mevrometostat (PF-06821497) / Pfizer - LARVOL DELTA

Modulation of enhancer of zeste homolog 2 (EZH2) pharmacodynamic markers and tumour gene expression by mevrometostat in combination with enzalutamide in patients with castration-resistant prostate cancer (CRPC) (EMUC 2025) - P1 | "Adapted and reused with permission. This abstract was accepted and previously presented at the 2025 Genitourinary Cancers Symposium."

Clinical • Combination therapy • PK/PD data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • EZH2

Safety and pharmacokinetics of mevrometostat in combination with enzalutamide in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) (EMUC 2025) - P1 | "Pts with mCRPC who received prior treatment with abiraterone or E, with evidence of progression per modified Prostate Cancer Working Group 3 criteria were included. Pfizer's generative artificial intelligence (AI) assisted technology, MAIA (Medical Artificial Intelligence Assistant) was used in the production of this abstract. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication."

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

C2321001: A Study of Mevrometostat for Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma (clinicaltrials.gov) - P1 | N=433 | Recruiting | Sponsor: Pfizer | Trial completion date: Mar 2026 ➔ Mar 2029 | Trial primary completion date: Mar 2026 ➔ May 2028

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

Mevrometostat (M) plus enzalutamide (E) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A randomised dose-expansion study (EMUC 2025) - P1 | "Materials & Methods Pts with mCRPC who received prior abiraterone, ≤1 prior chemotherapy in any setting, with progression per modified Prostate Cancer Working Group 3 criteria were included. Pfizer's generative artificial intelligence (AI) assisted technology, MAIA (Medical Artificial Intelligence Assistant) was used in the production of this abstract. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication."

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

PRC2 inhibition enhances AR inhibitor response to delay treatment relapse in castration-sensitive prostate cancer by restricting adaptation of tumor cells in preclinical studies (AACR-NCI-EORTC 2025) - P1 | "In vivo xenografts were dosed with ORIC-944 or EZH2 inhibitor mevrometostat, darolutamide, or the combinations...Transcriptional effects induced by combining ORIC-944 and ARI were comparable irrespective of ARI (i.e. darolutamide, apalutamide or enzalutamide)... These preclinical results position ORIC-944 as a potential best-in-class PRC2 inhibitor that induces luminal cell fate and restricts lineage TF accessibility in both CRPC and CSPC settings, thereby extending the duration of response to ARI treatment by disabling cellular plasticity and delaying prostate tumor adaptation. ORIC-944 is under clinical evaluation in combination with ARIs in a global Phase 1b study (NCT05413421)."

Preclinical • Tumor cell • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • FOXA1 • HNF1A • ONECUT2

Patient-reported outcomes in a randomised phase I study of mevrometostat (M) plus enzalutamide (E) vs E alone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (ESMO 2025) - P1 | "Methods Pts with progressive mCRPC who received prior abiraterone and ≤1 prior chemotherapy were randomised 1:1 to M (1250 mg BD [empty stomach]) + E (160 mg QD) or E alone. TTDD was significantly longer with M + E vs E for the FACT-P prostate cancer subscale. These findings are being validated in ongoing phase 3 studies."

Clinical • Metastases • P1 data • Patient reported outcomes • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

FTX-6274, an EED inhibitor, demonstrates robust efficacy in castration resistant prostate cancer (CRPC) (ESMO 2025) - "In vivo mouse xenograft studies in AR positive prostate cancer models revealed that FTX-6274 demonstrated significant tumor growth inhibition compared to the EZH2 inhibitor mevrometostat. Further, our results indicate that FTX-6274 may have the potential to enhance efficacy as a combination therapy with ARPI in CRPC. Legal entity responsible for the study Fulcrum Therapeutics, Inc."

Clinical • Castration-Resistant Prostate Cancer • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

This Study Will Explore Whether a Combination of the Investigational Drug Mevrometostat (PF-06821497) and Enzalutamide Will Work Better Than Taking Enzalutamide Alone in Participants With mCSPC Who Are ARPI naïve. (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Mevrometostat (M) in combination with enzalutamide (E) for androgen receptor pathway inhibitor (ARPI)-naïve patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): The phase 3, randomized MEVPRO‑2 study (DGU 2025) - P1, P3 | "In a phase 1 study (NCT03460977), objective responses to M+E were observed in pts with CRPC and prior abiraterone or E treatment...HRs and 95% CIs will be estimated using a Cox proportional hazards 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 • Addiction (Opioid and Alcohol) • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • EZH2

Mevrometostat (M) in combination with enzalutamide (E) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with abiraterone acetate (AA): The phase 3, randomized MEVPRO-1 study (DGU 2025) - P1, P3 | "Approximately 600 pts will be randomized 1:1 to M (875mg BID with food) + E (160mg QD), or physician's choice of E (160mg QD) or docetaxel (DTX; 75mg/m2 IV Q21D). Time-to-event endpoints will be compared between treatment arms using a stratified log-test and summarized using Kaplan–Meier analysis. HRs and 95% CIs will be estimated using a stratified Cox proportional hazards model."

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

This Study Will Explore Whether a Combination of the Investigational Drug Mevrometostat (PF-06821497) and Enzalutamide Will Work Better Than Taking Enzalutamide Alone in Participants With mCSPC Who Are ARPI naïve. (clinicaltrials.gov) - P3 | N=1000 | Not yet recruiting | Sponsor: Pfizer

New P3 trial • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

EZH2 Inhibition in Prostate Cancer: MEVPRO-1 Phase III Trial Update (UroToday) - P2 | N=600 | MEVPRO-1 (NCT06551324) | Sponsor: Pfizer | "Promising phase II data showed enzalutamide plus mevrometostat achieved 14 months progression-free survival versus 6 months with enzalutamide alone—a 50% reduction in progression risk. MEVPRO-1 is a 600-patient phase III trial randomizing patients with prior abiraterone progression to enzalutamide versus the combination. The mevrometostat dose was adjusted to 875mg twice daily with food to improve absorption and reduce gastrointestinal side effects...Additional trials MEVPRO-2 and MEVPRO-3 are planned, marking the beginning of EZH2 inhibition development in prostate cancer."

New trial • P2 data • Castration-Resistant Prostate Cancer

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 | " 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 an empty stomach. Further investigation of M + E in pts with mCRPC is warranted."

Clinical • Combination therapy • Metastases • Anemia • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Infectious Disease • Neutropenia • Oncology • Prostate Cancer • Septic Shock • 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 | "These data indicate that M at 1250 mg BID on an 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 CRPC."

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

Safety and pharmacokinetics of mevrometostat (M) in combination with enzalutamide (E) in patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2025) - P1 | "Pts with mCRPC who received prior treatment with abiraterone or E, with evidence of progression per modified Prostate Cancer Working Group 3 criteria were included. In pts with mCRPC treated with M + E, M 875 mg with food had an improved safety profile compared with M 1250 mg on an empty stomach. M 875 mg with food has similar plasma exposures to M 1250 mg on an empty stomach. M 875 mg with food + E was selected as the recommended dose for pivotal phase 3 studies."

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

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) - P1, P3 | "The optimal treatment sequence for patients with mCRPC who progress after first-line treatment with ARPI is not defined; a second ARPI or docetaxel are options used in real-world settings. Time to event endpoints will be compared between treatment arms using a stratified log-test. 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 • Anemia • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hepatocellular 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) - 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 • Addiction (Opioid and Alcohol) • Anemia • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Hormone Sensitive Prostate Cancer • Oncology • Pain • Prostate Cancer • Solid Tumor • EZH2

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 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