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    BIOMARKER:

    MAP2K1 P124L

    i
    Other names: MAP2K1, MAPKK1, MEK1, PRKMK1, Mitogen-activated protein kinase kinase 1
    Entrez ID:
    5604
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    6ms
    A Study of Mirdametinib on Its Own or in Combination With Fulvestrant in People With Solid Tumor Cancer (clinicaltrials.gov)
    P1b, N=6, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Sep 2027 --> Oct 2023 | Trial primary completion date: Sep 2027 --> Oct 2023
    Trial completion • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
    |
    ER positive • HR positive • HER-2 negative • MAP2K1 mutation • MAP2K1 P124L • MAP2K1 P124S • MAP2K2 mutation • MAP2K1 C121S • MAP2K1 F53L • MAP2K1 K57N • MAP2K1 P124
    |
    fulvestrant • mirdametinib (PD-0325901)
    10ms
    A Study of Mirdametinib on Its Own or in Combination With Fulvestrant in People With Solid Tumor Cancer (clinicaltrials.gov)
    P1b, N=6, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=150 --> 6
    Enrollment closed • Enrollment change • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
    |
    ER positive • HR positive • HER-2 negative • MAP2K1 mutation • MAP2K1 P124L • MAP2K1 P124S • MAP2K2 mutation • MAP2K1 C121S • MAP2K1 F53L • MAP2K1 K57N • MAP2K1 P124
    |
    fulvestrant • mirdametinib (PD-0325901)
    11ms
    A Study of Mirdametinib on Its Own or in Combination With Fulvestrant in People With Solid Tumor Cancer (clinicaltrials.gov)
    P1b, N=150, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2024 --> Sep 2027 | Trial primary completion date: Sep 2024 --> Sep 2027
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
    |
    ER positive • HR positive • HER-2 negative • MAP2K1 mutation • MAP2K1 P124L • MAP2K1 P124S • MAP2K2 mutation • MAP2K1 C121S • MAP2K1 F53L • MAP2K1 K57N • MAP2K1 P124
    |
    fulvestrant • mirdametinib (PD-0325901)
    over1year
    Investigating the Retained Inhibitory Effect of Cobimetinib against p.P124L Mutated MEK1: A Combined Liquid Biopsy and in Silico Approach. (PubMed, Cancers (Basel))
    The samples at different time points were collected from a BRAF-mutant melanoma patient who developed an early resistance to dabrafenib/trametinib...With an in silico modeling, we identified cobimetinib as an alternative MEK inhibitor, and consequently suggested a therapy switch to vemurafenib/cobimetinib...The cobimetinib administration led to an important reduction in the BRAF p.V600E and MEK1 p.P124L allele fractions and in the CMC number, features suggestive of a putative response. In summary, this study emphasizes the usefulness of a liquid biopsy-based approach combined with in silico simulation, to track real-time tumor evolution while assessing the best treatment option.
    Journal • Liquid biopsy
    |
    MAP2K1 (Mitogen-activated protein kinase kinase 1)
    |
    BRAF V600E • BRAF V600 • MAP2K1 P124L • MAP2K1 P124
    |
    Mekinist (trametinib) • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • Cotellic (cobimetinib)
    over2years
    A Study of Mirdametinib on Its Own or in Combination With Fulvestrant in People With Solid Tumor Cancer (clinicaltrials.gov)
    P1b, N=150, Recruiting, Memorial Sloan Kettering Cancer Center
    Clinical • New P1 trial • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
    |
    ER positive • HR positive • HER-2 negative • MAP2K1 mutation • MAP2K1 P124L • MAP2K1 P124S • MAP2K2 mutation • MAP2K1 C121S • MAP2K1 F53L • MAP2K1 K57N • MAP2K1 P124
    |
    fulvestrant • mirdametinib (PD-0325901)
    over3years
    [VIRTUAL] The Association Between MAP2K1 Mutation Class and Clinical Features in MAP2K1‑Mutant East Asian Non‑Small Cell Lung Cancer Patients (IASLC-WCLC 2020)
    Briefly, patients with (n=9) or without (n=5) co-occurring TP53 mutations had a median OS of 12.0 months and not up to now respectively (P=0.41); patients with (n=3) or without (n=11) co-occurring KRAS mutations had a median OS of not up to now and 12.0 months respectively (P=0.33); patients with (n=4) or without (n=10) co-occurring KRAS mutations had a median OS of 14.5 months and 12.0 months respectively (P=0.57); patients with (n=4) or without (n=23) co-occurring STK11 mutations had a median OS of 11.5 months and 12.0 months respectively (P=0.70). Conclusion MAP2K1 genetic alter occurs in a subset of NSCLC, and improved understanding of the implications of MAP2K1 aberrations is critical for the identification of therapeutic target candidates.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • MSH6 (MutS homolog 6)
    |
    TP53 mutation • STK11 mutation • MAP2K1 P124L • MAP2K1 P124