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Follicular LymphomaPhase 2NCT05994235

Tazemetostat and Mosunetuzumab in Untreated Follicular Lymphoma

A Phase 2 study testing Mosunetuzumab and Tazemetostat Pill in people with Follicular Lymphoma, run by Weill Medical College of Cornell University at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Follicular Lymphoma
What is being tested?
Mosunetuzumab and Tazemetostat Pill
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
1 siteUnited States
Study dates
1 Nov 2023to Oct 2033
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must meet the following criteria for study entry:
  • Signed Informed Consent Form
  • Age >=18 years at the time of signing Informed Consent Form
  • Ability to comply with the study protocol
  • Willing to follow lifestyle considerations as defined in Section 4.4
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
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  • Histologically documented FL:
  • Fluorodeoxyglucose avid lymphoma (i.e., positron emission tomography (PET) positive lymphoma)
  • At least 1 bi-dimensionally measurable nodal lesion (˃1.5 cm in its largest dimension by computed tomography (CT) scan), or at least 1 bi-dimensionally measurable extra-nodal lesion (˃1.0 cm in its largest dimension by CT scan)
  • Meet Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria or British National Lymphoma Investigation criteria to receive systemic therapy
  • GELF criteria utilization (GELFc) or BNLI will be used to inform systemic therapy according to clinical applications of the GELF criteria.
  • Received no prior systemic lymphoma therapy (local radiotherapy is not considered systemic therapy)
  • Availability of a representative tumor specimen and the corresponding pathology report at the time of diagnosis for confirmation of the diagnosis of FL and for EZH2 mutation testing.
  • Adequate hematologic function defined as follows:
  • Hemoglobin>= 8.0 g/dL
  • ANC >= 1.0 x 109/L
  • Platelet count >= 75 x 109/L
  • Adequate renal and hepatic function as defined as follows:
  • Measured or estimated creatinine clearance >= 30 mL/min by institutional standard method
  • AST or ALT <= 2.5 x the upper limit of normal (ULN)
  • Serum total bilirubin <=1.5 x ULN (or <= 3 x ULN for patients with Gilbert syndrome)

Who cannot join

  • Patients who meet any of the following criteria will be excluded from study entry:
  • Inability to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat
  • Grade 3b FL
  • History of transformation of indolent disease to diffuse large B cell lymphoma
  • Any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN)
  • Any prior history of T-LBL/T-ALL
Show all 47Show fewer
  • Active or history of CNS lymphoma or leptomeningeal infiltration
  • Prior standard or investigational systemic anti-cancer therapy for lymphoma. Patients who have received prior XRT will not be excluded
  • Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone (> 20 mg), azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1
  • The use of inhaled corticosteroids is permitted
  • The use of mineralocorticoids for management of orthostatic hypotension is permitted
  • Dexamethasone for nausea, B symptoms, or symptomatic or bulky disease is permitted with a maximum dose of 40 mg x5 days or equivalent
  • History of solid organ transplantation
  • Contraindication to tocilizumab
  • History of severe allergic or anaphylactic reaction to humanized, chimeric or murine monoclonal antibodies (MAbs)
  • Known hypersensitivity to biopharmaceuticals produced in CHO cells or any component of the mosunetuzumab or tazemetostat
  • Known active bacterial, viral, fungal, or other infection, or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1
  • Known or suspected chronic active Epstein-Barr virus (EBV) infection
  • Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
  • Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis, as determined by the principal investigator
  • Active Hepatitis B or Hepatitis C infection Note: Patients who are hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (HBcAb) positive, must be negative for hepatitis B virus (HBV) polymerase chain reaction (PCR) to be eligible for study participation. Patients who are positive for hepatitis C virus (HCV) antibody must be negative for HCV by PCR to be eligible for study participation
  • HIV positive with CD4 count <200 and not currently taking antiretroviral therapy
  • History of progressive multifocal leukoencephalopathy (PML)
  • Administration of a live, attenuated vaccine within 4 weeks before first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study
  • Patients must not receive live, attenuated vaccines (e.g., FluMist) while receiving study treatment or after the last dose until B-cell recovery to the normal ranges.
  • Inactivated influenza vaccination should be given during the influenza season only
  • Other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of the following:
  • Any of the following malignancies previously curatively treated: carcinoma in situ of the cervix, good-prognosis ductal carcinoma in situ of the breast, basal, or squamous cell skin cancer
  • Stage I melanoma, - Low-grade, early-stage localized prostate cancer
  • Any other previously treated malignancy that has been in remission without treatment for >= 2 years prior to enrollment
  • Active autoimmune disease requiring treatment
  • History of autoimmune disease, including, but not limited to: myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
  • Patients with a remote history of, or well-controlled autoimmune disease, with a treatment free interval from immunosuppressive therapy for 12 months may be eligible to enroll if judged to be safe by the investigator
  • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone are eligible
  • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
  • Patients with a history of disease-related immune thrombocytopenic purpura, or autoimmune hemolytic anemia may be eligible
  • Prior allogeneic stem cell transplant (SCT)
  • Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including, but not limited to, significant cardiovascular disease (e.g., New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)
  • Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1 Day 1 or anticipation of a major surgical procedure during the course of the study
  • Active CNS disease or underlying neurologic disease such as stroke or intracranial hemorrhage within 3 months prior to enrollment, history of seizure disorder, or history of neurogenerative disease
  • History of pneumonitis or interstitial lung disease
  • A positive SARS-CoV-2 test within 7 days of C1D1
  • Pregnant or lactating or intending to become pregnant during the study
  • Women of childbearing potential (WOCBP) must have 2 negative serum pregnancy test results (minimum sensitivity, 25 mIU/mL) prior to initiating therapy: at 10-14 days prior to Day 1 of Cycle 1 and within 24 hours prior of Day 1 of Cycle 1.
  • WOCBP must complete a pregnancy test at screening and every cycle of treatment
  • WOCBP are defined as any person with a uterus who has had a menstrual period in the last 12 months, unless surgically sterile (i.e. from hysterectomy or bilateral oophorectomy)
  • Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Weill Cornell Medicine/NewYork-Presbyterian Hospital

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase II Trial of Tazemetostat Plus Mosunetuzumab in Untreated Follicular Lymphoma

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.

