Safety and Efficacy of Pembrolizumab in Combination with Bevacizumab + CapeOX in the Neoadjuvant Treatment of RAS-mutated, BRAF Wild-type, Microsatellite-stabilized, Locally Advanced Colorectal Cancer

Inclusion criteria

• Age: ≥18 years;
• Confirmed RAS mutation and BRAF wild-type in LACRC by pathological histology or genetic sequencing.;
• ECOG Performance Status (PS) score of 0 or 1;
• Previously untreated;
• Microsatellite-stable status;
• Hematological parameters within normal limits: White blood cell count ≥4×10^9/L; Absolute neutrophil count ≥1.5×10^9/L; Platelets ≥100×10^9/L. Hemoglobin ≥90g/L;
• Normal renal function: Serum creatinine ≤1.5× upper limit of normal (ULN) or creatinine clearance (CrCl) >60 mL/min (calculated using Cockcroft-Gault formula): Female CrCl = (140 - age) × weight (kg) × 0.85 / (72 × Scr mg/dl)；Male CrCl = (140 - age) × weight (kg) × 1.00 / (72 × Scr mg/dl);
• Normal liver function: Serum total bilirubin ≤1.5× ULN; Aspartate aminotransferase (AST) ≤2.5× ULN; Alanine aminotransferase (ALT) ≤2.5× ULN;
• Female patients must have a negative pregnancy test before the study initiation (not applicable to bilateral oophorectomy and/or hysterectomy patients or postmenopausal patients);
• Signed written informed consent form.

Exclusion criteria

• Receiving anti-tumor therapy prior to enrollment, including but not limited to PD-1 inhibitors, CTLA-4 antibodies, EGFR monoclonal antibodies, EGFR-TKI, and anti-angiogenic drugs;
• History of autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome-associated vascular thrombosis, Wegener's granulomatosis, desiccation syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. (Note: Vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune disease, psoriasis not requiring systemic therapy, or patients not expected to have a relapse without external triggers may be allowed to enroll);
• Enrolled in another interventional clinical trial within 30 days prior to screening;
• History of other malignancies (except cured basal cell carcinoma of the skin);
• Presence of severe, poorly controlled co-morbidities such as heart failure, diabetes mellitus, hypertension, hepatic failure, renal failure, thyroid disease, psychiatric disorders, etc;
• Known HIV infection or active viral hepatitis or tuberculosis;
• Major surgery or planned surgery within 30 days prior to the first dose of the investigational drug;
• Hypersensitivity to the drugs used in the trial or their components;
• Pregnancy (confirmed by blood or urine HCG test) or breastfeeding women, or subjects of childbearing potential unwilling or unable to use effective contraception until at least 6 months after the last trial treatment;
• Deemed inappropriate for participation in the study by the investigator.
• Unwilling or unable to participate in the study or sign the informed consent form.