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Background <p>Acasunlimab is a PD-L1 × 4-1BB bispecific antibody that induces T-cell activation through conditional 4-1BB stimulation, which is dependent on simultaneous PD-L1 binding, while the acasunlimab PD-L1–specific arm inhibits PD-1/PD-L1 activity without 4-1BB binding. Acasunlimab may produce prolonged, synergistic antitumor responses in patients with advanced solid malignancies.</p> Methods <p>This phase 1, open-label, dose-escalation trial evaluated acasunlimab monotherapy and combination therapy with pembrolizumab in Japanese adult patients with advanced or metastatic solid tumors. Using a 3 + 3 design, patients received single intravenous acasunlimab infusions (15–800&#xa0;mg every 3&#xa0;weeks [Q3W]), or acasunlimab 100&#xa0;mg plus pembrolizumab 200&#xa0;mg Q3W. Primary endpoints included adverse events, dose-limiting toxicity (DLT), and pharmacokinetics. Pharmacodynamics and antitumor activity were also evaluated.</p> Results <p>Eighteen patients were enrolled with diverse tumor types. Grade 3 treatment-related adverse events (TRAEs) occurred in 5 of 15 patients receiving acasunlimab monotherapy and 1 of 3 patients who received acasunlimab plus pembrolizumab. No grade 4 or 5 TRAEs occurred, and no DLTs or TRAEs leading to death at any monotherapy or combination dose were reported. Pharmacokinetics for acasunlimab in Japanese patients were comparable to those in non-Japanese patients from other clinical studies. Six patients receiving acasunlimab monotherapy experienced a best overall response of stable disease, as did one patient receiving acasunlimab plus pembrolizumab.</p> Conclusions <p>Acasunlimab demonstrated a manageable safety profile, with comparable pharmacokinetics in Japanese and non-Japanese patients. Antitumor activity was demonstrated in a small number of patients with diverse tumor types.</p>

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A phase 1 dose-finding and pharmacokinetic study of acasunlimab alone or in combination with pembrolizumab in Japanese patients with advanced or metastatic solid tumors

  • 期刊论文

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  • 发表日期：

    2026年6月30日

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  • Noboru Yamamoto,
  • Gaurav Bajaj,
  • Homer C. Adams III,
  • Ami Takahashi,
  • Risa Fukushi,
  • Ulf Forssmann,
  • Edward Ramirez Ganoza,
  • Yasutoshi Kuboki

摘要

Background

Acasunlimab is a PD-L1 × 4-1BB bispecific antibody that induces T-cell activation through conditional 4-1BB stimulation, which is dependent on simultaneous PD-L1 binding, while the acasunlimab PD-L1–specific arm inhibits PD-1/PD-L1 activity without 4-1BB binding. Acasunlimab may produce prolonged, synergistic antitumor responses in patients with advanced solid malignancies.

Methods

This phase 1, open-label, dose-escalation trial evaluated acasunlimab monotherapy and combination therapy with pembrolizumab in Japanese adult patients with advanced or metastatic solid tumors. Using a 3 + 3 design, patients received single intravenous acasunlimab infusions (15–800 mg every 3 weeks [Q3W]), or acasunlimab 100 mg plus pembrolizumab 200 mg Q3W. Primary endpoints included adverse events, dose-limiting toxicity (DLT), and pharmacokinetics. Pharmacodynamics and antitumor activity were also evaluated.

Results

Eighteen patients were enrolled with diverse tumor types. Grade 3 treatment-related adverse events (TRAEs) occurred in 5 of 15 patients receiving acasunlimab monotherapy and 1 of 3 patients who received acasunlimab plus pembrolizumab. No grade 4 or 5 TRAEs occurred, and no DLTs or TRAEs leading to death at any monotherapy or combination dose were reported. Pharmacokinetics for acasunlimab in Japanese patients were comparable to those in non-Japanese patients from other clinical studies. Six patients receiving acasunlimab monotherapy experienced a best overall response of stable disease, as did one patient receiving acasunlimab plus pembrolizumab.

Conclusions

Acasunlimab demonstrated a manageable safety profile, with comparable pharmacokinetics in Japanese and non-Japanese patients. Antitumor activity was demonstrated in a small number of patients with diverse tumor types.