^
    5d
    DDRiver Solid Tumours 301: Tuvusertib (M1774) in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 301) (clinicaltrials.gov)
    P1, N=161, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Jan 2027 --> Jul 2026 | Trial primary completion date: Jan 2027 --> Jul 2026
    Trial completion date • Trial primary completion date • First-in-human
    |
    ARID1A (AT-rich interaction domain 1A) • ATRX (ATRX Chromatin Remodeler)
    |
    ATM mutation • ARID1A mutation
    |
    Zejula (niraparib) • tuvusertib (M1774)
    7d
    Combined Inhibition of ATR and Ribonucleotide Reductase Induces Synergistic Antineoplastic Activity in Osteosarcoma Cells. (PubMed, Cancer Rep (Hoboken))
    Our study demonstrates that combined inhibition of ATR and RNR was effective in osteosarcoma cells. These in vitro findings offer support for investigating in vivo the potential of a combination of ATR and RNR inhibitors as a new treatment strategy for osteosarcoma.
    Journal
    |
    CASP3 (Caspase 3) • CASP7 (Caspase 7)
    |
    TP53 mutation • TP53 wild-type
    |
    berzosertib (M6620) • Triapine (3-AP) • didox (NSC-324360)
    13d
    IB 2018-04: Targeting ATR in soft-tissue sarcomas: a randomized phase II study (2023-509499-41-00)
    P1/2, N=72, Completed, Institut Bergonie | Active, not recruiting --> Completed
    Trial completion
    |
    gemcitabine • berzosertib (M6620)
    15d
    Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial (clinicaltrials.gov)
    P1, N=51, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    CD4 (CD4 Molecule)
    |
    HER-2 positive • HER-2 amplification • HER-2 expression
    |
    Enhertu (fam-trastuzumab deruxtecan-nxki) • ceralasertib (AZD6738)
    19d
    NCI-2018-01648: Ceralasertib (AZD6738) Alone and in Combination With Olaparib or Durvalumab in Patients With Solid Tumors (clinicaltrials.gov)
    P2, N=83, Active, not recruiting, Rahul Aggarwal | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
    |
    ATM mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • ceralasertib (AZD6738)
    20d
    Tuvusertib (M1774) Human Mass Balance and Absolute Bioavailability Study (DDRIVER Solid Tumors 303) (clinicaltrials.gov)
    P1, N=12, Completed, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Active, not recruiting --> Completed
    Trial completion
    |
    tuvusertib (M1774)
    21d
    MONETTE: A Randomized Phase II Study of Ceralasertib plus Durvalumab or Ceralasertib Monotherapy in Patients with Advanced Melanoma Resistant to PD-(L)1 Inhibition. (PubMed, Clin Cancer Res)
    Both ceralasertib plus durvalumab and ceralasertib monotherapy demonstrated low response rates in anti-PD-(L)1-resistant advanced melanoma.
    P2 data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • GDF15 (Growth differentiation factor 15) • CD14 (CD14 Molecule)
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)
    25d
    Synergistic nanomedicine overcomes hypoxia-driven DNA repair to potentiate radiotherapy for lung adenocarcinoma. (PubMed, Theranostics)
    This study establishes a synergistic nanotherapeutic strategy to concurrently disrupt the HIF-1α/ATR axis and augment radiodynamic ROS production. By integrating biological pathway inhibition with damage amplification, our strategy effectively overcomes hypoxia-mediated radioresistance, offering a promising and translatable paradigm for enhancing RT outcomes in LUAD.
    Journal
    |
    HIF1A (Hypoxia inducible factor 1, alpha subunit)
    |
    ceralasertib (AZD6738)
    27d
    LATIFY: A Phase III Study of Ceralasertib Plus Durvalumab Versus Docetaxel in Patients With Non Small Cell Lung Cancer (NSCLC) Whose Disease Progressed On or After Prior Anti PD (L)1 Therapy And Platinum Based Chemotherapy (clinicaltrials.gov)
    P3, N=594, Active, not recruiting, AstraZeneca | Trial completion date: Oct 2026 --> Dec 2027
    Trial completion date
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR wild-type • ALK wild-type
    |
    Imfinzi (durvalumab) • docetaxel • ceralasertib (AZD6738)
    29d
    Targeting ATR and PI3Kα Pathways Promotes Ferroptosis in PIK3CA-Wildtype Platinum-Resistant Endometrial Cancer. (PubMed, Cancers (Basel))
    A panel of EC cell lines, including patient-derived models with varying PIK3CA mutation status and platinum sensitivity, was treated with camonsertib (ATR inhibitor) and inavolisib (PI3Kα inhibitor). Our findings establish dual ATR and PI3Kα inhibition as a genotype-informed therapeutic strategy for platinum-resistant EC. PIK3CA mutation status may influence the mode of cell death, supporting its use as a predictive biomarker for patient stratification in future clinical applications.
    Journal • PARP Biomarker • Platinum resistant
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CASP3 (Caspase 3) • ANXA5 (Annexin A5)
    |
    PIK3CA mutation
    |
    Itovebi (inavolisib) • camonsertib (RP-3500)
    1m
    ATR and PKMYT1 inhibition re-sensitize a subset of TNBC patient-derived models to carboplatin inducing mitotic catastrophe. (PubMed, Cancer Res Commun)
    Inhibiting ATR with BAY1895344 or AZD6738 re-sensitized carboplatin-resistant PDXCs and PDXs to carboplatin, resulting in an increase in DNA damage, and apoptosis. Molecular factors associated with response to the ATR inhibitor/carboplatin combination included low RNA levels of PKMYT1. These results underscore the pivotal roles of ATR and PKMYT1 in mediating resistance to carboplatin in TNBC and support targeting these pathways to overcome carboplatin resistance in this disease.
    Journal
    |
    FOXM1 (Forkhead Box M1) • CDK1 (Cyclin-dependent kinase 1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    carboplatin • ceralasertib (AZD6738) • elimusertib (BAY 1895344)
    1m
    Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC. (PubMed, Br J Cancer)
    Ceralasertib plus durvalumab was tolerated and associated with antitumour activity in advanced/metastatic NSCLC and HNSCC.
    P1 data • Journal
    |
    ATR (Ataxia telangiectasia and Rad3-related protein)
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)