Biomarker selection and the MEVPRO patient population

Dr. Agarwal asks Dr. Morgans whether the MEVPRO trials require EZH2 testing or any specific biomarker for enrollment. Dr. Morgans explains that the MEVPRO trials enroll biomarker-unselected metastatic castration-resistant prostate cancer (mCRPC) populations. EZH2 testing is not required, which is helpful because such testing is not part of standard clinical workflow.

She contrasts this with the PREDICT trial (run by the Alliance), which uses biomarker-directed allocation to identify patients with neuroendocrine prostate cancer signatures, RB loss, or functional RB loss, and which evaluates a different EZH2 inhibitor, valemetostat. Phase 1 data have shown durable antitumor activity in patients both with and without AR or TP53 mutations, providing the rationale for an unselected population in MEVPRO. Dr. Morgans emphasizes that an unselected design removes the need for specialized testing prior to treatment, making the approach feasible across academic and community practices.

Dr. Agarwal adds that EZH2 inhibitors may be most effective when introduced before clinical evidence of neuroendocrine differentiation emerges, raising the importance of moving these agents earlier in the disease course. Dr. Morgans agrees, noting that waiting until lineage transformation has occurred may limit benefit.

In the next episode, "MEVPRO-1 and MEVPRO-2: trial design and patient populations," Dr. Agarwal details the design, eligibility criteria, and clinical scenarios addressed by both MEVPRO trials.