RECRUITING Phase 2 / Phase 3 ClinicalTrials.gov

A Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) (MK-2140-003)

Sponsor: Merck Sharp & Dohme LLC • ClinicalTrials.gov ID: NCT05139017

Registry updated: 2026-10-15

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Description

The purpose of this Phase 2/3, randomized, multisite, open-label, dose confirmation, and expansion study is to evaluate the safety, and efficacy of zilovertamab vedotin (ZV) in combination with standard of care options for the treatment of rrDLBCL. This study will be divided into 2 parts: Dose Confirmation (Part 1) and Efficacy Expansion (Part 2) and will enroll participants who are at least 18 years of age with rrDLBCL. The hypotheses are: ZV in combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx) is superior to R-GemOx with respect to progression-free survival (PFS) per Lugano response criteria by blinded independent review committee (BICR); and that ZV in combination with bendamustine rituximab (BR) is superior to BR with respect to PFS per Lugano response criteria by BICR. With protocol amendment 4 (effective: 04-April-2024), enrollment in Cohort B (study arms Bendamustine Rituximab \[BR\] and ZV + BR) is discontinued. No efficacy outcome analysis and hypothesis testing will be conducted for Cohort B.

Interventions

Zilovertamab vedotin (Biological)
Intravenous (IV) Infusion 1.5 mg/kg, 1.75 mg/kg, 2.0 mg/kg, 2.25 mg/kg, 2.5 mg/kg
Rituximab (Biological)
IV Infusion 375 mg/m\^2
Gemcitabine (Drug)
IV Infusion 1000 mg/m\^2
Oxaliplatin (Drug)
IV Infusion 100 mg/m\^2
Bendamustine (Drug)
IV Infusion 90 mg/m\^2
Granulocyte Colony-Stimulating Factor (G-CSF) (Drug)
Prophylactic G-CSF will be administered at each cycle of zilovertamab vedotin as per the institutional guidelines.

Eligibility criteria

Inclusion Criteria: * Has a histologically confirmed diagnosis of Diffuse Large B-Cell Lymphoma (DLBCL). * Has radiographically measurable DLBCL per the Lugano Response Criteria, as assessed locally by the investigator. * Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 within 7 days prior to study treatment initiation. * Has adequate organ function. * Is able to provide new or archival tumor tissue sample not previously irradiated. Zilovertamab vedotin plus R-GemOx, or R-GemOx study arms: * Has relapsed or refractory DLBCL and is ineligible for or have failed autologous stem-cell transplant (ASCT) and have failed at least 1 line of prior therapy. * Has post-chimeric antigen receptor T (post-CAR-T) cell therapy failure or is ineligible for CAR-T cell therapy. Not applicable with protocol amendment 4: Zilovertamab vedotin plus Bendamustine Rituximab (BR), and Bendamustine Rituximab study arms: * Has relapsed or refractory DLBCL and is ineligible for or have failed ASCT and have failed at least 2 lines of prior therapy. * Has post-CAR-T therapy failure or is ineligible for CAR-T cell therapy. Exclusion Criteria: * Not applicable with protocol amendment 4: Has history of transformation of indolent disease to DLBCL * Has received solid organ transplant at any time. * Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL). * Has clinically significant (ie, active) cardiovascular disease or serious cardiac arrhythmia requiring medication. * Has ongoing graft-versus-host disease (GVHD) of any grade, or is receiving treatment for their GVHD. * Has clinically significant pericardial or pleural effusion. * Has ongoing Grade \>1 peripheral neuropathy. * Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. * Has a demyelinating form of Charcot-Marie-Tooth disease. * Has contraindication to any of the study intervention components including but not limited to prior anaphylactic reaction. * Has received prior systemic anticancer therapy, including investigational agents within 4 weeks prior to the first dose of study intervention. * Has received prior radiotherapy within 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. * Has ongoing corticosteroid therapy. * Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention. * Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma. Participants with prior CNS involvement are eligible if their CNS disease is in radiographic, cytological (for cerebrospinal fluid disease), and clinical remission. * Has an active infection requiring systemic therapy. * Has a known history of human immunodeficiency virus (HIV) infection. * Has a known active Hepatitis C virus infection. * Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.

