Recruiting

Phase 3

Zilovertamab Vedotin with Standard TreatmentA 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)

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06717347

Conditions

Diffuse Large B-Cell Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Zilovertamab vedotin

Rituximab

Cyclophosphamide

Doxorubicin

Rituximab Biosimilar

Study Details

Brief summary:

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.

Conditions

Diffuse Large B-Cell Lymphoma

Study ID

NCT06717347

Start date

Jan 27, 2025

Status verified date

Sep, 2026

Completion date

Mar 29, 2032

Anticipated

Primary completion date

Jul 2, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

1046 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

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, prednisolone, or methylprednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).

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

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, prednisolone, or methylprednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).

Interventions

Zilovertamab vedotin

IV infusion

Rituximab

IV infusion

Cyclophosphamide

IV infusion

Doxorubicin

IV infusion

Rituximab Biosimilar

IV infusion

Prednisone

Per Approved Product Label

Prednisolone

Oral administration

Vincristine

IV infusion

Rescue medication

Participants receive rescue medication per approved product label. The rescue medication is granulocyte colony-stimulating factor (G-CSF).

Methylprednisolone

Per Approved Product Label

Primary outcome measure

Progression-free survival (PFS) [ Time Frame: Up to ~ 50 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839 Trialsites@msd.com

Locations

USA Mitchell Cancer Institute ( Site 0173)

Recruiting

Mobile, Alabama, United States, 36604

Contacts

Study Coordinator

251-445-9875

Banner MD Anderson Cancer Center ( Site 0165)

Recruiting

Gilbert, Arizona, United States, 85234

Contacts

Study Coordinator

480-256-6444

Banner MD Anderson Cancer Center - University Medical Center Phoenix ( Site 0167)

Recruiting

Phoenix, Arizona, United States, 85006

Contacts

Study Coordinator

480-256-6444

The University of Arizona Cancer Center - North Campus ( Site 0124)

Recruiting

Tucson, Arizona, United States, 85719

Contacts

Study Coordinator

520-621-5497

Providence Medical Foundation-Oncology ( Site 0168)

Recruiting

Fullerton, California, United States, 92835

Contacts

Study Coordinator

714-446-5900

MemorialCare Health System - Long Beach Medical Center ( Site 9559)

Recruiting

Long Beach, California, United States, 90806

Contacts

Study Coordinator

652-241-9755

Cancer Blood and Specialty Clinic ( Site 0109)

Recruiting

Los Alamitos, California, United States, 90720

Contacts

Study Coordinator

562-200-0203

Cedars-Sinai Medical Center ( Site 0115)

Recruiting

Los Angeles, California, United States, 90048

Contacts

Study Coordinator

310-423-3277

Pacific Hematology Oncology Associates ( Site 0131)

Recruiting

San Francisco, California, United States, 94115

Contacts

Study Coordinator

415-923-3012

Lutheran Hospital - Cancer Centers of Colorado ( Site 0180)

Recruiting

Golden, Colorado, United States, 80401

Contacts

Study Coordinator

303-403-6381

Clermont Oncology Center ( Site 0182)

Recruiting

Clermont, Florida, United States, 34711

Contacts

Study Coordinator

352-242-1366

Bioresearch Partner ( Site 0157)

Recruiting

Hialeah, Florida, United States, 33013

Contacts

Study Coordinator

833-489-4968

Orlando Health Cancer Institute ( Site 0169)

Recruiting

Ocoee, Florida, United States, 34761

Contacts

Study Coordinator

321-843-7497

Mid Florida Hematology and Oncology Center ( Site 0172)

Recruiting

Orange City, Florida, United States, 32763

Contacts

Study Coordinator

386-774-1223

University Cancer & Blood Center, LLC ( Site 0141)

Recruiting

Athens, Georgia, United States, 30607

Contacts

Study Coordinator

706-353-2990

Edward Cancer Center ( Site 0197)

Recruiting

Naperville, Illinois, United States, 60540

Contacts

Study Coordinator

630-527-3788

Cancer Care Specialists of Illinois ( Site 0152)

Recruiting

O'Fallon, Illinois, United States, 62269

Contacts

Study Coordinator

618-416-7970

Fort Wayne Medical Oncology and Hematology ( Site 0149)

Recruiting

Fort Wayne, Indiana, United States, 46804

Contacts

Study Coordinator

260-436-0800

Cotton O'Neil Cancer Center ( Site 0108)

Recruiting

Topeka, Kansas, United States, 66606

Contacts

Study Coordinator

785-478-9495

University of Kentucky ( Site 0106)

Recruiting

Lexington, Kentucky, United States, 40536

Contacts

Study Coordinator

859-257-6006

Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0163)

Recruiting

Louisville, Kentucky, United States, 40207

Contacts

Study Coordinator

502-899-3366

Owensboro Medical Health System ( Site 0195)

Recruiting

Owensboro, Kentucky, United States, 42303

Contacts

Study Coordinator

270-688-1938

CHRISTUS St. Frances Cabrini Hospital Center for Cancer Care ( Site 0184)

Recruiting

Alexandria, Louisiana, United States, 71301

Contacts

Study Coordinator

318-448-6917

American Oncology Partners, P.A. ( Site 0185)

Recruiting

Bethesda, Maryland, United States, 20817

Contacts

Study Coordinator

301-571-2016

Trinity Health Saint Joseph Mercy Hospital Ann Arbor ( Site 9545)

Recruiting

Ann Arbor, Michigan, United States, 48106

Contacts

Study Coordinator

734-712-1000

Karmanos Cancer Institute ( Site 0174)

