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

This Phase III, randomized, double-blind, placebo-controlled study will compare the efficacy, safety, and pharmacokinetics of polatuzumab vedotin plus R-CHP versus R-CHOP in participants with previously untreated diffuse large B-cell lymphoma (DLBCL).


Eligibility Criteria:
Inclusion Criteria:

* 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
* 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 cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
* Adequate hematologic function
* Female participants: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and refrain from donating eggs.
* Male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom and agreement to refrain from donating sperm.

Exclusion Criteria:

* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
* Contraindication to any of the individual components of CHOP, including prior receipt 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 and classical 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-CD20 antibody
* 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 than lymphoma symptom control
* Participants with central nervous system (CNS) lymphoma (primary or secondary involvement), 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 or interpretation of results
* Evidence of significant, uncontrolled, concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease or pulmonary disease
* Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
* 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
* 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
* 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