Article (Scientific journals)
Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients With Non-Small Cell Lung Cancer Resistant or Refractory to Immune Checkpoint Inhibitors.
Barlesi, Fabrice; Isambert, Nicolas; Felip, Enriqueta et al.
2023In Oncologist
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Keywords :
Bintrafusp alfa; PD-L1; TGF-β; bifunctional; non-small cell lung cancer (NSCLC); Cancer Research; Oncology
Abstract :
[en] [en] BACKGROUND: Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor beta receptor II (a TGF-β "trap") fused to a human immunoglobulin G1 monoclonal antibody blocking programmed cell death 1 ligand 1 (PD-L1). We report the efficacy and safety in patients with non-small cell lung cancer (NSCLC) that progressed following anti-PD-(L)1 therapy. MATERIALS AND METHODS: In this expansion cohort of NCT02517398-a global, open-label, phase I trial-adults with advanced NSCLC that progressed following chemotherapy and was primary refractory or had acquired resistance to anti-PD-(L)1 treatment received intravenous bintrafusp alfa 1200 mg every 2 weeks until confirmed progression, unacceptable toxicity, or trial withdrawal. The primary endpoint was best overall response (by Response Evaluation Criteria in Solid Tumors version 1.1 adjudicated by independent review committee); secondary endpoints included safety. RESULTS: Eighty-three eligible patients (62 [74.7%] treated with ≥3 prior therapies) received bintrafusp alfa. Four patients (3 primary refractory, 1 acquired resistant) had confirmed partial responses (objective response rate, 4.8%; 95% CI, 1.3%-11.9%), and 9 had stable disease. Tumor cell PD-L1 expression was not associated with response. Nineteen patients (22.9%) experienced grade ≥3 treatment-related adverse events, most commonly asthenia (3 [3.6%]) and fatigue, eczema, and pruritus (2 each [2.4%]). One patient had grade 4 amylase increased. One patient died during treatment for pneumonia before initiation of bintrafusp alfa. CONCLUSION: Although the primary endpoint was not met, bintrafusp alfa showed some clinical activity and a manageable safety profile in patients with heavily pretreated NSCLC, including prior anti-PD-(L)1 therapy. Tumor responses occurred irrespective of whether disease was primary refractory or had acquired resistance to prior anti-PD-(L)1 therapy.
Disciplines :
Oncology
Author, co-author :
Barlesi, Fabrice;  Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France
Isambert, Nicolas;  Service d'oncologie médicale CLCC Georges-François Leclerc, Dijon, France
Felip, Enriqueta;  Oncology Department, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), UVic-UCC, IOB-Quiron, Barcelona, Spain
Cho, Byoung Chul;  Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
Lee, Dae Ho;  Department of Oncology, University of Ulsan College of Medicine, Seoul, Republic of Korea
Peguero, Julio;  Department of Research, Oncology Consultants, Houston, TX, USA
Jerusalem, Guy  ;  Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
Penel, Nicolas;  Department of Medical Oncology, Lille University, Medical School and Centre Oscar Lambret, Lille, France
Saada-Bouzid, Esma;  Department of Medical Oncology, Early Phase Trials Unit, Centre Antoine Lacassagne, Nice, France
Garrido, Pilar;  Lung Cancer Unit, University Hospital Ramón y Cajal (IRYCIS), Medical Oncology Department, Madrid, Spain
Helwig, Christoph;  Merck Healthcare KGaA, Darmstadt, Germany
Locke, George;  EMD Serono Research & Development Institute, Inc, Billerica, MA, USA (an affiliate of Merck KGaA
Ojalvo, Laureen S;  EMD Serono Research & Development Institute, Inc, Billerica, MA, USA (an affiliate of Merck KGaA
Gulley, James L ;  Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
More authors (4 more) Less
Language :
English
Title :
Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients With Non-Small Cell Lung Cancer Resistant or Refractory to Immune Checkpoint Inhibitors.
Publication date :
2023
Journal title :
Oncologist
ISSN :
1083-7159
eISSN :
1549-490X
Publisher :
Oxford University Press (OUP), England
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Merck [DE]
Available on ORBi :
since 16 February 2023

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