# Cobimetinib

Source: https://onco.cc/drugs/cobimetinib/  
OnCo record `cobimetinib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Cobimetinib is the MEK partner for vemurafenib, and the first drug approved for histiocytic neoplasms.

## Summary

Cobimetinib is an allosteric MEK1/2 inhibitor given 60 mg once daily for 21 days of each 28-day cycle with the BRAF inhibitor vemurafenib, blocking two consecutive steps of the MAPK pathway. coBRIM (2015) showed PFS of 12.3 versus 7.2 months when it was added to vemurafenib in BRAF V600 melanoma. It is also approved with atezolizumab and vemurafenib (IMspire150, 2020), the first checkpoint plus targeted triplet in melanoma, and alone for histiocytic neoplasms (2022), the first drug approved for that group of rare diseases. Retinopathy, photosensitivity and creatine kinase elevation are the characteristic toxicities. Its melanoma use is limited by competition from dabrafenib-trametinib and encorafenib-binimetinib, and the value of the IMspire150 triplet remains debated. For a newcomer, cobimetinib is the MEK partner for vemurafenib and the go-to drug for histiocytosis.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-07
- Brand: Cotellic
- Modality: Small-molecule kinase inhibitor (MEK1/2)
- Mechanism: Allosteric MEK1/2 inhibitor.
- Approvals: US 2015: BRAF V600 melanoma with vemurafenib; US 2020: With atezolizumab and vemurafenib in BRAF V600 melanoma; US 2022: Histiocytic neoplasms
- Dosing: Oral; 60 mg once daily for 21 days of each 28-day cycle, with vemurafenib

## Notes

- IMblaze370 tested cobimetinib with atezolizumab against regorafenib in previously treated, mostly microsatellite-stable metastatic colorectal cancer and found no difference in overall survival (8.87 against 8.51 months, hazard ratio 1.00), ending the hypothesis that MEK inhibition could make these tumours immunotherapy-sensitive.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Cobimetinib
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Cobimetinib

## Connected records

- cancers: [Advanced melanoma (unresectable stage III and stage IV)](https://onco.cc/cancers/advanced-melanoma/), [BRAF V600-mutant melanoma](https://onco.cc/cancers/braf-v600-melanoma/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Craniopharyngioma](https://onco.cc/cancers/craniopharyngioma/), [Erdheim-Chester disease](https://onco.cc/cancers/erdheim-chester-disease/), [Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms](https://onco.cc/cancers/histiocytoses/), [Melanoma](https://onco.cc/cancers/melanoma/), [Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement)](https://onco.cc/cancers/lch-multisystem/), [Rosai-Dorfman-Destombes disease](https://onco.cc/cancers/rosai-dorfman-disease/), [Single-system Langerhans cell histiocytosis (bone, skin or one other organ)](https://onco.cc/cancers/lch-single-system/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BRAF](https://onco.cc/targets/braf/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Vemurafenib](https://onco.cc/drugs/vemurafenib/)
- companies: [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- pathways: [Melanoma (KEGG map)](https://onco.cc/pathways/melanoma-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- trials: [A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors](https://onco.cc/trials/nct04931342/), [A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC)](https://onco.cc/trials/nct04302025/), [Belvarafenib in Combination With Cobimetinib in Patients With Locally Advanced or Metastatic NRAS-Mutant Melanoma](https://onco.cc/trials/nct07449754/), [CheckMate 142](https://onco.cc/trials/checkmate-142/), [coBRIM](https://onco.cc/trials/cobrim/), [CUPISCO](https://onco.cc/trials/cupisco/), [DETERMINE](https://onco.cc/trials/determine-trial/), [DETERMINE Trial Treatment Arm 05: Vemurafenib in Combination With Cobimetinib in Adult Patients With BRAF Positive Cancers.](https://onco.cc/trials/nct05768178/), [IMblaze370](https://onco.cc/trials/imblaze370/), [IMspire150](https://onco.cc/trials/imspire150/), [MyPathway](https://onco.cc/trials/mypathway/), [TAPUR (Targeted Agent and Profiling Utilization Registry)](https://onco.cc/trials/tapur/), [Testing A New Combination of Anti-cancer Immune Therapies, Atezolizumab and CDX-1127 (Varlilumab) With or Without the Addition of a Third Anti-cancer Drug, Cobimetinib, for Advanced-Stage Biliary Tract Cancer](https://onco.cc/trials/nct04941287/), [Using Tumor Models to Determine Treatments](https://onco.cc/trials/nct06813079/)
- people: [Grant McArthur](https://onco.cc/people/mcarthur-grant/)
- key papers: [Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease](https://onco.cc/key-papers/paper-rosai-dorfman-destombes-consensus-recommendations-blood-2018/), [Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis and treatment in the molecular era](https://onco.cc/key-papers/paper-erdheim-chester-disease-consensus-recommendations-blood-2020/)
- biomarkers: [BRAF V600E (and V600K)](https://onco.cc/biomarkers/braf-v600e/)

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