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.
M7824
PD-L1
TGF-β
bintrafusp alfa
glioblastoma
Journal
Neuro-oncology advances
ISSN: 2632-2498
Titre abrégé: Neurooncol Adv
Pays: England
ID NLM: 101755003
Informations de publication
Date de publication:
Historique:
entrez:
31
5
2021
pubmed:
1
6
2021
medline:
1
6
2021
Statut:
epublish
Résumé
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 The percentage of patients achieving disease control and the manageable safety profile may warrant further investigation of bintrafusp alfa in GBM.
Sections du résumé
BACKGROUND
BACKGROUND
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.
METHODS
METHODS
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.
RESULTS
RESULTS
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
CONCLUSIONS
CONCLUSIONS
The percentage of patients achieving disease control and the manageable safety profile may warrant further investigation of bintrafusp alfa in GBM.
Identifiants
pubmed: 34056607
doi: 10.1093/noajnl/vdab058
pii: vdab058
pmc: PMC8156979
doi:
Types de publication
Journal Article
Langues
eng
Pagination
vdab058Informations de copyright
© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
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