MRD assay to evaluate recurrence and response via a tumor-informed assessment: MARIA-Breast observational trial

TPS622 Background: The recognition that cancers release nucleic acids into the peripheral circulation of the patient has enabled a new paradigm for disease detection and surveillance. Detectable ctDNA in patients with solid tumors has been associated with disease prognosis pre-treatment, assessing response to therapy in the form of minimal residual disease (MRD), and monitoring for recurrence after curative intent treatment. Utilizing patient-specific genomic mutation profiling of an individual’s cancer from a tissue sample, in conjunction with the patient’s germline DNA, to create a personalized sequencing panel to then systematically analyze for a subset of these genetic mutations from ctDNA in blood is a strategy that has high sensitivity in detection of MRD. Studies have shown that pretreatment levels of ctDNA using this approach are a potential early indicator of disease recurrence after surgery, that ctDNA clearance may be an early predictor of favorable outcomes and have been shown to correlate with pathologic complete response (Forde et al. N Engl J Med. 2022, PMID:35403841), and that this approach has high sensitivity in its ability to detect recurrence for patients in advance of the current standard of care (Abbosh et al. Cancer Res (2020) 80 (16_Supplement): CT023). Methods: This is a multi-site, prospective, observational trial in the United States of 200 patients with early stage breast cancer undergoing curative intent treatment, who have FFPE tissue available from resection sufficient for a patient-specific bespoke MRD assay who are willing to provide serial whole blood specimens for ctDNA analysis. Participants are asked to provide study specimens prior to initial treatment intervention, after curative intent surgical resection, during adjuvant therapy (as applicable) and pre-recurrence follow-up. ctDNA will be analyzed with an NGS-based, tumor-informed MRD assay that identifies somatic mutations from DNA obtained from the patient’s tumor tissue, subtracts germline variants via NGS-based analysis of the patients germline DNA, and detects a selected set of between 18-50 tumor-specific ctDNA in their blood. All primary tumor specimens will undergo full exome sequencing using the Personalized Cancer Monitoring (PCM) assay. Impact of results of this CLIA-approved MRD assay on clinical decision making will be captured. The primary objective is to assess the ability of MRD to predict post-treatment recurrence. Further objectives are to correlate MRD status with pathologic complete response, determine the lead time to detection of recurrence compared to standard of care, and the association of MRD status with overall survival. Active enrollment started in March, 2022. Clinical trial information: NCT05219734 .