Lexington, Mass. – August 28, 2026
Agenus Inc. announced the publication of mature Phase 1b results evaluating botensilimab (BOT) plus balstilimab (BAL) in heavily pretreated patients with microsatellite-stable metastatic colorectal cancer (MSS mCRC) without active liver metastases. The peer-reviewed analysis, published in Clinical Cancer Research, included 123 patients who had received a median of three prior lines of therapy. The study reported a median overall survival of 21.2 months and a 33% three-year overall survival rate, while confirmed objective response rate was 21%. The publication also provided exploratory biomarker findings linking clinical activity with BOT’s Fc-enhanced immune-priming mechanism, including responses in tumors with low tumor mutational burden and no detectable PD-L1 expression. For cGxP.wire, the major development is the peer-reviewed validation of durable BOT+BAL activity in refractory MSS colorectal cancer, together with biological evidence supporting continued development of the combination in earlier disease settings.
Agenus Reports Durable Survival With BOT+BAL in MSS mCRC
The newly published analysis provides extended follow-up from the C-800-01 Phase 1b cohort, focusing on patients with MSS mCRC without active liver metastases, a population that has historically derived limited benefit from conventional checkpoint immunotherapy. Patients received botensilimab plus balstilimab after multiple previous treatments, with the cohort receiving a median of three prior lines of therapy. Median overall survival reached 21.2 months, while overall survival at 24 and 36 months was 41% and 33%, respectively. The confirmed objective response rate was 21%, including three complete responses and 23 partial responses, while median duration of response had not been reached, with responses lasting at least 37.4 months. Disease control was observed in 69% of patients at six weeks, and 17% of patients were alive and off systemic anticancer therapy at the last follow-up. These findings provide the primary clinical evidence highlighted by the publication and reinforce the durability of responses observed with the BOT+BAL combination.
BOT+BAL Activity Supports Immune Priming in “Cold” Tumors
A key focus of the publication was understanding why BOT+BAL may demonstrate activity in MSS colorectal cancer, where conventional immune checkpoint approaches have generally been less effective. Exploratory biomarker analyses found responses in patients whose tumors had low tumor mutational burden (TMB) and in tumors with no detectable PD-L1 expression. Neither biomarker was associated with response in the evaluable population, suggesting that clinical activity was not restricted to tumors with conventional characteristics associated with checkpoint sensitivity. Agenus designed botensilimab as an Fc-enhanced anti-CTLA-4 antibody intended to promote immune engagement beyond conventional CTLA-4 blockade. The proposed mechanism includes activating myeloid and antigen-presenting cells, enhancing T-cell priming, reducing intratumoral regulatory T-cell activity and reshaping the immunosuppressive tumor microenvironment. For cGxP.wire, these biomarker observations are particularly relevant because they provide a biological rationale for evaluating BOT+BAL in immunologically “cold” MSS tumors that have historically been difficult to treat with checkpoint therapies.
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Agenus Advances BOT+BAL Toward Earlier-Stage Cancer Treatment
The mature metastatic findings also support Agenus’ strategy of evaluating BOT+BAL earlier in the treatment pathway, including curative-intent neoadjuvant treatment of colon cancer. In an exploratory subgroup of 37 patients who had exhausted available later-line therapies, the combination produced a 22% objective response rate, median overall survival of 16.2 months and a 30% three-year overall survival rate, indicating that activity remained evident among heavily pretreated patients. Extended safety follow-up identified no new safety signals or treatment-related deaths, while immune-mediated diarrhea or colitis resolved in 98% of affected patients. Agenus has also reported neoadjuvant data from its NEST Phase 2 program and plans to continue development in neoadjuvant MSS colon cancer, including the planned Phase 3 ROBBIN trial. The company’s broader development strategy therefore seeks to move the combination beyond refractory metastatic disease toward earlier intervention, where immune priming before surgery could potentially provide a greater opportunity to alter disease outcomes. The current evidence remains based on early-stage and exploratory studies, making prospective randomized trials essential for confirming the benefit of BOT+BAL.
Source: Agenus, press relese
