Pharmacokinetics of infigratinib and its active metabolites in Chinese patients with advanced gastric cancer harboring FGFR2 gene amplification

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-max of 85.9 ng/mL and AUC(0-t) of 637 h*ng/mL. After 21-day dosing, geometric mean infigratinib C-max,C-ss of 204 ng/mL was reached at a median of 4.0 h; geometric mean AUC(0-24,ss) was 3060 h*ng/mL. The geometric mean R-ac,(Cmax) (%CV) and R-ac,(AUC0-24) (%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.