A Study to Assess Efficacy and Safety of Oral Tazemetostat in Adult Participants With Relapsed/Refractory Follicular Lymphoma That Does Not Have an "EZH2 Gain-of-function" Genetic Mutation

Inclusion Criteria:

* At least 18 years of age, inclusive, at the time of signing the informed consent form
* Histologically confirmed follicular lymphoma (FL) grades 1, 2, or 3A
* Previously treated with ≥1 prior systemic chemotherapy, immunotherapy, or chemo-immunotherapy consistent with those used in a US population, including but not limited to bendamustine, obinutuzumab, rituximab plus lenalidomide. Patients with only 1 prior line of therapy should not be eligible for available combination or monotherapies
* Documented relapsed, refractory, or progressive disease (PD) after treatment with systemic therapy (refractory defined as less than PR or as PD \<6 months after last dose)

  * Measurable disease as defined by Lugano Classification
  * Have provided sufficient tumour tissue block or unstained slides for EZH2 mutation and copy number gain (CNG) testing
* Wild-type EZH2 (ie, lacking GOF mutation). Note: If EZH2 GOF mutation status is known from site specific testing, WT patients can be enrolled with documentation of the testing, and additional archival tumour tissue or fresh lymph node biopsy taken before starting tazemetostat will be required for confirmatory testing of EZH2 GOF mutation status at study-specific laboratories. If EZH2 GOF mutation status is unknown, the results of central testing confirming wild-type (WT) EZH2 mutation status on an archival tumour sample, or a fresh lymph node biopsy is required before enrolment. (Archival tumour tissue collected within 15 months before the first dose is preferred, where feasible.)
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2
* Adequate time between prior anticancer therapy and first dose of tazemetostat as follows:

  * Cytotoxic chemotherapy: At least 21 days.
  * Noncytotoxic chemotherapy (eg, small molecule inhibitor): At least 14 days.
  * Monoclonal and/or bispecific antibodies or chimeric antigen receptor (CAR) T: At least 28 days.
  * Radiotherapy: At least 6 weeks from prior radioisotope therapy; at least 12 weeks from 50% pelvic or total body irradiation.
* Adequate liver function, by all of the following criteria:

  * Total bilirubin ≤1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome.
  * Alkaline phosphatase (ALP) (in the absence of bone disease), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN if the patient has liver metastases).
* Adequate renal function: Calculated creatinine clearance ≥30 mL/minute per the Cockcroft and Gault formula

  * Adequate bone marrow function, by all of the following criteria:
  * Absolute neutrophil count (ANC) ≥1000/mm3 (≥1.0 × 109/L) if no lymphoma infiltration of bone marrow OR ANC ≥750/mm3 (≥0.75 × 109/L) with bone marrow infiltration: Without growth factor support (filgrastim or pegfilgrastim) for at least 14 days.
  * Platelets ≥75,000/mm3 (≥75 × 109/L), evaluated at least 7 days after last platelet transfusion.
  * Haemoglobin ≥9.0 g/dL, though may receive transfusion
* Adequate coagulation, by both of the following criteria (NOTE: In patients with thromboembolism risk, prophylactic anticoagulation, or antiplatelet therapy at investigator discretion, is recommended):
* International normalized ratio (INR) ≤1.5 × ULN
* Activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless on warfarin, then INR ≤3.0).
* Women of childbearing potential (WOCBP) must have 2 negative pregnancy tests (beta-human chorionic gonadotropin \[β-hCG\] on-site urine or serum tests with a minimum sensitivity of 25 mIU/mL or equivalent units of β-hCG) during screening. The second of these screening pregnancy tests

Exclusion Criteria:

* Grade 3b FL, mixed histology FL, or FL that has histologically transformed to DLBCL.
* Malignancies other than FL.
* Any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or myeloproliferative neoplasm (MPN)
* Any prior history of T-cell lymphoblastic lymphoma (LBL)/T-cell acute lymphoblastic leukaemia (ALL)
* Major surgery within 4 weeks before the first dose of study intervention.
* Significant cardiovascular impairment.
* Prolongation of corrected QT interval using Fridericia's formula (QTcF) to ≥480 msec at screening or history of long QT syndrome
* Venous thrombosis or pulmonary embolism within 3 months before starting tazemetostat. Note: Patients with deep vein thrombosis/pulmonary embolism greater than 3 months before treatment are eligible but recommended to receive prophylaxis
* Uncontrolled active infection requiring systemic therapy
* Active viral infection with human immunodeficiency virus (HIV)
* History of hepatitis B or C, unless they have adequate liver function as defined by inclusion criteria and are hepatitis B surface antigen negative with undetectable hepatitis B virus (HBV) DNA and/or have undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) if HCV antibody positive
* History of solid organ transplant
* Prior exposure to tazemetostat or other inhibitor(s) of EZH2
* Taking medications that are known strong CYP3A inhibitors and strong or moderate CYP3A inducers (including St. John's wort)
* Pregnant or lactating/breastfeeding