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

Date

09 Oct 2016

Session

Genitourinary tumours, non-prostate

Presenters

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

Author affiliations

  • 1 Department Of Medicine Ditep, Gustave Roussy Cancer Campus and University Paris-Sud, 94805 - Villejuif/FR
  • 2 Medical Oncology, Institute Bergonié, 33076 - Bordeaux/FR
  • 3 Medical Oncology, Vall d´Hebron University Hospital and Institute of Oncology (VHIO), Barcelona/ES
  • 4 Medical Oncology, Hospital General Vall d´Hebrón, 08035 - Barcelona/ES
  • 5 Drug Development Unit, Sarah Cannon Research Institute, Nashville/US
  • 6 Internal Medicine/hematology-oncology, University of California Davis Cancer Center, 95817 - Sacramento/US
  • 7 Medical Oncology, US Oncology Research, The Woodlands/US
  • 8 Start Madrid, Early Clinical Drug Development Unit, START Madrid-CIOCC. Centro Integral Oncologico Clara Campal, 28050 - Madrid/ES
  • 9 Medical Oncology, START Madrid-FJD, Hospital Universitario Fundación Jiménez Díaz Hospital, Madrid/ES
  • 10 University Claude Bernard Lyon I, Centre Léon Bérard, 69008 - Lyon/FR
  • 11 Internal Medicine, University of New Mexico, Albuquerque/US
  • 12 Department Of Medicine, Rutgers University, New Brunswick/US
  • 13 Biostatistics, Janssen Research and Development, Raritan/US
  • 14 Oncology Translational Research, Janssen Research and Development, Raritan/US
  • 15 Compound Development, Janssen Research and Development, Raritan/US
  • 16 Experimental Medicine, Janssen Research and Development, Raritan/US
  • 17 Medical Oncology, Dana-Farber Cancer Institute, Boston/US
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Resources

Background

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.

Methods

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).

Results

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).

Conclusions

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

Funding

Janssen Research & Development, LLC

Disclosure

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.

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