Phase 1b trial of botensilimab plus balstilimab for microsatellite-stable mCRC without active liver metastases: extended follow-up

Microsatellite-stable metastatic colorectal cancer (MSS mCRC) has limited treatment options and responds poorly to conventional immunotherapy. A multicenter phase 1b trial in the USA evaluated botensilimab (BOT; Fc-enhanced anti-CTLA-4) plus balstilimab (BAL; anti-PD-1) in patients with MSS mCRC without active liver metastases. Extend follow-up (median 20.2 months; range 0.7-62.3) has now been published. Patients received BOT 1 or 2 mg/kg every 6 weeks plus BAL 3 mg/kg every 2 weeks for up tp 2 years, or until progression or unacceptable toxicity. The primary objective was safety/tolerability. As of December 2025, 103 patients were treated. The median number of prior lines was 3; range 1-0; 67% had ≥ 3 prior lines). The most common treatment-related adverse events were diarrhea (39%; grade ≥ 3: 38%), and fatigue (37%; grade ≥ 3: 2%). The objective response rate was 21% (95% CI 14-29) with median duration of response not reached (7.3-NR), the median progression-free survival was 4.0 months (2.8-4.1), and the median overall survival was 21.2 months (16.2-23.8; 36-months OS rate 33%). Efficacy was consistent in late line-exposed patients. The authors conclude that the combination of BOT and BAL demonstrated durable responses and long-term survival with manageable safety in previously treated MSS mCRC.