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Mevrometostat Plus Enzalutamide Confers a Survival Benefit for Patients With Hormone-Refractory mCRPC

Date : 2/2/2025 / Source:https://dailynews.ascopubs.org/

$Mevrometostat Plus Enzalutamide Confers a Survival Benefit for Patients With Hormone-Refractory mCRPC$

In an ongoing phase 1/2 trial, the novel combination of mevrometostat plus enzalutamide significantly extended progression-free survival (PFS) compared with enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC).
Median PFS was longer in the combination drug group (14.3 vs 6.2 months), resulting in a nearly 50% reduction in risk of disease progression.
Results from the study provided justification for phase 3 studies evaluating combination mevrometostat/enzalutamide as a potential new standard of care for patients with mCRPC.
In an ongoing phase 1/2 trial (NCT03460977), the novel combination of mevrometostat, an inhibitor of enhancer of zeste homolog 2 (EZH2), plus the androgen receptor pathway inhibitor enzalutamide significantly extended PFS versus enzalutamide alone in patients with mCRPC whose disease had previously progressed after abiraterone (LBA138).
Narrowing a Treatment Gap
Historically, the treatment of prostate cancer has focused on inhibiting the androgen receptor pathway, which is usually effective initially. Unfortunately, most patients treated with androgen receptor pathway inhibitors (ARPIs) eventually develop drug resistance, experience progression to metastatic disease, and then are considered incurable by current standards.¹ This has left investigators with unanswered questions about how to effectively decrease mortality in this population.
In 2018, he and his colleagues launched an open-label, multicenter phase 1/2 dose-escalation and dose-expansion study to explore safety outcomes and antitumor activity of mevrometostat—a robust and selective inhibitor of EZH2—among patients with relapsed or refractory CRPC, small cell lung cancer, or follicular lymphoma. The data being presented at the ASCO Genitourinary Cancers Symposium are from the CRPC population.
In the trial, 81 patients with mCRPC were randomly assigned to either a 1:1 dose of mevrometostat plus enzalutamide or enzalutamide alone. All patients had experienced disease progression on prior treatment with the ARPI abiraterone. The primary endpoint was radiographic PFS, and secondary endpoints included objective response and decline in prostate-specific antigen of 50% or greater (PSA₅₀) from baseline.
The median PFS was 14.3 months for the combination drug versus 6.2 months for enzalutamide alone, resulting in a nearly 50% reduction in risk of disease progression (HR 0.51, 90% CI [0.28, 0.95]). Additionally, objective response among patients with measurable disease at baseline was 26.7% for combination therapy and 14.3% for enzalutamide alone. Confirmed PSA₅₀ was double in the combination group compared with the single-therapy group (34.1% vs 15.4%).
Specifically, the MEVPRO-1 study (NCT06551324) is a randomized trial that is evaluating combination mevrometostat/enzalutamide in patients with mCRPC previously treated with abiraterone. It is being conducted at 34 sites across the United States and internationally.
Additionally, a second phase 3 clinical trial (NCT06629779) is seeking to better understand the mechanisms of action of combination mevrometostat/enzalutamide in patients with mCRPC who are treatment naive. This study also is recruiting, or soon will be, at numerous sites nationally and internationally.