at a mean of 6 copies in a background of 1 ng lung RNA. Operators from a range of educational backgrounds were provided a set of written Instructions for Use, with no additional training. Summary of data: The ASPYRE-Lung test was set up and performed at each test laboratory in as little as one day, using their existing real-time PCR instrument. The results demonstrated detection of the expected variants with consistent performance characteristics across the test sites and between users. Importantly, the sensitivity of detection was in line with, or superior to, the current gold standard. Conclusions: Biofidelity’s breakthrough ASPYRE technology enables a dramatic simplification of workflows, and the ultra-sensitive detection of actionable biomarkers using existing real-time PCR instruments. This work has demonstrated the ease with which independent laboratories can implement comprehensive multi-gene assays based on ASPYRE technology, utilizing their existing staff and infrastructure. This stands in stark contrast to alternative solutions, which typically require substantial investments in new instrumentation, skilled staff, IT infrastructure and bioinformatics. Taken together, ASPYRE promises to remove key barriers in cancer biomarker testing, enabling all patients to access the right treatment at the right time. Citation Format: Paulina Powalowska, Nicola Potts, Brandon A. Smith, Kala F. Schilter, Honey V. Reddi, Lan Beppu, Jerald Radich, Charles Massie, Quentin Vicentini, Tom Brown, Robert Osborne, Barnaby Balmforth. External user testing of Biofidelity’s ASPYRE-Lung assay demonstrates breakthrough capabilities and ease of use [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 4105.