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:

1. Previously untreated participants with cluster of differentiation 20 (CD20)-positive DLBCL, 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-rich large B-cell lymphoma; Epstein-Barr virus-positive DLBCL, NOS; anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma; human herpesvirus-8 (HHV8)-positive DLBCL, NOS; High-grade B-cell lymphoma with MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements (double-hit or triple-hit lymphoma); High-grade B-cell lymphoma, NOS
2. Availability of archival or freshly collected tumor tissue before study enrolment
3. International Prognostic Index (IPI) score of 2-5
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
5. Life expectancy greater than or equal to (>/=)12 months
6. Left ventricular ejection fraction (LVEF) >/= 50 percent (%) on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
7. Adequate hematologic function
8. Female participants: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and refrain from donating eggs.
9. Male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom and agreement to refrain from donating sperm.

Exclusion Criteria:

1. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
2. Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
3. Prior organ transplantation
4. Current Grade greater than (>) 1 peripheral neuropathy by clinical examination
5. Demyelinating form of Charcot-Marie-Tooth disease
6. History of indolent lymphoma
7. History of follicular lymphoma grade 3B
8. B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma (grey-zone lymphoma)
9. Primary mediastinal (thymic) large B-cell lymphoma
10. Burkitt lymphoma
11. 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-CD20 antibody
12. Prior use of any monoclonal antibody within 3 months of the start of Cycle 1
13. Prior therapy for DLBCL, with the exception of nodal biopsy
14. Corticosteroid use >30 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control
15. Participants with central nervous system (CNS) lymphoma (primary or secondary involvement), primary effusion DLBCL, and primary cutaneous DLBCL
16. Vaccination with live vaccines within 28 days prior to the start of Cycle 1
17. Any investigational therapy within 28 days prior to the start of Cycle 1
18. History of other malignancy that could affect compliance with the protocol or interpretation of results
19. Evidence of significant, uncontrolled, concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease or pulmonary disease
20. Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
21. History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction
22. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or significant infections within 2 weeks before the start of Cycle 1
23. Clinically significant liver disease, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
24. Prior radiotherapy to the mediastinal/pericardial region
25. Participants with suspected active or latent tuberculosis
26. Positive test results for chronic hepatitis B and hepatitis C infection
27. Known history of human immunodeficiency virus (HIV) seropositive status
28. Positive results for the human T-lymphotrophic 1 virus (HTLV-1)
29. Participants with a history of progressive multifocal leukoencephalopathy