Multicenter phase 1 trial of botensilimab plus balstilimab for relapsed or refractory microsatellite stable metastatic colorectal cancer

Microsatellite stable metastatic colorectal cancer (MSS mCRC) has responded poorly to immune checkpoint blockade. Botensilimab (BOT) is an Fc-enhanced anti-CTLA-4 antibody designed to expand therapy to cold/poorly immunogenic solid tumors. A multicenter phase 1 trial in the USA evaluated the combination of BOT with balstilimab (BAL, anti-PD-1 antibody) for relapsed or refractory (R/R) MSS mCRC. Interim analysis on 148 patients found treatment-related adverse events in 89% of patients, most commonly fatigue, diarrhea, and pyrexia. There were no grade 5 TRAEs, and the rate of discontinuation due to TRAEs was 12%. The objective response rate and disease control rate were 17% (95% CI 10-26) and 61% (51-71), respectively. During a median follow-up of 10.3 months (range 0.5-42.6) the median duration of response was not reached and the median progression-free survival was 3.5 months (95% CI 2.7-4.1). The authors conclude that the combination of BOT and BAL had a manageable safety profile and encouraging clinical activity among patients with R/R MSS mCRC.