CTNI-62 - Interim data on dual inhibition of post-radiogenic angio-vasculogenesis by olaptesed pegol (NOX-A12) and bevacizumab in glioblastoma from the first expansion arm of the phase 1/2 GLORIA trial.

Friday, November 17, 2023

7:30 PM – 9:30 PM PT

Location: Exhibit Hall A/B

Poster Presenter(s)

Frank A. Giordano

Department of Radiation Oncology, University Medical Center Mannheim
Mannheim, Baden-Wurttemberg, Germany

Author(s)

JL

Julian P. Layer

Department of Radiation Oncology, University Hospital Bonn
Bonn, Germany
SL

Sonia Leonardelli

Institute of Experimental Oncology, University Hospital Bonn
Bonn, Germany
LF

Lea L. Friker

Institute of Neuropathology, University Hospital Bonn
Bonn, Germany
CS

Christina Schaub

Division of Neurooncology, Department of Neurology, University Hospital Bonn
Bonn, Germany
Thomas Zeyen

Division of Neurooncology, Department of Neurology, University Hospital Bonn
Bonn, Germany
ES

Elena Sperk

Department of Radiation Oncology, Medical Faculty Mannheim, University of Heidelberg
Mannheim, Germany
PH

Peter Hambsch

Department of Radiotherapy, University Hospital Leipzig
Leipzig, Germany
Christoph Oster

Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Division of Clinical Neurooncology, University Medicine Essen, University Duisburg-Essen, Essen, Germany
Essen, Nordrhein-Westfalen, Germany
FG

Franziska Grau

Department of Neuroradiology, University Hospital Bonn
Bonn, United States
DP

Daniel Paech

Department of Neuroradiology, University Hospital Bonn
Bonn, Germany
WM

Wolf Müller

Institute of Neuropathology, University Hospital Leipzig
Leipzig, Germany
TP

Torsten Pietsch

University Hospital Bonn
Bonn, Nordrhein-Westfalen, Germany
LS

L. Christopher Schmeel

Department of Radiation Oncology, University Hospital Bonn
Bonn, Germany
OG

Oliver Grauer

Department of Neurology, University Hospital Münster
Münster, Nordrhein-Westfalen, Germany
Mirjam Renovanz

Department of Neurology & Interdisciplinary Neuro-Oncology, University Hospital Tübingen, Hertie Institute for Clinical Brain Research
Tübingen, Germany
Ghazaleh Tabatabai

University Hospital Tübingen and Eberhard Karls University Tübingen
Tübingen, Baden-Wurttemberg, Germany
Sied Kebir

Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Division of Clinical Neurooncology, University Medicine Essen, University Duisburg-Essen, Essen, Germany
Essen, Nordrhein-Westfalen, Germany
SB

Sotirios Bisdas

Department of Neuroradiology at the National Hospital for Neurology, London
London, United Kingdom
EG

Erdem Güresir

Department of Neurosurgery, University Hospital Leipzig
Leipzig, Germany
Martin Glas

Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Division of Clinical Neurooncology, University Medicine Essen, University Duisburg-Essen, Essen, Germany
Essen, Germany
CS

Clemens Seidel

Department of Radiotherapy and Radiation Oncology, University Hospital Leipzig, Leipzig, Germany
Leipzig, Germany
MH

Michael Hölzel

Institute of Experimental Oncology, University Hospital Bonn
Bonn, Germany
UH

Ulrich Herrlinger

Division of Clinical Neurooncology, Department of Neurology and Center for Integrated Oncology, University Hospital Bonn, Bonn, Germany
Bonn, Germany

Background: We recently reported favorable safety and preliminary efficacy signals for treatment with radiotherapy (RT), the CXCL12 neutralizing L-RNA aptamer olaptesed pegol (NOX-A12) and bevacizumab for glioblastoma (GBM) in the German multicenter phase 1/2 GLORIA trial (NCT04121455). Here, we report updated outcomes on dual inhibition of vasculogenesis (NOX-A12) and angiogenesis (bevacizumab).

Methods: Six patients with incompletely resected, MGMT-unmethylated GBM, ECOG≤ 2 were enrolled, receiving standard RT (60 Gy in 30 fractions), continuous i.v. infusions of NOX-A12 (600 mg/week) and i.v. infusions of bevacizumab (10 mg/kg q2w). The primary endpoint was safety. Secondary endpoints included radiographic response according to modified RANO criteria (mRANO) as well as perfusion/diffusion imaging.

Results: Combination treatment was well-tolerated and safe. Of all G≥2 AEs (n= 79), two G2 events (2.5%) were deemed related to NOX-A12 only. There were no dose-limiting toxicities and no treatment-related deaths. At a median follow-up of 14.6 months, one patient deceased due to distant leptomeningeal spread. Median overall survival (OS) has not yet been reached. With an overall response rate (ORR) of 83.3% under treatment, one patient achieved confirmed complete response (CR), four patients partial response (PR) and one patient stable disease (SD). The median best response under treatment was -68.9% (-53,8% to -100%) for target lesion sums and -100% (-99.9% to -100%) for non-target lesion (NTL) sums. In all three patients with NTLs at least one lesion disappeared. The median best change from baseline of the highly perfused-tumor fraction was -98.2% (-61.3% to -100%) and the median best change of the apparent diffusion coefficient was 24.9% (7.3% to 59.1%).

Conclusions: Interim data of the ongoing trial confirm the previously established safety profile of NOX-A12 for combinatory treatment with bevacizumab while demonstrating improved efficacy with deeper and longer-lasting responses and a higher ORR compared to treatment with RT and NOX-A12 only.