MEVPRO-1 and MEVPRO-2: trial design and patient populations

Dr. Morgans asks Dr. Agarwal to walk through the MEVPRO-1 and MEVPRO-2 trial designs. Dr. Agarwal explains that MEVPRO-1 enrolls post-abiraterone metastatic castration-resistant prostate cancer (mCRPC) patients who have progressed on abiraterone (in either the hormone-sensitive or castration-resistant setting) for at least 12 weeks. Patients are randomized 1:1 to enzalutamide 160 mg daily plus mevrometostat 875 mg twice daily with food versus a control arm of enzalutamide or docetaxel chemotherapy by physician choice. Eligibility requires Eastern Cooperative Oncology Group (ECOG) performance status 0–2 and life expectancy of at least 6 months. Key exclusions include prior enzalutamide or other direct androgen receptor inhibitors, prior radioligand therapy, prior PARP monotherapy, and prior chemotherapy for prostate cancer—except docetaxel in the metastatic hormone-sensitive setting.

Dr. Agarwal describes MEVPRO-2, which moves the combination earlier in mCRPC for patients never exposed to an androgen receptor pathway inhibitor (ARPI), including abiraterone. He notes this population is substantial: data presented at the American Urological Association (AUA) 2024 meeting showed most U.S. prostate cancer patients are diagnosed with localized disease and progress through PSA recurrence and androgen deprivation therapy (ADT) to mCRPC without an ARPI. These patients are commonly seen by urology and radiation oncology colleagues. MEVPRO-2 randomizes them to enzalutamide plus mevrometostat versus enzalutamide alone—no chemotherapy control given the ARPI-naïve state. Eligibility is stricter: ECOG 0–1 and life expectancy of 12 months or more.

Both trials use enzalutamide as the ARPI backbone, employ stratification factors, and have radiographic progression-free survival (rPFS) as the primary endpoint and overall survival as a key secondary endpoint.

In the next episode, "Endpoints and early efficacy signals from phase 1 and dose-expansion data," Dr. Morgans reviews the secondary endpoints and the early-phase data that informed the design of these phase 3 trials.