Population pharmacokinetics analysis of camidanlumab tesirine in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma

Purpose The objective of this analysis was to develop a population pharmacokinetic (PPK) model to characterize camidanlumab tesirine (Cami) pharmacokinetics based on the phase 1 study in relapsed/refractory lymphoma (NCT02432235). Methods An initial PPK model was developed based on a two-compartment model with parallel linear and nonlinear elimination pathways. Pharmacokinetic parameters were evaluated for correlation with potential demographic covariates; significant covariates were retained in the final model. Results In the final PPK model, baseline weight effects were included on clearance (CL), intercompartmental clearance (Q), and the volumes of distribution in the central (V-1) and peripheral (V-2) compartments. The baseline soluble CD25 (sCD25) effect was included on CL and maximum velocity of saturable clearance (V-max); sex effect was included on CL and V-1; and ethnicity effect was included on deconjugation clearance (CLdec). For a typical patient, CL and CLdec were 0.516 and 0.21 L/day, respectively (tAb elimination half-life: 18.72 days); V-1 and V-2 were 4.41 and 2.67 L, respectively; V-max was 0.49 mg/day; the Michaelis-Menten constant (K-m) was 0.409 mu g/mL; and the first-order rate for decrease of V-max (K-DES) was 0.0197/day. Cami exposure was higher for patients with low baseline sCD25, higher body weight, and females. Conclusions The final model described the observed data well, estimates of PK parameters were obtained, and covariates with significant effects on Cami exposure were identified. Altogether, this final PPK model provides a robust basis for analysis of Cami exposure-response relationships and further supports identification of the optimal Cami dosing schedule for patients with relapsed/refractory lymphoma.

Automated summary

The purpose of this study was to develop a population pharmacokinetic (PPK) model to characterize the pharmacokinetics of camidanlumab tesirine (Cami) in patients with relapsed/refractory lymphoma. The final model obtained estimates of pharmacokinetic parameters and identified covariates that significantly affect Cami exposure.