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RecruitingInterventionalPhase 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)

NCT ID: NCT06890884Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-06-16

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.

Arms & 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).

Outcome measures

Primary

  • Complete Response Rate (CRR) at End of Treatment (EOT) per Lugano Response Criteria

    CRR at EOT is defined as the percentage of participants who experience complete response (CR) per Lugano response criteria as assessed by blinded independent central review (BICR) at end of treatment. CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. Participants with missing data or who discontinue treatment or study prior to reaching EOT will be considered non-responders and included in the total number of participants.

    Time frame: Up to approximately 31 months

Secondary

  • Progression-free Survival (PFS) per Lugano Response Criteria

    Time frame: Up to approximately 51 months

  • Overall Survival (OS)

    Time frame: Up to approximately 87 months

  • Event-free Survival (EFS) per Lugano Response Criteria

    Time frame: Up to approximately 51 months

  • Duration of CR

    Time frame: Up to approximately 51 months

  • Number of participants who experience one or more adverse events (AEs)

    Time frame: Up to approximately 9 months

  • Number of participants who discontinue study intervention due to an AE

    Time frame: Up to approximately 6 months

  • Change From Baseline in Health-Related Quality Of Life (HRQoL) on Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Trial Outcome Index (TOI)

    Time frame: Baseline and up to Week 25

  • Change From Baseline in HRQoL on FACT-Lym Total Score

    Time frame: Baseline and up to Week 25

  • Change From Baseline in HRQoL on FACT-Lym Physical Well-being (PWB) (Items General Physical [GP]1 through GP7)

    Time frame: Baseline and up to Week 25

  • Change From Baseline in HRQoL on Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) Neurotoxicity Subscale Score

    Time frame: Baseline and up to Week 25

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (70)

Infirmary Cancer Care ( Site 0157)

Mobile, Alabama, 36607

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Ironwood Cancer & Research Centers ( Site 0204)

Chandler, Arizona, 85224

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Study Coordinator · Contact

Palo Verde Cancer Specialists ( Site 0105)

Glendale, Arizona, 85304

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Study Coordinator · Contact

City of Hope - Phoenix ( Site 0202)

Goodyear, Arizona, 85338

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Study Coordinator · Contact

Genesis Cancer and Blood Institute ( Site 0193)

Hot Springs, Arkansas, 71913

Recruiting
Study Coordinator · Contact

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

Burbank, California, 91505

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Study Coordinator · Contact

City of Hope Comprehensive Cancer Center ( Site 0191)

Duarte, California, 91010

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Study Coordinator · Contact

Bass Medical Group ( Site 0123)

Walnut Creek, California, 94598

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Study Coordinator · Contact

Rocky Mountain Cancer Centers (RMCC) ( Site 8001)

Aurora, Colorado, 80012

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Study Coordinator · Contact

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

Grand Junction, Colorado, 81505

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Study Coordinator · Contact

Medical Oncology Hematology Consultants (MOHC) ( Site 8007)

Newark, Delaware, 19713

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Study Coordinator · Contact

Georgetown University Medical Center ( Site 0117)

Washington D.C., District of Columbia, 20007

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Study Coordinator · Contact

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

Boca Raton, Florida, 33486

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Study Coordinator · Contact

Baptist MD Anderson Cancer Center ( Site 0176)

Jacksonville, Florida, 32207

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Study Coordinator · Contact

Mount Sinai Braman Comprehensive Cancer Center ( Site 0140)

Miami Beach, Florida, 33140

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Study Coordinator · Contact

Mid Florida Hematology and Oncology Center ( Site 0152)

Orange City, Florida, 32763

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Study Coordinator · Contact

Beacon Cancer Care ( Site 0142)

Post Falls, Idaho, 83854

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Study Coordinator · Contact

University of Chicago Medical Center ( Site 0126)

Chicago, Illinois, 60637

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Study Coordinator · Contact

Illinois Cancer Care ( Site 7005)

Peoria, Illinois, 61615

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Study Coordinator · Contact

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

Iowa City, Iowa, 52242

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Study Coordinator · Contact

Mission Blood & Cancer Care ( Site 0114)

Waukee, Iowa, 50263

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Study Coordinator · Contact

Saint Elizabeth Medical Center Edgewood ( Site 0141)

Edgewood, Kentucky, 41017

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Study Coordinator · Contact

Baptist Health Hardin ( Site 0154)

Elizabethtown, Kentucky, 42701

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Study Coordinator · Contact

Baptist Health Lexington ( Site 0127)

Lexington, Kentucky, 40503

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Study Coordinator · Contact

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

Louisville, Kentucky, 40207

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Study Coordinator · Contact

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

Baton Rouge, Louisiana, 70808

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Study Coordinator · Contact

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

Monroe, Louisiana, 71202

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Study Coordinator · Contact

Ochsner Clinic Foundation ( Site 0189)

New Orleans, Louisiana, 70121

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Louisiana State University Health Sciences Shreveport ( Site 0195)

