Precision-MRD: Prospective Observational Study of Biomarker-directed Systemic Therapy for Colorectal Cancer Patients With Minimal Residual Disease

Inclusion Criteria 1. Male or female subjects aged \> 18 years. 2. Histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma. 3. Stage II-IV disease per current AJCC staging criteria with no definitive radiographic evidence of disease following locoregional treatment. Small indeterminate lesions measuring \< 10 mm may be permitted at the discretion of the principal investigator. 4. Presence of one of the following targetable biomarkers on tumor or blood molecular testing: BRAF V600E mutation (Cohort A), KRAS G12C mutation (Cohort B), MSI-H status (Cohort C), and HER2 amplification (Cohort D). 5. Positive ctDNA blood test obtained \> 21 days after surgery or last administration of adjuvant therapy. 6. Prescribed one of the following standard-of-care targeted therapy regimens: BRAF V600E Inhibitor + anti-EGFR antibody for BRAF V600E-mutated tumors, KRAS G12C Inhibitor + anti-EGFR antibody for KRAS G12C-mutated tumors, anti-PD-1 antibody +/- anti-CTLA-4 antibody for MMRd/MSI-H tumors, or anti-HER2 therapies for HER2 amplified tumors. Exclusion Criteria 1. Prior exposure to the following classes of biomarker-directed therapies: BRAF V600E inhibitors, anti-EGFR antibodies, KRAS G12C inhibitors, anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies, or anti-HER2 therapies 2. Presence of a concurrent malignancy requiring active treatment 3. Inability to provide informed consent 4. Children will not be enrolled in this study 5. Pregnant women will not be enrolled in this study 6. Cognitively Impaired subjects will not be enrolled in this study