Lexington, Mass. — Agenus Inc. (Nasdaq: AGEN), an immuno-oncology company, announced three-year Phase 1b data from a fully enrolled cohort evaluating botensilimab plus balstilimab in patients with refractory microsatellite-stable metastatic colorectal cancer without active liver metastases.
The data were presented July 2 at the European Society for Medical Oncology Gastrointestinal Cancers Congress 2026 in Munich, Germany.
Botensilimab, or BOT, is an Fc-enhanced multifunctional anti–CTLA-4 antibody. Balstilimab, or BAL, is an anti–PD-1 antibody.
The fully enrolled 123-patient Phase 1b cohort showed median overall survival of 21.2 months, a three-year overall survival rate of 33%, and a survival curve plateau beyond two years. Agenus said 17% of patients were alive and off all systemic anticancer therapy at last follow-up.
The company said the results were reported in a heavily pretreated patient population where durable long-term survival is rarely seen. Extended safety follow-up showed no new safety signals, no treatment-related deaths, and 98% resolution of immune-mediated diarrhea or colitis.
BOT+BAL demonstrated long-term survival in patients who historically have had limited benefit from conventional immune checkpoint inhibitors and few durable treatment options after progression on standard therapies. Agenus said available later-line standards in refractory MSS metastatic colorectal cancer without active liver metastases have historically reported median overall survival of about 10 to 14 months in relevant analyses.
The data build on two-year overall survival results presented by Dr. Benjamin L. Schlechter of Dana-Farber Cancer Institute at ESMO GI 2025 and reflect an additional year of follow-up from the same cohort. With longer follow-up, the dataset includes 26 confirmed responses, while median duration of response was not reached. Twenty-one patients, or 17%, were alive and off all systemic anticancer therapy at last follow-up, including 13 responders.
“These three-year data are important because they show a pattern of benefit that is not typically expected in refractory MSS colorectal cancer,” said Benjamin L. Schlechter, M.D., of Dana-Farber Cancer Institute and presenting author of the study. “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.”
“BOT+BAL is not simply another checkpoint combination; it was designed to activate antitumor immunity in tumors that have been difficult to reach with conventional immunotherapy,” said Steven O’Day, M.D., Chief Medical Officer of Agenus. “With longer follow-up, we are seeing the elements that matter for a potentially differentiated immunotherapy regimen: durable survival, sustained responses, treatment-free intervals, and a manageable safety profile. These findings strengthen the foundation for BATTMAN and our broader development strategy in MSS colorectal cancer.”
The Phase 1b cohort included 123 patients with MSS metastatic colorectal cancer without active liver metastases. Patients had received a median of three prior lines of therapy. Sixty-seven percent 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.
Key efficacy results included median overall survival of 21.2 months, with 24-month and 36-month overall survival rates of 41% and 33%, respectively. The confirmed objective response rate was 21%, including three complete responses and 23 partial responses. Median duration of response was not reached, with responses ranging from 1.9 months to at least 37.4 months.
The disease control rate was 69% at six weeks, and the clinical benefit rate was 28% at 24 weeks. Tumor regression was observed in more than 40% of patients. Twenty-one patients, or 17%, were alive and off all systemic anticancer therapy, including 13 responders, with a subset remaining free from subsequent therapy or death for more than two years.
In a post hoc subgroup of 37 patients who had received at least one prior regimen of regorafenib, trifluridine/tipiracil with or without bevacizumab, or fruquintinib, BOT+BAL showed a confirmed objective response rate of 22%, median overall survival of 16.2 months, and a three-year overall survival rate of 30%. In this subgroup, median duration of response was 16.6 months, disease control rate was 70%, and clinical benefit rate at 24 weeks was 27%.
