(O21) Pharmacokinetic & Safety Assessment of a Novel Anti-CD20 mAb

Abstract: Background Lymphoma, is one of the most common cancers in dogs. Treatment outcomes of the corresponding human cancer have improved with the addition of B-cell-specific, anti-CD20 monoclonal antibodies (mAbs). Similar to human medicine, a novel canine anti-CD20mAb could significantly improve treatment options for dogs with B-cell lymphoma. Hypothesis/Objectives A novel anti-CD20 mAb has been developed with specific binding to canine CD20 and potent killing of target cells in in vitro assays. The purpose of this study was to evaluate the safety and PK/PD of novel anti-CD20mAb in dogs. Animals Healthy laboratory beagle dogs (n=23), ~4 years of age, were randomly selected to receive single or multiple doses of the anti-CD20mAb. Methods In vivo exposure, peripheral B-cell depletion, CBC, and serum chemistry were assessed post single- (0.2 – 10 mg/kg SC) and multiple-dose (0.05- 0.2 mg/kg SC or IV) administration. Serum concentrations were coupled with B-cell kinetics to predict drug effect. Results Detectable levels of drug were observed post SC administration in serum at all dose levels with a mean half-life of ~9.9 days and mean bioavailability of 79%. Drug was well-tolerated at the dose levels tested. With single-dose administration, CD21+ B-cells started to decline an 1-hour post-dose and were completely depleted by 24 hours in all dose groups with onset of recovery ~50 days. Conclusions and Clinical Importance This canine anti-CD20 mAb has good subcutaneous bioavailability and is well-tolerated in vivo at the doses tested. This drug may add to the arsenal of available therapeutics for management of canine lymphoma.