Toripalimab (PD-1) + CAPOX iTNT, with SCRT, lifts complete response to 61% in high-risk pMMR LARC

TORCH-iTNT (NCT06281405) is a randomized Phase 2 study in pMMR/MSS locally advanced rectal cancer (T3–4/N+M0) comparing 6 cycles of CAPOX (capecitabine/oxaliplatin) + toripalimab (PD-1 inhibitor) alone (Group A) vs short-course RT 25Gy/5 fractions then the same CAPOX+toripalimab (Group B). Among treated completers (n=137; A=65, B=72) with 97% carrying ≥1 MRI/clinical high-risk feature, overall complete response (cCR+pCR) was 36.9% (24/65) with CAPOX+toripalimab alone vs 61.1% (44/72) with SCRT→CAPOX+toripalimab; pCR among those resected was 35.2% (19/54) vs 44.9% (22/49), and watch-and-wait uptake was 7.7% (5/65) vs 30.6% (22/72). Grade 3–4 thrombocytopenia was similar (12% in both arms); 1 progression occurred per arm—these CR rates sit well above typical pCR rates with non–IO TNT regimens (20%–30% in Phase 3 TNT programs such as PRODIGE-23 and RAPIDO), suggesting SCRT may be doing meaningful immunologic “priming” here.