This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of mosunetuzumab (Mosun) + lenalidomide (Len) (Mosun + Len) in participants with follicular lymphoma (FL). This study will also compare the pharmacokinetics, pharmacodynamics, safety, efficacy, and immunogenicity of IV mosunetuzumab + len vs subcutaneous (SC) mosunetuzumab + len.

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• R/R FL after treatment with at least one prior systemic lymphoma therapy, which includes prior immunotherapy or chemoimmunotherapy
• Previously untreated participants with FL must require systemic therapy assessed by investigator based on the Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria and have a Follicular Lymphoma International Prognostic Index (FLIPI) score of 2-5
• Histologically documented FL of Grade 1, 2, or 3a, and that expresses CD20 at time of diagnosis as determined by the local laboratory
• Fluorodeoxyglucose avid lymphoma (i.e., positron emission tomography (PET) positive lymphoma)
• At least one bi dimensionally measurable nodal lesion (>1.5 cm in its largest dimension by PET- computed tomography (CT) scan), or at least one bi dimensionally measurable extranodal lesion (>1.0 cm in its largest dimension by PET-CT scan)
• Availability of a representative tumor specimen and the corresponding pathology report for confirmation of the diagnosis of FL
• Adequate hematologic function (unless due to underlying lymphoma, per the investigator) as defined by the protocol
• Negative HIV test at screening, with the following exception: Individuals with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/mL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months
• Normal laboratory values (unless due to underlying lymphoma) as defined by the protocol
• Agreement to comply with all local requirements of the Len risk minimization plan
• For women of childbearing potential: agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period, and for at least 12 months after the final dose of glofitamab, 28 days after the last dose of Len, 18 months after the last dose of G, 3 months after the final dose of tocilizumab, and 3 months after the final dose of Mosun. Women must refrain from donating eggs during this same period
• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm, with female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 2 months after the final dose of glofitamab, 28 days after last dose of Len, 18 months after the last dose of G, 3 months after the final dose of tocilizumab, and 3 months after the final dose of Mosun

Exclusion Criteria

• Any history of Grade 3b FL
• Suspicion or clinical evidence of transformed lymphoma at enrollment by investigator assessment
• Any history of disease transformation and/or diffuse large B-cell lymphoma (DLBCL)
• Documented refractoriness to an obinutuzumab monotherapy containing regimen in glofitamab-containing treatment combination
• Active or history of central nervous system (CNS) lymphoma or leptomeningeal infiltration
• Documented refractoriness to lenalidomide, defined as no response (partial response (PR) or complete response (CR)) within 6 months of therapy
• Prior standard or investigational anti-cancer therapy as specified by the protocol
• Clinically significant toxicity (other than alopecia) from prior treatment that has not resolved to Grade <=2 prior to Day 1 of Cycle 1
• Known history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis or evidence of active pneumonitis on screening chest CT scan
• Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1
• History of solid organ transplantation
• History of severe allergic or anaphylactic reaction to humanized, chimeric or murine MAbs
• Known sensitivity or allergy to murine products
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the glofitamab, Mosun, G, Len, or thalidomide formulation, including mannitol
• History of erythema multiforme, Grade >=3 rash, or blistering following prior treatment with immunomodulatory derivatives
• Known history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis or evidence of active pneumonitis on screening chest CT scan
• 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 infection or hemophagocytic syndrome
• Known history of macrophage activating syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH)
• Active Hepatitis B and Hepatitis C infection or autoimmune disease requiring treatment
• Prior allogenic hematopoietic stem cell transplant
• Known history of HIV positive status
• History of progressive multifocal leukoencephalopathy
• 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
• Other malignancy that could affect compliance with the protocol or interpretation of results
• Prior allogenic hematopoietic stem cell transplant (HSCT)
• Contraindication to treatment for thromboembolism prophylaxis
• Grade >=2 neuropathy
• 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 or significant pulmonary disease
• 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
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Inadequate hematologic function
• Any of the following abnormal laboratory values
• Pregnant or lactating or intending to become pregnant during the study
• Life expectancy < 3 months
• Unable to comply with the study protocol, in the investigator's judgment
• History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's or Medical Monitor'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

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