Inclusion Criteria

        All Subjects:

          1. Phase 1: Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Phase
             2: ECOG performance status of 0 to 2.

          2. Life expectancy ≥ 3 months before starting tazemetostat.

          3. Subjects with Hepatitis B or C are eligible on the condition that subjects have
             adequate liver function as defined by Inclusion Criterion #6 and are hepatitis B
             surface antigen negative and/or have undetectable hepatitis C virus (HCV) RNA.

          4. Adequate renal function defined as calculated creatinine clearance ≥40 mL/min per the
             Cockcroft and Gault formula or the local institutional standard formula.

          5. Adequate bone marrow function:

             a. Absolute neutrophil count (ANC) ≥750/mm^3 (≥0.75 x 10^9/L) - Without growth factor
             support (filgrastim or pegfilgrastim) for at least 14 days

             b. Platelets greater ≥ 75,000/mm^3 (≥75 x 10^9/L) - Evaluated after at least 7 days
             since last platelet transfusion

             c. Hemoglobin greater than or equal to 9.0 g/dL - May receive transfusion

          6. Adequate liver function:

               1. Total bilirubin ≤1.5 x the upper limit of normal (ULN) except for unconjugated
                  hyperbilirubinemia of Gilbert's syndrome

               2. Alkaline phosphatase (ALP) (in the absence of bone disease), alanine
                  aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3 x ULN (≤5 x ULN
                  if subject has liver metastases)

          7. Time between prior anticancer therapy and first dose of tazemetostat as below:

               1. Cytotoxic chemotherapy - At least 21 days

               2. Non-cytotoxic chemotherapy (eg. Small molecule inhibitor) - At least 14 days

               3. Nitrosoureas - At least 6 weeks

               4. Monoclonal antibody (ies) - At least 28 days

               5. Radiotherapy- At least 14 days from local site radiation therapy/At least 6 weeks
                  from prior radioisotope therapy/At least 12 weeks from 50% pelvic or total body
                  irradiation

               6. High dose therapy with autologous hematopoietic cell infusion - At least 60 days

               7. High dose therapy with allogeneic transplant - At least 90 days (if graft versus
                  host disease [GVHD] is present, must be < Grade 2) and no prohibited medications
                  per Exclusion Criteria #3)

             Note: Starting at Cycle 1 Day 1, subjects may receive no more than 10 mg of prednisone
             daily (or equivalent corticosteroid, excluding protocol-defined prednisolone dosing
             for subjects enrolled in Cohort 6) when used for treatment of lymphoma related
             symptoms, with the intent to taper by the end of Cycle 1.

          8. Males or females aged ≥ 18 years at the time of informed consent (Phase 2). Males or
             females aged ≥ 16 years at time of informed consent (Phase 1).

          9. Females must not be lactating or pregnant at screening or baseline (as documented by a
             negative beta-human chorionic gonadotropin [beta-hCG] test with a minimum sensitivity
             of 25 IU/L or equivalent units of beta-hCG). A separate baseline assessment is
             required if a negative screening pregnancy test was obtained more than 72 hours before
             the first dose of study drug. All females will be considered to be of childbearing
             potential unless they are postmenopausal (at least 12 months consecutive amenorrheic,
             in the appropriate age group, and without other known or suspected cause) or have been
             sterilized surgically (ie, bilateral tubal ligation, total hysterectomy or bilateral
             oophorectomy, all with surgery at least 1 month before dose). Females of childbearing
             potential must not have had unprotected sexual intercourse within 30 days prior to
             study entry and must agree to use a highly effective method of contraception, from the
             last menstrual period prior to randomization, during Treatment Cycles, and for 6
             months after the last final dose of study drug; any male partner must use a condom.
             Highly effective contraception is one that results in a failure rate of <1% per year
             when used consistently and correctly and includes:

               1. Double barrier methods of contraception such as condom plus diaphragm or
                  cervical/vault cap with spermicide.

               2. Placement of an intrauterine device.

               3. Established hormonal contraceptive methods: oral, injectable, or implant. Females
                  who are using hormonal contraceptives must have been on a stable dose of the same
                  hormonal contraceptive product for at least 4 weeks prior to dosing and must
                  continue to use the same contraceptive during the study and for 6 months after
                  study drug discontinuation.

             Female subjects exempt from this requirement are subjects who practice total
             abstinence or have a male partner who is vasectomized. If currently abstinent, the
             subject must agree to use a highly effective method of contraception as described
             above if they become sexually active during the Treatment Cycles, and for 6 months
             after study drug discontinuation.

         10. Male subjects must have had a successful vasectomy (with confirmed azoospermia) or
             they and their female partner must meet the criteria above (ie, not of childbearing
             potential or practicing highly effective contraception and use a condom throughout the
             study period and for 3 months after study drug discontinuation). Nonvasectomized male
             subjects must also agree to refrain from donating sperm from first dose of
             tazemetostat until 3 months following the last dose of tazemetostat.

