Phase II Study of Serplulimab Combined with First-Line Targeted Therapy, Chemotherapy, and Radiation in Advanced Colorectal Cancer

Inclusion Criteria: 1. Age ≥ 18 years, any gender; 2. Histologically confirmed metastatic colorectal cancer (Stage IV, UICC), with initially unresectable metastases or refusal of surgery; * Primary tumor located in the distal transverse colon, descending colon, sigmoid colon, and rectum, and RAS (KRAS and NRAS) and BRAF wild-type (Cohorts A and B); * Primary tumor located in the cecum, ascending colon, and proximal transverse colon, and RAS (KRAS and NRAS) mutant-type (Cohorts C and D); 3. Treatment-naive patients who have not received standard anti-tumor therapy; 4. At least one measurable tumor lesion per RECIST 1.1 criteria; 5. ECOG performance status of 0-1; 6. Patients with an expected survival time of ≥ 3 months and good organ function: * (1) Neutrophils ≥ 1.5 \* 10\^9/L; platelets ≥ 100 \* 10\^9/L; hemoglobin ≥ 9 g/dL; serum albumin ≥ 3 g/dL; * (2) Thyroid-stimulating hormone (TSH) ≤ upper limit of normal (ULN), T3 and T4 within normal ranges; * (3) Bilirubin ≤ 1.5 times ULN; ALT and AST ≤ 2 times ULN; * (4) Serum creatinine ≤ 1.5 times ULN, creatinine clearance rate ≥ 60 mL/min; * (5) International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN, unless the patient is receiving anticoagulant therapy and PT is within the expected therapeutic range of anticoagulants; * (6) Activated partial thromboplastin time (aPTT) ≤ 1.5 times ULN; 7. Female patients of childbearing potential must have a negative pregnancy test; female patients not of childbearing potential; male patients of reproductive potential and female patients of reproductive potential and at risk of pregnancy must agree to use adequate contraception throughout the study period, continuing until 12 months after the last dose of study treatment; 8. Signed and dated informed consent form indicating that the patient has been informed of all pertinent aspects of the study; 9. Patients willing and able to comply with visit schedule, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: 1. Pathologically diagnosed with other intestinal tumors, such as gastrointestinal stromal tumors; 2. No testing for RAS mutation status; 3. Resectable metastases or patients wishing to undergo metastasectomy; 4. Prior systemic therapy. Systemic therapy includes all of the following: chemotherapy agents such as fluoropyrimidines, irinotecan, and oxaliplatin, VEGF monoclonal antibodies (e.g., bevacizumab), EGFR monoclonal antibodies (cetuximab or panitumumab), small molecule TKIs, immune checkpoint inhibitors, etc.; 5. Uncontrolled active bleeding from the primary tumor or bowel obstruction; 6. Contraindications to immune checkpoint inhibitors; 7. Allergy to the therapeutic drugs and/or their excipients; 8. Previous treatment with PD-1 antibodies, PD-L1 antibodies, or CTLA-4 antibodies; 9. Received any form of radiation therapy within 4 weeks prior to enrollment; 10. Previous or concurrent other malignancies, except adequately treated non-melanoma skin cancer, in situ cervical cancer, or papillary thyroid carcinoma; 11. Active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); except autoimmune-mediated hypothyroidism on stable doses of thyroid replacement hormone, type I diabetes on stable doses of insulin, vitiligo, or childhood asthma/allergies that have resolved and do not require intervention in adulthood; 12. History of immunodeficiency, including HIV-positive, or other acquired/congenital immunodeficiency diseases, or history of organ transplantation and allogeneic bone marrow transplantation; 13. History of interstitial lung disease (excluding radiation pneumonitis not treated with steroids), non-infectious pneumonia; 14. Active tuberculosis infection identified by history or CT scan, or history of active tuberculosis infection within 1 year prior to enrollment, or history of active tuberculosis infection more than 1 year ago but without proper treatment; 15. Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10\^4 copies/mL), active hepatitis C (HCV antibody positive and HCV-RNA above the detection limit); 16. Severe dysfunction of the heart, lungs, or kidneys; 17. Hypertension not well controlled by antihypertensive medications (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg); 18. History of substance abuse, alcoholism, or drug addiction; 19. Any other factors judged by the investigator to potentially affect the safety or compliance of the patient with the study, such as serious concomitant disease (including mental illness), serious laboratory abnormalities, or other familial or social factors.