^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    DRUG:

    ceralasertib (AZD6738)

    i
    Other names: AZD6738, AZD 6738, AZD-6738
    Company:
    AstraZeneca
    Drug class:
    ATR inhibitor
    Related drugs:
    9d
    Testing the Addition of AZD6738 (Ceralasertib) to Immunotherapy to Increase Time Without Cancer for Patients With Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P3, N=630, Not yet recruiting, National Cancer Institute (NCI)
    New P3 trial • Checkpoint inhibition • Checkpoint block
    |
    PD-L1 (Programmed death ligand 1)
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)
    1m
    Molecular mechanisms restoring olaparib efficacy through ATR/CHK1 pathway inhibition in olaparib-resistant BRCA1/2MUT ovarian Cancer models. (PubMed, Biochim Biophys Acta Mol Basis Dis)
    Olaparib-resistant xenografts were treated with olaparib, ATR inhibitor (ATRi, ceralasertib), CHK1 inhibitor (CHK1i, MK-8776) or their combinations. Our collective findings indicate that ATR/CHK1 pathway inhibition restores the olaparib efficacy in resistant BRCA1/2MUT high-grade serous OC, highlighting promising approach for olaparib rechallenge of non-responsive patients. Uncovered mechanisms might improve our understanding of acquisition and overcoming resistance to olaparib in ovarian cancer.
    Preclinical • Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • VIM (Vimentin) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
    |
    BRCA2 mutation • BRCA1 mutation • VIM expression
    |
    Lynparza (olaparib) • ceralasertib (AZD6738) • MK-8776
    1m
    MONETTE: A Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Melanoma and Resistance to PD-(L)1 Inhibition (clinicaltrials.gov)
    P2, N=194, Active, not recruiting, AstraZeneca | Trial completion date: Jun 2025 --> Oct 2025
    Trial completion date • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)
    1m
    Phase II Study of Radiotherapy Followed by Durvalumab (MEDI4736) and Ceralasertib (AZD6738) in Stage III NSCLC Patients With Thoracic Relapses +/- Oligometastases After PACIFIC Regimen (AUSTRAL) (clinicaltrials.gov)
    P2, N=21, Not yet recruiting, Mario Negri Institute for Pharmacological Research
    New P2 trial
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)
    2ms
    EFFORT: Adavosertib with or Without Olaparib in Treating Patients with Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov)
    P2, N=104, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    HRD • BRCA mutation
    |
    Lynparza (olaparib) • adavosertib (AZD1775) • ceralasertib (AZD6738)
    2ms
    Chemo-Immunotherapy Followed by Durvalumab and Ceralasertib in Treatment Naïve Patients With Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=30, Recruiting, Muhammad Furqan | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025
    Trial completion date • Trial primary completion date
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • etoposide IV • ceralasertib (AZD6738)
    2ms
    ATR inhibition increases reliance on PARP-mediated DNA repair revealing an improved therapeutic strategy for cervical cancer. (PubMed, Gynecol Oncol)
    Our findings show that ATRi increased reliance on PARP for metabolic viability, the combination of ATRi and PARPi induced synthetic lethality in cervical cancer in vitro, and reduced tumor burden in vivo.
    Journal • PARP Biomarker
    |
    HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
    |
    Lynparza (olaparib) • ceralasertib (AZD6738)
    3ms
    D5330C00004: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents (clinicaltrials.gov)
    P1/2, N=466, Recruiting, AstraZeneca | Trial completion date: Jul 2026 --> Mar 2025 | Trial primary completion date: Jul 2026 --> Mar 2025
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    HER-2 negative • HRD • PALB2 mutation • RAD51C mutation • BRCA mutation • RAD51 mutation
    |
    Lynparza (olaparib) • carboplatin • Imfinzi (durvalumab) • ceralasertib (AZD6738) • saruparib (AZD5305)
    4ms
    D5330C00004: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents (clinicaltrials.gov)
    P1/2, N=466, Recruiting, AstraZeneca | Trial completion date: Dec 2026 --> Jul 2026 | Trial primary completion date: Dec 2026 --> Jul 2026
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    Lynparza (olaparib) • carboplatin • Imfinzi (durvalumab) • ceralasertib (AZD6738) • saruparib (AZD5305)
    4ms
    The PARP1 selective inhibitor saruparib (AZD5305) elicits potent and durable antitumor activity in patient-derived BRCA1/2-associated cancer models. (PubMed, Genome Med)
    Collectively, these results show that the novel PARP1 selective inhibitor AZD5305 yields a potent antitumor response in PDX models with HRD and delays PARPi resistance alone or in combination with carboplatin or ceralasertib, which supports its use in the clinic as a new therapeutic option.
