Abstract 5036: Analytical and clinical validity of Northstar Select, a quantitatively enhanced liquid biopsy assay for comprehensive genomic profiling of solid tumors

Abstract

Abstract Background: Liquid biopsy assays have emerged as vital tools in precision oncology. Among these assays, Comprehensive Genomic Profiling (CGP) tests in particular have improved treatment selection for late-stage solid tumor cancer patients by allowing for the detection via circulating tumor DNA (ctDNA) of somatic mutations in the tumor, many of which have corresponding targeted therapies. However, technical restrictions in the performance of such tests have limited their utility when ctDNA signal is low. BillionToOne’s Northstar Select assay is a new CGP test that achieves increased performance by addressing these limitations. Innovation: By using Quantitative Counting Template (QCT) technology, Northstar Select is able to track the yield of multiple processing steps, contributing to the higher sensitivity of the assay by maximizing the number of decoded molecules after sequencing. In addition, it employs chemistry and panel design optimizations, as well as novel algorithms for SNV, indel, CNV, fusion, and MSI calling to increase sensitivity and specificity. Analytical Performance: The performance of Northstar Select surpasses that of other commercially available tests for multiple mutation types, detecting more pathogenic and actionable mutations at low tumor DNA fraction while maintaining similarly high specificity. In analytical validation (N=103), limit of detection was determined to be 0.13-0.16% variant allele fraction (VAF) for SNVs and indels, 2.11 copies for copy number amplifications, 1.8 copies for copy number losses, 0.35% VAF for fusions, and 0.07% tumor fraction for MSI. Clinical Performance: Northstar Select was determined to have high clinical utility as well, with a study of clinical samples (N=481) from a variety of tumor types yielding <2% of reports with 0 mutations detected. A head-to-head comparison with other commercial liquid biopsy assays on a subset of the clinical samples (N=192) showed that the assay detected 115 additional pathogenic mutations in total, leading to a higher proportion of patients with at least one pathogenic mutation detected (90%) compared to comparators (79%). Conclusion: These results demonstrate that the Northstar Select assay is an innovative and high-performing diagnostic for treatment selection in oncology, leveraging quantitative approaches in process design, chemistry, and bioinformatics to offer superior analytical and clinical performance compared to the current landscape of liquid biopsy CGP tests. Citation Format: Xavier Bower, Jan Wignall, Joyce Zhu, Naomi Searle, Matthew Varga, Emilio Rosas-Linhard, Jason Luong, Esther Lin, Marie Simon, John ten Bosch, Wen Zhou. Analytical and clinical validity of Northstar Select, a quantitatively enhanced liquid biopsy assay for comprehensive genomic profiling of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5036.