mevrometostat (PF-06821497) / Pfizer - LARVOL DELTA

EZH2 inhibition as a therapeutic strategy for castration resistant prostate cancer in combination with AR-antagonist enzalutamide (AACR 2025) - "Similar combination benefit of PF-1497 and enzalutamide was observed across a panel of CRPC PDXs with anti-tumor activity enriched in AR-positive prostate cancer models, including tumors from patients who were refractory to anti-androgen therapies. Taken together, these data highlight the promise of EZH2 inhibition in treating prostate cancer and provide support for ongoing clinical study of PF-06821497 in combination with enzalutamide in mCRPC."

Combination therapy • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • EZH2

Embryonic ectoderm development protein (EED) inhibitor APG-5918 exhibits potent antitumor activity and synergizes with androgen receptor (AR) inhibitor enzalutamide in preclinical prostate cancer (PCa) models (AACR 2025) - "APG-5918 appeared to be more potent than two EZH2 inhibitors (tazemetostat, PF-06821497) and EED inhibitor ORIC-944 under the same experimental condition. APG-5918 alone or in combination with enzalutamide exhibited antitumor activity in preclinical PCa models, supporting EED inhibition (± AR antagonists) as a therapeutic strategy for PCa."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CCND1 • CDK4 • DNMT1 • MCL1 • SUZ12 • UHRF1

A Study to Learn How Different Tablets of the Study Medicine Mevrometostat Are Taken up Into the Blood in Healthy Adults (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Pfizer | N=16 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal

Mevrometostat, 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. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT03460977 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Combination therapy • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Modulation of enhancer of zeste homolog 2 (EZH2) pharmacodynamic (PD) markers and tumor gene expression by mevrometostat in combination with enzalutamide in patients with castration-resistant prostate cancer (CRPC). (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT03460977 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Combination therapy • PK/PD data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Safety and pharmacokinetics of mevrometostat (M) in combination with enzalutamide (E) in patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT03460977 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Combination therapy • Metastases • PK/PD data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Mevrometostat in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with abiraterone acetate: The phase 3, randomized MEVPRO-1 study. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT06551324 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Combination therapy • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Mevrometostat in combination with enzalutamide for androgen receptor pathway inhibitor (ARPI)-naïve patients with metastatic castration-resistant prostate cancer (mCRPC): The phase 3, randomized MEVPRO-2 study. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT06629779 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Combination therapy • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Mevrometostat Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma (clinicaltrials.gov) - P1 | N=343 | Recruiting | Sponsor: Pfizer | Trial completion date: Dec 2025 ➔ Mar 2026 | Trial primary completion date: Dec 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Follicular Lymphoma • Genito-urinary Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor

SES AUA 2025: Phase 1 Trial of Mevrometostat (PF-06821497), a Potent and Selective Inhibitor of EZH2, in CRPC (UroToday) - P1 | N=343 | NCT03460977 | Sponsor: Pfizer | "The 2025 SESAUA annual meeting featured a prostate cancer session and a presentation by Dr. Benjamin Garmezy discussing a phase 1 trial of mevrometostat (PF-06821497), a potent and selective inhibitor of EZH2, in CRPC....Median radiographic progression-free survival was 17.0 (95% CI 6.3, NE) months in all patients (n = 47), 17.1 (95% CI 6.2, NE) months for patients with prior abiraterone (without enzalutamide; n = 12), and 11.7 (95% CI 4.2, NE) months for patients with prior enzalutamide (± abiraterone; n = 35). Confirmed PSA50 was observed in 14.9% (95% CI 7.0, 31.4) of patients. In 22 patients with baseline measurable disease, objective response rate was 27.3% (95% CI 10.7, 50.2; 1 complete response, 5 partial responses). Geometric mean H3K27Me3 reduction was −75% (95% CI −93, −11) for mevrometostat plus enzalutamide (at mevrometostat 1250 mg BID) in tumor-paired biopsies (n = 6)."

P1 data • Castration-Resistant Prostate Cancer

Radiographic PFS in Metastatic CRPC More Than Doubles With Novel Combination (MedPageToday) - "An inhibitor of EZH2opens in a new tab or window, mevrometostat has a non-hormonal mechanism of action as compared with many other drugs for advanced prostate cancer. A phase I studyopens in a new tab or window of the drug showed single-agent activity, but given preclinical research showing that EZH2 contributes to enzalutamide resistance, a combination study was a rational approach, said Tanya Dorff."

Media quote

Modulation of enhancer of zeste homolog 2 (EZH2) pharmacodynamic markers and tumor gene expression by mevrometostat (PF-06821497) in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2025) - P1 | "These data indicate M at 1250 mg BID on empty stomach in combination with E effectively inhibits EZH2 in tumor tissue and may overcome drug resistance and/or enhance androgen targeting drug activity by restoring the function of tumor suppressor genes and blocking tumor cell proliferation and cell cycle progression. These data support dose recommendation for phase 3 pivotal studies and enhance understanding of mechanism of action for M+E in mCRPC."

Clinical • Combination therapy • Metastases • PK/PD data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AURKA • BMP7 • CDK1 • EZH2 • FOXM1 • IGFBP3 • RAD54L • TOP2A • TYMS

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. (ASCO-GU 2025) - P1, P3 | "Approximately 600 patients will be randomized 1:1 to receive mevrometostat (875mg BD with food) with enzalutamide (160mg QD), or physician's choice of enzalutamide (160mg QD) or docetaxel (75mg/m2 intravenously every 21d). Secondary endpoints include anti-tumor activity, safety, pharmacokinetics, ctDNA, and patient-reported outcomes. Stratified log-rank P-values, HRs, and 95% CIs will be estimated using a stratified Cox proportional hazard model, and Kaplan–Meier analysis will summarize time-to-event endpoints."

