Overview

This study is designed to explore the efficacy and safety of anti-PD-1 antibody plus bevacizumab and chemotherapy as first-line treatment for patients with RAS-mutant, microsatellite stable, metastatic colorectal cancer.

Eligibility

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.