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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)

RecruitingPhase 2

A Randomized, Open-label, Multicenter, Phase 2 Study Evaluating the Efficacy and Safety of Zilovertamab Vedotin (MK-2140) Plus R-CHP Versus Polatuzumab Vedotin Plus R-CHP in Treatment-naïve Participants With GCB Subtype of Diffuse Large B-cell Lymphoma (DLBCL)

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
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.

About the study

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.

What is being tested

Sponsor: Merck Sharp & Dohme LLC · Participants: 594 · Started: Apr 11, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT06890884

Locations in the U.S.

AlabamaInfirmary Cancer Care ( Site 0157), Mobile
ArizonaIronwood Cancer & Research Centers ( Site 0204), Chandler
Palo Verde Cancer Specialists ( Site 0105), Glendale
City of Hope - Phoenix ( Site 0202), Goodyear
ArkansasGenesis Cancer and Blood Institute ( Site 0193), Hot Springs
CaliforniaRoy and Patricia Disney Family Cancer Center - Providence Saint Joseph Medical Center ( Site 0135), Burbank
City of Hope Comprehensive Cancer Center ( Site 0191), Duarte
Bass Medical Group ( Site 0123), Walnut Creek
ColoradoRocky Mountain Cancer Centers (RMCC) ( Site 8001), Aurora
Colorado West Healthcare System-Grand Valley Oncology ( Site 0165), Grand Junction
DelawareMedical Oncology Hematology Consultants (MOHC) ( Site 8007), Newark
District of ColumbiaGeorgetown University Medical Center ( Site 0117), Washington D.C.
FloridaBoca Raton Regional Hospital-Lynn Cancer Institute ( Site 0130), Boca Raton
Baptist MD Anderson Cancer Center ( Site 0176), Jacksonville
Mount Sinai Braman Comprehensive Cancer Center ( Site 0140), Miami Beach
Mid Florida Hematology and Oncology Center ( Site 0152), Orange City
IdahoBeacon Cancer Care ( Site 0142), Post Falls
IllinoisUniversity of Chicago Medical Center ( Site 0126), Chicago
Illinois Cancer Care ( Site 7005), Peoria
IowaUniversity of Iowa-Holden Comprehensive Cancer Center ( Site 0139), Iowa City
Mission Blood & Cancer Care ( Site 0114), Waukee
KentuckySaint Elizabeth Medical Center Edgewood ( Site 0141), Edgewood
Baptist Health Hardin ( Site 0154), Elizabethtown
Baptist Health Lexington ( Site 0127), Lexington
Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0185), Louisville
LouisianaOur Lady of the Lake Physician Group-Medical Oncology ( Site 0180), Baton Rouge
Ochsner LSU Health - Monroe Medical Center, Family Medicine Clinic ( Site 0209), Monroe
Ochsner Clinic Foundation ( Site 0189), New Orleans
Louisiana State University Health Sciences Shreveport ( Site 0195), Shreveport
MassachusettsBeth Israel Deaconess Medical Center ( Site 0161), Boston
Dana Farber Cancer Institute ( Site 0111), Boston
MinnesotaMinnesota Oncology Hematology (MNO) ( Site 8004), Burnsville
MontanaBozeman Health Deaconess Hospital ( Site 0183), Bozeman
NebraskaNHO Revive Research Institute, LLC ( Site 0121), Lincoln
University Of Nebraska Medical Center ( Site 0110), Omaha
New JerseyAtlantic Health Morristown Medical Center ( Site 0163), Morristown
Valley Health Systems - Ridgewood Campus ( Site 0125), Paramus
New YorkRoswell Park Cancer Institute ( Site 0192), Buffalo
Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 0208), Mineola
Laura and Isaac Perlmutter Cancer Center at NYU Langone ( Site 0108), New York
SUNY Upstate Cancer Center ( Site 0178), Syracuse
Optum Medical Care, PC ( Site 0122), Westbury
North CarolinaUniversity of North Carolina Medical Center ( Site 0136), Chapel Hill
Novant Health Presbyterian Medical Center ( Site 0177), Charlotte
Novant Health Forsyth Medical Center ( Site 0206), Winston-Salem
OhioUniversity of Cincinnati Medical Center ( Site 0156), Cincinnati
Cleveland Clinic Main ( Site 0101), Cleveland
Fairview Hospital-Moll Cancer Center ( Site 0198), Cleveland
University Hospitals of Cleveland ( Site 0155), Cleveland
Cleveland Clinic - Hillcrest Hospital-Hillcrest Hospital Cancer Center ( Site 0199), Mayfield Heights
OregonProvidence Oncology and Hematology Clinic Westside ( Site 0179), Portland
Providence Portland Medical Center ( Site 0120), Portland
PennsylvaniaAbramson Cancer Center and Perelman Center for Advanced Medicine ( Site 0131), Philadelphia
Temple University Hospital ( Site 0133), Philadelphia
Alliance Cancer Specialists (ACS) ( Site 8010), Sellersville
Cancer Care Associates Of York ( Site 0174), York
South CarolinaMedical University of South Carolina ( Site 0153), Charleston
TennesseeTennessee Cancer Specialists ( Site 7004), Knoxville
SCRI Oncology Partners ( Site 7002), Nashville
TexasTexas Oncology - West Texas ( Site 8008), Amarillo
Texas Oncology - Central/South Texas ( Site 8006), Austin
UT Southwestern Medical Center ( Site 0190), Dallas
Texas Oncology - Northeast Texas ( Site 8002), Palestine
Texas Oncology - San Antonio ( Site 8009), San Antonio
UtahIntermountain Medical Center ( Site 0182), Murray
Intermountain Healthcare - St. George ( Site 0203), St. George
VirginiaVirginia Cancer Specialists, PC ( Site 8003), Manassas
VCU Health Adult Outpatient Pavillion ( Site 0138), Richmond
WashingtonNorthwest Cancer Specialists (Compass Oncology) ( Site 8000), Vancouver
WisconsinSSM Health Dean Medical Group ( Site 0106), Madison
Medical College of Wisconsin ( Site 0103), Milwaukee

Conditions

From ClinicalTrials.gov, data retrieved Sep 29, 2026. Each study sets its own eligibility; the study team decides who can join.