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Clin Pharmacokinet. 2015 Oct;54(10):1071-81. doi: 10.1007/s40262-015-0258-2.

Population Pharmacokinetics of ABT-806, an Investigational Anti-Epidermal Growth Factor Receptor (EGFR) Monoclonal Antibody, in Advanced Solid Tumor Types Likely to Either Over-Express Wild-Type EGFR or Express Variant III Mutant EGFR.

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Department of Clinical Pharmacology and Pharmacometrics, AbbVie Inc., One North Waukegan Road, AP13A, North Chicago, IL, 60064, USA.
Department of Clinical Pharmacology and Pharmacometrics, AbbVie Inc., One North Waukegan Road, AP13A, North Chicago, IL, 60064, USA.
Oncology Development, AbbVie Inc., North Chicago, IL, USA.



ABT-806 is a veneered 'humanized' recombinant IgG1κ antibody that is specific for a unique epitope of human epidermal growth factor receptor (EGFR) expressed only on tumor cells with the EGFRde2-7 (EGFRvIII) deletion mutant as well as tumors with wild-type amplified receptors. We aimed to develop a population pharmacokinetic model of ABT-806 in cancer patients, and to evaluate fixed versus body weight-based dosing regimens.


The pharmacokinetics of ABT-806 were evaluated in a phase I, open-label study in cancer patients following intravenous infusion of ABT-806 every other week. A total of 587 serum concentrations of ABT-806 from 61 patients were analyzed using non-linear mixed-effects modeling. The impact of body weight-based and fixed dosing of ABT-806 was evaluated using a simulation approach.


A two-compartment model with linear elimination was used to describe the serum concentration-time data of ABT-806. The population estimates of the apparent clearance from the central (CLc) and peripheral (CLp) compartments were 0.011 and 0.025 L/h, respectively. The apparent volume of distribution estimates of the central (V 1) and peripheral (V 2) compartments were 3.5 and 3.3 L, respectively. The estimates of inter-subject variability (percentage coefficient of variation) in CLc, CLp, V 1, and V 2 were 38, 37, 20, and 48 %, respectively. Albumin on CLc and body weight on V 1 were statistically significant covariates; however, they explained 18 and 30 % of the inter-individual variability of clearance and V 1, respectively. Simulation results indicated that fixed and body weight-based dosing regimens yield similar steady-state concentrations and overall variability.


ABT-806 demonstrated a unique pharmacokinetic profile compared to the marketed monoclonal antibodies against EGFR. The analysis indicates it is feasible to switch to fixed doses in subsequent clinical trials of ABT-806.

[Indexed for MEDLINE]

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