The Safety and Efficacy of Cetuximab Beta Plus Fruquintinib With or Without Immune Checkpoint Inhibitorrs in First-line Treatment of RAS/BRAF Wild Type Unresectable Metastatic Colorectal Cancer

Inclusion Criteria: 1）Subjects voluntarily join this study, sign the informed consent form, and demonstrate good compliance; 2) Age: 10-80 years old, ECOG PS score of 0-1. For patients aged 80-85, comprehensive functional assessments must be completed, and they may be enrolled if the investigator deems them tolerable, with an expected survival of over 3 months; 3) Histopathologically and/or cytologically confirmed, unresectable metastatic colorectal adenocarcinoma confirmed by MDT discussion (UICC/AJCC TNM staging system for colorectal cancer, 8th Edition, 2017); 4) At least one measurable lesion confirmed according to RECIST 1.1 criteria; 5) Adequate function of major organs, meeting the following criteria: 1. Hematological examination standards (no blood transfusion or use of hematopoietic growth factors for correction within 7 days prior to screening): 1. Hemoglobin (HGB) ≥ 90 g/L; 2. Absolute neutrophil count (NEUT) ≥ 1.5 × 10⁹/L; 3. Platelet count (PLT) ≥ 75 × 10⁹/L; 2. Biochemical tests must meet the following criteria: 1. Total bilirubin (TBIL) ≤ 1.5 × ULN (≤ 3 × ULN for subjects with Gilbert's syndrome); 2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN. If with liver metastases, ALT and AST ≤ 5 × ULN; 3. Serum creatinine (CR) ≤ 1.5 × ULN or creatinine clearance rate (CCR) ≥ 50 ml/min. 3. Coagulation function or thyroid function tests must meet the following criteria: 1. Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) ≤ 1.5 × ULN (without anticoagulant therapy); 2. Thyroid-stimulating hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels should be assessed (FT3 and FT4 may be substituted if T3/T4 are unavailable at the center). Subjects may be enrolled if T3 and T4 levels are normal. 4. Echocardiogram assessment: Left ventricular ejection fraction (LVEF) ≥ 50%. 5. Hepatitis B surface antigen (HBsAg) negative. If HBsAg positive, hepatitis B virus deoxyribonucleic acid (HBV-DNA) must be \< 2500 copies/mL or 500 IU/mL for enrollment. 6. HCV antibody negative or HCV-RNA negative subjects may enroll; if HCV-RNA positive, subjects must have alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN to enroll. Subjects with co-infection of hepatitis B and hepatitis C are excluded (positive for HBsAg or HBcAb, and positive for HCV antibody). 7. Female patients must meet one of the following conditions: 1. Postmenopausal (defined as no menses for at least 1 year, with no other confirmed causes besides menopause), or 2. Surgically sterilized (removal of ovaries and/or uterus), or 3. Of childbearing potential but must meet the following: * Serum/urine pregnancy test within 7 days prior to enrollment must be negative; * Agree to use contraception with a failure rate of \< 1% per year or maintain abstinence (avoiding heterosexual intercourse) (from signing the ICF until at least 6 months after the last dose of the study drug) (contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, correct use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, copper intrauterine devices, or condoms); * Must not be breastfeeding. 8. Male patients must meet the following: Agree to abstinence (avoiding heterosexual intercourse) or use contraception, as specified: When the partner is a woman of childbearing potential or is pregnant, the male patient must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose to prevent fetal drug exposure. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception. Exclusion Criteria: 1. Presence of MSI-H/dMMR patients. 2. Concurrent diseases and medical history: 1. Diagnosis of or concurrent other malignancies within the past 3 years. The following conditions are eligible for enrollment: Cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading the basement membrane)\]; 2. Multiple factors affecting oral medication (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, etc.); 3. History or tendency of gastrointestinal bleeding or perforation within 4 weeks prior to enrollment; 4. Patients with active inflammatory bowel disease within 4 weeks prior to enrollment; 5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage; 6. Unresolved toxicities from any prior antitumor therapy exceeding CTCAE Grade 1 (excluding alopecia and oxaliplatin-induced neurotoxicity ≤ Grade 2); 7. Major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to the start of study treatment (excluding gastrointestinal endoscopic biopsy); 8. Symptoms of active bleeding within 1 week prior to screening, without significant improvement or control; 9. Patients with any bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to study initiation, or presence of unhealed wounds, ulcers, or fractures; 10. Arterial/venous thrombotic events within 6 months, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; 11. History of psychoactive drug abuse with inability to abstain; 12. Patients with any severe and/or uncontrolled diseases, including: * Uncontrolled hypertension (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg after standard antihypertensive therapy); * Myocardial ischemia ≥ Grade 2, myocardial infarction, arrhythmias (including QTc ≥450 ms for males, QTc ≥470 ms for females), and congestive heart failure ≥ Grade 2 (New York Heart