PLX4032 is an oral and targeted drug that is designed to inhibit the BRAF cancer-causing mutation that occurs in about 50% of melanomas and about 8% of all solid tumors.
The randomised, controlled, phase 3 BRAF Inhibitor 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 milestone payment to Plexxikon from Roche, its co-development partner, under their 2006 collaboration agreement.
Reportedly, Plexxikon is also 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 enrollment ongoing.
BRIM3 is a phase 3 trial expected to enroll approximately 700 previously untreated melanoma patients who will be randomised one-to-one with PLX4032 at a dose of 960mg BID or dacarbazine (DTIC), a comparator drug approved for the treatment of metastatic melanoma.
In the study, the patients will be monitored for safety and efficacy endpoints. The primary endpoint of the trial is overall survival. Secondary endpoints include duration of response, progression-free survival and best overall response rate (BORR).
Whereas, BRIM2 is a phase 2 trial that is expected to enroll approximately 100 patients and is a single-arm study in previously treated melanoma patients. The trial is enrolling patients at 13 sites in the US and Australia.
Reportedly, the 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 and Plexxikon.
Peter Hirth, CEO of Plexxikon, said: “With some tumor shrinkage in nearly all mutation-positive melanoma patients, and 70% of patients achieving at least 30% tumor shrinkage in our most recent clinical study, PLX4032 has shown meaningful anti-tumor activity. The Phase 3 trial, with a primary endpoint of overall survival, will provide an assessment of clinical benefit of PLX4032 in a randomised, controlled study design, which should further build our registration program for this drug.
“We are hopeful that this accelerated development program will enable us to bring this new personalised medicine to melanoma patients as quickly as possible. PLX4032 represents the first drug in Plexxikon’s franchise of oncology drug candidates.”