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    DRUG:

    TOS-358

    i
    Other names: TOS-358
    Associations

    News

    Trials
    Company:
    Totus Medicines
    Drug class:
    PI3Kα inhibitor
    Related drugs:
    Associations

    News

    Trials
    1m
    TOS-358-001: A Study to Evaluate the Safety and Tolerability of TOS-358 in Women With HR+ HER2- Breast Cancer (clinicaltrials.gov)
    P1, N=241, Recruiting, Totus Medicines | N=175 --> 241
    Enrollment change
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    Ibrance (palbociclib) • Kisqali (ribociclib) • fulvestrant • TOS-358
    2ms
    TOS-358-001: A Study to Evaluate the Safety and Tolerability of TOS-358 in Women With HR+ HER2- Breast Cancer (clinicaltrials.gov)
    P1, N=175, Recruiting, Totus Medicines | N=100 --> 175
    Enrollment change
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    Ibrance (palbociclib) • Kisqali (ribociclib) • fulvestrant • TOS-358
    2ms
    TOS-358-001: A Study to Evaluate the Safety and Tolerability of TOS-358 in Women With HR+ HER2- Breast Cancer (clinicaltrials.gov)
    P1, N=241, Recruiting, Totus Medicines | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2026 --> Dec 2027
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    Ibrance (palbociclib) • Kisqali (ribociclib) • fulvestrant • TOS-358
    11ms
    TOS-358-001: A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With HR+ Breast Cancer and Other Select Solid Tumors (clinicaltrials.gov)
    P1, N=241, Recruiting, Totus Medicines | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    TOS-358
    over2years
    A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With Select Solid Tumors (clinicaltrials.gov)
    P1, N=241, Recruiting, Totus Medicines
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    TOS-358
    3years
    Inhibition of wild-type PI3Kα signaling is required for durable efficacy in PI3Kα mutant cancer cells due to robust re-activation of wild-type PI3Kα signaling (AACR 2023)
    Covalent molecules (namely TOS-358) achieved complete inhibition of pathway signaling in this format. Overall, this reveals the need to achieve sustained inhibition of both PI3Kα mutant and wild type signaling to achieve durable efficacy in PI3Kα mutant tumors.
    Clinical
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PIK3CA mutation
    |
    TOS-358
    3years
    TOS-358, a first-in-class covalent PI3Kα inhibitor, demonstrates superior efficacy and does not induce significant hyperglycemia at efficacious doses in multiple animal models (AACR 2023)
    Furthermore, we elucidate that previous reversible PI3Kα inhibitors lead to dramatic hyperglycemia due to their potent inhibition of multiple PI3K isoforms at effective concentrations of the molecules in a cellular setting. This data reveals that highly specific and potent covalent inhibition of PI3Kα leads to dramatically superior efficacy and an improved safety profile.
    Preclinical
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PIK3CA mutation
    |
    TOS-358
    3years
    Development and validation of a pharmacodynamic (PD) assay for TOS-358, the first covalent inhibitor of PI3Kα in clinical development (AACR 2023)
    We furthermore utilized this assay to explore the turnover rate of PI3Kα across multiple diverse tumor types, mutations, and tissues. This approach enables highly sensitive target engagement analysis of TOS-358 across multiple formats.
    Clinical • PK/PD data
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    TOS-358
    3years
    A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With Select Solid Tumors (clinicaltrials.gov)
    P1, N=241, Recruiting, Totus Medicines | Not yet recruiting --> Recruiting
    Enrollment open
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    TOS-358
    over3years
    A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With Select Solid Tumors (clinicaltrials.gov)
    P1, N=241, Not yet recruiting, Totus Medicines
    New P1 trial
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    TOS-358