Long-Term Safety of Tazemetostat for Lymphoma

(TRuST Trial)

No longer recruiting at 41 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Epizyme, Inc.

Must be taking: Tazemetostat

Disqualifiers: Other malignancy, Thrombocytopenia, Neutropenia, Anemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the long-term safety of tazemetostat for individuals with lymphoma, a type of blood cancer. Participants will continue receiving tazemetostat, either alone or with other treatments, as in a previous study. This trial suits those who have already benefited from tazemetostat in an earlier clinical trial and wish to continue. As a Phase 1, Phase 2 trial, the research aims to understand how the treatment works in people and assess its effectiveness in an initial, smaller group, offering participants a chance to contribute to important early-stage research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on combination therapy with tazemetostat, you may need to continue those medications as part of the study.

Is there any evidence suggesting that tazemetostat is likely to be safe for humans?

Research has shown that tazemetostat, a treatment for certain types of lymphoma, has been generally safe in earlier studies. In these studies, a few patients experienced serious side effects, such as a decline in overall health, stomach pain, pneumonia, and severe infections like sepsis. However, these serious side effects occurred in less than 2% of patients.

The FDA has already approved tazemetostat for other conditions, which provides some confidence in its safety. While risks exist, the treatment is generally safe when used under a doctor's care. Prospective trial participants should discuss possible side effects with their healthcare provider to make an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Tazemetostat is unique because it targets a specific enzyme called EZH2, which plays a role in the growth of certain cancer cells. Unlike traditional chemotherapy drugs that attack rapidly dividing cells broadly, tazemetostat offers a more targeted approach, potentially leading to fewer side effects. Researchers are excited about this treatment because it represents a novel way to tackle lymphoma, especially for patients who may not respond well to existing therapies like R-CHOP or targeted antibodies.

What evidence suggests that tazemetostat might be an effective treatment for lymphoma?

Research has shown that tazemetostat, which participants in this trial will receive, may effectively treat relapsed or hard-to-treat follicular lymphoma, a type of non-Hodgkin lymphoma. Studies have found that many patients experience tumor shrinkage or stabilization, indicating a positive overall response. In one study, 72.1% of patients did not see their cancer worsen for at least 24 months, suggesting that tazemetostat can help control the disease for a significant time. Additionally, the treatment is known for having fewer serious side effects, making it a potentially safer option for long-term use. ^{3 4 6 7 8}

Who Is on the Research Team?

Ipsen Medical Director

Principal Investigator

Ipsen

Are You a Good Fit for This Trial?

This trial is for people who have seen benefits from tazemetostat in previous studies, can follow the study rules, and are expected to live at least 3 more months. They should be currently taking tazemetostat alone or with other drugs and have good blood, kidney, and liver function. People can't join if they've stopped tazemetostat for over 2 weeks without approval, have another cancer (with some exceptions), or severe blood problems.

Inclusion Criteria

Has a life expectancy of ≥3 months.

Has voluntarily provided signed written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol.

I am benefiting from my current tazemetostat treatment.

Exclusion Criteria

I have another cancer besides the one being treated, but it's either been 5 years since I was disease-free, or it was a non-melanoma skin cancer or in situ carcinoma that was completely removed or treated.

I stopped taking tazemetostat for more than 14 days before joining this study.

I have a history of T-cell lymphoblastic lymphoma/leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Treatment

Participants continue to receive tazemetostat as dictated in their antecedent study for long-term safety assessment

Up to 7 years

Visits conducted per Standard of Care (SoC) as appropriate

Follow-up

Participants are monitored for safety, time to treatment failure, and overall survival

Up to 7 years

What Are the Treatments Tested in This Trial?

Interventions

• Tazemetostat

Trial Overview The focus of this study is on the long-term safety of a drug called tazemetostat. Participants are those who previously responded well to this medication either by itself or combined with other treatments in past research trials.

How Is the Trial Designed?

Group I: Open-label Tazemetostat Experimental Treatment 1 Intervention

Participants will continue to receive the same tazemetostat dose and schedule as specified in their antecedent tazemetostat protocol. For participants on combination therapy, the other therapeutic(s) must have been completed in the antecedent study or be provided by a source other than Epizyme if combination treatment is continued in this clinical rollover study.

Who Is Running the Clinical Trial?

Epizyme, Inc.

Lead Sponsor

Trials

34

Recruited

2,800+

Published Research Related to This Trial

In a phase II study involving 20 Japanese patients with relapsed or refractory B-cell non-Hodgkin lymphoma and EZH2 mutations, tazemetostat showed a high objective response rate of 76.5% in follicular lymphoma, with 35.3% achieving complete response.

