^
    2d
    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 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027
    Trial completion date • Trial primary completion date • First-in-human
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    ARID1A (AT-rich interaction domain 1A) • ATRX (ATRX Chromatin Remodeler)
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    ATM mutation • ARID1A mutation
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    Zejula (niraparib) • tuvusertib (M1774)
    4d
    ATR inhibitors: from targeting the DNA damage response to exploiting synthetic lethality-A paradigm shift in Cancer therapy. (PubMed, Bioorg Chem)
    We provide a detailed analysis of the structure-activity relationships (SAR) of leading clinical candidates, including berzosertib, ceralasertib, and elimusertib, focusing on strategic chemical modifications such as scaffold hopping and sulfoximine substitution to optimize selectivity and druggability. Critical challenges, specifically dose-limiting hematological toxicities and acquired resistance, are analyzed alongside the search for robust predictive biomarkers. By synthesizing current pharmacological and clinical data, this work outlines the trajectory for next-generation ATR-targeted precision medicine.
    Review • Journal
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    ATR (Ataxia telangiectasia and Rad3-related protein)
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    berzosertib (M6620) • ceralasertib (AZD6738) • elimusertib (BAY 1895344)
    5d
    Loss of BOK increases vulnerability of p53 deficient non-small cell lung cancer cells to ATR inhibition through its role in uridine metabolism. (PubMed, Cell Death Differ)
    We exploited this vulnerability by inhibiting the ATR-mediated DNA damage response pathway with the selective ATR inhibitor ceralasertib (AZD6738)...Given the frequent inactivation of p53 in lung cancer, our study offers a rationale for clinical exploration of ATR inhibitors, in combination with standard chemotherapy, in the context of reduced BOK function. Future investigations into the broader role of BOK in genomic stability and nucleotide metabolism may uncover additional therapeutic strategies for cancers with repressed BOK.
    Journal • IO biomarker
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    BCL2 (B-cell CLL/lymphoma 2)
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    ceralasertib (AZD6738)
    6d
    An Phase Ib/II Clinical Trial of TCC1727 Combination Therapy in Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=266, Recruiting, Beijing Tide Pharmaceutical Co., Ltd
    New P1/2 trial
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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    EGFR mutation • MSI-H/dMMR • BRAF mutation • NRAS mutation • RAS mutation • RET mutation • MET mutation
    |
    Lynparza (olaparib) • topotecan • Andewei (benmelstobart)
    8d
    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, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension • Checkpoint inhibition
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    Imfinzi (durvalumab) • ceralasertib (AZD6738)
    11d
    PEPN2112: Elimusertib for the Treatment of Relapsed or Refractory Solid Tumors (clinicaltrials.gov)
    P1/2, N=31, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2025 --> Mar 2026
    Trial completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • POLD1 (DNA Polymerase Delta 1) • FOXO1 (Forkhead box O1) • XRCC2 (X-Ray Repair Cross Complementing 2) • ATF1 (Activating Transcription Factor 1) • PAX3 (Paired Box 3)
    |
    elimusertib (BAY 1895344)
    12d
    A Study to Evaluate the Effect of Ceralasertib on Drug X, Drug Y and Drug Z (clinicaltrials.gov)
    P1, N=1, Terminated, AstraZeneca | N=20 --> 1 | Recruiting --> Terminated; The study terminated because the clinical development programme for Ceralasertib has been discontinued.
    Enrollment change • Trial termination
    |
    ceralasertib (AZD6738)
    13d
    Testing the Addition of an Anti-cancer Drug, Berzosertib, to the Usual Treatment (Radiation Therapy) for Chemotherapy-Resistant Triple-Negative and Estrogen and/or Progesterone Receptor Positive, HER2 Negative Breast Cancer (clinicaltrials.gov)
    P1, N=42, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Apr 2026 --> Feb 2027 | Trial completion date: Apr 2026 --> Feb 2027
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    HER-2 negative
    |
    berzosertib (M6620)
    13d
    Camonsertib, an ATRi, in Combination with Low-Dose Gemcitabine in Solid Tumors with DNA Damage Response (DDR) Aberrations: Preclinical and Phase 1b Results. (PubMed, Clin Cancer Res)
    Camonsertib and low-dose gemcitabine demonstrated preliminary clinical activity, but due to challenging tolerability further evaluation is warranted to identify the optimal dosing regimen and subset of patients who may benefit most from this combination.
    P1 data • Preclinical • Journal
    |
    ATR (Ataxia telangiectasia and Rad3-related protein)
    |
    gemcitabine • camonsertib (RP-3500)
    18d
    Novel therapeutic potential of the PARP inhibitor talazoparib in synovial sarcoma and its combined effect with ATR inhibitor. (PubMed, Discov Oncol)
    Talazoparib combined with ATR inhibitor possesses potential application as a therapeutic option for SS.
    Journal • PARP Biomarker
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    CHEK1 (Checkpoint kinase 1) • ANXA5 (Annexin A5)
    |
    Talzenna (talazoparib) • ceralasertib (AZD6738)
    1m
    POP-ART: A Study on Tuvusertib (Oral ATR Inhibitor) in Combination With PLX038 (Topo1 Inhibitor) in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=10, Terminated, Institut Curie | N=92 --> 10 | Trial completion date: Sep 2029 --> Nov 2025 | Recruiting --> Terminated | Trial primary completion date: Sep 2028 --> Nov 2025; Although no safety signal has been observed, given that the industrial development of tuvusertib has been halted regardless of the results, we see no scientific and ethical justification for continuing the study
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date
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    PLX038 • tuvusertib (M1774)
    1m
    Rb1 deficiency induces synthetic lethality with ATR and PKMYT1 coinhibition in breast cancer cell lines and patient-derived xenografts. (PubMed, Sci Transl Med)
    Here, we demonstrate that coinhibition of ATR (RP-3500) and PKMYT1 (RP-6306) induces synthetic lethality in Rb1-deficient breast cancers by disrupting both S-G2 and G2-M checkpoints...Clinically, a retrospective analysis of stage IV breast cancer datasets revealed that Rb1-low tumors display reduced DNA repair pathway activity in triple-negative and CDK4/6 inhibitor-resistant luminal breast cancers. These results identify Rb1 loss as a predictive biomarker for ATR/PKMYT1-targeted therapy, offering a potential precision treatment strategy for advanced breast cancers.
    Preclinical • Journal
    |
    RB1 (RB Transcriptional Corepressor 1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    camonsertib (RP-3500)