Phase 1b/2 study of ADG106, a 4-1BB/CD137 agonist, in combination with toripalimab in patients with advanced solid tumors

作者：Shaoyan Lin, Yuxiang Ma, Yongsheng Wang, Yunpeng Yang, Jinhui Xue, Yan Huang, Yuanyuan Zhao, Wenfeng Fang, Shaodong Hong, Yang Zhang, Qianwen Liu, Guizhong Liu, Xiaohong She, Jiping Zha, Songmao Zheng, Yan Li, Peter Luo, Li Zhang, Hongyun Zhao · 发表于：iScience · 年份：2025 · DOI：10.1016/j.isci.2025.112497 · 被引用次数：4 · 研究领域：Peptidase Inhibition and Analysis、Neuropeptides and Animal Physiology、Signaling Pathways in Disease

This phase 1b/2 clinical trial (NCT04775680) evaluated the safety, efficacy, pharmacokinetics and pharmacodynamics of ADG106, a ligand-blocking agonistic antibody targeting CD137 (4-1BB), combined with toripalimab in patients with advanced malignancies. ADG106 0.75–3 mg/kg plus toripalimab 240 mg were administered every 3 weeks. One dose-limiting toxicity occurred in 1 subject at 1.5 mg/kg and 2 in another subject at 3 mg/kg. Grade ≥ 3 treatment related adverse events occurred in 4/25 patients (16%). The overall disease control rate was 29.2% (7/24), including 1 partial response (PR) patient with a duration of response and a progression-free survival of 17.6 and 24.5 months. Circulating biomarkers suggested increased soluble CD137, CD3 − CD16 + CD56 + natural killer (NK) cells, interferon γ (IFN-γ), TNFα, and IL-6 after therapy. Elevated baseline memory T cells and PD-L1, activation of immune-related pathways, along with enhanced T cell proliferation and increased IFN-γ following treatment were observed in the PR patient. ADG106 in combination with toripalimab demonstrated a manageable safety profile but no efficacy conclusions could be drawn.