Extended Follow-up of Botensilimab plus Balstilimab in an Expanded Cohort of Microsatellite-Stable Metastatic Colorectal Cancer without Active Liver Metastases
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: PURPOSE: 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 AND METHODS: 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. RESULTS: 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]). CONCLUSIONS: 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.
Source: Clinical Cancer Research
Authors: Benjamin L. Schlechter, Marwan G. Fakih, Apostolia M. Tsimberidou, Andrea J. Bullock, Agustin Pimentel, Sunil Sharma, Heinz-Josef Lenz, Michael S. Gordon, Ghassan K. Abou-Alfa, Thomas U. Marron, Robert W. Lentz, Wells Messersmith, Ian Chau, Bruno Bockorny, Dhan Chand, Manushak Avagyan, Wei Wu, Benny Johnson, Joseph E. Grossman, Steven J. O’Day, Anthony B. El-Khoueiry, Neil H. Segal
Institutions: Dana-Farber Cancer Institute, City Of Hope National Medical Center, City of Hope, The University of Texas MD Anderson Cancer Center, Beth Israel Deaconess Medical Center, University of Miami, Sylvester Comprehensive Cancer Center, HonorHealth, University of Southern California, USC Norris Comprehensive Cancer Center, Memorial Sloan Kettering Cancer Center, Trinity College Dublin, Cornell University, Weill Cornell Medicine, Tisch Cancer Institute, University of Colorado Cancer Center, Royal Marsden Hospital, Agenus (United States)
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7204535243
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