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116 Evaluation of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in cervical cancer: data from phase 1 and phase 2 studies
  1. J Strauss1,
  2. F Braiteh2,
  3. E Calvo Aller3,
  4. M De Miguel3,
  5. A Cervantes4,
  6. WJ Edenfield5,
  7. T LI6,
  8. MA Rasschaert7,
  9. TW Park-Simon8,
  10. FL Munoz9,
  11. L Paz-Ares10,
  12. A Spira11,
  13. G Jehl12,
  14. I Dussault13,
  15. L Ojalvo13,
  16. J Gulley14 and
  17. S Allan15
  1. 1Center for Cancer Research, National Cancer Institute, National Institutes of Health, Laboratory of Tumor Immunology and Biology, Bethesda, MD, USA
  2. 2Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA
  3. 3START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain
  4. 4University of Valencia, Biomedical Research Institute INCLIVA, València, Spain
  5. 5Greenville Hospital System University Medical Center (ITOR), Greenville, SC, USA
  6. 6University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA
  7. 7Universitair Ziekenhuis Antwerpen, Antwerpen, Belgium
  8. 8Medizinische Hochschule Hannover, Hannover, Germany
  9. 9Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, CIBERONC, Madrid, Spain
  10. 10Hospital Universitario 12 de Octubre, Madrid, Spain
  11. 11Virginia Cancer Specialists, Fairfax, VA, USA
  12. 12Merck KGaA, Darmstadt, Germany
  13. 13EMD Serono Research and Development Institute, Inc., Billerica, MA, USA
  14. 14Center for Cancer Research, National Cancer Institute, National Institutes of Health, Genitourinary Malignancies Branch, Bethesda, MD, USA
  15. 15Tasman Oncology Research Ltd, Southport, QLD, Australia


Introduction/Background*The accelerated US Food and Drug Administration approval of pembrolizumab validated the efficacy of anti-PD-(L)1 therapy for patients with recurrent/metastatic cervical cancer; however, the objective response rate (ORR) with pembrolizumab was 14.3% in patients with PD-L1–expressing tumours. Human papillomavirus infection is implicated in >95% of cervical cancers and is linked to upregulation of TGF-β signalling. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β ‘trap’) fused to a human immunoglobulin G1 monoclonal antibody blocking PD-L1. We report pooled safety and efficacy in patients with pretreated, immune checkpoint inhibitor-naive, recurrent/metastatic cervical cancer treated with bintrafusp alfa in phase 1 (INTR@PID 001; NCT02517398) and phase 2 (study 012; NCT03427411) studies.

Methodology Patients received bintrafusp alfa 0.3-30 mg/kg (phase 1 dose escalation) or 1200 mg every 2 weeks (phase 1 dose expansion and phase 2) until progressive disease, unacceptable toxicity, or withdrawal. Treatment past progression was allowed. Primary endpoints were safety (phase 1 dose escalation) and best overall response per RECIST 1.1 (phase 1 dose expansion and phase 2).

Result(s)*As of May 15, 2020 (phase 1) and December 22, 2020 (phase 2), 39 patients had received bintrafusp alfa for a median duration of 2.8 months (range, 0.5-19.3). The median follow-up to data cutoff was 35.0 months and 24.1 months for the phase 1 and phase 2 studies, respectively. All patients had received prior anticancer therapy; 16 (41.0%) had received ≥3 regimens. Confirmed ORR was 28.2% (table 1); responses occurred irrespective of Moore criteria (phase 1), tumour histology, prior bevacizumab treatment, or radiation treatment. Median overall survival was 13.4 months. No new safety signals and no treatment-related deaths were observed; side effects were manageable.

Abstract 116 Table 1

Conclusion*Bintrafusp alfa had a manageable safety profile and demonstrated clinical activity in patients with heavily pretreated, immune checkpoint inhibitor-naive recurrent/metastatic cervical cancer.

© 2021 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2021 ASCO Annual Meeting. All rights reserved.

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