Phase 2 porustobart CTLA-4 antibody + pembrolizumab PD-1 antibody in resectable MSS colon cancer

This Phase 2, open-label, multicenter, randomized neoadjuvant trial tests whether adding porustobart (a CTLA-4–blocking monoclonal antibody) to pembrolizumab (a PD-1–blocking monoclonal antibody from Merck/MSD) can deepen immune-mediated tumor regression before surgery in resectable pMMR/MSS colon cancer (CT-staged T3/T4, M0). Solstice Oncology is sponsoring the study and compares two dosing schedules: pembrolizumab on Day 1 and Day 22 in both arms, with porustobart given either once (Day 1 only) or twice (Day 1 and Day 22). The primary goal is to see how often tumors show major pathologic response/pathologic eradication at resection, while characterizing immune-related toxicities typical of dual-checkpoint blockade. The key scientific angle is translating a PD-1 + CTLA-4 strategy into “immune-cold” MSS colon cancer (~85–90%+ of colon cancers), where PD-1 monotherapy has generally underperformed outside MSI-H/dMMR disease. Today’s care for resectable, locally advanced MSS colon cancer is upfront colectomy with adjuvant chemotherapy based on risk (often fluoropyrimidine + oxaliplatin), and in some settings neoadjuvant chemo is used; this trial explores whether brief pre-op immunotherapy can improve pathologic response and potentially long-term recurrence outcomes.