Inclusion Criteria:

1. Have voluntarily agreed to provide written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol.
2. Males or females are ≥18 years of age at the time of providing voluntary written informed consent.
3. Life expectancy ≥3 months before enrollment.
4. Subjects with a history of hepatitis B or C are eligible on the condition that subjects have adequate liver function as defined by Inclusion Criterion #15 and are hepatitis B surface antigen negative and/or have undetectable hepatitis C virus (HCV) RNA.
5. Have histologically confirmed FL, grades 1 to 3A.
6. Must have been previously treated with at least 1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy:
   1. Systemic therapy includes treatments such as:

   i. Rituximab monotherapy ii. Chemotherapy given with or without rituximab iii. Radioimmunoconjugates such as 90Y-ibritumomab tiuxetan and 131I-tositumomab.

   b. Systemic therapy does not include, for example: i. Local involved field radiotherapy for limited-stage disease ii. Helicobacter pylori eradication Prior investigational therapies will be allowed provided the subject has received at least

1 prior systemic therapy as discussed in Inclusion Criteria #6a. 7. Must have documented relapsed, refractory, or PD after treatment with systemic therapy (refractory defined as less than PR or disease progression <6 months after last dose).

8. Have measurable disease as defined by the Lugano Classification (Cheson, 2014).

9.Time between prior anticancer therapy and first dose of tazemetostat as follows:

1. Cytotoxic chemotherapy - At least 21 days.
2. Noncytotoxic 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 6 weeks from prior radioisotope therapy; at least 12 weeks from 50% pelvic or total body irradiation. 13. Adequate renal function defined as calculated creatinine clearance ≥40 mL/minute per the Cockcroft and Gault formula or local institutional standard formula.

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

   11. Adequate bone marrow function. 12. Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [β-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of β-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 treatment. All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutively amenorrhoeic, 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 dosing).

   13. 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 30 days after the final dose of study treatment, and have a male partner who uses a condom. Highly effective contraception includes:

   • Double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide.
   • Placement of an intrauterine device.
   • 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 30 days after study drug discontinuation.

NOTE: 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 treatment cycles, and for 30 days after study drug discontinuation. 14. All study participants enrolled must be registered into the mandatory Revlimid REMS™ program and be willing and able to comply with the requirements of the Revlimid REMS™ program as appropriate for the country in which the drug is being used.

a. Female subjects of childbearing potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS™ program. Female subjects exempt from this requirement are subjects who have been in natural menopause for at least 2 years OR have had both ovaries and/or uterus removed.

15. Male subjects must have had either a successful vasectomy 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 30 days after study drug discontinuation).

Exclusion Criteria:

All Subjects

1. Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
2. Prior exposure to lenalidomide for the treatment of FL.
3. Subjects who have mixed or transformed histology.
4. Has thrombocytopenia, neutropenia, or anemia of grade ≥3 (per CTCAE Version 5.0 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
5. Has a prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL).
6. Subjects with uncontrolled leptomeningeal metastases or brain metastases or history of previously treated brain metastases.
7. Subjects taking medications that are known potent cytochrome P450 (CYP)3A4 inducers/inhibitors (including St. John's wort) (Flockhart, 2007; U. S. Food and Drug Administration, February 2015).
8. Are unwilling to exclude Seville oranges, grapefruit juice, AND grapefruit from their diet.
9. Major surgery within 4 weeks before the first dose of study drug.

   a. Note: Minor surgery (eg, minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 3 weeks prior to enrollment.

10. Are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat.
11. 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.
12. Prolongation of corrected QT interval using Fridericia's formula (QTcF) to >480 msec at screening or history of long QT syndrome.
13. Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat.

    a. whereas subjects greater than 3 months since deep vein thrombosis/pulmonary embolism are eligible but recommended to receive prophylaxis.

14. Have an active infection requiring systemic therapy.
15. Known hypersensitivity to any component of tazemetostat, lenalidomide, or rituximab.
16. Inability to be treated with a Pneumocystis prophylaxis medication.
17. Have an active infection with hepatitis B virus (as measured by positive hepatitis B surface antigen), HCV (as measured by positive hepatitis C antibody), human immunodeficiency virus, OR human T-cell lymphotropic virus 1.

    a. Exceptions: Subjects with a history of hepatitis B or C who have normal ALT AND are hepatitis B surface antigen negative and/or have undetectable HCV RNA.

18. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the subject's participation in this study OR interfere with their ability to receive study treatment or complete the study.
19. Female subjects who are pregnant or breastfeeding.
20. Subjects who have undergone a solid organ transplant.
21. Subjects with malignancies other than FL. a. 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.