A Study of Tazemetostat in Combination With Various Treatments in Participants With Blood Cancer.

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 for Phase 1b and status 0 to 2 for Phase 2
Must have documented relapsed, refractory, or progressive disease after 2 lines of treatment with systemic therapy
Measurable disease
Demonstrate adequate organ function
Negative test results for acute or chronic hepatitis B virus (HBV) infection, hepatitis C virus (HCV) and human immunodeficiency virus
No ongoing clinically significant reactions to prior anticancer treatments
Willingness to follow pregnancy precautions and register into the mandatory REMS program in lenalidomide and pomalizdomide arms

Exclusion Criteria:

Presence or history of central nervous system involvement by lymphoma
Less than minimum washout period of prior anticancer therapy as specified by the protocol
Prior allogeneic haematopoietic stem cell transplantation
History of solid organ transplant
Major surgery within 4 weeks of the start of study drug.
Significant cardiac or cardiovascular impairment as specified by protocol
Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat
History of any bleeding disorder, peptic ulcer disease, or significant bleeding within the last 1 month prior to enrollment
Are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition
Patients with known active infection, or reactivation of a latent infection, as specified by the protocol
Known sensitivity or allergy to the study medications
Unwilling to refrain from eating or drinking grapefruit juice, Seville oranges, and grapefruits while on study
Prior exposure to tazemetostat
Any condition that places the subject at unacceptable risk if he/she were to participate in the study or that confounds the ability to interpret data from the study.
Prior history of myeloid malignancies or T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL)

For patients with DLBCL in Arm 1 (tazemetostat plus tafasitamab plus lenalidomide) or Arm 2 (tazemetostat plus lenalidomide):

- Prior exposure to lenalidomide

For patients with MCL in Arm 3 (tazemetostat plus acalabrutinib):

Prior exposure to a BTKi
Medical condition that would make treatment with a BTKi not reasonable (e.g. allergy to BTKi or mutations known not to respond to BTKi treatment or subjects unable to be transitioned off of proton pump inhibitors)

For patients with MM in Arm 4:

Prior exposure to pomalidomide
Untreated or impending spinal cord compression in subjects

For patients with FL in Arm 5:

Grade 3b, mixed histology, or FL that has histologically transformed to DLBCL.
History of significant neurological disorders, hemophagocytic lymphohistiocytosis (HLH), chronic active Epstein-Barr virus (EBV) infection, progressive multifocal leukoencephalopathy (PML), lung disease (ILD), drug-induced pneumonitis, autoimmune pneumonitis, and/or history of severe autoimmune disease