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

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 longestdimension as measured by CT or MRI

• Left ventricular ejection fraction (LVEF) >/=50% on cardiac multiple-gatedacquisition (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 oranaphylactic reactions to humanized or murine monoclonal antibodies, or knownsensitivity or allergy to murine products

• Prior solid organ transplantation

• Participants receiving systemic immunosuppressive agent such as, but not limited tocyclosporin, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factoragents within 4 weeks prior to first dose of study treatment

• Current Grade > 1 peripheral neuropathy by clinical examination or demyelinatingform 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 ofindolent 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-celllymphoma 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 CNSlymphoma

• Prior treatment with systemic immunotherapeutic agents

• Prior use of any monoclonal antibody for the purposes of treating cancer within 3months of the start of Cycle 1

• Any investigational therapy for the purposes of treating cancer within 28 days priorto 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 thanlymphoma symptom control

• History of other malignancy that could affect compliance with the protocol orinterpretation of results

• Significant or extensive history of cardiovascular disease

• Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than fordiagnosis

• 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 ofCycle 1 or anticipation that such a live, attenuated vaccine will be required duringthe study. Live vaccines during the study and until participants B cells recover areprohibited

• Any active infection within 7 days prior to Cycle 1 Day 1 that would impactparticipant safety

• Suspected active or latent tuberculosis

• Positive test results for chronic hepatitis B infection, hepatitis C, or the humanT-lymphotropic virus type 1 (HTLV-1)

• History of progressive multifocal leukoencephalopathy