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Toripalimab (IV given over 30 min at a dose of 3mg/m2 on day 1, every 2 weeks for 3 months) and Celecoxib (oral 200mg twice daily for 3 months) followed by surgical resection.

Cohort 1: Neoadjuvant treatment with toripalimab plus celecoxib for 3 months

Toripalimab (IV given over 30 min at a dose of 3mg/m2 on day 1, every 2 weeks for 3 months) followed by surgical resection.

Cohort 1: Neoadjuvant treatment with toripalimab monotherapy for 3 months

Toripalimab (IV given over 30 min at a dose of 3mg/m2 on day 1, every 2 weeks for 6 months) and Celecoxib (oral 200mg twice daily for 6 months) followed by surgical resection.

Cohort 2: Neoadjuvant treatment with toripalimab plus celecoxib for 6 months

Toripalimab (IV given over 30 min at a dose of 3mg/m2 on day 1, every 2 weeks for 6 months) followed by surgical resection.

Cohort 2: Neoadjuvant treatment with toripalimab monotherapy for 6 months

Yanhong Deng, M.D.

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.

Toripalimab With or Without Celecoxib as Neoadjuvant Therapy in Resectable dMMR/MSI-H Colorectal Cancer

Neoadjuvant PD-1 Blockade Toripalimab With or Without Celecoxib in Mismatch-repair Deficient or Microsatellite Instability-high Locally Advanced Colorectal Cancer (PICC): a Parallel-group, Randomized, Multi-cohort, Phase 2 Trial

Defined as the time from randomisation until the first occurrence of disease progression, second primary colorectal cancer, or death from any cause

Proportion of patients experiencing a pCR to perioperative PD-1 antibody

Defined as the time from randomization to death from any cause.

The proportion of patients achieved a complete resection with negative margin.

Assessed by evaluation of treatment-related adverse events

Any treatment-related delays in the planned surgery of no more than 28 days after the last preoperative toripalimab dose

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Toripalimab With or Without Celecoxib as Neoadjuvant Therapy in Resectable dMMR/MSI-H Colorectal Cancer	NCT03926338	Colorectal Canc... Mismatch Repair... Microsatellite ... Neoadjuvant The...	Cohort 1: Neoad... Cohort 1: Neoad... Cohort 2: Neoad... Cohort 2: Neoad...	18 Years - 100 Years	Sun Yat-sen University
Toripalimab With or Without Celecoxib as Neoadjuvant Therapy in Resectable dMMR/MSI-H Colorectal Cancer	NCT03926338	Colorectal Canc... Mismatch Repair... Microsatellite ... Neoadjuvant The...	Cohort 1: Neoad... Cohort 1: Neoad... Cohort 2: Neoad... Cohort 2: Neoad...	18 Years - 100 Years	Sun Yat-sen University
Toripalimab With or Without Celecoxib as Neoadjuvant Therapy in Resectable dMMR/MSI-H Colorectal Cancer	NCT03926338	Colorectal Canc... Mismatch Repair... Microsatellite ... Neoadjuvant The...	Cohort 1: Neoad... Cohort 1: Neoad... Cohort 2: Neoad... Cohort 2: Neoad...	18 Years - 100 Years	Sun Yat-sen University

Spots Global Cancer Trial Database for cohort 2: neoadjuvant treatment with toripalimab monotherapy for 6 months