Trial Outcomes & Findings for SYMPHONY-2, A Trial to Examine Combination of Tazemetostat With Rituximab in Subjects With Relapsed/Refractory Follicular Lymphoma (NCT NCT04762160)

Last Updated: 2024-03-25

Results Overview

ORR was defined as the percentage of participants with WT EZH2 status who achieved a complete response (CR) or partial response (PR) according to the 2014 Lugano Classification as assessed by investigator and blinded independent review committee (IRC). CR = complete metabolic response per positron emission tomography-computed tomography (PET-CT) based response or complete radiologic response per CT-based response. PR = partial metabolic response per PET-CT-based response or partial remission per CT-based response.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

Planned to be assessed during Cycles 3, 6, 12, 18, and 24.

Results posted on

2024-03-25

Participant Flow

This Phase 2, open-label study was conducted in participants with relapsed/refractory follicular lymphoma who received oral tazemetostat in combination with rituximab. The study was terminated early due to business reasons prior to enrolling the target number of participants needed to achieve target power and was insufficient to produce statistically reliable results.

This study was to include a 28-day screening period, a 2-year (24-cycle) treatment period, and a follow-up period. In treatment period, participants were to be treated in 28-day cycles with tazemetostat in combination with rituximab through Cycle 6 then tazemetostat alone through Cycle 24, for 24 months of therapy or until disease progression, unacceptable toxicity, or withdrawal of consent. Overall 5 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure	Tazmetostat in Combination With Rituximab Participants were to receive tazemetostat 800 milligram (mg) twice daily (BID) starting on Cycle 1 Day 1 until the end of Cycle 24, for 24 months of therapy or until study termination. Participants were also to receive rituximab, administered by either as subcutaneous (SC) injection or intravenous (IV) infusion according to the regional product prescribing information, labeling, and institutional guidelines. Rituximab was to be administered at a dose of 375 mg per square meter (m\^2) on Cycle 1 Days 1, 8, 15, and 22 and then on Day 1 of Cycles 3 through 6, accounting for an additional 4 doses (i.e., a total of 8 doses of rituximab in 6 cycles). Each cycle was 28 days.
Overall Study STARTED	5
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Tazmetostat in Combination With Rituximab Participants were to receive tazemetostat 800 milligram (mg) twice daily (BID) starting on Cycle 1 Day 1 until the end of Cycle 24, for 24 months of therapy or until study termination. Participants were also to receive rituximab, administered by either as subcutaneous (SC) injection or intravenous (IV) infusion according to the regional product prescribing information, labeling, and institutional guidelines. Rituximab was to be administered at a dose of 375 mg per square meter (m\^2) on Cycle 1 Days 1, 8, 15, and 22 and then on Day 1 of Cycles 3 through 6, accounting for an additional 4 doses (i.e., a total of 8 doses of rituximab in 6 cycles). Each cycle was 28 days.
Overall Study Study terminated early due to business reasons	5

Baseline Characteristics

SYMPHONY-2, A Trial to Examine Combination of Tazemetostat With Rituximab in Subjects With Relapsed/Refractory Follicular Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tazmetostat in Combination With Rituximab n=5 Participants Participants were to receive tazemetostat 800 mg BID starting on Cycle 1 Day 1 until the end of Cycle 24, for 24 months of therapy or until study termination. Participants were also to receive rituximab, administered by either as SC injection or IV infusion according to the regional product prescribing information, labeling, and institutional guidelines. Rituximab was to be administered at a dose of 375 mg/m\^2 on Cycle 1 Days 1, 8, 15, and 22 and then on Day 1 of Cycles 3 through 6, accounting for an additional 4 doses (i.e., a total of 8 doses of rituximab in 6 cycles). Each cycle was 28 days.
Age, Continuous	70.2 years STANDARD_DEVIATION 10.83 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Race/Ethnicity, Customized White	5 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants
Race/Ethnicity, Customized Other/Unknown	0 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Planned to be assessed during Cycles 3, 6, 12, 18, and 24.

