Advanced CCA patients (pts) who progressed after first-line chemotherapy have limited treatment options and poor prognosis. Aberrant fibroblast growth factor receptor (FGFR) signalling is a driver of the pathogenesis of CCA and is observed in 14-17% of pts. Erdafitinib, a potent oral pan-FGFR tyrosine kinase inhibitor, demonstrated encouraging clinical activity with manageable adverse events (AEs) in the Europe (EU)/United States (US) phase 1 study in solid tumours, including subjects with CCA.
LUC2001 is an open-label, multicenter, Ph2a study in advanced CCA pts with FGFR alterations, based on FoundationOne testing, who failed at least 1 prior systemic treatment. The primary endpoint is objective response rate (ORR; by RECIST 1.1). The secondary endpoints are disease control rate (DCR), safety and pharmacokinetics. Disease is evaluated every 8 weeks until disease progression (PD).
As of 20 March 2018, 150 CCA pts are molecularly screened; 25 have FGFR alterations, of whom 11 (with FGFR2 fusions  or FGFR 2  or 3  mutations) are dosed with continuous 8 mg once daily erdafitinib, all response evaluable. Median age is 53.0 years, ECOG score 0 and 1 in 6 and 5 pts, respectively, 8 males and 3 females. Median number of treatment cycles is 4.0 and median treatment duration is 3.5 months. There are 3 confirmed partial response (PR), 2 unconfirmed PR (uPR), 4 stable disease (SD), and 2 PD (both with FGFR3 mutations). The ORR (CR+PR+uCR+uPR) is 45.5%. The DCR (CR+PR+uCR+uPR+SD) is 81.8%. Six pts are still on treatment. The most common AEs (>30%) are hyperphosphatemia, dry mouth, stomatitis, diarrhea, nail disorder, and palmar-plantar erythrodysaesthesia syndrome. Seven pts experienced Grade 3 or higher AEs and 3 subjects had AEs leading to dose reduction. Three pts experienced non-drug related serious AEs (SAEs), while no AE led to treatment discontinuation or death. PK characteristics are consistent with data from other studies.
Erdafitinib shows encouraging clinical activity and tolerable safety profile in Asian and EU/US pts with FGFR-altered advanced CCA with high unmet medical need.
Clinical trial identification
Legal entity responsible for the study
Janssen (China) Research & Development Center, a division of Johnson & Johnson (China) Investment Ltd.
Janssen APMS China Research & Development.
H. Liao, J. Nie, M. Qing, J. Li, P. De Porre: Employee: Janssen Research and Development; Stock ownership: Johnson&Johnson. All other authors have declared no conflicts of interest.