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MDNA55: A locally administered IL4 guided toxin as a targeted treatment for recurrent glioblastoma.

Publication ,  Conference
Randazzo, D; Achrol, A; Aghi, MK; Bexon, M; Brem, S; Brenner, AJ; Butowski, NA; Chandhasin, C; Chowdhary, SA; Coello, M; Floyd, J; Kesari, S ...
Published in: Journal of Clinical Oncology
May 20, 2019

2039 Background: IL4 receptor (IL4R) is frequently and intensely expressed on a variety of human cancers and is associated with poor survival outcomes. Determining the role of the IL4R biomarker in glioblastoma (GBM) will be important for treatment with targeted therapies such as the IL4 fusion toxin MDNA55. Methods: A classification for IL4Rα expression in GBM tissues by H-Score was developed using a validated immunohistochemistry-based approach. MDNA55-05 is an open-label study of MDNA55 administered intratumorally via convection enhanced delivery in recurrent GBM. Levels of IL4Rα expression were assessed retrospectively in 24 subjects in the clinical trial and were correlated with GBM history, imaging responses and survival outcomes following treatment with MDNA55 to explore clinical validation. Results: Range, linearity, specificity and sensitivity testing using a rabbit polyclonal antibody to IL4Rα were performed using normal cortex (negative control) and a panel of normal human tissues and GBM cases from tissue banks. A total of 41 GBM samples were screened and grouped by reactivity thresholds: H-Scores ≥50 were observed in 95% of cases (39/41), H-Scores ≥200 were observed in 51% of cases (21/41), and H-Scores ≥250 were observed in 24% of cases (10/41). GBM tissues obtained at initial diagnosis from subjects enrolled in the trial show that moderate/high IL4R expression (H-Score > 75) was associated with shorter time to first relapse when compared to subjects with low IL4R expression (H-Score ≤ 75) (10.3 mos vs. 16.7 mos, respectively) after upfront standard-of-care treatment, consistent with published findings that IL4R expression is associated with more aggressive disease. Remarkable decreases in tumor size seen in some subjects following MDNA55 treatment were associated only with moderate/high IL4R expression and survival rate at 12 months in this group was also improved (OS12 = 55%) compared to subjects with low IL4R expression (OS12 = 30%). Conclusions: Treatment options for patients with recurrent GBM are very limited and positive outcomes remain rare. Targeting therapies such as MDNA55 by IL4R status may improve patient outcomes and help guide patient selection strategies for future clinical studies. Clinical trial information: NCT02858895.

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

May 20, 2019

Volume

37

Issue

15_suppl

Start / End Page

2039 / 2039

Location

Chicago, IL

Publisher

American Society of Clinical Oncology (ASCO)

Conference Name

2019 American Society of Clinical Oncology Annual Meeting

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Randazzo, D., Achrol, A., Aghi, M. K., Bexon, M., Brem, S., Brenner, A. J., … Sampson, J. H. (2019). MDNA55: A locally administered IL4 guided toxin as a targeted treatment for recurrent glioblastoma. In Journal of Clinical Oncology (Vol. 37, pp. 2039–2039). Chicago, IL: American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/JCO.2019.37.15_suppl.2039
Randazzo, Dina, Achal Achrol, Manish K. Aghi, Martin Bexon, Steven Brem, Andrew Jacob Brenner, Nicholas A. Butowski, et al. “MDNA55: A locally administered IL4 guided toxin as a targeted treatment for recurrent glioblastoma.” In Journal of Clinical Oncology, 37:2039–2039. American Society of Clinical Oncology (ASCO), 2019. https://doi.org/10.1200/JCO.2019.37.15_suppl.2039.
Randazzo D, Achrol A, Aghi MK, Bexon M, Brem S, Brenner AJ, et al. MDNA55: A locally administered IL4 guided toxin as a targeted treatment for recurrent glioblastoma. In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2019. p. 2039–2039.
Randazzo, Dina, et al. “MDNA55: A locally administered IL4 guided toxin as a targeted treatment for recurrent glioblastoma.Journal of Clinical Oncology, vol. 37, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 2039–2039. Manual, doi:10.1200/JCO.2019.37.15_suppl.2039.
Randazzo D, Achrol A, Aghi MK, Bexon M, Brem S, Brenner AJ, Butowski NA, Chandhasin C, Chowdhary SA, Coello M, Floyd J, Kesari S, Merchant F, Merchant N, Vogelbaum MA, Vrionis FD, Zabek M, Sampson JH. MDNA55: A locally administered IL4 guided toxin as a targeted treatment for recurrent glioblastoma. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2019. p. 2039–2039.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

May 20, 2019

Volume

37

Issue

15_suppl

Start / End Page

2039 / 2039

Location

Chicago, IL

Publisher

American Society of Clinical Oncology (ASCO)

Conference Name

2019 American Society of Clinical Oncology Annual Meeting

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences