• Subject aged ≥ 18 years.

• Eligible histologies include MCL, MZL (including splenic, nodal, and extranodal sub-types), and WM who received at least one line of prior systemic therapy and FL who received at least two prior lines of systemic therapy

• Measurable disease: at least one lesion \>1.5 cm in longest diameter or 1 extranodal lesion \>1 cm in the longest diameter.

⁃ -Note: For MZL, isolated splenomegaly and involvement of any biopsy proven extranodal site is considered measurable for this study. For MCL, clonal lymphocyte measured by flow cytometry is considered measurable. For WM, serum IgM level \>0.5 g/dL is considered measurable.

• Patients must have an indication for treatment.

‣ For R/R FL: active disease requiring treatment

⁃ For R/R MCL: active disease requiring treatment

⁃ For R/R MZL: active disease requiring treatment

⁃ For R/R WM: Meeting at least 1 criterion for treatment according to consensus panel criteria from the Seventh International Workshop on Waldenstrom's Macroglobulinemia68

• Recurrent fever, night sweats, weight loss, fatigue

∙ Hyperviscosity

∙ Lymphadenopathy which is either symptomatic or bulky (≥ 5 cm in maximum diameter)

∙ Symptomatic hepatomegaly and/or splenomegaly

∙ Symptomatic organomegaly and/or organ or tissue infiltration

∙ Peripheral neuropathy due to WM

∙ Symptomatic cryoglobulinemia

∙ Cold agglutinin anemia

∙ Immune hemolytic anemia and/or thrombocytopenia related to WM

∙ Nephropathy related to WM

∙ Amyloidosis related to WM

∙ Hemoglobin \<10 g/dL

∙ Platelet count \<100,000/mm3

• ECOG Performance Status ≤ 2.

• Adequate organ function as defined as:

‣ Hematologic:

• Absolute neutrophil count (ANC) ≥750 cells/mm3 (≥0.75 x 10\^9/L) independent of G-CSF support

∙ Platelet count ≥75,000 cells/mm\^3 (≥75 x 10\^9/L) independent of transfusion support.

⁃ Hepatic:

• Total Bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN with document liver involvement and/ or Gilbert's disease.

∙ AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN ----Subjects with liver involvement will be allowed to enroll with AST and ALT levels ≤ 5 x ULN.

⁃ Renal:

⁃ Estimated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula:

• Adequate coagulation, defined as activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) and prothrombin (PT) or (international normalized ratio (INR) not greater than 1.5 x ULN.

• Life expectancy of \>3 months, in the opinion of the investigator

• For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

‣ Women \< 50 years of age:

• Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and

∙ Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or

∙ Underwent surgical sterilization (bilateral oophorectomy or hysterectomy).

⁃ Women ≥ 50 years of age:

• Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or

∙ Had radiation-induced menopause with last menses \>1 year ago; or

∙ Had chemotherapy-induced menopause with last menses \>1 year ago; or

∙ Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).

• Female subjects of childbearing potential and male subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception and lactation requirements as described in Section 5.3.1 and 5.3.2.

• Subjects must agree to not breastfeed while on treatment or within 1 week of the last dose of tazemetostat or 2 weeks of zanubrutinib.

• Ability to swallow oral tablets

• Patients or their legal representatives must be able to read, understand, and provide informed consent to participate in the trial.

• Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.

• Time between prior anticancer therapy and first dose of tazemetostat as below:

‣ Cytotoxic chemotherapy - At least 21 days

⁃ Non-cytotoxic chemotherapy (e.g., small molecule inhibitor) - At least 14 days

⁃ Monoclonal antibody(ies) - At least 28 days

⁃ Radiotherapy

• At least 14 days from local site radiation therapy

∙ At least 6 weeks from prior radioisotope therapy

∙ At least 12 weeks from 50% pelvic or total body irradiation

⁃ High-dose therapy with autologous hematopoietic cell infusion - At least 60 days

⁃ CART cell therapy - At least 60 days

⁃ Moderate CYP3A inhibitors - At least 3 elimination half-lives

⁃ Moderate CYP3A inducers - At least 14 days

⁃ Strong CYP3A inducers or inhibitors - At least 14 days ----Note: Must be able to obtain zanubrutinib and anti-CD20 mAb commercially