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Open Access 01-07-2021 | Original Research Article

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGFβ and PD-L1, in Patients with Esophageal Squamous Cell Carcinoma: Results from a Phase 1 Cohort in Asia

Authors: Chia-Chi Lin, Toshihiko Doi, Kei Muro, Ming-Mo Hou, Taito Esaki, Hiroki Hara, Hyun Cheol Chung, Christoph Helwig, Isabelle Dussault, Motonobu Osada, Shunsuke Kondo

Published in: Targeted Oncology | Issue 4/2021

Abstract

Background

Patients with esophageal squamous cell carcinoma (SCC) have limited treatment options. Blocking transforming growth factor-β (TGFβ), which can be overexpressed in these tumors, may enhance responses to programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] inhibitors. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGFβ receptor II (TGFβRII) (a TGFβ “trap”) fused to a human IgG1 monoclonal antibody blocking PD-L1.

Objective

The objective of this study was to investigate the safety and efficacy of bintrafusp alfa in Asian patients with pretreated, PD-L1–unselected esophageal SCC.

Patients and Methods

In a phase 1 study, Asian patients with pretreated esophageal SCC received bintrafusp alfa 1200 mg every 2 weeks until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was safety/tolerability with a goal of exploring clinical activity.

Results

By the database cutoff of August 24, 2018, 30 patients (76.7% had two or more prior anticancer regimens) received bintrafusp alfa for a median of 6.1 weeks; two remained on treatment. Nineteen patients (63.3%) had treatment-related adverse events, seven (23.3%) with grade 3/4 events, and there were no treatment-related deaths. The confirmed objective response rate (ORR) per independent review was 10.0% (95% confidence interval [CI] 2.1–26.5); responses lasted 2.8–8.3 + months. All responses occurred in immune-excluded tumors. Investigator-assessed confirmed ORR was 20.0% (95% CI 7.7–38.6). Median overall survival was 11.9 months (95% CI 5.7–not reached).

Conclusions

Bintrafusp alfa demonstrated a manageable safety profile and efficacy in Asian patients with pretreated esophageal SCC.

Clinical Trials Registration

NCT02699515.

Available only for authorised users

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Title: Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGFβ and PD-L1, in Patients with Esophageal Squamous Cell Carcinoma: Results from a Phase 1 Cohort in Asia
Authors: Chia-Chi Lin
Toshihiko Doi
Kei Muro
Ming-Mo Hou
Taito Esaki
Hiroki Hara
Hyun Cheol Chung
Christoph Helwig
Isabelle Dussault
Motonobu Osada
Shunsuke Kondo
Publication date: 01-07-2021
Publisher: Springer International Publishing
Published in: Targeted Oncology / Issue 4/2021
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-021-00810-9

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