         11. Voluntary agreement to provide written informed consent and the willingness and
             ability to comply with all aspects of the protocol.

         12. Phase 1 only: Histologically and/or cytologically confirmed advanced or metastatic
             solid tumor or B-cell lymphomas that have progressed after treatment with approved
             therapies or for which there are no standard therapies available.

         13. Phase 2, Cohorts 1-6 only: Subjects must satisfy all of the following criteria:

               1. Have histologically confirmed DLBCL (including primary mediastinal B-cell
                  lymphoma), with relapsed or refractory disease following at least 2 lines of
                  prior standard therapy, including alkylator/anthracycline (unless
                  anthracycline-based chemotherapy is contraindicated)/anti-CD20-based therapy
                  (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone
                  [R-CHOP] or equivalent) AND must be considered unable to benefit from
                  intensification treatment with autologous hematopoietic stem cell transplantation
                  (ASCT) as defined by meeting at least 1 of the following criteria:

                    -  Relapsed following, or refractory to, previous ASCT

                    -  Did not achieve at least a partial response to a standard salvage regimen
                       (eg, rituximab, ifosfamide, carboplatin, and etoposide phosphate [R-ICE] or
                       rituximab, dexamethasone, cytarabine, and cisplatin [R-DHAP])

                    -  Ineligible for intensification treatment due to age or significant
                       comorbidity

                    -  Ineligible for intensification treatment due to failure to mobilize an
                       acceptable number of hematopoietic stem cells

                    -  Refused intensification treatment and/or ASCT or

        b .Have histologically confirmed FL, all grades. Subjects may have relapsed/refractory
        disease following at least 2 standard prior systemic treatment regimens where at least 1
        anti-CD20-based regimen was used. Subjects with prior radiotherapy will be included;
        however, radiotherapy alone will not be considered a systemic treatment regimen.

        c. Have provided sufficient archival tumor tissue that has been successfully tested for
        EZH2 mutation status and cell of origin (DLBCL only) at study specific laboratories
        allowing for allocation into an open cohort.

        d. Have measurable disease as defined by International Working Group-Non-Hodgkin's Lymphoma
        (IWG-NHL [Cheson, 2007])

        Exclusion Criteria

        All Subjects:

          1. Prior exposure to tazemetostat or other inhibitor(s) of EZH2.

          2. Subjects with leptomeningeal metastases or brain metastases or history of previously
             treated brain metastases.

          3. Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE 4.03 criteria) and
             any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).

          4. Has a prior history of T-cell lymphoblastic lymphoma(T-LBL) or T-cell lymphoblastic
             leukemia (T-ALL).

          5. Subjects taking medications that are known strong CYP3A inhibitors and strong or
             moderate CYP3A inducers (including St. Johns Wort) (see
             http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteracti
             onsLabeling/ucm080499.htm; http://medicine.iupui.edu/clinpharm/ddis/)

          6. Subjects unwilling to remove Seville oranges, grapefruit juice and grapefruit from
             their diet.

          7. Any prior treatment-related (i.e. chemotherapy, immunotherapy, radiotherapy)
             clinically significant toxicities that have not resolved to ≤ Grade 1 per CTCAE
             version 4.03 or prior treatment-related toxicities that are clinically unstable and
             clinically significant at time of enrollment.

          8. Major surgery within 4 weeks before the first dose of study drug. Note: Minor surgery
             (eg. minor biopsy of extracranial site, central venous catheter placement, shunt
             revision) is permitted within 3 weeks prior to enrollment.

          9. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled
             gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the
             bioavailability of tazemetostat.

         10. Significant cardiovascular impairment: history of congestive heart failure greater
             than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension,
             unstable angina, myocardial infarction, or stroke within 6 months of the first dose of
             study drug; or cardiac ventricular arrhythmia.

         11. Prolongation of corrected QT interval using Fridericia's formula (QTcF) to > 480 msec.

         12. Venous thrombosis or pulmonary embolism within the last 3 months before starting
             tazemetostat.

         13. Active infection requiring systemic therapy.

         14. Known hypersensitivity to any component of tazemetostat, prednisolone/prednisone
             (combination cohort only), or inability to be treated with a Pneumocystis prophylaxis
             medication (combination cohort only).

         15. Immunocompromised patients, including patients known to be infected with human
             immunodeficiency virus (HIV).

         16. Any other major illness that, in the investigator's judgment, will substantially
             increase the risk associated with the subject's participation in this study.

         17. Females who are pregnant or breastfeeding.

         18. Subjects who have undergone an organ transplant.

         19. Phase 2 only: Subjects with noncutaneous malignancies other than B-cell lymphomas.
             Exception: Subjects with another malignancy who have been disease-free for 5 years, or
             subjects with a history of a completely resected non-melanoma skin cancer or
             successfully treated in situ carcinoma are eligible.