PI-016 - EFFECT OF MILD AND MODERATE HEPATIC IMPAIRMENT ON QUIZARTINIB PHARMACOKINETICS.

H. Zahir¹, K. Lasseter², T. Marbury³, J. Rondon², Y. Bermudez¹, G. Gammon¹, Y. Mostafa Kamel¹, N. Said¹, C. Hsu¹, M. Abutarif¹, M. Zheng¹; ¹Daiichi Sankyo, Basking Ridge, NJ, USA, ²Clinical Pharmacology of Miami, Miami, FL, USA, ³Orlando Clinical Research Center, Orlando, FL, USA.

Background: Quizartinib (Q) is a receptor tyrosine kinase FLT3 inhibitor and a potential therapy for FLT3-ITD AML. Two phase 1, open-label studies (NCT04473664) were conducted to determine the effects of mild or moderate hepatic impairment (HI; based on Child-Pugh [CP] or National Cancer Institute-Organ Dysfunction Working Group criteria [NCI-ODWG]) on the pharmacokinetics (PK) of Q and its active metabolite AC886 compared with matched healthy controls (MHC).

Methods: Blood samples were collected before administration of a single 30-mg Q tablet on day 1, then afterward on days 1-21. The effect of mild or moderate HI on the PK of Q and AC886 were assessed by comparing Cmax, AUClast, and AUCinf in the HI subjects vs MHC using ANOVA.

Results: Subjects with mild HI (CP-A, n=8), moderate HI (CP-B, n=8; NCI-ODWG, n=6), and MHC (CP, n=14; NCI-ODWG, n=6) were enrolled and completed the studies. The effects of mild and moderate HI on Q PK are shown (Table). Q mean T1/2 was longer in CP-A (119h) and CP-B subjects (114h) vs MHC (88h) but was similar in NCI-ODWG moderate HI subjects (93.7h) and MHC (96.3h). Q was well tolerated.

Conclusion: Moderate HI was not associated with increase in Q exposure. Differences were not considered clinically meaningful. No dose adjustment of Q is required in patients with mild or moderate HI.

Table. Effect of Hepatic Impairment on Q and AC886 PK After Administration of Q 30 mg Tablet in Subjects With Mild (Child-Pugh A) or Moderate (Child-Pugh B or NCI-ODWG) Hepatic Impairment and MHC: ANOVA Modela