Sagittarius · A PRECISION MEDICINE TRIAL LEVERAGING BLOOD-BASED TUMOR GENOMICS TO OPTIMIZE TREATMENT IN OPERABLE STAGE III AND HIGH-RISK STAGE II COLON CANCER PATIENTS - THE SAGITTARIUS TRIAL

SAGITTARIUS aim to optimize the clinical management of locoregional stage II high-risk/stage III colon cancer (LRCC). Approximately half of all LRCC patients relapse within two years from time of curative surgery because of imaging-undetectable micro-metastatic residual disease (MMRD). Given the lack of reliable predictors of individual risk, LRCC patients are treated with a one-fits-all adjuvant chemotherapy. This gunshot approach results in either over- or under-treatment. Measuring circulating tumor DNA (ctDNA) in the patients’ bloodstream can diagnose MMRD. Retrospective studies show that ctDNA detection after surgery predicts cancer recurrence with high sensitivity and specificity. SAGITTARIUS will deploy a ctDNA assay to detect the absence, presence, or persistence of MMRD in individual patients. The diagnosis of MMRD will guide and personalize therapeutic interventions. SAGITTARIUS is a pragmatic trial whereby real-world patients are treated in two parallel trials based on their MMRD status and the genomic landscape of their tumors. ctDNA positive patients are randomized to conventional or personalized targeted therapy. ctDNA negative patients are randomized to a physician-driven therapy or a Wait&See strategy. The efficacy and effectiveness of this potentially ground-breaking new strategy of care will be measured via multiple outcomes, including safety and time to events variables, patient-reported outcome measures, and health-economics evaluation. Since colon cancer deaths are usually associated with metastases rather than local disease, MMRD will also reclassify how this disease is perceived by clinicians. This new prism will allow for treatment to be better matched against the tumor biology, also allowing for better monitoring – via ctDNA – to assess disease evolution in each patient, minimizing harm and maximizing the odds of cure. This action is part of the Cancer Mission cluster of projects on ‘Diagnosis and treatment.