50 Participants Needed

Tazemetostat + Mosunetuzumab for Follicular Lymphoma

TK
BH
Overseen ByBrittany Hobbie
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Weill Medical College of Cornell University
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

The goal of this study is to learn about the safety and effectiveness of the combination of tazemetostat pills in combination with mosunetuzumab injections for people with follicular lymphoma who haven't received treatment before. The investigators hypothesize that tazemetostat with mosunetuzumab has the potential to increase the efficacy of the product without compromising the safety. Tazemetostat is a drug that inhibits EZH2, an enzyme known to drive the development of B-cell lymphomas, and inhibiting it appears to have many effects that slow down lymphoma growth and enhance the immune system's ability to fight it. Tazemetostat is FDA-approved in previously treated follicular lymphoma and currently undergoing study in other lymphomas. Mosunetuzumab is a bispecific antibody therapy that is a therapeutic strategy that uses the immune system to fight lymphoma, called immunotherapy. Bispecific antibodies have two ends: one attaches to T cells in the immune system and the other attaches to lymphoma cells, helping guide our immune system to attack the cancer. Mosunetuzumab has been studied in follicular lymphoma that has previously been treated, with positive results. Mosunetuzumab is approved by the FDA to be given intravenously (directly into a vein) but is not yet approved by the FDA is not yet approved as an injection under the skin, which is how it is given in this study. They have not yet been studied in combination.

Will I have to stop taking my current medications?

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

What makes the drug combination of Tazemetostat and Mosunetuzumab unique for treating follicular lymphoma?

This drug combination is unique because it combines Mosunetuzumab, a bispecific antibody that engages T-cells to target cancer cells, with Tazemetostat, an oral inhibitor that targets a specific mutation in some follicular lymphoma cases. This approach offers a novel mechanism by combining immunotherapy with targeted therapy, potentially improving outcomes for patients who have not responded to other treatments.12345

Research Team

SY

Samuel Yamshon, M.D.

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for adults with untreated follicular lymphoma (Grades 1-3a) who can follow the study plan and are willing to use effective birth control. People with a history of certain blood cancers, severe infections like Hepatitis B/C or HIV, significant heart or lung disease, recent major surgery, CNS diseases, pregnancy, organ transplants, allergic reactions to monoclonal antibodies or active autoimmune diseases cannot join.

Inclusion Criteria

Ability to comply with the study protocol
Willing to use highly effective contraception, if of childbearing potential
I have not had any drug treatments for lymphoma, only local radiation if any.
See 1 more

Exclusion Criteria

My slow-growing lymphoma has changed into a more aggressive type.
I have or had brain lymphoma or cancer spread to the lining of my brain and spinal cord.
I have had an organ transplant.
See 20 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous mosunetuzumab and oral tazemetostat in 28-day cycles for up to 12 cycles

48 weeks
12 visits (in-person)

Response Assessment

Response assessments by PET/CT at 12 weeks, 30 weeks, and 48 weeks for ongoing response

48 weeks
3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years
1 visit (in-person)

Treatment Details

Interventions

  • Mosunetuzumab
  • Tazemetostat
Trial Overview The trial tests tazemetostat pills combined with mosunetuzumab injections in patients who haven't had prior treatments for follicular lymphoma. Tazemetostat targets an enzyme linked to lymphoma growth while mosunetuzumab directs the immune system against cancer cells. Their combination effectiveness and safety are under evaluation.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Subcutaneous Mosunetuzumab and Oral TazemetostatExperimental Treatment2 Interventions
50 patients will be enrolled and treated with standard dosing of subcutaneous mosunetuzumab, and with oral tazemetostat by mouth twice daily at standard dosing (800 mg twice daily) beginning at the same time as mosunetuzumab initiation.

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

🇪🇺
Approved in European Union as Lunsumio for:
  • Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
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Approved in United States as Lunsumio for:
  • Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Find a Clinic Near You

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials
1,103
Recruited
1,157,000+

Genentech, Inc.

Industry Sponsor

Trials
1,578
Recruited
569,000+
Ashley Magargee profile image

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway profile image

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Epizyme, Inc.

Industry Sponsor

Trials
34
Recruited
2,800+

Findings from Research

In a phase 2 study involving 90 patients with relapsed or refractory follicular lymphoma, mosunetuzumab achieved a complete response rate of 60%, significantly higher than the historical control rate of 14% with copanlisib, demonstrating its efficacy in this patient population.
The treatment was well tolerated, with the most common side effect being cytokine release syndrome, primarily mild to moderate in severity, and no treatment-related fatalities, indicating a favorable safety profile for outpatient administration.
Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study.Budde, LE., Sehn, LH., Matasar, M., et al.[2022]
The EZH2 inhibitor tazemetostat has shown promising efficacy in treating relapsed or refractory follicular lymphoma, with 3 out of 28 patients achieving complete responses and 17 achieving partial responses.
This trial highlights the potential of targeting EZH2 mutations in lymphoma treatment, suggesting that tazemetostat could be a valuable option for patients with this specific genetic alteration.
Positive Results for Tazemetostat in Follicular Lymphoma.[2019]
Tazemetostat is a first-in-class oral medication that selectively inhibits EZH2, a protein involved in gene regulation, and is particularly effective for patients with follicular lymphoma (FL) who have an EZH2 mutation, which occurs in about 25% of cases.
The drug has been approved for use in patients with relapsed FL after two or more prior treatments, providing a new option for those without other available therapies, regardless of their EZH2 mutation status.
The role of tazemetostat in relapsed/refractory follicular lymphoma.von Keudell, G., Salles, G.[2021]

References

Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. [2022]
Positive Results for Tazemetostat in Follicular Lymphoma. [2019]
The role of tazemetostat in relapsed/refractory follicular lymphoma. [2021]
Mosunetuzumab: First Approval. [2022]
Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting. [2023]