Efficacy and Safety of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting Transforming Growth Factor-β and Programmed Death-Ligand 1, Plus Chemotherapy in Patients With Stage IV NSCLC
Introduction: In a phase 1 study, bintrafusp alfa was found to have an encouraging clinical activity in patients with previously treated advanced NSCLC. This study evaluated the safety and efficacy of bintrafusp alfa with chemotherapy in patients with stage IV NSCLC regardless of the programmed deat...
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Elsevier
2025-01-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364324001188 |
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| author | Christian Rolfo, MD, PhD Laurent Greillier, MD, PhD Remi Veillon, MD, PhD Firas Badin, MD, MBA Francois Ghiringhelli, MD, PhD Nicolas Isambert, MD, PhD Astrid Paulus, MD, PhD Surendra Pal Chaudhary, MD Yulia Vugmeyster, PhD Masashi Sato, MSc Sandrine Hiret, MD, PhD |
| author_facet | Christian Rolfo, MD, PhD Laurent Greillier, MD, PhD Remi Veillon, MD, PhD Firas Badin, MD, MBA Francois Ghiringhelli, MD, PhD Nicolas Isambert, MD, PhD Astrid Paulus, MD, PhD Surendra Pal Chaudhary, MD Yulia Vugmeyster, PhD Masashi Sato, MSc Sandrine Hiret, MD, PhD |
| author_sort | Christian Rolfo, MD, PhD |
| collection | DOAJ |
| description | Introduction: In a phase 1 study, bintrafusp alfa was found to have an encouraging clinical activity in patients with previously treated advanced NSCLC. This study evaluated the safety and efficacy of bintrafusp alfa with chemotherapy in patients with stage IV NSCLC regardless of the programmed death-ligand 1 (PD-L1) expression status. Methods: In this open-label, phase 1b/2 study (NCT03840915), eligible patients were assigned to one of four cohorts. Patients with previously untreated metastatic NSCLC (cohorts A, B, and C) received bintrafusp alfa with chemotherapy as first-line treatment, whereas patients whose disease progressed on previous treatment with programmed cell death protein 1 or PD-L1 inhibitors (cohort D) received bintrafusp alfa with chemotherapy as second-line treatment. The primary objective of this study was to evaluate the safety and tolerability of bintrafusp alfa with chemotherapy. Results: Four serious and one nonserious treatment-emergent adverse events were considered dose-limiting toxicities, none of which were assessed as related to bintrafusp alfa by the investigator. Any-grade bintrafusp alfa-related adverse events occurred in 20.7% of patients in cohorts A+B+C and in 16.7% of patients in cohort D. Keratoacanthoma was the most common transforming growth factor-β inhibition-mediated skin lesion (cohorts A+B+C: 12.1% and cohort D: 8.3%). In cohorts A+B+C, the overall response rate was 48.3%, and in patients with PD-L1 tumor proportion score of more than or equal to 50.0%, it was 71.4%. On the basis of an interim analysis, the data were considered mature, and no further analysis has been planned. Conclusion: Bintrafusp alfa with chemotherapy was found to have a manageable safety profile and encouraging clinical activity in patients with stage IV NSCLC. |
| format | Article |
| id | doaj-art-454234dd3bf24a91acfdce53fdce92c9 |
| institution | Kabale University |
| issn | 2666-3643 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj-art-454234dd3bf24a91acfdce53fdce92c92025-01-20T04:17:53ZengElsevierJTO Clinical and Research Reports2666-36432025-01-0161100748Efficacy and Safety of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting Transforming Growth Factor-β and Programmed Death-Ligand 1, Plus Chemotherapy in Patients With Stage IV NSCLCChristian Rolfo, MD, PhD0Laurent Greillier, MD, PhD1Remi Veillon, MD, PhD2Firas Badin, MD, MBA3Francois Ghiringhelli, MD, PhD4Nicolas Isambert, MD, PhD5Astrid Paulus, MD, PhD6Surendra Pal Chaudhary, MD7Yulia Vugmeyster, PhD8Masashi Sato, MSc9Sandrine Hiret, MD, PhD10Center for Thoracic Oncology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York; Present affiliation: Arthur G. James Cancer Hospital and Solove Research Institute, Ohio State University Comprehensive Cancer Center, Columbus, Ohio; Corresponding author. Address for correspondence: Christian Rolfo, MD, PhD, Arthur G. James Cancer Hospital and Solove Research Institute, Ohio State University Comprehensive Cancer Center, Columbus, Ohio.Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille, FranceService des Maladies Respiratoires, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, FranceHematology and Oncology, Baptist Health Lexington, Lexington, KentuckyDepartment of Medical Oncology, Centre Georges-François Leclerc, Dijon, FrancePôle Régional de Cancérologie, CHU de Poitiers, Poitiers, FranceDepartment of Respiratory Medicine, CHU Sart Tilman, Liege, BelgiumEMD Serono, Billerica, MassachusettsEMD Serono, Billerica, MassachusettsMerck Biopharma Co., Ltd., Tokyo, Japan, an affiliate of Merck KGaA, Darmstadt, GermanyInstitut de Cancérologie de l’Ouest, 44805 Saint-Herblain, FranceIntroduction: In a phase 1 study, bintrafusp alfa was found to have an encouraging clinical activity in patients with previously treated advanced NSCLC. This study evaluated the safety and efficacy of bintrafusp alfa with chemotherapy in patients with stage IV NSCLC regardless of the programmed death-ligand 1 (PD-L1) expression status. Methods: In this open-label, phase 1b/2 study (NCT03840915), eligible patients were assigned to one of four cohorts. Patients with previously untreated metastatic NSCLC (cohorts A, B, and C) received bintrafusp alfa with chemotherapy as first-line treatment, whereas patients whose disease progressed on previous treatment with programmed cell death protein 1 or PD-L1 inhibitors (cohort D) received bintrafusp alfa with chemotherapy as second-line treatment. The primary objective of this study was to evaluate the safety and tolerability of bintrafusp alfa with chemotherapy. Results: Four serious and one nonserious treatment-emergent adverse events were considered dose-limiting toxicities, none of which were assessed as related to bintrafusp alfa by the investigator. Any-grade bintrafusp alfa-related adverse events occurred in 20.7% of patients in cohorts A+B+C and in 16.7% of patients in cohort D. Keratoacanthoma was the most common transforming growth factor-β inhibition-mediated skin lesion (cohorts A+B+C: 12.1% and cohort D: 8.3%). In cohorts A+B+C, the overall response rate was 48.3%, and in patients with PD-L1 tumor proportion score of more than or equal to 50.0%, it was 71.4%. On the basis of an interim analysis, the data were considered mature, and no further analysis has been planned. Conclusion: Bintrafusp alfa with chemotherapy was found to have a manageable safety profile and encouraging clinical activity in patients with stage IV NSCLC.http://www.sciencedirect.com/science/article/pii/S2666364324001188Bintrafusp alfaTGF-βBifunctionalStage IVNon–small cell lung cancer |
| spellingShingle | Christian Rolfo, MD, PhD Laurent Greillier, MD, PhD Remi Veillon, MD, PhD Firas Badin, MD, MBA Francois Ghiringhelli, MD, PhD Nicolas Isambert, MD, PhD Astrid Paulus, MD, PhD Surendra Pal Chaudhary, MD Yulia Vugmeyster, PhD Masashi Sato, MSc Sandrine Hiret, MD, PhD Efficacy and Safety of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting Transforming Growth Factor-β and Programmed Death-Ligand 1, Plus Chemotherapy in Patients With Stage IV NSCLC JTO Clinical and Research Reports Bintrafusp alfa TGF-β Bifunctional Stage IV Non–small cell lung cancer |
| title | Efficacy and Safety of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting Transforming Growth Factor-β and Programmed Death-Ligand 1, Plus Chemotherapy in Patients With Stage IV NSCLC |
| title_full | Efficacy and Safety of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting Transforming Growth Factor-β and Programmed Death-Ligand 1, Plus Chemotherapy in Patients With Stage IV NSCLC |
| title_fullStr | Efficacy and Safety of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting Transforming Growth Factor-β and Programmed Death-Ligand 1, Plus Chemotherapy in Patients With Stage IV NSCLC |
| title_full_unstemmed | Efficacy and Safety of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting Transforming Growth Factor-β and Programmed Death-Ligand 1, Plus Chemotherapy in Patients With Stage IV NSCLC |
| title_short | Efficacy and Safety of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting Transforming Growth Factor-β and Programmed Death-Ligand 1, Plus Chemotherapy in Patients With Stage IV NSCLC |
| title_sort | efficacy and safety of bintrafusp alfa a bifunctional fusion protein targeting transforming growth factor β and programmed death ligand 1 plus chemotherapy in patients with stage iv nsclc |
| topic | Bintrafusp alfa TGF-β Bifunctional Stage IV Non–small cell lung cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2666364324001188 |
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