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Clin Cancer Res. 2019 Aug 15;25(16):4888-4897. doi: 10.1158/1078-0432.CCR-18-3334. Epub 2019 May 14.

Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors.

Author information

1
Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif, France.
2
Institut Bergonie, Bordeaux, France.
3
Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
4
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
5
Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain.
6
Rutgers University, New Brunswick, New Jersey.
7
Dana-Farber Cancer Institute, Boston, Massachusetts.
8
START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain.
9
START Madrid-FJD, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
10
Washington University School of Medicine, St. Louis, Missouri.
11
Virginia Cancer Specialists Research Institute, Fairfax, Virginia; and US Oncology Research, The Woodlands, Texas.
12
Janssen Research & Development, Raritan, New Jersey.
13
Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. jtabernero@vhio.net.

Abstract

PURPOSE:

Here, we report results of the first phase I study of erdafitinib, a potent, oral pan-FGFR inhibitor.

PATIENTS AND METHODS:

Patients age ≥18 years with advanced solid tumors for which standard antineoplastic therapy was no longer effective were enrolled (NCT01703481). Parts 2 to 4 employed molecular screening for activating FGFR genomic alterations. In patients with such alterations, two selected doses/schedules identified during part 1 dose-escalation [9 mg once daily and 10 mg intermittently (7 days on/7 days off), as previously published (Tabernero JCO 2015;33:3401-8)] were tested.

RESULTS:

The study included 187 patients. The most common treatment-related adverse events were hyperphosphatemia (64%), dry mouth (42%), and asthenia (28%), generally grade 1/2 severity. All cases of hyperphosphatemia were grade 1/2 except for 1 grade 3 event. Skin, nail, and eye changes were observed in 43%, 33%, and 28% of patients, respectively (mostly grade 1/2 and reversible after temporary dosing interruption). Urothelial carcinoma and cholangiocarcinoma were most responsive to erdafitinib, with objective response rates (ORR) of 46.2% (12/26) and 27.3% (3/11), respectively, in response-evaluable patients with FGFR mutations or fusions. All patients with urothelial carcinoma and cholangiocarcinoma who responded to erdafitinib carried FGFR mutations or fusions. Median response duration was 5.6 months for urothelial carcinoma and 11.4 months for cholangiocarcinoma. ORRs in other tumor types were <10%.

CONCLUSIONS:

Erdafitinib shows tolerability and preliminary clinical activity in advanced solid tumors with genomic changes in the FGFR pathway, at two different dosing schedules and with particularly encouraging responses in urothelial carcinoma and cholangiocarcinoma.

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