ADG106（一种 4-1BB/CD137 激动剂）联合特瑞普利单抗治疗晚期实体瘤患者的 1b/2 期研究

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.