Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1–High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial

Byoung Chul Cho; Jong Seok Lee; Yi Long Wu; Irfan Cicin; Manuel Cobo Dols; Myung Ju Ahn; Kristof Cuppens; Rémi Veillon; Ernest Nadal; Josiane Mourão Dias; Claudio Martin; Martin Reck; Edward B. Garon; Enriqueta Felip; Luis Paz-Ares; Francoise Mornex; Everett E. Vokes; Alex A. Adjei; Clifford Robinson; Masashi Sato; Yulia Vugmeyster; Andreas Machl; Francois Audhuy; Surendra Chaudhary; Fabrice Barlesi

doi:10.1016/j.jtho.2023.08.018

Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1–High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial

Byoung Chul Cho, Jong Seok Lee, Yi Long Wu, Irfan Cicin, Manuel Cobo Dols, Myung Ju Ahn, Kristof Cuppens, Rémi Veillon, Ernest Nadal, Josiane Mourão Dias, Claudio Martin, Martin Reck, Edward B. Garon, Enriqueta Felip, Luis Paz-Ares, Francoise Mornex, Everett E. Vokes, Alex A. Adjei, Clifford Robinson, Masashi SatoYulia Vugmeyster, Andreas Machl, Francois Audhuy, Surendra Chaudhary, Fabrice Barlesi

Medical Oncology

Research output: Contribution to journal › Article › peer-review

Abstract

Introduction: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β “trap”) fused to a human immunoglobulin G1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), has exhibited clinical activity in a phase 1 expansion cohort of patients with PD-L1–high advanced NSCLC. Methods: This adaptive phase 3 trial (NCT03631706) compared the efficacy and safety of bintrafusp alfa versus pembrolizumab as first-line treatment in patients with PD-L1–high advanced NSCLC. Primary end points were progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 per independent review committee and overall survival. Results: Patients (N = 304) were randomized one-to-one to receive either bintrafusp alfa or pembrolizumab (n = 152 each). The median follow-up was 14.3 months (95% confidence interval [CI]: 13.1–16.0 mo) for bintrafusp alfa and 14.5 months (95% CI: 13.1–15.9 mo) for pembrolizumab. Progression-free survival by independent review committee was not significantly different between bintrafusp alfa and pembrolizumab arms (median = 7.0 mo [95% CI: 4.2 mo–not reached (NR)] versus 11.1 mo [95% CI: 8.1 mo–NR]; hazard ratio = 1.232 [95% CI: 0.885–1.714]). The median overall survival was 21.1 months (95% CI: 21.1 mo–NR) for bintrafusp alfa and 22.1 months (95% CI: 20.4 mo–NR) for pembrolizumab (hazard ratio = 1.201 [95% CI: 0.796–1.811]). Treatment-related adverse events were higher with bintrafusp alfa versus pembrolizumab; grade 3-4 treatment-related adverse events occurred in 42.4% versus 13.2% of patients, respectively. The study was discontinued at an interim analysis as it was unlikely to meet the primary end point. Conclusions: First-line treatment with bintrafusp alfa did not exhibit superior efficacy compared with pembrolizumab in patients with PD-L1–high, advanced NSCLC.

Original language	English (US)
Pages (from-to)	1731-1742
Number of pages	12
Journal	Journal of Thoracic Oncology
Volume	18
Issue number	12
DOIs	https://doi.org/10.1016/j.jtho.2023.08.018
State	Published - Dec 2023

Keywords

Bintrafusp alfa
NSCLC
PD-L1
Phase 3

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine

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10.1016/j.jtho.2023.08.018

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Cho, B. C., Lee, J. S., Wu, Y. L., Cicin, I., Dols, M. C., Ahn, M. J., Cuppens, K., Veillon, R., Nadal, E., Dias, J. M., Martin, C., Reck, M., Garon, E. B., Felip, E., Paz-Ares, L., Mornex, F., Vokes, E. E., Adjei, A. A., Robinson, C., ... Barlesi, F. (2023). Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1–High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial. Journal of Thoracic Oncology, 18(12), 1731-1742. https://doi.org/10.1016/j.jtho.2023.08.018

