LEXINGTON, Mass. — Agenus Inc. announced updated clinical results showing that its investigational immunotherapy combination, botensilimab and balstilimab (BOT/BAL), achieved a two-year overall survival rate of 42% in patients with microsatellite-stable metastatic colorectal cancer (MSS mCRC) without active liver metastases. The company also confirmed alignment with the U.S. Food and Drug Administration (FDA) on the design of a global Phase 3 registration trial, which will begin later this year.
The updated data were presented at the 2025 ESMO Gastrointestinal Cancers Congress (ESMO-GI) in Barcelona and represent a 40% increase in cohort size from earlier reports, with 123 patients now included. The study population consisted of individuals with advanced, treatment-resistant MSS mCRC, typically unresponsive to immunotherapy.
“These results reinforce the consistency and durability of the botensilimab plus balstilimab combination in a population that has historically seen minimal benefit from immune checkpoint blockade,” said Benjamin Schlechter, M.D., of Dana-Farber Cancer Institute, who presented the findings. “For patients with MSS colorectal cancer who have exhausted standard therapies, this combination is showing the kind of meaningful, long-lasting benefit we rarely see in this setting.”
Among patients treated with BOT/BAL in the third-line or later setting, the objective response rate was 20%, with a median duration of response of 16.6 months. The disease control rate was 69%, and the median overall survival reached 20.9 months. In a fourth-line or later subgroup, the two-year survival rate was 43%.
“Deep, durable responses and survival plateaus emerging at two years and beyond are rarely seen in microsatellite stable refractory colorectal cancer — they are usually only seen in highly immunogenic tumors,” said Steven O’Day, M.D., Chief Medical Officer of Agenus. “These data reinforce the potential for a chemo‑free option in a population with limited alternatives.”
No new safety concerns were reported, and immune-related side effects were described as manageable, with no treatment-related deaths.
At a July 1, 2025 End-of-Phase 2 meeting, the FDA agreed that the existing data support balstilimab’s role in the BOT/BAL combination and waived the requirement for a BOT monotherapy arm in the Phase 3 trial. The upcoming global registration trial, named BATTMAN (CCTG CO.33), is scheduled to launch in the fourth quarter of 2025.
Jennifer Buell, Ph.D., Executive Chairwoman of Agenus, called the FDA’s feedback a “pivotal step forward” and said the company will pursue all expedited regulatory pathways to accelerate availability. “We intend to use every expedited pathway—Fast Track, Real-Time Oncology Review, the new Commissioner’s National Priority Voucher Program, and other accelerated mechanisms—to bring this chemo-free option to patients who have exhausted all other treatments.”
Richard Goldberg, M.D., Chief Development Officer at Agenus, emphasized the urgency of bringing new treatments to patients. “Colorectal cancer is rising fastest in people under 50 and is projected to become the leading cause of cancer death in that age group by 2030,” he said. “Given the dismal five‑to‑eight‑month median survival with current late‑line therapies, making BOT/BAL available quickly is not just prudent — it is imperative.”
Agenus plans to present additional BOT/BAL data later this year and is continuing discussions with global regulatory agencies about expanding the combination’s use in earlier lines of colorectal cancer treatment.
