Serplulimab Plus Decitabine and CAPOX Before Surgery for Locally Advanced Colorectal Cancer

Inclusion criteria

• Voluntarily signs written informed consent before screening.
• Male or female, aged 18 years or older.
• Has at least one measurable lesion according to RECIST version 1.1.
• ECOG performance status score of 0 to 1.
• Histologically or pathologically confirmed colorectal adenocarcinoma with no prior antitumor treatment, staged as cT3/cT4N+M0 locally advanced colorectal cancer according to the AJCC/UICC 8th edition based on contrast-enhanced CT or MRI, with colonoscopy and/or diagnostic laparoscopy if clinically indicated.
• Planned to undergo surgery after neoadjuvant therapy according to clinical staging.
• Expected survival of more than 3 months.
• Adequate major organ function, meeting all of the following criteria:
• Hematology: neutrophil count ≥1.5 × 10^9/L, platelet count ≥100 × 10^9/L, hemoglobin ≥90 g/L, and white blood cell count ≥3.5 × 10^9/L, without blood transfusion, granulocyte colony-stimulating factor, or other hematopoietic growth factors within 14 days before screening.
• Hepatic function: ALT and AST ≤2.5 × upper limit of normal, and total bilirubin ≤1.5 × upper limit of normal, or ≤3 × upper limit of normal for patients with Gilbert syndrome.
• Renal function: serum creatinine ≤1.5 × upper limit of normal or creatinine clearance ≥60 mL/min.
• Coagulation function: activated partial thromboplastin time, international normalized ratio, and prothrombin time ≤1.5 × upper limit of normal.

Exclusion criteria

• Prior treatment with any antitumor therapy, including chemotherapy, radiotherapy, hormonal therapy, or molecular targeted therapy.
• Prior immunotherapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody, or any other antibody or drug targeting T-cell co-stimulation or immune checkpoint pathways.
• History of another malignancy within 5 years or concurrent malignancy, except cured carcinoma in situ of the cervix, non-melanoma skin cancer, or other malignancy treated with curative intent with no evidence of disease for at least 5 years.
• Pre-existing peripheral neuropathy of grade 2 or higher according to NCI-CTCAE version 5.0.
• Known active central nervous system metastasis and/or carcinomatous meningitis.
• History of severe hypersensitivity reaction to any component of a product or formulation similar to the study PD-1 antibody, or known severe hypersensitivity reaction to other monoclonal antibodies, oxaliplatin, capecitabine, or related compounds, defined as NCI-CTCAE version 5.0 grade 3 or higher.
• Known history of hereditary bleeding disorder or coagulation disorder associated with bleeding risk.
• Major surgery within 4 weeks before enrollment.
• Has not recovered from complications of prior surgery to grade 1 or lower according to CTCAE version 5.0, except alopecia and fatigue.
• Requires immunosuppressive medication within 2 weeks before enrollment or during the study, except intranasal, inhaled, topical, or local steroid injections; systemic corticosteroids at physiological doses equivalent to prednisone ≤10 mg/day; or short-term use of steroids for prevention or treatment of non-autoimmune allergic conditions for no more than 7 days.
• Active autoimmune disease or history of autoimmune disease with potential recurrence.
• Known history of interstitial lung disease or non-infectious pneumonitis.
• Known history of active tuberculosis.
• History of human immunodeficiency virus infection, other acquired or congenital immunodeficiency disease, organ transplantation, or stem cell transplantation.
• Positive hepatitis B surface antigen with HBV DNA ≥10^4 copies/mL or ≥2000 IU/mL at screening, or active hepatitis C defined as positive HCV antibody with HCV RNA above the lower limit of detection.
• Active or uncontrolled infection requiring systemic treatment within 2 weeks before enrollment.
• Receipt of a live viral vaccine within 4 weeks before enrollment.
• Intestinal obstruction, inflammatory bowel disease, extensive intestinal resection with chronic diarrhea, Crohn's disease, ulcerative colitis, or chronic diarrhea.
• Breastfeeding, or planning pregnancy during treatment and within 6 months after completion of treatment.
• Unwillingness to use effective contraception during treatment and within 6 months after completion of treatment, including male participants capable of fathering a child, female participants, and their male partners.
• Any other condition that, in the investigator's judgment, may affect protocol compliance or assessment of study endpoints and makes the participant unsuitable for this study.