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)

Abstract

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.

Keywords: biliary tract cancer; maintenance therapy; precision medicine; targeted therapy.

Figure 1

Trial flow chart. 1L-SoC, first-line standard of care; ABC, advanced biliary cancer; BE, Belgium; CR, complete response; ESCAT, ESMO Scale for Clinical Actionability of molecular Targets; FR, France; MTT, molecular targeted therapy; PD, progression of disease; PR, partial response; R, randomisation; SD, stable disease; UK, United Kingdom. ^aFor France and UK, informed consent will include consent to access to the molecular profiling tests. In Belgium, patients will be asked to consent to tumour genomic profiling carried out as part of the clinical trial.