Iparomlimab/Tuvonralimab Integrating With Total Neoadjuvant Therapy for pMMR/MSS Locally Advanced Rectal Cancer (IT-TNT)

In colorectal cancer (CRC), ICIs show strong therapeutic associations with microsatellite instability-high (MSI-H) status, while patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) tumors exhibit poor responses. Dual immunotherapy may represent a promising strategy for MSS populations. The Dutch NICHE trial reported a 27% pathological response rate (4/15) in MSS CRC patients with clinical stage I-III disease treated with neoadjuvant ipilimumab plus nivolumab. In advanced or metastatic CRC, a study by Jin Li et al. demonstrated that iparomlimab/tuvonralimab combined with bevacizumab and the XELOX regimen achieved an objective response rate of 70.6% (95% CI: 56.2%-82.5%). Radiotherapy may synergize with ICIs through multiple immunomodulatory mechanisms. For pMMR/MSS LARC, combining CRT with ICIs holds promise to overcome the "immune-cold" tumor microenvironment and improve therapeutic efficacy. In this clinical trial, the investigators aim to evaluate the efficacy and safety of integrating immunotherapy with CRT as a novel total neoadjuvant therapy for pMMR/MSS rectal cancer.

NCT Number	NCT07026422
Lead Sponsor	Shandong Cancer Hospital and Institute
Conditions	Rectal Malignant Neoplasms
Enrollment	54 participants
Start Date	2025-04-30
Primary Completion	2026-11-30 (estimated)
Study Completion	2028-05-30 (estimated)
Updated on ClinicalTrials.gov	2026-05-18