Mosunetuzumab in Patients With Newly Diagnosed Extranodal Marginal Zone Lymphoma

Inclusion Criteria: 1. Men and women aged 18 years or older at the time of signing informed consent. 2. Able and willing to sign the informed consent form (ICF). 3. Ability to comply with the trial protocol. 4. Histologically confirmed EMZL presenting with stage I-IV disease. 5. Previously untreated participants. 1. Participants with H. pylori-positive gastric EMZL who received an initial treatment with currently accepted antibiotics may be considered eligible if, after antibiotic regimen, participant has histologically confirmed MZL. 2. Participants who were previously treated with localized therapy (eg, radiation or surgery) and never received systemic therapy and present with recurrent disease are eligible upon histological confirmation of MZL. 6. Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥1 lesion that measures \>1.5 cm in the longest diameter (LDi) and ≥1.0 cm in the longest perpendicular diameter as assessed by CT or MRI, especially in extranodal sites, per response criteria for lymphomas (Cheson, et al., 2014). Imaging must be conducted within 6 weeks prior to the start of therapy. 1. Participants with skin EMZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that skin lesion measures ≥1.5 cm in diameter by tape measure and is documented by photo or there are multiple skin lesions measuring \>1 cm in diameter on the body and at least one of them is histologically confirmed as EMZL. 2. Participants with gastric EMZL histologically confirmed and need therapy but do not have measurable disease and in which response to treatment can be assessed by multiple random gastric biopsies per Groupe d'Etude des Lymphomes de l'Adult (GELA) criteria (Ruskoné Fourmestraux, et al., 2011). 3. Participants with conjunctival EMZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that conjunctival lesion measures ≥1 cm in diameter by tape measure and is documented by photo or there are multiple conjunctival lesions measuring together \>1.5 cm. At least one of the lesions needs be histologically confirmed as EMZL. 7. Participants must be willing to provide tissue biopsy from the most recent available archival tissue or undergo an incisional or excisional lymph node or tissue biopsy. If biopsy can be reviewed to confirm the diagnosis but there is no extra tissue for exploratory studies, such participants can still be enrolled in this trial. 8. Participant should have at least one of the following criteria for treatment initiation: * Threatened extranodal organ function * Involvement of ≥3 nodal sites, each with diameter of ≥3 cm * Any nodal or extranodal tumor mass with a diameter of ≥5 cm * B symptoms (fever ≥38 degrees Celsius of unclear etiology, night sweats, weight loss \>10% within the prior 6 months) or other symptoms attributed to disease or specific organ involvement associated with the relapse. * Risk of local compressive symptoms that may result in organ compromise * Splenomegaly or splenic lesion without splenomegaly * Leukopenia attributed to MZL (leukocytes \<1000/mm3) * Leukemia (\>5,000 lymphoma cells/mm3) * Requirement for transfusion or growth factor support attributed to lymphoma * Involvement of 2 or more extranodal sites, with tumor/lesion in each extranodal site ≥1 cm 9. Life expectancy \>3 months. 10. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 11. Adequate hematologic, hepatic, and renal function tested within 6 weeks prior to the start of therapy (values must not be achieved with growth factors): * Absolute neutrophil count (ANC) ≥1.0 × 10\^9/L. * Hemoglobin ≥8.0 g/dL. * Platelet count ≥ 75 × 10\^9/L. * Total bilirubin ≤1.5 × upper limit normal (ULN). Participants with documented history of Gilbert's syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible. * Alanine transaminase (ALT)/aspartate aminotransferase (AST) ≤3.0 × ULN or ≤5 × ULN in the presence of liver involvement by lymphoma. * Creatinine within normal institutional limits, or * calculated creatinine clearance ≥30 mL/min/1.73 m2 using the Modification of Diet in Renal Disease formula * calculated creatinine clearance ≥35 mL/min by the Cockcroft-Gault Equation (Cockcroft, 1976) * estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 using the Modification of Diet in Renal Disease formula for participants with creatinine levels above institutional normal (unless due to lymphoma) 12. Willingness to avoid pregnancy during the trial and for at least 90 days after the last dose of the trial intervention. Exclusion Criteria: 1. Evidence of diffuse large B cell lymphoma (DLBCL) transformation. Participants with presumptive evidence of transformation based on clinical assessment of factors such as, but not limited to, increasing lactate dehydrogenase, rapidly worsening disease, or frequent B-symptoms, must be ruled out for a transformation to a more aggressive disease, such as DLBCL. 2. History of central nervous system lymphoma (either primary or metastatic) or leptomeningeal disease. Participants with Dural MZL are eligible. 3. Patients that need immediate cytoreduction. 4. Concurrent or previous anticancer therapy (eg, chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization). 5. 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. 1. Steroids that are used for treatment of allergy or other underlying condition are permittable, but not steroids started to treat lymphoma. Participants recei