Agenus’s metastatic colorectal cancer (mCRC) combination therapy has continued to show benefit after three years of treatment, with a median overall survival (OS) of 21.2 months.
In the Phase Ib trial (NCT03860272), patients received a combination of botensilimab (BOT), an Fc-enhanced multifunctional anti–CTLA-4 antibody, plus balstilimab (BAL), an anti–PD-1 antibody. The trial enrolled 123 patients with refractory microsatellite-stable (MSS) mCRC without active liver metastases.
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Patients had already received a median of three prior lines of therapy; 67% had received at least three prior lines, 15% had received prior anti–PD-(L)1 with or without anti–CTLA-4 therapy, and 30% had received at least one later-line regimen of regorafenib, trifluridine/tipiracil with or without bevacizumab, or fruquintinib.
BOT+BAL demonstrated clinically meaningful long-term survival in a heavily pretreated patient population with historically limited benefit from conventional immune checkpoint inhibitors and few durable treatment options after progression on standard therapies. With extended follow-up, median OS was 21.2 months, and the three-year OS rate was 33%, with the Kaplan-Meier curve showing a plateau beyond two years.
The Kaplan-Meier curve is a visual, step-function graph that estimates the probability of a specific event, such as death or disease relapse occurring over a given period.
The confirmed objective response rate was 21%, including three complete responses and 23 partial responses. Median duration of response was not reached; and 21 patients, or 17%, were alive and off all systemic anticancer therapy at last follow-up, including 13 responders.
No new safety signals were observed and there were no treatment-related deaths. Immune-mediated diarrhoea/colitis resolved in 98% of affected patients, with a median time to resolution of 14 days from onset.
The data were presented at the European Society for Medical Oncology Gastrointestinal Cancers (ESMO GI) Congress 2026 on 2 July in Munich, Germany.
Dr Benjamin Schlechter of Dana-Farber Cancer Institute and presenting author of the study, said: “These three-year data are important because they show a pattern of benefit that is not typically expected in refractory MSS colorectal cancer. These are patients who had received multiple prior lines of therapy and had few remaining options. Seeing a subset of patients remain alive and off systemic anticancer therapy after treatment speaks to the clinical relevance of these results and the potential for botensilimab plus balstilimab to change expectations for what immunotherapy may achieve in this setting.”
The data build on the two-year OS data presented by Schlechter at ESMO GI 2025.
Agenus reports that approved later-line treatments in refractory MSS mCRC without active liver metastases have historically achieved a median OS of approximately 10–14 months in relevant analyses. As a result, the curve plateau is beyond two years, and the proportion of patients alive and off systemic anticancer therapy supports BOT+BAL’s durability of benefit.
This update comes shortly after Agenus confirmed it has enrolled the first patient in the Phase III BATTMAN trial, which is assessing BOT plus BAL in refractory, unresectable MSS or pMMR mCRC.
Agenus also completed a $141m strategic collaboration with Zydus Lifesciences to accelerate the global development and potential commercialisation of BOT/BAL in January 2026.
Under the agreement, Agenus has provided Zydus with exclusive rights to develop and commercialise BOT/BAL in Sri Lanka and India, with Agenus eligible for a 5% royalty on net sales from these markets.
