A Study to Evaluate Zilovertamab Vedotin (MK-2140) Combination With Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Previously Untreated DLBCL (MK-2140-010)

Inclusion Criteria

• Has histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL), by prior biopsy, based on local testing according to the WHO classification of neoplasms of the hematopoietic and lymphoid tissues
• Has positron emission tomography (PET) positive disease at screening, defined as 4 to 5 on the Lugano 5-point scale
• Has received no prior treatment for their DLBCL
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before randomization
• Has an ejection fraction ≥45% as determined by either echocardiogram (ECHO) or multigated acquisition (MUGA)
• Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART)
• Who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load prior to randomization
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening

Exclusion Criteria

• Has a history of transformation of indolent disease to DLBCL
• Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL) or Grey zone lymphoma
• Has Ann Arbor Stage I DLBCL
• Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication
• Has clinically significant pericardial or pleural effusion
• Has ongoing Grade >1 peripheral neuropathy
• Has a demyelinating form of Charcot-Marie-Tooth disease
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Has ongoing corticosteroid therapy
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed
• Known additional malignancy that is progressing or has required active treatment within the past 2 years
• Known active central nervous system (CNS) lymphoma
• Has active autoimmune disease that has required systemic treatment in the past 2 years
• Has active infection requiring systemic therapy
• Has concurrent active HBV (defined as HBsAg positive and detectable HBV DNA) and HCV (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid (RNA)) infection
• Has history of allogeneic tissue/solid organ transplant