Cobimetinib

Cobimetinib (formerly GDC-0973/XL518) is a selective inhibitor of MEK, also known as mitogen-activated protein kinase kinase. MEK is a dual specificity kinase that is a component of the RAS/RAF/MEK/ERK pathway. This pathway mediates signaling downstream of growth factor receptors, and is activated in a wide variety of human tumors. In preclinical studies, cobimetinib resulted in inhibition of MEK in RAS- or BRAF-mutant tumor models. Cobimetinib is being developed by Roche and Genentech (a member of the Roche Group) under a collaboration agreement with Exelixis.

Collaboration with Genentech

Exelixis discovered cobimetinib internally and advanced the compound into clinical phase 1 evaluation. In late 2006, Exelixis entered into a worldwide co-development agreement with Genentech, a member of the Roche Group, 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 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 collaboration agreement to provide up to 25% of the total sales force in the United States.

Regulatory Approvals to Treat Advanced Melanoma

On November 10, 2015, the U.S. Food & Drug Administration approved cobimetinib for the treatment of unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib. In the United States, cobimetinib is marketed as COTELLIC®. For more information on COTELLIC, including important safety information, please click here.

On November 25, 2015, the European Commission (EC) approved COTELLIC for use in combination with vemurafenib for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation. Roche was the sponsor of the Marketing Authorization Application, and the EC’s decision followed a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use delivered in September 2015.

COTELLIC received its first regulatory approval in Switzerland in August 2015, and was also approved in Canada in February 2016.

A Broad Development Program for Cobimetinib

Genentech (a member of the Roche Group) has been responsible for cobimetinib’s clinical development since Genentech opted to further develop the compound following determination of maximum tolerated dose in phase 1. Since then, the companies have undertaken a clinical development program aimed at evaluating cobimetinib’s potential in combination with a variety of investigational and approved therapies.

Additional clinical trials of cobimetinib include:

  • A phase 1b/2 combination study with RG7446, an anti-PDL1 antibody, with expansion cohorts in KRAS-mutant metastatic colorectal cancer, non-small cell lung cancer and melanoma.
  • A phase 1b combination trial evaluating the combination of vemurafenib, cobimetinib, and RG7446 in metastatic melanoma
  • A randomized phase 2 trial investigating the combination of cobimetinib and paclitaxel, a chemotherapy, versus paclitaxel on its own in first-line metastatic triple-negative breast cancer

For more information on cobimetinib clinical trials, please visit www.clinicaltrials.gov.

Cobimetinib is the subject of investigation in a variety of ongoing clinical trials; its safety and efficacy profile in these trials has not yet been established.