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.

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).

Inclusion Criteria:

1. Subjects must meet ALL criteria to be eligible for enrollment in this study.
2. Has demonstrated and continues to demonstrate clinical benefit from treatment with tazemetostat.
3. 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.
4. Has voluntarily provided signed written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol.
5. Has a life expectancy of ≥3 months.
6. 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:

1. 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.

2. 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.

3. Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE v5 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).

4. Has a prior history of T-LBL/T-ALL.

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications.

Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.

Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).