Conditions

DLBCL Diffuse Large B-Cell Lymphoma

Locations

Palo Verde Hematology/ Oncology Center, Ltd. ( Site 0175) — Glendale, Arizona, United States
Beverly Hills Cancer Center ( Site 0184) — Beverly Hills, California, United States
Bass Medical Group ( Site 0166) — Walnut Creek, California, United States
Innovative Clinical Research Institute ( Site 0122) — Whittier, California, United States
Boca Raton Regional Hospital- Lynn Cancer Institute ( Site 0163) — Boca Raton, Florida, United States
Clermont Oncology Center ( Site 0174) — Clermont, Florida, United States
BRP-Hialeah Hospital ( Site 0182) — Hialeah, Florida, United States
Illinois Cancer Specialists ( Site 8000) — Niles, Illinois, United States
Saint Elizabeth Medical Center Edgewood ( Site 0165) — Edgewood, Kentucky, United States
University of Kentucky Chandler Medical Center ( Site 0158) — Lexington, Kentucky, United States
Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0133) — Louisville, Kentucky, United States
University of Maryland ( Site 0123) — Baltimore, Maryland, United States
Dana-Farber Cancer Institute-Lymphoma ( Site 0111) — Boston, Massachusetts, United States
University of Massachusetts Medical School ( Site 0119) — Worcester, Massachusetts, United States
Corewell Health ( Site 0162) — Grand Rapids, Michigan, United States
St. Vincent Frontier Cancer Center-Research ( Site 0108) — Billings, Montana, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0188) — Grand Island, Nebraska, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0177) — Omaha, Nebraska, United States
Comprehensive Cancer Centers of Nevada ( Site 0168) — Las Vegas, Nevada, United States
Atlantic Health System ( Site 0116) — Morristown, New Jersey, United States
Presbyterian Rust Jorgensen Cancer ( Site 9506) — Rio Rancho, New Mexico, United States
New York Medical College ( Site 0113) — Valhalla, New York, United States
Alliance Cancer Specialists (ACS) ( Site 8001) — Horsham, Pennsylvania, United States
Tennessee Cancer Specialists ( Site 7000) — Knoxville, Tennessee, United States
Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 0156) — Nashville, Tennessee, United States
Blue Ridge Cancer Care ( Site 0169) — Roanoke, Virginia, United States
Hospital Italiano de Buenos Aires ( Site 2203) — Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Instituto de Investigaciones Clínicas Mar del Plata ( Site 2205) — Mar del Plata, Buenos Aires, Argentina
Hospital Aleman ( Site 2200) — Buenos Aites, Buenos Aires F.D., Argentina
Hospital Privado Universitario de Córdoba ( Site 2202) — Córdoba, Córdoba Province, Argentina
Instituto Alexander Fleming ( Site 2201) — CABA, Argentina
Townsville University Hospital ( Site 1800) — Townsville, Queensland, Australia
Grampians Health ( Site 1802) — Ballarat, Victoria, Australia
Royal Perth Hospital-Haematology ( Site 1801) — Perth, Western Australia, Australia
Hospital Erasto Gaertner ( Site 2302) — Curitiba, Paraná, Brazil
Liga Norte Riograndense Contra o Câncer ( Site 2305) — Natal, Rio Grande do Norte, Brazil
Hospital Paulistano ( Site 2300) — São Paulo, Brazil
Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0200) — Toronto, Ontario, Canada
Biocenter ( Site 2401) — Concepción, Biobio, Chile
IC La Serena Research ( Site 2405) — La Serena, Coquimbo Region, Chile
Oncocentro Valdivia ( Site 2407) — Valdivia, Los Ríos Region, Chile
FALP-UIDO ( Site 2400) — Santiago, Region M. de Santiago, Chile
Clínica Inmunocel ( Site 2404) — Santiago, Region M. de Santiago, Chile
Clínica RedSalud Vitacura ( Site 2409) — Santiago, Region M. de Santiago, Chile
Bradfordhill ( Site 2403) — Santiago, Region M. de Santiago, Chile
Beijing Cancer hospital ( Site 3000) — Beijing, Beijing Municipality, China
Chongqing University Cancer Hospital-Medical Oncology ( Site 3025) — Chongqing, Chongqing Municipality, China
Chongqing University Three Gorges Hospital ( Site 3026) — Chongqing, Chongqing Municipality, China
Sun Yat-sen University Cancer Center-Internal Medicine ( Site 3001) — Guangzhou, Guangdong, China
Zhujiang Hospital ( Site 3002) — Guangzhou, Guangdong, China
