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    DRUG:

    peposertib (M3814)

    i
    Other names: M3814, MSC2490484A, M 3814, M-3814, MSC-2490484A, MSC-2490484A
    Company:
    EMD Serono
    Drug class:
    DNA PK inhibitor
    Related drugs:
    4d
    ETCTN 10563: Testing Low-Dose Common Chemotherapy (Liposomal Doxorubicin) in Combination With an Anti-Cancer Drug, Peposertib, in Advanced Sarcoma (clinicaltrials.gov)
    P1, N=30, Recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> Nov 2026 | Trial primary completion date: May 2026 --> Nov 2026
    Trial completion date • Trial primary completion date
    |
    pegylated liposomal doxorubicin • Myocet (non-pegylated liposomal doxorubicin) • peposertib (M3814) • Duomeisu (pegylated liposomal doxorubicin)
    17d
    Radiation Medication (Radium-223 Dichloride) Versus Radium-223 Dichloride Plus Radiation Enhancing Medication (M3814) Versus Radium-223 Dichloride Plus M3814 Plus Avelumab (a Type of Immunotherapy) for Advanced Prostate Cancer Not Responsive to Hormonal Therapy (clinicaltrials.gov)
    P1/2, N=90, Recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2026 --> Apr 2027 | Trial primary completion date: Apr 2026 --> Apr 2027
    Trial completion date • Trial primary completion date
    |
    Bavencio (avelumab) • peposertib (M3814) • Xofigo (radium Ra-223 dichloride)
    2ms
    Targeting the Non-Homologous End-Joining Pathway Sensitizes MDM2-Amplified Liposarcoma to Doxorubicin by Enhancing p53-Mediated Senescence. (PubMed, Cancer Res)
    Three parallel genome-wide CRISPR-Cas9 knockout screens were conducted in DDLPS cells to sensitize to palbociclib (CDK4 inhibitor), nutlin-3a (MDM2 inhibitor) or doxorubicin...Genetic perturbation of TDP2 or pharmacological inhibition of DNA-PKcs using peposertib synergized with prolonged administration of low-dose doxorubicin to induce cell cycle arrest and senescence, and subsequent senolytic treatment with Bcl2 inhibitor navitoclax triggered senescent cells to undergo apoptosis...These findings provide a rationale for targeting the NHEJ pathway to enhance the efficacy of low-dose doxorubicin in DDLPS, highlighting a potential therapeutic strategy exploiting p53-mediated cell cycle arrest and senescence. Furthermore, this study provides evidence of maintained baseline p53 activity in MDM2-amplified DDLPS.
    Journal
    |
    CCNE1 (Cyclin E1) • MDM2 (E3 ubiquitin protein ligase) • CDK2 (Cyclin-dependent kinase 2) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) • E2F3 (E2F transcription factor 3)
    |
    Ibrance (palbociclib) • doxorubicin hydrochloride • navitoclax (ABT 263) • peposertib (M3814)
    3ms
    Testing the Combination of New Anti-cancer Drug Peposertib With Avelumab and Radiation Therapy for Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies (clinicaltrials.gov)
    P1/2, N=103, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting
    Enrollment closed • Tumor mutational burden
    |
    Bavencio (avelumab) • peposertib (M3814)
    4ms
    Testing the Combination of New Anti-cancer Drug Peposertib With Avelumab and Radiation Therapy for Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies (clinicaltrials.gov)
    P1/2, N=103, Suspended, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jul 2027 | Trial primary completion date: Dec 2025 --> Jul 2027
    Trial completion date • Trial primary completion date • Tumor mutational burden
    |
    Bavencio (avelumab) • peposertib (M3814)
    4ms
    Testing the Addition of an Anti-cancer Drug, M3814, to the Usual Treatment (Mitoxantrone, Etoposide, and Cytarabine) for Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=48, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting
    Enrollment closed
    |
    RARA (Retinoic Acid Receptor Alpha) • PML (Promyelocytic Leukemia) • CD4 (CD4 Molecule)
    |
    cytarabine • etoposide IV • mitoxantrone • peposertib (M3814) • Starasid (cytarabine ocfosfate)
    5ms
    NRG-HN008: Testing the Addition of M3814 (Peposertib) to Radiation Therapy for Patients With Advanced Head and Neck Cancer Who Cannot Take Cisplatin (clinicaltrials.gov)
    P1, N=21, Active, not recruiting, National Cancer Institute (NCI) | N=42 --> 21 | Trial completion date: Dec 2025 --> Dec 2026
    Enrollment change • Trial completion date
    |
    CD4 (CD4 Molecule)
    |
    peposertib (M3814)
    5ms
    Testing the Addition of An Anti-cancer Drug, M3814 (Peposertib), to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Pancreatic Neuroendocrine Tumors (clinicaltrials.gov)
    P1, N=29, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Jun 2026 | Trial primary completion date: Oct 2025 --> Jun 2026
    Trial completion date • Trial primary completion date
    |
    peposertib (M3814) • Lutathera (lutetium Lu 177 dotatate)
    5ms
    Testing the Combination of New Anti-cancer Drug Peposertib With Avelumab and Radiation Therapy for Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies (clinicaltrials.gov)
    P1/2, N=103, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension • Tumor mutational burden
    |
    Bavencio (avelumab) • peposertib (M3814)
    6ms
    Combined DNA-PK and PARP Inhibition as a Therapeutic Strategy in BRCA-Mutated Prostate Cancer: An in Vitro Pilot Study. (PubMed, Technol Cancer Res Treat)
    Scramble LNCaP, BRCA1 KO, and BRCA2 KO cells were treated with the PARPi talazoparib, the DNA-PK inhibitor nedisertib and their combination. Therapeutically targeting NHEJ presents a promising approach in treating BRCA-mutated PCa. Further in vivo investigations are required to assess the tolerability of this drug combination.
    Preclinical • Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • ANXA5 (Annexin A5)
    |
    BRCA mutation
    |
    Talzenna (talazoparib) • peposertib (M3814)
    7ms
    Peposertib and Radiation Therapy, Followed by Temozolomide for the Treatment of Patients With Newly Diagnosed MGMT Unmethylated Glioblastoma or Gliosarcoma (clinicaltrials.gov)
    P1, N=29, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2025 --> Dec 2027 | Trial primary completion date: Oct 2025 --> Dec 2027
    Trial completion date • Trial primary completion date
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    |
    temozolomide • peposertib (M3814)
    8ms
    NRG-HN008: Testing the Addition of M3814 (Peposertib) to Radiation Therapy for Patients With Advanced Head and Neck Cancer Who Cannot Take Cisplatin (clinicaltrials.gov)
    P1, N=42, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2025 --> Dec 2025 | Trial primary completion date: Sep 2025 --> Dec 2025
    Trial completion date • Trial primary completion date
    |
    CD4 (CD4 Molecule)
    |
    peposertib (M3814)