Botensilimab and Balstilimab Prove Notable OS in Patients with Advanced Solid Tumors

A phase 1b (NCT03860272)¹ clinical study examining patients with advanced solid tumors found that monoclonal antibodies botensilimab (AGEN1181) and balstilimab (AGEN2034) demonstrated notable overall survival (OS) with 2-year survival plateaus, supported by deep, durable responses and prolonged stable disease.

The findings of this trial were presented by Michael Gordon, MD, co-investigator of the study, at the 2025 European Society for Medical Oncology (ESMO) Congress on October 18 in Berlin, Germany.²

The median overall survival (OS) was 17.2 months. At 24 months, 39% of patients were alive.Further, the confirmed overall response rate (ORR) was 17% and was the same between both doses of botensilimab, at 1 mg/kg (95% CI, 12%-23%; n=33/192) and 2 mg/kg (95% CI, 11%-24%; n=25/147). The median duration of response (DOR) was 14.6 months, and the disease control rate (DCR) at 6 weeks was 66%.²

Regarding safety, there were no patient deaths related to the study. The frequency of adverse events (AEs) was lower in the botensilimab 1-mg dose. Overall, 85% of patients experienced AEs in any grade and 32% of patients experienced grade >3 AEs. The most common AEs reported were diarrhea/colitis, thyroid, hepatitis, skin, and pneumonitis.

Clinical benefits were observed in patients who did not have active liver metastases (LM). ORR was 13% in patients with active LM vs 19% in patients with no active LM, the median DOR was 9.8 months vs 16.6 months, clinical benefit rate (CBR) at 24 weeks was 21% vs 29%, median OS was 11.5 months vs 20.7 months, and 24-month OS was 29% vs 43%. Additionally, there was greater efficacy observed in I-O-naive patients vs patients who had previous I-O therapy.

The median age of patients was 61 and majority were female (n=242). Most patients had an ECOG score of 1 (n=234). Over 60% of patients had 3 or more prior therapies. Nearly 70% of patients had multiple metastatic disease, and 31% of patients had active liver metastases.

Patient eligibility criteria included but were not limited to patients having advanced solid tumors refractory to standard treatment and prior I-O therapy.

In the combination therapy arm, patients were treated with 1 or 2 mg/kg of botensilimab every 6 weeks and 3 mg/kg of balstilimab every 2 weeks. At the cutoff date in March 2025, 411 patients had been treated.

The pan tumor populations included microsatellite stable metastatic colorectal cancer (n=164), sarcoma (n=68), PD-1 relapsed or refractory (R/R) non–small cell lung cancer (n=58), ovarian cancer (n=46), and PD-(L)1 R/R hepatocellular carcinoma (n=19).

“Overall, these mature findings with a large trial dataset of botensilimab and balstilimab in refractory solid tumors reinforce and expand on our earlier data,” concluded Gordon during the presentation. “Across a range of cold I-O refractory and heavily pretreated tumors, patients demonstrated durable responses, high disease control rates, and remarkable survival extending beyond 2 years.”

DISCLOSURES: Gordon disclosed having a consulting or advisory role with Imaging Endpoints, Morphic Therapeutic, Viracta Therapeutics, Qualigen Therapuetics, OnQuality Pharmaceuticals, SpringWorks Therapeutics, and Deciphera.

REFERENCES:

1.Fc-Engineered Anti-CTLA-4 Monoclonal Antibody in Advanced Cancer. ClinicalTrials.gov. Updated February 6, 2025. Accessed October 20, 2025. https://www.clinicaltrials.gov/study/NCT03860272

2. Gordon M, Tsimberidou A, Schlechter B, et al. Emerging survival plateaus with botensilimab and balstilimab: Pan tumor data from a large phase Ib trial of advanced solid tumors.Presented at the European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract 1517MO.