Study of Tazemetostat as Single Agent in Solid Tumors or B-cell Lymphomas and in Combination With Prednisolone in DLBCL

Inclusion Criteria: 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 of at least 3 months before starting tazemetostat. 3. Voluntary agreement to provide written informed consent and willing to adhere to all protocol requirements 4. Subjects with Hepatitis B or C are eligible on the condition that subjects have adequate liver function and are hepatitis B surface antigen negative and/or have undetectable hepatitis C virus (HCV) RNA. 5. Adequate renal and liver function 6. Phase 1: Males or females aged ≥ 16 years at time of informed consent. Phase 2: Males or females aged ≥ 18 years at the time of informed consent . 7. Females must not be lactating or pregnant at screening or baseline as documented by a negative pregnancy test 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. 8. 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 9. 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. 10. Phase 2, Groups 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 2. Have histologically confirmed Follicular Lymphoma (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. 3. Have provided sufficient archival tumor tissue that has been successfully tested for EZH2 mutation status and cell of origin (DLBCL only) 4. Have measurable disease as defined by International Working Group-Non-Hodgkin's Lymphoma (IWG-NHL) Exclusion Criteria: 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) 6. Subjects unwilling to remove Seville oranges, grapefruit juice and grapefruit from their diet. 6. Any unstable or unresolved prior treatment-related (i.e. chemotherapy, immunotherapy, radiotherapy) toxicities at time of enrollment. 7. Major surgery within 4 weeks before the first dose of study drug. . 8. 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. 9. 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. 10. Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat. 11. Active infection requiring systemic therapy. 12. Immunocompromised patients, including patients known to be infected with human immunodeficiency virus (HIV). 13. Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study. 14. Females who are pregnant or breastfeeding. 15. 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.