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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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 languageEnglish
Pages (from-to)1731-1742
Number of pages12
JournalJournal of Thoracic Oncology
Volume18
Issue number12
DOIs
StatePublished - Dec 2023

Keywords

  • Bintrafusp alfa
  • NSCLC
  • PD-L1
  • Phase 3

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