NCT03926338: PICC

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

Recruiting now Phase 2 Last updated 20 November 2025

What this trial tests

Phase 2 trial testing Neoadjuvant toripalimab plus celecoxib for 6 cycles in Colorectal Cancer in 270 participants. Currently enrolling.

Timeline

10 May 2019

Primary endpoint
1 April 2027

1 April 2030

Quick facts

Lead sponsor	Sun Yat-sen University
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	single
Primary purpose	treatment
Enrollment	270
Start date	10 May 2019
Primary completion	1 April 2027
Estimated completion	1 April 2030
Sites	1 location across China

Drugs / interventions tested

• Neoadjuvant toripalimab plus celecoxib for 6 cycles — full drug profile →
• Neoadjuvant toripalimab monotherapy for 6 cycles — full drug profile →
• Neoadjuvant toripalimab plus celecoxib for 12 cycles — full drug profile →
• Neoadjuvant toripalimab monotherapy for 12 cycles — full drug profile →
• Toripalimab plus celecoxib as neoadjuvant or definitive therapy — full drug profile →

Conditions studied

• Colorectal Cancer — all drugs for Colorectal Cancer →
• Mismatch Repair-deficient (dMMR) — all drugs for Mismatch Repair-deficient (dMMR) →
• Microsatellite Instability-high (MSI-H) — all drugs for Microsatellite Instability-high (MSI-H) →
• Neoadjuvant Therapy — all drugs for Neoadjuvant Therapy →

Sponsor

Sun Yat-sen University

Who can join

Adults 18 to 75, any sex, with Colorectal Cancer or Mismatch Repair-deficient (dMMR). Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Comprehensive review of targeted therapy for colorectal cancer.
   Xie YH, Chen YX, Fang JY. · · 2020 · cited 1162× · PMID 32296018 · DOI 10.1038/s41392-020-0116-z
2. The updated landscape of tumor microenvironment and drug repurposing.
   Jin MZ, Jin WL. · · 2020 · cited 900× · PMID 32843638 · DOI 10.1038/s41392-020-00280-x
3. Neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, in mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer (PICC): a single-centre, parallel-group, non-comparative, randomised, phase 2 trial.
   Hu H, Kang L, Zhang J, Wu Z, et al · · 2022 · cited 214× · PMID 34688374 · DOI 10.1016/s2468-1253(21)00348-4
4. Neoadjuvant immune checkpoint blockade: A window of opportunity to advance cancer immunotherapy.
   Topalian SL, Forde PM, Emens LA, Yarchoan M, et al · · 2023 · cited 203× · PMID 37595586 · DOI 10.1016/j.ccell.2023.07.011
5. Cancer cell metabolism and antitumour immunity.
   De Martino M, Rathmell JC, Galluzzi L, Vanpouille-Box C. · · 2024 · cited 183× · PMID 38649722 · DOI 10.1038/s41577-024-01026-4
6. Immunotherapy efficacy on mismatch repair-deficient colorectal cancer: From bench to bedside.
   Lizardo DY, Kuang C, Hao S, Yu J, et al · · 2020 · cited 160× · PMID 33035640 · DOI 10.1016/j.bbcan.2020.188447
7. Decoding the spatiotemporal heterogeneity of tumor-associated macrophages.
   Chu X, Tian Y, Lv C. · · 2024 · cited 125× · PMID 39068459 · DOI 10.1186/s12943-024-02064-1
8. Immunotherapy with immune checkpoint inhibitors in colorectal cancer: what is the future beyond deficient mismatch-repair tumours?
   Huyghe N, Baldin P, Van den Eynde M. · · 2020 · cited 79× · PMID 32104582 · DOI 10.1093/gastro/goz061