Abstract 5034: Analytic validation of an ultra-sensitive tumor-informed circulating tumor DNA assay based on whole genome sequencing

Abstract Monitoring of circulating tumor DNA (ctDNA) levels has demonstrated utility in the detection of residual and recurrent disease after tumor resection, and as a prognostic indicator of patient outcome following initial therapy, in a wide range of cancers. Here we describe the analytic validation of the NeXT Personal® assay, an ultra-sensitive, quantitative, tumor-informed ctDNA assay for use in patients diagnosed with solid tumors. NeXT Personal utilizes whole genome sequencing (WGS) of tumor and normal samples and advanced noise suppression to accurately identify somatic variants and generate a patient-specific diagnostic panel based on up to ~1,800 single nucleotide variants. This personalized panel is used to test for the presence of ctDNA in the patient’s blood samples. The NeXT Personal validation was performed using 123 matched tumor, normal and plasma clinical sample sets representing 9 cancer types. The assay achieved 100% specificity on donor normal plasma samples with an in silico approach giving us a confidence interval of 99.87% to 100%. The analytical range measurements were performed using two paired tumor and normal cell lines, one of which is a commercially available MRD control. The detection threshold for the analytical range measurement was 1.68 parts per million (PPM) with a limit of detection at 95% (LOD95) of 3.52 PPM. Furthermore, NeXT Personal showed linearity over a range of 0.8 PPM to 300,000 PPM (Pearson correlation coefficient= 0.9998) with a limit of quant (LOQ) of 10 PPM. The assay also demonstrated strong performance across varying cfDNA input amounts from 2 ng to 30 ng. These studies demonstrate that NeXT Personal is an ultra-sensitive, highly specific, quantitative and robust assay, giving it the potential to detect residual disease and recurrence earlier than less sensitive assays. Citation Format: Josette Northcott, Gabor Bartha, Jason Harris, Shuyuan Ma, Manqing Hong, Qi Zhang, Richard Chen, John Lyle. Analytic validation of an ultra-sensitive tumor-informed circulating tumor DNA assay based on whole genome sequencing [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 5034.