XELOX +Bev +Tislelizumab for First-line Treatment of MSS/pMMR RAS-mutated mCRC

Inclusion Criteria: Histologically confirmed initially unresectable MSS/pMMR-type RAS-mutant metastatic colorectal adenocarcinoma; ECOG score of 0 or 1; Ability to swallow oral medications; Have at least one measurable lesion (according to RECIST v1.1 standard); No anti-tumor treatment has been received after recurrence and metastasis; Neoadjuvant or adjuvant chemotherapy containing fluorouracil drugs is allowed before or after radical resection of colorectal cancer, but the treatment needs to be completed for ≥ 6 months; if oxaliplatin is used in neoadjuvant or adjuvant chemotherapy, it includes The oxaliplatin regimen needs to be completed for ≥12 months; Adequate organ function: On the premise of no component blood transfusion within 14 days: white blood cells ≥ 3.5*10^9/L and neutrophils ≥ 1.5*10^9/L, hemoglobin ≥ 90g/L, platelets ≥ 100* 10^9/L; serum bilirubin ≤ 1.5 times the normal value, alanine aminotransferase (ALT) ≤ 2.5 times the normal value, aspartate aminotransferase (AST) ≤ 2.5 times the normal value; Urinary protein <2+. Or urine protein 2+ but 24-hour urine protein quantity ≤ 1 g; serum creatinine ≤ 1.5 times of normal value, creatinine clearance rate ≥ 60ml/min; Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ lower limit of normal value (50%); Expected survival period ≥ 3 months; Patients fully understand this research, voluntarily participate in this clinical trial and sign an informed consent; Women with reproductive potential (< 2 years after the last menstrual period) and men use effective contraceptive methods until half a year after the last treatment. Exclusion Criteria: Previously received bevacizumab or anti-CTLA4, anti-PD-1/PD-L1 therapeutic antibodies or pathway-targeted drugs; Received radiotherapy within 4 weeks before the evaluation; Symptomatic peripheral neuropathy > grade 2 (CTCAE5.0 standard); Received live vaccine or systemic immune stimulant (including but not limited to interferon or interleukin 2) within 1 month; HIV-positive and other immunodeficiency diseases; Active hepatitis B or hepatitis C (except for those who have been infected or cured before, that is, HBsAg negative and hepatitis B core antigen anti-HBc antibody positive; except for hepatitis C patients whose HCV RNA is negative by PCR); Existing autoimmune diseases or other diseases that require immunosuppressant treatment, except for type 1 diabetes; except for hypothyroidism that only requires hormone replacement therapy; skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, alopecia areata); inhaled or topical steroids or equivalent steroids in excess of 10 mg prednisone per day, except for inactive autoimmune disease on adrenal replacement therapy; Received systemic hormone therapy or treatment with a daily dose of more than 10 mg prednisone equivalent dose or other forms of immunosuppressive treatment within 7 days, but inhaled or topical steroids or daily application of more than 10 mg prednisone, etc. Except for inactive autoimmune diseases treated with adrenal replacement therapy with potent steroids; Have a history of organ transplantation; Uncontrolled central nervous system (CNC) metastasis (symptomatic or metastatic sites are midbrain, pons, medulla or spinal cord) or other central nervous system diseases; Those who have undergone major surgery, open biopsy or obvious traumatic trauma within 1 month, or who may need major surgery during the study period; those who have undergone open biopsy or obvious traumatic trauma, or may need major surgery during the study period; Combined with other malignant tumors other than intestinal cancer (except cured basal cell carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the cervix; the treatment of other malignant tumors has been completed for more than 1 year, and there is no clinical and imaging evidence of recurrence or progression except); Combined active and refractory infection; Cardiovascular diseases with clinical significance, such as cardiovascular accident (CVA) (≤ 6 months before treatment), myocardial infarction (≤ 6 months before treatment), unstable angina, chronic heart failure of NYHA ≥ 2 (CHF), uncontrolled arrhythmia; uncontrolled hypertension; thromboembolic or bleeding events within 6 months before treatment; Evidence of causing coagulation disease; With dysphagia, active peptic ulcer, complete or incomplete intestinal obstruction, active gastrointestinal bleeding, perforation, malabsorption syndrome or uncontrollable gastrointestinal inflammatory disease (such as Crohn's disease or ulcerative colon inflammation); Severe unhealed wounds/ulcers or severe fractures; Any serious acute or chronic medical condition that may affect the patient's participation in the study or interfere with the interpretation of the study results; There are mental illnesses, serious social and psychological illnesses, or researchers believe that there are factors that may affect research compliance; Pregnant or lactating women; No therapeutic anticoagulant or antiplatelet drugs or NSAIDs (aspirin ≤ 325 mg/day allowed); Severe allergic reaction to the test drug; Reluctance to use alternative therapies such as (but not limited to) bisphosphonates if receiving RANKL inhibitors (eg, denosumab).