Tyrosine Kinase Inhibitor (TKI) + Anti-PD-1 Antibody in TKI-responded Microsatellite Stability/Proficient Mismatch Repair (MSS/pMMR) Metastatic Colorectal Adenocarcinoma.

Inclusion Criteria:

• Subjects who voluntarily participated in the study, signed the written informedconsent form, and could comply with the protocol of study.
• Male or female of age 18-75 years.
• Subjects with colorectal adenocarcinoma who were histopathologically confirmed, andwith locally advanced (unresectable) or mCRC.
• Subjects who underwent standard antitumor therapies (fluorouracil, oxaliplatin,irinotecan were used, with or without administration of bevacizumab and/or cetuximab).
• Patients with MSS/pMMR mCRC (immunohistochemistry, polymerase chain reaction ornext-generation sequencing can be used).
• All adverse reactions associated with drug use or surgery were reduced to grade 0-1 (according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0) orto a level required by the protocol criteria.
• The presence of at least one measurable lesion by computed tomography (CT) or magneticresonance imaging (MRI).
• Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1.
• Subjects with life expectancy ≥ 12 weeks.
• Adequate important organs functions: bone marrow function (neutrophil count ≥ 1.5×10^9/L; platelet ≥ 80×10^9/L; hemoglobin ≥ 90 g/L), liver function (serum albumin ≥ 28 g/L; total bilirubin ≤ 1.5×upper limit of normal (ULN); alanine aminotransferaseand aspartate aminotransferase ≤ 3×ULN, or ≤ 5×ULN if liver metastases are present),renal function (serum creatinine ≤ 1.5×ULN or creatinine clearance (CrCl) ≥ 40 mL/min,using the Cockcroft-Gault formula; urine protein < 2+; 24h urinary protein content < 1.0 g/24h if urinary protein ≥ 2+ ), coagulation function (international normalizedratio or activated partial thromboplastin time ≤ 2×ULN), thyroid function (thyrotropin ≤ 1×ULN).

Exclusion Criteria:

• Known microsatellite instability high (MSI-H) mCRC.
• Participation in another study with intervention or drugs within the past 4 weeks.
• Performing surgery and incomplete recovery within the past 4 weeks.
• Subjects with active autoimmune diseases or with related history. Subjects withcontrolled type I diabetes or hypothyroidism with substitution therapy may be includedfor further screening.
• Any conditions requiring corticosteroids (> 10 mg per day of prednisone or equivalent)or immunosuppressive drugs as systemic treatment within the past 1 week.
• Other active malignancy within the past 5 years, except for the cured limited cancer (such as basal cell carcinoma, carcinoma in situ of the prostate or cervix, etc.).
• Subjects with history of hepatic encephalopathy or confirmed metastases to centralnervous system.
• Subjects with non-infectious pneumonia under steroid treatment within the past 6months.
• Suffering from chronic or active infections, fever (≥ 38.5℃) within the past 1 week,or white blood cell count > 15×10^9/L), requiring systemic anti-infective treatment atthe screening period, except for viral hepatitis.
• Subjects with any other abnormal condition that is inconsistent with the studymedication, or may increase the risk of the subject，according to investigators'judgment.
• Congenital or acquired immunodeficiency (such as human immunodeficiency virus).
• Subjects with active hepatitis B virus (HBV) (HBV surface antigen positive and HBV-DNA > 2000 IU/ml) or hepatitis C virus (HCV) (HCV antibody and HCV-RNA positive).
• Subject who received a live attenuated vaccine within the past 4 weeks, or vaccinationis planned during anti-PD-1 antibody treatment or within 5 months after the lasttreatment.
• More than mild pericardial effusion, massive pleural or/and peritoneal effusions needpuncture and drainage at the screening period.
• Subjects with symptomatic heart and cerebrovascular diseases: heart failure (New YorkHeart Association class III or IV, left ventricular ejection fraction < 50%),uncontrolled hypertension or arrhythmias, serious cardiovascular and cerebrovascularevents (acute coronary syndrome, stroke, thromboembolism, etc.) within the past 6months.
• Known allergy to targeted drugs.
• Women being pregnant, or during lactation, or planning to get pregnant during thetrial.
• Subjects with any other conditions judged by investigators would be excluded.