Trial Outcomes & Findings for A Study of Tazemetostat in Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma (NCT NCT03009344)

NCT ID: NCT03009344

Last Updated: 2022-11-10

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 7 participants
• Primary outcome timeframe: Cycle 0 and Cycle 1 (Cycle 0=4 days, Cycle 1=28 days)
• Results posted on: 2022-11-10

Participant Flow

Participants took part in the study at 2 investigative sites in Japan from 10 January 2017 to 17 June 2020.

A total of 7 participants were screened and enrolled to receive study treatment.

Participant milestones

Measure	Tazemetostat 800 mg 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.
Overall Study STARTED	7
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Measure	Tazemetostat 800 mg 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.
Overall Study Lack of Efficacy	5
Overall Study Withdrawal by Subject	1
Overall Study Adverse Event	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Tazemetostat 800 mg n=7 Participants 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.
Age, Continuous	72.3 years STANDARD_DEVIATION 8.12 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized Japanese	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 0 and Cycle 1 (Cycle 0=4 days, Cycle 1=28 days)

Population: 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.

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.

Outcome measures

Measure

Tazemetostat 800 mg n=6 Participants 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.

Number of Participants With Dose-limiting Toxicities (DLTs)

0 Participants

SECONDARY outcome

Timeframe: From the date of first dose up to 30 days after the last dose of study drug (up to 40 months)

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

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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	7 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	2 Participants

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)

Population: 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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Cmax: Maximum Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 Tazemetostat	988 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 62.1
Cmax: Maximum Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 ER-897387	790 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 78.8

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)

Population: 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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Tmax: Time to Reach Maximum Plasma Concentration (Cmax) of Tazemetostat and Its Metabolite ER-897387 Tazemetostat	1.97 hours Interval 0.95 to 4.08
Tmax: Time to Reach Maximum Plasma Concentration (Cmax) of Tazemetostat and Its Metabolite ER-897387 ER-897387	1.97 hours Interval 1.12 to 4.08

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-12 hours post-dose (Cycle 0 length=4 days)

Population: 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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
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 Tazemetostat	4080 nanogram*hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 61.3
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 ER-897387	4500 nanogram*hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 72.4

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)

Population: 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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
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 Tazemetostat	5180 ng*h/mL Geometric Coefficient of Variation 63.6
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 ER-897387	6540 ng*h/mL Geometric Coefficient of Variation 75.3

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)

Population: 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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
AUC(0-infinity): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of Tazemetostat and Its Metabolite ER-897387 Tazemetostat	5220 ng*h/mL Geometric Coefficient of Variation 63.2
AUC(0-infinity): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of Tazemetostat and Its Metabolite ER-897387 ER-897387	6570 ng*h/mL Geometric Coefficient of Variation 74.9

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)

Population: 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.

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

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Lambda z: Terminal Phase Elimination Rate Constant of Tazemetostat and Its Metabolite ER-897387 Tazemetostat	0.0925 per hour Geometric Coefficient of Variation 17.9
Lambda z: Terminal Phase Elimination Rate Constant of Tazemetostat and Its Metabolite ER-897387 ER-897387	0.0794 per hour Geometric Coefficient of Variation 16.9

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387 Tazemetostat (Cycle 0 Day 1)	7.76 hour Interval 5.24 to 9.32
T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387 Tazemetostat (Cycle 1 Day 15)	4.10 hour Interval 2.4 to 8.31
T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387 ER-897387 (Cycle 0 Day 1)	8.68 hour Interval 6.52 to 10.7
T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387 ER-897387 (Cycle 1 Day 15)	3.55 hour Interval 3.22 to 9.58

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)

Population: 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.

Outcome measures

Measure

Tazemetostat 800 mg n=7 Participants 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.

CL/F: Apparent Total Body Clearance of Tazemetostat

153 liter per hour (L/h) Geometric Coefficient of Variation 63.2

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

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]).

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Vz/F: Apparent Volume of Distribution at Terminal Phase of Tazemetostat Cycle 0 Day 1	1660 liter (L) Geometric Coefficient of Variation 64.1
Vz/F: Apparent Volume of Distribution at Terminal Phase of Tazemetostat Cycle 1 Day 15	1170 liter (L) Geometric Coefficient of Variation 93.0

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)

Population: 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.

