Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients With Non-Small Cell Lung Cancer Resistant or Refractory to Immune Checkpoint Inhibitors

Fabrice Barlesi (1) , Nicolas Isambert (2) , E. Felip , B. C. Cho , D. H. Lee , J. Peguero , G. Jerusalem , Nicolas Penel (3) , E. Saada-Bouzid , P. Garrido , C. Helwig , G. Locke , L. S. Ojalvo , J. L. Gulley

1 IGR - Institut Gustave Roussy
2 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
3 METRICS - Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Background Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor beta receptor II (a TGF-β “trap”) fused to a human immunoglobulin G1 monoclonal antibody blocking programmed cell death 1 ligand 1 (PD-L1). We report the efficacy and safety in patients with non-small cell lung cancer (NSCLC) that progressed following anti-PD-(L)1 therapy. Materials and Methods In this expansion cohort of NCT02517398—a global, open-label, phase I trial—adults with advanced NSCLC that progressed following chemotherapy and was primary refractory or had acquired resistance to anti-PD-(L)1 treatment received intravenous bintrafusp alfa 1200 mg every 2 weeks until confirmed progression, unacceptable toxicity, or trial withdrawal. The primary endpoint was best overall response (by Response Evaluation Criteria in Solid Tumors version 1.1 adjudicated by independent review committee); secondary endpoints included safety. Results Eighty-three eligible patients (62 [74.7%] treated with ≥3 prior therapies) received bintrafusp alfa. Four patients (3 primary refractory, 1 acquired resistant) had confirmed partial responses (objective response rate, 4.8%; 95% CI, 1.3%-11.9%), and 9 had stable disease. Tumor cell PD-L1 expression was not associated with response. Nineteen patients (22.9%) experienced grade ≥3 treatment-related adverse events, most commonly asthenia (3 [3.6%]) and fatigue, eczema, and pruritus (2 each [2.4%]). One patient had grade 4 amylase increased. One patient died during treatment for pneumonia before initiation of bintrafusp alfa. Conclusion Although the primary endpoint was not met, bintrafusp alfa showed some clinical activity and a manageable safety profile in patients with heavily pretreated NSCLC, including prior anti-PD-(L)1 therapy. Tumor responses occurred irrespective of whether disease was primary refractory or had acquired resistance to prior anti-PD-(L)1 therapy.

Mots clés: Bintrafusp alfa; TGF-beta; PD-L1; Bifunctional; Non-small cell lung cancer (NSCLC)

Domaines: Sciences du Vivant [q-bio]

Fabrice Barlesi, Nicolas Isambert, E. Felip, B. C. Cho, D. H. Lee, et al.. Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients With Non-Small Cell Lung Cancer Resistant or Refractory to Immune Checkpoint Inhibitors. Oncologist, 2022, Oncologist, 28, pp.258-267. ⟨10.1093/oncolo/oyac253⟩. ⟨hal-04560295⟩