Botensilimab (Fc-enhanced anti-CTLA-4) + balstilimab (anti–PD-1) posts 71% iRECIST DCR in chemo-free 1L “liver-sparing” MSS mCRC

BOT is a 2nd-gen Fc-modified anti-CTLA-4 designed to enhance Treg depletion and myeloid activation, and BAL is an anti–PD-1 antibody; they were tested in a Phase I/II first-line study in anatomically selected Stage IV MSS CRC without liver/bone/brain metastases (BBOpCo; NCT06268015). As of 1/5/2026, 13 patients were response-evaluable (15 enrolled; 1 withdrew; 5 too early), with 1 confirmed iPR and 4 iSD at 24 weeks, yielding a 71% iRECIST DCR on BOT/BAL alone; median freedom from chemo crossover was 8.7 months (median follow-up 4.3 months). Safety in 14 patients showed 7 Grade 3 irAEs (no Grade 4), with Grade 3 colitis most common (n=5) managed with early steroids plus infliximab; for benchmark, standard 1L cytotoxic regimens such as FOLFOX + bevacizumab typically deliver median PFS ~8–9 months, while EGFR-antibody + FOLFOX in RAS WT disease can drive high response rates (often ~50% ORR, and up to ~70%+ in some studies), so this early BOT/BAL signal reads more like “disease-holding/chemo-deferral” than “tumor-shrinking” versus SOC.