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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
MRT: Mean Residence Time of Tazemetostat and Its Metabolite ER-897387 Tazemetostat	8.25 hours Geometric Coefficient of Variation 29.3
MRT: Mean Residence Time of Tazemetostat and Its Metabolite ER-897387 ER-897387	10.7 hours Geometric Coefficient of Variation 31.0

SECONDARY outcome

Timeframe: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Tazemetostat and Its Metabolite ER-897387 Tazemetostat	4220 ng*h/mL Geometric Coefficient of Variation 42.6
AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Tazemetostat and Its Metabolite ER-897387 ER-897387	10200 ng*h/mL Geometric Coefficient of Variation 39.1

SECONDARY outcome

Timeframe: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Css,Av: Average Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 Tazemetostat	351 ng/mL Geometric Coefficient of Variation 42.7
Css,Av: Average Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 ER-897387	852 ng/mL Geometric Coefficient of Variation 39.0

SECONDARY outcome

Timeframe: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Css,Max: Maximum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 Tazemetostat	1170 ng/mL Geometric Coefficient of Variation 51.6
Css,Max: Maximum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 ER-897387	1800 ng/mL Geometric Coefficient of Variation 47.4

SECONDARY outcome

Timeframe: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Css,Min: Minimum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 Tazemetostat	88.4 ng/mL Geometric Coefficient of Variation 43.8
Css,Min: Minimum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 ER-897387	293 ng/mL Geometric Coefficient of Variation 46.7

SECONDARY outcome

Timeframe: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
PTF: Peak-trough Fluctuation Ratio of Tazemetostat and Its Metabolite ER-897387 Tazemetostat	303 percentage fluctuation Geometric Coefficient of Variation 40.8
PTF: Peak-trough Fluctuation Ratio of Tazemetostat and Its Metabolite ER-897387 ER-897387	171 percentage fluctuation Geometric Coefficient of Variation 39.8

SECONDARY outcome

Timeframe: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Tazemetostat and Its Metabolite ER-897387 Tazemetostat	1.05 hours Interval 0.88 to 2.03
Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Tazemetostat and Its Metabolite ER-897387 ER-897387	1.07 hours Interval 0.88 to 2.03

SECONDARY outcome

Timeframe: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

Outcome measures

Measure

Tazemetostat 800 mg n=7 Participants 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.

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

190 L/h Geometric Coefficient of Variation 42.6

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Rac (Cmax): Accumulation Ratio of Cmax for Tazemetostat and Its Metabolite ER-897387 Tazemetostat	1.19 ratio Geometric Coefficient of Variation 56.7
Rac (Cmax): Accumulation Ratio of Cmax for Tazemetostat and Its Metabolite ER-897387 ER-897387	2.28 ratio Geometric Coefficient of Variation 59.9

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Rac (AUC): Accumulation Ratio of AUC for Tazemetostat and Its Metabolite ER-897387 Tazemetostat	1.04 ratio Geometric Coefficient of Variation 37.6
Rac (AUC): Accumulation Ratio of AUC for Tazemetostat and Its Metabolite ER-897387 ER-897387	2.27 ratio Geometric Coefficient of Variation 58.5

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Rss: Steady State Accumulation Ratio of Tazemetostat and Its Metabolite ER-897387 Tazemetostat	0.809 ratio Geometric Coefficient of Variation 35.0
Rss: Steady State Accumulation Ratio of Tazemetostat and Its Metabolite ER-897387 ER-897387	1.56 ratio Geometric Coefficient of Variation 53.1

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Ae: Amount of Unchanged Drug Tazemetostat Excreted in Urine Cycle 0 Day 1	15.1 mg Geometric Coefficient of Variation 51.6
Ae: Amount of Unchanged Drug Tazemetostat Excreted in Urine Cycle 1 Day 15	6.81 mg Geometric Coefficient of Variation 33.7

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

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

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
Fe: Fraction of Tazemetostat Dose Excreted in Urine Cycle 0 Day 1	1.89 percentage of dose Geometric Coefficient of Variation 51.4
Fe: Fraction of Tazemetostat Dose Excreted in Urine Cycle 1 Day 15	0.852 percentage of dose Geometric Coefficient of Variation 33.8

SECONDARY outcome

Timeframe: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)

Population: 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.

