Biopharmaceutical firm Exelixis has presented updated results from an ongoing Phase Ib clinical trial of the BRAF inhibitor (BRAFi) vemurafenib in combination with the MEK inhibitor cobimetinib (GDC-0973/XL518).
The trial, BRIM7, is being conducted by Roche and Genentech, Exelixis's collaborator and a member of the Roche Group.
It is being conducted in patients with locally advanced/unresectable or metastatic melanoma carrying a BRAFV600 mutation.
Exelixis said the Phase Ib dose escalation study was designed to evaluate the safety and tolerability of cobimetinib in combination with vemurafenib.
The dose escalation stage of the trial included ten dosing cohorts of three to six patients and evaluated three different dosing schedules for the two active treatments.
Cohorts that met the protocol-specified criteria for MTD were expanded and included BRAFi-naïve or vemurafenib-progressing patients.
As of 21 June 2013, the company had treated 128 patients in which 65 patients had disease progression while receiving vemurafenib while 63 persons were BRAFi-naïve.
Of the 63 BRAFi-naïve patients, 42 were previously untreated and 21 had been treated with agents other than a BRAFi.
The company said dose-limiting toxicities were reported in one of six patients in the dose-escalation stage receiving 960mg of vemurafenib bid and 60mg of cobimetinib qd on a 21/7-day schedule (Grade 3 QT interval prolongation), and in one of five patients in the dose escalation stage receiving 960mg of vemurafenib bid and 80mg cobimetinib qd on a 14/14-day schedule.
Dose-limiting toxicities of Grade 3 mucositis and Grade 3 arthralgia were each observed in one of four patients in the dose-escalation stage receiving 960mg vemurafenib bid and 60mg cobimetinib qd on a 28/0-day schedule.
Two cohorts receiving 60mg of cobimetinib qd on a 21/7-day schedule with vemurafenib at either 720mg or 960mg bid were selected for expansion.
Exelixis president and CEO Michael Morrissey said the data presented today, while early-stage, suggest that the preliminary safety profile and activity of the investigational combination of cobimetinib and vemurafenib is promising in BRAFi-naïve patients.
"Importantly, responses in these patients generally occurred early in their course of treatment," Morrissey added.
"We are pleased with the progress Roche has made in advancing cobimetinib, and believe that this Exelixis-discovered compound warrants further study in melanoma, as people with this incurable disease desperately need new options."
Earlier this year, Exelixis received notice from Genentech which noted that the first patient was dosed in a Phase III pivotal trial (coBRIM) evaluating vemurafenib alone or in combination with cobimetinib in previously untreated patients with malignant melanoma harboring the BRAFV600 mutation.
The study is ongoing and currently enrolling patients worldwide and data from the trial is anticipated to be revealed in 2014.
Cobimetinib, an inhibitor of MEK, a serine/threonine kinase that is a component of the RAS/RAF/MEK/ERK pathway, is being developed by Genentech, a member of the Roche Group under a collaboration agreement with Exelixis.
Image: The study is being conducted in patients with locally advanced/unresectable or metastatic melanoma carrying a BRAFV600 mutation. Photo: courtesy of Jmh649.