Agenus Reports Deep Responses in Neoadjuvant Colon Cancer

LEXINGTON, Mass., Aug. 26, 2026

Agenus Highlights NEST Results in pMMR/MSS Colon Cancer

In the updated NEST analysis, 22 pMMR/MSS tumors were evaluated, with neoadjuvant BOT+BAL producing a 59% pathologic response rate, including a 41% major pathologic response rate (MPR) and a 32% pathologic complete response rate (pCR). Major pathologic response was defined as 10% or less viable tumor remaining, while pathologic complete response indicated no viable tumor in the resected tumor or adjacent lymph nodes. The findings are significant for Agenus because pMMR/MSS tumors have historically been less responsive to immune checkpoint approaches, creating a substantial unmet need in localized disease. The NEST treatment strategy administers immunotherapy before surgery, when the primary tumor, tumor-draining lymph nodes and surrounding immune microenvironment remain intact. Agenus is using the findings to support its planned global 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.

Agenus Reports ctDNA Clearance and No Observed Recurrences

The updated NEST publication also reported additional findings relevant to disease monitoring and long-term outcomes. Among patients with detectable circulating tumor DNA at baseline who had evaluable pre-surgical samples, 88% cleared ctDNA before surgery, while ctDNA remained undetectable following resection in all evaluated patients. At the data cutoff, no colorectal cancer recurrences had been observed across the NEST cohorts. Patients also proceeded to their planned surgical resections without treatment-related delays, supporting the feasibility of administering BOT+BAL before surgery. In the smaller dMMR/MSI-H subgroup, all four tumors achieved a major pathologic response, including two pathologic complete responses. Agenus also reported immune analyses showing increased CD8+ T-cell infiltration, reduced FOXP3+ regulatory T cells and increased CD8+/Treg ratios in responding tumors, suggesting immune remodeling within the tumor microenvironment. The company cautioned that comparisons with historical studies should be interpreted carefully because of differences in trial design, patient populations and follow-up

Agenus Advances BOT+BAL Toward Phase 3 ROBBIN Trial

The NEST findings strengthen Agenus’ strategy of moving BOT+BAL into earlier-stage colon cancer, where the objective is to reduce recurrence risk and improve long-term outcomes following curative-intent treatment. NEST was a single-center, open-label Phase 2 investigator-sponsored study involving 24 eligible patients with 26 resectable colorectal tumors, including 22 pMMR/MSS and four dMMR/MSI-H tumors. The study evaluated approximately four-week and eight-week pre-surgical treatment intervals, with patients proceeding to planned surgery. Agenus is also supporting NEST3, an actively enrolling multicenter Phase 2 investigator-sponsored study evaluating neoadjuvant BOT+BAL in advanced resectable colorectal cancer. The company said the longer NEST follow-up, deep tumor regression, ctDNA clearance, preserved surgical timing and immune changes provide support for the clinical hypothesis being tested in ROBBIN, which represents the next major development step for BOT+BAL in MSS/pMMR colon cancer. Botensilimab is an Fc-enhanced anti-CTLA-4 antibody designed to stimulate both innate and adaptive immune responses, while balstilimab is an anti-PD-1 antibody. Together, the agents are being investigated for their potential to overcome the immunosuppressive environment associated with tumors that have historically responded poorly to conventional immunotherapy.

Source: Agenus, press relese