Tazemetostat and Mosunetuzumab in Untreated Follicular Lymphoma

Running, not enrolling · Phase 2

Conditions studied: Follicular Lymphoma

In brief

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.

Key facts

Study ID

NCT05994235

Run by

Weill Medical College of Cornell University

People needed

23

Starts

2023-11-01

Expected to finish

2033-10-01

Last updated by the study team

2026-04-02

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• 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)

You may not qualify if…

• 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
• 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.

Where it is running

• Weill Cornell Medicine/NewYork-Presbyterian Hospital — New York, New York, United States

Full record on ClinicalTrials.gov

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