Xtalks Webinar DEC 17, 2020:
NeXT Liquid Biopsy: A High-Performance, Exome-Wide Liquid Biopsy Assay to Study Tumor Dynamics


Sean M. Boyle
Dan Norton

DEC 17:  8 am EST and 4 pm EST 

Title: NeXT Liquid Biopsy: A High-Performance, Exome-Wide Liquid Biopsy Assay to Study Tumor Dynamics  
Presenters: Sean M. Boyle, PhD and Dan Norton, MBA

NeXT Liquid Biopsy™, a first-of-its-kind, high-performance exome-wide liquid biopsy assay, is designed to complement ImmunoID NeXT™, providing a unique ability to further evaluate the cancer ecosystem, and advance the development of next-generation therapies. While solid tumor biopsies remain the standard for the interrogation of the cancer genome, the advent of liquid biopsies and multi-region tissue sampling has demonstrated that there can be more to a cancer’s genotypic profile than that found in a single tissue biopsy. Therefore, the combination of NeXT Liquid Biopsy and ImmunoID NeXT delivers the most comprehensive view of a cancer’s mutational landscape by evaluating both the tissue and the blood.

NeXT Liquid Biopsy enables investigation into key applications such as spatial and temporal heterogeneity of the tumor, clonal evolution and tumor dynamics in response to therapies, and mechanisms of acquired resistance. NeXT Liquid Biopsy is purpose-built to navigate the inherent variability of circulating tumor DNA (ctDNA), elucidating key areas of tumor biology not often addressed by targeted, commercially-available liquid biopsy panels.

To enable sensitive variant detection across 20,000 genes, our enhanced exome assay and chemistry achieves high sequencing depth of approximately 2,000X exome-wide, with additional boosted depth, 5000x, for 247 cancer-related genes. We developed a computational pipeline optimized to lower the noise floor for variant detection, providing sensitive monitoring and de novo detection of variants over multiple time points.

We evaluated the performance of our NeXT Liquid Biopsy platform in three ways. First, we assessed sensitivity. Analyzing SeraCare reference materials at multiple allele frequency (AF) dilutions, our platform identified all 25 SNVs at 1% AF and above present in the reference, and detected 24 out of 25 events at 0.5% dilution. To evaluate sensitivity at the whole-exome scale, we developed a cell culture media system that models the shedding of tumor DNA fragments seen in human plasma samples. We achieved >95% sensitivity for variants with AF>=2%, and between 85% to 92% for variants with AF of 1%-2%. Second, we estimated false-positive rates on a set of plasma samples using digital droplet PCR. Lastly, we demonstrated our ability to longitudinally monitor treatment response using a clinical cancer cohort on checkpoint therapy, profiling putative tumor evolution while on therapy.

In this presentation, we’ll highlight data demonstrating the genomic profiling and assay performance enabled by NeXT Liquid Biopsy through the evaluation of various reference standards and actual patient samples.