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Molecular targeted maintenance therapy versus standard of care in advanced biliary cancer: an international, randomised, controlled, open-label, phase III umbrella trial (SAFIR-ABC10—Precision Medicine)

Lookup NU author(s): Professor James WasonORCiD

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Abstract

© 2025 The AuthorsBackground: Advanced biliary tract cancers (ABCs) are a heterogeneous group of rare malignancies of the bile ducts and gall-bladder with a poor prognosis and limited treatment options. Cisplatin–gemcitabine (CISGEM) chemotherapy plus immunotherapy (durvalumab or pembrolizumab) is the current first-line standard of care (1L-SoC). ABCs frequently harbour actionable molecular alterations that suggest a high potential for benefit from molecular targeted therapies (MTTs). However, the assessment of potential first-line MTT treatments is hindered by the scarcity of ABCs harbouring a specific alteration and the time required to carry out tumour molecular profiling. Materials and methods: We detail here the design of SAFIR-ABC10, an international, randomised, phase III umbrella trial comparing the efficacy of sequential matched targeted therapy after four cycles (12 weeks) of 1L-SoC versus continued 1L-SoC in patients with ABC and an actionable molecular alteration [European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT) tier I or II]. The primary study endpoint is progression-free survival. Besides initial tumour and circulating DNA next-generation sequencing analysis, sequential blood and tumour sampling will be carried out to identify biomarkers of prognosis, response and acquired resistance. Perspectives: SAFIR-ABC10 is, to our knowledge, the first randomised, umbrella trial assessing the concept of precision medicine in ABC, the ideal setting for addressing this question with a high rate of targetable alterations.

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Author(s): Malka D, Borbath I, Lopes A, Couch D, Jimenez M, Vandamme T, Valle JW, Wason J, Ambrose E, Dewever L, De Bruyne I, Edeline J, Bridgewater J

Publication type: Article

Publication status: Published

Journal: ESMO Open

Year: 2025

Volume: 10

Issue: 5

Print publication date: 01/05/2025

Online publication date: 09/04/2025

Acceptance date: 02/04/2025

Date deposited: 22/04/2025

ISSN (electronic): 2059-7029

Publisher: Elsevier B.V.

URL: https://doi.org/10.1016/j.esmoop.2025.104540

DOI: 10.1016/j.esmoop.2025.104540

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