Open-Label, Multicenter, Two-Part, Phase 1 Study to Characterize Effects of a Moderate CYP3A Inhibitor on PK of Tazemetostat, Effects of Tazemetostat on PK of CYP2C8 and CYP2C19 Substrates, and Effect of Increased Gastric pH on PK of Tazemetostat in B-cell Lymphoma or Advanced Solid Tumor Patients

Inclusion criteria

• Male or female ≥ 18 years of age at time of consent
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Has the ability to understand informed consent and provided signed written informed consent

Must meet one of the following criteria:

• Has histologically confirmed diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL) and have relapsed or refractory disease following at least two lines of prior standard therapy, including alkylator/anthracycline (unless anthracycline-based chemotherapy is contraindicated)/anti-CD20-based therapy (R-CHOP; rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisolone or prednisone, or equivalent) AND must be considered unable to benefit from intensification treatment with autologous hematopoietic stem cell transplantation (ASCT), as defined by meeting at least one of the following criteria:
• Relapsed following, or refractory to, previous ASCT
• Did not achieve at least a partial response (PR) to a standard salvage regimen (e.g., R-ICE; rituximab, ifosfamide, carboplatin, etoposide, or R-DHAP; rituximab, dexamethasone, cytarabine, cisplatin)
• Ineligible for intensification treatment due to age or significant comorbidity
• Ineligible for intensification treatment due to failure to mobilize an acceptable number of hematopoietic stem cells
• Refused intensification treatment and/or ASCT Note: Subjects with prior radiotherapy will be included; however, radiotherapy alone will not be considered a separate systemic treatment regimen.

Note: Subjects with prior radiotherapy will be included; however, radiotherapy alone will not be considered a separate systemic treatment regimen.

OR

• Has histologically confirmed FL, all grades. Subjects must have relapsed/refractory disease following at least 2 standard lines of systemic therapy, including at least 1 anti-CD20-based regimen (eg, rituximab), as well as alkalating agents (eg, cyclophosphamide or bendamustine), and have no curative option with other available therapies OR have a contra-indication to their use. Subjects with prior ASCT may be included. Transformed disease is permitted.

Note: Subjects with prior radiotherapy will be included; however, radiotherapy alone will not be considered a separate systemic treatment regimen.

OR

• Histologically and/or cytologically confirmed advanced or metastatic solid tumor that has progressed after treatment with approved therapies or for which there are no standard therapies available
• Must have evaluable or measurable disease
• Has all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ≤ Grade 1 per NCI CTCAE, Version 4.03 or are clinically stable and not clinically significant, at time of consent
• Time required between the last dose of the latest therapy and the first dose of study drug:
• Chemotherapy: cytotoxic At least 21 days
• Chemotherapy: nitrosoureas At least 6 weeks
• Chemotherapy: non-cytotoxic (e.g., small molecule inhibitor) At least 14 days
• Monoclonal antibody (ies) At least 28 days
• Non-antibody immunotherapy (e.g., tumor vaccine) At least 42 days
• At least 14 days for stereotactic radiosurgery
• At least 12 weeks for craniospinal, ≥50% radiation of pelvis, or total body irradiation prior to first dose of study drug
• Autologous hematopoietic cell infusion after high dose therapy At least 60 days
• Hematopoietic growth factor At least 14 days
• Has adequate hematologic (bone marrow [BM] and coagulation factors), renal and hepatic function
• Hemoglobin ≥9 g/dL
• Platelets ≥75,000/mm3 (≥75 × 10^9/L)
• ANC: for patients with lymphoma ≥750/mm3 (≥0.75 × 10^9/L), for patients with advanced solid tumors ≥1,000/mm3 (≥1.0 × 10^9/L),
• PT <1.5 ULN
• PTT <1.5 ULN
• eGFR ≥ 50 mL/min/1.73 m2
• Conjugated bilirubin <1.5 × ULN
• AST <3 × ULN
• AL