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Other names | PF-06821497 |
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Formula | C22H24Cl2N2O5 |
Molar mass | 467.34 g·mol−1 |
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Mevrometostat (development code PF-06821497) is an investigational anticancer drug that functions as a potent and selective inhibitor of enhancer of zeste homolog 2 (EZH2). [1] [2] Currently under development by Pfizer, mevrometostat is being investigated primarily for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in combination with enzalutamide.
Mevrometostat is a small molecule inhibitor that targets EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2). [1] [3] EZH2 plays a crucial role in epigenetic regulation by modifying gene expression patterns that control cellular fate decisions, including differentiation and self-renewal. [1]
In prostate cancer, EZH2 dysregulation contributes to treatment resistance through multiple pathways, including:
Mevrometostat demonstrates dose-dependent EZH2 inhibition, leading to reactivation of tumor suppressor genes while suppressing genes involved in tumor progression. [5]
The primary clinical evaluation of mevrometostat is being conducted through a phase 1/2 dose-expansion study (NCT03460977) investigating the combination of mevrometostat with enzalutamide and androgen deprivation therapy in patients with mCRPC. [6]
The dose-expansion portion of this study enrolled patients with mCRPC who had previously received abiraterone, with evidence of disease progression per modified Prostate Cancer Working Group 3 criteria. [2]
In the randomized dose-expansion study, the combination of mevrometostat (1,250 mg twice daily on an empty stomach) plus enzalutamide demonstrated:
The median radiographic progression-free survival was 14.3 months with the combination therapy compared to 6.2 months with enzalutamide alone. [8]
Based on promising phase I/II results, Pfizer has initiated multiple phase 3 clinical trials:
The MEVPRO-1 study (NCT06551324) is a randomized phase 3 trial evaluating mevrometostat in combination with enzalutamide versus physician's choice of therapy in patients with mCRPC previously treated with abiraterone acetate. [9] [10]
The MEVPRO-2 study (NCT06629779) is evaluating mevrometostat plus enzalutamide in androgen receptor pathway inhibitor (ARPI)-naïve patients with mCRPC. [11] [12]
Pfizer has also initiated phase 3 trials evaluating mevrometostat plus enzalutamide in first-line metastatic castration-sensitive prostate cancer. [8] [13]
The most common adverse events considered related to mevrometostat treatment include:
Dose optimization studies found that mevrometostat 875 mg twice daily with food showed similar efficacy and better safety compared to the 1,250 mg dose on an empty stomach. [15]
Based on safety and pharmacokinetic findings from phase 1 trials, mevrometostat 875 mg twice daily with food was selected as the recommended dose for phase 3 clinical development in combination with enzalutamide. [16]
As of 2025, mevrometostat remains an investigational agent under clinical development by Pfizer. The drug has not received regulatory approval from the Food and Drug Administration (FDA), European Medicines Agency (EMA), or other regulatory authorities.