Long-Term Safety of Tazemetostat for Lymphoma

(TRuST Trial)

Recruiting at 36 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

58 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will provide continuing availability to tazemetostat for people that have previously completed participation in a tazemetostat study, either with monotherapy (single drug treatment) or combination therapy. The aim of the study will be to assess the long-term safety of tezemetostat.

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.

How is the drug tazemetostat unique for treating lymphoma?

Tazemetostat is unique because it is a first-in-class drug that specifically inhibits EZH2, an enzyme involved in cancer cell growth, and is taken orally. It is particularly effective for patients with certain genetic mutations in lymphoma, offering a targeted treatment option that differs from traditional chemotherapy. ^{1 2 3 4 5}

Research Team

Ipsen Medical Director

Principal Investigator

Ipsen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase II study of tazemetostat for relapsed or refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Tazemetostat: First Approval. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Phase 1 study of tazemetostat in Japanese patients with relapsed or refractory B-cell lymphoma. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of tazemetostat (EPZ-6438), a novel EZH2 inhibitor, by the Pediatric Preclinical Testing Program. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

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