Phase 2 trial of bintrafusp alfa as second-line therapy for patients with locally advanced/metastatic biliary tract cancers

Sep 24, 2026

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Phase 2, multicenter, single-arm evaluation assessed bintrafusp alfa in adults with locally advanced or metastatic chemorefractory biliary tract cancers after intolerance to or failure of first-line platinum chemotherapy. Treatment used 1200 mg administered intravenously every 2 weeks, with confirmed objective response rate by IRC as the primary endpoint and additional measures covering duration and durability of response, safety, progression-free survival, and overall survival. Among 159 enrolled patients, objective responses were observed and median efficacy and survival outcomes were reported alongside manageable toxicity.

LanguageEnglish

CategoryHealthcare

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Pages13

Reading Time33 min

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Abstract

Background and Aims

Approach and Results

Conclusions

Introduction

Disease overview and epidemiology

Prior treatments and relapse burden

DOI: 10.1097/HEP.0000000000000365 ORIGINAL ARTI C LE Phase 2 trial of bintrafusp alfa as second-line therapy for patients with locally advanced/metastatic biliary tract cancers Changhoon Yoo 1 | Milind M. Javle2 | Helena Verdaguer Mata3 | Filippo de Braud4 | Jörg Trojan5 | Jean-Luc Raoul6 | Jin Won Kim7 | Makoto Ueno8 | Choong-kun Lee9 | Susumu Hijioka 10 | Antonio Cubillo 11,12 | Junji Furuse8 | Nilofer Azad13 | Masashi Sato14 | Yulia Vugmeyster15 | Andreas Machl 15 | Marcis Bajars 16 | John Bridgewater17 | Do-Youn Oh18 | Mitesh J. Borad19 1Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea 2The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA 3Vall d’Hebron University Hospital, Barcelona, Spain 4IRCCS National Cancer Institute Foundation, Milan, Italy 5Goethe University Hospital, Frankfurt, Germany 6ICO- Site René Gauducheau, Saint-Herblain, France 7Seoul National University Bundang Hospital, Seongnam, South Korea 8Kanagawa Cancer Center, Yokohama, Kanagawa, Japan 9Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea 10National Cancer Center Hospital, Chuo, Tokyo, Japan 11HM Madrid Sanchinarro University Hospital, Clara Campal Comprehensive Cancer Center, Madrid, Spain 12UCJC HM Hospital School of Health Sciences, Madrid, Spain 13The Johns Hopkins Hospital, Baltimore, Maryland, USA 14Merck Biopharma Co. , Ltd. , Tokyo, Japan, an affiliate of Merck KGaA, Darmstadt, Germany 15EMD Serono, Billerica, Massachusetts, USA 16The Healthcare Business of Merck KGaA, Darmstadt, Germany 17UCL Cancer Institute, London, UK 18Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea 19Mayo Clinic Cancer Center, Phoenix, Arizona, USA Abbreviations: AE, adverse event; BTC, biliary tract cancer; CR, complete response, DOR, duration of response; ECOG, Eastern Cooperative Oncology Group; EHCC, extrahepatic cholangiocarcinoma; 5-FU, 5-fluorouracil; FGFR, fibroblast growth factor receptor; GC, gallbladder cancer; IDH, isocitrate dehydrogenase; IHCC, intrahepatic cholangiocarcinoma; NE, not evaluable; ORR, objective response rate; OS, overall survival; PD, progressive disease; PD-L1, programmed death ligand 1; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease. -- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- - This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © 2023 The Author(s) . Published by Wolters Kluwer Health, Inc. [758](758 | www.hepjournal.com)[ |](758 | www.hepjournal.com)[ www.hepjournal.com](758 | www.hepjournal.com) Hepatology. 2023;78:758–770 Correspondence Mitesh J. Borad, Mayo Clinic Cancer Center, 5881 E Mayo Boulevard, Phoenix, Arizona 85054, USA. Email: [borad.mitesh@mayo.edu](borad.mitesh@mayo.edu) | | Abstract | | | --- | --- | --- | | | Background and Aims: Biliary tract cancers are rare, heterogeneous cancers with poor prognoses. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β“trap”) fused to a human IgG1 monoclonal antibody blocking programmed death ligand 1, was evaluated in patients with locally advanced/metastatic chemorefractory biliary tract cancers.
Approach and Results: This multicenter, single-arm, open-label, phase 2 study (NCT03833661) enrolled adults with locally advanced or metastatic biliary tract cancer that was intole

FAQs

What population was enrolled in this phase 2 study?

Adults with locally advanced or metastatic biliary tract cancer that was intolerant to or had failed first-line systemic platinum-based chemotherapy were enrolled.

How was bintrafusp alfa administered, and what was the primary endpoint?

Bintrafusp alfa was given intravenously at 1200 mg every 2 weeks. The primary endpoint was confirmed objective response assessed by IRC using RECIST 1.1.

What were the key efficacy and safety findings?

Objective responses were achieved by a subset of patients, with reported median duration of response, progression-free survival, and overall survival. Grade 3 or higher adverse events occurred in 26.4% of patients, including one treatment-related death due to hepatic failure.

Sep 24, 2026

Uploaded by Fahsai