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    DRUG:

    Cotellic (cobimetinib)

    i
    Other names: GDC-0973, RG-7420, XL518, RO 5514041, RG7421, XL-518, R-7421, RO-5514041, GDC 0973, R 7421, GDC0973, R7421, RG 7421, RO5514041, XL 518
    Company:
    Exelixis, Roche
    Drug class:
    MEK1 inhibitor
    Related drugs:
    2d
    Inhibitory effect of lonafarnib on anaplastic thyroid carcinoma cell lines and a nude mouse xenograft model (PubMed, Zhejiang Da Xue Xue Bao Yi Xue Ban)
    Lonafarnib effectively suppresses the malignant progression of anaplastic thyroid carcinoma both in ATC cell lines and in a BALB/c nude mouse xenograft model. The mechanism involves inhibition of Ras farnesylation and the downstream ERK signaling pathway, leading to activation of Caspase-3/PARP-mediated apoptosis and GSDME-mediated pyroptosis.
    Preclinical • Journal • PARP Biomarker
    |
    CASP3 (Caspase 3) • ANXA5 (Annexin A5) • GSDME (Gasdermin E)
    |
    Cotellic (cobimetinib) • Lenvima (lenvatinib)
    14d
    Improving public cancer care by implementing precision medicine in Norway (2023-507894-16-00)
    P1/2, N=1000, Recruiting, Oslo University Hospital HF | N=6000 --> 1000
    Enrollment change
    |
    Avastin (bevacizumab) • Lynparza (olaparib) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • Rozlytrek (entrectinib) • imatinib • Alecensa (alectinib) • Cotellic (cobimetinib) • bortezomib • Piqray (alpelisib) • Zejula (niraparib) • Retevmo (selpercatinib) • Zykadia (ceritinib) • fulvestrant • Jemperli (dostarlimab-gxly) • Pemazyre (pemigatinib) • Tepmetko (tepotinib) • Tabrecta (capmatinib) • dexamethasone • Erivedge (vismodegib) • melphalan • dactinomycin • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf) • hydroxyurea
    16d
    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)
    29d
    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)
    29d
    Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
    P1/2, N=314, Terminated, Hoffmann-La Roche | Completed --> Terminated; Study was closed early as the sponsor decided not to continue development of certain treatment combinations.
    Trial termination
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • tiragolumab (RG6058) • Repatha (evolocumab) • camonsertib (RP-3500) • cibisatamab (RG7802) • ciforadenant (CPI-444) • zanzalintinib (XL092)
    1m
    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)
    1m
    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)
    1m
    NeoACTIVATE: Vemurafenib, Cobimetinib, Atezolizumab, and Tiragolumab in Treating Patients With High-Risk Stage III Melanoma (clinicaltrials.gov)
    P2, N=64, Completed, Mayo Clinic | Active, not recruiting --> Completed
    Trial completion
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600
    |
    Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Cotellic (cobimetinib) • tiragolumab (RG6058)
    1m
    Real-world effectiveness of molecular-matched therapies in salivary gland cancer. (PubMed, ESMO Open)
    Comprehensive molecular testing in SGC may allow access to MMT, with a subset of patients experiencing clinical benefit from this strategy.
    Journal • Real-world evidence • Tumor mutational burden • PD(L)-1 Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • ETV6 (ETS Variant Transcription Factor 6)
    |
    BRAF V600E • TMB-H • BRAF V600 • RAS wild-type • HRAS mutation
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Zelboraf (vemurafenib) • Vitrakvi (larotrectinib) • Cotellic (cobimetinib)
    2ms
    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)
    2ms
    COTESARC: MEK Inhibitor and a PDL1 Inhibitor Patients With Locally Advanced and/or Metastatic Soft Tissue Sarcoma (clinicaltrials.gov)
    P1/2, N=229, Completed, Centre Leon Berard | Active, not recruiting --> Completed
    Trial completion • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden)
    |
    FoundationOne® CDx
    |
    Tecentriq (atezolizumab) • Cotellic (cobimetinib)
    2ms
    Phase separation-based HTS identifies cobimetinib as a YAP-TEAD inhibitor that suppresses hyperactivated YAP-induced cancer progression. (PubMed, Sci Transl Med)
    The Hippo signaling pathway prevents unchecked cell growth, coordinates apoptosis, and preserves proper organ function. Furthermore, it bolstered the efficacy of the first-line drugs sorafenib and lenvatinib in inhibiting both hepatocellular carcinoma tumor growth and tumorigenesis. These findings establish a strategy for identifying and refining inhibitors of the YAP-TEAD complex in the treatment of cancers driven by aberrant YAP-TEAD activity.
    Journal
    |
    MAP2K1 (Mitogen-activated protein kinase kinase 1)
    |
    sorafenib • Cotellic (cobimetinib) • Lenvima (lenvatinib)