Agenus Inc. reported no cancer recurrences in two Phase 2 trials of its experimental drug combination for early-stage colon cancer, with median follow-up periods exceeding two years.
The NEST-1 and NEST-2 trials evaluated the combination of botensilimab and balstilimab as neoadjuvant therapy in 24 patients with resectable colorectal tumors. Data published in Clinical Cancer Research showed no recurrences after median follow-ups of 32.2 months in NEST-1 and 23.5 months in NEST-2, as of a March 31, 2026 cutoff.
Among 22 mismatch repair proficient/microsatellite stable (pMMR/MSS) tumors—representing roughly 85% of early-stage colorectal cancers—the combination achieved a 59% pathologic response rate. This included a 41% major pathologic response rate and a 32% pathologic complete response rate. All four mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) tumors responded, with two complete responses and two near-complete regressions of 98% and 99%.
Circulating tumor DNA (ctDNA) analysis showed 88% of patients with detectable baseline ctDNA cleared it prior to surgery, and ctDNA remained undetectable post-resection in all evaluated patients. No Grade 4 treatment-related adverse events, deaths, or study discontinuations occurred, and all patients proceeded to surgery without delays.
Agenus plans to advance the combination into a global randomized Phase 3 trial, ROBBIN, comparing neoadjuvant botensilimab and balstilimab followed by standard care against standard care alone in high-risk Stage II or Stage III MSS colon cancer patients.
