Phase III randomized studies of mevrometostat and enzalutamide in metastatic prostate cancer (MEVPRO-1 and MEVPRO-2): trial protocols

Phase I investigation of the enhancer of zeste homolog 2 inhibitor, mevrometostat, plus enzalutamide showed promising antitumor activity versus enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC) (NCT03460977). MEVPRO-1 (open label) and MEVPRO-2 (double blind) are ongoing, global, phase III, randomized studies evaluating efficacy and safety of mevrometostat plus enzalutamide in patients with mCRPC. MEVPRO-1 will include ~600 patients with ≥12 weeks of prior abiraterone treatment, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–2, testosterone ≤50 ng/dL, and life expectancy ≥6 months. MEVPRO-2 will include ~900 androgen receptor pathway inhibitor-naïve patients, with ECOG PS 0–1, testosterone ≤50 ng/dL, and life expectancy ≥12 months. Patients are randomized 1:1 to mevrometostat (875 mg twice daily with food) plus enzalutamide (160 mg once daily), or physician’s choice of enzalutamide or docetaxel (MEVPRO-1) or enzalutamide (MEVPRO-2). Primary endpoint is radiographic progression-free survival (rPFS) per Response Evaluation Criteria in Solid Tumors 1.1 (soft tissue) and Prostate Cancer Working Group 3 criteria (bone) assessed by blinded independent central review. Overall survival is a secondary objective. Kaplan–Meier analysis will summarize time-to-event endpoints. Safety will be assessed. Results will evaluate whether mevrometostat plus enzalutamide can provide clinical benefit in patients with mCRPC. <b>Clinical trial registration:</b>www.clinicaltrials.gov identifiers are NCT06551324 (MEVPRO-1) and NCT06629779 (MEVPRO-2). <b>What is this summary about?</b>This summary describes two ongoing, large, international clinical trials: MEVPRO-1 and MEVPRO-2. The trials will study a new treatment approach for patients with metastatic castration-resistant prostate cancer, a type of prostate cancer that has spread and no longer responds to standard hormone treatments. <b>Which medicines are being tested?</b>The trials are testing mevrometostat, a new medicine that blocks a protein called enhancer of zeste homolog 2 (EZH2), which helps cancer cells grow and survive. Mevrometostat will be given with enzalutamide, a standard medicine for advanced prostate cancer. <b>What are the designs of the MEVPRO-1 and MEVPRO-2 trials?</b>MEVPRO‑1 will include about 600 patients whose cancer has already progressed after treatment with abiraterone, a standard medicine for advanced prostate cancer. Patients will receive either mevrometostat plus enzalutamide or the doctor’s choice of enzalutamide alone or chemotherapy (docetaxel). MEVPRO‑2 will include about 900 patients who have not previously received abiraterone or other androgen‑receptor pathway inhibitor therapies. Patients will receive either mevrometostat plus enzalutamide or enzalutamide alone <b>What are the aims of the MEVPRO-1 and MEVPRO-2 trials?</b>The main goal of both MEVPRO-1 and MEVPRO-2 is to find out if adding mevrometostat to enzalutamide can stop the cancer from getting worse for longer than standard treatments. The studies will also look at overall survival, pain control, quality of life, and side effects to determine if the new combination provides better outcomes for patients.