PD-1 Antibody Combined With COX Inhibitor in MSI-H/dMMR or High TMB Colorectal Cancer

Inclusion Criteria: 1. Signed informed consent; able to comply with study and/or follow- up procedures; 2. Age:18-75 years old; 3. Histological or cytological documentation of colorectal cancer; 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 5. There must be documentation by CT scan, MRI, or intraoperative palpation that tumor is unresectable; 6. Have had at least one lines of chemotherapy fail or refuse to receive chemotherapy; 7. Histologically confirmed metastatic or primary colorectal cancer as dMMR/MSI-H or whole exon sequence confirmed tumor mutation burden higher than 1000; 8. Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: Hemoglobin (Hb) ≥ 90g/ L, absolute neutrophil count (ANC) ≥ 1.5×109/ L, platelet count ≥ 100×109/ L; Total bilirubin ≤ 1.5×the upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 ×ULN; Serum creatinine ≤1.5×the ULN. Exclusion Criteria: 1. Previous treatment with other therapy targeting T-cell costimulation or immune checkpoint pathways; 2. Active, known, or suspected autoimmune disease (except for type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition requiring only hormone replacement, or conditions not expected to recur in the absence of an external trigger); 3. A previous cancer active within the previous 5 years; 4. Subjects with known allergy to the study drugs or to any of its excipients; 5. Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment; 6. Heart failure grade III/IV (NYHA-classification); 7. Patients with active infection within 1 week before enrollment (infection caused by fever above 38 °C); 8. Patients with severe lung disease (interstitial pneumonia, pulmonary fibrosis, severe emphysema); 9. Patients with active gastrointestinal bleeding; 10. Patients with serious complications (intestinal obstruction, renal insufficiency, hepatic insufficiency, cerebrovascular disorders); 11. Psychiatric disease or a history of central nervous system disease that affects clinical treatment; 12. Receive other anti-tumor treatments (including anti-tumor immunotherapy, interventional therapy and intra-serosal injection of anti-tumor drugs) or participate in other interventional clinical trials within two weeks before enrollment; 13. Breast- feeding or pregnant women; 14. Lack of effective contraception; 15. The investigator determined that the patient was not eligible for this clinical trial.