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    DRUG:

    omipalisib (GSK2126458)

    i
    Other names: GSK2126458, GSK 458, GSK-2126458, GSK-458, 2126458, GSK 2126458
    Company:
    GSK
    Drug class:
    mTOR inhibitor, PI3K inhibitor
    Related drugs:
    20d
    NCI-2013-02103: Testing the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma (clinicaltrials.gov)
    P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027
    Trial completion date • Trial primary completion date • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    BRAF V600E • BRAF V600 • BRAF V600K
    |
    THXID® BRAF Kit • cobas® 4800 BRAF V600 Mutation Test
    |
    Mekinist (trametinib) • Tafinlar (dabrafenib) • navitoclax (ABT 263) • omipalisib (GSK2126458)
    2ms
    A proteogenomic gene signature defines prognostic subgroups highlighting PI3K/AKT/mTOR signaling pathway as a therapeutic vulnerability in myeloid malignancies. (PubMed, Cell Commun Signal)
    Together, our findings revealed shared molecular features across MPN and AML, identified a prognostic gene signature for risk stratification, and provided rationale for PI3K/mTOR inhibition as a promising therapeutic strategy in myeloid malignancies.
    Journal • Gene Signature
    |
    CDCP1 (CUB Domain Containing Protein 1)
    |
    omipalisib (GSK2126458)
    2ms
    Patient-Derived Xenograft Mouse Model of a Rare Gynecologic Malignancy: Personalized Medicine for the Treatment of Mesonephric-Like Adenocarcinoma. (PubMed, Cureus)
    We established a PDX model of MLA to facilitate personalized treatment for rare tumors.
    Preclinical • Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    Mekinist (trametinib) • carboplatin • paclitaxel • omipalisib (GSK2126458)
    3ms
    ADVL1521: Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia (clinicaltrials.gov)
    P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Oct 2026
    Trial completion date
    |
    NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
    |
    RAS mutation • CBL mutation
    |
    Mekinist (trametinib) • omipalisib (GSK2126458)
    3ms
    Targeting serine metabolism vulnerability in omipalisib-resistant acute myeloid leukemia with phosphoglycerate dehydrogenase inhibitors. (PubMed, Biomed Pharmacother)
    Furthermore, we found that, like OCI-AML cells, the exportin 1 (XPO1) inhibitors selinexor and eltanexor significantly induced cell cycle arrest and reduced PHGDH expression in OCI-AML3-OR cells. Therefore, treatment with PHGDH inhibitors could be a therapeutic strategy for refractory AML to PI3K/mTOR inhibitors. Relevant clinical trials are warranted.
    Journal • IO biomarker
    |
    XPO1 (Exportin 1) • PHGDH (Phosphoglycerate Dehydrogenase)
    |
    Xpovio (selinexor) • omipalisib (GSK2126458) • eltanexor (KPT-8602)
    4ms
    NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) (clinicaltrials.gov)
    P2, N=6452, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    MSI (Microsatellite instability) • CD4 (CD4 Molecule)
    |
    Opdivo (nivolumab) • Herceptin (trastuzumab) • Mekinist (trametinib) • Xalkori (crizotinib) • Tagrisso (osimertinib) • Gilotrif (afatinib) • Ibrance (palbociclib) • dasatinib • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • sunitinib • Kadcyla (ado-trastuzumab emtansine) • Balversa (erdafitinib) • Mektovi (binimetinib) • adavosertib (AZD1775) • Truqap (capivasertib) • Aliqopa (copanlisib) • fexagratinib (ABSK091) • sapanisertib (CB-228) • ipatasertib (RG7440) • taselisib (GDC-0032) • omipalisib (GSK2126458) • ulixertinib (BVD-523) • Erivedge (vismodegib) • Trazimera (trastuzumab-qyyp) • Fakzynja (defactinib) • GSK2636771 • Paletan (pertuzumab biosimilar) • relatlimab (BMS-986016) • ABP 206 (nivolumab biosimilar) • Pertuvia (pertuzumab biosimilar)
    5ms
    Changes in Melanoma Cell Morphology Following Inhibition of Cell Invasion by Third-Generation mTOR Kinase Inhibitors. (PubMed, Int J Mol Sci)
    The study used mTOR kinase inhibitors: Everolimus and Torkinib; dual PI3K/mTOR inhibitors BEZ-235 and Omipalisib; and the mTORC1/2 inhibitor OSI-027. These compounds were used both as monotherapy and in combination with the MEK1/2 inhibitor AS-703026...The morphology of cells also changed significantly: their thickness, volume, roughness, convexity of shape, and irregularity, which may be a good diagnostic and prognostic factor for the response to treatment. Our studies to date on the effect of three generations of mTOR kinase inhibitors on the inhibition of the invasion process, the activation of apoptosis, and the reduction in cell proliferation suggest that they may be an important target for anticancer therapy.
