A Phase 1/2, Open-label Study of Valemetostat in Combination With Rituximab and Lenalidomide in Relapsed or Refractory Follicular Lymphoma

To find a recommended dose of valemetostat that can be given in combination with rituximab and lenalidomide to patients with follicular lymphoma. The safety and effects of this drug combination will also be studied

Inclusion Criteria: Subjects must meet all of the eligibility criteria to be enrolled on this study. 1. Subjects ≥18 years of age at the time the ICF is signed. 2. Have histologically confirmed FL, grades 1-3A 3. Must have been previously treated with at least 1 prior systemic therapy followed by relapsed, refractory or progressive disease. a. Systemic therapy includes: i. Anti-CD20 monoclonal antibody in combination with chemotherapy ii. Anti-CD20 monoclonal antibody monotherapy iii. Anti-CD20 monoclonal antibody in combination with lenalidomide iv. Anti-CD20 monoclonal antibody plus investigational agent on protocol 4. Requiring systemic therapy as assessed by investigator based on tumor size, location, and/or GELF criteria. 5. Bi-dimensionally measurable disease, with at least one mass lesion ≥ 2 cm in longest diameter by CT, PET/CT, and/or MRI which was not previously irradiated. 6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 7. Adequate renal function defined as calculated creatinine clearance per the Cockcroft and Gault formula * In phase 1, creatinine clearance must be \>60 mL/minute * In Phase 2, creatinine clearance must be ≥30 mL/minute. 8. Adequate bone marrow function: 1. Absolute neutrophil count (ANC) ≥1,000/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. 2. Platelet ≥75,000/mm3 (≥75 × 109/L). Evaluated at least 7 days after platelet transfusion. 3. Hemoglobin \> 8.0 g/dL. Evaluated at least 7 days after RBC transfusion. 9. Adequate liver function: 1. Total bilirubin ≤1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome (eg, a gene mutation in UGT1A1), who can have total bilirubin \40 mIU/mL and estradiol \< 40 pg/mL (\10 mg daily prednisone equivalents). Note: Short-course systemic corticosteroids (eg, prevention/treatment for transfusion reaction) or use for a non-cancer indication (eg, adrenal replacement) is permissible 7. History of autologous stem cell transplant within 60 days prior to first dose of study drug 8. History of allogeneic stem cell transplant within 90 days prior to the first dose of study drug, and clinically significant graft-versus-host disease (GVHD) or GVHD requiring systemic immunosuppressive prophylaxis or treatment 9. Prior malignancy active within the previous 2 years except for locally curable cancer that is currently considered as cured, such as cutaneous basal or squamous cell carcinoma, superficial bladder cancer, or cervical carcinoma in situ, or an incidental histological finding of prostate cancer 10. Presence or history of central nervous system (CNS) involvement of lymphoma 11. Prior EZH inhibitor therapy 12. Current use of moderate or strong cytochrome P450 (CYP)3A inducers (See Appendix E) or inhibitors, or prior use of moderate or strong CYP3A within the past 2 weeks. 13. Current use of P-gp inducers and on narrow therapeutic index, sensitive P-gp substrates. 14. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of lenalidomide capsules, or put the study outcomes at undue risk 15. Human immunodeficiency virus (HIV), active Hepatitis C Virus, active Hepatitis B Virus infection, or any active systemic infection. Patients with inactive hepatitis B infection must adhere to hepatitis B reactivation prophylaxis unless contraindicated. 16. Clinically significant cardiovascular disease such asymptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification. 17. Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block. QT prolongation is not a significant ECG abnormality that would warrant exclusion. 18. Lactating or pregnant subjects