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Tan B, Khattak A, Felip E, et al. Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients with Esophageal Adenocarcinoma: Results from a Phase 1 Cohort. Target Oncol. 2021;16(4):435-446doi: 10.1007/s11523-021-00809-2.
Tan, B., Khattak, A., Felip, E., Kelly, K., Rich, P., Wang, D., Helwig, C., Dussault, I., Ojalvo, L. S., & Isambert, N. (2021). Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients with Esophageal Adenocarcinoma: Results from a Phase 1 Cohort. Targeted oncology, 16(4), 435-446. https://doi.org/10.1007/s11523-021-00809-2
Tan, Benjamin, et al. "Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients with Esophageal Adenocarcinoma: Results from a Phase 1 Cohort." Targeted oncology vol. 16,4 (2021): 435-446. doi: https://doi.org/10.1007/s11523-021-00809-2
Tan B, Khattak A, Felip E, Kelly K, Rich P, Wang D, Helwig C, Dussault I, Ojalvo LS, Isambert N. Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients with Esophageal Adenocarcinoma: Results from a Phase 1 Cohort. Target Oncol. 2021 Jul;16(4):435-446. doi: 10.1007/s11523-021-00809-2. Epub 2021 May 19. PMID: 34009501; PMCID: PMC8266790.
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Target Oncol. 2021 Jul;16(4):435-446. doi: 10.1007/s11523-021-00809-2. Epub 2021 May 19.

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients with Esophageal Adenocarcinoma: Results from a Phase 1 Cohort.

Targeted oncology

Benjamin Tan, Adnan Khattak, Enriqueta Felip, Karen Kelly, Patricia Rich, Ding Wang, Christoph Helwig, Isabelle Dussault, Laureen S Ojalvo, Nicolas Isambert

Affiliations

  1. Washington University School of Medicine, St Louis, MO, USA.
  2. Fiona Stanley Hospital, Perth, WA, Australia.
  3. Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), IOB-Quiron, UVic-UCC, Barcelona, Spain.
  4. University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
  5. Cancer Treatment Centers of America, Atlanta, GA, USA.
  6. Piedmont Healthcare, Atlanta, GA, USA.
  7. Henry Ford Cancer Institute, Detroit, MI, USA.
  8. Merck KGaA, Darmstadt, Germany.
  9. EMD Serono Research & Development Institute, Inc., Billerica, MA, USA.
  10. An affiliate of Merck KGaA, Darmstadt, Germany.
  11. Poitiers University Hospital, 2 rue de la Miléterie, BP 577, 86021, Poitiers, France. [email protected].

PMID: 34009501 PMCID: PMC8266790 DOI: 10.1007/s11523-021-00809-2

Abstract

BACKGROUND: Esophageal adenocarcinoma patients have limited treatment options. TGF-β can be upregulated in esophageal adenocarcinoma, and blocking this pathway may enhance clinical response to PD-(L)1 inhibitors. 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 IgG1 mAb blocking PD-L1.

OBJECTIVE: The objective of this study was to investigate the efficacy and safety of bintrafusp alfa in patients with advanced, post-platinum esophageal adenocarcinoma, unselected for PD-L1 expression.

PATIENTS AND METHODS: In this phase 1 study, patients with post-platinum, PD-L1-unselected esophageal adenocarcinoma received bintrafusp alfa 1200 mg every 2 weeks until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was confirmed best overall response per RECIST 1.1 by independent review committee (IRC).

RESULTS: By the database cutoff of 24 August 2018, 30 patients (80.0% had two or more prior anticancer regimens) received bintrafusp alfa for a median of 6.1 weeks. The confirmed objective response rate (ORR) per IRC was 20.0% (95% CI 7.7-38.6); responses lasted 1.3-8.3 months. Most responses (83.3%) occurred in tumors with an immune-excluded phenotype. Investigator-assessed confirmed ORR was 13.3% (95% CI 3.8-30.7). Nineteen patients (63.3%) had treatment-related adverse events: seven patients (23.3%) had grade 3 events; no grade 4 events or treatment-related deaths occurred.

CONCLUSIONS: Bintrafusp alfa showed signs of clinical efficacy with a manageable safety profile in patients with heavily pretreated, advanced esophageal adenocarcinoma.

CLINICAL TRIALS REGISTRATION: NCT02517398.

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