Multicenter phase 2 trial of neoadjuvant botensilimab with or without balstilimab in pMMR and dMMR colon cancer

Neoadjuvant immune checkpoint inhibitors (ICIs) are active in patients with deficient mismatch repair (dMMR) colon cancer (CC), whereas proficient mismatch repair (pMMR) CC is considered resistant to first-generation ICIs. In the multicenter phase 2 UNICORN trial, short-course preoperative botensilimab (BOT; anti-CTLA-4) alone or in combination balstilimab (BAL; anti-PD-1) was evaluated in patients with resectable, locally advanced CC. Twenty-eight patients with pMMR CC were enrolled in BOT (n=14) and BOT+BAL (n=14) cohorts; 28 patients with dMMR CC also were enrolled in BOT (n=14) and BOT+BAL (n=14) cohorts. The primary endpoint was centrally assessed pathological major response (pMR; ≤10% residual viable tumor) rate. The pMR rate was 0% (95% CI 0-23.2) in pMMR BOT, 36% (12.8-64.9) in pMMR BOT+BAL, 36% (12.8-64.9) in dMMR BOT, and 100% (76.8-100) in dMMR BOT+BAL. Eight (29%) and 15 (54%) of patients treated with BOT and BOT+BAL, respectively, experienced immune-related adverse events, most commonly flu-like symptoms and diarrhea. The authors conclude that preoperative BOT+BAL elicits pathological responses in patients with pMMR or dMMR CC, supporting the combination as a promising strategy to expand ICI benefits to the early-stage setting (visual abstract).