Recruiting

Phase 2

Zilovertamab Vedotin vs. Polatuzumab VedotinA 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)

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06890884

Conditions

Lymphoma, Large B-Cell, Diffuse

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Zilovertamab vedotin

Rituximab

Cyclophosphamide

Doxorubicin

Rituximab Biosimilar

Study Details

Brief summary:

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.

Conditions

Lymphoma, Large B-Cell, Diffuse

Study ID

NCT06890884

Start date

Apr 11, 2025

Status verified date

Sep, 2026

Completion date

Dec 16, 2032

Anticipated

Primary completion date

Dec 13, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

594 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 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).

active comparator: Polatuzumab vedotin + R-CHP

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).

Interventions

Zilovertamab vedotin

IV infusion

Rituximab

IV infusion

Cyclophosphamide

IV infusion

Doxorubicin

IV infusion

Rituximab Biosimilar

IV infusion

Prednisone

Oral administration or IV infusion

Prednisolone

Oral administration or IV infusion

Polatuzumab vedotin

IV infusion

Rescue Medication

Participants receive rescue medication at the investigators discretion, per approved product label. Recommended rescue medication is Granulocyte Colony-Stimulating Factor (G-CSF).

Primary outcome measure

Complete Response Rate (CRR) at End of Treatment (EOT) per Lugano Response Criteria [ Time Frame: Up to approximately 31 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

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

Locations

Infirmary Cancer Care ( Site 0157)

Recruiting

Mobile, Alabama, United States, 36607

Contacts

Study Coordinator

251-435-2273

Ironwood Cancer & Research Centers ( Site 0204)

Recruiting

Chandler, Arizona, United States, 85224

Contacts

Study Coordinator

480-314-6670

Palo Verde Cancer Specialists ( Site 0105)

Recruiting

Glendale, Arizona, United States, 85304

Contacts

Study Coordinator

602-978-6255

City of Hope - Phoenix ( Site 0202)

Recruiting

Goodyear, Arizona, United States, 85338

Contacts

Study Coordinator

602-883-1537

Genesis Cancer and Blood Institute ( Site 0193)

Recruiting

Hot Springs, Arkansas, United States, 71913

Contacts

Study Coordinator

501-624-7700

Roy and Patricia Disney Family Cancer Center - Providence Saint Joseph Medical Center ( Site 0135)

Recruiting

Burbank, California, United States, 91505

Contacts

Study Coordinator

818-840-0921

City of Hope Comprehensive Cancer Center ( Site 0191)

Recruiting

Duarte, California, United States, 91010

Contacts

Study Coordinator

626-218-2405

Bass Medical Group ( Site 0123)

Recruiting

Walnut Creek, California, United States, 94598

Contacts

Study Coordinator

925-433-8786

Rocky Mountain Cancer Centers (RMCC) ( Site 8001)

Recruiting

Aurora, Colorado, United States, 80012

Contacts

Study Coordinator

303-925-0700

Colorado West Healthcare System-Grand Valley Oncology ( Site 0165)

Recruiting

Grand Junction, Colorado, United States, 81505

Contacts

Study Coordinator

970-644-4460

Medical Oncology Hematology Consultants (MOHC) ( Site 8007)

Recruiting

Newark, Delaware, United States, 19713

Contacts

Study Coordinator

302-366-1200

Georgetown University Medical Center ( Site 0117)

Recruiting

Washington D.C., District of Columbia, United States, 20007

Contacts

Study Coordinator

202-444-2223

Boca Raton Regional Hospital-Lynn Cancer Institute ( Site 0130)

Recruiting

Boca Raton, Florida, United States, 33486

Contacts

Study Coordinator

561-955-4800

Baptist MD Anderson Cancer Center ( Site 0176)

Recruiting

Jacksonville, Florida, United States, 32207

Contacts

Study Coordinator

904-202-7300

Mount Sinai Braman Comprehensive Cancer Center ( Site 0140)

Recruiting

Miami Beach, Florida, United States, 33140

Contacts

Study Coordinator

305-674-2625

Mid Florida Hematology and Oncology Center ( Site 0152)

Recruiting

Orange City, Florida, United States, 32763

Contacts

Study Coordinator

386-774-1223

Beacon Cancer Care ( Site 0142)

Recruiting

Post Falls, Idaho, United States, 83854

Contacts

Study Coordinator

208-755-2804

University of Chicago Medical Center ( Site 0126)