    Preclinical • Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • RAD51 (RAD51 Homolog A)
    |
    Lynparza (olaparib) • carboplatin • ceralasertib (AZD6738) • saruparib (AZD5305)
    4ms
    A Study of AZD6738 and Acalabrutinib in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) (clinicaltrials.gov)
    P1, N=11, Active, not recruiting, Acerta Pharma BV | Trial completion date: Jun 2024 --> Aug 2026
    Trial completion date • Combination therapy
    |
    Calquence (acalabrutinib) • ceralasertib (AZD6738)
    4ms
    Olaparib in Combination With Either Durvalumab, Selumetinib, or Capivasertib or Ceralasertib Alone in Treating Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov)
    P2, N=132, Recruiting, OHSU Knight Cancer Institute | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA (Breast cancer early onset)
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Koselugo (selumetinib) • Truqap (capivasertib) • ceralasertib (AZD6738)
    5ms
    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 primary completion date: May 2025 --> Aug 2025
    Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    Imfinzi (durvalumab) • docetaxel • ceralasertib (AZD6738)
    5ms
    An Open-Label Phase 1 Study of Ceralasertib in Japanese Patients With Advanced Solid Malignancies (clinicaltrials.gov)
    P1, N=12, Completed, AstraZeneca | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Mar 2024
    Trial completion • Trial completion date • Metastases
    |
    ceralasertib (AZD6738)
    5ms
    PTEN Depletion Increases Radiosensitivity in Response to Ataxia Telangiectasia-Related-3 (ATR) Inhibition in Non-Small Cell Lung Cancer (NSCLC). (PubMed, Int J Mol Sci)
    Overall, our study demonstrates that ceralasertib and RT combined preferentially sensitises PTEN-depleted NSCLC models in vitro and in vivo, with no impact on early inflammatory response indicative of RP. These findings provide a rationale for evaluating ATR inhibition in combination with RT in NSCLC patients with PTEN mutations.
    Journal
    |
    PTEN (Phosphatase and tensin homolog)
    |
    ceralasertib (AZD6738)
    5ms
    Testing Olaparib and AZD6738 in IDH1 and IDH2 Mutant Tumors (clinicaltrials.gov)
    P2, N=50, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting
    Enrollment closed
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    Lynparza (olaparib) • ceralasertib (AZD6738)
    5ms
    D5330C00004: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents (clinicaltrials.gov)
    P1/2, N=466, Recruiting, AstraZeneca | Trial completion date: Aug 2026 --> Dec 2026 | Trial primary completion date: Aug 2026 --> Dec 2026
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    Lynparza (olaparib) • carboplatin • Imfinzi (durvalumab) • ceralasertib (AZD6738) • saruparib (AZD5305)
    5ms
    Novel Combinations of Immunotherapies or DNA Damage Repair Inhibitors in Platinum-Refractory Extensive-Stage Small-Cell Lung Cancer: The Phase II BALTIC Study. (PubMed, Clin Cancer Res)
    In BALTIC, all combination regimens demonstrated tolerable safety profiles, but antitumor activity was limited in refractory/resistant ES-SCLC. Among patients treated with durvalumab plus tremelimumab, an association of on-treatment reduction in ctDNA with longer OS suggests the potential use of ctDNA as a surrogate of treatment response, warranting further investigation.
