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)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 3

Conditions: Diffuse Large B-Cell Lymphoma

Treatments: Drug: Prednisone; Biological: Rituximab Biosimilar; Drug: Prednisolone; Drug: Rescue medication; Drug: Doxorubicin; Drug: Cyclophosphamide; Biological: Rituximab; Drug: Vincristine; Biological: Zilovertamab vedotin

Study type: Interventional

Funder types: Industry

Identifiers

NCT06717347

jRCT2061240099 (Other Identifier)

2140-010

2024-515566-13-00 (Registry Identifier)

MK-2140-010 (Other Identifier)

U1111-1309-3971 (Registry Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate if zilovertamab vedotin with standard treatment can help people live longer without the cancer growing or spreading than people who receive standard treatment alone.

Enrollment: 1,046 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

1,046 participants in 2 patient groups

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

Experimental group

Description:

Participants 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 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months) plus 2 cycles of rituximab or biosimilar for participants with high risk DLBCL. Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).

Treatment:

Biological: Zilovertamab vedotin

Biological: Rituximab

Drug: Doxorubicin

Drug: Cyclophosphamide

Drug: Rescue medication

Drug: Prednisolone

Biological: Rituximab Biosimilar

Drug: Prednisone

Rituximab + Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP)

Active Comparator group

Description:

Participants receive 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar, 1.4 mg/m\^2 vincristine administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months) plus 2 cycles of rituximab or biosimilar for participants with high risk DLBCL. Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).

Treatment:

Drug: Vincristine

Biological: Rituximab

Drug: Doxorubicin

Drug: Cyclophosphamide

Drug: Prednisolone

Biological: Rituximab Biosimilar

Drug: Prednisone