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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\u00a0mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    (24\u00a0h, day 1) combined with 1.0\u00a0mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    of tTF-NGR (1\u00a0h, days 2 and 3, q day 22) represents the approx. Maximum tolerated dose (MTD) and with 0.5\u00a0mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    tTF-NGR (days 2 and 3) the recommended starting dose for the randomized part of TRABTRAP. None of the 6 patients on 0.5\u00a0mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-40362-4","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T07:26:48Z","timestamp":1771486008000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trabectedin plus CD13-targeted tissue factor tTF-NGR against advanced relapsed or refractory soft tissue sarcoma: translational data, clinical safety and efficacy"],"prefix":"10.1038","volume":"16","author":[{"given":"Kathrin","family":"Hessling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Brand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Schw\u00f6ppe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirjam","family":"Gerwing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Pavelka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew F.","family":"Berdel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heike","family":"Hintelmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"Hamacher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"M\u00fcller-Tidow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerlinde","family":"Egerer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inga","family":"Gr\u00fcnewald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars H.","family":"Lindner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorit","family":"Di Gioia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith S.","family":"Hecker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Maurer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Pink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius","family":"Fried","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio A.","family":"Zapata Bonilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Marie","family":"Scheuble","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Lordick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Ivanyi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Fobker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Lenz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Gerss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torsten","family":"Kessler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang E.","family":"Berdel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Schliemann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"issue":"Suppl 5","key":"40362_CR1","doi-asserted-by":"publisher","first-page":"v198","DOI":"10.1093\/annonc\/mdq208","volume":"21","author":"PG Casali","year":"2010","unstructured":"Casali, P. 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Berdel reports personal fees and speaker honoraria from Abbvie, grants from the Innovative Medical Research Fund (IMF BE122204) of the University of Muenster and Clinical Scientist CareerS grant by the Deutsche Forschungsgemeinschaft (DFG493624047) all outside the submitted work. R. Hamacher reports personal fees from Lilly and Pharmamar, grants from Lilly, Novartis and Pharmamar, and grants from Clinical Scientist Academy from the University of Essen and DFG all outside the submitted work. C. M\u00fcller-Tidow reports grants from Pfizer and support for medical education activities from Pfizer, Janssen, Sanofi, AbbVie, Amgen, all outside of the submitted work. G. Egerer reports personal fees from Pharmamar and Springworks all outside the submitted work. L.H. Lindner reports personal fees from Novartis, Lilly, Eisai, EL Medconsult, Daiichi Sankyo, Pfizer, Boehringer Ingelheim, Glaxo Smith Kline, Springworks, and grants from Pharmamar, Bavarian Center for Cancer Research, and the federal ministry of research (BMBF), all outside the submitted work. D. Di Gioia reports personal fees from Pharmamar, Mundipharma, Lilly, Novartis, Merck, Roche Diagnostics and Celgene, all outside the submitted work. J.S. Hecker reports personal fees from Johnson and Johnson, Bristol-Myers-Squibb, Kite\/Gilead, Abbvie, Servier, Novartis, Roche, Iovance, Imatics, Philogen, Boehringer Ingelheim, Immunocore, Autolus, Kyverna, Takeda and grants from Jos\u00e9 Carreras Leukemia foundation, Fritz-Thyssen foundation, Else Kroener Fresenius foundation and Bavarian Center for Cancer Research (BZKF), all outside the submitted work. D. Pink reports grants (institutional) from Lilly, Pharmamar, Novartis, Clinigen, Bristol-Myers-Squibb, Recordati, Roche, Deciphera, Boehringer-Ingelheim and other institutional fees from Roche (adivisory role), PharmaMar (advisory role, lecture fee), Blueprint Medicines (lecture fee), and Boehringer-Ingelheim (advisory role, lecture fee), all outside the submitted work. S.A. Zapata Bonilla reports personal fees from Janssen-Cilag, Merck and Pharmamar and grants from GILEAD, Lilly, PharmaMar, Pfizer, and BeiGene, all outside the submitted work. F. Lordick reports personal fees from Amgen, Astellas, Astra Zeneca, BMS, Daiichi Sankyo, Eli Lilly, Falk Foundation, Incyte, MedUpdate, Merck, MSD, Page, Roche, Servier, and grants from AstraZeneca, Beigene, Bristol-Myers-Squibb (BMS), Daiichi Sankyo, Gilead, all outside the sumitted work. P. Ivanyi reports personal fees from Apogepha, Astra Zeneca, Astella, Bayer, BMS, Boehringer Ingelheim, ClinSol, Calliditas, CORE2ED, Deciphera, EISAI, EUSA, DKG-Onkoweb, FoFM Medical Academy, EMD-Serono, Merck Sharp & Dohme, Glaxo Smith Kline, H5-Oncology, ID Institut, Ipsen, Merck Serono (Global), MedKom, MTE-Academy, Metaplan, MSD, New Concept Oncology, Onkowissen-tv.de, Pharmamar, Pfizer, Roche, Schmitz-Communication, StreamedUP! Solution Academy, ThinkWired!, Vivantis, stock ownershib of BB-Biotech, and grants from Arbeitsgemeinschaft Internistische Onkologie in Germany, AstraZeneca, BMS, Calliditas, Cantata, EUSA, EISAI, GlaxoSmithKline, Ipsen, Lilly, Merck, Merck Sharp & Dohme (MSD), Nieders\u00e4chsische Krebsgesellschaft, Novartis, Pfizer, Roche, Serono, Stiftung Immunonkologie, and Wilhelm Sander Stiftung, and immaterial conflicts of interest Member of German Working Party Medical Oncology (AIO), Member of the German Cancer Society, ASCO Member, ESMO Member, Member of Oncological Working Party Hannover (OAK), Spokesman Interdisciplinary Working Party \u2013 Kidney Cancer (IAGN-DKG) (non-financial), Leading Group Head and Neck Cancer (Working party German Medical Oncologist (AIO)), IDMC Trial Adam, Steering Board Immunooncology Cooperative Group (ICOG-H), Clinical Trial Steering Committee CCC-H, all outside the submitted work. G. Lenz reports personal fees from ADC Therapeutics, AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Constellation, Genase, Genmab, Gilead, Hexal\/Sandoz, Immagene, Incyte, Janssen, Karyopharm, Lilly, Miltenyi, MorphoSys, MSD, NanoString, Novartis, PentixaPharm, Pierre Fabre, F. Hoffmann-La Roche Ltd, and Sobi and grants from AGIOS, AQUINOX, AstraZeneca, Bayer, Celgene, Gilead, Janssen, MorphoSys, Novartis, F. Hoffmann-La Roche Ltd, and Verastem, all outside the submitted work. T. Kessler reports travel and meeting grants from Beigene, all outside the submitted work. W.E. Berdel reports personal fees from Philogen and stock ownership of Philogen, all outside the submitted work. He is inventor on patents on vascular targeting with tissue factor-constructs. C. Schliemann reported personal fees from AbbVie, Astellas, AstraZeneca, BMS, Daiichi Sankyo, Laboratories Delbert, Jazz Pharmaceuticals, Novartis, Otsuka, Philogen, Pfizer, Roche and grants from Jazz Pharmaceuticals (institutional), all outside the submitted work. W.E. Berdel and C. Schw\u00f6ppe founded the company ANTUREC Pharmaceuticals GmbH, which is involved in the development of tTF-NGR. W.E. Berdel and A.F. Berdel are relatives. No competing interests were reported by the other authors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7389"}}