    P2 data • Journal • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1)
    |
    Lynparza (olaparib) • carboplatin • Imfinzi (durvalumab) • Imjudo (tremelimumab-actl) • adavosertib (AZD1775) • ceralasertib (AZD6738)
    5ms
    ATARI: ATr Inhibitor in Combination With Olaparib/Durvalumab (MEDI4736) in Gynaecological Cancers With ARId1A Loss or no Loss (clinicaltrials.gov)
    P2, N=174, Recruiting, Institute of Cancer Research, United Kingdom | N=40 --> 174 | Trial completion date: Mar 2023 --> Apr 2026 | Trial primary completion date: Mar 2023 --> Apr 2026
    Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
    |
    MUC16 (Mucin 16, Cell Surface Associated)
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • ceralasertib (AZD6738)
    5ms
    Olaparib With Ceralasertib in Recurrent Osteosarcoma (clinicaltrials.gov)
    P2, N=63, Recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Jun 2024 --> Dec 2024
    Trial primary completion date • Combination therapy
    |
    Lynparza (olaparib) • ceralasertib (AZD6738)
    6ms
    Hypoxia-Responsive Prodrug of ATR Inhibitor, AZD6738, Selectively Eradicates Treatment-Resistant Cancer Cells. (PubMed, Adv Sci (Weinh))
    In addition, ICT10336 exhibited a superior and efficient multicellular penetration ability in 3D tumor models, and selectively eradicated cells at the hypoxic core compared to AZD6738. In summary, the preclinical data demonstrate a new strategy of tumor-targeted delivery of ATR inhibitors with significant potential of enhancing the therapeutic index.
    Journal
    |
    HIF1A (Hypoxia inducible factor 1, alpha subunit)
    |
    ceralasertib (AZD6738)
    6ms
    Combination ATR and PARP Inhibitor (CAPRI) Trial With AZD6738 and Olaparib in Recurrent Ovarian Cancer (clinicaltrials.gov)
    P2, N=86, Active, not recruiting, University of Pennsylvania | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • MUC16 (Mucin 16, Cell Surface Associated)
    |
    Lynparza (olaparib) • ceralasertib (AZD6738)
    6ms
    MONETTE: A Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Melanoma and Resistance to PD-(L)1 Inhibition (clinicaltrials.gov)
    P2, N=194, Active, not recruiting, AstraZeneca | Trial completion date: Apr 2024 --> Jun 2025
    Trial completion date • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)
    6ms
    PLANETTE: A Study Investigating DNA-damage Response Agents in Molecularly Altered Advanced Cancer (clinicaltrials.gov)
    P2, N=54, Active, not recruiting, AstraZeneca | Trial completion date: Feb 2024 --> Feb 2025
    Trial completion date • Metastases
    |
    ATM (ATM serine/threonine kinase)
    |
    ceralasertib (AZD6738)
    6ms
    Inhibition of key DNA double strand break repair protein kinases enhances radiosensitivity of head and neck cancer cells to X-ray and proton irradiation. (PubMed, Cell Death Discov)
    Using inhibitors targeting ATM (AZD1390), ATR (AZD6738) and DNA-Pkcs (AZD7648), we observed that this led to significantly decreased clonogenic survival of HNSCC cell lines following both X-ray and proton irradiation. We confirmed that the inhibitors in combination with X-rays and protons led to DSB persistence, and increased micronuclei formation. Cumulatively, our data suggest that targeting DSB repair, particularly via ATM and DNA-Pkcs inhibition, can exacerbate the impact of ionising radiation in sensitising HNSCC cell models.
