Safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy from a first-in-human study of volrustomig, a novel PD-1/CTLA-4 bispecific antibody
- Author(s)
- Tran, B; Voskoboynik, M; Kim, SW; Lemech, C; Carcereny, E; Rha, SY; Ahn, MJ; Felip, E; Lee, KH; Castañón Álvarez, E; Yang, JC; Ascierto, PA; Provencio Pulla, M; Kondo, S; Kuboki, Y; Freeman, D; Song, X; Blando, J; Eck, S; Song, FJ; Tang, Z; Kuziora, M; Gainer, SD; Mitchell, P; Asare, J; Ayyoub, A; Achour, I; Subramaniam, DS; Im, SA;
- Journal Title
- Clinical Cancer Research
- Publication Type
- Online publication before print
- Abstract
- PURPOSE: Volrustomig is an IgG1 monovalent bispecific antibody engineered to preferentially target CTLA-4 on PD-1-positive T cells while providing adequate and durable PD-1 inhibition. The aim of this phase I, first-in-human study (NCT03530397) is to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics, and antitumor activity of volrustomig. This manuscript reports findings for the dose-exploration and immunotherapy-naïve expansion cohorts. PATIENTS AND METHODS: Patients aged ≥18 years who had histologically or cytologically confirmed advanced cancer, measurable disease, performance status of 0-1, and adequate organ and marrow function received volrustomig 2.25-2500 mg intravenously every 3 weeks until confirmed disease progression, initiation of alternative cancer therapy, unacceptable toxicity, or consent withdrawal. The primary objective in the dose-exploration phase was to evaluate the safety and tolerability, describe dose-limiting toxicities, and determine the maximum tolerated dose. Secondary objectives included assessment of preliminary antitumor activity and volrustomig pharmacokinetics. RESULTS: 86 patients received volrustomig treatment in the dose-exploration and immunotherapy-naïve expansion cohorts; 78 (90.7%) patients were immunotherapy-naïve. Common treatment-related adverse events (TRAEs) 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 one death. At doses ≥500 mg, volrustomig demonstrated robust peripheral and intra-tumoral T cell activation and proliferation at levels greater than those seen with approved PD-1/CTLA-4 regimens. Seventeen (19.8%) patients had objective responses, including 2 (2.3%) complete responses; median response duration was 17.5 months. CONCLUSIONS: These results support further development of volrustomig as monotherapy and in combination regimens, with phase 3 trials ongoing.
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1158/1078-0432.Ccr-25-3447
- Open Access at Publisher's Site
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Creation Date: 2026-03-10 04:07:06
Last Modified: 2026-03-10 04:07:14