Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-ß and PD-L1, in Patients With Non-Small Cell Lung Cancer Resistant or Refractory to Immune Checkpoint Inhibitors.
Oncologist
; 28(3): 258-267, 2023 03 17.
Article
en En
| MEDLINE
| ID: mdl-36571770
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-ß "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 ANDMETHODS:
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.Palabras clave
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Banco de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
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Antineoplásicos Inmunológicos
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Neoplasias Pulmonares
Límite:
Adult
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Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article