911P The development and application of a baseline-agnostic minimal residual disease assay

Liquid biopsy has become increasingly important in cancer diagnosis and disease progression monitoring. Personalized ctDNA detection for monitoring treatment efficacy and minimal residual disease (MRD) has been extensively studied due to its high detection sensitivity. However, a baseline sample is often lacking in the clinic. The goal of this study is to develop PredicineALERT, a multi-dimentional baseline-agnostic MRD assay. PredicineALERT is a baseline-agnostic MRD assay, including a targeted panel covering hotspot mutations and important cancer genes, PredicineCNB (a companion LP-WGS assay for copy number burden), and PredicineEPIC (a whole genome methylation assay). The analytical evaluation was based on titration of real-world clinical patient samples. Titration ratios ranged from 10% down to 0.0025% tumor fractions. DNA input amounts ranged from 30ng down to 1ng. The clinical evaluation was based on longitudinal samples from patients with different cancer indications, including mCRPC, CRC, breast cancer and NSCLC. PredicineALERT has been tested using plasma samples from 80 patients with mCRPC, CRC, breast cancer and NSCLC. The PredicieALERT assay demonstrated the high detection sensitivity (LOD < 0.01%) using 30ng input cfDNA. Further, PredicineCNB measures the copy number burden suitable for treatment response monitoring. PredicineEPIC measures the whole genome methylation profile. It has the advantage of low DNA damage and low input amount (down to 1ng). Concordance was observed between the pattern of CNB and methylation in most patient samples, with methylation providing the additional advantage of more robust and sensitive detection of cancer signals in general. In conclusion, the PredicinceALERT MRD assay demonstrates the successful implementation and application of a baseline agnostic, multiple-dimentional assay by integrating mutations, genome-wide copy number and DNA methylation. The results highlight advantages of this multi-faceted assay and serve as a guide for future clinical applications in MRD setting.