    Journal
    |
    ATR (Ataxia telangiectasia and Rad3-related protein)
    |
    ceralasertib (AZD6738) • AZD1390 • AZD7648
    7ms
    Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Patients With Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial (clinicaltrials.gov)
    P1, N=51, Recruiting, National Cancer Institute (NCI) | N=15 --> 51
    Enrollment change • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • RAS (Rat Sarcoma Virus) • CD4 (CD4 Molecule)
    |
    Enhertu (fam-trastuzumab deruxtecan-nxki) • ceralasertib (AZD6738)
    7ms
    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=563, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial completion date: May 2025 --> Aug 2025
    Enrollment closed • Trial completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    Imfinzi (durvalumab) • docetaxel • ceralasertib (AZD6738)
    7ms
    Chemo-Immunotherapy Followed by Durvalumab and Ceralasertib in Treatment Naïve Patients With Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=30, Recruiting, Muhammad Furqan | Trial completion date: May 2024 --> Sep 2024
    Trial completion date
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • etoposide IV • ceralasertib (AZD6738)
    7ms
    National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=423, Active, not recruiting, University of Birmingham | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024
    Trial completion date • Trial primary completion date • IO biomarker
    |
    NKX2-1 (NK2 Homeobox 1) • TP63 (Tumor protein 63)
    |
    Xalkori (crizotinib) • Tagrisso (osimertinib) • Ibrance (palbociclib) • Imfinzi (durvalumab) • docetaxel • Koselugo (selumetinib) • Truqap (capivasertib) • fexagratinib (ABSK091) • ceralasertib (AZD6738) • sitravatinib (MGCD516) • vistusertib (AZD2014)
    8ms
    PIONeeR: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (clinicaltrials.gov)
    P2, N=114, Active, not recruiting, Assistance Publique Hopitaux De Marseille | Recruiting --> Active, not recruiting | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Oct 2023 --> Oct 2024
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases • Immuno-oncology
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation • ALK rearrangement • ROS1 rearrangement
    |
    Imfinzi (durvalumab) • docetaxel • Orpathys (savolitinib) • ceralasertib (AZD6738) • oleclumab (MEDI9447) • monalizumab (IPH2201)
    8ms
    Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-sensitive epithelial ovarian cancer (cohort A). (ASCO 2024)
    C+O was well tolerated and active in pts with platinum sensitive HGSOC warranting further evaluation. Efficacy was seen regardless of the presence of tumor genomic instability.
    P2 data • Clinical • PARP Biomarker • BRCA Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ATR (Ataxia telangiectasia and Rad3-related protein) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C)
    |
    Myriad myChoice® CDx
    |
    Lynparza (olaparib) • ceralasertib (AZD6738)
    8ms
    DDR-Umbrella Study of DDR Targeting Agents in Advanced Biliary Tract Cancer (clinicaltrials.gov)
    P2, N=74, Active, not recruiting, Seoul National University Hospital | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial primary completion date • Metastases
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • ceralasertib (AZD6738)
    8ms
    AZD6738 Plus Durvalumab in Biliary Tract Cancer (clinicaltrials.gov)
    P2, N=26, Recruiting, Seoul National University Hospital | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial completion date • Trial primary completion date
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)
    8ms
    Discovery of a Meisoindigo-Derived PROTAC as the ATM Degrader: Revolutionizing Colorectal Cancer Therapy via Synthetic Lethality with ATR Inhibitors. (PubMed, J Med Chem)
    Notably, 9b-induced ATM degradation synergistically enhanced the efficacy of ATR inhibitor AZD6738 both in vitro and in vivo. This work establishes the synthetic lethality-inducing properties of ATR inhibitors in the ATM-deficient context, thereby providing new avenues to innovative therapies for colorectal cancer.
    Journal • Synthetic lethality
    |
    ATM (ATM serine/threonine kinase)
    |
    ceralasertib (AZD6738)
    9ms
    Targeting ATR Pathway in Solid Tumors: Evidence of Improving Therapeutic Outcomes. (PubMed, Int J Mol Sci)
    In addition, ATR inhibition plays a significant role in the activation of the immune system by increasing the tumor mutational burden and neoantigen load as well as by triggering the accumulation of cytosolic DNA and subsequently inducing the cGAS-STING pathway and the type I IFN response. Taken together, we review stimulating data showing that ATR kinase inhibition can alter the DDR network, the immune system, and their interplay and, therefore, potentially provide a novel strategy to improve the efficacy of antitumor therapy, using ATR inhibitors as monotherapy or in combination with genotoxic drugs and/or immunomodulators.
