Analytical validation of the Labcorp Plasma Complete test to enable precision oncology through solid tumor liquid biopsy comprehensive genomic profiling.
Authors: Verner Ellen , Valkenburg Kenneth C. , Maddox Cynthia , Gerding Kelly , Occean James , White James R , Morris Laine , Jackson Nesha , Dillon Sonomi , Jackson Jennifer B , Sausen Mark , Severson Eric A , Jensen Taylor J. , Eisenberg Marcia , Caveney Brian , Ramkissoon Shakti H , Greer Amy 
Published: June 2024

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Background: To help guide treatment decisions and enable clinical trial matching for cancer patients, tumor genomic profiling is an essential precision oncology tool. Liquid biopsy may be used as a complementary approach to assess tumor-specific DNA alterations circulating in the blood. The Labcorp Plasma Complete test is a next-generation-sequencing (NGS), cell-free DNA (cfDNA) comprehensive genomic profiling test that identifies actionable and clinically relevant variants in advanced and metastatic solid cancers across 521 genes. Methods: The Labcorp Plasma Complete test is a hybrid capture based, targeted NGS test, optimized for 25 ng of cfDNA input and is intended for variant detection in all solid cancer indications. The test interrogates all coding exons of 521 genes to comprehensively detect single nucleotide variants (SNVs) and insertion and deletions (indels). The test also reports copy number amplifications (CNAs) and gene translocations in 12 genes, and microsatellite instability (MSI). In total, 631 cancer patient plasma samples were evaluated by the test including lung, breast, colorectal, head and neck, pancreatic, gynecologic, and prostate cancers among other indications. Well-characterized reference samples (Genome in a Bottle) were utilized to assess analytical specificity. Contrived cell lines and clinical samples were utilized to establish analytical sensitivity, accuracy, as well as precision, reproducibility, and repeatability (PRR). Results: The test yielded results for 98.3% (620/631) of cases and identified variants in 94.7% (587/620) with a median of 6 variants per case. Clinically actionable variants were detected in 42.1% of clinical samples. Analytical specificity was ≥99.9999% for SNVs and 100% for indels, CNAs, translocations, and MSI. Analytical sensitivity (limit of detection, 95%) was verified for each variant type, with a median variant allele frequency (VAF) of 1.42% for SNVs and 1.43% for indels, 1.7-fold for amplifications, 0.35% fusion read fraction for translocations, and 0.82% VAF for MSI. The intra-laboratory PRR study resulted in 94.9% average percent agreement (APA) and 99.9% average negative agreement (ANA) for sequence variants (SNVs and indels) and 100% APA and ANA for CNAs, translocations, and MSI. Orthogonal assays including other NGS tests and digital PCR were utilized to assess Labcorp Plasma Complete accuracy which demonstrated an aggregate analytical concordance of 96.28% positive percent agreement and >99.9999% negative percent agreement for all variants. Conclusions: The analytical validation of the Labcorp Plasma Complete test demonstrates that the liquid biopsy approach is highly sensitive, specific, accurate, reproducible, and robust for comprehensive genomic profiling to complement tissue-based testing and inform clinical decision making.