Bintrafusp alfa versus pembrolizumab in patients with treatment-naive, PD-L1-high advanced non-small cell lung cancer: a randomized, open-label, phase 3 trial

Science and Research

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 IgG1 monoclonal antibody blocking PD-L1, has shown clinical activity in a phase 1 expansion cohort of patients with PD-L1-high, advanced non-small cell lung cancer (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 endpoints were progression-free survival (PFS) according to RECIST 1.1 per independent review committee (IRC) and overall survival (OS). RESULTS: Patients (N=304) were randomized 1:1 to receive either bintrafusp alfa or pembrolizumab (n=152 each). The median follow-up was 14.3 months (95% CI 13.1-16.0 months) for bintrafusp alfa and 14.5 months (95% CI 13.1-15.9 months) for pembrolizumab. PFS by IRC was not significantly different between bintrafusp alfa and pembrolizumab arms (median 7.0 months [95% CI 4.2 months-not reached (NR)] versus 11.1 months [95% CI 8.1 months-NR]; HR=1.232 [95% CI, 0.885-1.714]). Median OS was 21.1 months (95% CI 21.1 months-NR) for bintrafusp alfa and 22.1 months (95% CI: 20.4 months-NR) for pembrolizumab (HR=1.201 [95% CI, 0.796-1.811]). Treatment-related adverse events (TRAEs) were higher with bintrafusp alfa versus pembrolizumab; grade 3/4 TRAEs 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 endpoint. CONCLUSIONS: First-line treatment with bintrafusp alfa did not demonstrate superior efficacy compared with pembrolizumab in patients with PD-L1-high, advanced NSCLC.