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    7ms
    p70S6K/Akt dual inhibitor DIACC3010 is efficacious in preclinical models of gastric cancer alone and in combination with trastuzumab. (PubMed, Sci Rep)
    Of the 21 HER2-negative PDX models, DIACC3010 significantly inhibited the growth of 38%. Altogether, these results provide a path forward to validate the potential biomarkers of DIACC3010 sensitivity in GC and support clinical evaluation of DIACC3010 monotherapy and combination with trastuzumab in patients with HER2- negative and positive advanced GCs, respectively.
    Preclinical • Journal • Combination therapy
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    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
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    HER-2 positive • HER-2 negative • PIK3CA mutation
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    Herceptin (trastuzumab) • rupitasertib (DIACC3010)
    1year
    DIACC3010, optimized inhibitor of S6 kinase, combined with endocrine therapy, has potent antitumor activity in treatment-resistant ER-positive HER2-negative metastatic breast cancer (AACR 2023)
    We performed exploratory correlative analyses of the phase 1 trial in ER+ HER2-negative MBC patients in addition to nonclinical experiments to evaluate its role in the CDK4/6 and endocrine therapy (ET) resistant setting. DIACC3010 was evaluated as monotherapy, or combined with either trastuzumab or tamoxifen, in a multicenter phase 1 trial that accrued 101 patients with advanced/refractory solid tumors (Tsimberidou et al, J Hematol Oncol 2021 14(1):127). Exploratory analyses from the phase 1 trial, along with nonclinical efficacy in PDX models, demonstrate that DIACC3010 may have antitumor activity in MBC patients with ET resistance. Experiments are underway to assess nonclinical efficacy of DIACC3010 combination with elacestrant or CDK4/6 inhibitors in various models of ER+ MBC, including ET resistant.
    Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • RPS6 (Ribosomal Protein S6)
    |
    HER-2 positive • ER positive • HER-2 negative • ER mutation • ESR1 mutation • ER positive + HER-2 negative • CDK4 mutation
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    Herceptin (trastuzumab) • tamoxifen • Orserdu (elacestrant) • rupitasertib (DIACC3010)
    almost2years
    AKT inhibition in the central nervous system induces signaling defects resulting in psychiatric symptomatology. (PubMed, Cell Biosci)
    Our data elucidate the incidence and mechanisms of psychiatric AEs in patients treated with PI3K/AKT/mTOR inhibitors and emphasize the need for careful monitoring.
    Journal
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    AKT3 (V-akt murine thymoma viral oncogene homolog 3)
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    AKT1 mutation • AKT3 mutation
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    rupitasertib (DIACC3010)
    over2years
    Phase 1 study of M2698, a p70S6K/AKT dual inhibitor, in patients with advanced cancer. (PubMed, J Hematol Oncol)
    M2698 was well tolerated. Combined with trastuzumab or tamoxifen, M2698 demonstrated antitumor activity in patients with advanced breast cancer resistant to multiple standard therapies, suggesting that it could overcome treatment resistance. Trial registration ClinicalTrials.gov, NCT01971515. Registered October 23, 2013.
    Clinical • P1 data • Clinical Trial,Phase I • Journal
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • AKT2 (V-akt murine thymoma viral oncogene homolog 2)
    |
    Herceptin (trastuzumab) • tamoxifen • rupitasertib (DIACC3010)