LEXINGTON, Mass. — Agenus Inc. (Nasdaq: AGEN) announced the peer-reviewed publication of mature Phase 1b results evaluating botensilimab, or BOT, in combination with balstilimab, or BAL, in heavily pretreated patients with microsatellite-stable metastatic colorectal cancer without active liver metastases.
The analysis included 123 patients enrolled in the C-800-01 study who had received a median of three prior lines of therapy. Agenus said BOT+BAL produced a median overall survival of 21.2 months, while the three-year overall survival rate was 33%.
The results were published in Clinical Cancer Research in a paper titled “Extended Follow-Up of Botensilimab Plus Balstilimab in an Expanded Cohort of Microsatellite-Stable Metastatic Colorectal Cancer Without Active Liver Metastases.”
The publication builds on three-year efficacy data presented at the European Society for Medical Oncology Gastrointestinal Cancers Congress 2026 and includes additional biomarker analyses examining the mechanism behind the combination’s activity.
Microsatellite-stable tumors account for most metastatic colorectal cancer cases and historically have shown little or no benefit from conventional checkpoint immunotherapy. Agenus said available later-line treatments have reported median overall survival of about 10 to 14 months in patients with refractory MSS colorectal cancer without active liver metastases.
The Phase 1b results showed a confirmed objective response rate of 21%, including three complete responses and 23 partial responses. Median duration of response had not been reached, with some responses lasting at least 37.4 months.
The disease control rate was 69% at six weeks, while the clinical benefit rate was 28% at 24 weeks. At the latest follow-up, 17% of patients were alive and no longer receiving systemic anticancer therapy, including 13 patients who had responded to treatment.
Durable activity was observed despite relatively limited treatment exposure. Patients received a median of two doses of BOT and six doses of BAL.
Exploratory biomarker analyses showed responses among tumors with low tumor mutational burden and no detectable PD-L1 expression. Neither biomarker was associated with response, according to the company.
“These mature results are important because they show a pattern of durable activity in MSS colorectal cancer that is not limited to tumors with the conventional features associated with checkpoint sensitivity,” said Benjamin L. Schlechter, M.D., of Dana-Farber Cancer Institute and lead author of the publication. “In a heavily pretreated setting where patients have few remaining options, BOT+BAL compares favorably with what is typically expected from available later-line standard therapies in terms of tolerability, depth of response and duration of response. That is a meaningful clinical difference and provides important evidence that antitumor immunity can be generated even in tumors traditionally considered immunologically cold.”
BOT is an Fc-enhanced anti-CTLA-4 antibody designed to promote immune priming, while BAL is an anti-PD-1 antibody.
“BOT was specifically engineered to add Fc-mediated immune engagement to CTLA-4 blockade, with the goal of priming antitumor immunity in cancers that have historically been resistant to conventional checkpoint inhibition,” said Steven O’Day, M.D., Chief Medical Officer of Agenus. “This peer-reviewed publication connects the durable clinical activity observed in refractory MSS colorectal cancer with biomarker findings consistent with that biology. When considered alongside our emerging neoadjuvant data, these findings strengthen the rationale for evaluating BOT+BAL earlier in the disease course, where immune priming before surgery may offer the greatest opportunity to alter the trajectory of MSS colorectal cancer.”
In an exploratory subgroup of 37 patients who had exhausted available later-line therapies and received a median of five previous treatment lines, BOT+BAL produced a confirmed objective response rate of 22%. Median overall survival was 16.2 months, while the three-year overall survival rate was 30%.
Median duration of response in that subgroup was 16.6 months, with a disease control rate of 70% and a 24-week clinical benefit rate of 27%.
Agenus said the biomarker findings were consistent with BOT’s Fc-enhanced design, which is intended to engage activating Fc-gamma receptors on antigen-presenting and other myeloid cells, promote T-cell priming, reduce regulatory T cells within tumors and alter the immunosuppressive tumor microenvironment.
No new safety signals were identified during extended follow-up, and there were no treatment-related deaths. Immune-mediated diarrhea or colitis, the most common immune-mediated adverse event, resolved in 98% of affected patients, with a median resolution time of 14 days.
The objective response rate was 21% at both BOT dose levels studied — 1 mg/kg and 2 mg/kg. Agenus said lower rates of immune-mediated adverse events were observed with the 1 mg/kg BOT dose in combination with BAL.
The findings follow recently published Phase 2 NEST data evaluating neoadjuvant BOT+BAL in patients with resectable colon cancer. Agenus said the metastatic durability and biomarker findings provide additional rationale for studying the combination earlier in the disease course, including in curative-intent treatment.
The company plans to continue evaluating BOT+BAL in neoadjuvant MSS colon cancer, including through its planned Phase 3 ROBBIN trial.
C-800-01, or NCT03860272, is a first-in-human Phase 1b clinical trial evaluating botensilimab with or without balstilimab in patients with advanced solid tumors. The MSS metastatic colorectal cancer cohort without active liver metastases enrolled 123 patients who received BOT at either 1 mg/kg or 2 mg/kg every six weeks plus BAL at 3 mg/kg every two weeks.
The study’s primary endpoint was safety and tolerability. Secondary endpoints included objective response rate, duration of response, disease control rate and progression-free survival, while overall survival was an exploratory endpoint.
