- No colorectal cancer recurrences observed at updated median follow-up of 32.2 months in NEST-1 and 23.5 months in NEST-2
- In pMMR/MSS tumors, neoadjuvant BOT+BAL achieved 59% pathologic response, including 41% major pathologic response and 32% pathologic complete response
- 88% of evaluable patients cleared ctDNA before surgery, with no delays to planned surgical resection
- Longer follow-up and immune analysis provide clinical and biological support for Agenus’ planned global Phase 3 ROBBIN trial in curative-intent MSS/pMMR colon cancer
Agenus Inc. (NASDAQ:AGEN), a leader in immuno-oncology innovation, today announced the peer-reviewed publication of updated results from the investigator-sponsored Phase 2 NEST trial evaluating neoadjuvant botensilimab (BOT), Agenus’ multifunctional, Fc-enhanced anti-CTLA-4 antibody, and balstilimab (BAL), Agenus’ anti-PD-1 antibody, in patients with resectable colon cancer. The manuscript, titled "Neoadjuvant botensilimab/balstilimab for localized mismatch repair proficient and deficient colon cancer: Results of the NEST phase 2 clinical trial," was published in Clinical Cancer Research and is available here.
Earlier findings from NEST were presented at the 2025 ASCO Gastrointestinal Cancers Symposium. The publication provides longer follow-up and a fuller peer-reviewed analysis of tumor responses, circulating tumor DNA (ctDNA) dynamics, disease-free follow-up and immune changes in the tumor microenvironment.
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 (pMMR/MSS) tumors, 59% achieved a pathologic response, including 41% with a major pathologic response and 32% with a pathologic complete response.
MSS/pMMR tumors represent approximately 85% of early-stage colorectal cancers and have historically derived limited benefit from conventional immunotherapy treatment, particularly in metastatic disease.i,ii In localized colon cancer, treatment remains centered on surgery and chemotherapy, creating a need for approaches that may deepen response and reduce recurrence risk. Administering immunotherapy before surgery offers a distinct biological opportunity to activate the immune system while the primary tumor, tumor-draining lymph nodes and surrounding immune microenvironment remain intact.
The publication adds peer-reviewed clinical and biological support for Agenus’ previously announced decision to prioritize BOT+BAL in earlier-stage, curative-intent MSS colon cancer. Agenus is advancing ROBBIN, a planned global randomized Phase 3 trial evaluating 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, with event-free survival as the primary endpoint. NEST’s deep tumor regression, pre-surgical ctDNA clearance, preserved surgical timing and no observed recurrences at longer follow-up supports the clinical hypothesis ROBBIN is designed to test.