Performance of a tissue-free, molecular residual disease assay in colorectal, breast, and lung cancers from circulating tumor DNA.

Abstract

3042 Background: The Latitude test is a methylation-based, tissue-free molecular residual disease (MRD) test. In this study, we describe the improved performance of the assay in colorectal cancer (CRC) and its performance in an expanded set of indications including breast and lung cancer. Methods: The methylation-based, tissue-free ctDNA assay uses next-generation sequencing to query differentially methylated genomic regions in patients with CRC, breast, and lung cancer compared to cancer-free individuals in order to classify plasma samples as MRD positive (MRD+) or MRD negative (MRD-). Performance was evaluated in patients with cancer: CRC (N = 214), breast (N = 153), and lung (N = 148) with known ctDNA-positive results from Signatera (tumor-informed ctDNA testing) across a range of variant allele frequency (VAF) ranges, and cancer-free individuals (training set N = 531, validation set N = 200). Performance metrics, such as percent positive agreement (PPA) and specificity, were evaluated using cross validation in the cancer and cancer-free cohorts, respectively. Results: Among 214 CRC patients (VAF range: 0.003%-4.5%), PPA was 95.94% and specificity among all 200 cancer-free individuals was 99.50%. Among 153 breast cancer patients (VAF range: 0.002%-7.8%), PPA was 91.81%, which was maintained across subtypes, including HR+ (94.75%, N = 40), HER2+ (94.45%, N = 20), and triple-negative (87.94%, N = 29). Among the 164 cancer-free females, specificity of the breast tissue-free assay was 98.18%. Among 148 lung cancer patients (VAF range: 0.003%-5.8%), PPA was 92.63%, maintained across subtypes, including non-small cell lung cancer (92.54%, N = 112) and small cell lung cancer (95.23%, N = 25). Among all 200 cancer-free individuals, specificity of the lung tissue-free assay was 99.50%. Conclusions: These data demonstrate a high concordance between the Latitude tissue-free MRD assay and a clinically validated tumor-informed ctDNA assay across CRC, breast, and lung cancers, supporting the use of methylation-based biomarkers for informing prognosis and patient management.