Phase 3 Trial to Investigate Mevrometostat Combination in Metastatic Castration-Resistant Prostate Cancer

The phase 3 MEVPRO-1 clinical trial will investigate whether adding mevrometostat to enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) is safe and efficacious as a second-line therapy.

At the SUO 25^th Annual Meeting, Neeraj Agarwal, FASCO, MD, from the University of Utah Health, Salt Lake City, discussed the global, open-label trial during a poster session.

“Resistance to androgen receptor (AR) pathway inhibitors (eg, abiraterone, enzalutamide) in mCRPC may be driven by preservation of AR signaling through various mechanisms,” the researchers said.

However, they believe combination therapy with an enhancer of zeste homolog 2 (EZH2) inhibitor may help patients whose disease becomes resistant to treatment.

The trial, which is currently enrolling patients in five countries, will evaluate combination mevrometostat, a potent and selective small molecule EZH2 inhibitor, for radiographic progression-free survival (rPFS), overall survival (OS), and safety in patients who were previously treated with abiraterone acetate.

Patients must be 18 years or older with an ECOG performance status of 0-2 and castration testosterone levels ≤50 ng/dL. Moreover, they must have experienced disease progression on or after 12 weeks of abiraterone and have a life expectancy of at least 6 months.

Roughly 600 patients will be randomly selected to receive either 875 mg twice daily mevrometostat with 160 mg once daily enzalutamide or physician’s choice of 160 mg once daily enzalutamide or 75mg/m² docetaxel given intravenously every 21 days. The researchers will measure rPFS for up to two years and OS for approximately 4.5 years.

Previous findings from a phase 1 study of mevrometostat in adult patients with mCRPC who received prior abiraterone or enzalutamide treatment showed promising results for the use of mevrometostat combined with enzalutamide with manageable adverse events (AEs). The most common treatment-emergent AEs (TEAEs) related to mevrometostat were diarrhea, dysgeusia, and anemia. The researchers observed serious TEAEs in 6.4% of patients, but no treatment-related deaths.

MEVPRO-1’s primary completion date is December 2025.

Reference:

Agarwal N, Schweizer MT, Castro E, et al. Mevrometostat (pf-06821497) in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate: the phase 3, randomized mevpro-1 study. Poster #5. Presented at the 25th Annual Meeting of the Society of Urologic Oncology; December 4-6, 2024; Dallas, Texas.