Trabectedin plus CD13-targeted tissue factor tTF-NGR against advanced relapsed or refractory soft tissue sarcoma: translational data, clinical safety and efficacy
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/m<sup>2</sup> (24 h, day 1) combined with 1.0 mg/m<sup>2</sup> of tTF-NGR (1 h, days 2 and 3, q day 22) represents the approx. Maximum tolerated dose (MTD) and with 0.5 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 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.
Authors
- Inga Grünewald (ORCID: https://orcid.org/0000-0002-2800-4682)
- Andrew F. Berdel (ORCID: https://orcid.org/0000-0002-7120-2780)
- Anne-Marie Scheuble
- Marius Fried (ORCID: https://orcid.org/0000-0002-5216-9516)
- Christian Schwöppe (ORCID: https://orcid.org/0000-0001-9829-2731)
- Dorit Di Gioia
- Manfred Fobker
- Kathrin Heßling
- Christoph Schliemann (ORCID: https://orcid.org/0000-0003-1755-9583)
- Mirjam Gerwing (ORCID: https://orcid.org/0000-0002-1127-4336)
- Rainer Hamacher (ORCID: https://orcid.org/0000-0001-9655-1226)
- W Berdel
- Heike Hintelmann
- Tobias Keßler (ORCID: https://orcid.org/0000-0001-8350-7074)
- Stefanie Pavelka
- Georg Lenz
- Sabine Maurer
- Daniel Pink
- Philipp Ivanyi
- Judith S. Hecker
- L H Lindner
- Caroline Brand
- Carsten Müller-Tidow
- Sergio A. Zapata Bonilla
- Florian Lordick
- Wolfgang Hartmann
- Joachim Gerss
Institutions
- University of Applied Sciences Mainz (DE)
- Johannes Gutenberg University Mainz (DE)
- Heidelberg University (DE)
- Universitätsmedizin Greifswald (DE)
- University Hospital Heidelberg (DE)
- Medizinische Hochschule Hannover (DE)
- University Hospital Münster (DE)
- Translational Research in Oncology (FR)
- Helios Hospital Bad Saarow (DE)
- Essen University Hospital (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Scientific Reports
- Published
- 2026-02-19
- DOI
- https://doi.org/10.1038/s41598-026-40362-4
- Primary Topic
- Peptidase Inhibition and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Falk Foundation
- Amgen
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- American Society of Clinical Oncology
- Celgene
- F. Hoffmann-La Roche
- Les Laboratories Pierre Fabre
- BeiGene
- Incyte
- Springworks Therapeutics
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Eisai
- Astellas Pharma
- European Society for Medical Oncology
- Servier
- PharmaMar
- MorphoSys
- Ipsen
- Daiichi Sankyo Europe
- Cilag