GDC-0973 (XL518)

About GDC-0973 (XL518)

GDC-0973 is a potent, highly selective inhibitor of mitogen-activated protein kinase kinase, also known as MEK, a serine/threonine kinase that is a component of the RAS/RAF/MEK/ERK pathway. This pathway mediates signaling downstream of growth factor receptors, and is prominently activated in a wide variety of human tumors. In preclinical studies, oral dosing of GDC-0973 resulted in potent and sustained inhibition of MEK in RAS or BRAF mutant tumor models. GDC-0973 is being developed by Genentech, a member of the Roche Group, under a collaboration agreement with Exelixis.

Collaboration with Genentech

Exelixis discovered GDC-0973 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 GDC-0973 through the end of phase 1, at which point Genentech exercised its option to further develop the compound.

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. Exelixis has the option to co-promote in the United States.

Development Status

Preliminary data from BRIM7, a phase 1b dose escalation study conducted by Roche and Genentech, Exelixis’ collaboration partner, of GDC-0973 in combination with the BRAF inhibitor vemurafenib in patients with locally advanced/unresectable or metastatic melanoma carrying a BRAFV600 mutation, were presented in September 2012 at the European Society of Medical Oncology Annual Meeting (Abstract #LBA28).

As disclosed on ClinicalTrials.gov, a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial evaluating the combination of vemurafenib with GDC-0973 versus vemurafenib in previously untreated BRAFV600 mutation positive patients with unresectable locally advanced or metastatic melanoma was recruiting participants as of November 1, 2012.