Agenus Inc. announced results from an investigator-sponsored trial (IST) of botensilimab and balstilimab (BOT/BAL) in the neoadjuvant setting for colon cancer. Data were presented at the 2024 European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress in Munich, Germany. Enrollment: 20 patients were evaluable at the data cutoff with available pathology results, 17 microsatellite stable (MSS) and 3 high microsatellite instability (MSI-H).

Treatment Regimens: Both cohorts received one dose of botensilimab with balstilimab. The NEST-1 cohort received one additional dose of balstilimab two weeks later, whereas the NEST-2 cohort received up to 3 additional doses of balstilimab. Pathologic Response: In the NEST-2 cohort, 78% (7/9) of MSS patients achieved pathologic responses of at least 50% tumor regression, with 56% (5/9) reaching complete pathologic responses.

Surgical Outcomes and Safety: No surgeries were delayed due to adverse events, and no patients had unresolved immune related adverse events. Side effects were manageable, and no new safety concerns emerged. Botensilimab is a human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses.

Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.