Tislelizumab (PD-1) neoadjuvant drives 78.6% pCR + ctDNA MRD clears fast in dMMR/MSI-H colon cancer

Tislelizumab is an anti–PD-1 monoclonal antibody engineered to minimize Fcγ receptor binding; here it was given as neoadjuvant monotherapy (200mg IV Q3W ×4, then up to 8+ cycles per MDT) with tumor-informed ctDNA MRD tracking in a prospective pilot in locally advanced dMMR/MSI-H colon adenocarcinoma (n=40 enrolled; 39 treated; NCT06262581; median follow-up 13.6 months). Among resected patients (n=28), pCR was 78.6% (22/28) and MPR was 92.9% (26/28); 9 patients chose non-operative management after cCR, yielding an overall CR rate of 79.5%—numerically above historical surgery-first pCR rates (typically low single digits) and even higher than published neoadjuvant dual-checkpoint benchmarks in dMMR colon cancer like NICHE-2 (pCR 68%, MPR 95%). Grade 3 irAEs occurred in 10.3% (4/39; pneumonitis n=2, renal insufficiency n=1, stroke n=1) with no treatment-related deaths; MRD was positive at baseline in 96.6% (28/29 tested) and cleared in 48.3% after 1 cycle and 75.9% after 2 cycles, with 1 patient MRD-positive post-treatment after pneumonitis-driven discontinuation.