A Study of Tazemetostat in Adult Participants With Soft Tissue Sarcoma

NCT02601950 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: EZH-2022015-002469-41
• Study Type: interventional
• Target: 267
• Locations: 9 countries
• Sites: 32

Brief Summary

This study will include participants with various types of cancer known as soft-tissue sarcomas. Tissues that can be affected by soft tissue sarcomas include fat, muscle, blood vessels, deep skin tissues, tendons and ligaments. Soft tissue cancers are rare and can occur almost anywhere in the body. Part 1 of this trial will study the safety and the level that adverse effects of the study drug tazemetostat in combination with doxorubicin (current front line treatment) can be tolerated (known as tolerability). It is also designed to establish a recommended study drug dosage for the next part of the study. Part 2 will evaluate and compare how long participants live without their disease getting worse when receiving the study drug plus doxorubicin versus doxorubicin plus placebo (dummy treatment).

Conditions

Malignant Rhabdoid Tumors (MRT); Rhabdoid Tumors of the Kidney (RTK); Atypical Teratoid Rhabdoid Tumors (ATRT); Selected Tumors With Rhabdoid Features; Synovial Sarcoma; INI1-negative Tumors; Malignant Rhabdoid Tumor of Ovary; Renal Medullary Carcinoma; Epithelioid Sarcoma; Poorly Differentiated Chordoma (or Other Chordoma With Sponsor Approval); Any Solid Tumor With an EZH2 GOF Mutation

Outcome Measures

Primary Outcomes (3)

• Cohorts 1, 3, 4, 5, 6 and 7: Objective Response Rate (ORR)

  ORR was defined as percentage of participants who achieved a confirmed complete response (CR) or partial response (PR) based on the investigator review from start of treatment until progressive disease (PD) or start of subsequent anti-cancer therapy or cancer-related surgery, whichever was earlier, as per response assessment in neuro-oncology (RANO) criteria for primary brain tumors or response evaluation criteria in solid tumors (RECIST) version (v) 1.1 criteria for all other solid tumors. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must be \<10 millimeter (mm) in short axis. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as a reference, baseline sum of diameters. PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as a reference, smallest sum of diameters recorded since treatment started. In addition, sum must have an absolute increase from nadir of 5 mm.

  Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration: 28 days)

• Cohort 2: Progression-Free Survival (PFS) Rate at 16 Weeks of Treatment With Tazemetostat

  PFS was defined as the interval of time between the date of the first dose of study treatment and the earliest date of PD or death due to any cause, whichever comes first, as per RECIST v 1.1 criteria. PFS rate at 16 week was estimated. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as a reference, smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase from nadir of 5 mm.

  At 16 Weeks

• Cohort 8: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect or was medically significant. TEAEs were defined as AEs if one of the following conditions met: emerged after the time of first dose administration, having been absent prior to the first dose; re-emerged, having been present but stopped prior to the time of first dose administration; worsened in severity after the time of first dose administration relative to the pretreatment state, when the AE was continuous.

  From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment, approximately 148 weeks

Secondary Outcomes (7)

• All Cohorts: Duration of Response (DOR)

  Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration 28 days)

• All Cohorts: Progression-Free Survival (PFS)

  Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration 28 days)

• All Cohorts: Progression-Free Survival (PFS) Rate at Weeks 24, 32 and 56

  At Weeks 24, 32 and 56

• All Cohorts: Overall Survival (OS)

  Tumor assessment performed at screening and every 8 weeks beginning at Cycle 3 Day 1, until disease progression or the start of subsequent anti-cancer therapy, whichever occurred first, up to 5.75 years (cycle duration: 28 days)

• All Cohorts: Overall Survival (OS) Rate at Weeks 24, 32 and 56

  At Weeks 24, 32 and 56

Study Arms (1)

Open-label Tazemetostat

EXPERIMENTAL

All cohorts will receive 800 mg oral Tazemetostat twice a day in continuous 28-day cycles.

Drug: Tazemetostat

Interventions

Tazemetostat DRUG

Tazemetostat (EPZ-6438) is a selective small molecule inhibitor of the histone-lysine methyltransferase EZH2 gene

Also known as: EPZ-6438, E7438, IPN60200

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:

