^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    DRUG:

    gedatolisib (PF-05212384)

    i
    Other names: PF-05212384 , PKI-587, PF-5212384, PF 05212384, PKI 587
    Company:
    Celcuity, Pfizer
    Drug class:
    mTOR inhibitor, PI3K inhibitor, AKT inhibitor
    Related drugs:
    2ms
    Bypassing cisplatin resistance in Nrf2 hyperactivated head and neck cancer through effective PI3Kinase targeting. (PubMed, Br J Cancer)
    These findings emphasize the critical role of the PI3K-AKT-mTOR pathway in chemo-radiation resistant HNSCC and highlight the therapeutic potential of PI3K inhibitors in a disease that is refractory to all conventional therapeutic approaches.
    Journal
    |
    NOTCH1 (Notch 1)
    |
    cisplatin • gedatolisib (PF-05212384)
    2ms
    Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors (clinicaltrials.gov)
    P1, N=96, Recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Sep 2025 --> Dec 2025
    Trial primary completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    PIK3CA mutation
    |
    Ibrance (palbociclib) • gedatolisib (PF-05212384)
    4ms
    Gedatolisib Combined with Palbociclib and Letrozole in Patients with No Prior Systemic Therapy for Hormone Receptor Positive, HER2 Negative Advanced Breast Cancer. (PubMed, Clin Cancer Res)
    Gedatolisib plus palbociclib and letrozole demonstrated preliminary efficacy in patients with no prior systemic therapy for ABC. These results warrant further evaluation of gedatolisib added to standard-of-care, first-line therapy for HR+/HER2- ABC.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HR positive • HER-2 negative • PIK3CA mutation • HR positive + HER-2 negative
    |
    Ibrance (palbociclib) • letrozole • gedatolisib (PF-05212384)
    5ms
    A Pharmacologic Approach Against Glioblastoma-A Synergistic Combination of a Quinoxaline-Based and a PI3K/mTOR Dual Inhibitor. (PubMed, Int J Mol Sci)
    To mitigate resistance and improve potency and selectivity, we proposed the combination of a potent irreversible epidermal growth factor receptor inhibitor-LASSBio-1971-and a potent phosphatidylinositol-3-kinase/mammalian target of rapamycin dual inhibitor-Gedatolisib-through an in vitro phenotypic study using five human GB lines...They highlighted the synergistic response from their combination and its impact on migration reduction, G0/G1 cell cycle arrest, GB cytotoxicity, and apoptosis-inducing effects for different GB cell lines. The drug combination studies in phenotypic in vitro models made it possible to suggest a new potential treatment for glioblastoma that justifies further safety in in vivo phases of preclinical trials with the combination.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • mTOR (Mechanistic target of rapamycin kinase)
    |
    gedatolisib (PF-05212384)
    5ms
    Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/HER2- Breast Cancer (VIKTORIA-1) (clinicaltrials.gov)
    P3, N=701, Recruiting, Celcuity Inc | Trial primary completion date: Mar 2025 --> Jun 2025
    Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor)
    |
    ER positive • PIK3CA mutation • PGR positive
    |
    Ibrance (palbociclib) • Piqray (alpelisib) • fulvestrant • gedatolisib (PF-05212384)
    5ms
    Functional Analysis of the PI3K/AKT/mTOR Pathway Inhibitor, Gedatolisib, Plus Fulvestrant with and Without Palbociclib in Breast Cancer Models. (PubMed, Int J Mol Sci)
    The triplet combination was effective in treatment-naïve BC cell lines as well as in cell lines adapted to palbociclib and/or fulvestrant, regardless of PIK3CA/PTEN genetic alterations. Our findings provide a mechanistic rationale for conducting clinical studies evaluating gedatolisib in combination with CDK4/6 inhibitors and ET in HR+/HER2- ABC.
    Preclinical • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • fulvestrant • gedatolisib (PF-05212384)
    6ms
    Phase 3 Study of Gedatolisib as First-Line Treatment for Patients With HR-Positive, HER2-Negative Advanced Breast Cancer (VIKTORIA-2) (clinicaltrials.gov)
    P3, N=674, Recruiting, Celcuity Inc | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Ibrance (palbociclib) • Kisqali (ribociclib) • fulvestrant • gedatolisib (PF-05212384)
    6ms
    RESOLVE: Abemaciclib + Letrozole +/- Metformin, Zotatifin, or Gedatolisib in Endometrial or Low-Grade Serous Ovarian Cancer (clinicaltrials.gov)
    P2, N=180, Recruiting, Dana-Farber Cancer Institute | Active, not recruiting --> Recruiting | N=130 --> 180 | Trial completion date: Aug 2030 --> Aug 2031 | Trial primary completion date: Aug 2027 --> Aug 2028
    Enrollment open • Enrollment change • Trial completion date • Trial primary completion date
    |
    ER (Estrogen receptor)
    |
    ER positive
    |
    Verzenio (abemaciclib) • letrozole • gedatolisib (PF-05212384) • zotatifin (eFT226) • metformin • samotolisib (LY3023414)
    6ms
    The novel diarylurea derivative HPT-15 for potential treatment of triple-negative breast cancer via dual inhibition of the mTOR and MAPK pathways. (PubMed, Cell Signal)
    Molecular docking and dynamics simulations confirmed that HPT-15 exhibited superior binding stability with mTOR as compared to the dual-target inhibitor PKI-587...In vivo experiments further confirmed that HPT-15 effectively suppressed tumor growth without apparent toxic side effects. These findings promote the potential of HPT-15 for treatment of TNBC.
    Journal
    |
    EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)
    |
    gedatolisib (PF-05212384)
    6ms
    Phase I/II trial investigating gedatolisib plus talazoparib in advanced triple negative or BRCA1/2 positive, HER2 negative breast cancers. (PubMed, Breast Cancer Res Treat)
    The combination of gedatolisib and talazoparib is safe but did not meet the prespecified efficacy threshold for objective response rate. Additional preclinical studies of these pathways are warranted prior to future clinical trials of the combination.
    P1/2 data • Journal • BRCA Biomarker • PARP Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
    |
    HER-2 negative • HRD
    |
    Talzenna (talazoparib) • gedatolisib (PF-05212384)
    10ms
    Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors (clinicaltrials.gov)
    P1, N=96, Recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Jan 2025 --> Sep 2025
    Trial primary completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    PIK3CA mutation • PTEN loss
    |
    Ibrance (palbociclib) • gedatolisib (PF-05212384)