Abstract 3670: Reducing the patient burden for ctDNA biomarkers: Advancing small volume home-based collection technologies

Abstract There is broad consensus from regulatory agencies, clinicians and patients for the need to move to decentralized trials while focusing on patient-centric approaches with the COVID-19 pandemic being the catalyst. This requires the development of new sample collection capabilities and workflows to ensure that the necessary biomarkers can be measured. Circulating tumor DNA (ctDNA) has become an increasingly important biomarker for cancer detection and genetics, and monitoring patients during treatment. Typical measurements of ctDNA involve venous draws of 10mls of whole blood that require patients to be in clinic. Here, we test the feasibility of using a new collection device, Tasso+, to collect capillary blood for ctDNA analysis using the Guardant360 panel. A pilot of whole blood microsamples (1 mL) with a cfDNA yield of 0. 7-1. 4 ng/ml spiked to 0. 5% MAF with Seraseq ctDNA reference material. This resulted in detection of ~20% of the total expected variants across variant classes showing the feasibility of using the G360 panel to detect low volume/low MAF samples. Initial testing of Tasso+ collected samples revealed a 5-10x increase in high MW gDNA compared to traditional venipuncture. SPRI bead-based size selection was used in the extraction protocol to remove 95% of the high MW DNA, resulting in a 35% loss of target cfDNA fraction. Traditional venipuncture samples and Tasso+ samples were collected from 5 cancer patients and run using the G360 platform. Microsamples detected 75% of the variants across all variant classes found in venipuncture samples. Tasso+ lost sensitivity of variants when the MAF was 0. 5%. To expand usage of Tasso+ to at-home collection of blood for ctDNA analysis, we sought to determine if lyophilization of the Streck DNA BCT RUO tube reagent could still provide stability to samples and a potential framework for at-home collections. Venipuncture and Tasso+ samples were collected from control patients, pooled and spiked with Seraseq cfDNA reference material. Samples were aliquoted into standard liquid Streck tubes or tubes with lyophilized reagent at the concentration per manufacturer’s directions and evaluated for stability over time. The Tasso+ samples with a target MAF between 0. 5%-2. 0% detected ~26% of all variants compared to the standard samples with a similar MAF. Lyophilization of the Streck reagent had minimal effect (20% reduction in variants detected) on the reagent’s performance as there were approximately an equal number of total variants detected when comparing liquid and lyophilized samples for both the standard tubes and Tasso+ samples. Overall, these results provide support and a framework for using a home-based patient-centric sampling approach for monitoring ctDNA from cancer patients in clinical development. Citation Format: Brad R. Evans, Robert J. Foley, Steven M. Townson, Emily J. Welch, Kevin P. Bateman. Reducing the patient burden for ctDNA biomarkers: Advancing small volume home-based collection technologies 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 (6Suppl): Abstract nr 3670.