Toripalimab (PD-1) + celecoxib (COX-2) lifts pCR to 89% in dMMR/MSI-H locally advanced CRC (PICC-2)

Toripalimab is an anti–PD-1 monoclonal antibody, and celecoxib is an oral COX-2 inhibitor hypothesized to reshape the inflammatory tumor microenvironment to potentiate checkpoint blockade. In the open-label, multicentre, randomized Phase 2 PICC-2 trial in China (NCT03926338), patients with dMMR/MSI-H, cT3–T4 and/or N+ locally advanced colorectal cancer received neoadjuvant toripalimab q14d ×12 cycles with celecoxib (200mg BID, days 1–14 each cycle) vs toripalimab alone (n=55/arm); pCR was 89% (49/55) vs 69% (38/55) (absolute +19pp, p=0.014) with high treatment completion (89% both arms) and surgery rates (96% vs 93%). Grade 3 TRAEs were uncommon and similar (5% vs 7%; no grade 4–5), with notable events including tumor perforation (4% combo; 2% mono) and bowel obstruction (2% combo); this pCR rate sits above the ~68% pCR reported with short-course neoadjuvant nivolumab+ipilimumab in resectable dMMR colon cancer (NICHE-2), while remaining within the “very high response” range now typical for neoadjuvant ICI in this biomarker-defined setting.