A Study to Assess Long-term Safety of Tazemetostat in Adult Participants of All Ages With Any Disease Treated With Tazemetostat in a Previous Clinical Study (TRuST)

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors; Mesothelioma; Synovial Sarcoma; Renal Medullary Carcinoma; Diffuse Large B-cell Lymphoma (DLBCL); Follicular Lymphoma (FL); Non-Hodgkin Lymphoma (NHL); Epitheliod Sarcoma (ES)
• Intervention / Treatment: Drug: Tazemetostat

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Alexandra, Australia
    • Princess Alexandra Hospital
  • Clayton, Australia, 3168
    • Monash Medical Centre- Monash Campus
  • Geelong, Australia
    • Geelong Hospital
  • Melbourne, Australia, 3002
    • Peter Maccallum Cancer Institute
  • Monash, Australia
    • Monash Health
• Belgium
  • Leuven, Belgium, 3000
    • University Hospital (UZ) Leuven
• France
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Caen, France, 14033
    • CHU de Caen - Hopital Cote de Nacre
  • Lille, France, 59037
    • CHRU de Lile- Hopital Claude Huriez
  • Montpellier, France
    • CHU De Montpellier - Hopital Saint Eloi
  • Paris, France, 75010
    • Hôpital Saint Louis - AP-HP
  • Pierre-Bénite, France, 69310
    • Centre Hospitalier Lyon Sud
  • Rennes, France, 35033
    • CHU Rennes- Hopital Pontchaillou
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Villejuif, France, 94805
    • Gustave Roussay
• Poland
  • Krakow, Poland, 30-510
    • Pratia MCM Krakow
  • Warsaw, Poland
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Endokrynologii Onkologicznej i Medycyny Nuklearnej
• Ukraine
  • Kharkiv, Ukraine, 61024
    • S.P. Grigoreva Institute of Medical Radiology and Oncology of NAMS of Ukraine"
• United Kingdom
  • Glasgow, United Kingdom
    • Beatson, West of Scotland Cancer Centre
  • Leicester, United Kingdom, LEI 5WW
    • Oncology and Haematology Clinical Trials Unit
  • Liverpool, United Kingdom, L7 8XP
    • Clatterbridge Cancer Centre
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • Manchester, United Kingdom
    • The Christie NHS Foundation Trust
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center
  • California
    • Santa Fe, California, United States, 92024
      • California Cancer Associates for Research and Excellence, cCARE
  • Florida
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology Oncology Associates of the Treasure Coast - Port St. Lucie
    • Tampa, Florida, United States, 33612
      • Moffitt
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Astera Cancer Center
  • New York
    • New York, New York, United States, 10019
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Open-label Tazemetostat; 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; Tazemetostat (EPZ-6438) is a selective small molecule inhibitor of enhancer of Zeste homolog 2 (EZH2), a histone-lysine N-methyltransferase enzyme.; Other Names: EPZ-6438; E7438; IPN60200

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time to treatment failure (TTF) in subjects receiving tazemetostat	TTF, defined as the time from date of first dose of study drug to treatment discontinuation for any reason, including disease progression, treatment toxicity, subject preference, or death	The time from date of first dose of study treatment to treatment discontinuation for any reason including disease progression, treatment toxicity, subject preference or death, up to 7 years

Collaborators and Investigators

• Sponsor: Epizyme, Inc.
• Investigators: Study Director: Ipsen Medical Director, Ipsen

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2016
• Primary Completion (Actual): September 26, 2025
• Study Completion (Actual): September 26, 2025

Study Registration Dates

• First Submitted: August 5, 2016
• First Submitted That Met QC Criteria: August 17, 2016
• First Posted (Estimated): August 23, 2016

Study Record Updates

• Last Update Posted (Estimated): November 4, 2025
• Last Update Submitted That Met QC Criteria: October 31, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Epizyme; Tazverik; Tazemetostat (EPZ-6438)
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenoma; Neoplasms, Mesothelial; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, B-Cell; Lymphoma; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Hemic and Lymphatic Diseases; Mesothelioma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Sarcoma, Synovial; tazemetostat
• Other Study ID Numbers: EZH-501; 2015-004984-35 (EudraCT Number); 2023-510553-41-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No