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Advances in mCRPC

CE / CME

Advances in Metastatic Castration-Resistant Prostate Cancer: Biomarker-Driven Treatment Strategies and Emerging Therapeutic Approaches

ABIM MOC: maximum of 0.50 Medical Knowledge MOC point

Physicians: Maximum of 0.50 AMA PRA Category 1 Credit™

Released: July 20, 2026

Expiration: January 19, 2027

Neal D. Shore
Neal D. Shore, MD, FACS
CME/CE Information

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Mevrometostat: Epigenetic Therapy via EZH2 Inhibition

EZH2 is overexpressed in CRPC and is associated with a poor prognosis.23 Mevrometostat is an oral, selective EZH2 inhibitor that has been evaluated in multiple studies. When combined with an ARPI, studies have suggested mild GI toxicity and promising clinical activity.24-26

Mevrometostat functions through effects on gene transcription. Although ARPIs are effective, resistance inevitably develops. Mevrometostat is being evaluated as an oral, relatively well-tolerated therapy that may help address resistance to ARPI therapy. Trials are ongoing in both resistant and treatment-sensitive disease settings to determine whether this approach can help reduce resistance and potentially enhance sensitivity to ARPIs.

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Multipart, Phase I Trial of Mevrometostat

An ongoing phase I trial is investigating mevrometostat with enzalutamide vs enzalutamide alone in patients with relapsed or refractory mCRPC. Median rPFS was 14.3 months for the combination arm and 6.2 months for the monotherapy arm, with an HR of 0.51. This is an approximate 8-month improvement.26 Although this was a small study, the findings support continued phase III evaluation of EZH2 inhibition in mCRPC.

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Enzalutamide ± Mevrometostat in mCRPC: Safety

In terms of safety and tolerability, the most common TEAEs in the mevrometostat plus enzalutamide arm included asthenic conditions, diarrhea, decreased appetite, anemia, nausea, dysgeusia, and alopecia. Most common events were grade 1 or 2, although grade 3 or higher TEAEs and dose reductions occurred more often with the combination than with enzalutamide alone.26

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Key Ongoing Phase III Trials of Mevrometostat in mCRPC

The phase III MEVPRO-1 trial enrolled patients who were previously treated with abiraterone. Participants were randomized to mevrometostat and enzalutamide or docetaxel and enzalutamide. The phase III MEVPRO-2 trial is currently enrolling patients who are AR signaling inhibitor or abiraterone naive, who will be randomized to mevrometostat and enzalutamide or placebo and enzalutamide. The primary endpoint for both trials is rPFS.

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