mFOLFOX6 + Bevacizumab + PD-1 Monoclonal Antibody Vs. mFOLFOX6 in Locally Advanced pMMR/MSS CRC

Prior treatment

• Active tuberculosis (TB), ongoing anti-TB treatment, or anti-TB treatment within 1 year prior to trial screening.
• Administration of any live attenuated vaccine within 4 weeks prior to inclusion.
• Long-term use of immunosuppressants or systemic/topical corticosteroids (dose \>10 mg/day prednisolone or equivalent).

Other illness

• Arrhythmias requiring anti-arrhythmic treatment (except β-blockers or Digoxin), symptomatic coronary artery disease, myocardial ischemia (myocardial infarction within the past 6 months), or congestive heart failure (CHF) \> NYHA Class II.
• Severe hypertension that is not well controlled by medication.
• History of HIV infection or active chronic Hepatitis B or C (with high viral DNA load).
• Other active severe infections as defined by NCI-CTCAE v5.0.
• History of pelvic or abdominal radiotherapy.
• Multiple colorectal cancer or multiple primary tumors.
• Epilepsy requiring treatment (e.g., steroids or anti-epileptic drugs).
• History of other malignancies within the past 5 years.
• History of drug abuse, or medical, psychological, or social conditions that could interfere with patient participation or the evaluation of study results.
• Any active autoimmune disease or a history of autoimmune disease (including but not limited to interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism, and asthma requiring bronchodilators).
• Known or suspected allergy to any study-related drug.
• Any unstable condition that could compromise patient safety or compliance.

Other

• Evidence of distant metastasis beyond the pelvic region.
• Blood dyscrasias or organ dysfunction.
• Pregnant or breastfeeding women, or women of childbearing potential not using effective contraception.
• Refusal to provide signed informed consent.

• Histologically confirmed adenocarcinoma of the colon or upper rectum.
• Tumor biopsy immunohistochemical (IHC) identified pMMR, including all of the MSH1,MSH2,MSH6 and PMS2 protein expression and diagnosed as proficient mismatch repair(pMMR), or microsatellite stable (MSS) identified through next-generation sequencing or polymerase chain reaction.
• Clinical staging of cT4NxM0, with or without positive mesorectal fascia (MRF), and with or without extramural vascular invasion (EMVI); imaging confirms that the lower margin of the tumor is located above the peritoneal reflection (colon or upper rectum).
• Staging method: All patients must undergo chest, abdominal, and pelvic contrast-enhanced CT, rectal palpation, and high-resolution MRI. Positive perienteric lymph nodes (LNs) are defined as LNs with a short diameter ≥10 mm or LNs exhibiting typical metastatic shape and MRI characteristics. When staging results are contradictory, clinical data must be re-evaluated and confirmed by the central evaluation group. Distant metastases must be excluded through chest and abdominal contrast-enhanced CT and pelvic contrast-enhanced MRI.
• No symptoms of intestinal obstruction, or obstruction successfully relieved by proximal colostomy.
• No history of colorectal surgery.
• No prior chemotherapy or radiotherapy.
• No history of biopharmaceutical treatments (e.g., monoclonal antibody ), immunotherapy (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies), or treatment with investigational drugs.
• Endocrine therapy history: Not restricted.
• Signed informed consent obtained.