Data from Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy from a First-in-Human Study of Volrustomig, a Novel PD-1/CTLA-4 Bispecific Antibody

作者：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 A. Ascierto, Mariano Provencio, Shunsuke Kondo, Yasutoshi Kuboki, Daniel Freeman, Xuyang Song, Jorge Blando, Steven Eck, Florian Song, Zoey Tang, Michael Kuziora, Shelby D. Gainer, Patrick Mitchell, Julie M. Asare, Amal Ayyoub, Ikbel Achour, Deepa S. Subramaniam, Seock‐Ah Im · 年份：2026 · DOI：10.1158/1078-0432.c.8600817 · 研究领域：Medicine、Internal medicine、Oncology、Gastroenterology、Immunology、Pharmacology、Surgery

<div>AbstractPurpose: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 ...