On February 19, 2026 Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology, reported new translational and clinical biomarker data from its Phase 1b C-800-01 trial (NCT03860272) evaluating botensilimab (BOT), an Fc-enhanced anti–CTLA-4 antibody, in combination with balstilimab (BAL), an anti–PD-1 antibody. The data were presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Immuno-Oncology (AACR-IO) Conference in Los Angeles.
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The retrospective analyses demonstrate that survival with BOT+BAL is associated with the balance of two opposing biological factors: systemic inflammation in the blood (associated with poorer outcomes) and tumor immune activity within the tumor microenvironment (TME) (associated with more favorable outcomes). Notably, BOT+BAL enabled clinical benefit even at levels of immune infiltration typically considered insufficient for conventional checkpoint inhibitors, suggesting the Fc-enhanced mechanism lowers the threshold of baseline immunity required for activity. Integrating blood-based inflammatory markers with tumor immune features improved overall survival stratification in microsatellite-stable metastatic colorectal cancer (MSS mCRC), a population historically resistant to conventional checkpoint inhibitors.
Traditional biomarkers such as PD-L1 expression and tumor mutational burden have shown limited predictive value in MSS mCRC. These findings suggest that a broader view of inflammatory and immune biology may better define patients most likely to benefit from next-generation immunotherapy.
Durable Clinical Activity Across Historically "Cold" Tumor Types
In 341 efficacy-evaluable patients with advanced, treatment-refractory cancers and available biomarker data (data cutoff December 13, 2025):
Objective response rate (ORR): 17%
Clinical benefit rate (CBR): 26%
Median overall survival (OS): 17.2 months
24-month overall survival rate: 38%
Clinical activity was observed across tumor types commonly considered immunologically "cold," including MSS mCRC, ovarian cancer, sarcoma, and PD-1 relapsed or refractory non-small cell lung cancer. Notably, durable benefit was observed in patients both naïve to and resistant/refractory to prior anti–PD-(L)1/CTLA-4 therapies.
To better understand the biological drivers of these outcomes, integrated translational analyses evaluated both systemic inflammation and tumor microenvironment immune features.
Biomarker Insights Identify Patient Subgroups in Immunologically "Cold" Cancers
Systemic Inflammation Negatively Impacts Survival
Baseline indicators of systemic inflammation were significantly associated with shorter OS, including elevated neutrophil-to-lymphocyte ratio, C-reactive protein and other markers reflective of inflammatory and organ stress.
Even Low Immune-Infiltration of TME Associated with Longer Survival
Survival benefit was observed across immunologically "cold" tumors, including at low levels of tumor-infiltrating lymphocytes (≥34 cells/mm²), demonstrating activity beyond conventional checkpoint biomarker thresholds.
Integrated Blood and Tumor Biomarkers Improve Survival Stratification in MSS mCRC
Combining blood and tumor features distinguished biologically distinct MSS mCRC subgroups with markedly different survival outcomes (C-index up to 0.73).
Early Immune Activation Correlates with Benefit
Patients who experienced immune-mediated adverse events (imAEs) within the first 12 weeks of treatment demonstrated longer median OS (22.4 months vs. 13.7 months), consistent with distinct baseline immune features.
"These data show that outcomes with BOT+BAL are shaped by the interplay between systemic inflammation and tumor immune biology," said Dhan Chand, PhD, Vice President of Research and Development at Agenus. "By integrating blood- and tumor-based features, we are establishing a biologically grounded approach to patient stratification in immunologically ‘cold’ cancers such as MSS colorectal cancer, where conventional biomarkers provide limited guidance. Notably, the activity observed at low levels of immune infiltration further underscores the differentiated immune-modulating profile of botensilimab."
The poster (No. B036), titled "Systemic and Tumor-Microenvironment Inflammation Shape Outcomes in Patients with Immunologically Cold, Treatment-Refractory Tumors Treated with Fc-Enhanced Anti–CTLA-4 Botensilimab," was presented during the General Poster Session and is available in the Publications section of the Company’s website at www.agenusbio.com/publications
(Press release, Agenus, FEB 19, 2026, View Source [SID1234662797])