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.