NCT03926338RecruitingPhase 2

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

Neoadjuvant PD-1 Blockade by Toripalimab With or Without Celecoxib in Mismatch-repair Deficient or Microsatellite Instability-high Locally Advanced Colorectal Cancer (PICC)

Source: ClinicalTrials.gov · Last updated 20 Nov 2025

Brief summary (registry, in English)

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.

Status (registry): Recruiting
Phase (registry): Phase 2
Study type: Interventional
Enrollment: 270 (estimated)
First submitted: 20 Apr 2019
Start date: 10 May 2019
Primary completion date: 1 Apr 2027
Lead sponsor: Sun Yat-sen University
Diseases: Colorectal cancer
NCT number: NCT03926338

What you commit to

Study type: Interventional · Phase 2
Planned participants: 270
From 10 May 2019 to the primary completion date, 1 Apr 2027
1 site in 1 country
Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Prior treatment

Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization.
Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.
Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.

Other illness

Heart failure grade III/IV (NYHA-classification).
Subjects with known allergy to the study drugs or to any of its excipients.

Lab values

Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody, anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody or other drug/antibody that acts on T cell costimulation or checkpoint pathways.

Other

Breast- feeding or pregnant women
Lack of effective contraception.
With any distant metastasis.

Who the study is looking for

Willing and able to provide written informed consent.
Histological or cytological documentation of adenocarcinoma of the colon or rectum.
Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR).
Male or female subjects aged 18 to 75 years.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Determined CT or MRI scans (done within 14 days of registration) of the chest, abdomen and pelvis: locally advanced (cT3-4 or cN1-2 \[with the definition of a clinically positive lymph node being any node ≥ 1.0 cm\]).
Non complicated primary tumor (obstruction, perforation, bleeding).
No previous any systemic anticancer therapy for colorectal cancer disease.
Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment.

Age in the registry: 18 years to 75 years · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

Sites (1)

Sites in registry order. Pick your city on the disease page to sort them by distance.

Site	City	Country	Site status
The Sixth Affiliated Hospital of Sun Yat-sen University Coordinator of this site? Confirm its status	Guangzhou	China	Recruiting

Related publications

Neoadjuvant toripalimab plus celecoxib versus toripalimab monotherapy for mismatch repair-deficient or microsatellite instability-high, locally advanced colorectal cancer (PICC-2): an open-label, multicentre, randomised, phase 2 trial.Lancet Oncol · 2026 · PMID 42385761

This page is information, not medical advice. Discuss any trial with your doctor.