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    DRUG:

    merestinib (LY2801653)

    i
    Other names: LY2801653, LY-2801653, LY 2801653
    Company:
    Eli Lilly
    Drug class:
    c-MET inhibitor
    Related drugs:
    4ms
    A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer (clinicaltrials.gov)
    P2, N=309, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2025 --> Dec 2026
    Trial completion date
    |
    cisplatin • gemcitabine • Cyramza (ramucirumab) • merestinib (LY2801653)
    4ms
    Cooperative CCL2/CCR2 and HGF/MET signaling enhances breast cancer growth and invasion associated with metabolic reprogramming. (PubMed, Cancer Biol Ther)
    CCR2 knockout combined with Merestinib treatment inhibited growth, survival, and stromal reactivity of breast xenografts more than CCR2 or MET targeting alone. CCL2/CCR2 and HGF/MET cooperate to enhance breast cancer progression and metabolic reprogramming.
    Journal
    |
    CASP3 (Caspase 3) • CCL2 (Chemokine (C-C motif) ligand 2) • PCNA (Proliferating cell nuclear antigen) • CCR2 (C-C Motif Chemokine Receptor 2)
    |
    merestinib (LY2801653)
    1year
    A Study of Anti-PD-L1 Checkpoint Antibody (LY3300054) Alone and in Combination in Participants With Advanced Refractory Solid Tumors (clinicaltrials.gov)
    P1, N=164, Completed, Eli Lilly and Company | Active, not recruiting --> Completed
    Trial completion • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • MSI (Microsatellite instability)
    |
    MSI-H/dMMR • HER-2 overexpression • HER-2 negative
    |
    Verzenio (abemaciclib) • Cyramza (ramucirumab) • merestinib (LY2801653) • lodapolimab (LY3300054) • LY3321367
    over1year
    TKI type switching overcomes ROS1 L2086F in ROS1 fusion-positive cancers. (PubMed, NPJ Precis Oncol)
    Using Ba/F3 and NIH3T3 cell models, CRISPR/Cas9-edited isogenic wildtype and mutant patient-derived cell lines, and in vivo tumor growth studies, we compared type I TKIs (crizotinib, entrectinib, taletrectinib, lorlatinib, and repotrectinib) to type II TKIs (cabozantinib and merestinib) and the type I FLT3 inhibitor gilteritinib...While cabozantinib effectively inhibits ROS1 L2086F, its multi-kinase inhibitor nature highlights the need for more selective and better-tolerated TKIs to overcome kinase-intrinsic resistance. Gilteritinib may offer an alternative for targeting ROS1 L2086F with distinct off-target toxicities, but further studies are required to fully evaluate its potential in this setting.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    Xalkori (crizotinib) • Rozlytrek (entrectinib) • Lorbrena (lorlatinib) • Xospata (gilteritinib) • Cabometyx (cabozantinib tablet) • Augtyro (repotrectinib) • merestinib (LY2801653) • Ibtrozi (taletrectinib)
    over1year
    Altered ribosomal profile in acquired resistance and reversal associates with pathological response to chemotherapy in inflammatory breast cancer. (PubMed, NPJ Breast Cancer)
    Given the common hyperactivation of MAPK in IBC tumors, including rSUM149, we evaluated Merestinib, a multikinase inhibitor in clinical trials. It effectively targeted pERK and peIF4E pathways, suppressed downstream targets, induced cell death in drug-resistant rSUM149 cells, and showed synergistic effects with another tyrosine kinase inhibitor (Lapatinib) in parental cells. This underscores its significant impact on protein synthesis signaling, crucial for combating translational dependence in cancer cells. In summary, our study elucidates adaptive changes in IBC cells in response to therapy and treatment pauses, guiding precision medicine approaches for this challenging cancer type.
    Preclinical • Journal • IO biomarker
    |
    XPO1 (Exportin 1) • XIAP (X-Linked Inhibitor Of Apoptosis) • CDK1 (Cyclin-dependent kinase 1) • RPL5 (Ribosomal Protein L5) • SOD2 (Superoxide Dismutase 2)
    |
    lapatinib • merestinib (LY2801653)
    over1year
    A Study of Anti-PD-L1 Checkpoint Antibody (LY3300054) Alone and in Combination in Participants With Advanced Refractory Solid Tumors (clinicaltrials.gov)
    P1, N=215, Active, not recruiting, Eli Lilly and Company | Trial completion date: Mar 2024 --> Jul 2024
    Trial completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • MSI (Microsatellite instability)
    |
    MSI-H/dMMR • HER-2 overexpression • HER-2 negative
    |
    Verzenio (abemaciclib) • Cyramza (ramucirumab) • merestinib (LY2801653) • lodapolimab (LY3300054) • LY3321367
    over1year
    Merestinib In Non-Small Cell Lung Cancer And Solid Tumors (clinicaltrials.gov)
    P2; Trial completion date: Mar 2024 --> Oct 2023 | Active, not recruiting --> Terminated; Funding was pulled
    Trial completion date • Trial termination
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    MET exon 14 mutation
    |
    OncoPanel™ Assay
    |
    merestinib (LY2801653)
    almost2years
    A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer (clinicaltrials.gov)
    P2, N=309, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2023 --> Dec 2025
    Trial completion date • Metastases
    |
    cisplatin • gemcitabine • Cyramza (ramucirumab) • merestinib (LY2801653)
    almost2years
    A Study of Anti-PD-L1 Checkpoint Antibody (LY3300054) Alone and in Combination in Participants With Advanced Refractory Solid Tumors (clinicaltrials.gov)
    P1, N=215, Active, not recruiting, Eli Lilly and Company | Phase classification: P1a/1b --> P1 | Trial completion date: Dec 2023 --> Mar 2024
    Phase classification • Trial completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • MSI (Microsatellite instability)
    |
    MSI-H/dMMR • HER-2 overexpression • HER-2 negative
    |
    Verzenio (abemaciclib) • Cyramza (ramucirumab) • merestinib (LY2801653) • lodapolimab (LY3300054) • LY3321367
    almost3years
    Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates. (PubMed, Clin Cancer Res)
    We provide prospective, preliminary evidence that MET and FGFR are biologically active and safely targetable pathways in AML.
    Preclinical • Journal
    |
    FGFR (Fibroblast Growth Factor Receptor) • HGF (Hepatocyte growth factor)
    |
    HGF expression
    |
    merestinib (LY2801653) • LY2874455
    almost3years
    Enhancing nanoparticle paclitaxel antitumor response through targeted inhibition of c-Met pathway by merestinib in gastric cancer models. (ASCO-GI 2023)
    These findings suggest that merestinib has strong antitumor activity in GAC and exhibits an additive effect when administered with nab-paclitaxel. These results provide compelling evidence that this therapeutic approach may lead to a clinically relevant combination to improve GAC patients’ survival.
    Preclinical
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET expression
    |
    albumin-bound paclitaxel • merestinib (LY2801653)
    3years
    A Study of Anti-PD-L1 Checkpoint Antibody (LY3300054) Alone and in Combination in Participants With Advanced Refractory Solid Tumors (clinicaltrials.gov)
    P1a/1b, N=215, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2022 --> Dec 2023
    Trial completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • MSI (Microsatellite instability)
    |
    MSI-H/dMMR • HER-2 overexpression • HER-2 negative
    |
    Verzenio (abemaciclib) • Cyramza (ramucirumab) • merestinib (LY2801653) • lodapolimab (LY3300054) • LY3321367