Abstract 2298: Ultra-sensitive tumor-informed ctDNA assay predicts survival in advanced melanoma patients treated with immune checkpoint inhibition

• Published in: Cancer research (Chicago, Ill.) Ill.), 2023-04, Vol.83 (7_Supplement), p.2298-2298
• Main Authors: Keller, Laura, Heidrich, Isabel, Kött, Julian, Abbott, Charles W., Boyle, Sean, Pugh, Jason, Chen, Richard O., Geidel, Glen, Ronald, Simon, Schneider, Stephan W., Gebhardt, Christoffer, Pantel, Klaus
• Format: Article
• Language: English
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2023-2298

Introduction: Immune checkpoint inhibition (ICI) elicits clinical benefit in a subset of cancer patients and monitoring of ctDNA in peripheral blood might improve our ability to predict responses or resistance earlier than imaging. Here, we analyzed melanoma patients receiving ICI over several years using a novel tumor-informed ctDNA platform, and correlated the findings to clinical outcome. Methods: Plasma from 23 advanced melanoma patients was collected at ICI treatment cycles for up to 1,200 days and retrospectively profiled using NeXT Personal™ in this research study. NeXT Personal is a tumor-informed liquid biopsy assay that leverages whole-genome sequencing of tumor/normal samples to generate a personalized liquid biopsy panel for each patient consisting of up to 1,800 selected variants to enable ultra-sensitive molecular residual disease (MRD) detection down to 1-3 parts per million (PPM). Each bespoke panel also covers a fixed set of >2,100 known clinical and resistance loci for detecting variants emerging under therapeutic pressure. We compared NeXT Personal results with imaging and RECIST assessments for each patient. Results: Results showed ultra-high sensitivity for ctDNA with a wide dynamic range of detections from approximately 100,000 PPM down to 2.3 PPM. The median limit of detection was 1.97 PPM. Excluding patients with recent second-line therapy, 94% (17/18) of baseline samples were ctDNA positive (ctDNA+), including all patients who progressed. 37% (22/59) of on-treatment ctDNA+ detections were