^
    8ms
    NAUTILUS: OKI-179 Plus Binimetinib in Patients With Advanced Solid Tumors in the RAS Pathway (Phase 1b) and NRAS-mutated Melanoma (Phase 2) (clinicaltrials.gov)
    P1/2, N=36, Active, not recruiting, OnKure, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b --> P1/2 | N=73 --> 36
    Enrollment closed • Phase classification • Enrollment change • Metastases
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NF1 (Neurofibromin 1) • GNAQ (G Protein Subunit Alpha Q)
    |
    NRAS mutation • RAS mutation
    |
    Mektovi (binimetinib) • bocodepsin (OKI-179)
    8ms
    Overcoming doxorubicin resistance in triple-negative breast cancer using the class I-targeting HDAC inhibitor bocodepsin/OKI-179 to promote apoptosis. (PubMed, Breast Cancer Res)
    The addition of bocodepsin to doxorubicin resulted in synergistic antiproliferative activity in vitro, improved tumor growth inhibition in vivo, and promotion of apoptosis which makes this a promising combination to overcome doxorubicin resistance in TNBC. Bocodepsin is currently in clinical development and has a favorable toxicity profile compared to other HDAC inhibitors supporting the feasibility of evaluating this combination in patients with TNBC.
    Journal
    |
    ANXA5 (Annexin A5)
    |
    TP53 mutation
    |
    doxorubicin hydrochloride • bocodepsin (OKI-179)
    10ms
    First-in-Human Dose-Escalation Study of the Novel Oral Depsipeptide Class I-Targeting HDAC Inhibitor Bocodepsin (OKI-179) in Patients with Advanced Solid Tumors. (PubMed, Cancers (Basel))
    (4) OKI-179 has a manageable safety profile at the recommended phase 2 dose (RP2D) of 300 mg daily on a 4:3 schedule with prophylactic oral antiemetics. OKI-179 is currently being investigated with the MEK inhibitor binimetinib in patients with NRAS-mutated melanoma in the phase 2 Nautilus trial.
    P1 data • Journal • Metastases
    |
    NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation
    |
    Mektovi (binimetinib) • bocodepsin (OKI-179)
    1year
    Elucidating the direct effects of the novel HDAC inhibitor bocodepsin (OKI-179) on T cells to rationally design regimens for combining with immunotherapy. (PubMed, Front Immunol)
    In vivo comparisons demonstrated that stopping OKI-179 treatment during PD-1 blockade was superior to continuous treatment. These findings provide novel insight into the direct effects of HDAC inhibitors on T cells and that treatment schedules that take into account acute T cell effects should be considered when combined with immunotherapies in order to fully harness the tumor-specific T cell responses in patients.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    bocodepsin (OKI-179)
    over2years
    Nautilus: OKI-179 Plus Binimetinib in Patients With Advanced Solid Tumors in the RAS Pathway (Phase 1b) and NRAS-mutated Melanoma (Phase 2) (clinicaltrials.gov)
    P1b, N=73, Recruiting, OnKure, Inc.
    New P1 trial
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NF1 (Neurofibromin 1) • GNAQ (G Protein Subunit Alpha Q)
    |
    NRAS mutation
    |
    Mektovi (binimetinib) • bocodepsin (OKI-179)
    3years
    Rationale and design of a phase 1b/2 trial of OKI-179, an oral class 1-selective depsipeptide HDAC inhibitor, in combination with tamoxifen in patients with previously treated metastatic ER+ HER2- breast cancer (SABCS 2021)
    No abstract available
    Clinical • P1/2 data • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    tamoxifen • bocodepsin (OKI-179)
    over4years
    Histone-deacetylase inhibition sensitizes PD1 blockade-resistant B-cell lymphomas. (PubMed, Cancer Immunol Res)
    To study PD1 resistance, we used an isoform-selective histone deacetylase inhibitor (HDACi; OKI-179), and a mouse mature B-cell lymphoma, G1XP lymphoma, immunosuppressive features of which resemble those of human B-cell lymphomas, including downregulation of MHC class I and II, exhaustion of CD8 and CD4 tumor-infiltrating lymphocytes (TIL), and PD1-blockade resistance...Additionally, we found that different HDACi exhibited distinct effects on tumors and T cells, yet the same HDACi could differentially affect HLA expression on different human B-cell lymphomas. Our study highlights the immunological effects of HDACi on antitumor responses and suggests that optimal treatment efficacy requires personalized design and rational combination based on prognostic biomarkers (e.g., MHCs) and the individual profiles of HDACi.
    Journal • PD(L)-1 Biomarker
    |
    CD8 (cluster of differentiation 8)
    |
    TILs
    |
    bocodepsin (OKI-179)