    Journal
    |
    MMP2 (Matrix metallopeptidase 2) • MMP9 (Matrix metallopeptidase 9)
    |
    everolimus • dactolisib (RTB101) • omipalisib (GSK2126458) • pimasertib (AS703026) • AVTX-006 • torkinib (PP242)
    9ms
    Navitoclax, a Bcl-2/xL Inhibitor, and YM155, a Survivin Inhibitor, in Combination with Carboplatin, Effectively Inhibit Ovarian Cancer Tumor Growth. (PubMed, Mol Cancer Ther)
    Initial results showed that omipalisib, verteporfin, CA3, mitoxantrone, navitoclax, venetoclax, and YM155 had significant single-drug activity in either the ALDHlo or both the ALDHlo/ALDHhi cell populations...In vivo, the combination of navitoclax/YM155/carboplatin decreased ovarian cancer metastasis, decreased the percentage of ALDHhi ovarian cancer cells in tumors, and increased survival when compared with carboplatin treatment alone in xenograft models. Our results suggest that the combination of navitoclax/YM155/carboplatin has promise as a therapy for treating ovarian cancer.
    Journal
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    Venclexta (venetoclax) • carboplatin • navitoclax (ABT 263) • omipalisib (GSK2126458) • mitoxantrone • Visudyne (verteporfin) • sepantronium bromide (PC-002)
    10ms
    Combined Omipalisib and MAPK Inhibition Suppress PDAC Growth. (PubMed, Cancers (Basel))
    In vivo oral administration of combined Omipalisib/Trametinib treatment was significantly more effective than Omipalisib/SHP099 in reducing implanted tumor growth, and the Omipalisib/Trametinib treatment more effectively reduced tumor progression and prolonged survival in an aggressive genetically engineered mouse model of PDAC than either Omipalisib or Trametinib alone. Altogether, our data support a rationale for a dual treatment strategy targeting both PI3K and MAPK pathways in pancreatic cancers.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    KRAS mutation
    |
    Mekinist (trametinib) • omipalisib (GSK2126458) • SHP099
    10ms
    Trametinib and Docetaxel in Treating Patients With Recurrent or Stage IV KRAS Mutation Positive Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026
    Trial completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Mekinist (trametinib) • docetaxel • omipalisib (GSK2126458)
    11ms
    Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=96, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026
    Trial completion date • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCL2L2 (BCL2 Like 2)
    |
    KRAS mutation • NRAS mutation
    |
    Mekinist (trametinib) • navitoclax (ABT 263) • omipalisib (GSK2126458)
    11ms
    InfoScan: A New Transcript Identification Tool Based on scRNA-Seq and Its Application in Glioblastoma. (PubMed, Int J Mol Sci)
    Drug sensitivity assays indicated that neoplastic-stemness cells might be sensitive to omipalisib, a PI3K inhibitor, pointing to a potential therapeutic target. InfoScan offers a robust framework for exploring complex transcriptomic landscapes and characterizing rare cell populations, providing valuable insights into GBM biology and advancing precision cancer therapy.
    Journal
    |
    SPP1 (Secreted Phosphoprotein 1)
    |
    omipalisib (GSK2126458)