▎WuXiEdited by Kant Content Team

Recently, the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU) announced the first randomized progression-free survival (PFS) results from a Phase 1 clinical trial of Pfizer's EZH2 inhibitor mevrometostat, used in combination with the androgen receptor inhibitor Xtandi (enzalutamide), for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The abstract data shows,Mevrometostat andenzalutamideCombined use, withenzalutamideCompared with monotherapy, the risk of disease progression or death was reduced by 49%.Based on these positive results, Pfizer has launched two pivotal Phase 3 clinical trials and plans to initiate another Phase 3 clinical trial in the first half of 2025 to evaluate the efficacy of mevrometostat in combination with Xtandi as a first-line treatment for metastatic castration-sensitive prostate cancer (mCSPC). A previous press release from the company noted,Mevrometostat is expected to become the first EZH2 inhibitor for the treatment of prostate cancer.

This Phase 1 clinical trial enrolled mCRPC patients who had previously received treatment with abiraterone and up to one chemotherapy regimen. While on background androgen deprivation therapy (ADT), they were randomly assigned to receive mevrometostat plusenzalutamide, orenzalutamideMonotherapy. The primary endpoint of the study was radiographic progression-free survival (rPFS).

As of the data analysis on September 2, 2024, it included 81 patients. At a median follow-up time of 9.6 months,Mevrometostat PlusenzalutamideThe median rPFS for the group was 14.3 months (7.5 months, not evaluable).enzalutamideThe rPFS of the group was 6.2 months (4.1 months, 13.9 months). Mevrometostat/enzalutamideCombination andenzalutamideCompared to reducing the risk of disease progression or death by 49% (HR=0.51, 90% CI, 0.28, 0.95).

Moreover, among patients with evaluable lesions at baseline, mevrometostat/enzalutamideThe total response rate in the combination group was 26.7%.enzalutamideThis value was 15.4% in the single-agent group.

Mevrometostat is a selective, orally potent EZH2 inhibitor. EZH2 is a key regulator of gene transcription and is associated with cancer cell proliferation in prostate cancer.In preclinical models, mevrometostat withenzalutamideDemonstrates a synergistic effect, further inhibiting the proliferation of prostate cancer cell lines.

▲Introduction to Mevrometostat (Image Source: Pfizer Official Website)

Pfizer has launched two pivotal Phase 3 clinical trials in the second half of 2024, testing mevrometostat in treatment-naïve mCRPC patients and mCRPC patients previously treated with abiraterone.enzalutamideThe therapeutic effect of combination therapy. The company stated,Mevrometostat is expected to replace chemotherapy drugs received by patients with mCRPC after treatment and provide an option for these untreated patients.mCRPCPatients Provide New First-Line Treatment Options。

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