^
    4d
    A Study of SHR3680, HS-20093 and SHR2554 in Subjects With Prostate Cancer (clinicaltrials.gov)
    P2, N=218, Recruiting, Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting --> Recruiting
    Enrollment open
    |
    abiraterone acetate • zeprumetostat (SHR-2554) • AiRuiEn (rezvilutamide) • risvutatug rezetecan (GSK5764227)
    9d
    EZH2 Inhibition Restores Tumor Suppressor SFRP1 Activity by Reprogramming Extrachromosomal Circular DNA Dynamics in Ovarian Cancer. (PubMed, Biology (Basel))
    In this study, we systematically investigate the correlation between Tazemetostat, a highly selective EZH2 inhibitor, and alterations in the eccDNA landscape and transcriptional programs in ovarian cancer...By integrating multi-omics and spatial single-cell transcriptomics, we uncovered a novel epigenetic-eccDNA axis that may contribute to oncogenic plasticity and therapeutic resistance. This could result in a paradigm shift in targeting eccDNA-driven malignancies.
    Journal
    |
    SFRP1 (Secreted frizzled related protein 1)
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    Tazverik (tazemetostat)
    10d
    CDZR123A12107: A clinical trial to learn about the effects of DZR123 and JSB462 given together in men with advanced prostate cancer that has stopped responding to other treatments (2025-521880-10-00)
    P1/2, N=76, Recruiting, Novartis Pharma AG | Not yet recruiting --> Recruiting
    Enrollment open
    |
    docetaxel • Xtandi (enzalutamide) • abiraterone acetate • cabazitaxel • tulmimetostat (DZR123) • luxdegalutamide (ARV-766)
    10d
    Therapeutic Horizons in Targeting EZH2 With Dual and Non-PROTAC Inhibitor Molecules: Recent Achievements, Comparative Analysis, and Future Perspectives. (PubMed, Arch Pharm (Weinheim))
    Conversely, multitarget hybrids such as Olaparib-Tazemetostat (33) and Tazemetostat-resorcinol (170) maintained robust cellular efficacy through synergistic epigenetic and DNA-repair modulation. Future perspectives emphasize rational design strategies integrating dual targeting, computational modeling, and covalent functionalities to enhance therapeutic durability. Collectively, these advances explain the evolving therapeutic horizon of non-PROTAC and dual EZH2 inhibitors, offering an outline for next-generation EZH2 inhibitors.
    Clinical • Review • Journal • PARP Biomarker
    |
    EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • BRD4 (Bromodomain Containing 4) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    Lynparza (olaparib) • Tazverik (tazemetostat)
    11d
    Pyridone-based EZH2 inhibitor anticancer candidates: synthetic approaches, comparative analysis, and future perspectives. (PubMed, Future Med Chem)
    Comparative ADME and drug-likeness analyses highlight key molecular determinants of potency and pharmacokinetic performance. Finally, an outline is given on emerging opportunities and challenges shaping the future of pyridone-based EZH2 inhibitor rational design and optimization strategies for the development of next-generation anticancer candidates.
    Review • Journal • PARP Biomarker
    |
    PARP1 (Poly(ADP-Ribose) Polymerase 1) • BRD4 (Bromodomain Containing 4) • CDK9 (Cyclin Dependent Kinase 9) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    Tazverik (tazemetostat)
    16d
    Epigenetic regulation of NDGA and its synergistic inhibition with EZH2 inhibitors in prostate cancer via NRP1. (PubMed, Acta Pharmacol Sin)
    On the other hand, NDGA inhibited CBP/p300, decreased H3K27ac levels, and synergized with the EZH2 inhibitor EPZ6438 against PC3 cells. In conclusion, NDGA is a potential epigenetic antineoplastic agent that downregulates EZH2 and H3K27me3 through the NRP1 and PI3K/AKT/mTOR pathways and exerts a synergistic antitumor effect with H3K27ac and EZH2 inhibitors, suggesting that it could be a valuable therapeutic option for prostate cancer.
    Journal
    |
    EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • NRP1 (Neuropilin 1) • E2F1 (E2F transcription factor 1)
    |
    Tazverik (tazemetostat)
    16d
    Integrative bulk and single-cell transcriptomics link EZH2 to immunosuppressive programs and tumor-Treg crosstalk in castration-resistant prostate cancer. (PubMed, Front Immunol)
    For perturbation, the EZH2 inhibitor tazemetostat was evaluated in the CRPC-relevant C42 cell line with H3K27me3 readouts and transcriptomic profiling, with key changes validated by RT-qPCR...This multi-layer integrative analysis suggests that EZH2 is associated with proliferative malignant states and immunosuppressive microenvironment features in advanced PCa, including Treg-linked crosstalk. Transcriptomic profiling following EZH2 inhibition supports modulation of these programs by EZH2-targeted perturbation, while functional and causal mechanisms warrant further investigation.
    Journal
    |
    EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • PLCG2 (Phospholipase C Gamma 2) • SOCS3 (Suppressor Of Cytokine Signaling 3) • TIMP3 (TIMP Metallopeptidase Inhibitor 3)
    |
    Tazverik (tazemetostat)
    17d
    Tazemetostat and Palbociclib With CPX-351for R/R AML (clinicaltrials.gov)
    P1, N=24, Recruiting, Thomas Jefferson University | Suspended --> Recruiting | Trial completion date: Jan 2026 --> Jan 2029 | Trial primary completion date: Jan 2026 --> Jan 2028
    Enrollment open • Trial completion date • Trial primary completion date
    |
    Ibrance (palbociclib) • Vyxeos (cytarabine/daunorubicin liposomal formulation) • Tazverik (tazemetostat)
    17d
    DS3201-330: A Study of Valemetostat Tosylate Plus Pembrolizumab versus Pembrolizumab Alone in First-Line NSCLC Without Actionable Genomic Alterations (2024-519671-26-00)
    P1/2, N=21, Completed, Daiichi Sankyo Inc.
    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) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    PD-L1 expression • KRAS mutation
    |
    PD-L1 IHC 22C3 pharmDx
    |
    Keytruda (pembrolizumab) • Ezharmia (valemetostat)
    17d
    CDZR123A12107: A clinical trial to learn about the effects of DZR123 and JSB462 given together in men with advanced prostate cancer that has stopped responding to other treatments (2025-521880-10-00)
    P1/2, N=76, Not yet recruiting, Novartis Pharma AG
    New P1/2 trial
    |
    docetaxel • Xtandi (enzalutamide) • abiraterone acetate • cabazitaxel • tulmimetostat (DZR123) • luxdegalutamide (ARV-766)
    17d
    2024/3993 EZHiSWITCH: An open label phase II platform modular study exploring the efficacy and safety of the Valemetostat (EZH1/2 inhibitor) in patients with selected solid tumors. (2024-519788-16-00)
    P1/2, N=600, Not yet recruiting, Institut Gustave Roussy
    New P1/2 trial
    |
    ARID1A (AT-rich interaction domain 1A) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    Ezharmia (valemetostat)
    17d
    C2321008: A Study to Learn About the Investigational Medicine Called Mevrometostat (PF-06821497) in Men With Metastatic Castration-Sensitive Prostate Cancer Who Have Not Tried Novel Hormonal Therapy or Chemotherapy for Metastatic Prostate Cancer (MEVPRO-3) (2024-519369-24-00)
    P2/3, N=434, Recruiting, Pfizer Inc.
    New P2/3 trial
    |
    Xtandi (enzalutamide) • mevrometostat (PF-06821497)