Tazemetostat and Mosunetuzumab in Untreated Follicular Lymphoma

NCT05994235 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 23-0602618422-10025285
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Follicular Lymphoma

Keywords

Mosunetuzumab; Follicular Lymphoma; Tazemetostat

Outcome Measures

Primary Outcomes (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.

  Estimated day 336

Secondary Outcomes (7)

• Number of participants who experience cytokine release syndrome (CRS)

  Day 0 to Day 28

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

  Day 0 to Day 28

• Median Progression-Free Survival (PFS)

  For a maximum of approximately 10 years

• Median Overall Survival (OS)

  For a maximum of approximately 10 years

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

  Estimated to be day 336

Study Arms (1)

Subcutaneous Mosunetuzumab and Oral Tazemetostat

EXPERIMENTAL

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.

Drug: Mosunetuzumab; Drug: Tazemetostat Pill

Interventions

Mosunetuzumab DRUG

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.

Subcutaneous Mosunetuzumab and Oral Tazemetostat

Tazemetostat Pill DRUG

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.

Also known as: Tazverik

Subcutaneous Mosunetuzumab and Oral Tazemetostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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)

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Epizyme, Inc.: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Weill Cornell Medicine/NewYork-Presbyterian Hospital

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

tazemetostat

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Sarah Rutherford, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2023
• First Posted: August 16, 2023
• Study Start: November 1, 2023
• Primary Completion (Estimated): October 1, 2033
• Study Completion (Estimated): October 1, 2033
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)