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Verfasst von:Giordano, Frank Anton [VerfasserIn]   i
 Layer, Julian [VerfasserIn]   i
 Leonardelli, Sonia [VerfasserIn]   i
 Friker, Lea L. [VerfasserIn]   i
 Turiello, Roberta [VerfasserIn]   i
 Corvino, Dillon [VerfasserIn]   i
 Zeyen, Thomas [VerfasserIn]   i
 Schaub, Christina [VerfasserIn]   i
 Müller, Wolf [VerfasserIn]   i
 Sperk, Elena [VerfasserIn]   i
 Schmeel, Christopher [VerfasserIn]   i
 Sahm, Katharina [VerfasserIn]   i
 Oster, Christoph [VerfasserIn]   i
 Kebir, Sied [VerfasserIn]   i
 Hambsch, Peter [VerfasserIn]   i
 Pietsch, Torsten [VerfasserIn]   i
 Bisdas, Sotirios [VerfasserIn]   i
 Platten, Michael [VerfasserIn]   i
 Glas, Martin [VerfasserIn]   i
 Seidel, Clemens [VerfasserIn]   i
 Herrlinger, Ulrich [VerfasserIn]   i
 Hölzel, Michael [VerfasserIn]   i
Titel:L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy in newly-diagnosed glioblastoma
Titelzusatz:dose escalation of the phase I/II GLORIA trial
Verf.angabe:Frank A. Giordano, Julian P. Layer, Sonia Leonardelli, Lea L. Friker, Roberta Turiello, Dillon Corvino, Thomas Zeyen, Christina Schaub, Wolf Müller, Elena Sperk, Leonard Christopher Schmeel, Katharina Sahm, Christoph Oster, Sied Kebir, Peter Hambsch, Torsten Pietsch, Sotirios Bisdas, Michael Platten, Martin Glas, Clemens Seidel, Ulrich Herrlinger, Michael Hölzel
E-Jahr:2024
Jahr:28 May 2024
Umfang:14 S.
Fussnoten:Gesehen am 19.12.2024
Titel Quelle:Enthalten in: Nature Communications
Ort Quelle:[London] : Springer Nature, 2010
Jahr Quelle:2024
Band/Heft Quelle:15(2024), Artikel-ID 4210, Seite 1-14
ISSN Quelle:2041-1723
Abstract:The chemokine CXCL12 promotes glioblastoma (GBM) recurrence after radiotherapy (RT) by facilitating vasculogenesis. Here we report outcomes of the dose-escalation part of GLORIA (NCT04121455), a phase I/II trial combining RT and the CXCL12-neutralizing aptamer olaptesed pegol (NOX-A12; 200/400/600 mg per week) in patients with incompletely resected, newly-diagnosed GBM lacking MGMT methylation. The primary endpoint was safety, secondary endpoints included maximum tolerable dose (MTD), recommended phase II dose (RP2D), NOX-A12 plasma levels, topography of recurrence, tumor vascularization, neurologic assessment in neuro-oncology (NANO), quality of life (QOL), median progression-free survival (PFS), 6-months PFS and overall survival (OS). Treatment was safe with no dose-limiting toxicities or treatment-related deaths. The MTD has not been reached and, thus, 600 mg per week of NOX-A12 was established as RP2D for the ongoing expansion part of the trial. With increasing NOX-A12 dose levels, a corresponding increase of NOX-A12 plasma levels was observed. Of ten patients enrolled, nine showed radiographic responses, four reached partial remission. All but one patient (90%) showed at best response reduced perfusion values in terms of relative cerebral blood volume (rCBV). The median PFS was 174 (range 58-260) days, 6-month PFS was 40.0% and the median OS 389 (144-562) days. In a post-hoc exploratory analysis of tumor tissue, higher frequency of CXCL12+ endothelial and glioma cells was significantly associated with longer PFS under NOX-A12. Our data imply safety of NOX-A12 and its efficacy signal warrants further investigation.
DOI:doi:10.1038/s41467-024-48416-9
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.1038/s41467-024-48416-9
 kostenfrei: Volltext: https://www.nature.com/articles/s41467-024-48416-9
 DOI: https://doi.org/10.1038/s41467-024-48416-9
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:CNS cancer
 Radiotherapy
 Targeted therapies
 Translational research
K10plus-PPN:1913040577
Verknüpfungen:→ Zeitschrift

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