Details

Autor(en) / Beteiligte

• Strauss, Julius
• Gatti-Mays, Margaret E
• Cho, Byoung Chul
• Hill, Andrew
• Salas, Sébastien
• McClay, Edward
• Redman, Jason M
• Sater, Houssein A
• Donahue, Renee N
• Jochems, Caroline
• Lamping, Elizabeth
• Burmeister, Andrea
• Marté, Jennifer L
• Cordes, Lisa M
• Bilusic, Marijo
• Karzai, Fatima
• Ojalvo, Laureen S
• Jehl, Genevieve
• Rolfe, P Alexander
• Hinrichs, Christian S
• Madan, Ravi A
• Schlom, Jeffrey
• Gulley, James L

Titel

Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies

Ist Teil von

• Journal for immunotherapy of cancer, 2020-12, Vol.8 (2), p.e001395

Ort / Verlag

England: BMJ Publishing Group

Erscheinungsjahr

2020

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• BackgroundBintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor (TGF)-βRII (a TGF-β ‘trap’) fused to a human IgG1 mAb blocking programmed cell death ligand 1. This is the largest analysis of patients with advanced, pretreated human papillomavirus (HPV)-associated malignancies treated with bintrafusp alfa.MethodsIn these phase 1 (NCT02517398) and phase 2 trials (NCT03427411), 59 patients with advanced, pretreated, checkpoint inhibitor-naive HPV-associated cancers received bintrafusp alfa intravenously every 2 weeks until progressive disease, unacceptable toxicity, or withdrawal. Primary endpoint was best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1; other endpoints included safety.ResultsAs of April 17, 2019 (phase 1), and October 4, 2019 (phase 2), the confirmed objective response rate per RECIST V.1.1 in the checkpoint inhibitor-naive, full-analysis population was 30.5% (95% CI, 19.2% to 43.9%; five complete responses); eight patients had stable disease (disease control rate, 44.1% (95% CI, 31.2% to 57.6%)). In addition, three patients experienced a delayed partial response after initial disease progression, for a total clinical response rate of 35.6% (95% CI, 23.6% to 49.1%). An additional patient with vulvar cancer had an unconfirmed response. Forty-nine patients (83.1%) experienced treatment-related adverse events, which were grade 3/4 in 16 patients (27.1%). No treatment-related deaths occurred.ConclusionBintrafusp alfa showed clinical activity and manageable safety and is a promising treatment in HPV-associated cancers. These findings support further investigation of bintrafusp alfa in patients with advanced, pretreated HPV-associated cancers.