Cobimetinib

Cobimetinib (formerly GDC-0973/XL518) è un potente inibitore altamente selettivo del MEK anche conosciuto come protein chinasi mitogeno attivata. Il mEK è una serina/treonina chinasi che è un componente della via RAS/RAF/MEK/ERK. Questa via media segnalando il flusso dei recettori dei fattori di crescita ed è prevalentemente attivata in una ampia varietà di tumori. In studi preclinici dosi orali di cobimetinib risultavano in una potente e sostanziale riduzione del MEK in tumori RAS o BRAF mutanti. Cobimetinib è stato sviluppato da iRoche and Genentech sotto un accordo di collaborazione con Exelixis.

Exelixis discovered cobimetinib internally and advanced the compound to investigational new drug (IND) status. In late 2006, Exelixis entered into a worldwide co-development agreement with Genentech, under which Exelixis received initial upfront and milestone payments for signing the agreement and submitting the IND. Exelixis was responsible for development of cobimetinib through the initial phase 1 study, and Genentech exercised its option to develop the compound further  Exelixis is entitled to an initial equal share of U.S. profits and losses, which will decrease as sales increase, and will share equally in the U.S. marketing and commercialization costs. Exelixis is eligible to receive royalties on any sales of the product outside the United States. In November 2013, Exelixis exercised its option under the co-development agreement to provide up to 25% of the total sales force in the United States, should cobimetinib be approved.

Metastatic Melanoma: In July 2014, Genentech and Exelixis announced positive top-line results from coBRIM, the phase 3 pivotal trial evaluating cobimetinib in combination with vemurafenib in previously untreated patients with unresectable locally advanced or metastatic melanoma harboring a BRAFV600 mutation. coBRIM met its primary endpoint, delivering a statistically significant increase in progression-free survival for the combination as compared to vemurafenib alone. Based on the results from coBRIM, Genentech announced plans to initiate regulatory filings before the end of 2014.

Additional Trials Involving Cobimetinib
Additional phase 1 trials are ongoing assessing the ability to combine cobimetinib with other agents. These novel combinations are being studied in patients with advanced solid tumors. In some of these trials, entry is restricted to patients whose tumors carry specific genetic mutations. For more information on cobimetinib clinical trials, please visit www.ClinicalTrials.gov.