Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Discussion session - CNS tumours

5581 - Understanding Biological Activity, Tumor Response and Pseudoprogression in a Phase-2b Study of MDNA55 in Adults with Recurrent or Progressive Glioblastoma (GB)

Date

20 Oct 2018

Session

Poster Discussion session - CNS tumours

Presenters

Martin Bexon

Citation

Annals of Oncology (2018) 29 (suppl_8): viii122-viii132. 10.1093/annonc/mdy273

Authors

M.F. Bexon1, A. Achrol2, K. Bankiewicz3, A. Brenner4, N. Butowski5, S. Kesari6, F. Merchant7, R. Merchant7, D. Randazzo8, M. Vogelbaum9, M. Zabek10, J. Sampson8

Author affiliations

  • 1 Medical, Medicenna BioPharma, 77056 - Houston/US
  • 2 Neurovascular Surgery, Pacific Neurosciences Institute, Santa Monica/US
  • 3 Department Of Neurological Surgery, University of California San Francisco, 94143 - San Francisco/US
  • 4 Medical Oncology, University of Texas Health San Antonio, San Antonio/US
  • 5 Neurological Surgery, UCSF, San Francisco/US
  • 6 Department Of Translational Neurosciences And Neurotherapeutics, Pacific Neurosciences Institute, Santa Monica/US
  • 7 Clinical, Medicenna BioPharma, 77056 - Houston/US
  • 8 Department Of Neurosurgery, Duke University Medical Center, Durham/US
  • 9 Department Of Neurosurgery, Cleveland Clinic, Cleveland/US
  • 10 Neurovascular Surgery, Mazovian Brodnowski Hospital, Warsaw/PL
More

Resources

Abstract 5581

Background

MDNA55, a novel Interleukin-4 empowered cytokine fused to Pseudomonas exotoxin, binds to IL-4 receptor (IL-4R) overexpressed by GB and immunosuppressive cells of the tumor microenvironment. Understanding biological effects of MDNA55 and defining their time course requires multi-modal imaging. Consecutive increases in tumor size defined by Response Assessment in Neuro-Oncology (RANO) can result in premature withdrawal of subjects prior to evaluation of clinical benefit. Standard tumor response tools need optimizing for localized immunotherapies to capture delayed treatment benefit.

Methods

MDNA55-05 is a 52 subject, open-label, non-randomized, study of intratumoral delivery of ≤ 240 μg MDNA55 via ≤ 4 catheters in a single treatment in GB at 1st or 2nd recurrence, tumors ≤ 4 cm. Multimodality MRI determines tissue response and disease status using RANO-based criteria, combining contrast-enhanced and perfusion imaging.

Results

27 subjects, median age 51 (35 - 77) received 18 – 180 mg MDNA55. Prior treatments included surgery (N = 26), radiation (N = 25) and temozolomide (N = 25). Review of some early post-treatment MRIs show extensive changes to enhancement which could increase for up to 120 days then take another 6 months to resolve. Multi-modal MRI helps differentiate changes due to progression from local tissue reactions (pseudoprogression). Response patterns seen include early progression, early onset response and delayed onset response. Withdrawal of subjects without differentiating pseudoprogression from true progression can preclude the ability to fully assess therapeutic effect. A refined MDNA55 evaluation regimen consisting of multi-modal MRI and/or biopsies has been implemented to optimize the chance for increased therapeutic benefit.

Conclusions

These findings show biologic activity of MDNA55 in recurrent GB with appearances on imaging suggestive of disease control in some subjects. We illustrate how supportive diagnostic modalities are required for accurate response assessments and argue the importance of refining overall response tools according to treatment type.

Clinical trial identification

NCT02858895.

Legal entity responsible for the study

Medicenna Therapeutics.

Funding

Medicenna Therapeutics.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings