Phase 2
N=74
Study of the EZH2 Inhibitor Tazemetostat in Malignant Mesothelioma
Mesothelioma · BAP1 Loss of Function
Bottom Line
View on ClinicalTrials.gov: NCT02860286 ↗Enrolled (actual)
74
Serious AEs
8.1%
Results posted
Apr 2021
Primary outcome: Primary: Part 1: Pharmacokinetics Profile of Tazemetostat and Its Metabolite (Plasma): Cmax — 933 Ng/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Tazemetostat (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Epizyme, Inc.
- Primary completion
- Jun 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Pharmacokinetics Profile of Tazemetostat and Its Metabolite (Plasma): Cmax |
933 | — |
| PRIMARY Part 1: Pharmacokinetics Profile of Tazemetostat and Its Metabolite (Plasma): Tmax |
1.1 | — |
| PRIMARY Part 1: Pharmacokinetics Profile of Tazemetostat and Its Metabolite (Plasma): AUC(0-t) |
3650 | — |
| PRIMARY Part 1: Pharmacokinetics Profile of Tazemetostat and Its Metabolite (Plasma): AUC(0-∞) |
3410 | — |
| PRIMARY Part 1: Pharmacokinetics Profile of Tazemetostat and Its Metabolite (Plasma): t1/2 |
3.06 | — |
| PRIMARY Part 2: To Assess Disease Control Rate (DCR) Defined as Number of Subjects With Complete Response (CR), Partial Response (PR) and Stable Disease (SD) |
33; 20 | — |
| PRIMARY Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability |
13; 60; 5; 31; 8; 44 | — |
| SECONDARY Part 1 and 2: Objective Response Rate (ORR; Complete Response + Partial Response [CR + PR]) |
0; 2; 0; 0; 0; 2 | — |
| SECONDARY Progression-free Survival (PFS) |
12; 18 | — |
| SECONDARY Part 1 and 2: Overall Survival (OS) |
29.0; 41.0 | — |
| SECONDARY Part 1 and 2: To Evaluate the Duration of Response (DOR) in Subjects With Confirmed CR or PR |
0; 0; 0; 0; 0; 2 | — |
| SECONDARY Part 1: To Assess Disease Control Rate (DCR) Defined as Number of Subjects With Complete Response (CR), Partial Response (PR) and Stable Disease (SD) |
5; 1 | — |
Summary
This is a Phase 2, multicenter, open-label, 2-part, single-arm, 2-stage study of tazemetostat 800 mg two times a day (BID) administered orally. Screening of subjects to determine eligibility for the study will be performed within 21 days of the first planned dose of tazemetostat.
In Part 1: planned to enroll 12 subjects with relapsed or refractory malignant mesothelioma regardless of BAP1 status will be treated and undergo pharmacokinetics (PK) blood sample collection after a single tazemetostat 800 mg.
Part 2 plans to include 55 subjects with BAP1-deficient relapsed or refractory malignant mesothelioma.
Treatment with tazemetostat will continue until disease progression, unacceptable toxicity or withdrawal of consent, or termination of the study. Response assessment will be evaluated after 6 weeks of treatment and then every 12 weeks thereafter while on study.
Eligibility Criteria
Inclusion Criteria
- Age (at the time of consent) ≥18 years of age
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Has a life expectancy of >3 months
- Has mesothelioma (pleural, peritoneal, pericardial, tunica vaginalis) of any histology that is relapsed or refractory after treatment with at least one pemetrexed-containing regimen
- 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
- Part 2: Molecular evidence of BAP1 loss of function mutation present on local pathology, e.g., lack of nuclear BAP1 staining by immunohistochemistry (IHC) or evidence of loss of function by gene sequencing
- Has sufficient archival tumor tissue (a minimum of 10 slides or tumor block) available for central retrospective testing of BAP1 status
- 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 and not clinically significant, at time of enrollment
- Prior therapy(ies), if applicable, must be completed according to the criteria below prior to first dose of tazemetostat:
- Cytotoxic chemotherapy; at least 21 days since last dose
- Non-cytotoxic chemotherapy (e.g., small molecule inhibitor); at least 14 days since last dose
- Monoclonal antibody; at least three half-lives since the last dose
- Non-antibody immunotherapy (e.g., tumor vaccine); at least 42 days since last dose
- Radiotherapy, at least 14 days from last local site radiotherapy
- Hematopoietic growth factor; at least 14 days from last dose
- Investigational drug; 30 days or five half-lives, whichever is longer, from last dose
- Has measurable disease based on either modified RECIST [Nowak 2005] for thoracic disease or RECIST 1.1 elsewhere
- Has adequate hematologic (bone marrow and coagulation factors), renal, and hepatic function as defined by criteria below:
- Hemoglobin ≥9 mg/dL
- Platelets ≥100, 000/mm3 (≥100 × 109/L) without platelet transfusion for 7 days
- ANC ≥1000/mm3 (≥1.0 × 109/L) without growth factor support for 14 days
- Coagulation: Prothrombin time (PT) 3 months prior to study enrollment who are on anticoagulation therapy with low molecular weight heparin are eligible for this study.
- Is pregnant or breastfeeding.
Data sourced from ClinicalTrials.gov (NCT02860286). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.