A Study to Assess the Long-term Safety of Tazemetostat

Study Overview
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Brief Summary
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This study will provide continuing availability to tazemetostat for people that have previously completed participation in a tazemetostat study, either with monotherapy (single drug treatment) or combination therapy. The aim of the study will be to assess the long-term safety of tezemetostat.

Detailed Description
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This open-label, multicenter, global study will provide continuing access to tazemetostat therapy for subjects who have completed their participation in a prior tazemetostat study (either with monotherapy or combination therapy) without unacceptable toxicity, have not had evidence of tumor progression as defined by disease-appropriate standard criteria, and continue to receive clinical benefit from the therapy. Subjects will receive tazemetostat as dictated in their antecedent study. Visits will be conducted per Standard of Care (SoC) as appropriate in each country and as determined by the Investigator. Subjects will be followed for long-term safety in addition to time to treatment failure (TTF) and overall survival (OS).

Official Title
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Tazemetostat Rollover Study (TRuST): An Open-Label, Rollover Study

Conditions
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Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Synovial Sarcoma, Epitheliod Sarcoma (ES), Mesothelioma, Advanced Solid Tumors, Renal Medullary Carcinoma, Non-Hodgkin Lymphoma (NHL)

Intervention / Treatment
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* Drug: Tazemetostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet ALL criteria to be eligible for enrollment in this study. Has demonstrated and continues to demonstrate clinical benefit from treatment with tazemetostat. Is currently receiving tazemetostat as either monotherapy or in combination with other approved drug(s) or investigational agent(s) on an Epizyme-sponsored clinical trial or any other clinical trial being conducted with tazemetostat that is not sponsored by Epizyme (including but not limited to, investigator-initiated trials). For subjects on combination therapy, treatment with other therapeutic(s) must have been completed in the antecedent study or will be provided by a source other than Epizyme if combination therapeutics are continued in this study until disease progression, treatment toxicity, subject preference or death, up to approximately 7 years. Has voluntarily provided signed written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol. Has a life expectancy of ≥3 months. Has adequate hematologic, (bone marrow [BM] and coagulation factors), renal, and hepatic function. Subject must remain eligible for continued treatment with tazemetostat according to the eligibility and treatment criteria from the antecedent study Exclusion Criteria: Subjects meeting ANY of the following criteria must NOT be enrolled in this study: Has had an interruption of tazemetostat dosing of >14 days from the antecedent clinical study to starting the rollover study unless approved by the Medical Monitor. Has another malignancy other than the one for which they are receiving tazemetostat. • Exception: Subject who has been disease-free of a prior malignancy for 5 years or subject with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma is eligible. Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE v5 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS). Has a prior history of T-LBL/T-ALL.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label Tazemetostat<br>Participants will continue to receive the same tazemetostat dose and schedule as specified in their antecedent tazemetostat protocol. For participants on combination therapy, the other therapeutic(s) must have been completed in the antecedent study or be provided by a source other than Epizyme if combination treatment is continued in this clinical rollover study. | Drug: Tazemetostat<br>* Tazemetostat (EPZ-6438) is a selective small molecule inhibitor of enhancer of Zeste homolog 2 (EZH2), a histone-lysine N-methyltransferase enzyme.<br>* Other names: IPN60200;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events (AEs) and Treatment Emergent Adverse Event (TEAEs) | An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention Severity of adverse events experienced by all participants will be evaluated by the Investigator based on the CTCAE, version 5.0. | Until end of study an average of 7 years | 
| Duration of Study Drug Exposure | The average study drug exposure duration will be reported. | Until end of study an average of 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The overall survival (OS) | Defined as the interval of time between the date of the first dose of tazemetostat and the date of death due to any cause | Until end of study an average of 7 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epizyme, Tazverik, Tazemetostat (EPZ-6438)