Epcoritamab and Tazemetostat for the Treatment of Relapsed or Refractory Grade I-IIIa Follicular Lymphoma

Inclusion Criteria

• •Documented informed consent of the participant and/or legally authorized representative
• •* Assent, when appropriate, will be obtained per institutional guidelines
• •Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• •* If unavailable, exceptions may be granted with study principal investigator (PI) approval
• •Age: ≥ 18 years
• •Eastern Cooperative Oncology Group (ECOG) ≤ 2
• •Histologically confirmed follicular lymphoma, grades 1-3A
• •Relapsed/ refractory disease after at least one line of prior lymphoma therapy
• •Radiologically measurable lymphadenopathy (≥ 1.5 cm) or ≥ 1 measurable extranodal lesion (long axis \> 1.0 cm) on CT scan or magnetic resonance imaging (MRI)
• •Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
• •WITHOUT BONE MARROW INVOLVEMENT: Absolute neutrophil count (ANC) ≥ 1,000/mm\^3 (NOTE: Growth factor use is allowed to reach ANC)
• •WITH BONE MARROW INVOLVEMENT: ANC ≥ 500/mm\^3 (NOTE: Growth factor use is allowed to reach ANC)
• •WITHOUT BONE MARROW INVOLVEMENT: Platelets ≥ 50,000/mm\^3 (NOTE: Platelet transfusions are within 14 days of platelet assessment if thrombocytopenia is secondary to disease involvement)
• •WITH BONE MARROW INVOLVEMENT: Platelets ≥ 25,000/mm\^3 (NOTE: Platelet transfusions are within 14 days of platelet assessment if thrombocytopenia is secondary to disease involvement)
• •Total bilirubin ≤ 2 x upper limit of normal (ULN) (unless has Gilbert's disease or secondary to disease)
• •Aspartate aminotransferase (AST) ≤ 2.5 x ULN
• •Alanine aminotransferase (ALT) ≤ 2.5 x ULN
• •Creatinine clearance of ≥ 45 mL/min per 24 hour urine test or the Cockcroft-Gault formula
• •If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN; If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
• •If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN; If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
• •Fridericia's formula-corrected QT interval (QTcF) ≤ 480 ms (Note: To be performed within 28 days prior to day 1 of protocol therapy)
• •If seropositive for HIV, hepatitis C virus (HCV) or hepatitis B virus (HBV), nucleic acid quantitation must be performed. Viral load must be undetectable. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• •Meets other institutional and federal requirements for infectious disease titer requirements (Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy)
• •Women of childbearing potential (WOCBP): negative serum pregnancy test
• •Agreement by females of childbearing potential must agree to either abstain from heterosexual intercourse or to use two effective methods of birth control simultaneously (effective methods described below). The time period for effective contraceptive requirements begins ≥ 28 days prior to initiating tazemetostat and for the course of the study treatment period through at least 6 months after the last dose of tazemetostat, 4 months after the last dose of epcoritamab, or 4 months after the last dose of tocilizumab (if applicable), whichever is longer. Childbearing potential is defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only). Two effective methods includes one highly effective method and one barrier method.
• •* Highly effective methods:
• •* Intrauterine device (IUD)
• •* Intrauterine hormone-releasing system (IUS)
• •* Hormonal (stopping ovulation with two drugs \[estrogen and progesterone\]: oral, within the vagina, or on/under the skin; stopping ovulation with one drug progesterone-only: oral, injected, or on/under the skin). NOTE: Due to the potential of tazemetostat interference with hormonal contraception methods, use of these method requires that you add a barrier method of contraception (preferably male condom)
• •* Bilateral tubal ligation
• •* Partner's vasectomy (if medically confirmed there are no live sperm and sole sexual partner)
• •* Barrier methods:
• •* Male latex or synthetic condom
• •* Diaphragm
• •* Cervical cap
• •Agreement by males to either practice complete abstinence or agree to use a latex or synthetic condom, even with a successful vasectomy (medically confirmed azoospermia), during sexual contact with a female of childbearing potential from first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation. NOTE: Male subjects must not donate semen or sperm from first dose of tazemetostat, during study treatment (including during dose interruptions), and for 3 months after discontinuation of tazemetostat