Inclusion Criteria:

          1. Age at the time of consent ≥ 18 years.

          2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (Appendix

          3. Life expectancy of > 3 months.

          4. Histologically or cytologically confirmed adenocarcinoma of the prostate. Small cell
             or neuroendocrine tumors of the prostate are also permitted.

          5. Progressive disease in the setting of medical or surgical castration (ie, castration-
             resistant prostate cancer [CRPC]) by PCWG3 criteria for study entry.

               -  Evidence of disease progression by rising PSA or

               -  Soft tissue progression per RECIST 1.1 or

               -  Evidence of disease progression by observation of 2 new bone lesions since the
                  initiation of last systemic therapy.

          6. Metastatic prostate cancer disease, documented by imaging.

          7. Must have undergone bilateral orchiectomy (surgical castration) or be willing to
             continue GnRH analog or antagonist (medical castration).

          8. Surgically or medically castrated, with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L)
             at screening.

          9. Previously untreated with or progressed on a second generation androgen inhibitor
             (abiraterone, enzalutamide, or apalutamide).

         10. No prior treatment with cytotoxic chemotherapy for mCRPC is permitted. Up to six prior
             cycles of docetaxel received for castration-sensitive disease is permitted for those
             subjects prior to receiving enzalutamide or abiraterone/prednisone.

         11. Subjects must refrain from donating sperm starting at the planned first dose of
             tazemetostat until 3 months following the last dose of tazemetostat, 3 weeks following
             the last dose of abiraterone/prednisone, and 3 months following the last dose of
             enzalutamide.

         12. Subjects with a female partner of childbearing potential as defined in the protocol
             must:

               1. Be vasectomized, or

               2. Remain abstinent or use a condom starting at the planned first dose of
                  tazemetostat until 3 months following the last dose of tazemetostat, 3 weeks
                  following the last dose of abiraterone/prednisone, and 3 months following the
                  last dose of enzalutamide. The reliability of sexual abstinence should be
                  evaluated in relation to the duration of the clinical trial and the preferred and
                  usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation,
                  sympto-thermal, or post-ovulation methods) and withdrawal are not acceptable
                  methods of contraception.

         13. Female partners of subjects who are of child-fathering potential as defined in the
             protocol and who are, themselves, of childbearing potential as defined in the protocol
             must also adhere to one of the following:

               1. Placement of an intrauterine device or intrauterine system

               2. Established use of oral, injected, or implanted hormonal methods of contraception
                  plus an additional barrier method

               3. Progesterone-only oral contraception, where inhibition of ovulation is not the
                  primary mode of action.

        Exclusion Criteria:

          1. Known symptomatic brain metastases.

          2. Untreated or impending spinal cord compression.

          3. Treatment with any of the following for prostate cancer within the indicated timeframe
             prior to day 1 of starting study treatment:

               -  First generation: AR antagonists (eg, bicalutamide, nilutamide, flutamide) within
                  4 weeks.

               -  5-alpha-reductase inhibitors, ketoconazole, estrogens (including
                  diethylstilbesterol), or progesterones within 2 weeks.

               -  Chemotherapy (as permitted in inclusion criteria #10) within 3 weeks.

               -  Prior radionuclide therapy within 4 weeks.

               -  Another interventional product or standard agent in a clinical study within 28
                  days prior to the first planned dose of tazemetostat

          4. Severe concurrent disease, infection, or co-morbidity that, in the judgment of the
             Investigator, would make the subject inappropriate for enrollment.

          5. History of another invasive cancer within 3 years of randomization, with the exception
             of treated non-melanoma skin cancer, treated superficial bladder cancer, or fully
             treated cancers with a remote probability of recurrence in the opinion of both the
             Medical Monitor and Investigator.

          6. History of seizure or any condition that may predispose to seizure (eg, prior cortical
             stroke or significant brain trauma). History of sub clinical seizures manifested by
             loss of consciousness or transient ischemic attack within 12 months of randomization.
             However, subjects on medications with seizure lowering threshold will be admitted.

          7. Clinically significant cardiovascular disease including the following:

               -  Myocardial infarction within 6 months before screening.

               -  Uncontrolled angina within 3 months before screening.

               -  Congestive heart failure (New York Heart Association class 3 or 4), or a history
                  of congestive heart failure (New York Heart Association class 3 or 4), unless a
                  screening echocardiogram or multigated acquisition scan performed within 3 months
                  before randomization demonstrates a left ventricular ejection fraction

                    -  50% (Appendix 2).

               -  History of clinically significant ventricular arrhythmias (eg, sustained
                  ventricular tachycardia, ventricular fibrillation, torsades de pointes).

               -  History of Mobitz 2 second-degree or third-degree heart block without a permanent
                  pacemaker in place.

               -  Hypotension as indicated by systolic blood pressure <86 millimeters of mercury
                  (mmHg) at screening.

               -  Bradycardia as indicated by a heart rate of <45 beats per minute on the screening
                  ECG, and upon physical examination.

               -  Uncontrolled hypertension as indicated by systolic blood pressure >170 mmHg or
                  diastolic blood pressure >105 mmHg at screening.

          8. Gastrointestinal disorder affecting absorption (eg, gastrectomy, active peptic ulcer
             disease within 3 months before randomization).

          9. Major surgery within 4 weeks of randomization.

         10. For subjects taking abiraterone and prednisone, no evidence of hepatic impairment or
             classified as only Child-Pugh class A for hepatic impairment.

         11. Hypersensitivity reaction to the active pharmaceutical ingredient of tazemetostat,
             abiraterone, prednisone, or enzalutamide, or any of the other components of each
             individual agent under study.

         12. Is unwilling to exclude grapefruit juice, Seville oranges, and grapefruit from the
             diet and all foods that contain those fruits from time of enrollment to while on
             study.

         13. Is currently taking any prohibited medication(s) as described in Section 9.3.3.

         14. Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste
             homologue-2.

         15. Is immunocompromised (ie, has a congenital immunodeficiency). Subjects diagnosed with
             human immunodeficiency virus (HIV) are eligible to participate in the study if they
             meet the following criteria:

               -  No history of AIDS-defining opportunistic infections, or have not had an
                  opportunistic infection within the 12 months prior to enrollment.

               -  No history of AIDS-defining cancers (eg, Kaposi's sarcoma, aggressive B-cell
                  lymphoma, and invasive cervical cancer).

               -  Subjects may take prophylactic antimicrobials; however, subjects taking specific
                  antimicrobial drugs where there may be drug-drug interaction or overlapping
                  toxicities with study drugs must be excluded from study participation.

               -  Subjects should be on established anti-retroviral therapy for ≥4 weeks with an
                  HIV viral load of < 400 copies/mL and/or CD4+ T-cell (CD4+) count ≥ 350 cells/uL
                  prior to enrollment.

         16. Has a prior history of T-cell lymphoblastic lymphoma/ T-cell acute lymphoblastic
             leukemia.

         17. Is unable to take oral medications or has malabsorption syndrome or any other
             uncontrolled gastrointestinal condition (eg, nausea, diarrhea or vomiting) that might
             impair the bioavailability of study treatments.

         18. Subjects with hepatitis B or hepatitis C are ineligible to participate in the study
             unless they meet the following criteria:

               -  Do not have uncontrolled hepatitis B or C infection, are not on active
                  immunosuppressive therapy, and do not have a history of autoimmune disease
                  requiring ongoing systemic therapy.

               -  Subjects taking therapy for hepatitis where there may be a drug-drug interaction
                  or overlapping toxicities with study drugs must be excluded from study
                  participation.