A Study of Erdafitinib in Participants With Advanced Solid Tumors and Fibroblast Growth Factor Receptor (FGFR) Gene Alterations

2019 ◽  
Author(s):  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Solid Tumors ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Advanced Solid Tumors ◽  
Fibroblast Growth ◽  
Gene Alterations

Phase 1 study of JNJ-42756493, a pan-fibroblast growth factor receptor (FGFR) inhibitor, in patients with advanced solid tumors.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 2501-2501 ◽  
Author(s):  
Rastislav Bahleda ◽  
Rodrigo Dienstmann ◽  
Barbara Adamo ◽  
Anas Gazzah ◽  
Jeffrey R. Infante ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Solid Tumors ◽  
Fibroblast Growth Factor Receptor ◽  
Phase 1 ◽  
Growth Factor Receptor ◽  
Advanced Solid Tumors ◽  
Fibroblast Growth ◽  
Phase 1 Study

Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan–Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors

2015 ◽  
Vol 33 (30) ◽  
pp. 3401-3408 ◽  
Author(s):  
Josep Tabernero ◽  
Rastislav Bahleda ◽  
Rodrigo Dienstmann ◽  
Jeffrey R. Infante ◽  
Alain Mita ◽  
...  
Keyword(s):  
Growth Factor ◽  
Adverse Events ◽  
Fibroblast Growth Factor ◽  
Solid Tumors ◽  
Fibroblast Growth Factor Receptor ◽  
Human Study ◽  
Growth Factor Receptor ◽  
Advanced Solid Tumors ◽  
Fibroblast Growth ◽  
Grade 3

Purpose 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. Patients and 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. Conclusion 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.

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