Neoadjuvant botensilimab plus balstilimab - (NEST)

August 26, 2026: Agenus (NASDAQ: AGEN) reported a peer-reviewed publication in Clinical Cancer Research of updated Phase 2 NEST data for neoadjuvant botensilimab (BOT) plus balstilimab (BAL) in resectable colon/colorectal cancer.

At the March 31, 2026 cutoff, no colorectal cancer recurrences had been observed, with median follow-up of 32.2 months in NEST-1 and 23.5 months in NEST-2. In 22 pMMR/MSS tumors, BOT+BAL produced a 59% pathologic response rate, including 41% major pathologic response and 32% pathologic complete response. In four dMMR/MSI-H tumors, all achieved major pathologic response, including two pCRs and two near-complete regressions (98% and 99%). Among evaluable patients with detectable baseline ctDNA, 88% cleared ctDNA before surgery, and ctDNA remained undetectable after resection in all patients evaluated.

NEST was a single-center, open-label, single-arm Phase 2 study in 24 eligible patients with 26 tumors. Patients proceeded to planned surgery without treatment-related delays; no Grade 4 treatment-related adverse events, treatment-related deaths, or study discontinuations were reported.

Agenus said the results support its planned global randomized Phase 3 ROBBIN trial in previously untreated high-risk Stage II or Stage III MSS colon cancer, testing neoadjuvant BOT+BAL plus standard of care versus standard of care alone, with event-free survival as the primary endpoint. NEST3 (NCT07595874), a multicenter Phase 2 study, is enrolling; first patient was dosed in July 2026.