Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors.
OBJECTIVE
JNJ-42756493 is an orally administered pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor. This first-in-human study evaluates the safety, pharmacokinetics, and pharmacodynamics and defines the recommended phase II dose (RP2D) of JNJ-42756493.


METHODS
Eligible patients with advanced solid tumors received escalating doses of JNJ-42756493 from 0.5 to 12 mg administered continuously daily or JNJ-42756493 10 or 12 mg administered intermittently (7 days on/7 days off).


RESULTS
Sixty-five patients were enrolled. The most common treatment-emergent adverse events included hyperphosphatemia (65%), asthenia (55%), dry mouth (45%), nail toxicity (35%), constipation (34%), decreased appetite (32%), and dysgeusia (31%). Twenty-seven patients (42%) experienced grade ≥ 3 treatment-emergent adverse events, and one dose-limiting toxicity of grade 3 ALT elevation was observed at 12 mg daily. Maximum-tolerated dose was not defined. Nine milligrams daily was considered as the initial RP2D; however, tolerability was improved with intermittent schedules, and 10 mg administered on a 7-days-on/7-days-off schedule was considered the final RP2D. Pharmacokinetics were linear, dose proportional, and predictable, with a half-life of 50 to 60 hours. Dose-dependent elevations in serum phosphate, a manifestation of pharmacodynamic effect, occurred in all patients starting at 4 mg daily. Among 23 response-evaluable patients with tumor FGFR pathway alterations, four confirmed responses and one unconfirmed partial response were observed in patients with glioblastoma and urothelial and endometrial cancer (all with FGFR2 or FGFR3 translocations); 16 patients had stable disease.


CONCLUSIONS
JNJ-42756493 administered at 10 mg on a 7-days-on/7-days-off schedule achieved exposures at which clinical responses were observed, demonstrated pharmacodynamic biomarker activity, and had a manageable safety profile.
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium. jtabernero@vhio.net.
Josep
J
Tabernero
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Rastislav
R
Bahleda
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Rodrigo
R
Dienstmann
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Jeffrey R
JR
Infante
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Alain
A
Mita
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Antoine
A
Italiano
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Emiliano
E
Calvo
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Victor
V
Moreno
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Barbara
B
Adamo
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Anas
A
Gazzah
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Bob
B
Zhong
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Suso J
SJ
Platero
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Johan W
JW
Smit
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Kim
K
Stuyckens
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Moitreyee
M
Chatterjee-Kishore
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Jordi
J
Rodon
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Vijay
V
Peddareddigari
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Feng R
FR
Luo
Josep Tabernero, Rodrigo Dienstmann, Barbara Adamo, and Jordi Rodon, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona; Emiliano Calvo, START Madrid, Centro Integral Oncológico Clara Campal; Victor Moreno, START Madrid, Hospital Fundación Jiménez Díaz, Madrid, Spain; Rastislav Bahleda, Anas Gazzah, and Jean-Charles Soria, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif; Antoine Italiano, Institut Bergonié, Bordeaux, France; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Alain Mita, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Bob Zhong, Suso J. Platero, Moitreyee Chatterjee-Kishore, Vijay Peddareddigari, and Feng R. Luo, Janssen Research and Development, Raritan, NJ; and Johan W. Smit and Kim Stuyckens, Janssen Research and Development, Beerse, Belgium.
Jean-Charles
JC
Soria
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011810:Quinoxalines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011810:Quinoxalines; D017468:Receptors, Fibroblast Growth Factor; C000604580:erdafitinib