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    DRUG CLASS:

    MEK1 inhibitor

    Related drugs:
    1m
    A Study to Evaluate the Safety and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Nivolumab in Patients With NRAS-mutant Advanced Melanoma. (clinicaltrials.gov)
    P1, N=65, Active, not recruiting, Genentech, Inc. | Trial completion date: Jun 2027 --> Dec 2026 | Trial primary completion date: Jun 2027 --> Dec 2026
    Trial completion date • Trial primary completion date • IO biomarker
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    NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation
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    Opdivo (nivolumab) • Cotellic (cobimetinib) • belvarafenib (RG6185)
    1m
    A randomized phase 2 study of combination atezolizumab and varlilumab (CDX-1127) with or without cobimetinib in previously-treated unresectable biliary tract cancer. (PubMed, Clin Cancer Res)
    The combinations of atezolizumab and varlilumab with/without cobimetinib were safe but neither meaningfully improved outcomes in BTC treated in the later lines. Correlative tissue studies validated preclinical work that MEK inhibition increases CD8+TILs.
    P2 data • Journal
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    CD8 (cluster of differentiation 8) • CD27 (CD27 Molecule)
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    Tecentriq (atezolizumab) • Cotellic (cobimetinib) • varlilumab (CDX 1127)
    2ms
    BEAT-MBM: Bevacizumab and Atezolizumab With or Without Cobimetinib in Treating Patients With Untreated Melanoma Brain Metastases (clinicaltrials.gov)
    P2, N=29, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2028
    Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • PD-1 (Programmed cell death 1)
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    PD-L1 expression • BRAF V600 • BRAF wild-type
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    Avastin (bevacizumab) • Tecentriq (atezolizumab) • Cotellic (cobimetinib)
    2ms
    A vasculogenic mimicry subtype unveiled by integrated multi-omics predicts prognosis and guides immunotherapy in MIBC. (PubMed, Front Bioinform)
    Combined treatment with the MEK inhibitor TAK-733 and immune checkpoint inhibitors was proposed as a promising therapeutic strategy for this subgroup. This novel VM-based molecular subtyping system for MIBC shows strong potential for clinical application in prognosis prediction, immunotherapy response evaluation, and targeted drug discovery, providing a framework to guide personalized treatment strategies for MIBC patients.
    Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden)
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    REC-4881
    2ms
    MoST Addendum 12: Cancer Molecular Screening and Therapeutics (MoST) Program and ASPiRATION subprogram, Addendum 12 – substudies 27-30: Vemurafenib and Cobimetinib (ACTRN12620000861954)
    P2, N=64, Completed, University of Sydney | Active, not recruiting --> Completed
    Trial completion
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600 • BRAF positive
    |
    Zelboraf (vemurafenib) • Cotellic (cobimetinib)
    3ms
    MEK inhibitor cobimetinib increases calreticulin and induces immune modulation in TNBC. (PubMed, J Mol Med (Berl))
    Notably, we observed differential immunomodulatory effects of cobimetinib in tumor-bearing mice compared to non-tumor-bearing immunocompetent mice. Our findings indicate that MEK inhibition is associated with ICD-related molecular alterations, and that cobimetinib may contribute to immune modulation in TNBC.
    Journal • IO biomarker • CALR
    |
    CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • MAPK1 (Mitogen-activated protein kinase 1) • BAX (BCL2-associated X protein) • CASP8 (Caspase 8) • CALR (Calreticulin) • BAK1 (BCL2 Antagonist/Killer 1)
    |
    Cotellic (cobimetinib)
    3ms
    MEK interactions tune RAF kinase sensitivity to conformation-selective inhibition. (PubMed, Nat Chem Biol)
    Building on this insight, we developed cobimetinib analogs with enhanced sensitization properties. Together, our findings provide a mechanistic framework for understanding the cellular determinants of DFG-out-stabilizing inhibitor sensitivity and offer strategies for optimizing synergistic RAF-MEK inhibitor combinations.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    Cotellic (cobimetinib)
    3ms
    mTOR inhibition enhances the antitumor efficacy of pan-RAF-MEK blockade by inhibiting the ATF4-MTHFD2 pathway. (PubMed, Cell Death Dis)
    Human and murine models resistant to combined belvarafenib and cobimetinib exhibited elevated levels of ATF4 and MTHFD2 and were sensitive to sapanisertib. This study provides promising treatment opportunities for patients with non-BRAF-mutant melanomas, or those who relapse following belvarafenib and cobimetinib combination therapy.
    Journal
    |
    NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • ATF4 (Activating Transcription Factor 4) • MTHFD2 (Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 2)
    |
    BRAF mutation
    |
    Cotellic (cobimetinib) • sapanisertib (CB-228) • belvarafenib (RG6185)
    3ms
    Enasidenib in Combination With Cobimetinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=3, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: May 2027 --> Mar 2026 | Trial primary completion date: May 2027 --> Mar 2026
    Trial completion • Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • RIT1 (Ras Like Without CAAX 1)
    |
    KRAS mutation • IDH2 mutation • RAS mutation
    |
    Cotellic (cobimetinib) • Idhifa (enasidenib)
    3ms
    MAPKeeper 301: Atebimetinib + GnP as a First Line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma (clinicaltrials.gov)
    P3, N=510, Recruiting, Immuneering Corporation
    New P3 trial
    |
    gemcitabine • albumin-bound paclitaxel • atebimetinib (IMM-1-104)
    3ms
    A Phase 2 Study of Luvometinib Combined With Anlotinib in KRAS-mutated NSCLC (clinicaltrials.gov)
    P2, N=48, Not yet recruiting, Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
    New P2 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    Focus V (anlotinib) • Fumaining (luvometinib)
    4ms
    CONCERTO: Cobimetinib in Newly Diagnosed or HMA-treated CMML Patients With RAS Pathway Mutations (clinicaltrials.gov)
    P2, N=14, Active, not recruiting, University of Utah | N=29 --> 14
    Enrollment change
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCR (BCR Activator Of RhoGEF And GTPase) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
    |
    BRAF mutation
    |
    Cotellic (cobimetinib)