SkyGLO: This study is comparing how safe and effective adding a targeted therapy called glofitamab to a treatment regimen called Pola-R-CHP (which includes targeted therapy, chemotherapy and steroids) is in people with previously untreated CD20-positive large B-Cell lymphomaA Phase III, Multicenter, Randomized, Open-Label Study Comparing the Efficacy and Safety of Glofitamab (RO7082859) in Combination With Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (Pola-R-CHP) Versus Pola-R-CHP in Previously Untreated Patients With Large B-Cell Lymphoma

Exclusion

• Contraindication to any of the individual components of Pola-R-CHP or glofitamab, including prior receipt of anthracyclines, or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, or known sensitivity or allergy to murine products
• Prior solid organ transplantation
• Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease
• History of indolent lymphoma
• Current diagnosis of the following: Follicular lymphoma grade 3B; transformations of indolent B-cell lymphomas (e.g., de novo transformed follicular lymphoma); mediastinal grey zone lymphoma; primary mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma; primary large B-cell lymphoma of immune-privileged sites; primary effusion DLBCL; and primary cutaneous DLBCL
• Prior treatment with systemic immunotherapeutic agents
• Prior use of any monoclonal antibody for the purposes of treating cancer within 3 months of the start of Cycle 1
• Any investigational therapy for the purposes of treating cancer within 28 days prior to the start of Cycle 1
• Prior radiotherapy to the mediastinal/pericardial region
• Prior therapy for LBCL, with the exception of corticosteriods
• Corticosteroid use > 50 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Significant or extensive history of cardiovascular disease
• Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
• Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents
• Active autoimmune disease which is not well controlled by therapy
• Clinically significant liver disease
• Live, attenuated vaccine within 4 weeks before study treatment infusion on Day 1 of Cycle 1 or anticipation that such a live, attenuated vaccine will be required during the study. Live vaccines during the study and until participants B cells recover are prohibited
• Any active infection within 7 days prior to Cycle 1 Day 1 that would impact participant safety
• Suspected active or latent tuberculosis
• Positive test results for chronic hepatitis B infection, hepatitis C, or the human T-lymphotropic virus type 1 (HTLV-1)
• History of progressive multifocal leukoencephalopathy