Agenus Presents Promising BOT/BAL Neoadjuvant Pan-Cancer Data from NEOASIS Study at AACR Annual Meeting
Agenus Inc. (Nasdaq: AGEN), a clinical-stage immuno-oncology company focused on developing therapies designed to activate the body’s immune system to fight cancer, announced the presentation of new clinical data from the investigator-sponsored NEOASIS study. The data were shared during an oral session at the 2025 American Association for Cancer Research (AACR) Annual Meeting held in Chicago, Illinois.
The presentation highlighted the therapeutic potential of Agenus’ proprietary immunotherapy combination—botensilimab (BOT), a next-generation CTLA-4 antibody, and balstilimab (BAL), a PD-1 inhibitor—when administered as neoadjuvant treatment in early-stage, resectable solid tumors. The study evaluated this combination in both mismatch repair–deficient (dMMR/MSI-H) and mismatch repair–proficient (pMMR/MSS) tumors, extending beyond its prior applications in colorectal cancer and marking the first report of BOT/BAL use in other cancer types in the neoadjuvant setting.
“This marks a significant advancement in immunotherapy research,” said Dr. Myriam Chalabi of the Netherlands Cancer Institute, one of the principal investigators. “These initial results from the NEOASIS study suggest that two doses of botensilimab and balstilimab prior to surgery can induce substantial pathological responses in multiple tumor types, including triple-negative breast cancer, a historically difficult-to-treat disease. Importantly, these responses were achieved without dose-limiting toxicities or delays in surgical procedures, which speaks to the safety and feasibility of incorporating this regimen in a preoperative setting.”
Overview of the NEOASIS Trial: Expanding Immunotherapy Horizons
The NEOASIS study (NCT06279130) is a Phase 2 clinical trial designed to evaluate the efficacy and safety of botensilimab and balstilimab as neoadjuvant (pre-surgical) therapy for patients with early-stage, non-metastatic solid tumors. It represents the third such clinical evaluation of BOT/BAL in the neoadjuvant context, following previous trials that primarily focused on colorectal cancers.
The study includes two distinct patient cohorts based on mismatch repair status:
- dMMR/MSI-H (mismatch repair–deficient/microsatellite instability–high), and
- pMMR/MSS (mismatch repair–proficient/microsatellite stable).
Each cohort in the safety run-in phase included 10 patients, who received two cycles of combination immunotherapy. Patients were administered one dose of BOT (either 25 mg or 50 mg) plus BAL (450 mg) on Day 1 and again on Day 22. Surgical resection was then scheduled according to standard timelines.
Clinical Results: High Response Rates with Strong Safety Profile
dMMR/MSI-H Cohort (n=10)
This cohort comprised nine patients with colorectal cancer and one with duodenal cancer. The results were highly encouraging:
- Pathological response rate: 90%
- Major pathological response (MPR): 80%
- Pathological complete response (pCR): 70%
pMMR/MSS Cohort (n=10)
This group included patients with various tumor types:
- 6 with triple-negative breast cancer (TNBC)
- 2 with estrogen receptor-positive (ER+) breast cancer
- 1 with Merkel cell carcinoma
- 1 with sarcoma
The results for this more immunologically resistant cohort were also impressive:
- Pathological response rate: 80%
- MPR: 70%
- pCR: 20%
In the triple-negative breast cancer subgroup specifically, 63% of patients achieved a major pathological response after only two doses of immunotherapy—an outcome that is particularly notable given the limited responsiveness of TNBC to many immunotherapies and chemotherapies.
Crucially, no dose-limiting toxicities were observed at either BOT dose level, and all patients underwent surgery on schedule, indicating that the combination is not only effective but also well-tolerated in a preoperative setting.
Significance: Potential Paradigm Shift in Preoperative Cancer Care
The NEOASIS trial outcomes suggest that the BOT/BAL combination may offer a powerful new tool for treating solid tumors, particularly in the early-stage setting where surgical cure remains possible. By inducing substantial tumor regression prior to surgery, neoadjuvant immunotherapy can potentially reduce tumor burden, improve resectability, and possibly lower the risk of recurrence.
The BOT/BAL combination has been engineered to overcome the limitations of first-generation checkpoint inhibitors. Botensilimab, in particular, has been designed to improve immune activation while minimizing toxicities often associated with CTLA-4 inhibitors. Its Fc-enhanced design promotes improved T-cell priming and T-regulatory cell depletion within the tumor microenvironment, mechanisms thought to underlie its broad activity.
“The data from the NEOASIS study reinforce the expanding role of botensilimab and balstilimab as a potent immunotherapy combination in the neoadjuvant space,” said Dr. Steven O’Day, Chief Medical Officer at Agenus. “The high pathological response rates seen in both MSI-H and MSS tumors, including historically unresponsive cancers like triple-negative breast cancer and sarcoma, further support the notion that this regimen may have broad application across tumor types. This early success also strengthens our belief that immunotherapy has a vital role to play earlier in the course of disease.”
Next Steps: Efficacy Expansion and Broader Tumor Inclusion
The encouraging results from the safety run-in phase have enabled the progression to the efficacy expansion phase of the trial, which is currently ongoing. Additional patient data across a wider array of tumor types are being collected to better define the treatment’s impact and inform future development pathways.
Importantly, the inclusion of both immunologically “hot” tumors like MSI-H colorectal cancer and “cold” tumors like pMMR TNBC provides a compelling test of BOT/BAL’s versatility. By achieving major responses in both categories, the combination positions itself as a potential cornerstone of neoadjuvant immuno-oncology strategies.
Broader Implications for Agenus and the Immunotherapy Landscape
Agenus has increasingly focused its development strategy around botensilimab and balstilimab, with multiple ongoing studies across solid tumor types. The NEOASIS results add to a growing body of evidence suggesting that the BOT/BAL combination could become an important part of the treatment landscape not only in advanced settings but also in earlier stages of disease, where intervention can be curative.
The broader immuno-oncology field has long sought effective checkpoint regimens for pMMR tumors, which generally respond poorly to standard PD-1/PD-L1 monotherapy. These results from the NEOASIS study challenge that paradigm and offer renewed hope that immunotherapy can benefit a much wider population of patients when optimally designed and delivered.
The presentation of the NEOASIS study data at AACR 2025 underscores a potentially pivotal moment for Agenus and for the field of neoadjuvant cancer immunotherapy. The combination of botensilimab and balstilimab has demonstrated impressive activity across diverse tumor types—showing high pathological response rates, excellent tolerability, and no surgical delays. With these findings, Agenus continues to advance its vision of transforming cancer care through powerful, immune-driven solutions designed to benefit patients at every stage of their cancer journey.
