PI-043 - CHARACTERIZATION OF GEMTUZUMAB OZOGAMICIN PHARMACOKINETICS IN ADULT PATIENTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA FOLLOWING FRACTIONATED DOSING REGIMEN.

J. Li¹, J. Hibma¹, M. O'Gorman², F. McCush³, L. Kirkovsky¹, Y. Chen¹; ¹Pfizer, La Jolla, CA, USA, ²Pfizer, Groton, CT, USA, ³Pfizer, Chesterfield, MO, USA.

Background: Gemtuzumab ozogamicin (GO) is approved for the treatment of patients with CD33-positive acute myeloid leukemia (AML). No clinical pharmacokinetics (PK) was evaluated in pivotal Phase 3 trial following the new fractionated dosing regimen at 3 mg/m2 on Days 1, 4, and 7. This analysis was conducted using data from the postmarketing requirement study (NCT03727750) to characterize the PK of single-agent GO following the fractionated dosing regimen in patients with relapsed/refractory (R/R) AML.

Methods: PK data from the Phase 4, single arm, open-label study in 50 adult patients with R/R AML was included. GO population PK (popPK) was characterized using the structural components of a pre-established popPK model based on pooled data [N=407] (Hibma et al., 2019). Individual exposure metrics simulated from empirical bayes estimated popPK parameters and estimated by non-compartmental analysis (NCA) from this study were compared against simulated exposure metrics from the historical popPK model.

Results: A 2-compartment popPK model with both linear and time-dependent clearance (CL), and allometric body weight scaling on CL and volume of distribution adequately characterized total antibody PK in adult patients. The geometric mean AUC and Cmax of total antibody following the third dose from the Phase 4 study were 26820 ng.hr/mL and 586 ng/mL (NCA), and 23927 ng.hr/mL and 530 ng/mL (current popPK), versus 27997 ng.hr/mL and 654 ng/mL (historic popPK).

Conclusion: Overall, the clinical PK data from the fractionated dosing regimen for GO in this study confirm the validity of simulated data using a population modeling analysis. No new dose modifications for GO are warranted based on the current analyses.

Hibma J, Knight B. Population Pharmacokinetic Modeling of Gemtuzumab Ozogamicin in Adult Patients with Acute Myeloid Leukemia. Clin Pharmacokinet. 2019 Mar;58(3):335-347. doi: 10.1007/s40262-018-0699-5.