Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies. Issue 2 (15th December 2020)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Journal for immunotherapy of cancer. Volume 8:Issue 2(2020)
• Publication Date: 2020-12-15
• Subjects: programmed cell death 1 receptor; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2020-001395
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Background: Bintrafusp 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. Methods: In 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. Results: As 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. Conclusion: Bintrafusp 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.