Pemigatinib is a fibroblast growth factor receptor 1-3 inhibitor used to treat cholangiocarcinoma. A compartmental population pharmacokinetics model was developed using data from 318 patients with cancer enrolled in a phase 1 dose-escalation/dose-expansion study, a phase 1 Japanese PK bridging study, and a phase 2 cholangiocarcinoma study. The final model for pemigatinib was a 2-compartment disposition model with first-order absorption and linear elimination. All fixed- and random-effect parameters were estimated with good precision, and no apparent biases in the overall model fit were observed. For females, the estimated typical pemigatinib absorption rate constant (ka ) and oral clearance (CL/F) were estimated (1.49 L/h and 10.3 L/h, respectively). For males, the typical apparent clearance and ka are 19.0% higher and 56.5% lower, respectively, compared with females. Typical apparent volume of distribution of the central compartment (Vc /F) and peripheral compartment for a 73.3-kg patient was estimated to be 122.0 L and 80.1 L, respectively; both increased with body weight. Phosphate binder coadministration decreases typical pemigatinib CL/F by 14.1%. Proton pump inhibitor coadministration increases typical pemigatinib apparent Vc/F by 24.4%. Phosphate binders and sex contribute a <20% change to CL/F. The impact of the investigated covariates on pemigatinib pharmacokinetics are not clinically significant.
Keywords: FGFR inhibitor; INCB054828; advanced malignancy; pemigatinib; population pharmacokinetics.
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