Back to Search
Start Over
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.
- Source :
- Oncologist; Mar2023, Vol. 28 Issue 3, p258-267, 10p, 4 Charts, 3 Graphs
- Publication Year :
- 2023
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- THERAPEUTIC use of antineoplastic agents
LUNG cancer
TRANSFORMING growth factors-beta
IMMUNE checkpoint inhibitors
PROGRAMMED death-ligand 1
DRUG resistance
IMMUNOMODULATORS
LUNG tumors
GENE expression
TREATMENT effectiveness
RESEARCH funding
DESCRIPTIVE statistics
DATA analysis software
RECOMBINANT proteins
Subjects
Details
- Language :
- English
- ISSN :
- 10837159
- Volume :
- 28
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Oncologist
- Publication Type :
- Academic Journal
- Accession number :
- 163310448
- Full Text :
- https://doi.org/10.1093/oncolo/oyac253