• Age (at the time of consent/assent): ≥18 years of age
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Has provided signed written informed consent
• Has a life expectancy of \>3 months
• Has a malignancy:
• For which there are no standard therapies available (Cohorts 1, 3, 4 and 5)
• That is relapsed or refractory after treatment with an approved therapy(ies), defined as metastatic or non-resectable, locally advanced disease that has previously been treated with and progressed following approved therapy(ies) (Cohort 2)
• That has progressed within 6 months prior to study enrollment (Cohort 5 Expansion, Cohort 6 and Cohort 8 ONLY)
• Has a documented local diagnostic pathology of original biopsy confirmed by a Clinical Laboratory Improvement Amendments (CLIA/College of American Pathologists (CAP) or equivalent laboratory certification
• For Cohort 1 (rhabdoid tumors only), the following test results must be available by local laboratory: morphology and immunophenotypic panel consistent with rhabdoid tumors, and loss of INI1 or SMARCA4 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 or SMARCA4 loss or mutation when INI1 or SMARCA4 IHC is equivocal or unavailable
• For Cohort 2 (subjects with relapsed/refractory synovial sarcoma only), the following tests must be available by local laboratory: Morphology consistent with synovial sarcomas, and cytogenetics or fluorescence in situ hybridization (FISH) and/or molecular confirmation (e.g., DNA sequencing) of SS18 rearrangement t(X;18)(p11;q11)
• For Cohort 3, 4, 5, 7 and 8 (subjects with INI1-negative/aberrant tumors or any solid tumor with EZH2 GOF mutation only), the following test results must be available by local laboratory: Morphology and immunophenotypic panel consistent with INI1-negative tumors (not applicable for solid tumors with EZH2 GOF mutation), and loss of INI1 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 loss or mutation when INI1 IHC is equivocal or unavailable, or molecular evidence of EZH2 GOF mutation
• For Cohort 6 (subjects with ES undergoing optional tumor biopsy) only:
• Morphology and immunophenotypic panel consistent with ES (e.g., CD34, EMA, Keratin, and INI1)
• Has all prior treatment (i.e. chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ≤Grade 1 per CTCAE version 4.0.3 or are clinically stable and not clinically significant, at time of enrollment.

You may not qualify if:

• Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2 (EZH2)
• Has participated in another interventional clinical study and received investigational drug within 30 days or 5 half-lives, whichever is longer, prior to the planned first dose of tazemetostat
• Has known active CNS or any leptomeningeal metastasis of primary extra-cranial tumor.
• Has had a prior malignancy other than the malignancies under study - EXCEPTION: A subject who has been disease-free for 5 years, or a subject with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma is eligible
• Has had major surgery within 3 weeks prior to enrollment
• Has Thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE 4.03 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS). Has abnormalities known to be associated with MDS (e.g. del 5q, chr 7 abn) and MPN (e.g. JAK2 V617F) observed in cytogenetic testing and DNA sequencing.
• Has a prior history of T-LBL /T-ALL
• Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet
• 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
• Is currently taking any prohibited medication(s)
• Has an active infection requiring systemic treatment
• Is immunocompromised (i.e. has congenital immunodeficiency), including subjects known history of infection with human immunodeficiency virus (HIV)
• Has known active infection with hepatitis B virus or hepatitis C virus
• Has had a symptomatic venous thrombosis within 2 weeks prior to study enrollment -
• For subjects with CNS involvement (primary tumor or metastatic disease), have any active bleeding or new intratumoral hemorrhage of more than punctuate size of screening MRI obtained within 14 days of starting study drug or known bleeding diathesis or treatment with anti-platelet or anti-thrombotic agents

Sponsors & Collaborators

• Epizyme, Inc.: lead

Study Sites (32)

University of California San Francisco

San Francisco, California, 94115, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital - Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Metro South Hospital and Health Service via Princess Alexandra Hospital

Woolloongabba, QLD 4102, Australia

Location

Institut Jules Bordet Medical Oncology Clinic

Brussels, 1000, Belgium

Location

University Hospital Leuven

Leuven, 3000, Belgium

Location

Alberta Health Services

Edmonton, Alberta, T6G 1Z2, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 1X8, Canada

Location

McGill University Health Centre - Royal Victoria Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Institut Curie

Paris, 75248, France

Location

Hospital Pitie Salpetriere

Paris, 75651, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Children's Hospital Augsburg Klinikum

Augsburg, 86156, Germany

Location

Sarcoma Center HELIOS Klinikum Berlin

Berlin, 13125, Germany

Location

Instituto Nazionale Tumori - National Cancer Institute Via Giacomo Venezian

Milan, 20133, Italy

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

University College London Hospital

London, NW1 2PG, United Kingdom

Location

Royal Marsden Foundation Trust

London, SW3 6JJ, United Kingdom

Location

Related Publications (1)

• Gounder M, Schoffski P, Jones RL, Agulnik M, Cote GM, Villalobos VM, Attia S, Chugh R, Chen TW, Jahan T, Loggers ET, Gupta A, Italiano A, Demetri GD, Ratan R, Davis LE, Mir O, Dileo P, Van Tine BA, Pressey JG, Lingaraj T, Rajarethinam A, Sierra L, Agarwal S, Stacchiotti S. Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: an international, open-label, phase 2 basket study. Lancet Oncol. 2020 Nov;21(11):1423-1432. doi: 10.1016/S1470-2045(20)30451-4. Epub 2020 Oct 6.

  PMID: 33035459 DERIVED

Related Links

• Lay language results summary

MeSH Terms

Conditions

Sarcoma, Synovial; Sarcoma

Interventions

tazemetostat

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Medical Lead or Designee
• Organization: Epizyme, Inc.

clinicaltrials@epizyme.com

(855) 500-1011

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: November 11, 2015
• Study Start: December 22, 2015
• Primary Completion: February 26, 2024
• Study Completion: February 26, 2024
• Last Updated: June 22, 2025
• Results First Posted: March 11, 2025

Record last verified: 2025-06

Data Sharing

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

Locations

IT (1); GB (2); US (14); AU (2); FR (5); BE (2); CA (3); TW (1); DE (2)