Peking University Cancer Hospital and Institute, Beijing, China.
Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
Clin Transl Sci. 2024 Dec;17(12):e70091. doi: 10.1111/cts.70091.
Infigratinib, an FGFR1-3 selective oral tyrosine kinase inhibitor, has shown clinical activity in cancers with FGFR alterations. The pharmacokinetics (PK) of infigratinib and its major metabolites have been characterized in global populations. This study examined the PK profile of infigratinib and its metabolites in Chinese patients. In this phase II, open-label, single-arm study in China, patients with advanced gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJ) harboring FGFR2 gene amplification received 125 mg infigratinib orally once daily in a "3 weeks on, 1 week off" schedule for 28-day cycles. Plasma PK parameters were calculated with a non-compartmental model. Data were available from 21 patients (19 GC and two GEJ). After a single dose, peak infigratinib plasma concentration was reached at a median time of 3.1 h, with geometric mean C of 85.9 ng/mL and AUC of 637 hng/mL. After 21-day dosing, geometric mean infigratinib C of 204 ng/mL was reached at a median of 4.0 h; geometric mean AUC was 3060 hng/mL. The geometric mean R, (%CV) and R, (%CV) of infigratinib was 2.5 (113.8) and 5.1 (138.2), respectively. A steady state of infigratinib was reached after continuous dosing for 15 days. The metabolites accounting for >10% of infigratinib were BHS697 and CQM157. The PK profiles of infigratinib and its metabolites in Chinese patients with GC or GEJ were largely consistent with known PK profiles of infigratinib from global populations.
英菲格拉替尼是一种 FGFR1-3 选择性口服酪氨酸激酶抑制剂，在存在 FGFR 改变的癌症中显示出临床活性。英菲格拉替尼及其主要代谢物的药代动力学（PK）已在全球人群中得到描述。本研究考察了英菲格拉替尼及其代谢物在中国人患者中的 PK 特征。在这项中国的 II 期、开放标签、单臂研究中，患有 FGFR2 基因扩增的晚期胃癌（GC）或胃食管交界处腺癌（GEJ）患者接受每日一次口服 125mg 英菲格拉替尼，28 天为一个周期，方案为“3 周给药，1 周停药”。采用非房室模型计算血浆 PK 参数。数据来自 21 名患者（19 名 GC 和 2 名 GEJ）。单次给药后，英菲格拉替尼血浆峰浓度中位数达峰时间为 3.1 小时，几何均数 C 为 85.9ng/mL，AUC 为 637hng/mL。21 天给药后，中位达峰时间为 4.0 小时，几何均数 C 为 204ng/mL；几何均数 AUC 为 3060hng/mL。英菲格拉替尼的 R，（%CV）和 R，（%CV）分别为 2.5（113.8）和 5.1（138.2）。连续给药 15 天后达到英菲格拉替尼的稳态。占英菲格拉替尼>10%的代谢物为 BHS697 和 CQM157。GC 或 GEJ 中国患者的英菲格拉替尼及其代谢物的 PK 特征与英菲格拉替尼在全球人群中的已知 PK 特征基本一致。
