Safety and tolerability of bintrafusp alfa, a bifunctional fusion protein targeting TGFb and PD-L1, in asian patients with pretreated recurrent or refractory gastric cancer

Yoon Koo Kang, Yung Jue Bang, Shunsuke Kondo, Hyun Cheol Chung, Kei Muro, Isabelle Dussault, Christoph Helwig, Motonobu Osada, Toshihiko Doi

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16 Citations (Scopus)


Purpose: Patients with advanced gastric/gastroesophageal junction cancer (GC/GEJC) have limited treatment options after first-line therapy. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGFbRII receptor (a TGFb “trap”) fused to a human IgG1 antibody against programmed death ligand 1 (PD-L1), potentially offering a new treatment approach for these patients. We report results for bintrafusp alfa in GC/GEJC. Patients and Methods: Asian patients with recurrent GC/GEJC for whom standard therapy does not exist or for whom standard therapy has failed enrolled in this expansion cohort of an ongoing phase I trial and received bintrafusp alfa 1,200 mg once every 2 weeks until disease progression, unacceptable toxicity, or withdrawal. The primary objective was to assess safety/tolerability. Results: By July 23, 2018, 31 heavily pretreated patients received bintrafusp alfa for a median of 10.1 weeks; 3 patients remained on treatment. Six patients (19%) experienced grade 3 treatment-related adverse events (AE); no grade 4 events occurred. One on-treatment death occurred (sudden death); rupture of a preexisting thoracic aortic aneurysm was the suspected cause. Ten patients (32%) had immune-related AEs. The confirmed objective response rate per independent review committee was 16%; disease control rate was 26%. Median duration of response was 8.7 months (range, 2.4-12.4þ). Responses occurred irrespective of PD-L1 expression or microsatellite instability status and appeared to correlate with high tumor TGFB1 levels. Conclusions: In this first evaluation in Asian patients with heavily pretreated advanced GC/GEJC, bintrafusp alfa demonstrated a manageable safety profile and clinical activity.

Original languageEnglish
Pages (from-to)3202-3210
Number of pages9
JournalClinical Cancer Research
Issue number13
Publication statusPublished - 2020 Jul

Bibliographical note

Funding Information:
The authors thank the patients, investigators, coinvestigators, and the study teams at each of the participating centers and at Merck KGaA, Darmstadt, Germany. The authors thank Christian Ihling of Merck KGaA for his substantial contribution to the immune phenotype analysis. This trial was funded by Merck KGaA and is part of an alliance between Merck KGaA and GlaxoSmithKline. Medical writing support was provided by Lauren Rusnak, PhD, of ClinicalThinking, Inc, and funded by Merck KGaA and GlaxoSmithKline in accordance with Good Publication Practice (GPP3) guidelines (

Publisher Copyright:
© 2020 American Association for Cancer Research.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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