Single digit parts per million detection of molecular residual disease through integrated tumorinformed whole-genome sequencing analysis

Assessing molecular residual disease (MRD) through liquid biopsy for circulating tumor DNA (ctDNA) is a promising area of development in clinical cancer research, evaluates MRD through assessment of ctDNA in patients diagnosed with earlystage, solid tumor malignancies. Here we present results from proof of concept and feasibility optimization studies showing implementation of Labcorp Plasma Detect^TM (LPD) on the Ultima Genomics UG 100 sequencing platform (LPDv2), providing a 13.3-fold improvement in sensitivity over the current implementation in LPDv1. LPD utilizes a tumor-informed signature derived from circulating tumor DNA (ctDNA) through bioinformatic subtraction of patient-specific germline single nucleotide polymorphisms (SNPs) and mutations arising from clonal hematopoiesis. The LPD assay first establishes a Landmark baseline tumorinformed DNA signature via whole genome sequencing (WGS) of DNA from paired tumor (T: formalin-fixed paraffin-embedded (FFPE)) and normal samples (N: buffy coat). Using this tumorinformed signature and if present, ctDNA is subsequently detected in cell-free DNA (P: cfDNA derived from plasma) at prespecified Longitudinal timepoints.