Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies
Background Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor (TGF)-βRII (a TGF-β ‘trap’) fused to a human IgG1 mAb blocking programmed cell death ligand 1. This is the largest analysis of patients with advanced, pretrea...
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001395.full |
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| author | Renee N Donahue Jeffrey Schlom James L Gulley Ravi A Madan Caroline Jochems Elizabeth Lamping Julius Strauss Marijo Bilusic Fatima Karzai Christian S Hinrichs Edward McClay Jennifer L Marté Lisa M Cordes Andrew Hill Byoung Chul Cho Sébastien Salas Laureen S Ojalvo P Alexander Rolfe Margaret E Gatti-Mays Jason M Redman Houssein A Sater Andrea Burmeister Genevieve Jehl |
| author_facet | Renee N Donahue Jeffrey Schlom James L Gulley Ravi A Madan Caroline Jochems Elizabeth Lamping Julius Strauss Marijo Bilusic Fatima Karzai Christian S Hinrichs Edward McClay Jennifer L Marté Lisa M Cordes Andrew Hill Byoung Chul Cho Sébastien Salas Laureen S Ojalvo P Alexander Rolfe Margaret E Gatti-Mays Jason M Redman Houssein A Sater Andrea Burmeister Genevieve Jehl |
| author_sort | Renee N Donahue |
| collection | DOAJ |
| description | Background Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor (TGF)-βRII (a TGF-β ‘trap’) fused to a human IgG1 mAb blocking programmed cell death ligand 1. This is the largest analysis of patients with advanced, pretreated human papillomavirus (HPV)-associated malignancies treated with bintrafusp alfa.Methods In these phase 1 (NCT02517398) and phase 2 trials (NCT03427411), 59 patients with advanced, pretreated, checkpoint inhibitor-naive HPV-associated cancers received bintrafusp alfa intravenously every 2 weeks until progressive disease, unacceptable toxicity, or withdrawal. Primary endpoint was best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1; other endpoints included safety.Results As of April 17, 2019 (phase 1), and October 4, 2019 (phase 2), the confirmed objective response rate per RECIST V.1.1 in the checkpoint inhibitor-naive, full-analysis population was 30.5% (95% CI, 19.2% to 43.9%; five complete responses); eight patients had stable disease (disease control rate, 44.1% (95% CI, 31.2% to 57.6%)). In addition, three patients experienced a delayed partial response after initial disease progression, for a total clinical response rate of 35.6% (95% CI, 23.6% to 49.1%). An additional patient with vulvar cancer had an unconfirmed response. Forty-nine patients (83.1%) experienced treatment-related adverse events, which were grade 3/4 in 16 patients (27.1%). No treatment-related deaths occurred.Conclusion Bintrafusp alfa showed clinical activity and manageable safety and is a promising treatment in HPV-associated cancers. These findings support further investigation of bintrafusp alfa in patients with advanced, pretreated HPV-associated cancers. |
| format | Article |
| id | doaj-art-8d0952dbd2c84693b0a6b1394990bc11 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-8d0952dbd2c84693b0a6b1394990bc112025-08-20T02:13:27ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-001395Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignanciesRenee N Donahue0Jeffrey Schlom1James L Gulley2Ravi A Madan3Caroline Jochems4Elizabeth Lamping5Julius Strauss6Marijo Bilusic7Fatima Karzai8Christian S Hinrichs9Edward McClay10Jennifer L Marté11Lisa M Cordes12Andrew Hill13Byoung Chul Cho14Sébastien Salas15Laureen S Ojalvo16P Alexander Rolfe17Margaret E Gatti-Mays18Jason M Redman19Houssein A Sater20Andrea Burmeister21Genevieve Jehl22Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USACenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USACenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USANational Cancer Institute, Bethesda, Maryland, USALaboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland, USAGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USALaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USAGenitourinary Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USAGenitourinary Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USARutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA5 California Cancer Associates for Research and Excellence, Encinitas, California, USAGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA6 Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA19 Tasman Oncology Research Ltd, Southport, Queensland, Australia1Yonsei Cancer Center and Severance Hospital, Seoul, Republic of Korea4 CEPCM Assistance Publique des Hôpitaux de Marseille; Aix-Marseille Université, Marseille, France8 EMD Serono Research & Development Institute, Inc, Billerica, Massachusetts, USA; an affiliate of Merck KGaA, Darmstadt, Germany8 EMD Serono Research & Development Institute, Inc, Billerica, Massachusetts, USA; an affiliate of Merck KGaA, Darmstadt, GermanyPelotonia Institute for Immuno-Oncology, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA1National Cancer Institute, National Institutes of Health, Bethesda, MD, USA6 Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA6 Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA9 Merck KGaA, Darmstadt, GermanyBackground Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor (TGF)-βRII (a TGF-β ‘trap’) fused to a human IgG1 mAb blocking programmed cell death ligand 1. This is the largest analysis of patients with advanced, pretreated human papillomavirus (HPV)-associated malignancies treated with bintrafusp alfa.Methods In these phase 1 (NCT02517398) and phase 2 trials (NCT03427411), 59 patients with advanced, pretreated, checkpoint inhibitor-naive HPV-associated cancers received bintrafusp alfa intravenously every 2 weeks until progressive disease, unacceptable toxicity, or withdrawal. Primary endpoint was best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1; other endpoints included safety.Results As of April 17, 2019 (phase 1), and October 4, 2019 (phase 2), the confirmed objective response rate per RECIST V.1.1 in the checkpoint inhibitor-naive, full-analysis population was 30.5% (95% CI, 19.2% to 43.9%; five complete responses); eight patients had stable disease (disease control rate, 44.1% (95% CI, 31.2% to 57.6%)). In addition, three patients experienced a delayed partial response after initial disease progression, for a total clinical response rate of 35.6% (95% CI, 23.6% to 49.1%). An additional patient with vulvar cancer had an unconfirmed response. Forty-nine patients (83.1%) experienced treatment-related adverse events, which were grade 3/4 in 16 patients (27.1%). No treatment-related deaths occurred.Conclusion Bintrafusp alfa showed clinical activity and manageable safety and is a promising treatment in HPV-associated cancers. These findings support further investigation of bintrafusp alfa in patients with advanced, pretreated HPV-associated cancers.https://jitc.bmj.com/content/8/2/e001395.full |
| spellingShingle | Renee N Donahue Jeffrey Schlom James L Gulley Ravi A Madan Caroline Jochems Elizabeth Lamping Julius Strauss Marijo Bilusic Fatima Karzai Christian S Hinrichs Edward McClay Jennifer L Marté Lisa M Cordes Andrew Hill Byoung Chul Cho Sébastien Salas Laureen S Ojalvo P Alexander Rolfe Margaret E Gatti-Mays Jason M Redman Houssein A Sater Andrea Burmeister Genevieve Jehl Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies Journal for ImmunoTherapy of Cancer |
| title | Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies |
| title_full | Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies |
| title_fullStr | Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies |
| title_full_unstemmed | Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies |
| title_short | Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies |
| title_sort | bintrafusp alfa a bifunctional fusion protein targeting tgf β and pd l1 in patients with human papillomavirus associated malignancies |
| url | https://jitc.bmj.com/content/8/2/e001395.full |
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