A Clinical Study of Zilovertamab Vedotin (MK-2140) Plus Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Polatuzumab Vedotin Plus R-CHP in People With Diffuse Large B-cell Lymphoma (DLBCL) (MK-2140-011/waveLINE-011)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 2

Conditions: Lymphoma, Large B-Cell, Diffuse

Treatments: Drug: Prednisone; Drug: Cyclophosphamide; Biological: Rituximab Biosimilar; Biological: Zilovertamab vedotin; Drug: Doxorubicin; Drug: Rescue Medication; Biological: Polatuzumab vedotin; Drug: Prednisolone; Biological: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06890884

jRCT2021250001 (Registry Identifier)

2140-011

MK-2140-011 (Other Identifier)

2024-515526-89-00 (Registry Identifier)

waveLINE-011 (Other Identifier)

U1111-1309-2852 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 594 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

594 participants in 2 patient groups

Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP)

Experimental group

Description:

Participants will receive a dose of zilovertamab vedotin (1.75 mg/kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 6 cycles (up to approximately 4 months) plus 2 additional cycles of rituximab or biosimilar for participants with high risk DLBCL. Participants will also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 3-week cycle for up to 6 cycles (up to approximately 4 months).

Treatment:

Drug: Rescue Medication

Drug: Prednisolone

Biological: Rituximab

Drug: Doxorubicin

Biological: Zilovertamab vedotin

Biological: Rituximab Biosimilar

Drug: Prednisone

Drug: Cyclophosphamide

Polatuzumab vedotin + R-CHP

Active Comparator group

Description:

Participants will receive a dose of polatuzumab vedotin (1.8 mg/kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by IV infusion on Day 1 of each 3-week cycle for up to 6 cycles (up to approximately 4 months) plus 2 additional cycles of rituximab or biosimilar for participants with high risk DLBCL. Participants will also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 3-week cycle for up to 6 cycles (up to approximately 4 months).

Treatment:

Drug: Rescue Medication

Biological: Polatuzumab vedotin

Drug: Prednisolone

Biological: Rituximab

Drug: Doxorubicin

Biological: Rituximab Biosimilar

Drug: Prednisone

Drug: Cyclophosphamide