PD-1 Antibody Plus Bevacizumab and CAPOX as First-line Treatment for RAS-mut MSS mCRC

Inclusion Criteria:

* Histologically or cytologically confirmed non resectable, locally advanced or metastatic colorectal cancer;
* No previous anti-tumor treatment for metastatic diseases;
* KRAS/NRAS mutation;
* Eastern Cooperation Oncology Group (ECOG) performance status of 0-1;
* Life expectancy ≥ 3 months;
* Adequate organ and bone marrow functions:

Absolute neutrophil count≥1.5x10\^9/L; Platelet count≥100x10\^9/L; Hemoglobin≥9g/dL; Serum bilirubin\<1.5x the upper limit of normal(ULN); Alanine aminotransferase(ALT) and aspartate aminotransferase(AST)\<1.5x ULN; Serum creatinine\<1.5x ULN; Endogenous creatinine clearance rate ≥ 50ml / min;

* Women of childbearing age need to take effective contraceptive measures.

Exclusion Criteria:

* Previous treatment with vascular endothelial growth factor receptor (VEGFR) inhibitors or previous use of immune checkpoint inhibitors;
* With BRAF mutation or MSI-H status;
* Other untreated or concurrent tumors (except cervical carcinoma in situ, treated basal cell carcinoma or superficial bladder tumor, or if the tumor is cured and there is no evidence of disease for more than 3 years);
* Have received other systemic anti-tumor treatments, including chemotherapy, signal transduction inhibitors, hormone therapy and immunotherapy within 4 weeks before enrollment;
* There was central nervous system (CNS) metastasis or previous brain metastasis before enrollment;
* Have received any surgery or invasive treatment or operation within 4 weeks before enrollment;
* Have received Local anti-tumor therapy such as hepatic artery interventional embolization, liver metastasis cryoablation or radiofrequency ablation within 4 weeks before enrollment;
* Uncontrolled malignant ascites;
* Participated in other clinical trials within 4 weeks before enrollment, and received corresponding experimental drug treatment;
* Allergic to the study drug or any of its adjuvants;
* International normalized ratio (INR) \> 1.5 or partially activated prothrombin time (APTT) \> 1.5 × ULN；
* The researchers judged clinically significant electrolyte abnormalities;
* Hypertension that cannot be controlled by drugs, which is specified as: systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg; Patients currently have poorly controlled diabetes (fasting glucose level is greater than CTCAE grade 2 after regular treatment);
* Patients with dysphagia, active peptic ulcer, intestinal obstruction, active gastrointestinal bleeding, peptic perforation, malabsorption syndrome or uncontrolled intestinal inflammatory diseases;
* Any disease or state affecting drug absorption before enrollment, or the patient cannot take oral medication;
* Patients with obvious evidence of bleeding tendency or medical history within 3 months before enrollment, hemoptysis or thromboembolism within 12 months;
* Cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe / unstable angina pectoris or coronary artery bypass grafting within 6 months before enrollment; Congestive heart failure, New York Heart Association (NYHA) grade \> 2; ventricular arrhythmia requiring drug treatment; LVEF (left ventricular ejection fraction) \< 50%;
* Active infection or serious infection that is not controlled by drug (≥CTCAE v5.0 Grade 2）;
* History of clinically significant hepatic disease, including, but not limited to, known hepatitis B virus (HBV) infection with HBV DNA positive (copies ≥1×10\^4/ml or \>2000 IU/ml); known hepatitis C virus infection with HCV RNA positive (copies ≥1×10\^3/m); hepatitis and cirrhosis;
* Women who are pregnant or lactating;
* Urinary protein ≥ ++, and the 24-hour urine protein quantification is greater than 1.0g;
* Have any other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other conditions that makes the subject not suitable for enrolling according to the judgment of the investigator.