Read the detailed description

This is a phase II, open-label study. Fifty patients will be enrolled and treated with standard dosing of SC mosunetuzumab, and with oral tazemetostat by mouth twice daily at standard dosing (800 mg twice daily) beginning at the same time as mosunetuzumab initiation. Response assessments by PET/CT will occur post-mosunetuzumab at Cycle 4, Day 1 (+/- 3 days) and again at the end of treatment. If a participant has a complete response (CR) at Cycle 4 and/or cycle 8, then they will receive a total of 8 cycles of mosunetuzumab. If the patient has a partial response or stable disease at Cycle 4 and Cycle 8, then they will receive a total of 12 cycles of mosunetuzumab. All participants will receive 12 cycles of tazemetostat, unless discontinued from treatment early for disease progression or other protocol-defined reasons. Treatment with steroids, tocilizumab, growth factors, tumor lysis prophylaxis, and antibiotics may be used as per standard of care at our institution. Dose modifications are permitted for toxicity. Correlative studies will be performed prior to and following tazemetostat treatment and peripheral blood collections prior to post-mosunetuzumab treatment, which will give additional descriptive data for use in correlative analyses.

Being tested
Mosunetuzumab, Tazemetostat Pill
Keywords
Mosunetuzumab, Follicular Lymphoma, Tazemetostat
Medical subject headings
Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MosunetuzumabDrug

    Mosunetuzumab will be administered in weekly dose increments ("step-up dosing") during Cycle 1 and then on Day 1 of each cycle. Mosunetuzumab will be given in 28-day cycles for up to 12 cycles. Mosunetuzumab will be administered SC at the dose of 5 mg on Day 1, 45 mg on Day 8, and 45 mg on Day 15 in Cycle 1. Beginning with Cycle 2, it will be administered SC at the dose of 45 mg on Day 1. Each cycle lasts 4 weeks.

  • Tazemetostat PillDrug

    Also called Tazverik

    Oral tazemetostat will be administered by mouth twice daily at standard dosing (800 mg twice daily) beginning at the same time as mosunetuzumab initiation until disease progression, unacceptable toxicity, or consent is withdrawn. Patients will remain on tazemetostat for up to twelve 28-day cycles from initiation of mosunetuzumab.

Study groups in NCT05994235
Study groupRoleWhat they receive
Subcutaneous Mosunetuzumab and Oral TazemetostatExperimental50 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.
Receives: Drug: Mosunetuzumab; Drug: Tazemetostat Pill

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants who achieve a complete response (CR) by completion of therapy, as determined by the Lugano Criteria

    The proportion of patients who achieve complete response as per the Lugano criteria will be calculated and their 90% confidences will be computed with Clopper-Pearson method via exact binomial distribution.

    Measured: Estimated day 336

Secondary outcomes (7)

  1. Number of participants who experience cytokine release syndrome (CRS)

    CRS will be assessed per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading

    Measured: Day 0 to Day 28

  2. Number of participants who experience Immune effector cell-associated neurotoxicity syndrome (ICANS)

    ICANS will be assessed per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading

    Measured: Day 0 to Day 28

  3. Median Progression-Free Survival (PFS)

    PFS is defined as the duration of time from start of treatment to time of progression or death from any cause. Patients will be followed for a maximum of approximately 10 years from the start of treatment.

    Measured: For a maximum of approximately 10 years

  4. Median Overall Survival (OS)

    OS is defined as the duration of time from start of treatment to death from any cause. Patients will be followed for a maximum of approximately 10 years from the start of treatment.

    Measured: For a maximum of approximately 10 years

  5. Objective Response Rate (ORR) at the time of therapy completion, as defined by Lugano Criteria

    ORR is defined as the proportion of patients who have a partial or complete response to therapy

    Measured: Estimated to be day 336

  6. Number of participants who achieve a Complete Response (CR) per Lugano's Criteria

    Response and progression are evaluated according to the Lugano criteria for lymphoma response.

    Measured: For a maximum of approximately 10 years

  7. Median Duration of Response

    The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease or death due to any cause, whichever occurs first is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

    Measured: For a maximum of approximately 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2023
  2. Study start1 Nov 2023
  3. Primary completionOct 2033 (estimated)
  4. Study completionOct 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05994235
Sponsor's protocol ID
23-06026184
Other IDs
22-10025285
Status last verified
Mar 2026
First submitted
8 Aug 2023
Last updated
2 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Mosunetuzumab and Tazemetostat Pill in people with Follicular Lymphoma, run by Weill Medical College of Cornell University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants who achieve a complete response (CR) by completion of therapy, as determined by the Lugano Criteria (time frame: Estimated day 336). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05994235.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2026.

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