Yang et al. Anti-PD-1/CTLA-4 Dual Immunotherapy for LARC

This is a prospective, multicenter, randomized controlled trial aimed at comparing different radiotherapy fractionation regimens combined with sequential dual immunotherapy versus traditional chemoradiotherapy in neoadjuvant treatment for locally advanced rectal cancer (LARC). A total of 342 pMMR/MSS LARC patients will be enrolled and randomly assigned in a 1:1:1 ratio to short-course radiotherapy (5×5Gy) followed by sequential dual immunotherapy (paromlimab + tuvonralimab + CAPEOX), long-course radiotherapy followed by sequential dual immunotherapy, or conventional long-course chemoradiotherapy. The primary endpoint is the complete response rate (pCR + cCR). Secondary endpoints include the proportion of patients adopting the "watch-and-wait" strategy, disease-free survival, overall survival, and safety. This study innovatively explores the synergistic mechanism of different radiotherapy fractionations with dual immunotherapy, optimizes the timing of immunotherapy initiation, and constructs a clinical-imaging-pathology multimodal efficacy prediction model, aiming to advance LARC treatment from empirical to precision therapy while achieving organ and function preservation.

NCT Number	NCT07596290
Lead Sponsor	Beijing Friendship Hospital Collaborators: Peking University Cancer Hospital & Institute, Peking Union Medical College
Conditions	Locally Advanced Rectal Adenocarcinoma, Neoadjuvant Chemoradiation, Neoadjuvant Immunotherapy
Enrollment	342 participants
Start Date	2026-07-15
Primary Completion	2028-12-31 (estimated)
Study Completion	2030-12-31 (estimated)
Updated on ClinicalTrials.gov	2026-06-17