Agenus reports a 72% pathologic complete response and 83% major pathologic response with BOT+BAL in 18 patients in the Phase 2 NEOASIS dMMR colon cancer cohort.
Written By: Charvi Kalal, PharmD
Reviewed By: Pharmacally Editorial Team
Agenus Inc. reported early Phase 2 results on October 25, 2026, from the mismatch repair-deficient (dMMR) colon cancer cohort of NEOASIS (NCT06279130), an investigator-initiated study sponsored by the Netherlands Cancer Institute (NKI). The combination of botensilimab (BOT), an Fc-enhanced anti-CTLA-4 antibody, and balstilimab (BAL), an anti-PD-1 antibody, achieved a major pathologic response (MPR) in 83% of 18 patients and a pathologic complete response (pCR) in 72%. The findings were presented at the European Society for Medical Oncology (ESMO) Congress 2026.
Study Design and Treatment
NEOASIS is a single-centre Phase 2 platform study evaluating neoadjuvant BOT+BAL in patients with resectable solid tumours, irrespective of mismatch repair status. The dMMR colon cancer cohort included 18 patients with non-metastatic, resectable disease.
Patients received botensilimab 50 mg on Day 1 and balstilimab 450 mg on Days 1 and 22, followed by planned surgery within eight weeks. The primary endpoint was MPR, defined as 10% or less residual viable tumour.
The six-week regimen was designed to evaluate whether a short course of immunotherapy before surgery could produce substantial tumour regression. Unlike strategies that require prolonged systemic treatment, this approach investigates the potential of brief neoadjuvant exposure in a biomarker-defined population.
Pathologic Responses and Follow-up
MPR occurred in 15 of 18 patients (83%), meeting the study’s primary endpoint. A pCR was reported in 13 patients (72%), indicating no residual cancer in the assessed surgical specimens. Overall, 17 of 18 patients had a pathologic response.
The cohort included patients with substantial local tumour burden. All tumours were at least T3, 67% were T4, and 72% of patients had regional lymph-node involvement.
At a median follow-up of 15 months, all 18 patients were alive and 16 remained recurrence-free. The announcement does not provide sufficient detail to characterise the outcomes of the other two patients.
One patient with concurrent colon and rectal tumours achieved a complete response in the rectal tumour and elected to preserve the rectum. No regrowth was reported at seven months. This individual observation provides a rationale for further investigation of organ preservation but does not establish its safety or durability as a general treatment strategy.
Safety and Development Plans
Immune-related adverse events were reported as predominantly Grade 1 or 2. One patient experienced Grade 3 colitis, which resolved with treatment. Seventeen patients underwent surgery as planned, while one required earlier surgery on Day 41 because of ileus and achieved a pCR.
The announcement does not provide a complete breakdown of adverse events, limiting assessment of the overall safety profile.
NKI investigators are enrolling a dMMR rectal cancer cohort to investigate whether neoadjuvant BOT+BAL could support organ preservation in selected patients. Agenus is also developing the short-course combination strategy in microsatellite-stable (MSS) colon cancer, a biologically distinct population that requires separate clinical evaluation.
According to Agenus, the agents have received marketing authorisations in Armenia for eligible adults with previously treated MSS metastatic colorectal cancer without active liver metastases. The combination remains investigational outside Armenia and is not approved by the US Food and Drug Administration.
Clinical Interpretation
The NEOASIS findings provide an early signal that six weeks of BOT+BAL can produce substantial pathologic responses in locally advanced dMMR colon cancer, including in patients with T4 tumours or regional lymph-node involvement. The 72% pCR rate is notable given the small cohort and short treatment duration.
However, the study included only 18 patients at a single centre and had no control arm. Because dMMR tumours can respond strongly to immune checkpoint inhibition, these results cannot establish whether adding botensilimab improves outcomes over PD-1 blockade alone. Pathologic response is also not equivalent to proven improvement in recurrence-free or overall survival.
The median follow-up of 15 months is insufficient to establish long-term disease control, while the single rectal organ-preservation observation cannot support broader conclusions about avoiding surgery. The announcement also does not establish that BOT+BAL can replace surgery, postoperative treatment or other established management strategies.
Larger controlled studies with longer follow-up are needed to clarify the durability of responses, the contribution of each agent, the safety profile and the potential role of this short-course approach in clinical practice.
Reference
Agenus Reports 72% of Patients with Locally Advanced dMMR Colon Cancer Had No Cancer Remaining at Surgery Following Six Weeks of BOT+BAL in Phase 2 NEOASIS Study at ESMO 2026, agenus, 25 October 2026
Pan-tumor Neoadjuvant Basket Study of Immune Check-point Inhibition and Novel Immuno-oncology Combinations (NEOASIS), ClinicalTrials.gov ID NCT06279130
About the Writer
Charvi Kalal (LinkedIn) is a Pharm.D intern and aspiring medical writer with hands-on experience in medical writing, clinical research, pharmacovigilance, and clinical pharmacy. She has experience in medical content writing through CliMed, along with exposure to ADR monitoring, prescription analysis, patient counselling, literature review, and research documentation. Her research focuses on ADR monitoring and reporting in breast cancer patients receiving targeted therapy. With certifications in GCP, biomedical research, scientific writing, and clinical research, she is passionate about transforming scientific evidence into accurate, engaging, and accessible healthcare content.