Cobimetinib

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.

• COTELLIC ® 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.ICD-10: C43.9

• None. None.contraindicated

Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of COTELLIC with vemurafenib for patients with melanoma. ( 2.1 ) 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. ( 2.2 ) 2.1 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 . 2.2 Recommended Dosage The recommended dosage regimen of COTELLIC 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 [see Clinical Studies (14) ] . Take COTELLIC with or without food [see Clinical Pharmacology (12.3) ] . If a dose of COTELLIC is missed or if vomiting occurs when the dose is taken, resume dosing with the next scheduled dose. 2.3 Dose Modifications Concurrent CYP3A Inhibitors Do not take strong or moderate CYP3A inhibitors while taking COTELLIC. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking COTELLIC 60 mg, reduce COTELLIC dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume previous dose of COTELLIC 60 mg [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] .

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. ( 5.1 ) 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. The safety of COTELLIC has not been established in patients with decreased left ventricular ejection fraction (LVEF). Evaluate LVEF before treatment, after one month of treatment, then every 3 months thereafter during treatment with COTELLIC. ( 5.3 , 2.3 ) Severe Dermatologic Reactions : Monitor for severe skin rashes. Interrupt, reduce, or discontinue COTELLIC. ( 5.4 , 2.3 ) Serous Retinopathy and Retinal Vein Occlusion : Perform an ophthalmological evaluation at regular intervals and for any visual disturbances. Permanently discontinue COTELLIC for retinal vein occlusion (RVO). ( 5.5 , 2.3 ) Hepatotoxicity : Monitor liver laboratory tests during treatment and as clinically indicated. ( 5.6 , 2.3 ) Rhabdomyolysis : Monitor creatine phosphokinase periodically and as clinically indicated for signs and symptoms of rhabdomyolysis. ( 5.7 , 2.3 ) Severe Photosensitivity : Advise patients to avoid sun exposure. ( 5.8 , 2.3 ) Embryo-Fetal Toxicity : Can cause fetal harm.

The following adverse reactions are discussed in greater detail in other sections of the label: New Primary Cutaneous Malignancies [see Warnings and Precautions (5.1) ] Hemorrhage [see Warnings and Precautions (5.2) ] Cardiomyopathy [see Warnings and Precautions (5.3) ] Serious Dermatologic Reactions [see Warnings and Precautions (5.4) ] Serous Retinopathy and Retinal Vein Occlusion [see Warnings and Precautions (5.5) ] Hepatotoxicity [see Warnings and Precautions (5.6) ] Rhabdomyolysis [see Warnings and Precautions (5.7) ] Severe Photosensitivity [see Warnings and Precautions (5.8) ] Unresectable or Metastatic Melanoma: Most common adverse reactions for COTELLIC (≥20%) are diarrhea, photosensitivity reaction, nausea, pyrexia, and vomiting. The most common (≥5%) Grade 3-4 laboratory abnormalities are increased GGT, increased CPK, hypophosphatemia, increased ALT, lymphopenia, increased AST, increased alkaline phosphatase, hyponatremia. ( 6.1 ) Histiocytic neoplasms: Most common adverse reactions (≥20%) are acneiform dermatitis, diarrhea, infection, fatigue, nausea, edema, dry skin, maculopapular rash, pruritus, dyspepsia, vomiting, dyspnea and urinary tract infections. The most common (≥5%) grade 3-4 lab abnormalities include: Hyponatremia, increased blood creatine phosphokinase, hypokalemia, increased blood creatinine, increased AST, hypocalcemia, lymphopenia, leukopenia, anemia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Lactation: Do not breastfeed while taking COTELLIC. ( 8.2 ) 8.1 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 [see Clinical Pharmacology (12.1) ]. There are no available data on the use of COTELLIC during pregnancy. In animal reproduction studies, oral administration of cobimetinib in pregnant rats during organogenesis was teratogenic and embryotoxic at exposures (AUC) that were 0.9 to 1.4-times those observed in humans at the recommended human dose of 60 mg [see Data ] . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Data Animal Data Administration of cobimetinib to pregnant rats during the period of organogenesis resulted in increased post-implantation loss, including total litter loss, at exposures (AUC) of 0.9–1.4 times those in humans at the recommended dose of 60 mg. Post-implantation loss was primarily due to early resorptions. Fetal malformations of the great vessels and skull (eye sockets) occurred at the same exposures.

