Cover Image

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Heßling, Kathrin (Author) , Brand, Caroline (Author) , Schwöppe, Christian (Author) , Gerwing, Mirjam (Author) , Pavelka, Stefanie (Author) , Berdel, Andrew F. (Author) , Hintelmann, Heike (Author) , Hamacher, Rainer (Author) , Müller-Tidow, Carsten (Author) , Egerer, Gerlinde (Author) , Hartmann, Wolfgang (Author) , Grünewald, Inga (Author) , Lindner, Lars H. (Author) , Di Gioia, Dorit (Author) , Hecker, Judith S. (Author) , Maurer, Sabine (Author) , Pink, Daniel (Author) , Fried, Marius (Author) , Zapata Bonilla, Sergio A. (Author) , Scheuble, Anne-Marie (Author) , Lordick, Florian (Author) , Ivanyi, Philipp (Author) , Fobker, Manfred (Author) , Lenz, Georg (Author) , Gerss, Joachim (Author) , Kessler, Torsten (Author) , Berdel, Wolfgang E. (Author) , Schliemann, Christoph (Author)
Format: Article (Journal)
Language:English
Published: 19 February 2026
In: Scientific reports
Year: 2026, Volume: 16, Pages: 1-13
ISSN:2045-2322
DOI:10.1038/s41598-026-40362-4
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41598-026-40362-4
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41598-026-40362-4
Get full text
Author Notes: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
Description
Summary: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.
Item Description:Veröffentlicht: 19. Februar 2026
Gesehen am 13.04.2026
Physical Description:Online Resource
ISSN:2045-2322
DOI:10.1038/s41598-026-40362-4

Similar Items