Plexxikon Inc announced that enrolment has been initiated and the first patient has been dosed in a pivotal phase-3 trial of PLX4032 (RG7204) in patients with metastatic melanoma. PLX4032 is a novel, oral and highly targeted drug that is designed to inhibit the BRAF cancer-causingmutation that occurs in about 50 percent of melanomas and about eight percent of all solid tumours. The randomized, controlled, phase-3 'BRAFInhibitor in Melanoma' (BRIM3) trial in previously untreated patients is part of the planned registration program for PLX4032. The initiation of the phase-3 trial has triggered a significant milestone payment to Plexxikon from Roche, its co-development partner, under their 2006 collaboration agreement. Plexxikon also is entitled to receive additional payments for further milestone achievements as well as royalties on sales of PLX4032. A phase-2 trial (BRIM2) in previously treated melanoma patients was initiated in September 2009, with enrolment ongoing.

“With some tumour shrinkage in nearly all mutation-positive melanoma patients, and 70 per cent of patients achieving at least 30 per cent tumour shrinkage in our most recent clinical study, PLX4032 has shown meaningful anti-tumour activity. The phase-3 trial, with a primary endpoint of overall survival, will provide an assessment of clinical benefit of PLX4032 in a randomized, controlled study design, which should further build our registration program for this drug,” stated K Peter Hirth, chief executive officer of Plexxikon. “We are hopeful that this accelerated development program will enable us to bring this new personalized medicine to melanoma patients as quickly as possible. PLX4032 represents the first drug in Plexxikon’s promising franchise of oncology drug candidates.”

BRIM3 is a phase-3 trial expected to enroll approximately 700 previously untreated melanoma patients who will be randomized one-to-one with PLX4032 at a dose of 960 mg BID or dacarbazine (DTIC), a comparator drug approved for the treatment of metastatic melanoma. Patients will be monitored throughout the study for safety and efficacy endpoints. The primary endpoint of this trial is overall survival. Secondary endpoints include duration of response, progression-free survival and best overall response rate (BORR). The BRIM3 trial is a multicenter study being conducted at approximately 100 sites, including sites in the United States, Australia, Europe and Canada, with sites continuing to open through Q2 2010.

BRIM2 is a phase-2 trial expected to enrol approximately 100 patients and is a single-arm study in previously treated melanoma patients. This trial is enrolling patients at 13 sites in the US and Australia.

Patients enrolling in both BRIM3 and BRIM2 are being selected using an investigational companion diagnostic test that detects the BRAF mutation. This diagnostic is being co-developed in parallel with PLX4032 by Roche Molecular Systems, Inc. and Plexxikon.

Plexxikon is a leader in the structure-guided discovery and development of novel small molecule pharmaceuticals to treat human disease.