Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Glioblastoma at First Recurrence or Progression
Grade IV Astrocytoma
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Objective Response Rate (ORR) [ Time Frame: 12 months ]ORR, determined by independent blinded review
- Overall Survival (OS) [ Time Frame: 12 months ]OS, time from treatment until death
- Progression Free Survival (PFS) [ Time Frame: 12 months ]PFS, time from treatment until disease progression or death
- Duration of response (DOR) [ Time Frame: 12 months ]DOR, time from treatment until disease progression or death among those subjects achieving a complete response (CR) or partial response (PR) to treatment
- Duration of clinical benefit (DOCB) [ Time Frame: 12 months ]DOCB, time from treatment until disease progression or death among those subjects achieving a complete response (CR), partial response (PR), or stable disease (SD)
- Serious adverse events (SAEs) [ Time Frame: 12 months ]Incidence of SAEs
- Treatment emergent adverse events (AEs) [ Time Frame: 12 months ]Incidence of Treatment-Emergent AEs
- Electrocardiogram (ECG) [ Time Frame: 0-2 days ]Incidence of clinically significant ECG findings
- Karnofsky Performance Score (KPS) [ Time Frame: 12 months ]Changes since baseline
- Detection of MDNA55 in serum [ Time Frame: 14 days ]Serum samples will be collected to determine levels of MDNA55 in serum
- Anti-MDNA55 antibody [ Time Frame: 12 months ]Serum samples will be collected to determine anti-drug antibody titers
- Neutralizing antibody titer [ Time Frame: 12 months ]If presence of anti-MDNA55 antibody is found in any sample analyzed, further immunogenicity assessments will be carried out for determination of antibody neutralization potential
|Study Start Date:||October 2016|
|Estimated Study Completion Date:||August 2018|
|Estimated Primary Completion Date:||July 2018 (Final data collection date for primary outcome measure)|
Single infusion of MDNA55 at a fixed concentration of 1.5 μg/mL. Administration will employ convection enhanced delivery (CED).
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02858895
|United States, California|
|University of California San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Nurse Line 415-353-2652|
|Principal Investigator: Nicholas Butowski, MD|