MRD assay to evaluate recurrence and response via a tumor informed assessment: MARIA-Colorectal Cancer Observational trial.

Abstract

TPS242 Background: The detection of ctDNA in patients with colorectal cancer (CRC) is emerging as a potential biomarker to identify patients at high risk of relapse, assess treatment response and monitor for recurrence. Solid tumors are currently monitored by imaging studies, tumor markers and clinical symptoms and recent studies suggest tumor-informed molecular residual disease (MRD) testing may outperform these current methods and may serve as a prognostic biomarker to aid in the identification of patients at high risk of relapse (Reinert et al, 2019; Christensen et al, 2019; Coombes et al, 2019). Recent studies have demonstrated that tumor-informed MRD testing can detect relapse prior to detection with imaging in CRC and while interventional trials are needed, this may provide an opportunity for therapeutic intervention (Reinert et al, 2019; Kotani et al, 2023). This study utilizes the Invitae Personalized MonitoringTM (PCM) test, a highly sensitive tumor-informed MRD test (Zhao et al, 2023), to monitor early stage CRC patients. Methods: MARIA is a multi-site, prospective, observational trial in the United States of 200 newly diagnosed patients with early stage (high risk stage II, stage III and stage IV oligometastases) CRC undergoing curative intent treatment. Formalin fixed paraffin embedded (FFPE) tissue from the biopsy or surgical specimen is utilized to create the PCM test. Tumor tissue and a matched normal blood sample will undergo whole exome sequencing to identify 18-50 unique tumor variants to create a patient specific panel (PSP) for ctDNA analysis. Participants are asked to provide serial plasma specimens for ctDNA analysis at baseline, post surgical landmark and surveillance time points. A clinical report will be provided to the ordering physician. Physicians will be asked to complete a case report form for each participant when the first result is reported and every 6 months. The primary endpoint is to evaluate the correlation between the PCM test result at the landmark timepoint and the patient’s 24 month recurrence risk. Secondary endpoints include evaluating the impact on patient outcomes attributable to MRD result-based changes to treatment or clinical management, correlating between the PCM result at the baseline time point and patient recurrence risk and outcomes and investigating the lead time of PCM positivity over clinical/imaging based evidence of recurrence. Active enrollment started in March, 2022. Clinical trial information: NCT05219734 .