On July 6, 2026 Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, reported three-year landmark Phase 1b data from the fully enrolled C-800-01 cohort evaluating botensilimab (BOT), an Fc-enhanced multifunctional anti–CTLA-4 antibody, plus balstilimab (BAL), an anti–PD-1 antibody, in patients with refractory microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) without active liver metastases. The data were presented at the European Society for Medical Oncology Gastrointestinal Cancers (ESMO GI) Congress 2026 on July 2 in Munich, Germany.
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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 overall survival was 21.2 months and the three-year overall survival rate was 33%, with the Kaplan-Meier curve showing a plateau beyond two years.
Available later-line standards in refractory MSS mCRC without active liver metastases have historically reported median overall survival of approximately 10–14 months in relevant analyses, reflecting a treatment setting in which few patients have historically remained alive at later landmark timepoints and pivotal studies have generally focused on median survival rather than mature 36-month overall survival outcomes.i In this context, the survival profile, curve plateau beyond two years, and proportion of patients alive and off systemic anticancer therapy support the durability of benefit observed with BOT+BAL in this fully enrolled 123-patient Phase 1b cohort.
The data build on the two-year overall survival results presented by Dr. Benjamin L. Schlechter of Dana-Farber Cancer Institute at ESMO (Free ESMO Whitepaper) GI 2025 and reflect an additional year of follow-up from the same cohort. With longer follow-up, the dataset now includes 26 confirmed 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.
"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 (NCT03860272) cohort included 123 patients with MSS mCRC without active liver metastases. Patients had 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.
Key Efficacy Results:
Median overall survival: 21.2 months, with 24-month and 36-month overall survival rates of 41% and 33%, respectively
Confirmed objective response rate: 21%, including three complete responses and 23 partial responses
Median duration of response: not reached; responses ranged from 1.9 months to at least 37.4 months
Disease control rate: 69% at six weeks
Clinical benefit rate: 28% at 24 weeks
Tumor regression: observed in more than 40% of patients
Treatment-free survival: 21 patients or 17%, were alive and off all systemic anticancer therapy, including 13 responders with a subset of patients remaining free from subsequent therapy or death for more than two years
In a post hoc late-line–exposed 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%.
Safety Results
With extended follow-up, no new safety signals were observed and there were no treatment-related deaths. Immune-mediated diarrhea/colitis resolved in 98% of affected patients, with a median time to resolution of 14 days from onset.
Treatment-related immune-mediated diarrhea/colitis was the most common immune-mediated adverse event (42%; grade ≥3, 15%). The selected Phase 3 regimen of BOT 1 mg/kg plus BAL demonstrated improved tolerability, with lower rates of immune-mediated diarrhea/colitis (27%; grade ≥3, 10%) than the 2 mg/kg regimen.
Together, the mature efficacy, treatment-free survival, and extended safety findings support continued evaluation of BOT+BAL in MSS mCRC and provide rationale for the ongoing randomized Phase 3 BATTMAN trial evaluating BOT+BAL in refractory MSS/proficient mismatch repair (pMMR) metastatic colorectal cancer.
Presentation Details
Abstract Title: Botensilimab + Balstilimab in Microsatellite-Stable Metastatic Colorectal Cancer Without Active Liver Metastases: Extended Follow-Up and 3-Year Survival
Presenter: Benjamin L. Schlechter, M.D.; Dana-Farber Cancer Institute, Boston, MA, USA
Final Publication Number: 91P
Congress: European Society for Medical Oncology Gastrointestinal Cancers Congress 2026
Location: ESMO (Free ESMO Whitepaper) GI, 2026 | Munich, Germany
Poster Availability: The poster is available on the Agenus publications page.
About the C-800-01 Study (NCT03860272)
C-800-01 is a first-in-human Phase 1b clinical trial evaluating botensilimab with or without balstilimab in patients with advanced solid tumors. The MSS mCRC without active liver metastases cohort enrolled 123 patients who received BOT 1 mg/kg or 2 mg/kg every six weeks plus BAL 3 mg/kg every two weeks. The primary endpoint was safety and tolerability. Secondary endpoints included objective response rate, duration of response, disease control rate, and progression-free survival. Exploratory endpoints included overall survival and clinical benefit rate.
(Press release, Agenus, JUL 6, 2026, View Source [SID1234669076])