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

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.

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Journal
Clinical Cancer Research
Published
2026-08-28
DOI
https://doi.org/10.1158/1078-0432.ccr-26-1610
Primary Topic
Colorectal Cancer Treatments and Studies
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article
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article

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

Benny Johnson, Anthony B. El-Khoueiry, Ian Chau, Sunil Sharma et al.
Clinical Cancer Research
Colorectal Cancer Treatments and Studies
article

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

Benny Johnson, Anthony B. El-Khoueiry, Ian Chau, Sunil Sharma, Apostolia Maria Tsimberidou, Heinz‐Josef Lenz, Manushak Avagyan, Robert W. Lentz, Thomas U. Marron, Steven O’Day, Marwan Fakih, Neil H. Segal, Benjamin L. Schlechter, Bruno Bockorny, Michael S. Gordon, Andrea J. Bullock, Joseph E. Grossman, Wells A. Messersmith, Dhan Chand, Ghassan K. Abou‐Alfa, Agustin Pimentel, Wei Wu
article en

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.

Clinical Cancer Research
University of Southern California (US), Beth Israel Deaconess Medical Center (US), Royal Marsden NHS Foundation Trust (GB), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), Agenus (United States) (US), City of Hope (US), Dana-Farber Cancer Institute (US), Royal Marsden Hospital (GB), Tisch Hospital (US), HonorHealth (US), University of Colorado Cancer Center (US), Sylvester Comprehensive Cancer Center (US), University of Colorado Anschutz Medical Campus (US), University of Colorado Denver (US)
Good health and well-being
Openalex Percentile: Top 13%
Colorectal Cancer Treatments and Studies
DOIOpen Access PDFOpenAlex
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