^
    7ms
    Investigating Overlapping Immune-related Genetic Markers in Cholangiocarcinoma and Inflammatory Bowel Disease for Predictive Prognosis. (PubMed, J Immunother)
    This study also predicted potential small molecule drugs that might be effective for the treatment of CHOL, such as Umbralisib and Tamoxifen. In conclusion, this study provides new biomarkers and potential targets for diagnosis, prognosis assessment, and treatment of CHOL and IBD.
    Journal
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    SPP1 (Secreted Phosphoprotein 1) • CCR7 (Chemokine (C-C motif) receptor 7) • OSMR (Oncostatin M Receptor) • PIK3R3 (Phosphoinositide-3-Kinase Regulatory Subunit 3) • S100P (S100 calcium binding protein P)
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    tamoxifen • Ukoniq (umbralisib)
    9ms
    Targeting PI3K in Cancer Treatment: A Comprehensive Review with Insights from Clinical Outcomes. (PubMed, Eur J Pharmacol)
    Some PI3K inhibitors such as idelalisib, copanlisib, duvelisib, alpelisib, and umbralisib have received FDA-approval, and are effective in the treatment of breast cancer and haematologic malignancies. The resistance mechanisms provide barriers to the sustained efficacy of PI3K-targeted treatments. This study reviews recent advancements in PI3K inhibitors, covering their clinical status, mechanism of action, resistance mechanisms, and strategies to overcome resistance.
    Clinical data • Review • Journal
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    PTEN (Phosphatase and tensin homolog)
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    PTEN mutation
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    Piqray (alpelisib) • Aliqopa (copanlisib) • Zydelig (idelalisib) • Copiktra (duvelisib) • Ukoniq (umbralisib)
    10ms
    Treatment of Relapsed/Refractory CLL Patients With PI3Kδ Inhibitor and Anti-CD20 Antibody Rapidly Decreases Tumor Burden but Could Induce Resistance. (PubMed, Am J Hematol)
    The clinical trial utilized 1)a therapeutic anti-CD20 monoclonal antibody (mAb), ublituximab, which destroys CLL cells by an antibody-dependent cellular phagocytosis (ADCP) mechanism; 2)a B cell receptor (BCR) signaling inhibitor, umbralisib, which blocks PI3Kẟ; 3)and an anti-apoptosis inhibitor, venetoclax, which blocks cell survival promoted by BCL-2 that stops mitochondria from initiating apoptosis. Standard high dose (375 mg/m2) anti-CD20 antibody treatment significantly decreased CLL surface CD20 levels, potentially limiting treatment efficacy. Anti-CD20 antibody plus B cell receptor signaling inhibition reduced CLL cell counts and lymph node tumors, enabling BCL-2 inhibitor treatment to avoid tumor lysis syndrome.
    Journal
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    PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
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    Venclexta (venetoclax) • Ukoniq (umbralisib) • Briumvi (ublituximab-xiiy)
    1year
    Acalabrutinib, Umbralisib and Ublituximab Regimen (AU2) Demonstrates High Response Rate and Undetectable Molecular Minimal Residual Disease (MRD) in Patients (pts) with De Novo Mantle Cell Lymphoma (MCL) (ASH 2024)
    Two pts were switched to zanubrutinib due to PD on U2, both achieved response. AU2 is a highly effective regimen in pts with previously untreated MCL, including those with high-risk genetics (100% CR rate), and achieves a high molecular uMRD rate. Pts who develop progressive disease can be effectively salvaged with subsequent therapies.
    Clinical • IO biomarker • Minimal residual disease
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    TP53 (Tumor protein P53)
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    TP53 mutation
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    clonoSEQ
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    Brukinsa (zanubrutinib) • Calquence (acalabrutinib) • Ukoniq (umbralisib) • Briumvi (ublituximab-xiiy)
    1year
    Acalabrutinib, Umbralisib, and Ublituximab (AU2) In Relapsed and Untreated CLL (clinicaltrials.gov)
    P2, N=60, Active, not recruiting, Jennifer R. Brown, MD, PhD | Trial primary completion date: Dec 2023 --> Dec 2026
    Trial primary completion date
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    Calquence (acalabrutinib) • Ukoniq (umbralisib) • Briumvi (ublituximab-xiiy)
    1year
    Acalabrutinib, Umbralisib, and Ublituximab (AU2) In Relapsed and Untreated CLL (clinicaltrials.gov)
    P2, N=60, Active, not recruiting, Jennifer R. Brown, MD, PhD | Trial primary completion date: Jan 2025 --> Dec 2023
    Trial primary completion date
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    Calquence (acalabrutinib) • Ukoniq (umbralisib) • Briumvi (ublituximab-xiiy)
    over1year
    Post-marketing safety concern of PI3K inhibitors in the cancer therapies: an 8-year disproportionality analysis from the FDA adverse event reporting system. (PubMed, Expert Opin Drug Saf)
    Alpelisib (inhibiting PI3Kα), copanlisib (inhibiting PI3Kα andPI3Kδ), duvelisib (inhibiting PI3Kδ and PI3Kγ), and idelalisib (inhibitingPI3Kδ) were developed to target the PI3K pathway...The safety profiles of the five PI3K inhibitorsvary concerning adverse events. These findings could guide drug selection andinform future prospective research.
    P4 data • Journal • Adverse events
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    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
    |
    Piqray (alpelisib) • Aliqopa (copanlisib) • Zydelig (idelalisib) • Copiktra (duvelisib) • Ukoniq (umbralisib)
    over1year
    SWOG S1608: Obinutuzumab With or Without Umbralisib, Lenalidomide, or Combination Chemotherapy in Treating Patients With Relapsed or Refractory Grade I-IIIa Follicular Lymphoma (clinicaltrials.gov)
    P2, N=95, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed
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    CD4 (CD4 Molecule)
    |
    lenalidomide • doxorubicin hydrochloride • Gazyva (obinutuzumab) • cyclophosphamide • vincristine • Ukoniq (umbralisib) • Belrapzo (bendamustine RTD)
    over1year
    Evaluate the Efficacy and Safety of TGR-1202 in Participants With Chronic Lymphocytic Leukemia Who Are Intolerant to Prior Therapy (clinicaltrials.gov)
    P2, N=51, Terminated, TG Therapeutics, Inc. | Completed --> Terminated; (Strategic/Business Decision)
    Trial termination
    |
    Ukoniq (umbralisib)
    over1year
    TG-1701-101: Study of TG-1701, an Irreversible Bruton's Tyrosine Kinase Inhibitor, in Patients With B-Cell Malignancies (clinicaltrials.gov)
    P1, N=172, Terminated, TG Therapeutics, Inc. | Active, not recruiting --> Terminated; Strategic/Business Decision
    Trial termination
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    Ukoniq (umbralisib) • Briumvi (ublituximab-xiiy) • edralbrutinib (TG-1701)
    over1year
    TGR-1202 + Ruxolitinib PMF PPV-MF PET-MF MDS/MPN Polycythemia Vera Resistant to Hydroxyurea (clinicaltrials.gov)
    P1, N=60, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> May 2024
    Trial completion • Trial completion date
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    Jakafi (ruxolitinib) • Ukoniq (umbralisib) • hydroxyurea
    over1year
    A Phase I/Ib Safety and Efficacy Study of the PI3K-delta Inhibitor TGR-1202 and Ibrutinib in Patients With CLL or MCL (clinicaltrials.gov)
    P1, N=45, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Mar 2024 --> Aug 2023
    Trial completion • Trial completion date • Combination therapy
    |
    Imbruvica (ibrutinib) • Ukoniq (umbralisib)