A short course of two immunotherapy drugs before surgery left no viable tumor in 93% of patients with a particular form of resectable colon cancer, and no patient who received the combination has seen their cancer return, according to results from the Phase 2 UNICORN trial published in Nature Medicine.
The findings, announced by developer Agenus Inc. on November 2, 2026, cover 56 patients treated across four non-randomized cohorts at centers in Italy. They suggest that for some patients, a few weeks of treatment before the operation may do more than shrink a tumor. It may change what surgeons find when they get there.
What the Trial Found
UNICORN enrolled patients with locally advanced colon cancer that had not spread, staging them as cT3-4 N0/N+ M0. Four groups of 14 patients each received either botensilimab alone or botensilimab plus balstilimab, split by the tumor’s mismatch repair status. Botensilimab is an investigational anti-CTLA-4 antibody; balstilimab is an investigational anti-PD-1 antibody.
The primary endpoint was major pathologic response, meaning 10% or less viable tumor remained at surgery. In the group with mismatch repair deficient, or dMMR, disease who received both drugs, all 14 patients met that bar. Thirteen of them, 93%, had a pathologic complete response, with no viable tumor left in the primary tumor or lymph nodes.
In the mismatch repair proficient, or pMMR, group on the combination, 36% achieved a major pathologic response and 29% a complete response. Overall, 71% of those patients had at least 50% tumor reduction after one dose of botensilimab and two doses of balstilimab. The pMMR group given botensilimab alone had no major responses, though 43% had partial tumor regression.
Why pMMR Matters
For families who have sat in an oncologist’s office hearing the words “microsatellite stable,” the pMMR result may be the part worth reading twice. That form of colon cancer has largely been considered resistant to immunotherapy. The UNICORN data challenges that assumption in the curative-intent setting, said Filippo Pietrantonio, head of the Gastrointestinal Oncology Unit at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan and the trial’s principal investigator.
“The purpose of moving treatment earlier is not simply to shrink the tumor before surgery,” Pietrantonio said in a news release. “It is to prevent the disease from returning and ultimately increase the number of patients who may be cured.”
Agenus placed the numbers in context: first-generation CTLA-4/PD-1 combinations have shown major
Sources
- Neoadjuvant BOT + BAL Yields Pathologic Responses in pMMR/dMMR Colon Cancer | CancerNetwork
- Neoadjuvant Botensilimab/Balstilimab Shows Activity in Colon Cancer | Targeted Onc – Immunotherapy, Biomarkers, and Cancer Pathways
- Agenus Announces Nature Medicine Publication of Multicenter UNICORN Phase 2 Trial Demonstrating Deep Responses with Neoadjuvant BOT+BAL in Resectable Colon Cancer
- Neoadjuvant BOT + BAL Yields Pathologic Responses in pMMR/dMMR Colon Cancer | CancerNetwork
- Agenus Announces Nature Medicine Publication of Multicenter UNICORN Phase 2 Trial Demonstrating Deep Responses with Neoadjuvant BOT+BAL in Resectable Colon Cancer
Photo: National Cancer Institute / Unsplash (Unsplash License)
