Inclusion Criteria:

          -  Written informed consent and HIPAA authorization for release of personal health
             information

          -  As determined by the enrolling physician or protocol designee, ability of the
             participant to understand and comply with study procedures for the entire length of
             the study

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2

          -  Have a diagnosis of histologically confirmed metastatic colorectal cancer with primary
             tumor located beyond the splenic flexure. Histologic confirmation of a colorectal
             primary tumor is acceptable if accompanied by radiographic evidence of metastatic
             disease.

               -  For Cohort A: Participants must enroll for study treatment in the first or
                  second-line metastatic setting. Participants may receive 1 month of standard
                  chemotherapy in the metastatic setting and still be eligible to initiate protocol
                  therapy in the first-line setting. Adjuvant or neoadjuvant therapy does not count
                  as a line of therapy even if given in the setting of metastatic disease
                  (oligometastatic), unless disease recurrence was noted within 6 months of
                  completing the last dose of the adjuvant of neoadjuvant therapy.

               -  For Cohort B: Participants must have had at least stable disease (per treatment
                  physician) on a prior EGFR inhibitor containing regimen and it must be at least 4
                  months since the prior anti-EGFR inhibitor treatment was completed. Participants
                  previously enrolled in Cohort A can later enroll in Cohort B should the
                  eligibility criteria be met.

          -  Evaluable disease according to RECIST v1.1. Participants do not have to have
             measureable disease.

          -  Participants with prior brain metastasis may be considered if they have completed
             their treatment for brain metastasis at least 4 weeks prior to study registration,
             have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic.

          -  Demonstrate adequate organ function; all screening labs to be obtained within 7 days
             prior to registration. Note minimum platelet requirement differs between Cohort A and
             B.

               -  Absolute Neutrophil Count (ANC) ≥ 1,000 / mcL

               -  Platelets ≥ 50,000 / mcL (Cohort A); ≥ 75,000 mcL (Cohort B)

               -  Serum creatinine OR measured or calculated creatinine clearance (GFR can also be
                  used in place of creatinine or CrCl) ≤ 2.0 X upper limit of normal (ULN) OR ≥ 60
                  mL/min for subject with creatinine levels > 2.0 X institutional ULN

               -  Bilirubin ≤ 1.5 × ULN OR direct bilirubin ≤ ULN for subjects with bilirubin
                  levels >1.5 x ULN

               -  Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 5 × ULN

               -  Albumin ≥ 2.5 mg/dL

          -  Females of childbearing potential must have a negative serum pregnancy test within 7
             days of registration and not be breastfeeding. Females are considered of child bearing
             potential unless they are surgically sterile (have undergone a hysterectomy, bilateral
             tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at
             least 12 consecutive months.

          -  Females of childbearing potential and males must be willing to abstain from
             heterosexual activity or to use 2 forms of effective methods of contraception from the
             time of informed consent until 120 days after treatment discontinuation. The two
             contraception methods can be comprised of two barrier methods, or a barrier method
             plus a hormonal method.

          -  Tumor must be mismatch repair (MMR) proficient as determined by microsatellite
             instability or immunohistochemistry for MMR proteins

               -  Microsatellite instability (MSI) testing must be MSI-stable or MSI-low.

               -  Or IHC for MMR proteins must demonstrate intact MMR proteins.

          -  Standard tumor molecular profiling with no pathologic variants in KRAS or NRAS or BRAF
             V600 mutations.

          -  Participants must not have known additional malignancy that is requiring systemic
             treatment. Participants taking hormonal treatments for breast or prostate cancer are
             still eligible.

          -  No major surgery within prior 2 weeks of treatment initiation.

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to panitumumab or cetuximab, including known severe
             hypersensitivity reactions to monoclonal antibodies.

          -  Participants must have no metastatic cancer lesions greater than 3.5cm in diameter.
             Any number of metastatic lesions will be allowed.