Abstract
Background
MDNA55 is an 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 outcome.
Method
MDNA55-05 is an open-label, single-arm Phase 2b study of MDNA55 in recurrent GBM (rGBM) patients with an aggressive form of GBM (
de novo GBM,
IDH wild-type, and non-resectable at recurrence) on their 1
st or 2
nd 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 hours. 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 sub-group (n=32) consisting of IL4R High and IL4R Low patients treated with high dose MDNA55 (>180 ug) showed 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.
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου