ATIM-30. COMBATING RECURRENT GLIOBLASTOMA WITH MDNA55, AN INTERLEUKIN-4 RECEPTOR TARGETED IMMUNOTHERAPY, THROUGH MRI-GUIDED CONVECTIVE DELIVERY

Abstract

MDNA55, an IL4R-directed toxin, is being studied in a Phase 2b trial in recurrent GBM (rGBM) patients at first or second relapse. MDNA55 is co-infused with Gadolinium-based contrast agent and delivered as a single intratumoral infusion using Convection Enhanced Delivery (CED). Primary endpoint is median Overall Survival (mOS) and secondary endpoint is objective response rate (ORR) assessed by mRANO-based criteria incorporating advanced imaging modalities. Enrollment is complete (n=46). Current safety data show similar profile to previous MDNA55 trials with no systemic toxicities or drug related deaths. Current mOS in subjects treated with low doses of MDNA55 (median 63µg; n=21) is 11.8 months. When stratified by IL4R expression, a biomarker for more aggressive GBM, IL4R+ve subjects (mOS 15.2 months; n=8) show a survival advantage of 7 months compared to IL4R-ve subjects (mOS 8.1 months; n=10). Updated survival and response outcomes including subjects receiving the high dose (median 180µg; n=25) and stratification by IL4R expression will be reported. Review of serial imaging within 90 days following MDNA55 treatment demonstrated tumor shrinkage or stabilization from baseline in 19/42 evaluable subjects (disease control rate of 45%). To account for initial pseudo-progression in some subjects, tumor response was also assessed from nadir: 83% (35/42) showed disease control. Multi-parametric MRI biomarkers including relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) measurements demonstrated distinct imaging phenotypes among different disease states (pseudo-progression vs true-progression, pseudo-response vs true-response) and improved response staging. This trial is advancing neurosurgical methods for CED, potential of IL4R expression as a biomarker to select GBM patients most likely to benefit from MDNA55 treatment, and optimal use of multi-parametric MRI as an adjunct to clinical decision making. The improved survival and disease control seen after only a single infusion of MDNA55, especially in IL4R+ve subjects, may provide promising clinical benefit for rGBM patients.