Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

B-cell Lymphoma

Participants will receive oral tazemetostat at a starting dose of 800 milligrams (mg) as a single dose (Cycle 0) and 800 mg twice a day as continuous dosing (Cycle 1 and later) (Cycle 0 duration=4 days) (Cycle 1 and later duration= 28 days).

Tazemetostat

This is a multicenter, single-arm, open-label, Phase 1 study to assess the tolerability, safety, pharmacokinetics, and preliminary anti-tumor activity of tazemetostat in participants with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).

A Study of Tazemetostat in Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

A Phase 1 Study of Tazemetostat in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) were defined as: 1) Grade 4 neutropenia for greater than (\>) 7 days; 2) greater than or equal to (\>=) Grade 3 febrile neutropenia; 3) Grade 4 thrombocytopenia and Grade 3 thrombocytopenia with bleeding; 4) Grade 4 anemia or anemia requiring erythrocyte transfusion; 5) \>=Grade 3 nausea, vomiting, or diarrhea that persisted \>7 days despite maximal medical therapy; 6) \>=Grade 3 non-hematological laboratory abnormalities with clinical symptoms that persisted \>7 days; 7) Other Grade 3 toxicity lasting \>7 days or Grade 4 non-hematological toxicity of any duration; 8) Failure to administer \>=75 percent (%) of the planned administration number of study drug in Cycle 1 as a result of treatment-related toxicity. Here, number of participants who had DLT were reported.

TEAE was defined as an adverse event (AE) that emerged during time from first dose to 30 days following last dose of drug, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to pretreatment state, when AE was continuous. Number of participants with TEAEs were reported based on their safety assessments of laboratory tests, physical examination, regular measurement of vital signs, body weight, echocardiograms/multigated acquisition (MUGA) scans to assess left ventricular ejection fraction, eastern cooperative oncology group-performance status (ECOG-PS) and electrocardiograms parameter values. SAE was defined as untoward medical occurrence that at any dose resulted in death; was life threatening; resulted in persistent or significant disability; was congenital anomaly or medically important due to other reasons than above mentioned criteria.

Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.

Vz/F for Cycle 0 Day 1 was calculated as Dose divided by (\[lambda z\]\*\[AUC0-infinity\]) and for Cycle 1 Day 15 was calculated as Dose divided by (\[lambda z\]\*\[AUC0-tau\]).

MRT of tazemetostat and its metabolite ER-897387 was calculated as MRT=AUMC(0-infinity)/AUC(0-infinity), where AUMC(0-infinity) was the area under the first moment curve extrapolated to infinity and AUC(0-infinity) was area under the concentration-time curve from zero time extrapolated to infinite time.

The PTF within complete dosing interval at steady state, calculated as PTF (%) = (\[Cmax - Cmin\]/Cav) multiplied by 100. Here, Cmin means the minimum plasma concentration, Cmax means the maximum plasma concentration and Cav means the average plasma concentration of drug and metabolite.

Rac (Cmax) was calculated as the ratio of maximum observed concentration at steady state (Css,max) on Cycle 1 Day 15 divided by Cmax on Cycle 0 Day 1.

Rac (AUC) was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-12 hours) on Cycle 0 Day 1.

Rss was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-infinity) on Cycle 0 Day 1.

The fraction of dose excreted in urine was calculated as: Cumulative amount of unchanged drug excreted in urine (Ae)/Dose\*100.

Objective response was assessed by investigator based on the Lugano Classification (CT-Based) response criteria. Objective response rate was defined as the percentage of participants who had a Best Overall Response (BOR) of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Eisai Co., Ltd.

The safety analysis set included all participants who received at least 1 administration of the study drug.

Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.

Tazemetostat 800 mg

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Japanese

Race/Ethnicity, Customized

The safety/efficacy analysis set included all participants who received at least 1 administration of the study drug.

Inquiry Service

DLT analysis set included all participants who completed treatment Cycles 0 and 1 without major protocol deviations with at least 75% of treatment compliance in Cycle 1 and were assessed for DLT, and participants who experienced DLT during Cycles 0 and 1. Participants with less than 75% treatment compliance in Cycle 1 due to a reason other than toxicity up to Cycle 1 Day 28 were not included in this analysis set.

Number of Participants With Dose-limiting Toxicities (DLTs)

TEAEs

SAEs

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

ER-897387

The pharmacokinetic (PK) analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.

Cmax: Maximum Plasma Concentration of Tazemetostat and Its Metabolite ER-897387

The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.

Tmax: Time to Reach Maximum Plasma Concentration (Cmax) of Tazemetostat and Its Metabolite ER-897387

AUC(0-12 Hours): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose of Tazemetostat and Its Metabolite ER-897387

AUC(0-t Hours): Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Tazemetostat and Its Metabolite ER-897387

AUC(0-infinity): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of Tazemetostat and Its Metabolite ER-897387

Lambda z: Terminal Phase Elimination Rate Constant of Tazemetostat and Its Metabolite ER-897387

Tazemetostat (Cycle 0 Day 1)

Tazemetostat (Cycle 1 Day 15)

ER-897387 (Cycle 0 Day 1)

ER-897387 (Cycle 1 Day 15)

T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387

CL/F: Apparent Total Body Clearance of Tazemetostat

Cycle 0 Day 1

Cycle 1 Day 15

Vz/F: Apparent Volume of Distribution at Terminal Phase of Tazemetostat

MRT: Mean Residence Time of Tazemetostat and Its Metabolite ER-897387

AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Tazemetostat and Its Metabolite ER-897387

Css,Av: Average Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387

Css,Max: Maximum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387

Css,Min: Minimum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387

PTF: Peak-trough Fluctuation Ratio of Tazemetostat and Its Metabolite ER-897387

Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Tazemetostat and Its Metabolite ER-897387

CLss/F: Apparent Total Body Clearance of Tazemetostat at Steady State

Rac (Cmax): Accumulation Ratio of Cmax for Tazemetostat and Its Metabolite ER-897387

Rac (AUC): Accumulation Ratio of AUC for Tazemetostat and Its Metabolite ER-897387

Rss: Steady State Accumulation Ratio of Tazemetostat and Its Metabolite ER-897387

The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. Here number analyzed "n" signifies participants who were evaluable for this outcome measure at given time points.

Ae: Amount of Unchanged Drug Tazemetostat Excreted in Urine

Fe: Fraction of Tazemetostat Dose Excreted in Urine

CLR: Renal Clearance of Tazemetostat

The efficacy analysis set included all participants who received at least 1 administration of the study drug.

Percentage of Participants With Objective Response

Participants received tazemetostat 800 milligram (mg) tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until disease progression (PD), development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.

Spots Global Cancer Trial Database for A Study of Tazemetostat in Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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