Cetuximab in Third Line for Mutant APC, TP53 and RAS Patients With Refractory Metastatic Colorectal Cancer

Inclusion Criteria: * Male or female subject aged ≥ 18 years. * Histologically confirmed metastatic colorectal adenocarcinoma with mutant APC, TP53 and KRAS genes as determined by the local Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory are eligible. All RAS mutations are allowed (KRAS, Neuroblastoma RAS (NRAS), HRAS). Patients with wild type KRAS, APC or TP53 are ineligible. * Progression or unwanted toxicities on at least 2 prior lines of treatment including 5-Fluorouracil, oxaliplatin and irinotecan-based regimen * Study participants must have measurable disease by RECIST 1.1 criteria by CT or MRI. * Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2. * Study participants with treated and/or stable brain metastases are allowed * Study participants must have anticipated life expectancy \> 3 months * Adequate organ function as defined as: * Hematologic: * Absolute neutrophil count (ANC) ≥ ≥1000/µL * Platelet count ≥ 100,000/mm3 * Hemoglobin ≥ 9 g/dL * Hepatic: * Serum Bilirubin ≤ 2 x ULN or ≤ 3 x ULN for subjects with Gilbert's syndrome * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times the upper limit of normal (ULN; or 5.0 times the ULN in the setting of liver metastases) * Renal: * Serum creatinine ≤1.5 times the ULN, or creatinine clearance (measured via 24-hour urine collection) ≥40 mL/minute (that is, if serum creatinine is \>1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed) * For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women \< 50 years of age: * Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and * Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or * Underwent surgical sterilization (bilateral oophorectomy or hysterectomy). * Women ≥ 50 years of age: * Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or * Had radiation-induced menopause with last menses \>1 year ago; or * Had chemotherapy-induced menopause with last menses \>1 year ago; or * Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy). * Female subjects of childbearing potential and male subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 12 months after last study treatment administration. * Male subjects must agree to use a condom during intercourse for the duration of study therapy and for at least 12 months after last study treatment administration. * Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior cancer therapy, unless considered clinically not significant by the treating investigator. * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. Exclusion Criteria: * Prior use of systemic anti-EGFR therapy including cetuximab or panitumumab is not allowed but prior use irinotecan, oxaliplatin, regorafenib or Trifluridine/Tipiracil (TAS-102) is allowed * Study participants with prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of the investigational regimen, as determined by the investigator * Study participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease who need immediate central nervous system (CNS)-specific treatment during first cycle of treatment as determined by the treating physician. --Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the first dose of study treatment. * Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions: * The patient has clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency. * The patient has uncontrolled or poorly-controlled hypertension (\>180 mmHg systolic or \> 130 mmHg diastolic. * Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[subjects may not receive the drug through a feeding tube\], social/ psychological issues, etc.) * Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment. --Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial. * Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and tuberculosis (TB) testing in line with local practice), hepatitis B (known positive hepatitis B virus (HBV) surface antigen (HBsAg) result), or hepatitis C. --Note: Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody (anti-HBc) and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. * Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study. * Known prior severe hypersensitivity attributed to compounds of chemical or biologic composition similar to those of cetuximab, or if the patient had red meat allergy/tick bite history (NCI CTCAE v5.0 Grade ≥ 3). * Live attenuated and inactive vaccinations within 4 weeks of the first dose of study treatment and while on trial is prohibited. Coronavirus Disease 19 (COVID-19) vaccines are allowed * The patient is pregnant or breast-feeding.