A Phase II Study to Explore the Neoadjuvant Treatment of Serplulimab Combined with CAPEOX + Celecoxib in the Treatment of Locally Advanced Rectal Cancer
Colorectal cancer of Mismatch Repair-proficient (pMMR)/ Microsatellite Stability (MSS) accounts for approximately 85% of all colorectal cancer patients, which might be insensitive to immunotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy, such as CAPEOX regimen, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Celecoxib, a COX-2 inhibitor, can improve the immune microenvironment and have a potential to synergy with immunotherapy. Chemotherapy can improve the immunogenicity of cancer cells that might enhance the efficacy of immunotherapy. The aim of this study is to explore whether chemotherapy and cyclooxygenase (COX) inhibitors combined with anti-PD-1 monoclonal antibody (mAb) could improve efficacy for resectable colorectal cancer patient with the pMMR/MSS phenotype.
• Willing and able to provide written informed consent.
• Male or female subjects ≧ 18 years ≦ 75 of age.
• Histological or cytological documentation of adenocarcinoma of the rectum.
• No previous any systemic anticancer therapy for rectal cancer disease.
• The lower margin of the tumor is less than 10cm from the anus verge.
• cT2N1-2M0, cT3N0-2M0, cT4N0-2M0 MSS with MRF(-) assessed by MRI.
• Primary tumor can be detected by CT or MRI.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Eligible tumor tissues were identified for MSI/MMR assays.
⁃ Hepatitis B Surface Antigen (HBsAg) (-).
⁃ If HBsAg (+) , HBV-DNA must be less than 2500 copies/mL or 500 IU/mL to be enrolled.
⁃ Patients with HCV antibody (-) or HCV-RNA negative can be enrolled. Aspartate aminotransferase (AST) must be ≤ 3 x ULN for the lab. If HCV-RNA is positive, patients with both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) performed ≤3×ULN could be enrolled. Patients infected with both hepatitis B virus and hepatitis C virus should be excluded (positive for HBsAg or HBcAb and positive for HCV antibodies).