TY - JOUR
T1 - Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma
T2 - Results of a phase IIb trial
AU - Sampson, John H.
AU - Achrol, Achal Singh
AU - Aghi, Manish K.
AU - Bankiewicz, Krystof
AU - Bexon, Martin
AU - Brem, Steven
AU - Brenner, Andrew
AU - Chandhasin, Chandtip
AU - Chowdhary, Sajeel
AU - Coello, Melissa
AU - Ellingson, Benjamin M.
AU - Floyd, John R.
AU - Han, Seunggu
AU - Kesari, Santosh
AU - Mardor, Yael
AU - Merchant, Fahar
AU - Merchant, Nina
AU - Randazzo, Dina
AU - Vogelbaum, Michael
AU - Vrionis, Frank
AU - Wembacher-Schroeder, Eva
AU - Zabek, Miroslaw
AU - Butowski, Nicholas
N1 - Publisher Copyright:
© The Author(s) 2023.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - 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.
AB - 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.
KW - Convection Enhanced Delivery (CED)
KW - IL4R
KW - MDNA55
KW - immunotherapy
KW - recurrent glioblastoma
KW - treatment outcome
UR - http://www.scopus.com/inward/record.url?scp=85160969226&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85160969226&partnerID=8YFLogxK
U2 - 10.1093/neuonc/noac285
DO - 10.1093/neuonc/noac285
M3 - Article
C2 - 36640127
AN - SCOPUS:85160969226
SN - 1522-8517
VL - 25
SP - 1085
EP - 1097
JO - Neuro-oncology
JF - Neuro-oncology
IS - 6
ER -