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

Abstract

Bintrafusp alfa; NSCLC; PD-L1Bintrafusp alfa; NSCLC; PD-L1Bintrafusp alfa; NSCLC; PD-L1Introduction 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.The trial was sponsored by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder identification: 10.13039/100009945) and was previously part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline. The healthcare business of Merck KGaA, Darmstadt, Germany provided the trial drugs. The investigators worked with the healthcare business of Merck KGaA, Darmstadt, Germany on the trial design, collection and analysis of data, and interpretation of results. The authors thank the patients and their families, investigators, co-investigators, and the study teams at each of the participating centers and the healthcare business of Merck KGaA, Darmstadt, Germany. The medical writing support was provided by Joyce Lee, PhD, ClinicalThinking, which was funded by the healthcare business of Merck KGaA, Darmstadt, Germany, and was previously part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3)