PI voluntarily closed the study.

This study is an open-label, single-arm, pilot, perioperative study of EZH2 inhibition in patients undergoing Radical Prostatectomy (RP). The EZH2 inhibition is intended to increase the sensitivity of the underlying tumor to the patient's immune system.

Given the absence of data in this setting, we propose to pilot this experience with 4 weeks of tazemetostat at doses known to be clinically safe and effective at inducing clinical effects via inhibition of EZH2 as established for follicular lymphoma and epithelioid sarcoma: 800 mg twice daily with or without food.

Prior to tazemetostat, blood will be collected (4 tubes) for immune cells, Circulating Tumor Cells, and plasma. This will be repeated at the time of RP. RP tissues will be collected.

Additionally, patients will have a week lead-in to wear a FitBit Charge 5TM device (or similar model) to continuously monitor physical activity from baseline up until end of study. The start of the week lead-in will be considered the baseline visit. Subjects will also be asked to continue wearing the device until end of study and option to continue for up to 2 years after end of study in follow-up.

Inclusion Criteria:

• Men electing to undergo radical prostatectomy with preoperative tissue available
• Able to take oral medications
• Age ≥18 years
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Adequate organ function
• Men with partners of childbearing potential, must have had a successful vasectomy (with medically confirmed lack of sperm that are alive) OR must either practice complete abstinence or agree to use adequate contraception
• Inclusion criteria for remote monitoring component of study with Fitbit only (failure to meet inclusion criterion for Fitbit-monitoring portion of study should not preclude participating in treatment trial): Access to a device (e.g., smart phone, tablet) that has the capability to sync to the Fitbit. Note: access can be via family member, friend, caregiver, or study-designated device provided by study member

Exclusion Criteria:

• Active intercurrent illness or malignancy requiring therapy outside of prostate cancer
• History of bleeding disorders
• Concurrent use of anti-platelet agents or therapeutic anticoagulants with the exception of low-dose aspirin (81 mg daily) or NSAIDs for pain/inflammation.

Concurrent use of strong and moderate CYP3A inhibitors and inducers

• Subjects who have previously received tazemetostat
• Currently participating in a study using an investigational, medicinal anti-cancer agent within 4 weeks prior to first dose of tazemetostat
• Exclusion criteria for remote monitoring component of study with Fitbit only (failure to meet exclusion criterion for Fitbit-monitoring portion of study should not preclude participating in treatment trial): Using a pacemaker, implantable cardiac defibrillator, neurostimulator, cochlear implants (removable hearing aids permitted), or other electronic medical equipment, per PI's discretion.