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

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article numbere001395
JournalJournal for ImmunoTherapy of Cancer
Issue number2
Publication statusPublished - 2020 Dec 15

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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