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    DRUG:

    AZD1390

    i
    Other names: AZD1390, AZD 1390, AZD-1390
    Company:
    AstraZeneca
    Drug class:
    ATM kinase inhibitor
    Related drugs:
    15d
    Radiosensitisation of Head and Neck Cancer Cells to Protons of Increasing LET Through Targeting DNA Double Strand Break Repair. (PubMed, Cells)
    We demonstrate that inhibitors against ATR (AZD6738), and particularly ATM (AZD1390) and DNA-Pkcs (AZD7648), could significantly decrease clonogenic survival of HNSCC cell lines following PBT at both low and relatively high LET (~2 keV/µm and ~8 keV/µm, respectively). We confirmed that the inhibitors in combination with PBT led to DSB persistence through neutral comet assays and monitoring γH2AX/53BP1 foci. We also show that this strategy can enhance the sensitivity of patient-derived organoids of HNSCC to PBT of both low and high LET, highlighting this as a strategy which should be exploited further.
    Journal
    |
    ATR (Ataxia telangiectasia and Rad3-related protein) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
    |
    ceralasertib (AZD6738) • AZD1390 • AZD7648
    29d
    GCAR-7213: Trial Designed To Evaluate Multiple Regimens In Newly Diagnosed and Recurrent Glioblastoma (GBM) (2024-511452-40-00)
    P2/3, N=120, Active, not recruiting, Global Coalition For Adaptive Research Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    IDH wild-type
    |
    AZD1390 • Hepacid (pegargiminase) • Vyglxia (troriluzole)
    2ms
    GBM AGILE: A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma (clinicaltrials.gov)
    P2/3, N=2250, Recruiting, Global Coalition for Adaptive Research | N=1280 --> 2250
    Enrollment change
    |
    IDH wild-type
    |
    temozolomide • Stivarga (regorafenib) • lomustine • VT1021 • AZD1390 • Hepacid (pegargiminase) • paxalisib (GDC-0084) • dianhydrogalactitol (VAL-083) • Vyglxia (troriluzole) • tinostamustine (EDO-S101)
    3ms
    Testing the Addition of an Anti-Cancer Drug, AZD1390, During Radiation Therapy for Newly Diagnosed High Grade Glioma, Diffuse Midline Glioma, or Diffuse Intrinsic Pontine Glioma (clinicaltrials.gov)
    P1, N=54, Recruiting, Children's Oncology Group | Initiation date: Feb 2026 --> Jun 2025
    Trial initiation date
    |
    IDH wild-type
    |
    AZD1390
    5ms
    SADDRIN-1: Sarcomas and DDR-Inhibition; a Combined Modality Study (clinicaltrials.gov)
    P1, N=12, Terminated, The Netherlands Cancer Institute | N=30 --> 12 | Trial completion date: Jul 2028 --> Dec 2025 | Recruiting --> Terminated; Endpoint has been reached.
    Enrollment change • Trial completion date • Trial termination
    |
    Imfinzi (durvalumab) • AZD1390
    5ms
    DNA Damage Sensing and TP53 Function as Modulators of Sensitivity to Calicheamicin-Based Antibody-Drug Conjugates for Acute Leukemia. (PubMed, Cancers (Basel))
    These results support further evaluation of combination therapies with corresponding small-molecule inhibitors (currently pursued for therapy of other cancers) toward clinical testing as novel strategies to increase the efficacy of CLM-based ADCs such as GO and InO.
    Journal • PARP Biomarker
    |
    TP53 (Tumor protein P53)
    |
    TP53 mutation • TP53 wild-type
    |
    Besponsa (inotuzumab ozogamicin) • Mylotarg (gemtuzumab ozogamicin) • idasanutlin (RG7388) • AZD1390 • lartesertib (M4076)
    9ms
    ATM inhibitors in cancer radiotherapy: Mechanisms, clinical development, and future directions. (PubMed, Eur J Med Chem)
    Inhibitors such as KU-55933, KU-60019, and AZD1390 have shown the potential to sensitize cancer cells to radiotherapy by impairing DNA repair, thereby enhancing treatment efficacy...Currently, none have gained approval from the FDA or EMA, but six candidates, AZD1390, AZD0156, ZN-B-2262, SYH2051, WSD0628 and M3541 are in clinical trials, often as adjuncts to radiotherapy or in combination with PARP inhibitors. Their safety and effectiveness, however, are still under investigation. This review synthesizes ATM's dual roles and the therapeutic promise of targeting ATM in cancer radiotherapy.
    Review • Journal • PARP Biomarker
    |
    CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    |
    AZD1390 • KU-55933 • AZD0156 • M3541 • WSD0628
    10ms
    GBM AGILE: A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma (clinicaltrials.gov)
    P2/3, N=1280, Recruiting, Global Coalition for Adaptive Research | Trial completion date: Jun 2028 --> Jun 2030 | Trial primary completion date: Jun 2026 --> Jun 2028
    Trial completion date • Trial primary completion date
    |
    IDH wild-type
    |
    temozolomide • Stivarga (regorafenib) • lomustine • VT1021 • AZD1390 • Hepacid (pegargiminase) • paxalisib (GDC-0084) • dianhydrogalactitol (VAL-083) • Vyglxia (troriluzole)
    1year
    Testing the Addition of an Anti-Cancer Drug, AZD1390, During Radiation Therapy for Newly Diagnosed High Grade Glioma, Diffuse Midline Glioma, or Diffuse Intrinsic Pontine Glioma (clinicaltrials.gov)
    P1, N=54, Recruiting, Children's Oncology Group | Not yet recruiting --> Recruiting | Initiation date: May 2025 --> Feb 2026
    Enrollment open • Trial initiation date
    |
    AZD1390
    1year
    CONCORDE: A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC (clinicaltrials.gov)
    P1, N=200, Recruiting, University of Leeds | Trial primary completion date: Apr 2025 --> Mar 2026
    Trial primary completion date
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • ceralasertib (AZD6738) • AZD1390 • saruparib (AZD5305)
    1year
    Testing the Addition of an Anti-Cancer Drug, AZD1390, During Radiation Therapy for Newly Diagnosed High Grade Glioma, Diffuse Midline Glioma, or Diffuse Intrinsic Pontine Glioma (clinicaltrials.gov)
    P1, N=54, Not yet recruiting, Children's Oncology Group
    New P1 trial
    |
    AZD1390
    over1year
    A Study of AZD1390 and Stereotactic Body Radiotherapy (SBRT) for People with Metastatic Solid Tumor Cancer (clinicaltrials.gov)
    P1, N=54, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    AZD1390