Toripalimab Plus Celecoxib for dMMR/MSI-H Locally Advanced Colorectal Cancer

NCT06903858 | Recruiting Phase 2

• 1 other identifier: CSWOG-C08
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

The PICC-3 study is a multicentre, single-arm, phase II trial evaluating toripalimab plus celecoxib in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced colorectal cancer. The trial uses a response-adapted treatment strategy, whereby patients with clinical complete response (cCR) after therapy may enter a non-operative management pathway, while patients without cCR proceed to surgery. Response assessment is based on imaging, endoscopy, biopsy evaluation, and ctDNA analysis.

Conditions

Colorectal Cancer; Microsatellite Instability High; Mismatch Repair Deficiency

Keywords

PD-1 blockade; Toripalimab; COX-2 inhibitor; Celecoxib; Non-operative Management

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS)

  the time from the first dose of study treatment to the occurrence of one of the following events: locally progressive disease of the primary tumour precluding curative-intent surgery, R2 resection, local recurrence after R0 or R1 resection, unsalvageable local regrowth during non-operative management, distant metastasis, a second primary colorectal cancer, or death from any cause, whichever occurs first.

  3 years

Secondary Outcomes (5)

• Pathological complete response (pCR) rate

  3 years

• Clinical complete response (cCR) rate

  3 years

• Complete response (CR) rate

  3 years

• Overall survival (OS)

  5 years

• Incidence of treatment-related adverse events

  3 years

Study Arms (1)

Toripalimab plus celecoxib

EXPERIMENTAL

Toripalimab is administered intravenously at 3 mg/kg over 30 minutes once every 2 weeks for a total of 12 doses. Celecoxib is administered orally at 200 mg twice daily for 6 months. Patients achieving clinical complete response (cCR) are recommended for non-operative management, whereas patients without cCR are recommended to undergo curative-intent surgery.

Drug: Toripalimab plus celecoxib; Procedure: Non-operative management; Procedure: Curative-intent surgery

Interventions

Toripalimab plus celecoxib DRUG

Toripalimab is administered intravenously at 3 mg/kg over 30 minutes once every 2 weeks for a total of 12 doses. Celecoxib is administered orally at 200 mg twice daily for 6 months.

Toripalimab plus celecoxib

Non-operative management PROCEDURE

Patients achieving clinical complete response (cCR) according to comprehensive response assessment, including imaging, endoscopy, digital rectal examination (if applicable), and ctDNA evaluation, may undergo non-operative management.

Toripalimab plus celecoxib

Curative-intent surgery PROCEDURE

Patients who do not achieve cCR will undergo curative-intent surgery.

Toripalimab plus celecoxib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent and willingness/compliance with study procedures.
• Age ≥18 years.
• Histologically confirmed colorectal adenocarcinoma.
• ECOG performance status 0-1.
• Locally advanced primary tumor (T3/T4 and/or N+) confirmed by CT/MRI (pelvic MRI for rectal cancer).
• dMMR (IHC) or MSI-H (PCR) status.
• No prior anti-cancer therapy for colonrectal cancer (surgery/chemotherapy/targeted therapy/radiation).
• Adequate organ function
• For women of childbearing potential: negative pregnancy test and contraception use during and for 3 months post-treatment. Male participants with fertile partners must use contraception.
• Willingness to adhere to study requirements.

You may not qualify if:

• Presence of distant metastases (M1) confirmed by CT/MRI or PET-CT (at least covering the chest, abdomen, and pelvis).
• Complete intestinal obstruction, active bleeding, or perforation requiring emergency surgery.
• Inability to achieve complete resection of the primary colorectal tumor.
• History or concurrent active malignancy (except malignancies cured ≥5 years ago or adequately treated carcinoma in situ).
• Prior treatment with anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies, or other drugs/antibodies targeting T-cell co-stimulation or checkpoint pathways.
• Major surgery (e.g., laparotomy, thoracotomy, organ resection via laparoscopy) or severe trauma within 4 weeks before enrollment (surgical incision must be fully healed).
• Thromboembolic events (e.g., cerebrovascular accident, transient ischemic attack, pulmonary embolism, deep vein thrombosis) within 12 months before enrollment.
• Active coronary artery disease, severe/unstable angina, or newly diagnosed angina/myocardial infarction within 12 months before enrollment.
• New York Heart Association (NYHA) Class II or higher congestive heart failure (see Appendix 3).
• HIV infection, AIDS, or untreated active hepatitis (HBV-DNA ≥500 IU/mL; HCV-RNA above detection limit).
• Active inflammatory bowel disease or other colorectal disorders causing chronic diarrhea.
• Active, known, or suspected autoimmune disease (exceptions: stable conditions like type 1 diabetes, hypothyroidism on hormone replacement, or skin disorders without systemic treatment, e.g., vitiligo, psoriasis, alopecia).
• Interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases (e.g., diabetes, hypertension, pulmonary fibrosis, acute pneumonia).
• Residual toxicity ≥Grade 2 (per CTCAE v5.0) from prior therapies (except anemia, alopecia, skin pigmentation).
• Known or suspected hypersensitivity to any study-related drugs.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

The Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Turcot syndrome

Interventions

toripalimab; Celecoxib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Yanhong Deng, MD.

CONTACT

020-38379762; dengyanh@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Prospective, Multicenter, Single-arm, Phase II

Study Record Dates

• First Submitted: March 28, 2025
• First Posted: April 1, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2031
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)