Analytical Validation of the Labcorp Plasma Complete Test, a Cell-Free DNA Comprehensive Genomic Profiling Tool for Precision Oncology

Abstract

To help guide treatment decisions and trial matching, tumor genomic profiling is an essential precision oncology tool. Liquid biopsy, a complementary approach to tissue testing, can assess tumor-specific DNA alterations circulating in the blood. Labcorp Plasma Complete is a next-generation sequencing, cell-free DNA comprehensive genomic profiling test that identifies clinically relevant somatic variants across 521 genes in advanced and metastatic solid cancers. Over 800 unique sequencing libraries across 27 cancer types were evaluated to establish analytical sensitivity, specificity, accuracy, and precision, reproducibility, and repeatability (PRR). Sensitivity was verified for each variant type, with a median variant allele frequency (VAF) of 1.25% and 1.27% for panel-wide single nucleotide variants (SNVs) and insertions/deletions (indels) (sequence mutations), respectively, with <1% VAF sensitivity observed for clinically actionable variants, 1.72-fold for copy number amplifications (CNAs), 0.48% fusion read fraction for translocations, and 0.47% sequence mutation VAF for microsatellite instability-high (MSI-H). Specificity was 99.9999% for SNVs and 100% for other variant types. PRR resulted in 94.9% average positive agreement (APA) and 99.9% average negative agreement (ANA) for sequence mutations and 100% APA and ANA for CNAs, translocations, and MSI-H. Orthogonal assays were utilized to assess accuracy, demonstrating concordance of 97.4% positive percent agreement and >99.99997% negative percent agreement across all variants. Overall, the test demonstrates high sensitivity, specificity, accuracy, and robustness to enable informed clinical decision-making.