Neoadjuvant Serplulimab & Bevacizumab With FOLFOX vs. FOLFOX Alone in RAS/BRAF WT, pMMR/MSS CRC Patients

Inclusion Criteria:

• Age ≥18 and ≤75 years old

• Histologically confirmed colorectal adenocarcinoma

• Radiological and/or pathological confirmation of liver metastases, with ≤5 lesions

• Genetic testing and/or immunohistochemistry confirmation of RAS, BRAF wild-type, andpMMR/MSS

• Absence of extrahepatic metastases confirmed by CT, MRI, or PET/CT (if necessary)

• Primary colorectal tumor has been or can be radically resected

• Liver metastatic lesions are resectable (including radiofrequency ablation andSBRT), and postoperative NED (no evidence of disease) is expected. Resectable livermetastases are specifically defined as ① ≤5 metastatic lesions; ② R0 resection canbe performed (including radiofrequency ablation and SBRT); ③ Sufficient residualliver volume is expected after resection; ④ At least one hepatic vein can bepreserved after resection, with preserved blood flow in and out of the residualliver and preserved bile ducts, and can preserve at least two adjacent liversegments; ⑤ No extrahepatic metastases.

• No prior anti-tumor therapy for liver metastases, except for surgical resection ofprimary lesions

• Normal hematological function (platelets >90×109/L; white blood cells >3×109/L;neutrophils >1.5×109/L)

• Serum bilirubin ≤1.5 times the upper limit of normal (ULN), transaminases ≤5 timesULN, alkaline phosphatase ≤2.5 ULN, no ascites, normal coagulation function, albumin ≥35g/L

• Liver function classified as Child-Pugh grade A

• Serum creatinine below the upper limit of normal (ULN), or calculated creatinineclearance rate >50ml/min (using Cockcroft-Gault formula)

• ECOG performance status 0-1

• Expected lifespan >3 months

• Signed written informed consent

• Willing and able to be followed up until death or end of study or study termination.

Exclusion Criteria:

• Diagnosis of colorectal cancer with distant extrahepatic metastases

• Prior chemotherapy, targeted therapy, intervention, or immunotherapy for livermetastases

• No planned surgical resection for liver metastatic lesions

• Received oxaliplatin-containing adjuvant chemotherapy regimen within the past oneyear

• Any toxicity residuals from previous chemotherapy, excluding alopecia, such asperipheral neuropathy ≥NCI CTC v3.0 grade 2

• Use of immunosuppressive drugs one week prior to study treatment initiation,excluding topical corticosteroids via nasal, inhalational, or other routes orphysiological doses of systemic corticosteroids (i.e., not exceeding 10 mg/day ofprednisone or equivalent) or steroids used for prevention of contrast agent allergy

• Interstitial lung disease requiring corticosteroid treatment

• Known active autoimmune disease requiring symptomatic treatment or with a history ofsuch disease within the past 2 years. Patients with vitiligo, psoriasis, alopecia,or Graves' disease who have not required systemic treatment within the past 2 years,patients with hypothyroidism requiring only thyroid hormone replacement therapy, andpatients with type I diabetes requiring only insulin replacement therapy can beincluded

• Known history of primary immunodeficiency

• Patients with active tuberculosis

• History of allogeneic organ or hematopoietic stem cell transplantation

• Known allergy to any monoclonal antibody or chemotherapy drug (Fluorouracil,oxaliplatin) preparation or excipient component

• Bleeding tendency or coagulation disorder

• Significant symptoms of intestinal obstruction

• Hypertensive crisis or hypertensive encephalopathy

• Severe uncontrolled systemic complications such as infection or diabetes

• Clinically severe cardiovascular diseases such as cerebrovascular accident (within 6months before enrollment), myocardial infarction (within 6 months beforeenrollment), hypertension that remains uncontrolled after appropriate drugtreatment, unstable angina pectoris, congestive heart failure (NYHA 2-4), orarrhythmia requiring medication

• Past or physical examination showing central nervous system diseases (such asprimary brain tumor, epilepsy uncontrolled by standard treatment, any history ofbrain metastasis, or stroke)

• Diagnosis of other malignant tumors within the past 5 years (excluding basal cellcarcinoma and/or carcinoma in situ of the cervix after radical surgery)

• Patients who received any investigational drug therapy within the last 28 days priorto the study

• Pregnant or lactating women and women of childbearing age not using or refusing touse effective non-hormonal contraception (intrauterine devices, barriercontraception combined with spermicidal gel, or sterilization surgery) or men withreproductive potential unwilling or unable to comply with the study protocol