Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy from a First-in-Human Study of Volrustomig, a Novel PD-1/CTLA-4 Bispecific Antibody
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: PURPOSE: Volrustomig is an IgG1 monovalent bispecific antibody engineered to preferentially target cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on programmed cell death protein 1 (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 article 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, a performance status of 0 or 1, and adequate organ and marrow function received volrustomig 2.25 to 2,500 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 safety and tolerability, describe dose-limiting toxicities, and determine the maximum tolerated dose. Secondary objectives included the assessment of preliminary antitumor activity and volrustomig pharmacokinetics. RESULTS: Eighty-six 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 (TRAE) 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 intratumoral 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; the median response duration was 17.5 months. CONCLUSIONS: These results support further development of volrustomig as monotherapy and in combination regimens, with phase III trials ongoing. See related commentary by Park and Gainor, p. 2803.
Source: Clinical Cancer Research
Authors: Ben Tran, Mark Voskoboynik, Sang-We Kim, Charlotte Lemech, Enric Carcereny, Sun Young Rha, Myung-Ju Ahn, Enriqueta Felip, Ki Hyeong Lee, Eduardo Castañón Álvarez, James Chih-Hsin Yang, Paolo Antonio Ascierto, Mariano Provencio Pulla, Shunsuke Kondo, Yasutoshi Kuboki, Daniel Freeman, Xuyang Song, Jorge Blando, Steven Eck, Florian J. Song, Zoey Tang, Michael Kuziora, Shelby D. Gainer, Patrick Mitchell, Julie Asare, Amal Ayyoub, Ikbel Achour, Deepa S. Subramaniam, Seock-Ah Im
Institutions: Peter MacCallum Cancer Centre, Alfred Health, Monash University, Asan Medical Center, University of Ulsan, Institut Català d'Oncologia, Yonsei University, Yonsei University Health System, Yonsei Cancer Hospital, Samsung Medical Center, Sungkyunkwan University, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Chungbuk National University Hospital, Clinica Universidad de Navarra, Universidad de Navarra, National Taiwan University, National Taiwan University Hospital, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Hospital Universitario Puerta de Hierro Majadahonda, Tokyo Women's Medical University, National Cancer Centre Japan, National Cancer Center Hospital East, AstraZeneca (United States), Seoul National University, Seoul National University Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7129464004