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

Eligibility 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
• * 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 \> 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
• * Known or suspected chronic active Epstein-Barr viral infection
• * Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• * 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