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

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

  • J Immunother Cancer. 2020 Dec;8(2):e001395. doi: 10.1136/jitc-2020-001395.
Julius Strauss # 1,  Margaret E Gatti-Mays # 1,  Byoung Chul Cho 2,  Andrew Hill 3,  Sébastien Salas 4,  Edward McClay 5,  Jason M Redman 6,  Houssein A Sater 6,  Renee N Donahue 1,  Caroline Jochems 1,  Elizabeth Lamping 6,  Andrea Burmeister 6 7,  Jennifer L Marté 6,  Lisa M Cordes 6,  Marijo Bilusic 6,  Fatima Karzai 6,  Laureen S Ojalvo 8,  Genevieve Jehl 9,  P Alexander Rolfe 8,  Christian S Hinrichs 6,  Ravi A Madan 6,  Jeffrey Schlom 1,  James L Gulley 10
Affiliations

Affiliations

  • 1 Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • 2 Yonsei University College of Medicine, Seoul, Republic of Korea.
  • 3 Tasman Oncology Research Ltd, Southport, Queensland, Australia.
  • 4 CEPCM Assistance Publique des Hôpitaux de Marseille; Aix-Marseille Université, Marseille, France.
  • 5 California Cancer Associates for Research and Excellence, Encinitas, California, USA.
  • 6 Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • 7 Leidos Biomedical Research, Frederick, Maryland, USA.
  • 8 EMD Serono Research & Development Institute, Inc, Billerica, Massachusetts, USA; an affiliate of Merck KGaA, Darmstadt, Germany.
  • 9 Merck KGaA, Darmstadt, Germany.
  • 10 Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA gulleyj@mail.nih.gov.
  • # Contributed equally.
PMID: 33323462 DOI: 10.1136/jitc-2020-001395
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.

Keywords

programmed cell death 1 receptor.

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