    Review • Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • ATM (ATM serine/threonine kinase)
    |
    ceralasertib (AZD6738)
    9ms
    AZD6738 for Patients With Progressive MDS or CMML (clinicaltrials.gov)
    P1, N=52, Recruiting, Massachusetts General Hospital | Trial primary completion date: May 2022 --> May 2024
    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 • U2AF1 mutation
    |
    ceralasertib (AZD6738)
    10ms
    The novel ATR inhibitor M1774 induces replication protein overexpression and broad synergy with DNA-targeted anticancer drugs. (PubMed, Mol Cancer Ther)
    As single agent, M1774 suppressed cancer cell viability at nanomolar concentrations, showing greater activity than ceralasertib and berzosertib, but less potency than gartisertib and elimusertib in the small-cell lung cancer H146, H82, and DMS114 cell lines. Low dose of M1774 was found highly synergistic with a broad spectrum of clinical DDAs including TOP1 inhibitors (SN-38/irinotecan, topotecan, exatecan, and exatecan), the TOP2 inhibitor etoposide, cisplatin, the RNA polymerase II inhibitor lurbinectedin, and the PARP inhibitor talazoparib in various models including cancer cell lines, patient-derived organoids, and mouse xenograft models. Furthermore, we demonstrate that M1774 reverses chemoresistance to anticancer DDAs in cancer cells lacking SLFN11 expression, suggesting that SLFN11 can be utilized for patient selection in upcoming clinical trials.
    Journal • PARP Biomarker
    |
    SLFN11 (Schlafen Family Member 11) • PLK1 (Polo Like Kinase 1) • CHEK1 (Checkpoint kinase 1) • CCNB1 (Cyclin B1) • CDC45 (Cell Division Cycle 45)
    |
    SLFN11 expression
    |
    cisplatin • Talzenna (talazoparib) • etoposide IV • irinotecan • berzosertib (M6620) • ceralasertib (AZD6738) • topotecan • elimusertib (BAY 1895344) • Zepzelca (lurbinectedin) • tuvusertib (M1774) • gartisertib (M4344)
    10ms
    Testing Olaparib and AZD6738 in IDH1 and IDH2 Mutant Tumors (clinicaltrials.gov)
    P2, N=50, Suspended, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025
    Trial completion date • Trial primary completion date
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation
    |
    Lynparza (olaparib) • ceralasertib (AZD6738)
    10ms
    Efficacy and safety of ceralasertib in the PLANETTE study in patients (pts) with ATM-altered advanced solid tumors (ASTs) or metastatic castration-resistant prostate cancer (mCRPC) (AACR 2024)
    Responses to ceralasertib monotherapy were limited in ATM-altered tumors, despite reaching target plasma levels. Alternative pt selection and combination treatment strategies are being explored.
    Clinical • Metastases
    |
    ATM expression
    |
    FoundationOne® CDx
    |
    ceralasertib (AZD6738)
    10ms
    CONCORDE: A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC (clinicaltrials.gov)
    P1, N=200, Recruiting, University of Leeds | Trial completion date: May 2027 --> Mar 2028 | Trial primary completion date: Mar 2023 --> Apr 2025
    Trial completion date • Trial primary completion date • Combination therapy
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • ceralasertib (AZD6738) • AZD1390 • saruparib (AZD5305)
    10ms
    The ATR inhibitor ceralasertib potentiates cancer checkpoint immunotherapy by regulating the tumor microenvironment. (PubMed, Nat Commun)
    The Ataxia telangiectasia and Rad3-related (ATR) inhibitor ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit in melanoma and lung cancer patients who progressed on immunotherapy. IFNI also promotes anti-proliferative effects of ceralasertib on tumor cells. Here, we report that broad immunomodulatory changes following intermittent ATR inhibition underpins the clinical therapeutic benefit and indicates its wider impact on antitumor immunity.
    Journal
    |
    CD8 (cluster of differentiation 8)
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)
    10ms
    Chemo-Immunotherapy Followed by Durvalumab and Ceralasertib in Treatment Naïve Patients With Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=30, Recruiting, Muhammad Furqan | Trial primary completion date: Dec 2023 --> Mar 2024
    Trial primary completion date
    |
    cisplatin • carboplatin • Imfinzi (durvalumab) • etoposide IV • ceralasertib (AZD6738)