Safety, pharmacokinetic, and pharmacodynamics of erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, in patients with advanced or refractory solid tumors.
Article Details
- CitationCopy to clipboard
Nishina T, Takahashi S, Iwasawa R, Noguchi H, Aoki M, Doi T
Safety, pharmacokinetic, and pharmacodynamics of erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, in patients with advanced or refractory solid tumors.
Invest New Drugs. 2018 Jun;36(3):424-434. doi: 10.1007/s10637-017-0514-4. Epub 2017 Sep 30.
- PubMed ID
- 28965185 [ View in PubMed]
- Abstract
Introduction This phase 1, open-label, multicenter, single-arm, dose-escalation study aimed to evaluate safety, pharmacokinetics (PK), and pharmacodynamics of erdafitinib (JNJ-42756493), an oral selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, and to determine the recommended phase 2 dose in Japanese patients with advanced or refractory solid tumors. Methods Three to 6 patients were enrolled into sequentially escalating dose cohorts (erdafitinib 2, 4, or 6 mg) with a daily dosing schedule of 21-day cycles or a 7 days-on/7 days-off intermittent schedule (erdafitinib 10 mg or 12 mg) of 28-day cycles. Results Nineteen patients received escalating doses of erdafitinib with a daily or intermittent schedule. The most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia (73.7%), nausea (36.8%), stomatitis (26.3%), dysgeusia (26.3%) and dry mouth (21.1%). The maximum tolerated dose was not reached in this study. No Grade 3 or higher TEAEs, or serious TEAEs were noted and no clinically significant changes in vital signs, laboratory parameters, and electrocardiogram readings were observed. However, one case of dose-limiting toxicity in the 12 mg intermittent dosing group was observed: Grade 2 detachment of retinal pigment epithelium (bilateral) with treatment discontinuation. The maximum plasma concentrations of erdafitinib exhibited a dose-dependent increase. The median tmax ranged from 2 to 3 h after the initial dose to 2-6 h following multiple daily dosing. Based on the safety and PK data, the 10 mg 7 days-on/7 days-off regimen was determined as the recommended phase 2 dose in this study. Conclusions Erdafitinib was well tolerated in Japanese patients with advanced or refractory solid tumors. TRIAL REGISTRATION: NCT01962532.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Erdafitinib Fibroblast growth factor receptor 1 Protein Humans YesInhibitorDetails Erdafitinib Fibroblast growth factor receptor 2 Protein Humans YesInhibitorDetails Erdafitinib Fibroblast growth factor receptor 3 Protein Humans YesInhibitorDetails Erdafitinib Fibroblast growth factor receptor 4 Protein Humans YesInhibitorDetails