Cho, BC, Lee, JS, Wu, YL, Cicin, I, Dols, MC, Ahn, MJ, Cuppens, K, Veillon, R, Nadal, E, Dias, JM, Martin, C, Reck, M, Garon, EB, Felip, E, Paz-Ares, L, Mornex, F, Vokes, EE, Adjei, AA, Robinson, C, Sato, M, Vugmeyster, Y, Machl, A, Audhuy, F, Chaudhary, S & Barlesi, F 2023, 'Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1–High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial', Journal of Thoracic Oncology, vol. 18, no. 12, pp. 1731-1742. https://doi.org/10.1016/j.jtho.2023.08.018

@article{d2c42782b23f45eba2b9ca51c7b8e7c7,

title = "Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1–High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial",

abstract = "Introduction: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β “trap”) fused to a human immunoglobulin G1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), has exhibited clinical activity in a phase 1 expansion cohort of patients with PD-L1–high advanced NSCLC. Methods: This adaptive phase 3 trial (NCT03631706) compared the efficacy and safety of bintrafusp alfa versus pembrolizumab as first-line treatment in patients with PD-L1–high advanced NSCLC. Primary end points were progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 per independent review committee and overall survival. Results: Patients (N = 304) were randomized one-to-one to receive either bintrafusp alfa or pembrolizumab (n = 152 each). The median follow-up was 14.3 months (95% confidence interval [CI]: 13.1–16.0 mo) for bintrafusp alfa and 14.5 months (95% CI: 13.1–15.9 mo) for pembrolizumab. Progression-free survival by independent review committee was not significantly different between bintrafusp alfa and pembrolizumab arms (median = 7.0 mo [95% CI: 4.2 mo–not reached (NR)] versus 11.1 mo [95% CI: 8.1 mo–NR]; hazard ratio = 1.232 [95% CI: 0.885–1.714]). The median overall survival was 21.1 months (95% CI: 21.1 mo–NR) for bintrafusp alfa and 22.1 months (95% CI: 20.4 mo–NR) for pembrolizumab (hazard ratio = 1.201 [95% CI: 0.796–1.811]). Treatment-related adverse events were higher with bintrafusp alfa versus pembrolizumab; grade 3-4 treatment-related adverse events occurred in 42.4% versus 13.2% of patients, respectively. The study was discontinued at an interim analysis as it was unlikely to meet the primary end point. Conclusions: First-line treatment with bintrafusp alfa did not exhibit superior efficacy compared with pembrolizumab in patients with PD-L1–high, advanced NSCLC.",

keywords = "Bintrafusp alfa, NSCLC, PD-L1, Phase 3",

author = "Cho, {Byoung Chul} and Lee, {Jong Seok} and Wu, {Yi Long} and Irfan Cicin and Dols, {Manuel Cobo} and Ahn, {Myung Ju} and Kristof Cuppens and R{\'e}mi Veillon and Ernest Nadal and Dias, {Josiane Mour{\~a}o} and Claudio Martin and Martin Reck and Garon, {Edward B.} and Enriqueta Felip and Luis Paz-Ares and Francoise Mornex and Vokes, {Everett E.} and Adjei, {Alex A.} and Clifford Robinson and Masashi Sato and Yulia Vugmeyster and Andreas Machl and Francois Audhuy and Surendra Chaudhary and Fabrice Barlesi",

note = "Publisher Copyright: {\textcopyright} 2023 International Association for the Study of Lung Cancer",

year = "2023",

month = dec,

doi = "10.1016/j.jtho.2023.08.018",

language = "English (US)",

volume = "18",

pages = "1731--1742",

journal = "Journal of Thoracic Oncology",

issn = "1556-0864",

publisher = "International Association for the Study of Lung Cancer",

number = "12",

}

TY - JOUR

T1 - Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1–High Advanced NSCLC

T2 - A Randomized, Open-Label, Phase 3 Trial

AU - Cho, Byoung Chul

AU - Lee, Jong Seok

AU - Wu, Yi Long

AU - Cicin, Irfan

AU - Dols, Manuel Cobo

AU - Ahn, Myung Ju

AU - Cuppens, Kristof

AU - Veillon, Rémi

AU - Nadal, Ernest

AU - Dias, Josiane Mourão

AU - Martin, Claudio

AU - Reck, Martin

AU - Garon, Edward B.

