Titre :

Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in advanced squamous cell carcinoma of the head and neck: results from a phase I cohort.

Auteur(s) :

Cho, Byoung Chul [Auteur]
Yonsei University
Daste, Amaury [Auteur]
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Ravaud, Alain [Auteur]
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Salas, Sébastien [Auteur]
Hôpital de la Timone [CHU - APHM] [TIMONE]
Isambert, Nicolas [Auteur]
Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] [UNICANCER/CRLCC-CGFL]
Mcclay, Edward [Auteur]
Awada, Ahmad [Auteur]

Borel, Christian [Auteur]
Centre Paul Strauss [CRLCC Paul Strauss]
Ojalvo, Laureen S. [Auteur]
Helwig, Christoph [Auteur]
Merck [Darmstadt]
Rolfe, P. Alexander [Auteur]
Gulley, James L. [Auteur]
National Institutes of Health [Bethesda, MD, USA] [NIH]
Penel, Nicolas [Auteur]
METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Titre de la revue :

Journal for Immunotherapy of Cancer

Nom court de la revue :

J Immunother Cancer

Numéro :

8

Date de publication :

2020-07-11

ISSN :

2051-1426

Mot(s)-clé(s) en anglais :

head and neck neoplasms
immunotherapy
clinical trials as topic

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Background We report the clinical activity and safety of bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor β (TGF-β)RII receptor (a TGF-β ...
Lire la suite >Background We report the clinical activity and safety of bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor β (TGF-β)RII receptor (a TGF-β ‘trap’) fused to a human IgG1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), in patients with heavily pretreated squamous cell carcinoma of the head and neck (SCCHN). Methods In this phase I dose-expansion cohort, patients with advanced SCCHN not amenable to curative therapy that progressed/recurred after platinum therapy in the recurrent/metastatic setting, or <6 months after platinum therapy in the locally advanced setting, received bintrafusp alfa 1200 mg intravenously every 2 weeks. The primary endpoint was confirmed best overall response (BOR; Response Evaluation Criteria for Solid Tumors (RECIST) 1.1) per independent review committee (IRC); other endpoints included BOR per investigator and safety. Results As of August 24, 2018, 32 patients had received bintrafusp alfa (median follow-up 86.4 weeks; range 2–97). Per IRC, the confirmed objective response rate (ORR) was 13% (95% CI 4% to 29%; 4 partial responses (PR)); 4 patients had stable disease (SD) (disease control rate 34%; 95% CI 19% to 53%). Per investigator, there were 5 PRs (ORR, 16%), including 2 patients who developed delayed PRs after initial disease increase (total clinical response rate 22%). Responses (ORRs) were observed in patients with PD-L1-positive (12%), PD-L1-negative (17%; 73-10 antibody for immunohistochemistry), human papillomavirus (HPV)-positive (33%) and HPV-negative tumors (5%). Grade 3 treatment-related adverse events (TRAEs) were reported in 11 patients (34%), with no grade 4 TRAEs or treatment-related deaths. Conclusions Bintrafusp alfa showed clinical activity across subgroups of PD-L1 expression and in HPV-positive tumors and had a manageable safety profile in patients with heavily pretreated advanced SCCHN. Activity in HPV-positive tumors is favorable compared with historical data from PD-L1 inhibitors and is being further investigated in an ongoing study of HPV-associated tumors.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille

Collections :

• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Date de dépôt :

2023-11-15T08:30:26Z
2023-12-19T14:12:17Z