The FNIH Biomarkers Consortium initiated a public-private partnership (PPP) to assess new methods of evaluating MRD and response to AML. The project has established a library of reagents for assay development and an assay network for testing new technologies. This presentation will describe steps to support MRD as a validated surrogate endpoint in AML as well as other FNIH efforts design and build standards for liquid biopsy tools.

Successful implementation of Precision Oncology requires accurate and timely biomarker data to inform patient treatment strategies. Blood-based testing has many intrinsic advantages over tissue-based testing. The FDA has approved 5 plasma-based CDx assays for treatment selection. New applications, such as early cancer detection and molecular residual disease, are in development with the body of clinical evidence and reimbursement, which will lead to greater adoption of liquid biopsies. Trial designs and results from recent studies will be discussed, along with how this data is moving the needle in favor of liquid biopsy for optimal Precision Oncology outcomes.

Both liquid and tissue biopsies are exploitable for molecular profiling that enables a precision oncology strategy. Liquid biopsies are mainly “blood” biopsies, but other fluids—ascites, pleural fluid, and cerebrospinal fluid—can also be sampled. Both tissue and liquid biopsies yield DNA for next-generation sequencing. Liquid biopsies can also be interrogated in other ways as well, examining also circulating tumor cells (CTCs) for DNA, RNA, protein, and functional assays.

Cell-free circulating tumor DNA (ctDNA) assays have been adopted to monitor therapeutic response in both early- and late-stage cancer. However, tests currently available require deep-targeted sequencing to detect cancer-specific mutations at low mutant allele frequency (MAF) levels in the circulation. Recently, we developed a tumor-agnostic approach called DELFI Tumor Fraction (DELFI-TF), a Bayesian probabilistic model designed to predict plasma tumor fractions based on genome-wide fragmentation-related features.

Checkpoint inhibitor immunotherapy(CII) has provided significant benefits in improving outcomes of metastatic cutaneous melanoma patients. One of the major problems to date is early identification of treatment responses. We applied a unique ddPCR assay to monitor ILF2 amplification as a cfDNA biomarker to monitor melanoma patients before, during, and post treatment in AJCC stage III/IV patients. The assay can identify real-time status of patients disease status and responses. In parallel, tumor biopsy were assessed to identify level of ILF2 amplification; this was shown to correlate to tumor metatastasis progression. Various types of approved CIIs were assessed in melanoma patients.