EZH2 inhibitor landscape and final remarks

Dr. Agarwal asks Dr. Morgans to contextualize mevrometostat among other EZH2-directed strategies in prostate cancer. Dr. Morgans notes that tazemetostat has been studied in mCRPC, but the relevant trial is no longer recruiting and the agent has been voluntarily withdrawn from its prior approved indications. Valemetostat is being investigated in the Alliance PREDICT trial in patients with RB loss, neuroendocrine prostate cancer signature, or functional RB loss—a biomarker-directed population. Tulmimetostat is also being studied as an EZH2 inhibitor in early-phase advanced tumor studies. She also highlights ongoing work on EZH2 PROTAC degraders and combination strategies beyond MEVPRO, including EZH2 plus PARP and EZH2 plus chemotherapy.

Dr. Morgans then summarizes the overarching opportunity: the MEVPRO program harnesses EZH2 inhibition to potentially prevent neuroendocrine differentiation, prolong sensitivity to enzalutamide, and address an unselected mCRPC population in both the post-abiraterone (MEVPRO-1) and androgen receptor pathway inhibitors–naïve (MEVPRO-2) settings. Combined with practical referral pathways and strong community communication, this approach can make these studies broadly accessible.

In closing remarks, Dr. Agarwal acknowledges patients and their families who place their trust in clinicians when considering investigational therapy, and recognizes the multidisciplinary teams—community oncologists, urologists, primary care clinicians, nurses, coordinators, and research staff—who make these studies possible.

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