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Study Coordinator

773-702-5550

Illinois Cancer Care ( Site 7005)

Recruiting

Peoria, Illinois, United States, 61615

Contacts

Study Coordinator

309-240-6040

University of Iowa-Holden Comprehensive Cancer Center ( Site 0139)

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Study Coordinator

319-356-4200

Mission Blood & Cancer Care ( Site 0114)

Recruiting

Waukee, Iowa, United States, 50263

Contacts

Study Coordinator

515-282-2921

Saint Elizabeth Medical Center Edgewood ( Site 0141)

Recruiting

Edgewood, Kentucky, United States, 41017

Contacts

Study Coordinator

859-301-2000

Baptist Health Hardin ( Site 0154)

Recruiting

Elizabethtown, Kentucky, United States, 42701

Contacts

Study Coordinator

270-706-5065

Baptist Health Lexington ( Site 0127)

Recruiting

Lexington, Kentucky, United States, 40503

Contacts

Study Coordinator

859-260-6100

Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0185)

Recruiting

Louisville, Kentucky, United States, 40207

Contacts

Study Coordinator

502-899-3366

Our Lady of the Lake Physician Group-Medical Oncology ( Site 0180)

Recruiting

Baton Rouge, Louisiana, United States, 70808

Contacts

Study Coordinator

225-374-0320

Ochsner LSU Health - Monroe Medical Center, Family Medicine Clinic ( Site 0209)

Recruiting

Monroe, Louisiana, United States, 71202

Contacts

Study Coordinator

318-330-0000

Ochsner Clinic Foundation ( Site 0189)

Recruiting

New Orleans, Louisiana, United States, 70121

Contacts

Study Coordinator

504-703-1340

Louisiana State University Health Sciences Shreveport ( Site 0195)

Recruiting

Shreveport, Louisiana, United States, 71103

Contacts

Study Coordinator

318-813-1057

Beth Israel Deaconess Medical Center ( Site 0161)

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Study Coordinator

617-667-2100

Dana Farber Cancer Institute ( Site 0111)

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Study Coordinator

877-442-3324

Minnesota Oncology Hematology (MNO) ( Site 8004)

Recruiting

Burnsville, Minnesota, United States, 55337

Contacts

Study Coordinator

952-892-7190

Bozeman Health Deaconess Hospital ( Site 0183)

Recruiting

Bozeman, Montana, United States, 59715

Contacts

Study Coordinator

406-414-3749

NHO Revive Research Institute, LLC ( Site 0121)

Recruiting

Lincoln, Nebraska, United States, 68506

Contacts

Study Coordinator

402-484-4900

University Of Nebraska Medical Center ( Site 0110)

Recruiting

Omaha, Nebraska, United States, 68198

Contacts

Study Coordinator

402-559-5600

Atlantic Health Morristown Medical Center ( Site 0163)

Recruiting

Morristown, New Jersey, United States, 07960

Contacts

Study Coordinator

973-971-6608

Valley Health Systems - Ridgewood Campus ( Site 0125)

Recruiting

Paramus, New Jersey, United States, 07652

Contacts

Study Coordinator

201-447-8000

Roswell Park Cancer Institute ( Site 0192)

Recruiting

Buffalo, New York, United States, 14263

Contacts

Study Coordinator

716-845-2300

Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 0208)

Recruiting

Mineola, New York, United States, 11501

Contacts

Study Coordinator

516-663-2988

Laura and Isaac Perlmutter Cancer Center at NYU Langone ( Site 0108)

Recruiting

New York, New York, United States, 10016

Contacts

Study Coordinator

212-731-6000

SUNY Upstate Cancer Center ( Site 0178)

Recruiting

Syracuse, New York, United States, 13210

Contacts

Study Coordinator

315-464-8200

Optum Medical Care, PC ( Site 0122)

Recruiting

Westbury, New York, United States, 11590

Contacts

Study Coordinator

646-872-8630

University of North Carolina Medical Center ( Site 0136)

Recruiting

Chapel Hill, North Carolina, United States, 27514

Contacts

Study Coordinator

984-974-1000

Novant Health Presbyterian Medical Center ( Site 0177)

Recruiting

Charlotte, North Carolina, United States, 28204

Contacts

Study Coordinator

704-384-4000

Novant Health Forsyth Medical Center ( Site 0206)

