Serplulimab Combined With CAPOX and Bevacizumab as Neoadjuvant Therapy for Locally Advanced Colorectal Cancer

Prior treatment

• Prior anti-tumor therapy including chemotherapy, radiotherapy, hormonal therapy or molecular-targeted therapy.
• Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibodies, or other agents targeting T-cell co-stimulatory or immune-checkpoint pathways.
• Major surgical procedure within 4 weeks prior to screening.
• Not recovered from prior surgical complications with residual toxicity \>Grade 1 (NCI-CTCAE v5.0), excluding alopecia and fatigue.
• Requirement for immunosuppressive medication within 2 weeks before screening or during study treatment, except for:
  • Intranasal, inhaled, topical or intra-articular corticosteroids.
  • Physiological-dose systemic corticosteroids (≤10 mg/day prednisone or equivalent).
  • Short-term (≤7 days) corticosteroids for prophylaxis or treatment of non-autoimmune allergic conditions.
• Active or uncontrolled infection requiring systemic therapy within 2 weeks prior to screening.
• Receipt of live-virus vaccine within 4 weeks prior to screening.

Other illness

• History of severe hypersensitivity reaction (NCI-CTCAE v5.0 ≥Grade 3) to anti-PD-1 monoclonal antibodies, other monoclonal antibodies, oxaliplatin, S-1 or related compounds.
• History of hereditary bleeding disorders or coagulopathy with high bleeding risk.
• Active or history of recurrent autoimmune disease.
• History of interstitial lung disease or non-infectious pneumonitis.
• Known active tuberculosis (Mycobacterium tuberculosis) infection.
• Human immunodeficiency virus (HIV) positive, other acquired or congenital immunodeficiency, history of organ transplantation or stem-cell transplantation.
• Hepatitis B or C virology findings at screening meeting any of the following:
  • HBsAg-positive with HBV-DNA ≥10⁴ copies/mL or ≥2000 IU/mL (antiviral therapy may be administered for HBV carriers at investigator's discretion).
  • Active hepatitis C: HCV-antibody-positive with detectable HCV-RNA above assay lower limit.
• Bowel obstruction, or history of inflammatory bowel disease, extensive bowel resection with chronic diarrhea, Crohn's disease, ulcerative colitis or chronic diarrhea.
• Any other condition that, in the investigator's opinion, would compromise study compliance or outcome assessment, making the subject unsuitable for study participation.

Age

• History of other malignant tumors within 5 years or concurrent other malignancies, except for cured carcinoma in situ of cervix, non-melanoma skin cancer, or other malignancies with ≥5 years disease-free survival after curative treatment.

Other

• Peripheral neuropathy ≥Grade 2 per NCI-CTCAE v5.0.
• Known active central nervous system metastases and/or carcinomatous meningitis.
• Lactating females, or females planning pregnancy during study treatment or within 6 months after treatment completion.
• Subjects (fertile males, females and their male partners) unwilling to use effective contraception during study treatment and for 6 months after treatment completion.

• Voluntarily provide written informed consent prior to screening.
• Male or female subjects aged ≥18 years.
• At least one measurable lesion per RECIST 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Histologically or pathologically confirmed locally advanced rectal adenocarcinoma, cT3/cT4N+M0 stage per AJCC/UICC 8th edition, with distance from anal verge ≤10 cm. Diagnosis is confirmed by contrast-enhanced CT/MRI, supplemented by colonoscopy and diagnostic laparoscopy if necessary; no prior anti-tumor treatment.
• Scheduled for surgical resection following neoadjuvant therapy based on clinical staging.
• Expected survival of more than 3 months.
• No emergency indications such as bowel obstruction, bleeding or perforation.
• Adequate major organ function as follows (no blood transfusion, granulocyte-colony stimulating factor (G-CSF) or other hematopoietic growth factor support within 14 days prior to screening):
  • Hematology: Absolute neutrophil count ≥1.5×10⁹/L, platelet count ≥100×10⁹/L, hemoglobin ≥90 g/L, white blood cell count ≥3.5×10⁹/L.
  • Liver function: ALT and AST ≤2.5×ULN; total bilirubin ≤1.5×ULN (≤3×ULN for patients with Gilbert syndrome).
  • Renal function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min.
  • Coagulation function: APTT, INR, PT ≤1.5×ULN.