Phase 2 botensilimab CTLA-4 antibody + balstilimab PD-1 antibody in early MSS rectal cancer.

This prospective, multi-site, non-randomized Phase 2 study (RECTIFY-1) tests neoadjuvant dual-checkpoint blockade in early, resectable rectal adenocarcinoma that is microsatellite stable / mismatch repair proficient (MSS/MMRp)—a group that typically does not benefit from PD-1 alone. Patients staged T1–T2 N0 M0 by MRI and considered candidates for upfront surgery (without standard neoadjuvant therapies) receive a single IV dose of botensilimab (an Fc-enhanced anti–CTLA-4 monoclonal antibody) on Day 1, followed by balstilimab (an anti–PD-1/CD279 monoclonal antibody) IV every 2 weeks for up to 6 months. The goal is to characterize safety and estimate efficacy signals (including tumor response) in the pre-operative window, potentially enabling less intensive local therapy in selected patients. Botensilimab and balstilimab are developed by Agenus, while Dana-Farber Cancer Institute sponsors this academic trial—an important angle because it explores whether intensified immunotherapy can “turn on” immune responsiveness in MSS rectal cancer. For T1–T2 N0 early rectal cancer today, care is typically surgical resection (often local excision or total mesorectal excision depending on risk features), with chemoradiation reserved for more locally advanced or higher-risk situations.