Tazemetostat + Mosunetuzumab for Follicular Lymphoma

Overseen By Brittany Hobbie

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Disqualifiers: Grade 3b FL, Myeloid malignancies, CNS lymphoma, Autoimmune disease, Cardiovascular disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 16

Duration: 48 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with follicular lymphoma, a type of blood cancer. The researchers aim to determine if tazemetostat pills combined with mosunetuzumab injections are safe and effective as a first-time treatment. Tazemetostat slows cancer growth and boosts the immune system, while mosunetuzumab (also known as Lunsumio) helps the immune system target and destroy cancer cells. The trial seeks participants diagnosed with follicular lymphoma who have not received any prior systemic treatment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer therapy.

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.

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

Research has shown that tazemetostat is generally well-tolerated by patients with follicular lymphoma. The FDA has already approved it for patients who have had previous treatments, indicating its relative safety. Serious side effects are uncommon.

Mosunetuzumab has been tested in patients with prior treatments for follicular lymphoma and has shown to help keep the cancer away for a long time. It is approved for intravenous use but not yet for subcutaneous injection. Studies found that side effects were manageable, with some patients experiencing mild to moderate reactions.

Although these two drugs have not been tested together, their individual safety records are promising. This trial aims to determine their efficacy and safety when used in combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of tazemetostat and mosunetuzumab for follicular lymphoma because it offers a unique approach compared to standard treatments like chemoimmunotherapy. Tazemetostat is an EZH2 inhibitor, targeting a specific genetic mutation that can drive cancer growth, which is different from the broad attack on cancer cells used in chemotherapy. Mosunetuzumab is a bispecific antibody that directs the immune system to attack cancer cells more precisely. This combination not only targets the cancer more specifically but also aims to enhance the body's own immune response, potentially leading to better outcomes with fewer side effects.

What evidence suggests that the combination of tazemetostat and mosunetuzumab could be effective for follicular lymphoma?

Research shows that tazemetostat, a drug that blocks a specific enzyme, can slow the growth of follicular lymphoma and help the immune system combat it. This drug is already approved for patients previously treated for this type of cancer. Mosunetuzumab, another treatment, boosts the immune system to attack cancer and has demonstrated good results in patients with follicular lymphoma, leading to long-lasting improvements. It is approved for intravenous use but not yet for subcutaneous injection. In this trial, participants will receive a combination of subcutaneous mosunetuzumab and oral tazemetostat. Although these two treatments have not been tested together, their individual successes suggest they might work well in combination to treat follicular lymphoma. ^{1 5 6 7 8}

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 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

I have not had any drug treatments for lymphoma, only local radiation if any.

Ability to comply with the study protocol

Willing to use highly effective contraception, if of childbearing potential

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Subcutaneous Mosunetuzumab and Oral Tazemetostat Experimental Treatment 2 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

Approved in United States as Lunsumio for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

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

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Epizyme, Inc.

Industry Sponsor

Trials

34

Recruited

2,800+

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive Results for Tazemetostat in Follicular Lymphoma. [2019]

Mosunetuzumab, a bispecific antibody targeting CD20 and CD3, has received conditional approval in the EU for treating adults with relapsed or refractory follicular lymphoma after at least two prior therapies.

This approval marks a significant milestone in the development of mosunetuzumab, highlighting its potential as a new treatment option for patients with difficult-to-treat lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab: First Approval. Kang, C.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of tazemetostat in relapsed/refractory follicular lymphoma. von Keudell, G., Salles, G.[2021]

Mosunetuzumab, the first bispecific antibody approved for lymphoma, shows significant efficacy in treating relapsed or refractory follicular lymphoma, with an overall response rate of 80% and a complete response rate of 60%.

The approval of mosunetuzumab was based on a phase 2 trial involving patients who had undergone at least two prior lines of systemic therapy, highlighting its potential as a new treatment option for challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting. Cao, Y., Marcucci, EC., Budde, LE.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05994235

NCT05994235 | Tazemetostat and Mosunetuzumab in ... Mosunetuzumab has been studied in follicular lymphoma that has previously been treated, with positive results. Mosunetuzumab is approved by the FDA to be given ...

2. ashpublications.org ashpublications.org/blood/article/145/7/708/525779/Long-term-3-year-follow-up-of-mosunetuzumab-in

Long-term 3-year follow-up of mosunetuzumab in relapsed or ... Three-year follow-up of mosunetuzumab in R/R FL after ≥2 prior therapies showed long-lasting remissions and meaningful survival outcomes.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37981564/

Indirect Treatment Comparisons of Mosunetuzumab With ... ITCs suggest that mosunetuzumab may lead to superior outcomes over tazemetostat (in EHZ2wild-type patients) and PI3K inhibitors and may be a promising ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124064000

Mosunetuzumab is Cost-Effective Compared with ... This study found that mosunetuzumab is a cost-effective treatment vs alternative novel treatment options, for adult patients with 3L+ R/R FL.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38712895/

Cost-effectiveness analysis of mosunetuzumab for ... Mosunetuzumab is estimated to be cost-effective compared with approved regimens except R-Len for the treatment of adults with R/R FL.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11863491/

Long-term 3-year follow-up of mosunetuzumab in relapsed ... Three-year follow-up of mosunetuzumab in R/R FL after ≥2 prior therapies showed long-lasting remissions and meaningful survival outcomes.

7. ctsearchsupport.org ctsearchsupport.org/clinical-trials/tazemetostat-and-mosunetuzumab-in-untreated-follicular-lymphoma

Two drugs, mosunetuzumab and tazemetostat, to treat ... To find out if the combination of mosunetuzumab and tazemetostat is safe and works well to treat follicular lymphoma that has not yet been ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265023021298

Indirect Treatment Comparisons of Mosunetuzumab With ... We conducted indirect treatment comparisons (ITCs) to compare the efficacy and tolerability of mosunetuzumab with those of available treatments used in this ...