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

This is an interventional treatment trial for Colorectal Cancer focused on measuring MSI-H, dMMR, PD-1 antibody, COX inhibitor, tumor mutation burden Read More

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.