Phase 1b/2 study of ADG106, a 4-1BB/CD137 agonist, in combination with toripalimab in patients with advanced solid tumors
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<sup>-</sup>CD16<sup>+</sup>CD56<sup>+</sup> 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.
Authors
- Peter Luo (ORCID: https://orcid.org/0000-0001-5719-1897)
- Xiaohong She
- Jinhui Xue (ORCID: https://orcid.org/0000-0002-9791-2940)
- Songmao Zheng (ORCID: https://orcid.org/0000-0002-7727-0928)
- Qianwen Liu (ORCID: https://orcid.org/0000-0002-4665-5673)
- Shaodong Hong (ORCID: https://orcid.org/0000-0002-5632-6857)
- Guizhong Liu (ORCID: https://orcid.org/0000-0001-9149-4576)
- Yunpeng Yang (ORCID: https://orcid.org/0000-0001-6987-2219)
- Li Zhang (ORCID: https://orcid.org/0000-0002-9507-7320)
- Yang Zhang (ORCID: https://orcid.org/0000-0002-3002-4367)
- Yan Li (ORCID: https://orcid.org/0000-0001-7612-3953)
- Wenfeng Fang (ORCID: https://orcid.org/0000-0002-6440-8246)
- Yan Huang (ORCID: https://orcid.org/0000-0002-9698-2701)
- Yuxiang Ma
- Yuanyuan Zhao (ORCID: https://orcid.org/0000-0003-4264-7665)
- Shaoyan Lin
- Yongsheng Wang (ORCID: https://orcid.org/0009-0007-6865-4325)
- Jiping Zha
- Hongyun Zhao
Institutions
- Sun Yat-sen University (CN)
- Sichuan University (CN)
- West China Medical Center of Sichuan University (CN)
- West China Hospital of Sichuan University (CN)
- Sun Yat-sen University Cancer Center (CN)
Publication Details
- Journal
- iScience
- Published
- 2025-04-22
- DOI
- https://doi.org/10.1016/j.isci.2025.112497
- Citations
- 3
- Primary Topic
- Peptidase Inhibition and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 3.14
Funders
- National Natural Science Foundation of China
- Basic and Applied Basic Research Foundation of Guangdong Province