Short-Course Radiotherapy Followed by CAPOX With or Without Iparomlimab and Tuvonralimab in pMMR/MSS Locally Advanced Rectal Cancer

This multicenter, randomized, controlled, phase III trial evaluates whether adding iparomlimab and tuvonralimab injection to CAPOX consolidation chemotherapy after short-course radiotherapy improves tumor response in patients with treatment-naive, proficient mismatch repair/microsatellite-stable (pMMR/MSS) locally advanced rectal adenocarcinoma. Eligible patients will be randomly assigned in a 1:1 ratio to receive short-course radiotherapy followed by CAPOX plus iparomlimab and tuvonralimab, or short-course radiotherapy followed by CAPOX alone. After total neoadjuvant therapy, patients with a clinical complete response may undergo a Watch-and-Wait strategy, whereas other patients will undergo total mesorectal excision according to standard clinical practice. The primary endpoint is complete response rate, defined as pathologic complete response after surgery or clinical complete response sustained for more than 1 year. Secondary endpoints include 3-year relapse-free survival, 3-year overall survival, sphincter preservation rate, and grade 3-4 acute adverse events. Exploratory analyses will assess tissue and blood biomarkers associated with treatment response.

NCT Number	NCT07686640
Lead Sponsor	Shandong Cancer Hospital and Institute
Conditions	Local Advanced Rectal Cancer, Radiotherapy, Immunotherapy
Enrollment	180 participants
Start Date	2026-07-15
Primary Completion	2029-07-15 (estimated)
Study Completion	2030-07-15 (estimated)
Updated on ClinicalTrials.gov	2026-07-08