This is a Phase II, multicenter, open-label, single arm, 2-stage study of tazemetostat 800 mg BID administered orally in continuous 28 day cycles. 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 fivecohorts based on tumor type: - Cohort 1 (Closed for enrollment): MRT, RTK, ATRT, or selected tumors with rhabdoid features, including small cell carcinoma of the ovary hypercalcemic type [SCCOHT], also known as malignant rhaboid tumor of the ovary [MRTO] - Cohort 2 (Closed for enrollment): Relapsed or refractory synovial sarcoma with SS18-SSX rearrangement - Cohort 3 (Closed for enrollment): Other INI1 negative tumors or any solid tumor with an EZH2 gain of function (GOF) mutation, including: epithelioid malignant peripheral nerve sheath tumor (EMPNST), extraskeletal myxoid chondrosarcoma (EMC), myoepithelial carcinoma, other INI1-negative malignant tumors with Sponsor approval (e.g., dedifferentiated chordoma) any solid tumor with an EZH2 GOF mutation including but not limited to Ewing's sarcoma and melanoma - Cohort 4 (Closed for enrollment): Renal medullary carcinoma (RMC) - Cohort 5 (Closed for enrollment): Epithelioid sarcoma (ES) - Cohort 6 (Closed for enrollment): Epithelioid sarcoma (ES) undergoing mandatory tumor biopsy - Cohort 7 (Opened for enrollment): Poorly differentiated chordoma (or other 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.
Name: Tazemetostat
Description: Tazemetostat (EPZ-6438) is a selective small molecule inhibitor of the histone-lysine methyltransferase EZH2 geneType: DrugOpen-label Tazemetostat
Description: The number of subjects with CR, PR, or stable disease (SD) at 16 week assessment
Measure: Progression-free survival (PFS) rate for Cohort 2 (Relapsed/Refractory Synovial Sarcoma) Time: 16 weeks of treatmentDescription: The number of subjects with confirmed CR, PR or SD at 32 week assessment
Measure: Disease control rate (DCR) in subjects with epithelioid sarcoma (Cohort 5) and epithelioid sarcoma undergoing mandatory biopsy (Cohort 6) following oral administration of tazemetostat 800 mg BID Time: 32 weeks of treatmentDescription: ORR (confirmed CR+PR, RECIST 1.1)
Measure: Overall response rate ORR for Cohort 2 (relapsed/refractory synovial sarcoma) and Cohort 6 (epithelioid sarcoma undergoing mandatory biopsy) Time: Assessed every 8 weeks for duration of study participation which is estimated to be 24 monthsDescription: The time from date of first dose of study treatment to the earlier of the date of first documented disease progression or date of death due to any cause
Measure: PFS for each cohort Time: 24, 32 and 56 weeks of treatmentDescription: The time from the date of the first dose of study treatment to the date of death due to any cause
Measure: OS for each cohort Time: 24, 32 and 56 weeks of treatmentDescription: IHC assessments of changes in the level of H3K27-Me3 following tazemetostat dosing
Measure: Investigate the pharmacodynamics (PD) effects of tazemetostat in tumor tissue Time: At week 8Single Group Assignment
There is one SNP
JAK2 V617F) observed in cytogenetic testing and DNA sequencing. --- V617F ---