In a phase Ib study reported in the Journal of Clinical Oncology, Wilky et al found that the combination of botensilimab (Fc-enhanced anti–CTLA-4 antibody) and balstilimab (anti–PD-1 antibody) yielded activity in patients with relapsed or refractory metastatic sarcomas.
Study Details
In the trial, 64 patients were enrolled from sites in the United States and United Kingdom between October 2020 and January 2024. Patients received botensilimab at 1 mg/kg (n = 47) or 2 mg/kg once every 6 weeks in combination with balstilimab at 3 mg/kg once every 2 weeks for up to 2 years. Patients had received a median of three lines of previous therapy (range = 0–10).
Key Findings
Among 52 patients evaluable for efficacy, 10 (19.2%, 95% confidence [CI] = 9.6%–32.5%) had objective responses (all partial). Median duration of response was 21.7 months (95% CI = 1.9 months to not reached). An additional 24 patients (46.2%) had stable disease; the disease control rate was 65.4%. Responses were achieved in 5 of 18 patients (27.8%, 95% CI = 9.7%–53.5%) with angiosarcoma, with response rates of 33.3% in visceral and 22.2% in cutaneous subtypes. Median progression-free survival was 4.4 months (95% CI = 2.8–6.1 months), with a 6-month rate of 36%.
Among the 64 patients in the safety population, the most common treatment-related adverse events of any grade were diarrhea/colitis (35.9%), fatigue (26.6%), and pyrexia (21.9%). Grade 3 treatment-related adverse events (no grade 4 or 5 treatment-related events were observed) occurred in 17.2% of patients, most commonly diarrhea/colitis (6.3%) and immune-mediated enterocolitis (3.1%). Treatment-related adverse events led to discontinuation of treatment in 12.5% of patients. Any-grade immune-mediated treatment-related adverse events occurred in 51.6% of patients, most commonly diarrhea/colitis (35.9%), skin reactions (17.2%), and hypothyroidism (10.9%), and were grade 3 in 12.5%, most commonly diarrhea/colitis (7.8%).
The investigators concluded: “The combination of [botensilimab plus balstilimab] demonstrated promising efficacy and safety in a large cohort of heavily pretreated sarcoma patients. This encouraging activity warrants further investigation.”
Breelyn A. Wilky, MD, of the University of Colorado Cancer Center, Aurora, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Agenus Inc. For full disclosures of the study authors, visit ascopubs.org.
