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.
∙ 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)