Outcome measures

Measure	Tazemetostat 800 mg n=7 Participants 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.
CLR: Renal Clearance of Tazemetostat Cycle 0 Day 1	2.62 L/h Geometric Coefficient of Variation 15.2
CLR: Renal Clearance of Tazemetostat Cycle 1 Day 15	1.62 L/h Geometric Coefficient of Variation 25.6

SECONDARY outcome

Timeframe: From the date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first (up to 39 months)

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

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.

Outcome measures

Measure

Tazemetostat 800 mg n=7 Participants 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.

Percentage of Participants With Objective Response

57.1 percentage of participants Interval 18.4 to 90.1

Adverse Events

Tazemetostat 800 mg

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tazemetostat 800 mg n=7 participants at risk 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.
Gastrointestinal disorders Intestinal perforation	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the tongue	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.

Other adverse events

Measure	Tazemetostat 800 mg n=7 participants at risk 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.
Blood and lymphatic system disorders Thrombocytopenia	42.9% 3/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Blood and lymphatic system disorders Anaemia	28.6% 2/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Blood and lymphatic system disorders Leukopenia	28.6% 2/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Blood and lymphatic system disorders Neutropenia	28.6% 2/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Blood and lymphatic system disorders Lymphopenia	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Eye disorders Dry eye	28.6% 2/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Gastrointestinal disorders Constipation	42.9% 3/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Gastrointestinal disorders Abdominal discomfort	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Gastrointestinal disorders Anal fissure	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Gastrointestinal disorders Cheilitis	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Gastrointestinal disorders Epigastric discomfort	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Gastrointestinal disorders Gastritis	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Gastrointestinal disorders Nausea	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Gastrointestinal disorders Proctalgia	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Gastrointestinal disorders Toothache	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
General disorders Fatigue	28.6% 2/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
General disorders Asthenia	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
General disorders Malaise	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
General disorders Oedema peripheral	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
General disorders Pyrexia	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Infections and infestations Nasopharyngitis	71.4% 5/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Infections and infestations Influenza	28.6% 2/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Infections and infestations Oral herpes	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Infections and infestations Paronychia	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Injury, poisoning and procedural complications Muscle strain	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Investigations Blood creatinine increased	28.6% 2/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Investigations Alanine aminotransferase increased	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Investigations Aspartate aminotransferase increased	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Investigations Blood alkaline phosphatase increased	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Investigations Blood triglycerides increased	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Investigations Gamma-glutamyltransferase increased	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Investigations Weight decreased	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Metabolism and nutrition disorders Hyperphosphatasaemia	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Metabolism and nutrition disorders Hypophosphataemia	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	42.9% 3/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Musculoskeletal and connective tissue disorders Arthralgia	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Musculoskeletal and connective tissue disorders Back pain	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Musculoskeletal and connective tissue disorders Bursitis	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Musculoskeletal and connective tissue disorders Haemarthrosis	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Musculoskeletal and connective tissue disorders Synovial cyst	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Nervous system disorders Dysgeusia	42.9% 3/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Nervous system disorders Neuropathy peripheral	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Nervous system disorders Peripheral sensory neuropathy	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Psychiatric disorders Insomnia	28.6% 2/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Psychiatric disorders Middle insomnia	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Respiratory, thoracic and mediastinal disorders Cough	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Skin and subcutaneous tissue disorders Dry skin	28.6% 2/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Skin and subcutaneous tissue disorders Rash	28.6% 2/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Skin and subcutaneous tissue disorders Alopecia	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Skin and subcutaneous tissue disorders Nail disorder	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Skin and subcutaneous tissue disorders Skin swelling	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Vascular disorders Hypertension	14.3% 1/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.
Gastrointestinal disorders Stomatitis	28.6% 2/7 • From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) The safety analysis set included all participants who received at least 1 administration of the study drug.

Additional Information

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