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Patients in the Phase 1 portion of the study.

Patients with R/R FL with mutant EZH2 treated with tazemetostat as a single agent in Phase 2 of the study.

Patients with R/R FL with wild-type EZH2 treated with tazemetostat as a single agent in Phase 2 of the study.

Patients with R/R DLBCL treated with tazemetostat as a single agent or tazemetostat in combination with prednisolone in Phase 2 of the study.

Patients who received 800 mg of tazemetostat, BID, administered in continuous 28-day cycles.

Tazemetostat

Patients who received 40 mg/m\^2 prednisolone once daily on Days 1-5 and 15-19 of Cycles 1-4.

Patients who received 100 mg to 1600 mg of tazemetostat, BID, administered in continuous 28-day cycles.

Ipsen Medical Director

This is an open-label, multicenter, Phase 1/2 study of tazemetostat as a single agent in subjects with advanced solid tumors or with B-cell lymphomas and tazemetostat in combination with prednisolone in subjects with diffuse large B-cell lymphoma (DLBCL).

This is a multicenter, open-label, Phase 1/2 study conducted in two parts: The Phase 1 part comprised dose escalation and expansion to establish the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) when tazemetostat was given twice daily (BID) orally on a continuous basis. Additionally, in separate cohorts in Phase 1, the effect of food on the bioavailability of tazemetostat as well as the drug-drug interaction (DDI) potential of tazemetostat were evaluated. The Phase 2 part was initiated once the RP2D was established. Phase 2 enrolled subjects with relapsed/ refectory (R/R) DLBCL (Cohorts 1-3 and 6) and subjects with R/R FL (Cohorts 4 and 5) for the determination of efficacy and safety of tazemetostat monotherapy (Cohorts 1-5) and of tazemetostat in combination with prednisolone (Cohort 6) with placement determined by centrally confirmed histology, cell of origin (COO), and enhancer of zeste homologue 2 (EZH2) mutation status.

Study of Tazemetostat as Single Agent in Solid Tumors or B-cell Lymphomas and in Combination With Prednisolone in DLBCL

An Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat as a Single Agent in Subjects With Advanced Solid Tumors or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With Diffuse Large B Cell Lymphoma

Recommended Phase 2 dose (RP2D) of tazemetostat as administered orally twice daily (BID), continuously in 28-day cycles in subjects with advanced solid tumors or with relapsed and/or refractory B cell lymphomas as determined by incidence, seriousness, toxicity grade, and relatedness of treatment emergent dose limiting toxicities

Number of patients achieving an objective response (CR or PR)/number of patients treated x 100%. ORR was calculated as the percentage of patients with a confirmed complete response (CR) or partial response (PR) relative to the total number of patients in the analysis population per response evaluation criteria in solid tumors (RECIST) version (v)1.1. Complete Response (CR) was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

The time (in months) from the date of the initial response (CR or PR, whichever was first) until the date of the first documented disease progression per an Independent Review Committee (for Groups 1 and 2), per Investigator (Group 3), or death due to any cause. Patients who were alive and progression free at the time of the analysis were censored at the last date where the patient was known to be in response. Note: the DOR was censored, meaning data collection was stopped early for analysis, making the top limit of the 95% confidence interval not estimable (NE). Per RECIST v.1.0, CR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. The PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

The time (in months) from the date of first dose of tazemetostat until the earliest date of disease progression or death from any cause. Per RECIST v1.0, CR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. The PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

Epizyme, Inc.

The safety population included all patients in the Intent-to-treat (ITT) population set who had at least 1 post-dose safety observation recorded. MedDRA v17.1 for Phase 1 and MedDRA v18.1 for Phase 2.

Patients received tazemetostat 100 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 1: Tazemetostat 100 mg

Patients received tazemetostat 200 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 1: Tazemetostat 200 mg

Patients received tazemetostat 400 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 1: Tazemetostat 400 mg

Patients received tazemetostat 800 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 1: Tazemetostat 800 mg

Patients received tazemetostat 1600 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 1: Tazemetostat 1600 mg

Patients received tazemetostat 200 mg as a single oral dose on Day -8 either after fasting for 8 hours before dosing or immediately after consuming a high-fat breakfast on Day -8. Following a 7-day washout period, patients crossed over to receive the second tazemetostat 200 mg single oral dose on Day -1 in the opposite condition (fed or fasted).

