Extended Follow-up of Botensilimab plus Balstilimab in an Expanded Cohort of Microsatellite-Stable Metastatic Colorectal Cancer without Active Liver Metastases
14 affiliations
- 1Dana-Farber Cancer Institute, Boston, Massachusetts.
- 2City of Hope Comprehensive Cancer Center, Duarte, California.
- 3University of Texas, MD Anderson Cancer Center, Houston, Texas.
- 4Beth Israel Deaconess Medical Center, Boston, Massachusetts.
- 5University of Miami, Sylvester Comprehensive Cancer Center, Miami, Florida.
- 6HonorHealth Research Institute, Scottsdale, Arizona.
- 7University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, California.
- 8Memorial Sloan Kettering Cancer Center, New York, New York.
- 9Weill Cornell Medical College, New York, New York.
- 10Trinity College Dublin, Dublin, Ireland.
- 11Mount Sinai, Tisch Cancer Center, New York, New York.
- 12University of Colorado Cancer Center, Aurora, Colorado.
- 13The Royal Marsden Hospital, London, United Kingdom.
- 14Agenus Inc., Lexington, Massachusetts.
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 Ib cohort evaluating botensilimab [BOT; Fc-enhanced anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4)] plus balstilimab [BAL; anti–programmed cell death protein 1 (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 plus BAL 3 mg/kg every 2 weeks up to 2 years or until progression or unacceptable toxicity. The 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)]. The median prior lines was 3 (range, 1–10; 67% had ≥3 prior lines). The most common treatment-related adverse events were diarrhea (39%; grade ≥3, 8%) and fatigue (37%; grade ≥3, 2%). The ORR was 21% [95% confidence interval (CI), 14–29]. The median DOR was not reached (NR; 95% CI, 7.3–NR), the median PFS was 4.0 months (95% CI, 2.8–4.1), and the 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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BibTeX
@article{schlechter2026extended,
title = {{Extended Follow-up of Botensilimab plus Balstilimab in an Expanded Cohort of Microsatellite-Stable Metastatic Colorectal Cancer without Active Liver Metastases}},
author = {Benjamin L. Schlechter and Marwan G. Fakih and Apostolia M. Tsimberidou and Andrea J. Bullock and Agustin Pimentel and Sunil Sharma and Heinz-Josef Lenz and Michael S. Gordon and Ghassan K. Abou-Alfa and Thomas U. Marron and Robert W. Lentz and Wells Messersmith and Ian Chau and Bruno Bockorny and Dhan Chand and Manushak Avagyan and Wei Wu and Benny Johnson and Joseph E. Grossman and Steven J. O’Day and Anthony B. El-Khoueiry and Neil H. Segal},
journal = {Clinical Cancer Research},
year = {2026},
month = aug,
doi = {10.1158/1078-0432.ccr-26-1610},
url = {https://doi.org/10.1158/1078-0432.ccr-26-1610},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Extended Follow-up of Botensilimab plus Balstilimab in an Expanded Cohort of Microsatellite-Stable Metastatic Colorectal Cancer without Active Liver Metastases
AU - Benjamin L. Schlechter
AU - Marwan G. Fakih
AU - Apostolia M. Tsimberidou
AU - Andrea J. Bullock
AU - Agustin Pimentel
AU - Sunil Sharma
AU - Heinz-Josef Lenz
AU - Michael S. Gordon
AU - Ghassan K. Abou-Alfa
AU - Thomas U. Marron
AU - Robert W. Lentz
AU - Wells Messersmith
AU - Ian Chau
AU - Bruno Bockorny
AU - Dhan Chand
AU - Manushak Avagyan
AU - Wei Wu
AU - Benny Johnson
AU - Joseph E. Grossman
AU - Steven J. O’Day
AU - Anthony B. El-Khoueiry
AU - Neil H. Segal
PY - 2026
DA - 2026/08/28
JO - Clinical Cancer Research
DO - 10.1158/1078-0432.ccr-26-1610
UR - https://doi.org/10.1158/1078-0432.ccr-26-1610
AB - 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 Ib cohort evaluating botensilimab [BOT; Fc-enhanced anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4)] plus balstilimab [BAL; anti–programmed cell death protein 1 (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 plus BAL 3 mg/kg every 2 weeks up to 2 years or until progression or unacceptable toxicity. The 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)]. The median prior lines was 3 (range, 1–10; 67% had ≥3 prior lines). The most common treatment-related adverse events were diarrhea (39%; grade ≥3, 8%) and fatigue (37%; grade ≥3, 2%). The ORR was 21% [95% confidence interval (CI), 14–29]. The median DOR was not reached (NR; 95% CI, 7.3–NR), the median PFS was 4.0 months (95% CI, 2.8–4.1), and the 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.
SN - 1078-0432
SN - 1557-3265
ER -