Cobimetinib

What it is and how it works

Mechanism of Action 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. In mice implanted with tumor cell lines expressing BRAF V600E, cobimetinib inhibited tumor cell growth. Cobimetinib and vemurafenib target two different kinases in the RAS/RAF/MEK/ERK pathway.

Indications

® is a kinase inhibitor indicated: For the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib. ( 1.1 , 14.1 ) As a single agent for the treatment of adult patients with histiocytic neoplasms. ( 1.2 , 14.2 ) Unresectable or Metastatic Melanoma COTELLIC ® is indicated for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib. Histiocytic Neoplasms COTELLIC®, as a single agent, is indicated for the treatment of adult patients with histiocytic neoplasms.

Dosage and administration (summary)

Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of COTELLIC with vemurafenib for patients with melanoma. The recommended dose is 60 mg orally once daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity. Take COTELLIC with or without food. Patient Selection for Treatment of Melanoma Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with COTELLIC with vemurafenib. Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics .

Contraindications

None. None.

Warnings and precautions

Review the Full Prescribing Information for vemurafenib for information on the serious risks of vemurafenib. New primary malignancies, cutaneous and non-cutaneous : Monitor patients for new malignancies prior to initiation of therapy, while on therapy, and for up to 6 months following the last dose of COTELLIC. Hemorrhage : Major hemorrhagic events can occur with COTELLIC. Monitor for signs and symptoms of bleeding. ( 5.2 , 2.3 ) Cardiomyopathy : The risk of cardiomyopathy is increased in patients receiving COTELLIC with vemurafenib compared with vemurafenib as a single agent.

Pregnancy

Pregnancy Risk Summary Based on findings from animal reproduction studies and its mechanism of action, COTELLIC can cause fetal harm when administered to a pregnant woman . There are no available data on the use of COTELLIC during pregnancy.

Storage and supply

Storage and Stability: Store at room temperature below 30°C (86°F).

Source: Cobimetinib (Cotellic) — US FDA prescribing information, 2026-07-29, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.