Population: The study was terminated early due to business reasons and only five participants were enrolled, of whom only three were evaluable. No summary statistics are available given the limited data from the small number of evaluable participants and individual participant data are also not presented to protect the privacy of the individuals.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Planned to be assessed from first dose of study drug to earliest date of disease progression or death as assessed up to 24 months by an IRC

PFS was defined as the time from first dose of study drug to the time of the earliest date of CR or PR per the 2014 Lugano Classification or death, whichever occurred first, as assessed by an IRC. CR= complete metabolic response per PET-CT based response or complete radiologic response per CT-based response. PR= partial metabolic response per PET-CT-based response or partial remission per CT-based response.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Planned to be assessed from earliest date of CR or PR to documented progression or death as assessed up to 24 months by an IRC

DOR was defined as the time from the earliest date of CR or PR per the 2014 Lugano Classification to documented progression or death, whichever comes first, as assessed by an IRC. CR= complete metabolic response per PET-CT based response or complete radiologic response per CT-based response. PR= partial metabolic response per PET-CT-based response or partial remission per CT-based response.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Planned to be assessed at the following timepoints: Cycles 3, 6, 12, 18, and 24

ORR was assessed according to 2014 Lugano Classification, in the pooled group regardless of mutation status and in a subset of participants with MT EZH2.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Planned to be assessed at the following timepoints: Cycle 3, Cycle 6, Cycle 12, Cycle 18, and Cycle 24.

ORR was assessed according to 2014 Lugano Classification, in rituximab refractory participants.

Outcome measures

Outcome data not reported

Adverse Events

Tazmetostat in Combination With Rituximab

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tazmetostat in Combination With Rituximab n=5 participants at risk Participants were to receive tazemetostat 800 mg BID starting on Cycle 1 Day 1 until the end of Cycle 24, for 24 months of therapy or until study termination. Participants were also to receive rituximab, administered by either as SC injection or IV infusion according to the regional product prescribing information, labeling, and institutional guidelines. Rituximab was to be administered at a dose of 375 mg/m\^2 on Cycle 1 Days 1, 8, 15, and 22 and then on Day 1 of Cycles 3 through 6, accounting for an additional 4 doses (i.e., a total of 8 doses of rituximab in 6 cycles). Each cycle was 28 days.
Gastrointestinal disorders Gastrointestinal haemorrhage	20.0% 1/5 • Number of events 3 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Cardiac disorders Cardiac failure acute	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Cardiac disorders Myocardial infarction	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Gastrointestinal disorders Abdominal pain	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).

Other adverse events

Other adverse events
Measure	Tazmetostat in Combination With Rituximab n=5 participants at risk Participants were to receive tazemetostat 800 mg BID starting on Cycle 1 Day 1 until the end of Cycle 24, for 24 months of therapy or until study termination. Participants were also to receive rituximab, administered by either as SC injection or IV infusion according to the regional product prescribing information, labeling, and institutional guidelines. Rituximab was to be administered at a dose of 375 mg/m\^2 on Cycle 1 Days 1, 8, 15, and 22 and then on Day 1 of Cycles 3 through 6, accounting for an additional 4 doses (i.e., a total of 8 doses of rituximab in 6 cycles). Each cycle was 28 days.
Skin and subcutaneous tissue disorders Urticaria	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Psychiatric disorders Insomnia	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Cardiac disorders Cardiomegaly	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Ear and labyrinth disorders Ear pain	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Eye disorders Foreign body sensation in eyes	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Nervous system disorders Headache	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Injury, poisoning and procedural complications Infusion related reaction	40.0% 2/5 • Number of events 2 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Injury, poisoning and procedural complications Contusion	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Gastrointestinal disorders Haematochezia	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Musculoskeletal and connective tissue disorders Flank pain	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Infections and infestations Urinary tract infection	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Reproductive system and breast disorders Testicular oedema	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Musculoskeletal and connective tissue disorders Groin pain	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Infections and infestations Impetigo	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Blood and lymphatic system disorders Thrombocytopenia	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Renal and urinary disorders Nephrolithiasis	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Investigations Blood creatinine increased	40.0% 2/5 • Number of events 2 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Blood and lymphatic system disorders Microcytic anaemia	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Gastrointestinal disorders Diarrhoea	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Respiratory, thoracic and mediastinal disorders Epistaxis	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Injury, poisoning and procedural complications Fall	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Nervous system disorders Brachial plexopathy	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Skin and subcutaneous tissue disorders Alopecia	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Skin and subcutaneous tissue disorders Pruritus	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Musculoskeletal and connective tissue disorders Joint swelling	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
General disorders Fatigue	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Respiratory, thoracic and mediastinal disorders Cough	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Respiratory, thoracic and mediastinal disorders Dyspnoea	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).
Respiratory, thoracic and mediastinal disorders Pleuritic pain	20.0% 1/5 • Number of events 1 • Treatment-emergent adverse events were assessed from the date of first dose of study treatment (Day 1) until 30 days after discontinuation of study treatment (approximately 462 days). The Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety evaluation, regardless of EZH2 mutation status (MT or WT).

Additional Information

Medical Director

Ipsen

Phone: see email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER