Overview

Researchers are looking for ways to treat germinal center B-cell-like diffuse large B-cell lymphoma (GCB DLBCL). DLBCL is a fast-growing blood cancer that affects B-cells. GCB is a type of DLBCL that affects young B-cells that are still maturing.

The goal of this study is to learn if more people who receive zilovertamab vedotin (MK-2140) and R-CHP have the cancer respond (go away) than those who receive polatuzumab vedotin and R-CHP.

Eligibility

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• Has histologically confirmed diagnosis of germinal center B-cell (GCB) subtype of diffuse large B-cell lymphoma (DLBCL), by prior biopsy, according to the World Health Organization (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.
• Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART).
• Participants 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:

The main exclusion criteria include but are not limited to the following:

• 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.
• 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 active HBV (defined as HBsAg positive and detectable HBV deoxyribonucleic acid (DNA)) and HCV (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid (RNA)) infection.
• Has history of stem cell/solid organ transplant.