781PD - Safety and activity of the pan–fibroblast growth factor receptor (FGFR) inhibitor erdafitinib in phase 1 study patients with advanced urothelial ca...

Date 09 October 2016
Event ESMO 2016 Congress
Session Genitourinary tumours, non-prostate
Topics Urothelial Cancers
Presenter Jean-Charles Soria
Citation Annals of Oncology (2016) 27 (6): 266-295. 10.1093/annonc/mdw373
Authors J. Soria1, A. Italiano2, A. Cervantes3, J. Tabernero4, J. Infante5, P.N. Lara6, A. Spira7, E. Calvo8, V. Moreno9, J. Blay10, R. Lauer11, N. Chan12, B. Zhong13, A. Ademi Santiago-Walker14, J. Bussolari15, F.R. Luo16, H. Xie16, P. Hammerman17
  • 1Department Of Medicine Ditep, Gustave Roussy Cancer Campus and University Paris-Sud, 94805 - Villejuif/FR
  • 2Medical Oncology, Institute Bergonié, 33076 - Bordeaux/FR
  • 3Medical Oncology, Vall d´Hebron University Hospital and Institute of Oncology (VHIO), Barcelona/ES
  • 4Medical Oncology, Hospital General Vall d´Hebrón, 08035 - Barcelona/ES
  • 5Drug Development Unit, Sarah Cannon Research Institute, Nashville/US
  • 6Internal Medicine/hematology-oncology, University of California Davis Cancer Center, 95817 - Sacramento/US
  • 7Medical Oncology, US Oncology Research, The Woodlands/US
  • 8Start Madrid, Early Clinical Drug Development Unit, START Madrid-CIOCC. Centro Integral Oncologico Clara Campal, 28050 - Madrid/ES
  • 9Medical Oncology, START Madrid-FJD, Hospital Universitario Fundación Jiménez Díaz Hospital, Madrid/ES
  • 10University Claude Bernard Lyon I, Centre Léon Bérard, 69008 - Lyon/FR
  • 11Internal Medicine, University of New Mexico, Albuquerque/US
  • 12Department Of Medicine, Rutgers University, New Brunswick/US
  • 13Biostatistics, Janssen Research and Development, Raritan/US
  • 14Oncology Translational Research, Janssen Research and Development, Raritan/US
  • 15Compound Development, Janssen Research and Development, Raritan/US
  • 16Experimental Medicine, Janssen Research and Development, Raritan/US
  • 17Medical Oncology, Dana-Farber Cancer Institute, Boston/US



Erdafitinib (JNJ-42756493) is a potent, oral pan-FGFR tyrosine kinase inhibitor that demonstrated encouraging preliminary clinical activity and manageable adverse events (AEs) in its first-in-human phase 1 study in advanced solid tumors (NCT01703481). Here we report results from patients with urothelial carcinoma (UC) from this study.


This 4-part study enrolled patients age ≥ 18 years with advanced solid tumors. Dose escalation (Part 1) followed a 3 + 3 design, with patients receiving ascending doses of erdafitinib either once daily (QD) or intermittently (7 days on/7 days off). Subsequent parts of the study (Part 2, pharmacodynamics cohort; Parts 3 and 4, dose-expansion cohorts for recommended phase 2 doses of 9 mg QD and 10 mg intermittently, respectively) required documented FGFR-biomarker positive disease (including activating mutations and translocations; or other FGFR-activating aberrations, Parts 2 and 3).


Twenty-eight patients with UC were treated at 2 mg QD (n = 1), 9 mg QD (n = 12), 10 mg intermittent (n = 13), 12 mg QD (n = 1), or 12 mg intermittent (n = 1). Across these dose levels, median treatment duration was 3.3 mo. The most common drug-related AEs were hyperphosphatemia (57%), dry mouth (50%), diarrhea (46%), and dry skin (46%); all of these were grade 1 or 2 severity, except for 1 case of grade 3 hyperphosphatemia (4%) and 2 cases of grade 3 diarrhea (7%). The most common grade ≥3 AEs were anemia (18%), hand-foot syndrome (14%), and stomatitis (11%). Among FGFR-positive, response evaluable patients (as of 22 Apr 2016), the objective response rate (Complete Response + Partial Response [PR]) was 43.5% (10/23; 95% CI 23.2%, 65.5%); 17.4% (4/23) had stable disease. 6/11(54.5%) patients treated at 9 mg QD and 4/11(36.4%) patients treated 10 mg intermittent achieved PR. With a median follow-up of 3.8 mo, median duration of response was 7.2 mo (95% CI 3.3, 15.3) and progression-free survival was 5.1 mo (95% CI 2.8, 5.9).


Erdafitinib produces encouraging clinical activity and tolerability in patients with FGFR-positive UC, warranting further study.

Clinical trial identification

NCT01703481; Release date: March 22, 2012

Legal entity responsible for the study

Janssen Research & Development, LLC


Janssen Research & Development, LLC


J-C. Soria: Honoraria: Johnson and Johnson. A. Cervantes: Research funding: Janssen. J. Tabernero: Consultant/Advisory: Amgen, Boehringer Ingelheim, Celgene, Chugai, Imclone, Lilly, Merck, Merck Serono, Millennium, Novartis, Roche, Sanofi, Symphogen and Taiho. P.N. Lara: Research funding: Johnson & Johnson. A. Spira: Consultant/Advisory: Novartis, Clovis, Roche, Astellas, Ariad Honoraria: Roche, Ariad, Clovis Research funding: Janssen . B. Zhong, A. Ademi Santiago-Walker, J. Bussolari, F.R. Luo, H. Xie: Employee of Janssen Research & Development and Johnson & Johnson stock holder. P. Hammerman: Consultant/Advisory: Janssen Honoraria: Janssen. All other authors have declared no conflicts of interest.