A Study of Tazemetostat in Participants 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.