Ctni-52. Survival Outcomes in Recurrent Glioblastoma (rgbm) Patients Treated With a Single Intra-tumoral Administration of Bizaxofusp, an Il-4r-targeting Toxin, in a Phase Iib Trial
Year: 2023
Type: conference-abstract
Abstract: BACKGROUND Bizaxofusp (MDNA55) is an IL4R-targeting toxin in development for recurrent (r)GBM, a universally fatal disease with mOS of 6-9 months. IL-4R is overexpressed in GBM and surrounding tumor microenvironment, with high expression associated with poor clinical outcome. Method: Efficacy and safety were evaluated in a single-arm, open-label, multi-center Ph2 study using convection-enhanced delivery of Bizaxofusp. The primary endpoint of mOS was compared to results from a blinded eligibility-matched external control arm (ECA). OS was defined as time from relapse to death/censor. IL-4R expression was determined by immunohistochemistry of available archival tumor tissues from both arms. RESULTS Bizaxofusp showed an acceptable safety profile at doses of up to 240 μg. Forty-four subjects were treated with Bizaxofusp per protocol; 81 ECA subjects met the eligibility criteria of the study. The Bizaxofusp group had a significantly longer mOS (12.85 months compared to 7.7 months for ECA; HR, 0.62; 95% CI, 0.42-0.89). Amongst the unmethylated MGMT and high IL-4R sub-groups, subjects treated with Bizaxofusp had significantly longer mOS when compared to the ECA. Eleven patients (25%) treated with Bizaxofusp survived >24 months; 3 patients were still alive (29.9, 32.8 and 40.1 months) at last follow-up. High IL-4R expression was associated with improved survival (mOS, 15.8 versus 9.8 months; HR, 0.7; 95% CI, 0.39-1.46) at all doses. However at high doses (180 μg) subjects with low IL-4R expression had significantly longer survival versus low dose Bizaxofusp (mOS, 15.4 versus 9.1 months; HR, 0.28; 95% CI, 0.09-0.91). CONCLUSION In patients with rGBM, a single treatment of Bizaxofusp resulted in significantly improved OS compared to eligibility-matched ECA. High-dose Bizaxofusp was equally effective irrespective of IL4R expression. A Phase 3 registration trial will use a novel hybrid design with a propensity-matched ECA comprising two-thirds of the control arm, setting a new precedent for GBM clinical trials.
Source: Neuro-Oncology
Authors: John Sampson, Achal Singh Achrol, Manish Aghi, Krystof Bankiewicz, Martin Bexon, Steven Brem, Andrew Brenner, Sajeel Chowdhary, Melissa Coello, Annick Desjardins, Benjamin Ellingson, John Floyd, Seunggu Han, Santosh Kesari, Yael Mardor, Fahar Merchant, Rosemina Merchant, Dina Randazzo, Michael A Vogelbaum, Frank Vrionis, Eva Wembacher-Schroeder, Minh D To, Miroslaw Zabek, Nicholas Butowski
Institutions: Duke University, Loma Linda University Medical Center, University of California, San Francisco, The Ohio State University, University of Pennsylvania, Mays Cancer Center at UT Health San Antonio, Boca Raton Regional Hospital, University of California, Los Angeles, The University of Texas at San Antonio Health Science Center, Stanford University, Sheba Medical Center, Duke Medical Center, Moffitt Cancer Center, Brainlab (Germany)
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4388590454