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    DRUG:

    tuvusertib (M1774)

    i
    Other names: M1774, M 1774, MSC2584415A, VXc-400, VR 1363004, M-1774, MSC 2584415A, VR1363004, VXc 400, MSC-2584415A, VR-1363004, VXc400, VRT-1363004, VRT1363004, VRT 1363004
    Company:
    EMD Serono
    Drug class:
    ATR inhibitor
    Related drugs:
    3d
    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
    |
    ARID1A (AT-rich interaction domain 1A) • ATRX (ATRX Chromatin Remodeler)
    |
    ATM mutation • ARID1A mutation
    |
    Zejula (niraparib) • tuvusertib (M1774)
    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
    |
    PLX038 • tuvusertib (M1774)
    2ms
    M9466 Alone or in Combination in Advanced Solid Tumors (DDriver 501) (clinicaltrials.gov)
    P1, N=141, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    abiraterone acetate • prednisone • tuvusertib (M1774) • M9466 • prednisolone
    2ms
    The ATR inhibitor tuvusertib (M1774) sensitizes prostate carcinoma to natural killer cell-mediated cytotoxicity, which is further augmented by the IL-15 receptor superagonist N-803. (PubMed, Cancer Immunol Immunother)
    Enhanced avelumab-mediated antibody-dependent cell-mediated cytotoxicity and lysis by PD-L1 targeting high-affinity NK (PD-L1 t-haNK) cells were observed in tuvusertib-treated DU145. In vivo in the DU145 PCa xenograft model, tuvusertib and N-803 combination therapy demonstrated marked and significant antitumor efficacy relative to either monotherapy, eliciting superior tumor growth control and prolonging survival. Our findings support further investigation into the use of ATRi with immune checkpoint blockade and/or immune-stimulating agents in prostate cancer.
    Journal
    |
    BCL2L1 (BCL2-like 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • IL15 (Interleukin 15) • TNFRSF10B (TNF Receptor Superfamily Member 10b) • NKG2D (killer cell lectin like receptor K1)
    |
    Bavencio (avelumab) • Anktiva (nogapendekin alfa inbakicept-pmln) • tuvusertib (M1774) • PD-L1.t-haNK
    4ms
    Tuvusertib (M1774) Human Mass Balance and Absolute Bioavailability Study (DDRIVER Solid Tumors 303) (clinicaltrials.gov)
    P1, N=12, Active, not recruiting, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    tuvusertib (M1774)
    4ms
    Study of Tuvusertib (M1774) in Combination With DNA Damage Response Inhibitor or Immune Checkpoint Inhibitor (DDRiver Solid Tumors 320) (clinicaltrials.gov)
    P1, N=120, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed • Checkpoint inhibition • IO biomarker
    |
    Bavencio (avelumab) • tuvusertib (M1774) • lartesertib (M4076)
    4ms
    Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302) (clinicaltrials.gov)
    P2, N=63, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Recruiting --> Active, not recruiting | N=130 --> 63
    Enrollment closed • Enrollment change
    |
    Zejula (niraparib) • tuvusertib (M1774) • lartesertib (M4076)
    6ms
    Integrated Population Pharmacokinetic, Pharmacodynamic, and Safety Analyses to Inform Dosage Selection in the Clinical Development of the ATR Inhibitor Tuvusertib. (PubMed, Clin Pharmacol Ther)
    The analysis supports tuvusertib 180 mg QD 2w on/1w off as the RDE and 100 mg QD as the no-regret dose for clinical evaluation. This example underscores the value of integrated quantitative pharmacology analyses to inform dose selection using a totality of evidence approach.
    PK/PD data • Journal
    |
    ARID1A (AT-rich interaction domain 1A)
    |
    ARID1A mutation
    |
    tuvusertib (M1774)
    6ms
    Testing the Effect of M1774 on Hard-to-Treat Refractory SPOP-mutant Prostate Cancer (clinicaltrials.gov)
    P2, N=20, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting
    Enrollment closed
    |
    SPOP (Speckle Type BTB/POZ Protein)
    |
    tuvusertib (M1774)
    6ms
    M9466 Alone or in Combination in Advanced Solid Tumors (DDriver 501) (clinicaltrials.gov)
    P1, N=141, Recruiting, EMD Serono Research & Development Institute, Inc. | N=96 --> 141 | Trial completion date: Mar 2026 --> Feb 2027 | Trial primary completion date: Mar 2026 --> Feb 2027
    Enrollment change • Trial completion date • Trial primary completion date
    |
    abiraterone acetate • prednisone • tuvusertib (M1774) • M9466 • prednisolone
    7ms
    Tuvusertib (M1774) in Combination With Cemiplimab in Participants With Non-Squamous NSCLC (DDRiver NSCLC 322) (clinicaltrials.gov)
    P1/2, N=61, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial primary completion date: May 2025 --> Mar 2026
    Trial primary completion date
    |
    Libtayo (cemiplimab-rwlc) • tuvusertib (M1774)
    7ms
    Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302) (clinicaltrials.gov)
    P2, N=130, Recruiting, EMD Serono Research & Development Institute, Inc. | N=60 --> 130
    Enrollment change
    |
    Zejula (niraparib) • tuvusertib (M1774) • lartesertib (M4076)