A Study Comparing the Efficacy and Safety of Polatuzumab Vedotin With Rituximab-Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Diffuse Large B-Cell Lymphoma

Inclusion Criteria:

• Previously untreated participants with cluster of differentiation 20 (CD20)-positiveDLBCL, including one of the following diagnoses by 2016 World Health Organization (WHO) classification of lymphoid neoplasms: DLBCL, not otherwise specified (NOS)including germinal center B-cell type, activated B-cell type; T-cell/histiocyte-richlarge B-cell lymphoma; Epstein-Barr virus-positive DLBCL, NOS; anaplastic lymphomakinase (ALK)-positive large B-cell lymphoma; human herpesvirus-8 (HHV8)-positiveDLBCL, NOS; High-grade B-cell lymphoma with MYC and B-cell lymphoma 2 (BCL2) and/orB-cell lymphoma 6 (BCL6) rearrangements (double-hit or triple-hit lymphoma);High-grade B-cell lymphoma, NOS

• Availability of archival or freshly collected tumor tissue before study enrolment

• International Prognostic Index (IPI) score of 2-5

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

• Life expectancy greater than or equal to (>/=)12 months

• Left ventricular ejection fraction (LVEF) >/= 50 percent (%) on cardiacmultiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)

• Adequate hematologic function

• Female participants: Agreement to remain abstinent (refrain from heterosexualintercourse) or use contraceptive methods and refrain from donating eggs.

• Male participants: agreement to remain abstinent (refrain from heterosexualintercourse) or use a condom and agreement to refrain from donating sperm.

Exclusion Criteria:

• History of severe allergic or anaphylactic reactions to humanized or murinemonoclonal antibodies or known sensitivity or allergy to murine products

• Contraindication to any of the individual components of CHOP, including priorreceipt of anthracyclines

• Prior organ transplantation

• Current Grade greater than (>) 1 peripheral neuropathy by clinical examination

• Demyelinating form of Charcot-Marie-Tooth disease

• History of indolent lymphoma

• History of follicular lymphoma grade 3B

• B-cell lymphoma, unclassifiable, with features intermediate between DLBCL andclassical Hodgkin lymphoma (grey-zone lymphoma)

• Primary mediastinal (thymic) large B-cell lymphoma

• Burkitt lymphoma

• Prior treatment with cytotoxic drugs within 5 years of screening for any condition (example [e.g.], cancer, rheumatoid arthritis) or prior use of any anti-CD20antibody

• Prior use of any monoclonal antibody within 3 months of the start of Cycle 1

• Prior therapy for DLBCL, with the exception of nodal biopsy

• Corticosteroid use >30 mg/day of prednisone or equivalent, for purposes other thanlymphoma symptom control

• Participants with central nervous system (CNS) lymphoma (primary or secondaryinvolvement), primary effusion DLBCL, and primary cutaneous DLBCL

• Vaccination with live vaccines within 28 days prior to the start of Cycle 1

• Any investigational therapy within 28 days prior to the start of Cycle 1

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

• Evidence of significant, uncontrolled, concomitant diseases that could affectcompliance with the protocol or interpretation of results, including significantcardiovascular disease or pulmonary disease

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

• History or presence of an abnormal electrocardiogram (ECG) that is clinicallysignificant in the investigator's opinion, including complete left bundle branchblock, second- or third-degree heart block, or evidence of prior myocardialinfarction

• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or significantinfections within 2 weeks before the start of Cycle 1

• Clinically significant liver disease, including active viral or other hepatitis,current alcohol abuse, or cirrhosis

• Prior radiotherapy to the mediastinal/pericardial region

• Participants with suspected active or latent tuberculosis

• Positive test results for chronic hepatitis B and hepatitis C infection

• Known history of human immunodeficiency virus (HIV) seropositive status

• Positive results for the human T-lymphotrophic 1 virus (HTLV-1)

• Participants with a history of progressive multifocal leukoencephalopathy