AU - Felip, Enriqueta

AU - Paz-Ares, Luis

AU - Mornex, Francoise

AU - Vokes, Everett E.

AU - Adjei, Alex A.

AU - Robinson, Clifford

AU - Sato, Masashi

AU - Vugmeyster, Yulia

AU - Machl, Andreas

AU - Audhuy, Francois

AU - Chaudhary, Surendra

AU - Barlesi, Fabrice

PY - 2023/12

Y1 - 2023/12

N2 - Introduction: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β “trap”) fused to a human immunoglobulin G1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), has exhibited clinical activity in a phase 1 expansion cohort of patients with PD-L1–high advanced NSCLC. Methods: This adaptive phase 3 trial (NCT03631706) compared the efficacy and safety of bintrafusp alfa versus pembrolizumab as first-line treatment in patients with PD-L1–high advanced NSCLC. Primary end points were progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 per independent review committee and overall survival. Results: Patients (N = 304) were randomized one-to-one to receive either bintrafusp alfa or pembrolizumab (n = 152 each). The median follow-up was 14.3 months (95% confidence interval [CI]: 13.1–16.0 mo) for bintrafusp alfa and 14.5 months (95% CI: 13.1–15.9 mo) for pembrolizumab. Progression-free survival by independent review committee was not significantly different between bintrafusp alfa and pembrolizumab arms (median = 7.0 mo [95% CI: 4.2 mo–not reached (NR)] versus 11.1 mo [95% CI: 8.1 mo–NR]; hazard ratio = 1.232 [95% CI: 0.885–1.714]). The median overall survival was 21.1 months (95% CI: 21.1 mo–NR) for bintrafusp alfa and 22.1 months (95% CI: 20.4 mo–NR) for pembrolizumab (hazard ratio = 1.201 [95% CI: 0.796–1.811]). Treatment-related adverse events were higher with bintrafusp alfa versus pembrolizumab; grade 3-4 treatment-related adverse events occurred in 42.4% versus 13.2% of patients, respectively. The study was discontinued at an interim analysis as it was unlikely to meet the primary end point. Conclusions: First-line treatment with bintrafusp alfa did not exhibit superior efficacy compared with pembrolizumab in patients with PD-L1–high, advanced NSCLC.

AB - Introduction: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β “trap”) fused to a human immunoglobulin G1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), has exhibited clinical activity in a phase 1 expansion cohort of patients with PD-L1–high advanced NSCLC. Methods: This adaptive phase 3 trial (NCT03631706) compared the efficacy and safety of bintrafusp alfa versus pembrolizumab as first-line treatment in patients with PD-L1–high advanced NSCLC. Primary end points were progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 per independent review committee and overall survival. Results: Patients (N = 304) were randomized one-to-one to receive either bintrafusp alfa or pembrolizumab (n = 152 each). The median follow-up was 14.3 months (95% confidence interval [CI]: 13.1–16.0 mo) for bintrafusp alfa and 14.5 months (95% CI: 13.1–15.9 mo) for pembrolizumab. Progression-free survival by independent review committee was not significantly different between bintrafusp alfa and pembrolizumab arms (median = 7.0 mo [95% CI: 4.2 mo–not reached (NR)] versus 11.1 mo [95% CI: 8.1 mo–NR]; hazard ratio = 1.232 [95% CI: 0.885–1.714]). The median overall survival was 21.1 months (95% CI: 21.1 mo–NR) for bintrafusp alfa and 22.1 months (95% CI: 20.4 mo–NR) for pembrolizumab (hazard ratio = 1.201 [95% CI: 0.796–1.811]). Treatment-related adverse events were higher with bintrafusp alfa versus pembrolizumab; grade 3-4 treatment-related adverse events occurred in 42.4% versus 13.2% of patients, respectively. The study was discontinued at an interim analysis as it was unlikely to meet the primary end point. Conclusions: First-line treatment with bintrafusp alfa did not exhibit superior efficacy compared with pembrolizumab in patients with PD-L1–high, advanced NSCLC.

KW - Bintrafusp alfa

KW - NSCLC

KW - PD-L1

KW - Phase 3

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DO - 10.1016/j.jtho.2023.08.018

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Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1–High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial

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ASJC Scopus subject areas

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