Node-Sparing Short-Course Radiotherapy Sequential Chemotherapy and PD-1 Inhibitor for Mid/Low pMMR/MSS Rectal Cancer (MODIFI-RC-II)

Most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) and respond poorly to PD-1 inhibitors. Radiotherapy can enhance tumor antigen release and improve responsiveness to PD-1 blockade in MSS/pMMR rectal cancer. Tumor-draining lymph nodes (TDLNs) are critical sites for anti-tumor immune activation, but radiation-induced damage and fibrosis may impair lymphatic drainage and immune responses. Previous studies have reported a remarkable pathologic complete response (pCR) rate of 77.8% using node-sparing radiotherapy in locally advanced rectal cancer. This study aims to evaluate whether node-sparing short-course radiotherapy followed by sequential chemotherapy and PD-1 blockade can improve complete response rate in the phase II part and event-free survival in phase III part, together with sphincter preservation, treatment tolerance, and prognosis in patients with mid-low pMMR/MSS rectal cancer.

NCT Number	NCT06958432
Lead Sponsor	Sixth Affiliated Hospital, Sun Yat-sen University
Conditions	Rectal Cancer, Neoadjuvant Therapies, Immune Checkpoint Therapy, Radiotherapy
Enrollment	430 participants
Start Date	2025-05-01
Primary Completion	2030-12-31 (estimated)
Study Completion	2031-12-31 (estimated)
Updated on ClinicalTrials.gov	2025-08-07