Phase 1: Food Effect (All Patients)

Patients received tazemetostat 800 mg orally BID continuously starting on Day 1, with a single oral dose of midazolam 2 mg administered on Day -1 and then on Day 15. Post Day 15, patients continued to receive tazemetostat 800 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 1: Tazemetostat 800 mg + Midazolam 2 mg

Patients with R/R FL with mutant EZH2 treated with tazemetostat as a single agent in Phase 2 of the study. Patients received 800 mg of tazemetostat, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 2 Group 1: Tazemetostat in R/R FL With Mutant EZH2

Patients with R/R FL with wild-type EZH2 treated with tazemetostat as a single agent in Phase 2 of the study. Patients received 800 mg of tazemetostat, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 2 Group 2: Tazemetostat in R/R FL With Wild-Type EZH2

Patients with R/R DLBCL received 800 mg of tazemetostat monotherapy, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 2 Group 3: Tazemetostat in R/R DLBCL Monotherapy

Patients received tazemetostat 800 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent. In addition, these patients also received prednisolone 40 mg/m\^2 on Days 1 to 5 and 15 to 19 from Cycle 1 to Cycle 4 post which tazemetostat monotherapy was continued.

Phase 2 Group 4: Tazemetostat + Prednisolone in R/R DLBCL Combination Therapy

Patients received tazemetostat 200 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent

Patients received tazemetostat 800 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent

Patients with R/R FL with mutant EZH2 treated with tazemetostat as a single agent in Phase 2 of the study. Patients received 800 mg of tazemetostat, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Tazemetostat: Patients who received 800 mg of tazemetostat, BID, administered in continuous 28-day cycles.

Patients with R/R FL with wild-type EZH2 treated with tazemetostat as a single agent in Phase 2 of the study. Patients received 800 mg of tazemetostat, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Tazemetostat: Patients who received 800 mg of tazemetostat, BID, administered in continuous 28-day cycles.

Patients with R/R DLBCL received 800 mg of tazemetostat monotherapy, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Tazemetostat: Patients who received 800 mg of tazemetostat, BID, administered in continuous 28-day cycles.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Medical Lead or Designee

Patients in the Phase 1 portion of the study. Tazemetostat: Patients who received 100 mg to 1600 mg of tazemetostat, BID, administered in continuous 28-day cycles.

Phase 1

Recommended Phase 2 Dose (RP2D) of Tazemetostat as a Single-Agent and in Combination With Prednisolone (Phase 1 Only)

Objective Response Rate (ORR; Complete Response + Partial Response [CR + PR]) (Phase 2)

Phase 2 Group 4: Tazemetostat + Prednisone in R/R DLBCL Combination Therapy

Patients who had a complete or partial response per an Independent Review Committee. Note: the DOR for some patients was censored, meaning data collection was stopped early for analysis making the top limit of the 95% confidence interval not estimable.

Duration of Response for Tazemetostat as a Single Agent or in Combination With Prednisolone (Phase 2 Only)

Patients who had a response event per Independent Review Committee.

Progression Free Survival for Tazemetostat as a Single Agent or in Combination With Prednisolone (Phase 2 Only)

Patients received tazemetostat 100 milligrams (mg) tablets orally twice daily (BID) in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Patients with R/R FL with mutant enhancer of zeste homolog 2 (EZH2) treated with tazemetostat as a single agent in Phase 2 of the study. Patients received 800 mg of tazemetostat, orally BID, administered in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent.

Phase 2 Group 1: Tazemetostat in Relapsed/Refractory (R/R) Follicular Lymphoma (FL) With Mutant EZH2

Phase 2 Group 3: Tazemetostat in R/R Diffuse Large B-cell Lymphoma (DLBCL) Monotherapy

Patients received tazemetostat 800 mg tablets orally BID in continuous 28-day treatment cycles until confirmed disease progression, unacceptable toxicity, or withdrawal of consent. In addition, these patients also received prednisolone 40 mg/meter square (m\^2) on Days 1 to 5 and 15 to 19 from Cycle 1 to Cycle 4 post which tazemetostat monotherapy was continued.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Tazemetostat as Single Agent in Solid Tumors or B-cell Lymphomas and in Combination With Prednisolone in DLBCL	NCT01897571	B-cell Lymphoma... Advanced Solid ... Diffuse Large B... Follicular Lymp... Transformed Fol... Primary Mediast...	Tazemetostat Prednisolone Tazemetostat	16 Years -	Ipsen
Study of Tazemetostat as Single Agent in Solid Tumors or B-cell Lymphomas and in Combination With Prednisolone in DLBCL	NCT01897571	B-cell Lymphoma... Advanced Solid ... Diffuse Large B... Follicular Lymp... Transformed Fol... Primary Mediast...	Tazemetostat Prednisolone Tazemetostat	16 Years -	Ipsen

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