Clinical • Combination therapy • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Mevrometostat (PF-06821497) in combination with enzalutamide for androgen receptor pathway inhibitor (ARPI)-naïve patients with metastatic castration-resistant prostate cancer (mCRPC): The phase 3, randomized MEVPRO-2 trial. (ASCO-GU 2025) - P1, P3 | "In a nonrandomized, phase 1 dose-escalation study, objective responses to mevrometostat with enzalutamide were observed in patients with CRPC and prior abiraterone or enzalutamide treatment (NCT03460977; Schweizer MT, et al...Hazard ratios and 95% confidence intervals will be estimated using a Cox proportional hazard model, stratified by prior docetaxel and presence of hepatic metastases. P-values will be provided using a stratified log-rank test. Safety and tolerability will also be assessed."

Clinical • Combination therapy • Metastases • P3 data • Castration-Resistant Prostate Cancer • Castration-Sensitive Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • EZH2

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. (ASCO-GU 2025) - P1 | " Pts with mCRPC who received prior abiraterone, ≤1 prior chemotherapy in any setting, with evidence of progression per modified Prostate Cancer Working Group 3 criteria were included. M+E shows improved outcomes vs E in pts with mCRPC, with a manageable AE profile. In M+E combination, M 875 mg with food has similar plasma exposure as M 1250 mg on empty stomach. Further investigation of M+E in pts with mCRPC is warranted."

Clinical • Combination therapy • Late-breaking abstract • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Pfizer's investigational candidate combo cuts prostate cancer progression by 49% in phase 1 (FierceBiotech) - P1 | N=343 | NCT03460977 | Sponsor: Pfizer | "The data, centering an investigational small molecule EZH2 inhibitor called mevrometostat, were initially scheduled for a Feb. 13 presentation at the ASCO Genitourinary Cancers Symposium in San Francisco....For the 41 patients receiving both mevrometostat and Xtandi (enzalutamide), median radiographic progression-free survival was 14.3 months. The result compared with 6.2 months for the 40 patients who received only Xtandi. For the 15 patients who received the investigational combo and had measurable disease at baseline, the overall response (OR) rate was 26.7%. This is compared to a 14.3% OR rate for the 14 eligible patients on enzalutamide."

P1 data • Castration-Resistant Prostate Cancer

Pfizer to Showcase Advancements Across Genitourinary Cancers at ASCO GU Cancers Symposium (Pfizer Press Release) - "From the pipeline, the first randomized progression-free survival (PFS) data from the ongoing Phase 1 dose-escalation study for mevrometostat plus XTANDI reinforce the potential of this investigational combination for patients with mCRPC. Additional pipeline presentations include updated data and real-world evidence for different types of bladder cancer, supporting the development of two potential transformative treatments, disitamab vedotin, an investigational antibody-drug conjugate (ADC), and sasanlimab, an investigational subcutaneous PD-1 blocker."

P1 data • Real-world evidence • Bladder Cancer • Castration-Resistant Prostate Cancer

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of PF-06821497 (Mevrometostat) in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer (MEVPRO-2) (ChiCTR) - P3 | N=900 | Sponsor: West China Hospital of Sichuan University; West China Hospital of Sichuan University

New P3 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Learn How Different Tablets of the Study Medicine Mevrometostat Are Taken up Into the Blood in Healthy Adults (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Pfizer | Trial completion date: Apr 2025 ➔ Sep 2025 | Initiation date: Dec 2024 ➔ Apr 2025 | Trial primary completion date: Apr 2025 ➔ Sep 2025

Trial completion date • Trial initiation date • Trial primary completion date

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 (SUO 2024) - P1 | "Approximately 600 patients will be randomized 1:1 to receive mevrometostat (875mg BD with food) with enzalutamide (160mg QD), or physician's choice of enzalutamide (160mg QD) or docetaxel (75mg/m 2 intravenously every 21d). Stratified log-rank P -values, HRs, and 95% CIs will be estimated using a stratified Cox proportional hazard model, and Kaplan–Meier analysis will summarize time-to-event endpoints. "

Clinical • Combination therapy • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Learn How the Medicine Called [14C] PF-06821497 is Taken up Into and Removed From the Body. (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion

A Study to Learn How the Medicine Called [14C] PF-06821497 is Taken up Into and Removed From the Body. (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Learn How Different Tablets of the Study Medicine Mevrometostat Are Taken up Into the Blood in Healthy Adults (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Pfizer

New P1 trial

Phase 1 trial of mevrometostat (PF-06821497), a potent and selective inhibitor of enhancer of zeste homolog 2 (EZH2), in castration-resistant prostate cancer (CRPC) (PCF 2024) - P1 | "Mevrometostat plus enzalutamide shows activity in both post-abiraterone without enzalutamide and post-enzalutamide (± abiraterone) patients with CRPC, with evidence of tumor PD modulation and a manageable safety profile. Further investigation is warranted."

P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • TP53

A Study to Learn How PF-06821497 (Mevrometostat) Works in Men With Metastatic Castration-resistant Prostate Cancer. (clinicaltrials.gov) - P3 | N=900 | Recruiting | Sponsor: Pfizer

Metastases • New P3 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor