Yoo, Changhoon;
Javle, Milind M;
Verdaguer Mata, Helena;
de Braud, Filippo;
Trojan, Jörg;
Raoul, Jean-Luc;
Kim, Jin Won;
... Borad, Mitesh J; + view all
(2023)
Phase 2 trial of bintrafusp alfa as second-line therapy for patients with locally advanced/metastatic biliary tract cancers.
Hepatology
, 78
pp. 758-770.
10.1097/HEP.0000000000000365.
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Abstract
BACKGROUND AIMS: Biliary tract cancers are rare, heterogeneous cancers with poor prognosis. 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 mAb blocking PD-L1, was evaluated in patients with locally advanced/metastatic chemorefractory biliary tract cancers. APPROACH RESULTS: This multicenter, single-arm, open-label, phase 2 study (NCT03833661) enrolled adults with locally advanced or metastatic biliary tract cancer that was intolerant to or had failed first-line systemic platinum-based chemotherapy. Patients received 1200 mg bintrafusp alfa intravenously Q2W. Primary endpoint was confirmed objective response according to RECIST 1.1 assessed by IRC. Secondary endpoints included DOR, durable response rate, safety, PFS, and OS.Between March 2019 and January 2020, 159 patients were enrolled. Median follow-up was 16.1 (range, 0.0-19.3) months; 17 patients (10.7%; 95% CI, 6.4% -16.6%) achieved objective response. Median DOR was 10.0 (range, 1.9-15.7) months; 10 patients (6.3%; 95% CI, 3.1%- 11.3%) had a durable response (≥6 mo). Median PFS was 1.8 months (95% CI, 1.7-1.8 mo); median OS was 7.6 months (95% CI, 5.8-9.7 mo). OS rates were 57.9% (6-month) and 38.8% (12-month). Grade ≥3 AEs occurred in 26.4% of patients, including one treatment-related death (hepatic failure). Frequent grade ≥3 adverse events included anemia (3.8%), pruritus (1.9%), and increased alanine aminotransferase (1.9%). CONCLUSIONS: Although this study did not meet its prespecified primary endpoint, bintrafusp alfa demonstrated clinical activity as second-line treatment in this hard-to-treat cancer, with durable responses and a manageable safety profile.
| Type: | Article |
|---|---|
| Title: | Phase 2 trial of bintrafusp alfa as second-line therapy for patients with locally advanced/metastatic biliary tract cancers |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1097/HEP.0000000000000365 |
| Publisher version: | https://doi.org/10.1097/HEP.0000000000000365 |
| Language: | English |
| Additional information: | © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10174868 |
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