This is a Phase II, multicenter, open-label, single arm, 2-stage study of tazemetostat 800 mg BID administered orally. Screening of subjects to determine eligibility for the study will be performed within 21 days of the first planned dose of tazemetostat. Eligible subjects will be enrolled into one of three cohorts based on tumor type:

• Cohort 1: MRT, RTK, ATRT, or selected tumors with rhabdoid features
• Cohort 2: Relapsed or refractory synovial sarcoma with SS18-SSX rearrangement
• Cohort 3: Other INI1-deficient/aberrant tumors, including: Epithelioid sarcoma (ES), Epithelioid malignant peripheral nerve sheath tumor (EMPNST), Extraskeletal myxoid chondrosarcoma (EMC), Myoepithelial carcinoma, Renal medullary carcinoma (RMC), Other INI1-negative malignant tumors (e.g., dedifferentiated chordoma) with Sponsor approval

Treatment with tazemetostat will continue until disease progression, unacceptable toxicity or withdrawal of consent, or termination of the study. Response assessment will be evaluated after 8 weeks of treatment and then every 8 weeks thereafter while on study.