Early-Line Anti-EGFR Therapy for Retreatment in Select Patients with Metastatic Colorectal Cancer

Inclusion Criteria

• Must provide written consent and agree to share personal health information.
• Must be able to understand and follow study procedures for the entire study duration.
• Have a performance status score of 0 to 2, indicating full activity or some restriction in strenuous activities.
• Have a confirmed diagnosis of metastatic colorectal cancer with the primary tumor located beyond the splenic flexure.
• For Cohort A: Must enroll for treatment in the first or second-line metastatic setting. Can have received 1 month of standard chemotherapy in the metastatic setting and still be eligible.
• For Cohort B: Must have had stable disease on a prior EGFR inhibitor regimen and at least 4 months since the last treatment.
• For Cohort C: Must have had prior FOLFOX treatment with no prior use of irinotecan or anti-EGFRi.
• Must have evaluable disease according to specific criteria.
• Participants with prior brain metastasis may be eligible if they have completed treatment at least 4 weeks prior, are off corticosteroids for 2 weeks, and are asymptomatic.
• Must have adequate organ function as shown by specific lab tests.
• Females of childbearing potential must have a negative pregnancy test and not be breastfeeding.
• Must agree to use effective contraception during the study and for 120 days after treatment.
• Tumor must be mismatch repair proficient.
• Must have no pathologic variants in KRAS, NRAS, or BRAF V600 mutations in baseline tumor profiling.
• Must not have another malignancy requiring systemic treatment.
• No major surgery within 2 weeks of treatment initiation (4 weeks if receiving bevacizumab).
• Must not have severe allergic reactions to study drugs or similar compounds.
• Must not have metastatic cancer lesions greater than 3.5 cm in diameter.