Intervention: Tazemetostat
Trial phase: Phase 2
ATC code: L01XX72
SMILES: CCN(c1cc(-c2ccc(CN3CCOCC3)cc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)C1CCOCC1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 5
Group description: Participants were to receive tazemetostat 800 mg BID starting on Cycle 1 Day 1 until the end of Cycle 24, for 24 months of therapy or until study termination. Participants were also to receive rituximab, administered by either as SC injection or IV infusion according to the regional product prescribing information, labeling, and institutional guidelines. Rituximab was to be administered at a dose of 375 mg/m^2 on Cycle 1 Days 1, 8, 15, and 22 and then on Day 1 of Cycles 3 through 6, accounting for an additional 4 doses (i.e., a total of 8 doses of rituximab in 6 cycles). Each cycle was 28 days.
Eligibility criteria:
Inclusion Criteria:

Men and women of 18 years of age and older
Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol
Eastern Cooperative Oncology Group (ECOG) score of 0 </=, 1 or 2
Life expectancy (in the opinion of the investigator) of >3 months before enrollment
Have histologically confirmed FL, Grade 1 to 3a. Subjects may have R/R disease following at least 2 standard prior systemic treatment regimens where at least 1 anti- CD20-based regimen was used
Treatment recommended in accordance with the Groupe d'Etude des Lymphomes b Folliculaires (GELF) criteria

Meet the following laboratory parameters:

Absolute neutrophil count (ANC) ≥ 750 cells/μL (0.75 x 109/L), or ≥ 500 cells/μL (0.50 x 109/L) in subjects with documented bone marrow involvement
Platelet count ≥ 50,000 cells/μL (50 x 109/L), or ≥ 30,000 cells/μL (30 x 109/L) in subjects with documented bone marrow involvement, and without transfusion dependence
Hemoglobin ≥ 8 g/dL
Serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤ Incl3.0 x ULN, unless related to disease involvement
Total bilirubin ≤ 1.5 x ULN, unless due to disease involvement, Gilbert's syndrome, or hemolytic anemia
Estimated creatinine clearance (ie, estimated glomerular filtration rate [eGFR] using Cockcroft-Gault) ≥ 40 mL/min
At least one bi-dimensionally measurable nodal lesion > 1.5 cm in its longest diameter by computed tomography (CT) scan or magnetic resonance imaging (MRI)
Any clinically significant toxicity related to a prior anticancer treatment (ie, chemotherapy, immunotherapy, and/or radiotherapy), except for alopecia, either resolved to ≤ Grade 1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 or is clinically stable and no longer clinically significant
Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection
Negative test results for hepatitis C virus (HCV) and human immunodeficiency virus (HIV).
Females of childbearing potential (FCBP) must have a negative serum pregnancy test (beta-human chorionic gonadotropin [β-hCG] test with a minimum sensitivity of 25 mIU/mL or equivalent units of β-hCG) at screening and within 24 hours prior to the first dose of study drug.
FCBP must either practice complete abstinence or agree to use a highly effective method of contraception beginning at least 28 days prior to the first dose of study drug, during study treatment (including during dose interruptions), for 6 months after tazemetostat discontinuation, and for 12 months after rituximab discontinuation. .
Male subjects must have had a successful vasectomy (with medically confirmed azoospermia) OR must either practice complete abstinence or agree to use a latex or synthetic condom during sexual contact with a FCBP from the first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation.

Exclusion Criteria:

Prior exposure to Tazemetostat or other inhibitor(s) of EZH2
Grade 2b, mixed histology, or transformed FL

Treatment with any of the following anticancer therapies within the timeframe of a specific treatment prior to first dose of study drug:

Cytotoxic chemotherapy within 21 days
Noncytotoxic chemotherapy (e.g. small molecule inhibitor) within 14 days
Nitrosoureas within 6 weeks
Prior immunotherapy within 4 weeks
Radiotherapy- within 6 weeks from prior radioisotope therapy; within 12 weeks from 50% pelvic or total body irradiation
Any investigational treatment within 4 weeks or at least 5 half lives, whichever is shorter
History of solid organ transplant
Major surgery within 4 weeks of the start of study treatment
Thrombocytopenia, neutropenia, or anemia of Grade > 3 (per CTCAE v5.0 criteria) or any prior history of myeloid malignancies, including MDS/AML or MPN
Prior history of T-LBL/T-ALL
Unwillingness to exclude grapefruit juice-containing products, Seville oranges, and grapefruits from the diet and/ or consumed within 1 week of the first dose of study drug
Subjects taking medications that are known strong cytochrome P450 (CYP)3A inhibitors and strong or moderate CYP3A inducers (including St. John's wort)
Any uncontrolled illness
History of clinically significant cardiovascular abnormalities
History of clinically significant gastrointestinal (GI) conditions
Other diagnosis of cancer that is likely to require treatment in the next 2 years
Females who are pregnant or lactating/breastfeeding
Received a live virus vaccination within 28 days of first dose of rituximab
Concurrent participation in a separate investigational therapeutic study
Psychiatric illness/social situations that would interfere with study compliance