Pharmacokinetics (PK) of 2 Dosing Regimens of Palifermin in Patients (Pts) with Hematologic Malignancies (HM) Undergoing High-Dose Chemoradiotherapy and Hematopoietic Stem Cell Transplantation (HSCT).

For pts with HM undergoing HSCT, oral mucositis (OM) is a frequent and debilitating complication that negatively impacts treatment outcomes, patient quality of life, and healthcare resources. Palifermin reduces the incidence and duration of severe OM in the HSCT setting. This phase 1 open-label study assessed the PK of 2 palifermin dosing regimens. Methods: Pts were 18 to 76 years old with HM and a Karnofsky performance score ≥70%. Palifermin was administered intravenously once daily as follows: 60 mcg/kg/day [d] for 3 consecutive days on d -11, -10, and -9 before conditioning (total body irradiation [TBI] + etoposide + cyclophosphamide) and following HSCT on d 0, 1 and 2 (part A) and a single dose of 180 mcg/kg (part B) before conditioning on d -11 and after HSCT on d 0. In part A (6 total doses), PK parameters were assessed after the 1^st, 3^rd, 4^th, and 6^th doses. In part B (2 total doses), assessments were made after each dose administration (d -11 and d 0). Results: In part A, 13 pts received palifermin; in part B, 12 pts received the single dose on d -11 and 11 pts received the single dose on d 0. For both dosing regimens, palifermin concentrations declined rapidly (≥98% decrease) in the first 30 minutes postdose, followed by a slight increase in mean concentrations between 1 and 4 hours and then a terminal decay phase. Respective mean (SD) PK parameter values for the 2 dosing regimens are shown in Table 1. In part A, mean AUC_0-t values were comparable between doses 1 and 3 (within 15%) and 1 and 4 (within 1%). In part B, mean PK parameter values were similar (within 10% of each other) between doses 1 and 2. The mean AUC after the first 180 mcg/kg dose in part B was approximately 4-fold higher than that after the first 60 mcg/kg dose in part A. Mean half-life values ranged between 3.3 to 5.7 hours in part A and the value was 5.4 hours in part B. Conclusion: The PK data in pts receiving HSCT were consistent with approximately dose-linear PK in the dose range of 60 and 180 mcg/kg, with no observed accumulation, based on AUC, after 3 daily doses of 60 mcg/kg in this pt population in the HSCT setting.