Scholarlink

<p>Trabectedin is standard for r/r soft tissue sarcomas. tTF-NGR accumulates in tumor vasculature leading to tumor vascular occlusion and tumor infarction. Both compounds in sequence could trap trabectedin inside tumors and increase its efficacy, which then optimizes the pro-coagulatory activity of tTF-NGR. This report summarizes translational data and results of the safety run-in patient cohort of the TRABTRAP trial combining trabectedin plus tTF-NGR. A dose of trabectedin of 1.5&#xa0;mg/m<sup>2</sup> (24&#xa0;h, day 1) combined with 1.0&#xa0;mg/m<sup>2</sup> of tTF-NGR (1&#xa0;h, days 2 and 3, q day 22) represents the approx. Maximum tolerated dose (MTD) and with 0.5&#xa0;mg/m<sup>2</sup> tTF-NGR (days 2 and 3) the recommended starting dose for the randomized part of TRABTRAP. None of the 6 patients on 0.5&#xa0;mg/m<sup>2</sup> tTF-NGR had dose-limiting toxicity (DLT). Higher doses or additional days of application of tTF-NGR led to grade 3 DLT including early troponin T high sensitivity increase, a reversible non-ST-elevation myocardial infarction in one patient, and reversible thromboembolic events. Pharmacokinetics explain the difference of the MTD between the phase I study and in TRABTRAP. Experimental and clinical efficacy and tolerability of the combination between trabectedin and tTF-NGR supports the active randomized part of TRABTRAP.</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

Trabectedin plus CD13-targeted tissue factor tTF-NGR against advanced relapsed or refractory soft tissue sarcoma: translational data, clinical safety and efficacy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月19日

查看全文
  • Kathrin Hessling,
  • Caroline Brand,
  • Christian Schwöppe,
  • Mirjam Gerwing,
  • Stefanie Pavelka,
  • Andrew F. Berdel,
  • Heike Hintelmann,
  • Rainer Hamacher,
  • Carsten Müller-Tidow,
  • Gerlinde Egerer,
  • Wolfgang Hartmann,
  • Inga Grünewald,
  • Lars H. Lindner,
  • Dorit Di Gioia,
  • Judith S. Hecker,
  • Sabine Maurer,
  • Daniel Pink,
  • Marius Fried,
  • Sergio A. Zapata Bonilla,
  • Anne-Marie Scheuble,
  • Florian Lordick,
  • Philipp Ivanyi,
  • Manfred Fobker,
  • Georg Lenz,
  • Joachim Gerss,
  • Torsten Kessler,
  • Wolfgang E. Berdel,
  • Christoph Schliemann

摘要

Trabectedin is standard for r/r soft tissue sarcomas. tTF-NGR accumulates in tumor vasculature leading to tumor vascular occlusion and tumor infarction. Both compounds in sequence could trap trabectedin inside tumors and increase its efficacy, which then optimizes the pro-coagulatory activity of tTF-NGR. This report summarizes translational data and results of the safety run-in patient cohort of the TRABTRAP trial combining trabectedin plus tTF-NGR. A dose of trabectedin of 1.5 mg/m2 (24 h, day 1) combined with 1.0 mg/m2 of tTF-NGR (1 h, days 2 and 3, q day 22) represents the approx. Maximum tolerated dose (MTD) and with 0.5 mg/m2 tTF-NGR (days 2 and 3) the recommended starting dose for the randomized part of TRABTRAP. None of the 6 patients on 0.5 mg/m2 tTF-NGR had dose-limiting toxicity (DLT). Higher doses or additional days of application of tTF-NGR led to grade 3 DLT including early troponin T high sensitivity increase, a reversible non-ST-elevation myocardial infarction in one patient, and reversible thromboembolic events. Pharmacokinetics explain the difference of the MTD between the phase I study and in TRABTRAP. Experimental and clinical efficacy and tolerability of the combination between trabectedin and tTF-NGR supports the active randomized part of TRABTRAP.