News
Article
Author(s):
The treatment combination was associated with median radiographic progression-free survival of 14.3 months vs 6.2 months with enzalutamide alone.
Treatment of metastatic castration-resistant prostate cancer (mCRPC) with the investigational agent mevrometostat (PF-06821497) in combination with enzalutamide (Xtandi) appears to confer benefit for patients, according to data to be presented this week at the 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco, California.1
Investigators, led by Michael Schweizer, MD, associate professor of medical oncology at Fred Hutchinson Cancer Center in Seattle, Washington, reported that the treatment combination was associated with median radiographic progression-free survival (rPFS) of 14.3 months vs 6.2 months with enzalutamide alone.
In their abstract, the investigators reported, “Dose exploration of mevrometostat + enzalutamide [plus] androgen deprivation therapy (ADT) showed a manageable safety profile with evidence of EZH2 pharmacodynamic inhibition, objective response (OR), and decline in prostate-specific antigen of ≥50% from baseline (PSA50) in patients with mCRPC (NCT03460977).” At ASCO GU, the authors presented data from an open-label, randomized, dose-expansion component of the study.
Patients with mCRPC were eligible for inclusion in the study if they had received prior abiraterone acetate (Zytiga), 1 or fewer prior chemotherapy in any setting, and had evidence of progression as defined by modified Prostate Cancer Working Group 3 criteria. The cohort, which was receiving androgen deprivation therapy, was randomly assigned 1:1 to receive oral mevrometostat 1250 mg twice daily on an empty stomach plus enzalutamide 160 mg once daily or to enzalutamide, stratified by prior chemotherapy.
The study’s primary end points were rPFS per investigator assessment as well as safety. Secondary end points included objective response by RECIST 1.1, PSA50, and pharmacokinetics.
A total of 81 patients were included in the study; 41 received mevrometostat plus enzalutamide and 40 received enzalutamide alone. Median follow-up was 9.6 months (interquartile range, 3.1-14.5 months). Median patient age was 70 years (range, 48-86 years) for the combination group and 71.5 years (range, 50-86 years) for the enzalutamide-alone group. The investigators reported that 43.9% of patients in the combination group and 45.0% of patients in the enzalutamide-alone group had received prior taxane therapy.
According to the data presented at ASCO GU, the OR rate in patients who had measurable disease at baseline (15 patients in the combination group and 14 patients in the enzalutamide group) was 26.7% (95% CI: 7.8-55.1) for the combination group and 14.3% (range, 1.8-42.8) for the enzalutamide-alone group. The investigators observed a confirmed PSA50 in 34.1% (95% CI: 20.1-50.6) of patients in the combination group and 15.4% (95% CI: 6.0-31.3) for the enzalutamide-alone group.
Regarding safety, the most common treatment-emergent adverse events (TEAEs) in the combination group included diarrhea (78.0%), decreased appetite (58.5%), dysgeusia (58.5%). The most common TEAEs in the in the enzalutamide-alone group included asthenic conditions (42.5%), nausea (25.0%), and anemia (22.5%). Grade 3 or higher TEAEs were observed in 53.7% of patients in the combination group bs 42.5% in the enzalutamide-alone group.
According to a news release from Pfizer, mevrometostat is an “investigational selective inhibitor of enhancer of zeste homolog 2.” The company also noted that it has “initiated 2 pivotal phase 3 trials for mevrometostat plus [enzalutamide] in 2024 and expects to start a phase 3 study of mevrometostat plus [enzalutamide] in first-line mCSPC [metastatic castration-sensitive prostate cancer] during the first half of 2025.”2
REFERENCES
1. Schweizer M, Calvo M, Moreno V, et al. Mevrometostat (PF-06821497), an enhancer of zeste homolog 2 (EZH2) inhibitor, in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC): A randomized dose-expansion study. Presented at: American Society of Clinical Oncology Genitourinary Cancers Symposium. February 13-15, 2025. San Francisco, California. Abstract LBA138. https://meetings.asco.org/abstracts-presentations/243221
2. Pfizer to showcase advancements across genitourinary cancers at ASCO GU Cancers Symposium. News release. Pfizer. January 28, 2025. Accessed February 12, 2025. https://www.businesswire.com/news/home/20250127366998/en/Pfizer-to-Showcase-Advancements-Across-Genitourinary-Cancers-at-ASCO-GU-Cancers-Symposium