Agenus Announces Updated NEST Phase 2 Publication Reporting Deep Pathologic Responses and No Observed Recurrences with Neoadjuvant BOT+BAL in Resectable Colon Cancer
Agenus , 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.
“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. These results strengthen the rationale for our phase 3 ROBBIN trial and for evaluating BOT+BAL in a curative-intent setting, where the goal is to reduce the risk of recurrence and improve long-term outcomes.”
NEST was a single-center, open-label, single-arm Phase 2 study that enrolled 24 eligible patients with 26 resectable colorectal tumors, including 22 pMMR/MSS tumors and four dMMR/MSI-H tumors. The study evaluated two pre-surgical treatment intervals; approximately four weeks in NEST-1 and approximately eight weeks in NEST-2. Patients in both cohorts proceeded to planned surgical resection without treatment-related delays.
About Agenus
Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants. Agenus has robust end-to-end development capabilities, across commercial, research and discovery. Agenus is headquartered in Lexington, MA.
About Botensilimab (BOT)
Botensilimab (BOT) is a human multifunctional, Fc-enhanced anti-CTLA-4 antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, reducing intratumoral regulatory T cells, activating myeloid cells and inducing durable memory responses.
About Balstilimab (BAL)
Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. It has been evaluated in more than 900 patients to date and has demonstrated clinical activity and a favorable tolerability profile in several tumor types.
