Cell-free microRNA (cfmiR) assessment of blood offers opportunities to monitor early detection of cancer and monitor cancer patients during progression and treatment. We have used a platform assessing >2000 miR using an NGS-based assay. The assay demonstrated the sensitivity and specificity of the cfmiR detection in multiple types of solid tumors that include GBM, melanoma, renal, breast, and prostate cancers. cfmiR provides an alternative molecular biomarker to assess MRD in early- and late-stage solid tumor progression. These cfmiR analyses offer alternatives to cancer cfDNA patient analysis in detection of MRD.

This session will provide an overview of the FNIH Biomarker Consortium’s Measurable Residual Disease (MRD) projects, including successes in Acute Lymphoblastic Leukemia and Multiple Myeloma, and new programs in Acute Myeloid Leukemia and MGUS. MRD will be discussed in context of FNIH efforts to support widespread use of liquid biopsy, including the design and development of quality control materials for ctDNA testing. Efforts to support effective clinical research and therapeutic decision-making, and coordination with regulatory oversight, will be discussed in coordination with the International Liquid Biopsy Standardization Alliance (ILSA) and the development and objectives of this FDA recognized Collaborative Community.

Liquid biopsies could improve cancer care but require higher sensitivity. Here, I will describe our team’s efforts to push DNA sequencing to its limits and overcome the massive in vivo bottlenecks that constrain cancer detection. I will present (i) clinical validation of MAESTRO mutation enrichment sequencing for MRD, (ii) development of CODEC 'single duplex' sequencing, and (iii) proof-of-principle for the first liquid biopsy priming agents: injections to improve cancer detection.

ctDNA-based MRD has many utilities for solid tumor indications across the patient journey and in supporting drug development. Currently, challenges remain to integrating MRD in a clinical setting, including gaps in existing guidance and a lack of standardization around assays and studies. The efforts of consortia can provide value in moving the validation, implementation, and standardization of MRD assays forward in the clinical setting.

Minimal residual disease (MRD) is defined as evidence for the presence of persisting cancer cells below the threshold of conventional methods for disease detection. While MRD testing has clear prognostic utility and is increasingly adopted as a surrogate endpoint for drug efficacy, modalities, thresholds, and standards vary considerably. Here, we focus on the landscape of molecular MRD testing, utility in drug development, and efforts to standardize such as through BloodPAC.

The precision medicine era has ushered in an abundance of analytically valid assays for tumor-specific biomarkers. This profusion of novel assays confounds the selection of the optimal technologies to advance towards clinical validation, the dedicated sequence of trials needed to demonstrate that the biomarker for the purpose of a specific context of use. Deciding factors include an assay’s performance and potential utility for the patient population with the unmet need.

Circulating tumor DNA (ctDNA) has become the focal point of molecular diagnostics development in oncology due to its various clinical applications in cancer care management and its relative ease of sample collection and use. Regulatory-approved liquid biopsies using ctDNA have been available for several years, but they have not been widely adopted in clinical practice. We will review the current and expected clinical adoption of this practice-changing cancer diagnostics tool.

Human Leukocyte Antigen (HLA) loss of heterozygosity (LOH) is a mechanism of resistance to immunotherapy modalities that involve T-cell recognition and killing of cancer cells through T-cell receptor (TCR) engagement with peptide-MHC complexes. These immunotherapy modalities include immune checkpoint inhibition (ICI), engineered-TCR T cells, tumor-infiltrating lymphocytes (TIL), and bispecific antibodies. A liquid biopsy assay for detecting HLA LOH in cancer patients will be presented, along with results from validation experiments.

Significant advances have been made in ctDNA detection in oncology. ctDNA analysis offer advantages such as minimally invasive collection, easily repeatable collection, being representative of all cancer lesions and representing tumor heterogeneity. This presentation will focus on various clinical applications of ctDNA as a biomarker with examples and discuss opportunities and challenges of integrating ctDNA-based biomarkers into clinical trials with respect to patient selection, patient stratification, response, and resistance monitoring.

Circulating tumor DNA (ctDNA) has been used for prognostication and treatment monitoring. We evaluated ctDNA as potential biomarker for response to lorlatinib, a third-generation ALK inhibitor in patients with previously untreated ALK-positive advanced NSCLC in the ongoing Phase 3 CROWN study (NCT03052608). Molecular responses were calculated using mean variant allele frequency (VAF), longitudinal change in VAF, and ratio to baseline, and analyzed for association with clinical outcome parameters (progression-free survival [PFS]). Comparing molecular responders vs non-responders to lorlatinib, responders had longer PFS (HR, 0.37; 95% CI, 0.16-0.85). Early ctDNA dynamics predicted better outcomes with lorlatinib.