Surgical efficacy of neoadjuvant mono-immunotherapy for T ₄ -deficient mismatch repair colon cancer: A prospective, single-arm, phase II trial.

Abstract

145 Background: Given that Deficient Mismatch Repair (dMMR) colon cancer patients respond poorly to conventional chemotherapy but immunotherapy significantly improves pCR rates in this population, this study aims to explore whether neoadjuvant immunotherapy can increase the rate of R0 resection with preservation of adjacent organs in dMMR T4 colon cancer patients and investigate the optimal regimen of immunotherapy. Methods: This single-arm, open-label, phase II trial was conducted at Peking Union Medical College Hospital in China. Patients were eligible for enrollment if they had immunohistochemically confirmed colon adenocarcinoma with confirmation of dMMR and clinical T 4 stage (defined as a tumor has invaded the serosal surface [cT 4a ] or has invaded or adhered to adjacent organs or structures [cT 4b ]). All patients are planned to receive three cycles of camrelizumab (200mg intravenously administered at the beginning of each cycle every 3 weeks) followed by radical surgery. Surgery was scheduled 2–4 weeks after three cycles. The primary endpoint of this study was the R0 resection rate in all patients who received surgery (defined as resection with a microscopic negative margin). Secondary endpoints included the rate of pCR (defined as no residual viable tumor in either the tumor bed or the lymph nodes), tumor regression grade (TRG), the incidence of adverse event (AE) during neoadjuvant immunotherapy. Results: A total of 18 patients with clinical T 4 stage and dMMR colon cancers were deemed eligible for enrollment and 17 patients were included in per-protocol set analysis from April 2024 to July 2025. The primary endpoint was evaluable in 17 patients, with 16 patients having R0 resection of 94.1%. Pathological response was observed in 14 of 16 patients, including 11 with pathological complete response. The pCR associated with a decreased trend density of PD-L1+ cells [139.3 (99.0, 272.6) cells/mm 2 vs 323.1 (114.3, 528.2) cells/mm 2 , P =0.157]. All patients experienced treatment-related AEs (100%) during neoadjuvant immunotherapy. Sixteen patients (94.1%) had Grade 1-2 AEs, while 1 patients had Grade 3 AE. Conclusions: Three cycles of mono-immunotherapy appear to be a regimen for patients with dMMR T 4 colon cancer with acceptable surgical efficacy and safety. Clinical trial information: NCT06215677 .