CXCL12 inhibition in MGMT unmethylated glioblastoma - Results of an early proof-of-concept assessment in the multicentric phase I/II GLORIA trial (NCT04121455)
Frank A. Giordano, Julian P. Layer, Sonia Leonardelli, Lea Friker, Clemens Seidel, Thomas Zeyen, Christina Schaub, Elena Sperk, Franziska Grau, Daniel Paech, Alexander Radbruch, Katharina Sahm, Sied Kebir, Peter Hambsch, Thorsten Pietsch, Martin Glas, Sotirios Bisdas, Michael Hölzel, Ulrich Herrlinger
Abstract #: CTNI-43
Frank.Giordano@ukbonn.de
@FrankGiordanoJr
Disclosures
Research Grants: Carl Zeiss Meditec AG, NOXXON Pharma AG, Elekta AB, GUERBET SA
Personal Fees: Carl Zeiss Meditec AG, Roche Pharma AG, NOXXON Pharma AG, Bristol- Myers Squibb, MSD Sharp and Dohme, Medac GmbH, GUERBET SA, AstraZeneca
Stocks: Implacit GmbH, NOXXON Pharma AG
Employee: University Hospital Bonn, MVZ Venusberg GmbH
Non-financialsupport: Oncare GmbH, Opasca GmbH
The trial presented within this presentation is sponsored by NOXXON Pharma AG, Berlin, Germany.
Statements given in this presentation may reflect personal opinions and experiences and do not
necessarily reflect the opinions of NOXXON.
- 2 -
Background and rationale
Olaptesed pegol (OLA, NOX-A12)
RNA Spiegelmer (L-stereoisomer)
Ceradini, Nat Med 2004 Greenfield, J Clin Invest. 2010
Kioi, J Clin Invest. 2010 Liu, Neuro Oncol. 2014
OLA
CXCR4, C-X-C Motif Chemokine Receptor 4 (receptor for CXCL12) BMDC, bone marrow derived cells
TME, tumor microenvironment
- 3 -
binds & neutralizes
CXCL12
GLORIA Phase I/II Trial
Key inclusion criteria:
- Newly-diagnosedsupratentorial glioblastoma WHO IV
- unmethylated MGMT promoter
- Incomplete resection/biopsy only
- ECOG ≤ 2
RT | |
60 Gy (2 Gy x 30) | |
40.05 Gy (2.67 Gy x 15) | |
OLA (NOX-A12) | Follow- |
continuous i.v. infusion at three doses (200, 400, 600 mg/week) | up |
Inclusion | 6 | 26 |
Safety monitoring
Advanced MRI (perfusion/diffusion)
CODEX® (multiplexed immunofluorescence imaging)
Primary Endpoint: Safety as per # of patients with treatment-related adverse events
Secondary Endpoints: OLA/NOX-A12 plasma levels, tumor vascularization/perfusion (advanced MRI), PFS-6, mPFS, OS, QoL, NANO
- 4 -
CONSORT of GLORIA and controls
GLORIA
11 screened
2 excluded
9 enrolled
3 cohort 1 | RT + 200 mg/week | |||||
9 advanced MRI | ||||||
OLA | ||||||
3 cohort 2 | RT + 400 mg/week | |||||
1 CODEX* | ||||||
OLA | ||||||
3 cohort 3 | RT + 600 mg/week | |||||
OLA | ||||||
** Only performed for paired samples from 1st and 2nd surgery.
- Matched per MGMT promoter methylation status and extent of resection.
- Patients in the control cohort needed to have at least 3 consecutive scans.
Matched Imaging Control Cohort**
25 screened
12 no advanced MRI
13 advanced MRI
7 CODEX*
21 no paired samples
28 screened
CODEX Control Cohort
- 5 -
Attachments
- Original Link
- Original Document
- Permalink
Disclaimer
Noxxon Pharma NV published this content on 19 November 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 22 November 2021 11:24:10 UTC.