Predictive Factors for Outcomes of Fruquintinib Plus Immunotherapy in Colorectal Cancer

Inclusion Criteria:

• Signed the Informed Consent Form
• Ages: 18-75 Years (concluding 18 and 75 Years)
• Pathologically confirmed unresectable metastatic colorectal cancer
• Failure to 2st line therapy
• pMMR/MSS type
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy greater than 3 months
• At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan,larger than 20 mm in diameter by conventional CT scan) according to RECIST1.1
• Sufficient organ functions as follows (any blood transfusion or cell growth factor usewithin 14 days before enrollment is not allowed): Absolute Neutrophil Count (ANC) ≥1.5×109/L Platelet Count of ≥175×109/L; Hemoglobin≥90g/L;Total Bilirubin (TBIL) ≤1.5 x ULN; ALT and /or AST<1.5 x ULN; If there is liver metastasis,then ALT and/or AST<3.0 x ULN; Serum Creatinine (SCr) ≤1.5×ULN; Endogenous creatinineclearance rate ≥50ml / min；
• Man and woman who childbearing potential agrees to use adequate contraception
• Willingness to provide enough tumor tissues for PD-L1 expression test

Exclusion Criteria:

• Patients could not obey the study protocol.
• Previous therapy with VEGFR Inhibitor or anti-PD-1 antibody.
• Other malignancy within 5 years prior to study enrolment, except for cervicalcarcinoma in situ, basal or squamous cell skin cancer.
• Known brain or CNS metastases.
• Patients with any active autoimmune disease or a documented history of autoimmunedisease within 4 weeks prior to enrollment.
• Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• Uncontrolled malignant ascites.
• Clinically significant cardiovascular diseases, including but not limited to acutemyocardial infarction, severe / unstable angina pectoris or coronary artery bypassgrafting within 6 months before enrollment; Congestive heart failure, New York HeartAssociation (NYHA) grade > 2; ventricular arrhythmia requiring drug treatment; LVEF (left ventricular ejection fraction) < 50%.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drugexcipients.
• Participation in another clinical trial with any experimental drug within 4 weeksprior to enrollment.
• Clinically significant electrolyte abnormalities judged by researchers.
• Systolic blood pressure > 140mmHg or diastolic blood pressure > 90mmHg regardless ofany antihypertensive drugs.
• Poorly controlled diabetes before enrollment.
• Any factors that influence the usage of oral administration and patients cannot takefruquintinib orally.
• Active gastric and duodenal ulcer, ulcerative colitis or uncontrolled hemorrhage inGI, or other conditions that may cause GI bleeding and perforation as determined bythe investigator.
• Patients with obvious evidence of bleeding tendency or medical history within 3 monthsbefore enrollment, hemoptysis or thromboembolism within 12 months.
• Active infection or serious infection that is uncontrolled by drug (NCI CTCAE v. 5.0Grade ≥ 2).
• History of clinically significant hepatic disease, including hepatitis B virus (HBV)infection with HBV DNA positive (copies ≥1×104/ml or >2000IU/ml); known hepatitis Cvirus infection with HCV RNA positive (copies ≥1×103/ml).
• Persisting toxicity related to prior therapy (NCI CTCAE v. 5.0 Grade > 1).
• Pregnant or breastfeeding female patient.
• Receive blood transfusion, blood products and hematopoietic factors such as albuminand granulocyte colony stimulating factor (G-CSF) within 14 days prior to enrollment.
• Other severe acute or chronic medical conditions including metabolic disorder,physical examination or laboratory abnormalities that may increase the risk associatedwith study participation or study treatment administration or may interfere with theinterpretation of study results and, in the judgment of the investigator, would makethe patient inappropriate for entry into this study.
• Urinary protein ≥ ++, and the 24-hour urine protein quantification is greater than 1.0g.
• Use of immunosuppressive medication, or systemic/local immunosuppressivecorticosteroids for complication.
• Patients considered unsuitable for inclusion in this study by the investigator.