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)

BACKGROUND: 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.