RecruitingPhase 2NCT06890884

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)

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)


Sponsor

Merck Sharp & Dohme LLC

Enrollment

594 participants

Start Date

Apr 11, 2025

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria6

  • 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 Criteria15

  • 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.

Interventions

BIOLOGICALZilovertamab vedotin

IV infusion

BIOLOGICALRituximab

IV infusion

DRUGCyclophosphamide

IV infusion

DRUGDoxorubicin

IV infusion

BIOLOGICALRituximab Biosimilar

IV infusion

DRUGPrednisone

Oral administration or IV infusion

DRUGPrednisolone

Oral administration or IV infusion

BIOLOGICALPolatuzumab vedotin

IV infusion

DRUGRescue Medication

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


Locations(112)

Infirmary Cancer Care ( Site 0157)

Mobile, Alabama, United States

Palo Verde Cancer Specialists ( Site 0105)

Glendale, Arizona, United States

Genesis Cancer and Blood Institute ( Site 0193)

Hot Springs, Arkansas, United States

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

Burbank, California, United States

Bass Medical Group ( Site 0123)

Walnut Creek, California, United States

Rocky Mountain Cancer Centers (RMCC) ( Site 8001)

Aurora, Colorado, United States

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

Grand Junction, Colorado, United States

Medical Oncology Hematology Consultants (MOHC) ( Site 8007)

Newark, Delaware, United States

Georgetown University Medical Center ( Site 0117)

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

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

Boca Raton, Florida, United States

Baptist MD Anderson Cancer Center ( Site 0176)

Jacksonville, Florida, United States

Mount Sinai Cancer Center ( Site 0140)

Miami Beach, Florida, United States

Mid Florida Hematology and Oncology Center ( Site 0152)

Orange City, Florida, United States

Beacon Cancer Care ( Site 0142)

Post Falls, Idaho, United States

University of Chicago Medical Center ( Site 0126)

Chicago, Illinois, United States

Illinois Cancer Care ( Site 7005)

Peoria, Illinois, United States

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

Iowa City, Iowa, United States

Mission Blood & Cancer Care ( Site 0114)

Waukee, Iowa, United States

Saint Elizabeth Medical Center Edgewood ( Site 0141)

Edgewood, Kentucky, United States

Baptist Health Hardin ( Site 0154)

Elizabethtown, Kentucky, United States

Baptist Health Lexington ( Site 0127)

Lexington, Kentucky, United States

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

Louisville, Kentucky, United States

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

Baton Rouge, Louisiana, United States

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

Monroe, Louisiana, United States

Louisiana State University Health Sciences Shreveport ( Site 0195)

Shreveport, Louisiana, United States

Minnesota Oncology Hematology (MNO) ( Site 8004)

Burnsville, Minnesota, United States

Bozeman Health Deaconess Hospital ( Site 0183)

Bozeman, Montana, United States

NHO Revive Research Institute, LLC ( Site 0121)

Lincoln, Nebraska, United States

University Of Nebraska Medical Center ( Site 0110)

Omaha, Nebraska, United States

Atlantic Health Morristown Medical Center ( Site 0163)

Morristown, New Jersey, United States

Valley Health Systems - Ridgewood Campus ( Site 0125)

Paramus, New Jersey, United States

Erie County Medical Center ( Site 0175)

Buffalo, New York, United States

Roswell Park Cancer Institute ( Site 0192)

Buffalo, New York, United States

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

Mineola, New York, United States

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

New York, New York, United States

SUNY Upstate Cancer Center ( Site 0178)

Syracuse, New York, United States

Clinical Research Alliance ( Site 0122)

Westbury, New York, United States

University of North Carolina Medical Center ( Site 0136)

Chapel Hill, North Carolina, United States

Novant Health Presbyterian Medical Center ( Site 0177)

Charlotte, North Carolina, United States

Novant Health Forsyth Medical Center ( Site 0206)

Winston-Salem, North Carolina, United States

University of Cincinnati Medical Center ( Site 0156)

Cincinnati, Ohio, United States

University Hospitals of Cleveland ( Site 0155)

Cleveland, Ohio, United States

Fairview Hospital-Moll Cancer Center ( Site 0198)

Cleveland, Ohio, United States

Cleveland Clinic Main ( Site 0101)

Cleveland, Ohio, United States

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

Mayfield Heights, Ohio, United States

Providence Portland Medical Center ( Site 0120)

Portland, Oregon, United States

Providence Oncology and Hematology Clinic Westside ( Site 0179)

Portland, Oregon, United States

Alliance Cancer Specialists (ACS) ( Site 8010)

Horsham, Pennsylvania, United States

Cancer Care Associates Of York ( Site 0174)

York, Pennsylvania, United States

Tennessee Cancer Specialists ( Site 7004)

Knoxville, Tennessee, United States

SCRI Oncology Partners ( Site 7002)

Nashville, Tennessee, United States

Texas Oncology - West Texas ( Site 8008)

Amarillo, Texas, United States

Texas Oncology - Central/South Texas ( Site 8006)

Austin, Texas, United States

Texas Oncology - Northeast Texas ( Site 8002)

Palestine, Texas, United States

Texas Oncology - San Antonio ( Site 8009)

San Antonio, Texas, United States

The University of Texas Health Science Center at Tyler dba UT Health East Texas HOPE Cancer Center ( Site 0145)