Recruiting

Detroit, Michigan, United States, 48201

Contacts

Study Coordinator

800-527-6266

Corewell Health ( Site 0130)

Recruiting

Grand Rapids, Michigan, United States, 49503

Contacts

Study Coordinator

616-486-6180

The University of Mississippi Medical Center ( Site 0161)

Recruiting

Jackson, Mississippi, United States, 39216

Contacts

Study Coordinator

601-984-5601

Circuit Clinical - SSM Health Cancer Care DePaul ( Site 0166)

Recruiting

Bridgeton, Missouri, United States, 63044

Contacts

Study Coordinator

636-673-3083

Truman Medical Center ( Site 0122)

Recruiting

Kansas City, Missouri, United States, 64108

Contacts

Study Coordinator

816-404-4418

Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 0178)

Recruiting

Billings, Montana, United States, 59102

Contacts

Study Coordinator

406-238-6685

OptumCare Cancer Care ( Site 0121)

Recruiting

Las Vegas, Nevada, United States, 89102

Contacts

Study Coordinator

702-724-8787

Comprehensive Cancer Centers of Nevada ( Site 0113)

Recruiting

Las Vegas, Nevada, United States, 89169

Contacts

Study Coordinator

702-622-9699

Cancer Care Specialists ( Site 9582)

Recruiting

Reno, Nevada, United States, 89511

Contacts

Study Coordinator

7753290222x230

New York Oncology Hematology, P.C. ( Site 0129)

Recruiting

Albany, New York, United States, 12206

Contacts

Study Coordinator

518-262-6696

Icahn School of Medicine at Mount Sinai ( Site 0164)

Recruiting

New York, New York, United States, 10029

Contacts

Study Coordinator

212-241-6500

New York Cancer and Blood Specialists ( Site 9000)

Recruiting

Shirley, New York, United States, 11967

Contacts

Study Coordinator

631-675-5075

East Carolina University ( Site 0159)

Recruiting

Greenville, North Carolina, United States, 27834

Contacts

Study Coordinator

252-816-2273

Sanford Health Roger Maris Cancer Center ( Site 0189)

Recruiting

Fargo, North Dakota, United States, 58102

Contacts

Study Coordinator

701-234-6161

Oncology_Hematology Care Clinical Trials, LLC (OHC) ( Site 8002)

Recruiting

Cincinnati, Ohio, United States, 45242

Contacts

Study Coordinator

513-751-2273

Kaiser Permanente Interstate Medical Office - Central ( Site 0181)

Recruiting

Portland, Oregon, United States, 97227

Contacts

Study Coordinator

503-331-5600

Prisma Health - Upstate ( Site 0158)

Recruiting

Greenville, South Carolina, United States, 29605

Contacts

Study Coordinator

864-679-3900

Sanford Cancer Center ( Site 0143)

Recruiting

Sioux Falls, South Dakota, United States, 57104

Contacts

Study Coordinator

605-328-8000

The University of Tennessee Medical Center ( Site 0142)

Recruiting

Knoxville, Tennessee, United States, 37920

Contacts

Study Coordinator

865-305-9000

Texas Oncology - DFW ( Site 8000)

Recruiting

Dallas, Texas, United States, 75246

Contacts

Study Coordinator

214-370-1000

Houston Methodist Cancer Center ( Site 0154)

Recruiting

Houston, Texas, United States, 77030

Contacts

Study Coordinator

713-363-8009

Joe Arrington Cancer Research and Treatment Center ( Site 0183)

Recruiting

Lubbock, Texas, United States, 79410

Contacts

Study Coordinator

806-725-8000

Texas Oncology - Gulf Coast ( Site 8003)

Recruiting

The Woodlands, Texas, United States, 77380

Contacts

Study Coordinator

281-296-0365

University of Virginia Cancer Center ( Site 0138)

Recruiting

Charlottesville, Virginia, United States, 22903

Contacts

Study Coordinator

434-243-7773

Virginia Cancer Institute ( Site 0148)

Recruiting

Richmond, Virginia, United States, 23229

Contacts

Study Coordinator

804-287-3000

Blue Ridge Cancer Care ( Site 0132)

Recruiting

Roanoke, Virginia, United States, 24014

Contacts

Study Coordinator

540-982-0237

Vista Oncology ( Site 4201)

Recruiting

Olympia, Washington, United States, 98506

Contacts

Study Coordinator

360-413-8880

SSM Health Dean Medical Group ( Site 0140)

Recruiting

Madison, Wisconsin, United States, 53715

Contacts

Study Coordinator

608-410-2700

Cross Cancer Institute ( Site 0205)

Recruiting

Edmonton, Alberta, Canada, T6G 1Z2

Contacts

Study Coordinator

780-432-8771

Queen Elizabeth II Health Sciences Centre ( Site 0207)

Recruiting

Halifax, Nova Scotia, Canada, B3H 2Y9

Contacts

Study Coordinator

902-473-4642

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0208)

Recruiting

Hamilton, Ontario, Canada, L8V 5C2

Contacts

Study Coordinator

9053879495

Lakeridge Health - The R.S. McLaughlin Durham Regional Cancer Centre (MDRCC) ( Site 0206)

Recruiting

Oshawa, Ontario, Canada, L1G 2B9

Contacts

Study Coordinator

9055768711

Sunnybrook Research Institute ( Site 0204)

Recruiting

Toronto, Ontario, Canada, M4N 3M5

Contacts

Study Coordinator

4164804662

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Sep 25, 2026

Last verified

Sep, 2026

Keywords

Lymphoma, Large B-Cell, Diffuse

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-08. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-09-25. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.