In December 2010, Tekmira announced the initiation of patient dosing in a Phase 1 human clinical trial for TKM-PLK1 in patients with advanced solid tumors. The Phase 1 clinical trial, conducted at oncology centers in the United States, is an open label, multi-dose, dose escalation study designed to evaluate the safety, tolerability and pharmacokinetics of TKM-PLK1 as well as determine the maximum tolerated dose. Secondary objectives of the trial are to measure tumor response and the pharmacodynamic effects of TKM-PLK1 in patients providing biopsies.
Interim results from this Phase 1 study, employing a unique LNP developed for oncology applications, show that TKM-PLK1 was generally well tolerated. To date, TKM-PLK1 has been administered to 21 patients at doses ranging from 0.15 mg/kg to 0.90 mg/kg; a total of 105 doses have been administered. Patients are dosed on an aggressive once weekly protocol with each cycle consisting of three doses followed by a rest week. Pharmacokinetic data from this study showed that Cmax (peak serum concentration of drug) and area under the curve (AUC) were dose proportional, with no evidence of drug accumulation, and that the pharmacokinetic profile of TKM-PLK1 is maintained through multiple cycles of treatment. Pre-clinical animal pharmacokinetic data were predictive for the observed results in man. Importantly, the data confirm that the drug exposure levels achieved in this trial, incorporating Tekmira's proprietary LNP formulation specifically designed to facilitate siRNA delivery to disseminated disease sites, are several fold greater than were achieved in clinical trials using earlier LNP formulations. The most common grade 1-2 adverse events were nausea and fever/chills. There were no dose-dependent changes in liver function tests. Grade 2 infusion-related reactions were observed in 19% of patients. Dose-limiting toxicities observed to date include transient thrombocytopenia in one patient (at 0.9 mg/kg) and hypoxia/dyspnea in one patient (at 0.9 mg/kg). Based on these data, patient enrollment is continuing at 0.75 mg/kg. Once complete, results from the Phase 1 clinical trial, including additional measures of drug activity, will be presented at forthcoming scientific meeting.