A Study to Compare the Blood Levels and Safety of Tazemetostat in Participants With Advanced Cancer and Moderate/Severe Liver Impairment to Participants With Advanced Cancer and Normal Liver Function

NCT04241835 | Terminated Phase 1 FDA Drug

• 3 other identifiers: EZH-12012019-003368-362024-517141-13-00
• Study Type: interventional
• Target: 18
• Locations: 5 countries
• Sites: 14

Brief Summary

This main aim of this trial will be to study the blood levels (known as pharmacokinetics) of the study drug tazemetostat. The pharmacokinetics of the study drug in participants with advanced solid tumors and moderate or severe hepatic (liver) impairment will be compared with participants with advanced malignancies and normal hepatic function. An advanced malignancy is a cancer that has recurred (come back) after prior treatment or hasn't controlled with treatment. The trial will also study the safety of the study drug in participants (how well it is tolerated).

Conditions

Hepatic Impairment; Advanced Malignant Solid Tumor

Outcome Measures

Primary Outcomes (7)

• To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, AUC0-t: area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration

  When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with participants with advanced malignancies and normal hepatic function.

  0 to 72 hours post dose on Day 1 and Day 15

• To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, AUC0-∞: area under the plasma concentration-time curve from time 0 extrapolated to infinity

  When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with participants with advanced malignancies and normal hepatic function

  0 to 72 hours post dose on Day 1 and Day 15

• To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, AUC0-8: area under the plasma concentration-time curve from time 0 to 8 hours post dose

  When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with participants with advanced malignancies and normal hepatic function

  0 to 8 hours post dose on Day 1 and Day 15

• To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, Cmax: observed maximum plasma concentration

  When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function

  0 to 72 hours post dose on Day 1 and Day 15

• To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, Tmax: observed time at Cmax

  When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function

  0 to 72 hours post dose on Day 1 and Day 15

• To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, t1/2: terminal elimination half-life

  When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function

  0 to 72 hours post dose on Day 1 and Day 15

• To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, fu: unbound fraction of drug in plasma

  When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function

  Pre-dose, 3 hours, 24 hours, and 72 hours post-dose

Secondary Outcomes (1)

• To evaluate the number of participants with adverse events (AEs) as assessed by CTCAE v5.0

  Through study completion, an average of 1 year

Study Arms (1)

Open label Tazemetostat

EXPERIMENTAL

Part 1: Participants will receive a single oral 800 mg dose on day 1, and twice daily from day 5 to day 14. Participants will return to the clinical study unit on an out-patient basis from day 15 to day 18. A single oral 800 mg dose of tazemetostat will be administered on day 15. Part 2: Will begin on day 19 and participants continuing treatment in Part 2 will receive tazemetostat (oral 800 mg dose) tablets to be taken twice daily in repeated 28-day cycles.

Drug: Tazemetostat

Interventions

Tazemetostat DRUG

Tazemetostat (EPZ-6438) in tablet form at a dose of 800 mg once daily on days 1 and 15 and twice daily on days 5 to 14 of the first 28-day cycle. Participants may continue tazemetostat treatment at 800 mg twice daily in additional 28-day cycles until progression or unacceptable toxicity.

Also known as: EPZ-6438, IPN60200, Tazverik®

Open label Tazemetostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18 years age at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Has the ability to understand informed consent and provided signed written informed consent.
• Life expectancy of \> 3 months.
• Histologically and/or cytologically confirmed advanced metastatic or unresectable solid tumors has progressed after treatment for which there are no standard therapies available OR histologically and/or cytologically confirmed hematological malignancies that have relapsed, or refractory disease following at least 2 standard lines of systemic therapy for which there are no standard therapies available.
• Must have evaluable or measurable disease.
• Has all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ≤ Grade 1 per NCI CTCAE, Version 5.0 or are clinically stable and not clinically significant, at time of consent.
• All subjects must have completed any prior chemotherapy, targeted therapy and major surgery, ≥ 28 days before study entry. For daily or weekly chemotherapy without the potential for delayed toxicity, a washout period of 14 days may be acceptable, and questions related to this can be discussed with the Medical Monitor.
• Has adequate hematologic (bone marrow \[BM\] and coagulation factors), and renal function.
• Able to swallow and retain orally-administered medication and without clinically significant gastrointestinal abnormalities that could alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
• Subjects with abnormal hepatic function will be eligible and will be grouped according to established criteria. Subjects with active hemolysis will be excluded.
• Manual differential with no significant morphologic abnormalities on complete blood count (CBC) testing.
• Male subjects must have had a successful vasectomy OR must either practice complete abstinence or agree to use a latex or synthetic condom during sexual contact with a female of childbearing potential from the first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation.
• Females of childbearing potential must have a negative serum pregnancy test at screening and within 24 hours prior to the first dose of study drug. All females will be considered of childbearing potential unless they are naturally postmenopausal or have been sterilized.
• Females of childbearing potential (FCBP) must either practice complete abstinence or agree to use a highly effective method of contraception beginning at least 28 days prior to the first dose of study drug, during study treatment (including during dose interruptions), and for 6 months after study drug discontinuation.

You may not qualify if:

• Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
• Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression as documented by CT or MRI scan, analysis of cerebrospinal fluid or neurological exam. Subjects with primary glioblastoma multiforme are excluded.
• Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders. Subjects on anticoagulation with low molecular weight heparin are allowed.
• Known hypersensitivity to any of the components of tazemetostat.
• Concurrent investigational agent or anticancer therapy. NOTE: Megestrol (Megace) if used as an appetite stimulant is allowed.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements.
• Have a known active infection with hepatitis B virus (HBV, as measured by positive hepatitis B surface antigen, hepatitis C virus (HCV, as measured by positive hepatitis C antibody), OR human T-cell lymphotropic virus 1.
• Subjects taking medications that are known potent CYP3A4 inducers/inhibitors (including St. John's Wort).
• Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from 24 hours prior to the first dose of study drug until the last dose of study drug.
• Any condition or medical problem in addition to the underlying malignancy and organ dysfunction that the Investigator feels would pose unacceptable risk.
• Has thrombocytopenia, neutropenia, or anemia of grade ≥3 (per CTCAE 5.0 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
• Has abnormalities known to be associated with MDS and myeloproliferative neoplasms (MPN) observed in cytogenetic testing and DNA sequencing.
• Has a prior history of T-LBL/T-ALL.
• Ingestion of alcohol and smoking is not permitted any time during the study.
• History of drug abuse (including alcohol) within the last 6 months prior to screening.

Sponsors & Collaborators

• Epizyme, Inc.: lead
• Sponsor GmbH: collaborator

Study Sites (14)

Florida Cancer Specialists & Research Institute

Lake Mary, Florida, 32746, United States

Location

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

Location

Hematology Oncology Consultants

Royal Oak, Michigan, 48073, United States

Location

Comprehensive Cancer Center of Nevada

Las Vegas, Nevada, 89014, United States

Location

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Antwerp University Hospital

Edegem, Antwerp, 2650, Belgium

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Institut de Cancérologie Strasbourg Europe

Strasbourg, France

Location

MedPolonia

Poznan, Greater Poland Voivodeship, 60693, Poland

Location

Summit Clinical Research, s.r.o

Bratislava, 831 01, Slovakia

Location

MeSH Terms

Interventions

tazemetostat

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2019
• First Posted: January 27, 2020
• Study Start: January 15, 2020
• Primary Completion: March 12, 2025
• Study Completion: March 12, 2025
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1); BE (1); FR (3); US (8); SL (1)