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    DRUG:

    ceralasertib (AZD6738)

    i
    Other names: AZD6738, AZD 6738, AZD-6738
    Company:
    AstraZeneca
    Drug class:
    ATR inhibitor
    Related drugs:
    15d
    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 2025 --> Oct 2026
    Trial completion date
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR wild-type • ALK wild-type
    |
    Imfinzi (durvalumab) • docetaxel • ceralasertib (AZD6738)
    1m
    The Prognostic and Predictive Impact of Circulating Tumour DNA Levels in Patients with Advanced Breast Cancer Enrolled on the plasmaMATCH Trial. (PubMed, Clin Cancer Res)
    Baseline low ctDNA levels predict response to targeted therapy, potentially suggesting shared mechanisms between high ctDNA release and resistance to therapy. Both baseline ctDNA levels and on-treatment dynamics are a promising surrogate endpoint for drug development, with clearance of ctDNA being a robust cross-therapy surrogate for outcome.
    Journal • BRCA Biomarker • PARP Biomarker • Circulating tumor DNA
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
    |
    Guardant360® CDx • GuardantOMNI
    |
    Lynparza (olaparib) • ceralasertib (AZD6738)
    2ms
    S2409: Using Biomarker Tests to Select and Test New, Personalized Treatments for Extensive Stage Small Cell Lung Cancer, PRISM Study (clinicaltrials.gov)
    P2, N=900, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting
    Enrollment open
    |
    SLFN11 (Schlafen Family Member 11)
    |
    Imfinzi (durvalumab) • etoposide IV • ceralasertib (AZD6738) • saruparib (AZD5305) • monalizumab (IPH2201)
    2ms
    AZD6738 for Patients With Progressive MDS or CMML (clinicaltrials.gov)
    P1, N=52, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: May 2024 --> Apr 2025
    Enrollment closed • Trial completion date • Trial primary completion date
    |
    SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
    |
    SF3B1 mutation
    |
    ceralasertib (AZD6738)
    2ms
    LOTOS: A Study to Investigate Efficacy and Safety of Ceralasertib Plus Durvalumab in Participants Aged ≥ 18 Years With Advanced or Metastatic Non-small Cell Lung Cancer Whose Disease Progressed on or After Prior Anti-PD-(L)1 Therapy and Platinum-based Chemotherapy (clinicaltrials.gov)
    P2, N=39, Active, not recruiting, AstraZeneca | Trial completion date: Jul 2025 --> Jan 2027
    Trial completion date
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR wild-type • ALK wild-type
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)
    2ms
    Combination ATR and PARP Inhibitor (CAPRI) Trial With AZD6738 and Olaparib in Recurrent Ovarian Cancer (clinicaltrials.gov)
    P2, N=123, Completed, University of Pennsylvania | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Jul 2025 | Trial primary completion date: Dec 2025 --> Jul 2025
    Trial completion • Trial completion date • Trial primary completion date
    |
    HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • MUC16 (Mucin 16, Cell Surface Associated)
    |
    HRD • BRCA mutation
    |
    Lynparza (olaparib) • ceralasertib (AZD6738)
    3ms
    Multicenter Phase II Study of Olaparib and the ATR Inhibitor Ceralasertib in Metastatic Castration-Resistant Prostate Cancer (TRAP). (PubMed, JCO Precis Oncol)
    Combining ceralasertib with olaparib had limited activity in patients with HRP mCRPC. HRRm response rate was not greater than previous single-agent PARP inhibitor clinical trials.
    P2 data • Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
    |
    Lynparza (olaparib) • ceralasertib (AZD6738)
    3ms
    Nuclear cGAS mediated Replication Stress and Mitotic Catastrophe can Overcome Gemcitabine Resistance. (PubMed, Cancer Lett)
    Gemcitabine induces nuclear cGAS accumulation independent of STING-mediated immune activation. The binding of nuclear cGAS to γH2AX at double strand DNA breaks (DSBs) plays a pivotal role in RS activation and mitotic catastrophe in gemcitabine and AZD6738 treated cells.
    Review • Journal
    |
    ATR (Ataxia telangiectasia and Rad3-related protein) • STING (stimulator of interferon response cGAMP interactor 1) • CGAS (Cyclic GMP-AMP Synthase) • RPA2 (Replication Protein A2)
    |
    gemcitabine • ceralasertib (AZD6738)
    3ms
    ATRiBRAVE: Restoring Sensitivity To Immunotherapy In Advanced Triple Negative Breast Cancer Exploiting Ceralasertib Priming Followed By Combined Durvalumab/Nab-Paclitaxel (clinicaltrials.gov)
    P2, N=37, Recruiting, IFOM ETS - The AIRC Institute of Molecular Oncology | Trial completion date: Nov 2025 --> Dec 2029 | Trial primary completion date: May 2025 --> Dec 2027
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 amplification • ER negative
    |
    Imfinzi (durvalumab) • albumin-bound paclitaxel • ceralasertib (AZD6738)
    4ms
    PHOENIX DDR/Anti-PD-L1 Trial: A Pre-surgical Window of Opportunity and Post-surgical Adjuvant Biomarker Study of DNA Damage Response Inhibition With or Without Anti-PD-L1 Immunotherapy in Patients With Neoadjuvant Treatment Resistant Residual Triple Negative Breast Cancer (clinicaltrials.gov)
    P2, N=119, Recruiting, Institute of Cancer Research, United Kingdom | N=81 --> 119 | Trial completion date: Dec 2025 --> Jun 2029 | Trial primary completion date: Mar 2023 --> Dec 2026
    Enrollment change • Trial completion date • Trial primary completion date • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    HER-2 negative • ER negative
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • ceralasertib (AZD6738)
    4ms
    ATR expression as a prognostic biomarker in KRAS-mutated non-small cell lung cancer. (PubMed, J Thorac Dis)
    Despite recent breakthroughs in direct KRAS G12C inhibitors (e.g., sotorasib and adagrasib), the therapeutic efficacy of these inhibitors remains limited; the median progression-free survival of KRAS-mutated NSCLC patients rarely exceeds 6 months, and actionable therapies for non-G12C variants are lacking...Additionally, the drug sensitivity analysis identified two compounds (i.e., AZ20 and AZD6738) that were sensitive to ATR expression. ATR holds promise as both a prognostic marker and therapeutic target for KRAS-mutated NSCLC. Our findings may assist in the prediction of prognosis and the development of novel targeted therapies for this disease.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • ATR (Ataxia telangiectasia and Rad3-related protein)
    |
    KRAS mutation • KRAS wild-type • RAS wild-type
    |
    Lumakras (sotorasib) • Krazati (adagrasib) • ceralasertib (AZD6738)
    4ms
    PLANETTE: A Study Investigating DNA-damage Response Agents in Molecularly Altered Advanced Cancer (clinicaltrials.gov)
    P2, N=54, Completed, AstraZeneca | Active, not recruiting --> Completed
    Trial completion
    |
    ATM (ATM serine/threonine kinase)
    |
    ATM mutation
    |
    ceralasertib (AZD6738)