^
    5d
    Dual PI3Kδ/γ inhibition enhances radiotherapy-induced antitumor immunity via macrophage-dependent cGAS-STING-type I interferon signaling. (PubMed, Biochem Biophys Res Commun)
    In the syngeneic CT26 model, dual PI3Kδ/γ inhibition (BR101801 or duvelisib), unlike selective PI3Kδ inhibition (idelalisib), synergized with RT (7.5 Gy) to suppress tumor growth and induce durable immune memory. Furthermore, blockade of the IFN-I receptor abolished CD8+ T cell infiltration and M2-like macrophage suppression, abrogating antitumor efficacy and confirming the requirement for IFN-I signaling. These findings identify macrophage-driven activation of the cGAS-STING-IFN-I axis as a key mechanism by which dual PI3Kδ/γ inhibition potentiates RT, providing a strong scientific rationale for its development as an immunomodulatory radiosensitizer.
    Journal
    |
    CD8 (cluster of differentiation 8) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • STING (stimulator of interferon response cGAMP interactor 1) • CGAS (Cyclic GMP-AMP Synthase)
    |
    Zydelig (idelalisib) • Copiktra (duvelisib) • bosmolisib (BR101801)
    1m
    Duvelisib Plus Docetaxel In Recurrent/Metastatic HNSCC (clinicaltrials.gov)
    P2, N=26, Completed, Glenn J. Hanna | Active, not recruiting --> Completed
    Trial completion
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    docetaxel • Copiktra (duvelisib)
    2ms
    Expression Modulation of Immune Inhibitory Molecules by Small Molecule Inhibitor Drugs in Leukemic Cells of Chronic Lymphocytic Leukemia. (PubMed, Iran J Pharm Res)
    This study examined the effects of signaling pathway inhibitors ibrutinib, idelalisib, duvelisib, and venetoclax on the expression of immune checkpoint ligands: Programmed death ligand 1 (PD-L1), galectin-9 (Gal-9), cluster of differentiation (CD)200, CD155, and herpes virus entry mediator (HVEM) in CLL leukemic cells. Altogether, the treatment of leukemic cells with different SMIs in this study indicated increased or decreased variations in the expression level of immune checkpoint inhibitory ligands in CLL. Therefore, these mechanisms should be considered for further treatment approaches, especially for combinational strategies.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • CD200 (CD200 Molecule) • PVR (PVR Cell Adhesion Molecule) • LGALS9 (Galectin 9)
    |
    PD-L1 expression
    |
    Venclexta (venetoclax) • Imbruvica (ibrutinib) • Zydelig (idelalisib) • Copiktra (duvelisib)
    2ms
    Combination of HDAC inhibitor and PI3K inhibitor suppresses autophagy and induces apoptosis via cytoplasmic IκBα stabilization in p53-mutant diffuse large B-cell lymphoma. (PubMed, Cell Death Discov)
    In this study, we systematically validated the synergistic therapeutic potential of HDAC inhibitor chidamide and PI3K inhibitor duvelisib in p53+ DLBCL through cellular models, in vivo experiments, and clinical samples. This acetylation promoted histone H1.5-IκBα interactions, further stabilizing IκBα and attenuating p65 nuclear trafficking. Our findings identify a novel and potent therapeutic strategy for p53+ DLBCL, warranting clinical translation.
    Journal • P53mut
    |
    TP53 (Tumor protein P53) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • HDAC2 (Histone deacetylase 2) • NFKBIA (NFKB Inhibitor Alpha 2)
    |
    TP53 mutation • TP53 wild-type
    |
    Copiktra (duvelisib) • Epidaza (chidamide)
    3ms
    A051902: Testing the Addition of Duvelisib or CC-486 to the Usual Treatment for Peripheral T-Cell Lymphoma (clinicaltrials.gov)
    P2, N=170, Suspended, Alliance for Clinical Trials in Oncology | Recruiting --> Suspended
    Trial suspension
    |
    PD-1 (Programmed cell death 1) • TNFRSF8 (TNF Receptor Superfamily Member 8) • BCL6 (B-cell CLL/lymphoma 6) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • ICOS (Inducible T Cell Costimulator) • MME (Membrane Metalloendopeptidase)
    |
    TNFRSF8 expression
    |
    doxorubicin hydrochloride • cyclophosphamide • etoposide IV • Copiktra (duvelisib) • vincristine • prednisone • Onureg (azacitidine oral)
    4ms
    A Phase 1b/2 Study of IPI-145 Plus FCR in Previously Untreated, Younger Patients With CLL (clinicaltrials.gov)
    P1/2, N=32, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jul 2025 --> Jul 2026
    Trial completion date
    |
    Rituxan (rituximab) • cyclophosphamide • Copiktra (duvelisib) • fludarabine IV
    4ms
    A Study of Alectinib and Duvelisib in People With Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma (ALK+ALCL) (clinicaltrials.gov)
    P1, N=30, Recruiting, Memorial Sloan Kettering Cancer Center | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Alecensa (alectinib) • Copiktra (duvelisib)
    5ms
    Intermittent Duvelisib Dosing in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (clinicaltrials.gov)
    P2, N=15, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2025 --> Nov 2025
    Trial completion date
    |
    BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1) • FCER2 (Fc Fragment Of IgE Receptor II)
    |
    Chr t(11;14)
    |
    Copiktra (duvelisib) • ETP-47187
    5ms
    Duvelisib and Venetoclax in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL) (clinicaltrials.gov)
    P1/2, N=12, Recruiting, Jonsson Comprehensive Cancer Center | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Venclexta (venetoclax) • Copiktra (duvelisib)
    6ms
    A long-lasting PI3Kδ inhibitor zandelisib forms a water-shielded hydrogen bond with p110δ and demonstrates sustained inhibitory effects. (PubMed, Am J Cancer Res)
    The binding kinetics of zandelisib, parsaclisib, idelalisib, and duvelisib to PI3Kδ were evaluated using surface plasmon resonance (SPR) analysis with the BiacoreTM system, and their binding in living cells was confirmed using the NanoBRETTM TE Intracellular Kinase Assay system. The crystal structure of PI3Kδ in complex with zandelisib was determined at 2.5 Å resolution, revealing the benzimidazole group in zandelisib formed a hydrogen bond to the side chain of Lys779 in p110δ, the catalytic subunit of PI3Kδ. These studies demonstrated a longer duration of action of zandelisib compared to the other compounds, which was attributable to the hydrogen bond between zandelisib and Lys779 in p110δ.
    Journal
    |
    PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
    |
    Zydelig (idelalisib) • Copiktra (duvelisib) • parsaclisib (INCB50465) • zandelisib (ME-401)
    6ms
    A Study of Ruxolitinib and Duvelisib in People With Lymphoma (clinicaltrials.gov)
    P1, N=70, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2026 --> Aug 2027 | Trial primary completion date: Aug 2026 --> Aug 2027
    Trial completion date • Trial primary completion date
    |
    CD8 (cluster of differentiation 8)
    |
    Jakafi (ruxolitinib) • Copiktra (duvelisib)
    6ms
    Duvelisib Following Chimeric Antigen Receptor T-Cell Therapy (clinicaltrials.gov)
    P1, N=42, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    Copiktra (duvelisib)