Abstract IA08: Use of liquid biopsy to facilitate drug development in early-stage disease—FDA perspective

Abstract

Abstract Background: With advances in precision oncology, liquid biopsies have shown promise as a minimally invasive means to potentially diagnose cancer, detect resistance mutations and monitor tumor evolution, predict relapse, provide prognosis, and guide treatment decisions. One unique setting for the use of liquid biopsy to facilitate drug development is in early-stage disease where there is the potential for use in patient selection, prognostication, and drug activity demonstration. Discussion: From the regulatory and clinical trial perspective, liquid biopsies can be used as prognostic biomarkers to identify the likelihood of disease recurrence in early-stage cancer. For example, circulating cell-free tumor DNA (ctDNA) in an adjuvant cancer setting affords the potential to select a high-risk population that could be utilized as a stratification factor, or selection of an enriched high-risk population in which specific drug development could be pursued. Use of liquid biopsy as a putative surrogate endpoint or efficacy-response biomarker, in this setting, would require a large body of evidence demonstrating biologic plausibility, demonstration of studies of prognostic value of the surrogate endpoint for the clinical outcome, and evidence from clinical trials (or meta-analysis) that the treatment effects on the biomarker correlate to the long-term outcome. Another use of liquid biopsy as an efficacy-response biomarker could allow for go or no-go decision making earlier on in drug development, which could also be applied in the adjuvant setting. Conclusions: Liquid biopsies will continue to play a role in the clinical management of malignancies and have the potential to support drug approval and become more broadly incorporated and utilized in early-stage clinical trials. Citation Format: Julia A. Beaver. Use of liquid biopsy to facilitate drug development in early-stage disease—FDA perspective [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA08.