This is a single-arm, open-label, multicenter study in approximately 43 adults with primary (de novo) Glioblastoma that has recurred or progressed after failure of first-line therapy [according to Response Assessment in Neuro-Oncology (RANO) criteria]. Eligible subjects will receive intratumoral infusion of MDNA55 administered via convection-enhanced delivery (CED).
An Open-Label Non-Randomized, Multi-Center Phase-2 Study of Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Glioblastoma at First Recurrence or Progression
The study drug, MDNA55, is a fusion protein comprising a genetically engineered Interleukin-4 (IL-4) linked to a modified version of the Pseudomonas aeruginosa exotoxin A (PE). MDNA55 binds to the IL-4 receptor (IL4R), over-expressed by cancer cells and non-malignant immunosuppressive cells of the tumor microenvironment (TME), and delivers a potent cell-killing agent, PE. The target, IL4R, is an ideal but under-exploited target for the development of cancer therapeutics, as it is frequently and intensely expressed on a wide variety of human carcinomas. Expression levels of IL4R are low on the surface of healthy and normal cells, but increase several-fold on cancer cells. A majority of cancer biopsy and autopsy samples from adult and pediatric brain tumors, including recurrent glioblastoma biopsies, have been shown to over-express the IL4R. Cells that do not express the IL4R biomarker do not bind to MDNA55 and are, therefore, not subject to PE-mediated effects.
This is a single-arm, open-label, multicenter study in approximately 43 adults with primary (de novo) Glioblastoma that has recurred or progressed after failure of standard first-line therapy (according to RANO criteria). The study will be conducted at up to 10 clinical sites following institutional review board approval and completed informed consent.
Subjects that meet the study eligibility criteria will undergo surgery associated with study drug administration. MDNA55 will be administered locally by convection-enhanced delivery (CED).
Post-treatment follow-up assessment of safety will be performed 14 days after CED infusion. Thereafter, efficacy and safety assessments will be performed at 30, 60, 120, 180, 270, and 360 days after CED infusion. Subjects who discontinue before the Day 360 visit will undergo all the procedures scheduled for the Day 360 visit at the time of discontinuation.
Glioblastoma Grade IV Astrocytoma Glioblastoma Multiforme High grade glioma malignant glioma recurrent glioblastoma recurrent GBM recurrent GB glioblastoma (GB) glioblastoma multiforme (GBM) progressive glioblastoma Interleukin-4
Open to people ages 18 years and up
Requirements for organ and marrow function as follows:
adequate bone marrow function: leukocytes> 2,000/μL; absolute neutrophil count
1,000/μL; platelets> 100,000/μL
Any prior therapy for Glioblastoma other than that which is considered standard of care for primary Glioblastoma, including but not limited to the following:
Tumor with geometric features that make them difficult to adequately cover the tumor volume with infusate by using CED catheters; these tumors include the following:
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