General Information

Cotellic (cobimetinib) is a kinase inhibitor.

Cotellic is specifically indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib.

Cotellic is supplied as a tablet for oral administration. The recommended dose is 60 mg (three 20 mg tablets) orally taken once daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity. Take Cotellic with or without food. If a dose is missed or if vomiting occurs when the dose is taken, resume dosing with the next scheduled dose.

Clinical Results

FDA Approval

The FDA approval of Cotellic was based on a randomized clinical study of 495 patients with previously untreated, BRAF V600 mutation-positive melanoma that was advanced or could not be removed by surgery. All subjects received vemurafenib and were then randomly selected to also take either Cotellic or a placebo. On average, subjects taking Cotellic plus vemurafenib experienced a delay in the amount of time it took for their disease to worsen (approximately 12.3 months after starting treatment) compared to approximately 7.2 months after starting treatment for those taking vemurafenib only. In addition, subjects taking Cotellic plus vemurafenib lived longer, with approximately 65 percent of subjects alive 17 months after starting treatment as compared to half of those taking vemurafenib only. Additionally, 70 percent of those taking Cotellic plus vemurafenib experienced complete or partial shrinkage of their tumors, compared to 50 percent among those taking vemurafenib plus placebo.

Mechanism of Action

Cotellic (cobimetinib) is a reversible inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase 1 (MEK1) and MEK2. MEK proteins are upstream regulators of the extracellular signal related kinase (ERK) pathway, which promotes cellular proliferation. BRAF V600E and K mutations result in constitutive activation of the BRAF pathway which includes MEK1 and MEK2.