Metabolism

The pharmacokinetics of cobimetinib was studied in healthy subjects and cancer patients. Cobimetinib exhibits linear pharmacokinetics in the dose range of 3.5 to 100 mg (i.e., 0.06 to 1.7 times the recommended dosage).

There is no information on overdosage of COTELLIC.

• Nov 10, 2015NDANDA206192Genentech Inc

1. 1Off Label Use45610%
2. 2Diarrhoea43710%
3. 3Rash3919.0%
4. 4Pyrexia3638.4%
5. 5Death2495.7%
6. 6Nausea2295.3%
7. 7Fatigue2144.9%
8. 8Vomiting1854.3%
9. 9No Adverse Event1824.2%
10. 10Acute Kidney Injury1383.2%
11. 11Asthenia1313.0%
12. 12Photosensitivity Reaction1282.9%
13. 13Rash Maculo-papular1242.9%
14. 14Anaemia1202.8%
15. 15Drug Reaction With Eosinophilia And Systemic Symptoms1202.8%

The 10 most recently updated of 122 ClinicalTrials.gov registrations naming Cobimetinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Atezolizumab, Cobimetinib, and Eribulin in Treating Patients With Chemotherapy Resistant Metastatic Inflammatory Breast Cancer
  Active not recruiting · Phase 2 · Interventional · 37 enrolled · M.D. Anderson Cancer Center
  NCT03202316updated 2026-06-10
• Vemurafenib and Cobimetinib in Treating Patients With BRAF V600E Mutation Positive Craniopharyngioma
  Active not recruiting · Phase 2 · Interventional · 24 enrolled · Alliance for Clinical Trials in Oncology
  NCT03224767updated 2026-06-10
• A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC)
  Recruiting · Phase 2 · Interventional · 99 enrolled · Genentech, Inc.
  NCT04302025updated 2026-06-09
• A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors
  Active not recruiting · Phase 2 · Interventional · 176 enrolled · Hoffmann-La Roche
  NCT04931342updated 2026-06-08
• A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC)
  Active not recruiting · Phase 2 · Phase 3 · Interventional · 1,000 enrolled · Hoffmann-La Roche
  NCT03178552updated 2026-06-05
• TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer
  Recruiting · Phase 2 · Interventional · 4,200 enrolled · American Society of Clinical Oncology
  NCT02693535updated 2026-05-29
• Testing the Combination of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers
  Active not recruiting · Phase 1 · Interventional · 42 enrolled · National Cancer Institute (NCI)
  NCT05691504updated 2026-05-13
• A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer)
  Terminated · Phase 1 · Phase 2 · Interventional · 314 enrolled · Hoffmann-La Roche
  NCT03337698updated 2026-05-12
• A Phase IB/II Study of Alectinib Combined With Cobimetinib in Advanced ALK-Rearranged (ALK+) NSCLC
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 16 enrolled · Massachusetts General Hospital
  NCT03202940updated 2026-05-08
• Enasidenib in Combination With Cobimetinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
  Completed · Phase 1 · Interventional · 3 enrolled · City of Hope Medical Center
  NCT05441514updated 2026-05-05

Frequently asked questions

How does Cobimetinib work?

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.

What is Cobimetinib used for?

According to FDA labeling, Cobimetinib carries indications including: COTELLIC ® 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Cobimetinib?

Cobimetinib is classified as Mitogen-activated protein kinase (MEK) inhibitors, Kinase Inhibitor, Kinase Inhibitors, Protein Kinase Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Cobimetinib?

Cobimetinib is marketed under brand names including Cotellic.

What are the contraindications for Cobimetinib?

Cobimetinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.