• A novel, chemo-sparing strategy (BBoPCO): introducing BOT+BAL in 1L MSS mCRC to extend survival and reduce use of cytotoxic chemotherapy

Agenus Inc. (NASDAQ:AGEN), a leader in immuno-oncology, today announced that preliminary results from an investigator-sponsored study evaluating botensilimab (BOT) in combination with balstilimab (BAL) in first-line microsatellite stable colorectal cancer (MSS CRC) will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2026, taking place April 18–23 in San Diego, CA.

The BBoPCO study (Botensilimab and Balstilimab Optimization in Colorectal Cancer; NCT06268015) is the first trial of its kind to advance a combination immunotherapy approach in the first-line setting for MSS mCRC, evaluating BOT+BAL in patients without liver, bone, or brain metastases—a population historically resistant to immunotherapy. This investigator-sponsored study was expanded to a Phase 2 and reflects a growing shift toward introducing immunotherapy earlier in the disease course, with the goal of harnessing the immune system to reduce reliance on chemotherapy and improve durability of response.

Colorectal cancer remains a leading cause of cancer-related death worldwide, with rising incidence in younger populations, and treatment continues to rely heavily on intensive, toxic chemotherapy regimens that can significantly impact quality of life, with neuropathy, organ toxicity, decrease fertility, among others. Despite advances, patients with MSS mCRC, which accounts for approximately 95% of metastatic cases, have seen limited benefit from conventional immunotherapy, underscoring a critical unmet need.

Botensilimab, an Fc-enhanced multifunctional anti-CTLA-4 antibody, is designed to activate both innate and adaptive immune responses, while balstilimab (anti–PD-1) is designed to sustain immune activity. Together, the combination is intended to target complementary immune pathways and expand the potential of immunotherapy in traditionally "cold" tumors.

The BBOpCo study adds to a growing body of research evaluating BOT+BAL across earlier lines of therapy and in settings where immune activation may have greater impact.