Phase 1 clinical trial investigating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AB821 in adult patients with locally advanced or metastatic melanoma and other solid tumor malignancies (NCT 07027488).

作者：Harriet M. Kluger, David A. Braun, Ivana M. Djuretic, Michael E. Hurwitz, Jeffrey Joseph Ishizuka, David A. Schoenfeld, Mario Sznol, Mark Sayles, Thuy Thanh Thi Tran · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.16_suppl.tps2687 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Monoclonal and Polyclonal Antibodies Research、Immunotherapy and Immune Responses

TPS2687 Background: In recent years, T-cell enhancement strategies have achieved notable survival benefits in patients with cancer. While cytokine therapy with both IL-2 and IL-21 demonstrate anti-cancer activity through enhanced proliferation, survival and function of antigen specific CD8+ T cells, their use is limited by off-target effects and rapid clearance. AB821 is a fusion of a CD8-targeting antibody that binds to the CD8αβ heterodimer on CD8+ T cells and an IL-21 mutein containing a mutation that attenuates affinity for the IL-21receptor. In pre-clinical experiments, AB821 promotes CD8+ T-effector cell cytotoxicity and CD8+ T-cell memory and demonstrates both robust tumor growth inhibition and minimal toxicity in immune checkpoint inhibitor refractory tumor models. Notably, AB821 avoids activation of other IL-21R-expressing cell types, including CD4+ T cells, NK cells, B cells, dendritic cells, intermediate monocytes, and nonclassical monocytes, that can act as pharmacologic sinks or contribute to off-target toxicity. Methods: This first-in-human phase 1 dose-escalation clinical trial is designed to assess the safety, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary anti-tumor activity of AB821 monotherapy administered every 2 weeks (Q2W) in patients (pts.) with recurrent locally advanced or metastatic melanoma and other immune-responsive solid tumor malignancies. Pts. with melanoma are required to have previously been treated with an inhibitor of PD...