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    16d
    A Study to Learn How the Medicine Called [14C] PF-06821497 is Taken up Into and Removed From the Body. (clinicaltrials.gov)
    P1, N=6, Not yet recruiting, Pfizer
    New P1 trial
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    mevrometostat (PF-06821497)
    11ms
    Discovery of targeted therapies for cancer patients: CDK2/4/6 inhibitor Ebvaciclib and EZH2 inhibitor PF-06821497 (ACS-Fall 2023)
    Ebvaciclib, is a CDK2/4/6 inhibitor designed to be co-dosed with hormone therapy (letrozole or fulvestrant) to treat HR+ breast cancer. PF-06821497 is an EZH2 inhibitor currently being evaluated alone and in combination with enzalutamide to treat patients with castration resistant prostate cancer who have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression. Discovery, synthesis, and early clinical results will be presented.
    Clinical
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    Xtandi (enzalutamide capsule) • abiraterone acetate • fulvestrant • letrozole • ebvaciclib (PF-06873600) • mevrometostat (PF-06821497)
    12ms
    PF-06821497 Treatment Of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma (clinicaltrials.gov)
    P1, N=267, Recruiting, Pfizer | Trial completion date: Apr 2025 --> Nov 2025 | Trial primary completion date: Apr 2025 --> Nov 2025
    Trial completion date • Trial primary completion date
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    mevrometostat (PF-06821497)
    almost3years
    EZH2i EPZ-6438 and HDACi vorinostat synergize with ONC201/TIC10 to activate integrated stress response, DR5, reduce H3K27 methylation, ClpX and promote apoptosis of multiple tumor types including DIPG. (PubMed, Neoplasia)
    EZH2i EPZ-6438 (tazemetostat) or PF-06821497 and HDACi vorinostat were combined with ONC201 to treat multiple cancer cell lines and cell viability and histone modifications were analyzed. Although synergy was observed with ONC201 and vorinostat, there was no significant increase in H3K27 acetylation in cell lines including DIPG as compared to vorinostat alone, and in some cases the acetylation was less than vorinostat alone at 72 H. H3K27 methylation reduction correlated with synergy from combinations of either EPZ-6438 or vorinostat with ONC201 or triple combination. Our findings provide a rationale for combination of ONC201 and epigenetic modulators including triple therapy for in vivo and clinical testing in treatment of human malignancies including brain tumors and DIPG.
    Journal
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    ATF4 (Activating Transcription Factor 4) • DRD2 (Dopamine Receptor D2)
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    EZH2 mutation
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    Zolinza (vorinostat) • Tazverik (tazemetostat) • dordaviprone (ONC201) • mevrometostat (PF-06821497)
    3years
    [VIRTUAL] The integrated stress response (ISR) is involved in the synergistic combinatorial efficacy of ONC201 and epigenetic modulators in brain tumor cell lines (AACR 2021)
    EPZ-6438 or PF-06821497 decreased H3K27 tri-methylation. Our study results unravel potent synergy between ONC201 and EZH2i, highlight the role of ISR in the synergy, and provide further insights into the role of H3K27me3 in ONC201 drug sensitivity.
    Preclinical • PARP Biomarker
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    ATF4 (Activating Transcription Factor 4)
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    EZH2 mutation
    |
    Tazverik (tazemetostat) • dordaviprone (ONC201) • mevrometostat (PF-06821497)