Botensilimab (Fc-enhanced anti–cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti–PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas
Breelyn A. Wilky, Gary K. Schwartz, Michael S. Gordon, Anthony B. El-Khoueiry, Andrea J. Bullock, Brian S. Henick, Mark Agulnik, Arun S. Singh, Daruka Mahadevan, Justin Stebbing, Chloé Delépine, Dhan Chand, Manushak Avagyan, Wei Wu, Benny Johnson, Joseph E. Grossman, Steven O’Day, Jonathan C. Trent, Robin L. Jones, Apostolia M. Tsimberidou
Abstract
PURPOSE: Outcomes for patients with advanced sarcomas are poor and there is a high unmet need to develop novel therapies. The purpose of this phase I study was to define the safety and efficacy of botensilimab (BOT), an Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody, plus balstilimab (BAL), an anti-PD-1 antibody, in advanced sarcomas. METHODS: BOT was administered intravenously (IV) at 1 mg/kg or 2 mg/kg once every 6 weeks in combination with BAL IV at 3 mg/kg once every 2 weeks for up to 2 years. The primary end point was to determine dose-limiting toxicities during the dose-escalation period. Secondary end points include objective response rate (ORR), duration of response (DOR), disease control rate, and progression-free survival (PFS) by RECIST 1.1. Exploratory end points include assessing patient biomarkers including tumor mutational burden, cytokines, and PD-L1 expression. RESULTS: Overall, 64 patients with sarcoma were treated; all were evaluable for safety and 52 for efficacy. The most common treatment-related adverse event (TRAE) was diarrhea/colitis occurring in 35.9% of patients, with grade 3 in 6.3% of patients. No grade 4 or 5 TRAEs were reported. For all evaluable patients, ORR was 19.2% (95% CI, 9.6 to 32.5), and 27.8% (95% CI, 9.7 to 53.5) for evaluable patients with angiosarcoma (n = 18); 33.3% in visceral and 22.2% in cutaneous subtypes. Median PFS for evaluable patients was 4.4 months (95% CI, 2.8 to 6.1), with a 6-month PFS rate of 36% (95% CI, 22 to 50) and a median DOR of 21.7 months (95% CI, 1.9 to not reached). CONCLUSION: The combination of BOT/BAL demonstrated promising efficacy and safety in a large cohort of heavily pretreated sarcoma patients. This encouraging activity warrants further investigation (ClinicalTrials.gov identifier: NCT03860272).