Cetuximab Plus Irinotecan in Patients With NeoRAS Wild-type Metastatic Colorectal Cancer In Third-line Therapy

Inclusion Criteria: 1. Age ≥ 18 years. 2. Histologically confirmed colorectal adenocarcinoma. 3. Patients with initial RAS mutant, BRAF wild-type left-sided mCRC. 4. Progression after standard first-line and second-line therapy (previously treated with fluorouracil compounds, oxaliplatin and irinotecan). 5. Tumor progression within 3 months during or after irinotecan-containing regimen. 6. Blood-based ctDNA testing shows that both RAS and BRAF genes are wild-type after second-line therapy progression . 7. There are objectively measurable lesions according to RECIST v1.1 criteria. 8. Normal hematologic function (platelets \> 90 × 109/L; leukocytes \> 3 × 109/L; neutrophils \> 1.5 × 109/L; hemoglobin \> 8.0g/100ml). 9. Serum bilirubin ≤ 1.5 x the upper limit of normal (ULN) and transaminases ≤ 5 x ULN. 10. Normal coagulation function, albumin ≥ 35 g/L. 11. Liver function: Child-Push score: Class A. 12. Serum creatinine \< 1.5 x ULN, or calculated creatinine clearance ≥ 50 ml/min (using the Cockcroft Gault formula). 13. ECOG PS score 0-2. 14. Life expectancy \> 3 months. 15. Sign written informed consent. 16. Willing and able to be followed up until death or end of study or study termination. Exclusion Criteria: 1. Primary right-sided mCRC. 2. dMMR/MSI-H mCRC. 3. Patients with initial RAS wild-type or BRAF mutant mCRC. 4. ctDNA testing shows that RAS or BRAF gene is mutant mCRC after second-line therapy. 5. Serious arterial embolism or ascites. 6. Serious bleeding tendency or coagulation disorder. 7. Serious uncontrolled systemic complications such as infection or diabetes. 8. Clinically significant cardiovascular disease such as cerebrovascular accident (within 6 months prior to enrollment), myocardial infarction (within 6 months prior to enrollment), uncontrolled hypertension despite appropriate medical treatment. Unstable angina, congestive heart failure (NYHA class 2-4), cardiac arrhythmia requiring medication. 9. History or physical evidence of central nervous system disease (e.g., primary brain tumor, epilepsy uncontrolled by standard of care, any history of brain metastases or stroke). 10. Other malignancies (except cutaneous basal cell carcinoma and/or cervical carcinoma in situ of the cervix and/or thyroid carcinoma after radical surgery) within the past 5 years. 11. Hypersensitivity to any drug in the study. 12. Pregnant and lactating women. 13. Women of childbearing age (\< 2 years after last menstruation) or men of fertile potential who are not using or refuse to use effective non-hormonal contraception (intrauterine contraceptive ring, barrier contraceptives combined with spermicidal gel, or surgical sterilization). 14. Unable or unwilling to comply with the study protocol. 15. Patients with any other diseases, dysfunction caused by metastatic lesions, or suspected disease found by physical examination, indicating possible contraindications to the use of the investigational drug or putting the patients at high risk of treatment-related complications.