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

Trial Summary

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.

What data supports the effectiveness of the drug Tazemetostat for Non-Hodgkin's Lymphoma?

Research shows that Tazemetostat has demonstrated promising results in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, especially those with an EZH2 mutation, with a high response rate and manageable side effects. ^{1 2 3 4 5}

How is the drug Tazemetostat unique for treating non-Hodgkin's lymphoma?

Tazemetostat is unique because it is an oral drug that specifically inhibits EZH2, a protein involved in cancer cell growth, and has shown promising results in patients with relapsed or refractory non-Hodgkin's lymphoma, especially those with EZH2 mutations. It offers a different mechanism of action compared to other treatments like PI3K inhibitors, with a potentially better safety profile. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a clinical trial to evaluate the feasibility and safety of giving tazemetostat followed by standard of care CAR T cell infusion in previously treated diffuse large b-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). The investigators hypothesis is that this combination has the potential to significantly improve the ability of CART cells to recognize and kill lymphoma cells without a significant impact on safety. Participants will receive the tazemetostat pills before and after receiving their CAR T cell therapy, for up to 12 months after CAR T cell administration. Patients will be followed for up to 5 years.

Research Team

Samuel Yamshon, M.D.

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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

Active treatment for another cancer

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

I do not have any ongoing serious infections.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

References

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

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

2. 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]

3. United States 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. [2022]

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

Tazemetostat: First Approval. [2021]

5. 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]