Recruiting

Winston-Salem, North Carolina, United States, 27103

Contacts

Study Coordinator

336-718-5000

University of Cincinnati Medical Center ( Site 0156)

Recruiting

Cincinnati, Ohio, United States, 45219

Contacts

Study Coordinator

513-584-1000

University Hospitals of Cleveland ( Site 0155)

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Study Coordinator

216-286-3867

Fairview Hospital-Moll Cancer Center ( Site 0198)

Recruiting

Cleveland, Ohio, United States, 44111

Contacts

Study Coordinator

216-444-6833

Cleveland Clinic Main ( Site 0101)

Recruiting

Cleveland, Ohio, United States, 44195

Contacts

Study Coordinator

216-444-6833

Cleveland Clinic - Hillcrest Hospital-Hillcrest Hospital Cancer Center ( Site 0199)

Recruiting

Mayfield Heights, Ohio, United States, 44124

Contacts

Study Coordinator

216-444-6833

Providence Portland Medical Center ( Site 0120)

Recruiting

Portland, Oregon, United States, 97213

Contacts

Study Coordinator

503-216-6300

Providence Oncology and Hematology Clinic Westside ( Site 0179)

Recruiting

Portland, Oregon, United States, 97225

Contacts

Study Coordinator

503-216-6300

Abramson Cancer Center and Perelman Center for Advanced Medicine ( Site 0131)

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Study Coordinator

215-662-2867

Temple University Hospital ( Site 0133)

Recruiting

Philadelphia, Pennsylvania, United States, 19140

Contacts

Study Coordinator

215-707-8712

Alliance Cancer Specialists (ACS) ( Site 8010)

Recruiting

Sellersville, Pennsylvania, United States, 18960

Contacts

Study Coordinator

215-706-2034

Cancer Care Associates Of York ( Site 0174)

Recruiting

York, Pennsylvania, United States, 17403

Contacts

Study Coordinator

484-371-5102

Medical University of South Carolina ( Site 0153)

Recruiting

Charleston, South Carolina, United States, 29425

Contacts

Study Coordinator

843-792-2529

Tennessee Cancer Specialists ( Site 7004)

Recruiting

Knoxville, Tennessee, United States, 37909

Contacts

Study Coordinator

865-862-0998

SCRI Oncology Partners ( Site 7002)

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

Study Coordinator

615-329-7274

Texas Oncology - West Texas ( Site 8008)

Recruiting

Amarillo, Texas, United States, 79124

Contacts

Study Coordinator

806-358-8654

Texas Oncology - Central/South Texas ( Site 8006)

Recruiting

Austin, Texas, United States, 78705

Contacts

Study Coordinator

512-427-9400

UT Southwestern Medical Center ( Site 0190)

Recruiting

Dallas, Texas, United States, 75390

Contacts

Study Coordinator

214-648-3111

Texas Oncology - Northeast Texas ( Site 8002)

Recruiting

Palestine, Texas, United States, 75801

Contacts

Study Coordinator

903-727-2200

Texas Oncology - San Antonio ( Site 8009)

Recruiting

San Antonio, Texas, United States, 78240

Contacts

Study Coordinator

210-595-5300

Intermountain Medical Center ( Site 0182)

Recruiting

Murray, Utah, United States, 84107

Contacts

Study Coordinator

801-507-3630

Intermountain Healthcare - St. George ( Site 0203)

Recruiting

St. George, Utah, United States, 84790

Contacts

Study Coordinator

801-507-3630

Virginia Cancer Specialists, PC ( Site 8003)

Recruiting

Manassas, Virginia, United States, 20110

Contacts

Study Coordinator

703-554-6800

VCU Health Adult Outpatient Pavillion ( Site 0138)

Recruiting

Richmond, Virginia, United States, 23219

Contacts

Study Coordinator

315-383-8748

Northwest Cancer Specialists (Compass Oncology) ( Site 8000)

Recruiting

Vancouver, Washington, United States, 98684

Contacts

Study Coordinator

360-944-9889

SSM Health Dean Medical Group ( Site 0106)

Recruiting

Madison, Wisconsin, United States, 53715

Contacts

Study Coordinator

608-252-8000

Medical College of Wisconsin ( Site 0103)

Recruiting

Milwaukee, Wisconsin, United States, 53226

Contacts

Study Coordinator

414-805-6700

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Sep 3, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-09-03.