Multinational first-in-human phase 1 study of volrustomig for advanced cancer

Volrustomig is a bispecific antibody engineered to preferentially target CTLA-4 on PD-1-positive T cells while providing adequate and durable PD-1 inhibition. A multinational, first in human phase 1 study evaluated volrustomig in adult patients with histologically or cytologically confirmed advanced cancer, measurable disease, performance status 0-1, and adequate organ and marrow function. Patients received volrustomig 2.25-2500 mg intravenously every 3 weeks until progression or unacceptable toxicity. Results for the dose-exploration and immunotherapy-naïve expansion cohorts have now been published. Eighty-six patients (90.7% immunotherapy-naïve) received volrustomig. Common treatment-related adverse events were pruritus (30.2%), hypothyroidism (26.7%), hyperthyroidism (24.4%), and rash (24.4%); TRAEs led to treatment discontinuation in 33.7% of patients and to one death. At doses ≥ 500 mg, volrustomig demonstrated robust peripheral and intratumoral T cell activation and proliferation at levels greater than those seen with approved anti-PD-1/CTLA-4 regimens. Seventeen patients (19.8%) had objective responses with a median duration of 17.5 months. Two patients (2.3%) had complete responses. The authors conclude that these results support further study of volrustomig.