NCT06903858

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

Neoadjuvant Toripalimab Plus Celecoxib in Mismatch-repair Deficient or Microsatellite Instability-high Locally Advanced Colorectal Cancer (PICC-3): a Multicenter, Single-arm, Phase 2 Trial

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 105 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Several Phase II studies have demonstrated the feasibility, effectiveness, and good tolerability of neoadjuvant immune checkpoint inhibitor (ICI) treatment for localized dMMR colorectal and rectal cancers. The significant clinical and pathological complete response rates offer the possibility of avoiding surgical resection. dMMR colorectal cancers are generally larger and more advanced than pMMR tumors, often requiring more extensive surgery with associated risks such as anastomotic leakage, ureteral injury, and infection. If oncological outcomes are not affected (requiring long-term follow-up), non-surgical treatment becomes an attractive option for localized dMMR colorectal cancer. Moreover, pelvic radiotherapy, the standard for locally advanced rectal cancer, causes both short-term and long-term adverse effects (e.g., bowel and bladder dysfunction, fistula, infertility), significantly impacting quality of life. Total mesorectal excision also carries risks of complications and sexual dysfunction, often requiring a stoma, making organ preservation a more urgent need for rectal cancer patients. Phase II trials and the international "watch-and-wait" database have confirmed the feasibility and safety of organ preservation for pMMR locally advanced rectal cancer. Therefore, the high clinical and pathological complete response rates achieved by neoadjuvant immunotherapy for dMMR/MSI-H rectal cancer offer promising prospects for non-surgical treatment.

Conditions

• Colorectal Cancer (CRC)
• PD-1 Inhibitor
• Neoadjuvant Immunotherapy
• Celecoxib
• Watch &Amp; Wait

Interventions

Type	Name	Description
DRUG	Toripalimab combined with celecoxib	Toripalimab is administered via intravenous infusion at 3 mg/kg over 30 minutes (initial infusion time is 60 minutes), once every two weeks, for a total of 12 doses before surgery. Celecoxib is taken orally at 200 mg per dose, twice daily, for a duration of 6 months.
PROCEDURE	Curative resection of colorectal cancer	Patients who do not achieve cCR based on radiographic imaging (CT/MRI of chest, abdomen, pelvis, and rectal MRI), endoscopy, and digital rectal examination (if applicable) are recommended to undergo curative resection of colorectal cancer.
OTHER	Watch-and-wait strategy	Patients achieving clinical complete response (cCR) based on radiographic imaging (CT/MRI of chest, abdomen, pelvis, and rectal MRI), endoscopy, and digital rectal examination (if applicable) are recommended to adopt a watch-and-wait strategy.

Timeline

• Start date: 2025-04-01
• Primary completion: 2028-04-01
• Completion: 2031-04-01
• First posted: 2025-04-01
• Last updated: 2025-04-01

Locations

1 site across 1 country: China