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Title: Bintrafusp alfa (M7824), a bifunctional fusion protein targeting TGF-β and PD-L1: results from a phase I expansion cohort in patients with recurrent glioblastoma.
Austin Authors: Khasraw, Mustafa;Weller, Michael;Lorente, David;Kolibaba, Kathryn;Lee, Chee Khoon;Gedye, Craig;I de La Fuente, Macarena;Vicente, David;Reardon, David A;Gan, Hui K ;Scott, Andrew M ;Dussault, Isabelle;Helwig, Christoph;Ojalvo, Laureen S;Gourmelon, Carole;Groves, Morris
Affiliation: University Hospital and University of Zurich, Zurich, Switzerland
Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Austin Brain Tumor Center, Austin, Texas, USA
ICO Site René Gauducheau, Saint-Herblain, France
Hospital Universitari i Politècnic La Fe, Valencia, Spain
Hospital Universitario Virgen Macarena, Seville, Spain
EMD Serono Research & Development Institute, Inc., Billerica, Massachusetts, USA
St George Hospital, Kogarah, New South Wales, Australia
Calvary Mater Newcastle, Waratah, New South Wales, Australia
Royal North Shore Hospital, St Leonards, New South Wales, Australia
University of Sydney, Sydney, New South Wales, Australia
Olivia Newton-John Cancer Research Institute
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Medicine (University of Melbourne)
Molecular Imaging and Therapy
Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
Merck KGaA, Darmstadt, Germany
Compass Oncology, US Oncology Research, Vancouver, Washington, USA
Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, USA
Issue Date: 9-Apr-2021
Date: 2021-01
Publication information: Neuro-Oncology Advances 2021; 3(1): vdab058
Abstract: For patients with recurrent glioblastoma (rGBM), there are few options following treatment failure with radiotherapy plus temozolomide. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β "trap") fused to a human IgG1 antibody blocking PD-L1. In this phase I, open-label expansion cohort (NCT02517398), patients with rGBM that progressed after radiotherapy plus temozolomide received bintrafusp alfa 1200 mg Q2W until disease progression, unacceptable toxicity, or trial withdrawal. Response was assessed per RANO criteria. The primary endpoint was disease control rate (DCR); secondary endpoints included safety. As of August 24, 2018, 35 patients received bintrafusp alfa for a median of 1.8 (range, 0.5-20.7) months. Eight patients (22.9%) experienced disease control as assessed by an independent review committee: 2 had a partial response, 4 had stable disease, and 2 had non-complete response/non-progressive disease. Median progression-free survival (PFS) was 1.4 (95% confidence interval [CI], 1.2-1.6) months; 6- and 12-month PFS rates were 15.1% and 11.3%, respectively. Median overall survival (OS) was 5.3 (95% CI, 2.6-9.4) months; 6- and 12-month OS rates were 44.5% and 30.8%, respectively. The DCR (95% CI) was 66.7% (22.3-95.7%) for patients with IDH-mutant GBM (n = 6) and 13.8% (3.9-31.7%) for patients with IDH-wild-type GBM (n = 29). Disease control was seen regardless of PD-L1 expression. Twenty-five patients (71.4%) experienced treatment-related adverse events (grade ≥3; 17.1% [n = 6]). The percentage of patients achieving disease control and the manageable safety profile may warrant further investigation of bintrafusp alfa in GBM.
DOI: 10.1093/noajnl/vdab058
ORCID: 0000-0003-3249-9849
Journal: Neuro-Oncology Advances
PubMed URL: 34056607
Type: Journal Article
Subjects: M7824
bintrafusp alfa
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