LEXINGTON, Mass. — Agenus Inc. said updated results from the investigator-sponsored Phase 2 NEST trial showed deep pathologic responses and no observed colorectal cancer recurrences among patients treated with neoadjuvant botensilimab and balstilimab before surgery.
The peer-reviewed findings were published in Clinical Cancer Research and provide longer follow-up from the NEST study, which evaluated botensilimab, or BOT, Agenus’ Fc-enhanced anti-CTLA-4 antibody, in combination with balstilimab, or BAL, its anti-PD-1 antibody, in patients with resectable colon cancer.
At the March 31, 2026 data 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.
Among 22 mismatch repair proficient/microsatellite stable, or pMMR/MSS, tumors, 59% achieved a pathologic response. That included a 41% major pathologic response rate and a 32% pathologic complete response rate.
Agenus said 88% of evaluable patients with detectable circulating tumor DNA at baseline cleared ctDNA before surgery. All patients proceeded to planned surgical resection without treatment-related delays.
“NEST provides important context for Agenus’ strategic focus on neoadjuvant BOT+BAL in MSS colon cancer,” said Steven O’Day, M.D., Chief Medical Officer of Agenus. “With longer follow-up now extending beyond two years across both NEST cohorts, the findings show BOT+BAL can generate deep tumor responses and immune activation before surgery, without delaying surgery.”
The NEST trial was a single-center, open-label, single-arm Phase 2 study that enrolled 24 eligible patients with 26 resectable colorectal tumors. The study included 22 pMMR/MSS tumors and four mismatch repair deficient/microsatellite instability-high, or dMMR/MSI-H, tumors.
All four dMMR/MSI-H tumors achieved a major pathologic response, including two pathologic complete responses and two tumors with near-complete regression of 98% and 99%.
Analysis of paired tumor samples also showed changes in the tumor immune microenvironment among responding tumors, including increased CD8+ T-cell infiltration, reduced FOXP3+ regulatory T cells and higher CD8+/Treg ratios.
Agenus said the findings provide additional biological support for botensilimab’s Fc-enhanced mechanism and its potential activity in pMMR/MSS tumors, which have historically shown limited response to conventional immunotherapy, particularly in metastatic disease.
No Grade 4 treatment-related adverse events, treatment-related deaths or study discontinuations were reported.
“The NEST results reinforce a major opportunity in colorectal cancer to use immunotherapy earlier, before surgery, when the primary tumor and immune system are still positioned to generate a coordinated anti-tumor response,” said Pashtoon M. Kasi, M.D., M.S., Medical Director of GI Medical Oncology at City of Hope Orange County and Rad Family Chair in Gastrointestinal Oncology.
Agenus is now preparing the global randomized Phase 3 ROBBIN trial, which is designed to evaluate neoadjuvant BOT+BAL followed by standard of care versus standard of care alone in previously untreated patients with high-risk Stage II or Stage III MSS colon cancer. Event-free survival will serve as the primary endpoint.
The company is also supporting NEST3, an actively enrolling multicenter Phase 2 investigator-sponsored study led by Pashtoon M. Kasi, M.D., M.S. The study is expected to enroll about 100 patients across 11 U.S. sites, with the first patient dosed in July 2026.
