Xenova Group plc has begun patient enrolment in two pivotal Phase III clinical trials for tariquidar, in which tariquidar is being used as an adjunctive treatment in combination with first-line chemotherapy for non-small cell lung cancer (NSCLC) patients.
Discovered by Xenova, tariquidar, a P-glycoprotein (P-gp) inhibitor, is being developed for the treatment of multidrug resistance (MDR) in cancer with QLT Inc, Xenova's partner for North America.
The two double-blind, randomised, placebo-controlled trials are being carried out in patients with stage IIIb/IV NSCLC at approximately 100 centres located throughout North America and Europe. Patients will receive as first-line therapy paclitaxel/carboplatin and either tariquidar or placebo in one trial and vinorelbine and either tariquidar or placebo in the second. Approximately 1,000 patients will be recruited in total.
The trials are designed to demonstrate the ability of tariquidar to enhance the effectiveness of chemotherapeutic agents affected by MDR and the primary end-point of both trials is overall survival. An interim analysis is planned for mid-2003.
It is anticipated that, on successful completion of the Phase III programme, QLT will file for approval of tariquidar in North America for use in combination with first-line chemotherapy in advanced NSCLC by the end of 2005. NSCLC is the first of several indications for which tariquidar will be investigated. A Phase IIb trial with tariquidar in patients with refractory breast cancer is also underway at the University of Texas MD Anderson Cancer Center.
In August 2001, Xenova signed an exclusive licence agreement with Vancouver-based QLT Inc for the development and marketing in the United States, Canada and Mexico of Xenova's P-gp inhibitor, XR9576 (tariquidar) for the treatment of MDR in cancer.
Under the terms of the agreement, QLT have assumed responsibility for the further development of tariquidar, including Phase III trials, all regulatory filings and the manufacture and sale of tariquidar within those territories covered by the agreement. QLT made an immediate upfront licence payment to Xenova of US$10m (£7.1m) and will provide up to US$45m (£32.0m) in funding for all development activities related to Phase III clinical studies for tariquidar in North America and Europe. Milestones of up to US$50m (£35.6m) and royalties in the range of 15 to 22 per cent depending on the level of North American sales are also receivable by Xenova.