Tyler, Texas, United States

Intermountain Medical Center ( Site 0182)

Murray, Utah, United States

Intermountain Healthcare - St. George ( Site 0203)

St. George, Utah, United States

Virginia Cancer Specialists, PC ( Site 8003)

Manassas, Virginia, United States

VCU Health Adult Outpatient Pavillion ( Site 0138)

Richmond, Virginia, United States

Northwest Cancer Specialists (Compass Oncology) ( Site 8000)

Vancouver, Washington, United States

SSM Health Dean Medical Group ( Site 0106)

Madison, Wisconsin, United States

Medical College of Wisconsin ( Site 0103)

Milwaukee, Wisconsin, United States

AZ Sint-Maarten, Campus Leopoldstraat 2 ( Site 0306)

Mechelen, Antwerpen, Belgium

Cliniques Universitaires Saint-Luc ( Site 0302)

Brussels, Bruxelles-Capitale, Region de, Belgium

Hopital de Jolimont ( Site 0304)

Haine-Saint-Paul, Hainaut, Belgium

UZ Leuven ( Site 0301)

Leuven, Vlaams-Brabant, Belgium

AZ Delta ( Site 0303)

Roeselare, West-Vlaanderen, Belgium

Uniklinik Erlangen ( Site 0412)

Erlangen, Bavaria, Germany

Universitaetsklinikum Wuerzburg ( Site 0401)

Würzburg, Bavaria, Germany

St Vincent's University Hospital ( Site 0502)

Dublin, Dublin, Ireland

Mater Misercordiae University Hospital ( Site 0501)

Dublin, Ireland

University Hospital Limerick ( Site 0503)

Limerick, Ireland

Soroka Medical Center ( Site 0606)

Beersheba, Israel

Rambam Health Care Campus ( Site 0604)

Haifa, Israel

Edith Wolfson Medical Center ( Site 0602)

Holon, Israel

Haddasah Medical Center ( Site 0601)

Jerusalem, Israel

Rabin Medical Center ( Site 0607)

Petah Tikva, Israel

Sheba Medical Center ( Site 0603)

Ramat Gan, Israel

ZIV Medical Center ( Site 0605)

Safed, Israel

IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" ( Site 0707)

Meldola, Forli-Cesena, Italy

Istituto Clinico Humanitas ( Site 0704)

Rozzano, Milano, Italy

Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo ( Site 0703)

Alessandria, Italy

Istituto Europeo di Oncologia ( Site 0701)

Milan, Italy

Universita degli Studi di Napoli Federico II ( Site 0705)

Napoli, Italy

Az. Osp. Ospedali Riuniti VILLA SOFIA-CERVELLO ( Site 0702)

Palermo, Italy

Arcispedale Santa Maria Nuova ( Site 0706)

Reggio Emilia, Italy

Aichi Cancer Center ( Site 1007)

Nagoya, Aichi-ken, Japan

Fujita Health University Hospital ( Site 1003)

Toyoake, Aichi-ken, Japan

Hokkaido University Hospital ( Site 1004)

Sapporo, Hokkaido, Japan

National Hospital Organization Sendai Medical Center ( Site 1005)

Sendai, Miyagi, Japan

Kansai Medical University Hospital ( Site 1006)

Hirakata, Osaka, Japan

Shimane University Hospital ( Site 1002)

Izumo, Shimane, Japan

Nippon Medical School Hospital ( Site 1001)

Bunkyo, Tokyo, Japan

National Cancer Center Hospital ( Site 1009)

Chūō, Tokyo, Japan

Nagasaki University Hospital ( Site 1008)

Nagasaki, Japan

Pratia MCM Krakow ( Site 0804)

Karkow, Lesser Poland Voivodeship, Poland

Szpital Specjalistyczny im. Jedrzeja Sniadeckiego w Nowym Saczu ( Site 0806)

Nowy Sącz, Lesser Poland Voivodeship, Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0803)

Warsaw, Masovian Voivodeship, Poland

Uniwersyteckie Centrum Kliniczne ( Site 0802)

Gdansk, Pomeranian Voivodeship, Poland

Pratia Onkologia Katowice ( Site 0801)

Katowice, Silesian Voivodeship, Poland

Bristol Haematology and Oncology Centre ( Site 0908)

Bristol, Bristol, City of, United Kingdom

Stoke Mandeville Hospital ( Site 0917)

Aylesbury, Buckinghamshire, United Kingdom

Royal Devon & Exeter Hospital ( Site 0910)

Exeter, Devon, United Kingdom

University Hospitals Plymouth NHS Trust ( Site 0905)

Plymouth, Devon, United Kingdom

The James Cook University Hospital ( Site 0909)

Middlesbrough, England, United Kingdom

Lincoln County Hospital ( Site 0906)

Lincoln, Lincolnshire, United Kingdom

Guy s & St Thomas NHS Foundation Trust ( Site 0904)

London, London, City of, United Kingdom

Hammersmith Hospital ( Site 0915)

London, London, City of, United Kingdom

Churchill Hospital ( Site 0903)

Oxford, Oxfordshire, United Kingdom

Clatterbridge Cancer Centre - Liverpool ( Site 0911)

Liverpool, United Kingdom

Christie Hospital NHS Trust ( Site 0901)

Manchester, United Kingdom

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