At the ESMO Congress 2026, Emma van den Berg (Amsterdam, Netherlands) presented results from the Phase II NEOASIS study (NCT06279130), evaluating neoadjuvant botensilimab plus balstilimab in patients with non-metastatic, resectable mismatch repair-deficient (dMMR) colorectal cancer.
The findings were presented on October 25, 2026, during the Colon Cancer poster session (837P), under the title “Neoadjuvant botensilimab plus balstilimab in MMR deficient colorectal cancer: Results from the NEOASIS study.”
Commenting on the findings in an October 25 press release from Agenus, Steven J. O’Day, MD, Chief Medical Officer of Agenus, stated:
“These results show how much a short course of BOT+BAL can accomplish before surgery, even in patients whose cancer had already grown through the bowel wall or reached the lymph nodes.”
Why Was NEOASIS Conducted?
Immune checkpoint inhibition has demonstrated substantial activity in dMMR colorectal cancer. However, the optimal immunotherapy regimen, safety, and potential for organ-preserving treatment approaches remain under investigation. Botensilimab is an Fc-enhanced anti-CTLA-4 antibody, while balstilimab targets PD-1. The Phase II NEOASIS platform study was designed to investigate pathological responses to short-course neoadjuvant botensilimab plus balstilimab across different mismatch repair-proficient (pMMR) and dMMR tumours.
The analysis presented at ESMO 2026 focused on the dMMR colorectal cancer cohort, evaluating the pathological response and safety of this combination before surgery.
NEOASIS Study Design and Methods
NEOASIS is a Phase II platform study evaluating neoadjuvant botensilimab plus balstilimab across different resectable solid tumours. The dMMR colorectal cancer cohort included 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 surgery within eight weeks. The primary endpoint was MPR, defined as 10% or less residual viable tumour (RVT).
The study used Simon’s two-stage design. Eight patients were included in the first stage, with expansion to 18 patients if more than two achieved MPR. The primary endpoint would be met if at least seven of 18 patients achieved MPR.
Key Findings from NEOASIS
A total of 18 patients received neoadjuvant botensilimab plus balstilimab. The median age was 58 years, and 61% of patients were male. All patients had at least clinical T3 disease, while 67% had cT4 tumours.
Commenting on the findings, Myriam Chalabi, MD, PhD, principal investigator of NEOASIS at the Netherlands Cancer Institute, stated in the Agenus press release:
“Nearly three out of four patients with locally advanced disease, had no cancer remaining at surgery after a single dose of botensilimab and two doses of balstilimab. These dMMR colon cancer results build on the responses we first reported across multiple tumor types in NEOASIS and support continued investigation of BOT+BAL before surgery. Our ongoing rectal cancer cohort is exploring whether deep responses like these, with a short duration of neoadjuvant BOT+BAL, can allow selected patients to preserve their organs and quality of life without compromising cancer outcomes.”
Pathological Response
Pathological responses were observed in 17 of 18 patients following neoadjuvant treatment. The MPR rate was 83% (15/18), including 13 patients (72%) who achieved a pathological complete response. Two patients had a partial pathological response, defined as 10%–50% residual viable tumour.
One patient did not achieve a pathological response and had 70% residual viable tumour. With 15 major pathological responses among 18 treated patients, the study met its prespecified primary endpoint.
Surgical Outcomes and Organ Preservation
One patient had synchronous colon and rectal tumours. Following neoadjuvant treatment, the rectal tumour demonstrated a complete endoscopic response, and the patient opted for an organ-preserving approach for the rectal lesion. Surgery was performed for the colon tumour, which showed a partial pathological response.
One patient with a partial pathological response and positive lymph nodes subsequently received adjuvant chemotherapy. These findings included an individual case of rectal organ preservation, although the study did not establish organ preservation as an alternative to surgery for the broader dMMR colorectal cancer population.
Safety Outcomes
Grade 1–2 immune-related adverse events (irAEs) were reported in 72% of patients. The most commonly reported events were flu-like symptoms (24%), rash (20%), and hypothyroidism (20%).
One patient developed Grade 3 colitis, which resolved following treatment with infliximab and corticosteroids. The second dose of balstilimab was omitted in this patient, who did not achieve a pathological response. Two patients without pre-existing obstructive symptoms developed ileus.
One underwent surgery as planned, while the other underwent earlier surgery on Day 41. Both patients achieved a pathological complete response, and pathological examination revealed stricturing tumours. The investigators described the neoadjuvant combination as safe, although clinically significant complications, including Grade 3 colitis and ileus requiring earlier surgery, were observed.
Conclusions
The Phase II NEOASIS study demonstrated high rates of pathological response following short-course neoadjuvant botensilimab plus balstilimab in patients with non-metastatic, resectable dMMR colorectal cancer.
Major pathological response was achieved in 83% of patients (15/18), including a pathological complete response in 72% (13/18), meeting the study’s prespecified primary endpoint. Grade 1–2 immune-related adverse events occurred in 72% of patients. One Grade 3 colitis event and two cases of ileus were reported.
The study also described one patient with synchronous colon and rectal tumours who underwent colon surgery while opting for organ preservation of the rectal lesion after a complete endoscopic response.
The investigators concluded that neoadjuvant botensilimab plus balstilimab demonstrated a high pathological response rate with an acceptable safety profile, supporting further evaluation in dMMR colorectal cancer.
Additional investigation is ongoing within the NEOASIS platform, including a dedicated rectal cancer organ-preservation cohort. The small sample size and preliminary findings mean that further evidence is needed to establish the role of this regimen and its potential for organ-preserving treatment strategies.
