Pharmacokinetics, pharmacodynamics and efficacy of pemigatinib (a selective inhibitor of fibroblast growth factor receptor 1–3) monotherapy in Chinese patients with advanced solid tumors: a phase i clinical trial

耐受性 药代动力学 药效学 医学 不利影响 临床终点 人口 分配量 内科学 胃肠病学 生物利用度 临床研究阶段 曲线下面积 药理学 实体瘤疗效评价标准 成纤维细胞生长因子受体1 泌尿科 临床试验 肿瘤科 受体 成纤维细胞生长因子 环境卫生
作者
Ting Deng,Le Zhang,Yehui Shi,Guiying Bai,Yueyin Pan,Aizong Shen,Xinghua Han,Zhaoyi Yang,Mingxia Chen,Hui Zhou,Yang Luo,Shirui Zheng,Yi Ba
出处
期刊:Investigational New Drugs [Springer Science+Business Media]
卷期号:41 (6): 808-815 被引量:1
标识
DOI:10.1007/s10637-023-01396-x
摘要

Abstract Pemigatinib is a selective fibroblast growth factor receptor (FGFR)1–3 inhibitor and has demonstrated acceptable tolerability and clinical activity in advanced solid tumors in Western population. This phase I trial evaluated pharmacokinetics/pharmacodynamics (PK/PD) characteristics, preliminary safety and efficacy of pemigatinib in Chinese patients with advanced, solid tumors. Patients with unresectable advanced or metastatic solid tumors bearing FGF/FGFR1-3 alterations received oral pemigatinib at 13.5 mg once daily (QD) on a 2-weeks-on/1-week-off schedule. The primary endpoint was PK/PD characteristics; secondary endpoints were safety and efficacy. Twelve patients were enrolled (median age: 61 years, 58.3% males). PK data demonstrated pemigatinib (13.5 mg QD) was rapidly absorbed with a geometric mean elimination half-life of 11.3 h. The geometric mean values of maximum serum concentration and area under the plasma concentration–time curve from 0 to 24 h at steady state were 215.1 nmol/L and 2636.9 h·nmol/L, respectively. The mean clearance adjusted by bioavailability at steady state was low (11.8 L/h), and the apparent oral volume of distribution was moderate (170.5 L). The PD marker, serum phosphate level, increased on days 8 and 15 of cycle 1 (mean: 2.25 mg/dL, CV% [percent coefficient of variation]: 31.3%) and decreased to baseline post 1 week off. Three (25.0%) patients experienced grade ≥ 3 treatment-emergent adverse events. Partial response was confirmed in one patient with FGFR1-mutant esophageal carcinoma and one with FGFR2-mutant cholagiocarcinoma. Pemigatinib had similar PK/PD characteristics to Western population and demonstrated an acceptable safety profile and potential anti-cancer benefit in Chinese patients with FGF/FGFR1-3 altered, advanced, solid tumor. (ClinicalTrials.gov: NCT04258527 [prospectively registered February 6, 2020]).
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