Open-Label, Multi-Center, Two-Part, Ph1 Study to Characterize the PKs of an Intravenous Micro-Dose of [14C]-Tazemetostat (EPZ 6438) and the ADME of an Oral [14C]-Labeled Dose of Tazemetostat in Subjects With B-Cell Lymphomas or Adv Solid Tumors

NCT03010982 | Completed Phase 1 FDA Drug

• 2 other identifiers: EZH-1032016-002166-32
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 1, open-label, two-part study designed to characterize the PK of an IV dose of approximately 12 µg tazemetostat that contains approximately 500 nCi of \[14C\] tazemetostat and the ADME of an oral dose of 800 mg tazemetostat that contains approximately 400 µCi of \[14C\]-labeled tazemetostat in three subjects with B-cell lymphomas or advanced solid tumors.

Conditions

Diffuse Large B Cell Lymphoma; Primary Mediastinal Lymphoma; Mantle-Cell Lymphoma; Follicular Lymphoma; Marginal Zone Lymphoma; Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Plasma PK of [14C] tazemetostat, tazemetostat, and its metabolite EPZ-6930 after IV administration of approximately 12 µg of [14C] tazemetostat containing approximately 500 nCi of radioactivity and oral BID administration of 800 mg tazemetostat (AUC 0-7)

  Day 15

• Total recovery and relative excretion of radioactivity in urine and feces after an oral 800 mg dose of [14C] tazemetostat containing approximately 400 µCi (14.8 MBq) of radioactivity

  Day 16

Secondary Outcomes (7)

• Estimate tazemetostat absolute bioavailability (F) after repeated oral administration of 800 mg BID (AUC 0-12 and AUC 0-~)

  Day 15

• Compare the total radioactivity concentration-time profiles in blood and plasma after oral administration of [14C] tazemetostat (AUC 0-t, AUC 0-12, AUC 0-~)

  Day 16

• Determine peak plasma concentration (Cmax) after oral administration of [14C] tazemetostat

  Day 16

• Determine the plasma terminal half-life (t1/2) after oral administration of [14C] tazemetostat

  Day 16

• Plasma PK of tazemetostat and EPZ6930 after administration of an oral 800 mg dose of [14C] tazemetostat containing approximately 400 µCi (14.8 MBq) of radioactivity (Plasma AUC 0-t, AUC 0-12)

  Day 16

Study Arms (1)

Tazemetostat and [14C] Tazemetostat

EXPERIMENTAL

* Tazemetostat 800 mg BID orally as tablets continuously starting on Day 1, with the exception of the morning dose on Day 16; * A single IV dose of approximately 12 µg tazemetostat that contains approximately 500 nCi of \[14C\] tazemetostat on Day 15; * A single oral dose of 800 mg tazemetostat as a solution containing approximately 400 µCi (14.8 MBq) of \[14C\] tazemetostat on Day 16.

Drug: Tazemetostat and [14C] Tazemetostat

Interventions

Tazemetostat and [14C] Tazemetostat DRUG

Tazemetostat is a selective oral small molecule inhibitor of EZH2.

Also known as: E7438, EPZ-6438

Tazemetostat and [14C] Tazemetostat

Eligibility Criteria

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

You may qualify if:

• Male ≥ 18 years of age at time of consent
• Female ≥ 18 years of age at time of consent and of non-childbearing potential. A woman is considered to be of non-childbearing potential if she has reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause) or has undergone surgical sterilization (removal of ovaries and/or uterus). Note: Postmenopausal state will be confirmed with FSH test completed during the screening period.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Has a life expectancy of \>3 months
• Has EITHER histologically confirmed B-cell lymphomas including but not limited to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), primary mediastinal B-cell lymphoma (PMBCL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), or Hodgkin lymphoma (HL) and has relapsed or refractory disease following at least two lines of prior standard therapy, including alkylator/anthracycline (unless anthracycline-based chemotherapy is contraindicated)/anti-CD20-based therapy (R-CHOP, rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisolone or dexamethasone, or equivalent for non-Hodgkin lymphoma), AND must be considered unable to benefit from intensification treatment with autologous hematopoietic stem cell transplantation (ASCT) , as defined by meeting at least one of the following criteria:
• Relapsed following, or refractory to, previous ASCT
• Did not achieve at least a partial response to a standard salvage regimen (e.g., R-ICE, rituximab, ifosfamide, carboplatin, etoposide, or R-DHAP, rituximab, dexamethasone, cytarabine, cisplatin)
• Ineligible for intensification treatment due to age or significant comorbidity
• Ineligible for intensification treatment due to failure to mobilize an acceptable number of hematopoietic stem cells
• Refused intensification treatment and/or ASCT
• Histologically and/or cytologically confirmed advanced or metastatic solid tumor that has progressed after treatment with approved therapies or for which there are no standard therapies available
• May have evaluable or measurable disease
• Has all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ≤ Grade 1 per CTCAE, version 4.03 or are clinically stable, at time of consent
• Time between the last dose of the latest therapy and the first dose of study drug:
• Chemotherapy: cytotoxic - at least 21 days

You may not qualify if:

• Subjects meeting ANY of the following criteria must NOT be enrolled in this study:
• Has participated in a study in which \[14C\] was administered within the last 6 months prior to screening for this study
• Has CNS or leptomeningeal metastasis
• Has had a prior malignancy other than the malignancies under study Exception: Subject who has been disease-free for 3 years, or a subject with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible
• Has had major surgery within 3 weeks prior to enrollment NOTE: Minor surgery (e.g., minor biopsy, central venous catheter placement) is permitted within 3 weeks prior to enrollment
• Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study
• Has cardiovascular impairment, history of congestive heart failure greater than NYHA Class II uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of tazemetostat; or ventricular cardiac arrhythmia requiring medical treatment
• Subjects taking medications that are known potent CYP3A4 inducers/inhibitors (including St. John's Wort) from 14 days prior to the first dose of study medications (see http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm; or http://medicine.iupui.edu/clinpharm/ddis/ for a list of potent CYP3A4 inducers and inhibitors).
• Has an active infection requiring systemic treatment
• Is immunocompromised, including subjects with known history of infection with human immunodeficiency virus (HIV)
• Has known history of chronic infection with hepatitis B virus (hepatitis B surface antigen positive) or hepatitis C virus (detectable HCV RNA)
• Has had a venous thrombosis or pulmonary embolism within the 3 months prior to study enrollment.
• NOTE: Subjects with a history of a deep vein thrombosis \>3 months prior to study enrollment who are on anticoagulation therapy with low molecular weight heparin are eligible for this study.
• Has known hypersensitivity to any of the components of study drug
• Is unable to take oral medications, malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea or vomiting) that might impair the bioavailability of study drug

Sponsors & Collaborators

• Epizyme, Inc.: lead

Study Sites (2)

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, United Kingdom

Location

Royal Liverpool and Broadgreen University Hospital Trust

Liverpool, L7 8XP, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone

Interventions

tazemetostat

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

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 19, 2016
• First Posted: January 5, 2017
• Study Start: June 20, 2018
• Primary Completion: January 8, 2019
• Study Completion: January 8, 2019
• Last Updated: March 22, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)