Shreveport, Louisiana, 71103

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Study Coordinator · Contact

Dana Farber Cancer Institute ( Site 0111)

Boston, Massachusetts, 02215

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Minnesota Oncology Hematology (MNO) ( Site 8004)

Burnsville, Minnesota, 55337

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Study Coordinator · Contact

Bozeman Health Deaconess Hospital ( Site 0183)

Bozeman, Montana, 59715

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Study Coordinator · Contact

NHO Revive Research Institute, LLC ( Site 0121)

Lincoln, Nebraska, 68506

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University Of Nebraska Medical Center ( Site 0110)

Omaha, Nebraska, 68198

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Study Coordinator · Contact

Atlantic Health Morristown Medical Center ( Site 0163)

Morristown, New Jersey, 07960

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Study Coordinator · Contact

Valley Health Systems - Ridgewood Campus ( Site 0125)

Paramus, New Jersey, 07652

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Study Coordinator · Contact

Erie County Medical Center ( Site 0175)

Buffalo, New York, 14215

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Study Coordinator · Contact

Roswell Park Cancer Institute ( Site 0192)

Buffalo, New York, 14263

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Study Coordinator · Contact

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

Mineola, New York, 11501

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Study Coordinator · Contact

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

New York, New York, 10016

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Study Coordinator · Contact

SUNY Upstate Cancer Center ( Site 0178)

Syracuse, New York, 13210

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Study Coordinator · Contact

Clinical Research Alliance ( Site 0122)

Westbury, New York, 11590

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Study Coordinator · Contact

University of North Carolina Medical Center ( Site 0136)

Chapel Hill, North Carolina, 27514

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Study Coordinator · Contact

Novant Health Presbyterian Medical Center ( Site 0177)

Charlotte, North Carolina, 28204

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Study Coordinator · Contact

Novant Health Forsyth Medical Center ( Site 0206)

Winston-Salem, North Carolina, 27103

Recruiting
Study Coordinator · Contact

University of Cincinnati Medical Center ( Site 0156)

Cincinnati, Ohio, 45219

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Study Coordinator · Contact

University Hospitals of Cleveland ( Site 0155)

Cleveland, Ohio, 44106

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Study Coordinator · Contact

Fairview Hospital-Moll Cancer Center ( Site 0198)

Cleveland, Ohio, 44111

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Study Coordinator · Contact

Cleveland Clinic Main ( Site 0101)

Cleveland, Ohio, 44195

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Study Coordinator · Contact

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

Mayfield Heights, Ohio, 44124

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Study Coordinator · Contact

Providence Portland Medical Center ( Site 0120)

Portland, Oregon, 97213

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Study Coordinator · Contact

Providence Oncology and Hematology Clinic Westside ( Site 0179)

Portland, Oregon, 97225

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Study Coordinator · Contact

Temple University Hospital ( Site 0133)

Philadelphia, Pennsylvania, 19140

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Study Coordinator · Contact

Alliance Cancer Specialists (ACS) ( Site 8010)

Sellersville, Pennsylvania, 18960

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Study Coordinator · Contact

Cancer Care Associates Of York ( Site 0174)

York, Pennsylvania, 17403

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Study Coordinator · Contact

Medical University of South Carolina ( Site 0153)

Charleston, South Carolina, 29425

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Study Coordinator · Contact

Tennessee Cancer Specialists ( Site 7004)

Knoxville, Tennessee, 37909

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Study Coordinator · Contact

SCRI Oncology Partners ( Site 7002)

Nashville, Tennessee, 37203

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Study Coordinator · Contact

Texas Oncology - West Texas ( Site 8008)

Amarillo, Texas, 79124

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Study Coordinator · Contact

Texas Oncology - Central/South Texas ( Site 8006)

Austin, Texas, 78705

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Study Coordinator · Contact

Texas Oncology - Northeast Texas ( Site 8002)

Palestine, Texas, 75801

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Study Coordinator · Contact

Texas Oncology - San Antonio ( Site 8009)

San Antonio, Texas, 78240

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Study Coordinator · Contact

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

Tyler, Texas, 75701

Completed

Intermountain Medical Center ( Site 0182)

Murray, Utah, 84107

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Study Coordinator · Contact

Intermountain Healthcare - St. George ( Site 0203)

St. George, Utah, 84790

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Study Coordinator · Contact

Virginia Cancer Specialists, PC ( Site 8003)

Manassas, Virginia, 20110

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Study Coordinator · Contact

VCU Health Adult Outpatient Pavillion ( Site 0138)

Richmond, Virginia, 23219

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Study Coordinator · Contact

Northwest Cancer Specialists (Compass Oncology) ( Site 8000)

Vancouver, Washington, 98684

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SSM Health Dean Medical Group ( Site 0106)

Madison, Wisconsin, 53715

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Medical College of Wisconsin ( Site 0103)

Milwaukee, Wisconsin, 53226

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