The safety profile of tazemetostat was manageable, with the most common serious side effect being lymphopenia, and only four patients discontinuing treatment due to adverse events, indicating it could be a viable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of tazemetostat for relapsed or refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan. Izutsu, K., Ando, K., Nishikori, M., et al.[2021]

In a phase I study involving seven Japanese patients with relapsed or refractory B-cell non-Hodgkin lymphoma, tazemetostat demonstrated a promising objective response rate of 57%, indicating its potential effectiveness in treating this type of cancer.

The treatment was well-tolerated, with no dose-limiting toxicities observed and only mild adverse events such as thrombocytopenia and dysgeusia reported, suggesting a favorable safety profile for tazemetostat.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of tazemetostat in Japanese patients with relapsed or refractory B-cell lymphoma. Munakata, W., Shirasugi, Y., Tobinai, K., et al.[2021]

Tazemetostat, a selective EZH2 inhibitor, showed significant antitumor activity specifically in rhabdoid tumor xenografts, with 71% of these models demonstrating improved event-free survival compared to controls.

The treatment effectively reduced H3K27me3 levels in most tumors, indicating its mechanism of action, but it did not show consistent efficacy against other tumor types, suggesting a need for further research, especially in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of tazemetostat (EPZ-6438), a novel EZH2 inhibitor, by the Pediatric Preclinical Testing Program. Kurmasheva, RT., Sammons, M., Favours, E., et al.[2022]

Tazemetostat is the first targeted treatment approved by the FDA for epithelioid sarcoma, marking a significant advancement in therapy for this rare cancer.

In a phase II trial, tazemetostat showed a response rate of 15% in patients, with 67% of those responses lasting at least 6 months, indicating its potential efficacy in managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First EZH2 Inhibitor Approved-for Rare Sarcoma. [2020]

Tazemetostat (Tazverik™) is the first approved treatment specifically for adults and adolescents aged 16 years and older with locally advanced or metastatic epithelioid sarcoma, receiving accelerated approval in January 2020 in the USA.

The recommended dosage is 800 mg taken orally twice daily, and Tazemetostat is also being studied for other cancers, including diffuse large B-cell lymphoma and follicular lymphoma, indicating its potential broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tazemetostat: First Approval. Hoy, SM.[2021]

Citations

1. tazverik.com tazverik.com/hcp/follicular-lymphoma/clinical-trial-results

Clinical Trial Results in R/R Follicular Lymphoma Efficacy results, including overall response rate (ORR) and duration of response (DOR) with TAZVERIK® (tazemetostat) in R/R follicular lymphoma patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8427481/

Tazemetostat for patients with relapsed or refractory follicular ... Our results have shown that tazemetostat, an investigational EZH2 inhibitor, has anti-tumour activity in patients with relapsed or refractory follicular ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19064

Efficacy and safety of tazemetostat in patients with ... Conclusions: Relapsed/refractory FL and DLBCL responds well to Tazemetostat in terms of ORR, PFS, and DOR, with a relatively low incidence of ...

4. tazverik.com tazverik.com/hcp/follicular-lymphoma

TAZVERIK® (tazemetostat) HCP | R/R Follicular Lymphoma In 99 clinical study patients with relapsed or refractory follicular lymphoma receiving TAZVERIK 800 mg twice daily: Serious adverse reactions occurred in 30% ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11513718/

Tazemetostat for relapsed/refractory B-cell non-Hodgkin ... The 24-month and 36-month PFS rates were 72.1% (95% confidence interval [CI] 41.5%–88.6%) and 64.1% (95% CI 33.7%–83.4%), respectively. The ...

6. tazverik.com tazverik.com/hcp/follicular-lymphoma/safety-and-tolerability

Safety & Tolerability in R/R Follicular Lymphoma Serious adverse reactions occurring in ≥2% of patients taking TAZVERIK included general physical health deterioration, abdominal pain, pneumonia, sepsis, and ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/213400s000lbl.pdf

TAZVERIK (tazemetostat) - accessdata.fda.gov The safety of TAZVERIK was evaluated in two cohorts (Cohorts 4 and 5) of Study E7438-G000-101 that enrolled patients with relapsed or refractory follicular ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19045

Efficacy and safety of oral tazemetostat, an EZH2 inhibitor, ... The results showed a 55% tumor response rate and 49.6% progression-free survival (PFS) at 1 year, but only 10% achieved PFS at 2 years. While ...