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    DRUG:

    emibetuzumab (LY2875358)

    i
    Other names: LY2875358, LA480, LA-480, LY-2875358
    Company:
    Eli Lilly, Innovent Biologics
    Drug class:
    c-MET inhibitor
    Related drugs:
    5ms
    Balise: A Study of LY2875358 in Participants With Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations (clinicaltrials.gov)
    P2, N=150, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2023 --> Dec 2024
    Trial completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR exon 19 deletion + EGFR L861Q
    |
    erlotinib • emibetuzumab (LY2875358)
    over1year
    Balise: A Study of LY2875358 in Participants With Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations (clinicaltrials.gov)
    P2, N=150, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2022 --> Dec 2023
    Trial completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR exon 19 deletion + EGFR L861Q
    |
    erlotinib • emibetuzumab (LY2875358)
    almost2years
    A Randomized, Open-Label Phase II Study Evaluating Emibetuzumab Plus Erlotinib and Emibetuzumab Monotherapy in MET Immunohistochemistry Positive NSCLC Patients with Acquired Resistance to Erlotinib. (PubMed, Clin Lung Cancer)
    Acquired resistance to erlotinib in MET diagnostic (+) patients was not reversed by emibetuzumab plus erlotinib or emibetuzumab monotherapy, although a subset of patients obtained clinical benefit.
    P2 data • Preclinical • Clinical Trial,Phase II • Journal
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET amplification • MET expression
    |
    erlotinib • emibetuzumab (LY2875358)
    over2years
    Balise: A Study of LY2875358 in Participants With Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations (clinicaltrials.gov)
    P2, N=150, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2021 --> Dec 2022
    Clinical • Trial completion date
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X
    |
    erlotinib • emibetuzumab (LY2875358)
    over3years
    MARCH Proteins Mediate Responses to Antitumor Antibodies. (PubMed, J Immunol)
    We report that MET surface expression is reduced by MARCH1, 4, or 8-mediated ubiquitination and that emibetuzumab-induced MET ubiquitination contributes to its capacity to downregulate MET and inhibit human tumor cell proliferation. Thus, MARCH E3 ligases can act as cofactors for antitumor Abs that target cell surface proteins, suggesting that the MARCH protein repertoire of cells is a determinant of their response to such Abs.
    Journal
    |
    MET (MET proto-oncogene, receptor tyrosine kinase) • HGF (Hepatocyte growth factor) • SLC3A2 (Solute Carrier Family 3 Member 2)
    |
    MET expression
    |
    emibetuzumab (LY2875358)
    over3years
    Balise: A Study of LY2875358 in Participants With Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations (clinicaltrials.gov)
    P2, N=150, Active, not recruiting, Eli Lilly and Company | Trial completion date: Jul 2021 --> Dec 2021
    Clinical • Trial completion date
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X
    |
    erlotinib • emibetuzumab (LY2875358)
    almost4years
    [VIRTUAL] T-cell recruitment tumor lysis via a novel c-MET/CD3 bispecific antibody (AACR-II 2020)
    Various kinase inhibitor and monoclonal antibody (e.g. Emibetuzumab and Onartuzumab) have been developed to block the HGF/c-MET interactions, however, those kinase-inhibiting-based therapeutics have shown limited success in clinical trials...An example of this design strategy is the FDA-approved bispecific antibody blinatumomab...Collectively, the novel c-MET/CD3 bispecific antibody can provide immunotherapy for c-MET-overexpressing tumors which conventional antibody or small molecular inhibitor might not. These findings also support the immunotherapeutic effects on combination of T-cell dependent bispecific antibody and immune checkpoint blockade.
    PD(L)-1 Biomarker • IO biomarker
    |
    MET (MET proto-oncogene, receptor tyrosine kinase) • NCAM1 (Neural cell adhesion molecule 1)
    |
    MET overexpression
    |
    Blincyto (blinatumomab) • emibetuzumab (LY2875358) • onartuzumab (RG3638)
    over5years
    Balise: A Study of LY2875358 in Participants With Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations (clinicaltrials.gov)
    P2, N=150, Recruiting, Eli Lilly and Company
    Clinical • New P2 trial
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X
    |
    erlotinib • emibetuzumab (LY2875358)