^
    8ms
    Phase 1 Study of ONO-7475 With and Without ONO-4538 in Subjects Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=24, Completed, Ono Pharmaceutical Co. Ltd | Suspended --> Completed | N=84 --> 24 | Trial completion date: Apr 2023 --> Nov 2022
    Trial completion • Enrollment change • Trial completion date • Metastases
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    Opdivo (nivolumab) • tamnorzatinib (ONO-7475)
    2years
    Identification of ADRN-specific, MES-specific, and pan-subtype therapeutic targets in neuroblastoma (AACR 2022)
    MES neuroblastoma cell lines are more sensitive to small molecule AXL inhibitors (Cabozantinib, NPS-1034, and ONO-7475) compared to ADRN cell lines. Here we have identified and prioritized ADRN-specific, MES-specific, and pan-subtype neuroblastoma therapeutic targets and suggest AXL-targeted therapy may eliminate both MES-dominant neuroblastoma cells and immune cell populations that contribute to an immunosuppressive microenvironment.
    PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • CD276 (CD276 Molecule) • GAS6 (Growth arrest specific 6) • L1CAM (L1 cell adhesion molecule) • PRRX1 (Paired Related Homeobox 1)
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    PD-L1 overexpression
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    Cabometyx (cabozantinib tablet) • tamnorzatinib (ONO-7475)
    over2years
    AXL/MERTK inhibitor ONO-7475 potently synergizes with venetoclax and overcomes venetoclax resistance to kill FLT3-ITD acute myeloid leukemia. (PubMed, Haematologica)
    Compared to ONO-7474 monotherapy, the combination of ONO- 7475/ABT-199 was even more potent in reducing leukemic burden and prolonging survival of mice in both model systems. These results suggest the ONO-7475/ABT-199 combination may be effective for acute myeloid leukemia therapy.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3) • AXL (AXL Receptor Tyrosine Kinase) • MERTK (MER Proto-Oncogene, Tyrosine Kinase)
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    FLT3 mutation • MCL1 overexpression • MCL1 expression
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    Venclexta (venetoclax) • tamnorzatinib (ONO-7475)
    over4years
    ONO-7475, a novel AXL inhibitor, suppresses the adaptive resistance to initial EGFR-TKI treatment in EGFR-mutated non-small lung cancer. (PubMed, Clin Cancer Res)
    These results demonstrate that ONO-7475 suppresses the emergence and maintenance of tolerant cells to the initial EGFR-TKIs, osimertinib or dacomitinib, in AXL-overexpressing EGFR-mutated NSCLC cells, suggesting that ONO-7475 and osimertinib is a highly potent combination for initial treatment.
    Journal
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    EGFR (Epidermal growth factor receptor)
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    Tagrisso (osimertinib) • Vizimpro (dacomitinib) • tamnorzatinib (ONO-7475)