Colorectal CancerPhase 2PICC-3NCT06903858
Toripalimab Plus Celecoxib for dMMR/MSI-H Locally Advanced Colorectal Cancer
A Phase 2 study testing Toripalimab plus celecoxib, Non-operative management and Curative-intent surgery in people with Colorectal Cancer and Microsatellite Instability High, run by Sun Yat-sen University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Microsatellite Instability High, Mismatch Repair Deficiency
- What is being tested?
- Toripalimab plus celecoxib, Non-operative management and Curative-intent surgery
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2025to 1 Apr 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
- Pregnancy or lactation.
- Women of childbearing potential (last menstruation <2 years ago) or fertile men unwilling to use effective non-hormonal contraception.
- Any unstable medical condition compromising safety or protocol compliance.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The Sixth Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510655
Yanhong Deng, MD., 020-38379762, dengyanh@mail.sysu.edu.cn
About this study
Official title: Toripalimab Plus Celecoxib With Response-adapted Non-operative Management for Mismatch Repair-deficient or Microsatellite Instability-high Locally Advanced Colorectal Cancer (PICC-3): a Multicenter, Single-arm, Phase 2 Trial
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.
Read the detailed description
Patients with dMMR/MSI-H locally advanced colorectal cancer have shown high sensitivity to neoadjuvant immune checkpoint inhibitor. Several phase II studies have demonstrated high rates of clinical complete response (cCR) and pathological complete response (pCR), supporting the feasibility and safety of immunotherapy in localized dMMR/MSI-H colorectal cancer.
Radical surgery for locally advanced colorectal cancer is associated with substantial perioperative morbidity and long-term functional consequences. In particular, total mesorectal excision for rectal cancer may result in bowel, urinary, and sexual dysfunction, and some patients may require temporary or permanent stoma formation. Therefore, organ preservation and non-operative management have become important treatment goals for selected patients with colorectal cancer who achieve complete clinical response after neoadjuvant therapy.
Previous studies have demonstrated the feasibility and safety of non-operative management after immune checkpoint inhibitor in patients with dMMR/MSI-H rectal cancer, while emerging evidence suggests that this strategy may also be feasible in selected patients with colon cancer following immunotherapy.
- Being tested
- Toripalimab plus celecoxib, Non-operative management, Curative-intent surgery
- Keywords
- PD-1 blockade, Toripalimab, COX-2 inhibitor, Celecoxib, Non-operative Management
- Medical subject headings
- Colorectal Neoplasms, Turcot syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Toripalimab plus celecoxibDrug
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.
Non-operative managementProcedure or surgery
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.
Curative-intent surgeryProcedure or surgery
Patients who do not achieve cCR will undergo curative-intent surgery.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Toripalimab plus celecoxib; Procedure: Non-operative management; Procedure: Curative-intent surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (5)
Pathological complete response (pCR) rate
the percentage of subjects with no residual viable tumor in the resected primary tumor specimen and all sampled regional lymph nodes after radical surgery (ypT0N0).
Measured: 3 years
Clinical complete response (cCR) rate
the percentage of subjects achieving no evidence of residual tumour on comprehensive response assessment, including imaging, endoscopy with negative biopsy findings, digital rectal examination (if applicable), and ctDNA evaluation.
Measured: 3 years
Complete response (CR) rate
the percentage of subjects achieving pathological complete response (pCR) after surgery or clinical complete response (cCR) with non-operative management.
Measured: 3 years
Overall survival (OS)
the time from the first dose of study treatment to death from any cause.
Measured: 5 years
Incidence of treatment-related adverse events
incidence and severity of treatment-related adverse events, graded according to CTCAE version 5.0.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2025
- Study start1 Jun 2025
- Primary completion1 Apr 2028 (estimated)
- Study completion1 Apr 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective, Multicenter, Single-arm, Phase II
- Masking
- None (open label)
- Enrolment
- 105 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yanhong Deng, Sixth Affiliated Hospital, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06903858
- Sponsor's protocol ID
- CSWOG-C08
- Acronym
- PICC-3
- Status last verified
- May 2026
- First submitted
- 28 Mar 2025
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Toripalimab Plus Celecoxib With Response-adapted Non-operative Management for Mismatch Repair-deficient or Microsatellite Instability-high Locally Advanced Colorectal Cancer (PICC-3): a Multicenter, Single-arm, Phase 2 Trial
- ClinicalTrials.gov ID
- NCT06903858
- Acronym / sponsor ID
- PICC-3 / CSWOG-C08
- Keywords
- PD-1 blockade, Toripalimab, COX-2 inhibitor, Celecoxib, Non-operative Management
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 105 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Jun 2025 (actual)
- Primary completion
- 1 Apr 2028 (estimated)
- Study completion
- 1 Apr 2031 (estimated)
- First posted
- 1 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Patients with dMMR/MSI-H locally advanced colorectal cancer have shown high sensitivity to neoadjuvant immune checkpoint inhibitor. Several phase II studies have demonstrated high rates of clinical complete response (cCR) and pathological complete response (pCR), supporting the feasibility and safety of immunotherapy in localized dMMR/MSI-H colorectal cancer.
Radical surgery for locally advanced colorectal cancer is associated with substantial perioperative morbidity and long-term functional consequences. In particular, total mesorectal excision for rectal cancer may result in bowel, urinary, and sexual dysfunction, and some patients may require temporary or permanent stoma formation. Therefore, organ preservation and non-operative management have become important treatment goals for selected patients with colorectal cancer who achieve complete clinical response after neoadjuvant therapy.
Previous studies have demonstrated the feasibility and safety of non-operative management after immune checkpoint inhibitor in patients with dMMR/MSI-H rectal cancer, while emerging evidence suggests that this strategy may also be feasible in selected patients with colon cancer following immunotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective, Multicenter, Single-arm, Phase II
| Arm | Type | Receives |
|---|---|---|
| Toripalimab plus celecoxib | Experimental | Drug: Toripalimab plus celecoxib, Procedure: Non-operative management, Procedure: Curative-intent surgeryToripalimab 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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).
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Toripalimab plus celecoxibToripalimab 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. | Drug | Toripalimab plus celecoxib |
| Non-operative managementPatients 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. | Procedure or surgery | Toripalimab plus celecoxib |
| Curative-intent surgeryPatients who do not achieve cCR will undergo curative-intent surgery. | Procedure or surgery | Toripalimab plus celecoxib |
Primary outcome
Event-free survival (EFS)
Time frame: 3 years
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.
5 secondary outcomes
Pathological complete response (pCR) rate
Time frame: 3 years
Clinical complete response (cCR) rate
Time frame: 3 years
Complete response (CR) rate
Time frame: 3 years
Overall survival (OS)
Time frame: 5 years
Incidence of treatment-related adverse events
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Toripalimab plus celecoxib, Non-operative management and Curative-intent surgery in people with Colorectal Cancer and Microsatellite Instability High, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yanhong Deng, MD. (020-38379762, dengyanh@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival (EFS) (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.