Agenus Inc. announced completion of the planned patient enrollment in ACTIVATE-Colorectal, a randomized Phase 2 trial in advanced colorectal cancer (CRC) evaluating the efficacy and safety of botensilimab (BOT) as monotherapy and in combination with balstilimab (BAL) or standard of care in patients with metastatic heavily pre-treated colorectal cancer. The phase 2 study follows an expanded phase 1 study of over 100 patients with a median of four prior lines of therapy and with 25% having failed previous immunotherapy. At ESMO GI earlier this year, data from the phase 1 study were presented.

Among the evaluable patients (n=69) who did not have active liver metastases, a confirmed objective response rate of 23% and a median overall survival of 20.9 months were observed. Agenus is exploring global accelerated approval strategies for CRC. The totality of data from the phase 1 and 2 studies will contribute to a planned Biologics License Application to the U.S. FDA in 2024.

The U.S. FDA has granted Fast Track designation for BOT/BAL in patients with non-MSI-H/dMMR metastatic colorectal cancer and no active liver involvement who are resistant or intolerant to a fluoropyrimidine, oxaliplatin, and irinotecan, and who have also received a VEGF inhibitor, an EGFR inhibitor and/or a BRAF inhibitor, if indicated. Botensilimab is an investigational multifunctional anti-CTLA-4 immune activator 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 other 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. Approximately 600 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus?

investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers.