Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients with Esophageal Adenocarcinoma: Results from a Phase 1 Cohort
| العنوان: | Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients with Esophageal Adenocarcinoma: Results from a Phase 1 Cohort |
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| المؤلفون: | Adnan Khattak, Christoph Helwig, Isabelle Dussault, Enriqueta Felip, Laureen S. Ojalvo, Patricia Rich, Nicolas Isambert, Benjamin Tan, Ding Wang, Karen Kelly |
| المساهمون: | Institut Català de la Salut, [Tan B] Washington University School of Medicine, St Louis, MO, USA. [Khattak A] Fiona Stanley Hospital, Perth, WA, Australia. [Felip E] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, Barcelona, Spain. [Kelly K] University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA. [Rich P] Cancer Treatment Centers of America, Atlanta, GA, USA. Piedmont Healthcare, Atlanta, GA, USA. [Wang D] Henry Ford Cancer Institute, Detroit, MI, USA, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Targeted Oncology Scientia |
| بيانات النشر: | Springer International Publishing, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cancer Research, Esophageal Neoplasms, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias del esófago [ENFERMEDADES], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Gastroenterology, B7-H1 Antigen, Cohort Studies, 0302 clinical medicine, Antineoplastic Agents, Immunological, Transforming Growth Factor beta, Clinical endpoint, Pharmacology (medical), Original Research Article, Receptor, Esòfag - Malalties, Aged, 80 and over, biology, Càncer - Tractament, Middle Aged, Citocines - Immunologia, Oncology, 030220 oncology & carcinogenesis, Cohort, Toxicity, Other subheadings::Other subheadings::/administration & dosage [Other subheadings], Adult, medicine.medical_specialty, medicine.drug_class, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Transforming Growth Factor beta [CHEMICALS AND DRUGS], Adenocarcinoma, Monoclonal antibody, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Esophageal Neoplasms [DISEASES], 03 medical and health sciences, Internal medicine, PD-L1, medicine, Humans, Adverse effect, Aged, aminoácidos, péptidos y proteínas::péptidos::péptidos y proteínas de señalización intercelular::citocinas::factor de crecimiento transformador beta [COMPUESTOS QUÍMICOS Y DROGAS], Otros calificadores::Otros calificadores::/administración & dosificación [Otros calificadores], business.industry, digestive system diseases, 030104 developmental biology, biology.protein, business, Transforming growth factor |
| الوصف: | Adenocarcinoma esofàgic; Bintrafusp Alfa Adenocarcinoma Esofágico; Bintrafusp Alfa Esophageal Adenocarcinoma; Bintrafusp Alfa Background Esophageal adenocarcinoma patients have limited treatment options. TGF-β can be upregulated in esophageal adenocarcinoma, and blocking this pathway may enhance clinical response to PD-(L)1 inhibitors. 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 mAb blocking PD-L1. Objective The objective of this study was to investigate the efficacy and safety of bintrafusp alfa in patients with advanced, post-platinum esophageal adenocarcinoma, unselected for PD-L1 expression. Patients and Methods In this phase 1 study, patients with post-platinum, PD-L1–unselected esophageal adenocarcinoma received bintrafusp alfa 1200 mg every 2 weeks until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was confirmed best overall response per RECIST 1.1 by independent review committee (IRC). Results By the database cutoff of 24 August 2018, 30 patients (80.0% had two or more prior anticancer regimens) received bintrafusp alfa for a median of 6.1 weeks. The confirmed objective response rate (ORR) per IRC was 20.0% (95% CI 7.7–38.6); responses lasted 1.3–8.3 months. Most responses (83.3%) occurred in tumors with an immune-excluded phenotype. Investigator-assessed confirmed ORR was 13.3% (95% CI 3.8–30.7). Nineteen patients (63.3%) had treatment-related adverse events: seven patients (23.3%) had grade 3 events; no grade 4 events or treatment-related deaths occurred. Conclusions Bintrafusp alfa showed signs of clinical efficacy with a manageable safety profile in patients with heavily pretreated, advanced esophageal adenocarcinoma. This trial was funded by Merck KGaA, Darmstadt, Germany, and is part of an alliance between Merck KGaA and GlaxoSmithKline. Merck KGaA provided the study drug and worked with investigators on the trial design and plan, collection and analysis of data, and interpretation of results. Funding for a professional medical writer with access to the data was provided by Merck KGaA and GlaxoSmithKline. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1776-260X 1776-2596 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e97a3a2f9f0541844dcc1e45b1de664Test http://europepmc.org/articles/PMC8266790Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6e97a3a2f9f0541844dcc1e45b1de664 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1776260X 17762596 |
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