Cobimetinib

Cobimetinib is a MEK inhibitor and belongs to the group of kinase inhibitors. Cobimetinib is used in combination with the BRAF inhibitor vemurafenib for the treatment of advanced melanoma with the BRAF V600 mutation.

The antitumor and antiproliferative effects of cobimetinib are based on inhibition of the MAPK pathway through inhibition of MEK kinase. Cobimetinib enhances the effect of vemurafenib and may counteract adverse effects of the BRAF inhibitor. The mean half-life of cobimetinib is approximately 44 hours. Cobimetinib enhances the effect of vemurafenib and may counteract adverse effects of the BRAF inhibitor (e.g., development of squamous cell carcinoma). Cobimetinib is metabolized by CYP3A and UGT2B7 Corresponding drug-drug interactions are possible.

The recommended dose of cobimetinib is 60 mg (3 tablets of 20 mg each) once daily.

The most common possible side effects include high blood pressure, bleeding, chorioretinopathy, indigestion, papulo-pustular exanthema, rhabdomyolysis or symptomatic CPK elevations, photosensitivity and fever.

Cotellic®

Cobimetinib was granted orphan drug designation by the FDA in 2014 for BRAFV600 mutated malignant melanoma. In November 2015, the U.S. Food and Drug Administration approved cobimetinib for unresectable or metastatic melanoma with a BRAF V600Eor V600K mutation in combination with vemurafenib (Zelboraf). Cobimetinib is not indicated for the treatment of patients with BRAF wild-type melanoma.

1. Ribas A. et al. (2014) Combination of vemurafenib and cobimetinib in patients with advanced BRAF(V600)-mutated melanoma: a phase 1b study. Lancet Oncol 15: 954-965
2. Information from the manufacturer