MO01.29 Randomized, Open-Label Study of Bintrafusp Alfa vs. Pembrolizumab as First-Line (1L) Treatment in Patients with PD-L1–Expressing Advanced Non-Small Cell Lung Cancer (NSCLC)

TGF-β promotes tumor progression via immune suppression, induction of epithelial-mesenchymal transition, and angiogenesis. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. Preclinical data demonstrated that the bifunctional nature of bintrafusp alfa might allow for colocalized inhibition of two nonredundant immunosuppressive pathways (TGF-β and PD-L1) within the tumor microenvironment. In an expansion cohort of a global phase 1 study (NCT02517398), bintrafusp alfa showed encouraging efficacy and tolerability at the recommended phase 2 dose (RP2D) of 1200 mg intravenously (IV) every 2 weeks (Q2W) as second-line treatment in patients with NSCLC; the objective response rate was 85.7% in patients with high PD-L1 tumor expression. Observed data support the hypothesis that bintrafusp alfa may be superior to other PD-(L)1 inhibitors, including pembrolizumab, for the treatment of NSCLC. This study (NCT03631706) will evaluate bintrafusp alfa treatment in patients with advanced NSCLC in the 1L setting on the basis of its promising antitumor activity and manageable safety profile. Here we present an adaptive, multicenter, phase 3, open-label, randomized, controlled trial comparing bintrafusp alfa vs pembrolizumab in the 1L treatment of patients with metastatic NSCLC with high PD-L1 expression levels. Patients in this study must have a histologically confirmed diagnosis of advanced NSCLC with high PD-L1 expression on tumor cells. ECOG performance status must be 0 or 1. Patients must not have received prior systemic treatment for advanced NSCLC, and those with tumors with actionable mutations (for which targeted therapy is locally approved) are not eligible. Patients will receive bintrafusp alfa 1200 mg Q2W or pembrolizumab 200 mg every 3 weeks as an IV infusion until confirmed disease progression, unacceptable toxicity, or trial withdrawal. This study has dual primary endpoints of progression-free survival and overall survival. Secondary endpoints include safety, objective response, and duration of response. Estimated enrollment is up to 584 patients. © 2020 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO-SITC Clinical Immuno-Oncology Symposium. All rights reserved.