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

Primary Objective

• To estimate the rate of ctDNA clearance at 6 months following initiation of biomarker-directed targeted therapy in colorectal cancer (CRC) participants with minimal residual disease (MRD).

Secondary Objectives

• To evaluate dynamics of ctDNA mutant allele fractions following initiation of biomarker-directed targeted therapy in MRD-positive CRC participants.
• To estimate the rate of disease recurrence at 1 year following initiation of biomarker-directed targeted therapy in MRD-positive CRC participants.

Inclusion criteria

• Male or female subjects aged > 18 years.
• Histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma.
• 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.
• 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).
• Positive ctDNA blood test obtained > 21 days after surgery or last administration of adjuvant therapy.
• 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

• 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
• Presence of a concurrent malignancy requiring active treatment
• Inability to provide informed consent
• Children will not be enrolled in this study
• Pregnant women will not be enrolled in this study
• Cognitively Impaired subjects will not be enrolled in this study