Tazemetostat + CAR T Therapy for Non-Hodgkin's Lymphoma

Overseen By Nicole Santos

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Weill Medical College of Cornell University

Must be taking: Tazemetostat

Disqualifiers: HIV, Hepatitis B/C, Pregnancy, 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

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding tazemetostat to standard CAR T cell therapy can help treat certain types of lymphoma, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). Researchers aim for this combination to enhance CAR T cells' ability to locate and destroy cancer cells while maintaining safety. Participants take tazemetostat before and after CAR T cell treatment over approximately a year. Ideal candidates have already tried other treatments for these specific lymphomas and qualify for CAR T cell therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this novel combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tazemetostat has a good safety record for treating certain types of B-cell non-Hodgkin lymphoma. Studies have found that patients taking tazemetostat alone generally tolerate it well, with many experiencing positive outcomes. For those with specific genetic changes, response rates were quite high.

Less specific information is available about combining tazemetostat with CAR T-cell therapy. However, both treatments have promising safety records individually. Tazemetostat has been safely used in other contexts. While this trial is in the early stages and safety data is still being collected, existing evidence from past uses of tazemetostat suggests it could be a safe option for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Tazemetostat combined with CAR T-cell therapy is unique because it enhances the standard treatment approach for Non-Hodgkin's Lymphoma. Most treatments for this condition, like chemotherapy or radiation, target rapidly dividing cells, but Tazemetostat works differently. It inhibits EZH2, an enzyme that can be overactive in some cancers, potentially making cancer cells more vulnerable to attack. By administering Tazemetostat before and after CAR T-cell therapy, researchers hope to improve the effectiveness of the immune cells in targeting and destroying cancer cells, offering a potentially more powerful and targeted treatment option.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin's Lymphoma?

Research has shown that tazemetostat yields promising results for treating B-cell non-Hodgkin lymphoma that has recurred or resisted other treatments. It has been particularly beneficial for patients who haven't succeeded with other therapies. Studies indicate that tazemetostat can shrink tumors and has a good safety profile with fewer serious side effects. In this trial, participants will receive a combination of tazemetostat and CAR T-cell therapy. Together, tazemetostat may enhance CAR T cells' ability to locate and destroy lymphoma cells. This combination could improve outcomes for people with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). ^{1 4 5 6 7}

Who Is on the Research Team?

Samuel Yamshon, M.D.

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for people with certain B-cell lymphomas (DLBCL, FL, or MCL) who have tried at least two other treatments and are eligible for standard CAR T cell therapy. It's not open to those with active HIV or hepatitis infections, pregnant or breastfeeding individuals, anyone with uncontrolled infections, or patients being treated for another cancer.

Inclusion Criteria

I am eligible for CAR T cell therapy.

I have undergone at least 2 previous treatments.

I have been diagnosed with DLBCL, FL, or MCL.

Exclusion Criteria

I do not have an active HIV or hepatitis B/C infection.

Active treatment for another cancer

I do not have any ongoing serious infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Tazemetostat Pre-Treatment

Participants receive tazemetostat 800 mg twice daily by mouth for at least 1 week prior to apheresis

1 week

CAR T Cell Therapy

Participants undergo apheresis, receive lymphodepletion chemotherapy, and then CAR T cell infusion

3 weeks

Multiple visits for apheresis, chemotherapy, and infusion

Tazemetostat Post-Treatment

Tazemetostat is resumed after recovery of platelets and neutrophil counts and continued for up to 6 months in complete responders and up to 12 months in partial responders

6-12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Tazemetostat

Trial Overview The study tests the combination of a drug called tazemetostat in pill form followed by standard CAR T cell therapy. The goal is to see if this combo can better target and kill lymphoma cells without greatly increasing risks. Participants will take tazemetostat before and after their CAR T treatment for up to a year.

How Is the Trial Designed?

Group I: Tazemetostat and CAR T-Cell Therapy Experimental Treatment 1 Intervention

Tazemetostat is being administered prior to, and following, standard of care CAR T cell therapy. The use of tazemetostat in this way is investigational.

Tazemetostat is already approved in United States, European Union for the following indications:

Approved in United States as Tazverik for:

• Epithelioid sarcoma
• Follicular lymphoma

Approved in European Union as Tazverik for:

• Epithelioid sarcoma

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

American Society of Clinical Oncology

Collaborator

Trials

40

Recruited

148,000+

Applebaum Foundation

Collaborator

Trials

1

Recruited

20+

Epizyme, Inc.

Industry Sponsor

Trials

34

Recruited

2,800+

Published Research Related to This Trial

Tazemetostat demonstrated a significantly lower risk of grade ≥3 treatment-emergent adverse events compared to several PI3K inhibitors (idelalisib, duvelisib, copanlisib, umbralisib), indicating a better safety profile for patients with relapsed/refractory follicular lymphoma.

The objective response rate (ORR) for tazemetostat was comparable to that of the PI3K inhibitors, suggesting that while tazemetostat is safer, it maintains similar efficacy in treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Matching-Adjusted Indirect Comparison of Single-Arm Trials in Patients with Relapsed or Refractory Follicular Lymphoma Who Received at Least Two Prior Systemic Treatments: Tazemetostat was Associated with a Lower Risk for Safety Outcomes Versus the PI3-Kinase Inhibitors Idelalisib, Duvelisib, Copanlisib, and Umbralisib. Proudman, D., Nellesen, D., Gupta, D., et al.[2022]

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]

Citations

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

Tazemetostat for relapsed/refractory B-cell non-Hodgkin ... Long-term oral monotherapy with tazemetostat showed favorable efficacy and safety profiles, indicating that it may be a useful third-line or later treatment ...

2. withpower.com withpower.com/trial/phase-1-lymphoma-6-2023-7a391

Tazemetostat + CAR T Therapy for Non-Hodgkin's ... Research shows that Tazemetostat has demonstrated promising results in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, especially those with ...

3. ashpublications.org ashpublications.org/ashclinicalnews/news/2613/Tazemetostat-for-Patients-with-Pretreated-Non

Tazemetostat for Patients with Pretreated Non-Hodgkin ... "Preliminary findings suggest that continued tazemetostat treatment has the potential to translate into tumor regression over a prolonged period ...

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

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

5. aacrjournals.org aacrjournals.org/clincancerres/article/26/13/3145/82523/A-LYSA-Phase-Ib-Study-of-Tazemetostat-EPZ-6438

A LYSA Phase Ib Study of Tazemetostat (EPZ-6438) plus R ... We report the results of the phase Ib tazemetostat plus R-CHOP combination (NCT02889523), in patients 60 to 80 years of age with newly diagnosed diffuse large ...

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

Efficacy and safety of oral tazemetostat, an EZH2 inhibitor, ... Early trials demonstrated its promising efficacy and safety, but long-term outcomes remain unclear. This meta-analysis evaluates the efficacy ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9892962/

EZH2 inhibition by tazemetostat: mechanisms of action, safety ... Phase II trials have shown objective response rates of 69% for patients with lymphoma-carrying EZH2 mutations and 35% for those with wild-type EZH2 without ...