Extended Follow-Up of Botensilimab Plus Balstilimab in an Expanded Cohort of Microsatellite-Stable Metastatic Colorectal Cancer Without Active Liver Metastases.

Abstract

Microsatellite-stable metastatic colorectal cancer (MSS mCRC) has limited treatment options and responds poorly to conventional immunotherapy. We report extended follow-up results from a fully-enrolled, phase 1b cohort evaluating botensilimab (BOT; Fc-enhanced anti-CTLA-4) plus balstilimab (BAL; anti-PD-1) in patients with MSS mCRC and no active liver metastases (NLM). Patients received BOT 1 or 2 mg/kg every 6 weeks (Q6W) plus BAL 3 mg/kg Q2W up to 2 years or until progression or unacceptable toxicity. Primary objective was safety/tolerability. Efficacy endpoints included objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS); overall survival (OS) was exploratory. Patients with prior regorafenib, trifluridine/tipiracil±bevacizumab, or fruquintinib ("late-line exposed") were analyzed post hoc. As of December-13-2025, 123 patients were treated (median follow-up, 20.2 months [range, 0.7-62.3]). Median prior lines was 3 (range, 1-10; 67% had ≥3 prior lines). Most common treatment-related adverse events were diarrhea (39%; grade ≥3, 8%) and fatigue (37%; grade ≥3, 2%). ORR was 21% (95% CI, 14-29). Median DOR was not reached (NR; 95% CI, 7.3-NR), median PFS was 4.0 months (95% CI, 2.8-4.1), and median OS was 21.2 months (95% CI, 16.2-23.8; 36-month OS, 33% [95% CI, 24-43]). Efficacy was consistent in late-line-exposed patients (n=37; ORR, 22% [95% CI, 10-38]; median OS, 16.2 months [95% CI, 9.7-31.3]). BOT+BAL demonstrated durable responses, long-term survival, and manageable safety in previously-treated MSS mCRC NLM, including in late-line-exposed patients. These results support further evaluation.