Toripalimab With or Without Celecoxib as Neoadjuvant Therapy in Resectable dMMR/MSI-H Colorectal Cancer
Status:
Recruiting
Trial end date:
2022-05-01
Target enrollment:
Participant gender:
Summary
Colorectal cancer of Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high
(MSI-H) accounts for approximately 15% of all colorectal cancer patients, with a higher
proportion in right colon cancer. Previous studies have found that colon cancer patients with
dMMR/MSI-H cannot benefit from 5-fluorouracil (5-FU) adjuvant chemotherapy. Once patients
have distant metastases, they are not sensitive to traditional palliative chemotherapy, and
the prognosis is significantly worse than that of mismatch repair-proficient
(pMMR)/microsatellite stability (MSS). A phase II clinical study of anti-PD-1 immunotherapy
based on mismatch repair (MMR) status published in 《N Engl J Med》 showed that the objective
response rate (ORR) of advanced colorectal cancer patients with dMMR received anti-PD-1 is
40%, and a longer response time can be obtained compared to conventional chemotherapy.
Anti-PD-1 neoadjuvant therapy has proven to be safe and feasible in lung cancer, bladder
cancer and malignant melanoma, and can achieve more than 40% of major pathological response.
However, there are no reports of anti-PD-1 neoadjuvant therapy for the dMMR/MSI-H colorectal
cancer. Therefore, the aim of this study was to find the best multidisciplinary treatment for
resectable colorectal cancer patient with the dMMR/MSI-H phenotype and to explore whether
cyclooxygenase (COX) inhibitors combined with anti-PD-1 monoclonal antibody (mAb) could
further improve efficacy.