An Open-Label Study Comparing Glofitamab and Polatuzumab Vedotin + Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone Versus Pola-R-CHP in Previously Untreated Patients With Large B-Cell Lymphoma

The purpose of this study is to compare the efficacy and safety of glofitamab in combination with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) vs Pola-R-CHP in participants with previously untreated CD20-positive large B-cell lymphoma (LBCL).

Inclusion Criteria: * Previously untreated participants with CD20-positive LBCL * Ability to provide tumor tissue * International prognostic index (IPI) score 2-5 * Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2 * At least one bi-dimensionally measurable lesion, defined as \> 1.5 cm in its longest dimension as measured by CT or MRI * Left ventricular ejection fraction (LVEF) \>/=50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO) * Adequate hematologic function * Negative HIV test at screening with exceptions as defined by the protocol * Negative SARS-CoV-2 antigen or PCR test Exclusion Criteria: * 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 * Participants receiving systemic immunosuppressive agent such as, but not limited to cyclosporin, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 4 weeks prior to first dose of study treatment * Current Grade \> 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease * History of indolent lymphoma (e.g., Follicular Lymphoma, Marginal Zone Lymphoma, Waldenstrom macroglobulinemia) * 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 (encompassing primary diffuse large B-cell lymphoma of the CNS, primary large B-cell lymphoma of the vitreoretina and primary large B-cell lymphoma of the testis); primary effusion DLBCL; and primary cutaneous DLBCL, leg type * Primary or secondary CNS lymphoma at the time of recruitment or history of CNS lymphoma * 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 \> 30 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control * History of other malignant or non-malignant diseases 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 * Known or suspected chronic active Epstein-Barr viral infection * Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) * Active autoimmune disease requiring treatment * 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