Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial

John H. Sampson, Achal Singh Achrol, Manish K. Aghi, Krystof Bankiewicz, Martin Bexon, Steven Brem, Andrew Brenner, Chandtip Chandhasin, Sajeel Chowdhary, Melissa Coello, Benjamin M. Ellingson, John R. Floyd, Seunggu Han, Santosh Kesari, Yael Mardor, Fahar Merchant, Nina Merchant, Dina Randazzo, Michael Vogelbaum, Frank VrionisEva Wembacher-Schroeder, Miroslaw Zabek, Nicholas Butowski

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background. MDNA55 is an interleukin 4 receptor (IL4R)-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R is overexpressed in GBM as well as cells of the tumor microenvironment. High expression of IL4R is associated with poor clinical outcomes. Methods. MDNA55-05 is an open-label, single-arm phase IIb study of MDNA55 in recurrent GBM (rGBM) patients with an aggressive form of GBM (de novo GBM, IDH wild-type, and nonresectable at recurrence) on their 1st or 2nd recurrence. MDNA55 was administered intratumorally as a single dose treatment (dose range of 18 to 240 ug) using convection-enhanced delivery (CED) with up to 4 stereo-tactically placed catheters. It was co-infused with a contrast agent (Gd-DTPA, Magnevist®) to assess distribution in and around the tumor margins. The flow rate of each catheter did not exceed 10μL/min to ensure that the infusion duration did not exceed 48 h. The primary endpoint was mOS, with secondary endpoints determining the effects of IL4R status on mOS and PFS. Results. MDNA55 showed an acceptable safety profile at doses up to 240 μg. In all evaluable patients (n = 44) mOS was 11.64 months (80% one-sided CI 8.62, 15.02) and OS-12 was 46%. A subgroup (n = 32) consisting of IL4R High and IL4R Low patients treated with high-dose MDNA55 (>180 ug) showed the best benefit with mOS of 15 months, OS-12 of 55%. Based on mRANO criteria, tumor control was observed in 81% (26/32), including those patients who exhibited pseudo-progression (15/26). Conclusions. MDNA55 demonstrated tumor control and promising survival and may benefit rGBM patients when treated at high-dose irrespective of IL4R expression level.

Original languageEnglish (US)
Pages (from-to)1085-1097
Number of pages13
JournalNeuro-oncology
Volume25
Issue number6
DOIs
StatePublished - Jun 1 2023

Keywords

  • Convection Enhanced Delivery (CED)
  • IL4R
  • MDNA55
  • immunotherapy
  • recurrent glioblastoma
  • treatment outcome

ASJC Scopus subject areas

  • Clinical Neurology
  • Oncology
  • Cancer Research

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