Scholarlink

<p>CD40 activation on dendritic cells (DCs) enhances tumor antigen cross-priming of tumor-specific cytotoxic T lymphocytes, strengthening anticancer immune responses. RO7300490 is a fibroblast activation protein (FAP)-targeted CD40 agonist antibody. In this phase I study, 80 patients with advanced and/or metastatic solid tumors received RO7300490 biweekly (dose range 16–1,100 mg). The primary objective was to evaluate safety and tolerability. Secondary/exploratory objectives included pharmacokinetics, antitumor activity and pharmacodynamics. Treatment-related adverse events (TRAEs) occurred in 53 patients (66.3%) and were mostly grade 1–2. Grade 3–4 TRAEs (3.8%) and TRAEs leading to discontinuation (2.5%) were uncommon. No grade 5 TRAEs were reported. RO7300490 showed target-mediated drug disposition, with sustained exposure at higher doses. No objective responses and limited clinical activity (disease control rate 42.5%) were observed despite rapid and persistent tumor uptake of radiolabeled RO7300490. Intratumoral pharmacodynamic activity was demonstrated by a significant increase in DC-LAMP<sup>+</sup> DC density in paired tumor biopsies. An increase in B cell density was also observed, along with the formation of pretertiary lymphoid structures, co-organized in focal micro-neighborhoods with DCs. In summary, treatment with a tumor-targeted CD40 agonist antibody is feasible, clinically manageable and induces immunomodulation of the tumor microenvironment. ClinicalTrials.gov registration: <a href="http://clinicaltrials.gov/ct2/show/NCT04857138">NCT04857138</a>.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Safety and activity of RO7300490, a bispecific CD40 agonist targeted to fibroblast activation protein, in patients with advanced solid tumors: a single-arm, multicenter, first-in-human, phase 1 trial

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月1日

查看全文
  • Ignacio Melero,
  • Bernhard Reis,
  • Corinne Rusterholz,
  • Alexandra Epp,
  • Nicole A. Kratochwil,
  • Chun Wu,
  • Michael Hettich,
  • Georgios Kazantzidis,
  • Natascha Rieder,
  • Petra C. Schwalie,
  • Solveig Badillo,
  • Nadine Kumpesa,
  • Andreas Thommen,
  • Danielle J. Vugts,
  • Victor Moreno,
  • Julia Lostes Bardaji,
  • Eduardo Castanon Alvarez,
  • Carlos E. de Andrea,
  • Iben Spanggaard,
  • Dae Ho Lee,
  • James Spicer,
  • Fiona Thistlethwaite,
  • Do-Youn Oh,
  • Antoine Hollebecque,
  • Olivera Cirovic,
  • Stefan N. Symeonides

摘要

CD40 activation on dendritic cells (DCs) enhances tumor antigen cross-priming of tumor-specific cytotoxic T lymphocytes, strengthening anticancer immune responses. RO7300490 is a fibroblast activation protein (FAP)-targeted CD40 agonist antibody. In this phase I study, 80 patients with advanced and/or metastatic solid tumors received RO7300490 biweekly (dose range 16–1,100 mg). The primary objective was to evaluate safety and tolerability. Secondary/exploratory objectives included pharmacokinetics, antitumor activity and pharmacodynamics. Treatment-related adverse events (TRAEs) occurred in 53 patients (66.3%) and were mostly grade 1–2. Grade 3–4 TRAEs (3.8%) and TRAEs leading to discontinuation (2.5%) were uncommon. No grade 5 TRAEs were reported. RO7300490 showed target-mediated drug disposition, with sustained exposure at higher doses. No objective responses and limited clinical activity (disease control rate 42.5%) were observed despite rapid and persistent tumor uptake of radiolabeled RO7300490. Intratumoral pharmacodynamic activity was demonstrated by a significant increase in DC-LAMP+ DC density in paired tumor biopsies. An increase in B cell density was also observed, along with the formation of pretertiary lymphoid structures, co-organized in focal micro-neighborhoods with DCs. In summary, treatment with a tumor-targeted CD40 agonist antibody is feasible, clinically manageable and induces immunomodulation of the tumor microenvironment. ClinicalTrials.gov registration: NCT04857138.