The First Affiliated Hospital of Henan University of Science &Technology ( Site 3029) — Luoyang, Henan, China
Henan Cancer Hospital-hematology department ( Site 3013) — Zhengzhou, Henan, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 3017) — Wuhan, Hubei, China
The First Affiliated Hospital of Nanchang University ( Site 3004) — Nanchang, Jiangxi, China
Jiangxi Provincial Cancer Hospital ( Site 3005) — Nanchang, Jiangxi, China
The First Hospital of Jilin University-Hematology ( Site 3012) — Changchun, Jilin, China
Fudan University Shanghai Cancer Center ( Site 3009) — Shanghai, Shanghai Municipality, China
Sichuan Cancer hospital-Oncology ( Site 3021) — Chengdu, Sichuan, China
West China Hospital of Sichuan University-Head and Neck Oncology ( Site 3016) — Chengdu, Sichuan, China
Zhejiang Cancer Hospital ( Site 3014) — Hangzhou, Zhejiang, China
The First Affiliated Hospital Zhejiang University School of Medicine ( Site 3027) — Hangzhou, Zhejiang, China
Hospital Pablo Tobon Uribe ( Site 0804) — Medellín, Antioquia, Colombia
FUNDACION CTIC CENTRO DE TRATAMIENTO E INVESTIGACION SOBRE CANCER LUIS CARLOS SARMIENTO ANGULO ( Site 0801) — Bogotá, Bogota D.C., Colombia
Instituto Médico de Alta Tecnologia S.A.S ( Site 0803) — Montería, Departamento de Córdoba, Colombia
Oncologos del Occidente ( Site 0800) — Pereira, Risaralda Department, Colombia
Fundacion Valle del Lili ( Site 0802) — Cali, Valle del Cauca Department, Colombia
Hospital Metropolitano - Sede Lindora ( Site 2500) — Santa Ana, Provincia de San José, Costa Rica
CIMCA ( Site 2501) — San José, Costa Rica
Aarhus Universitetshospital, Skejby ( Site 1701) — Aarhus, Central Jutland, Denmark
centre hospitalier lyon sud-Service Hématologie ( Site 0702) — Pierre-Bénite, Rhone, France
Pitie Salpetriere University Hospital-Clinical haematology ( Site 0700) — Paris, France
Evangelismos General Hospital of Athens ( Site 0900) — Athens, Attica, Greece
Regional General Hospital of Athens "Laiko" ( Site 0901) — Athens, Attica, Greece
University Hospital of Alexandroupolis ( Site 0903) — Alexandroupoli, East Macedonia and Thrace, Greece
MEDI-K ( Site 2602) — Guatemala City, Guatemala
Private Practice- Dr. Rixci Augusto Lenin Ramírez ( Site 2601) — Guatemala City, Guatemala
CELAN,S.A ( Site 2603) — Guatemala City, Guatemala
Queen Mary Hospital ( Site 3100) — Hong Kong, Hong Kong
Princess Margaret Hospital ( Site 3101) — Hong Kong, Hong Kong
Emek Medical Center-Hematology Unit ( Site 1102) — Afula, Israel
Carmel Hospital ( Site 1103) — Haifa, Israel
Hadassah Medical Center ( Site 1100) — Jerusalem, Israel
Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1203) — Rozzano, Milano, Italy
IRCCS - AOU di Bologna-Istituto di Ematologia "L. e A. Seragnoli" ( Site 1200) — Bologna, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1202) — Naples, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS -ISTITUTO DI EMATOLOGIA ( Site 1204) — Roma, Italy
Hokkaido University Hospital ( Site 3202) — Sapporo, Hokkaido, Japan
Tokai University Hospital ( Site 3212) — Isehara, Kanagawa, Japan
Mie University Hospital ( Site 3210) — Tsu, Mie-ken, Japan
Kansai Medical University Hospital ( Site 3203) — Hirakata, Osaka, Japan
Tokyo Metropolitan Komagome Hospital ( Site 3200) — Bunkyo, Tokyo, Japan
The Jikei University Hospital ( Site 3208) — Minato, Tokyo, Japan
University of Yamanashi Hospital ( Site 3201) — Chūō, Yamanashi, Japan
National Hospital Organization Kyushu Cancer Center ( Site 3204) — Fukuoka, Japan
Fukushima Medical University Hospital ( Site 3207) — Fukushima, Japan
University Hospital,Kyoto Prefectural University of Medicine ( Site 3209) — Kyoto, Japan
University of Miyazaki Hospital ( Site 3211) — Miyazaki, Japan
Osaka Metropolitan University Hospital ( Site 3205) — Osaka, Japan
Yamagata University Hospital ( Site 3206) — Yamagata, Japan
Health Pharma Professional Research S.A. de C.V: ( Site 2700) — Mexico City, Mexico City, Mexico
Medivest Centro de Investigación Integral ( Site 2704) — Chihuahua City, Mexico
Centro de Infusion Superare ( Site 2701) — Mexico City, Mexico
Aotearoa Clinical Trials ( Site 0501) — Auckland, New Zealand
Clínicas AUNA Sede Chiclayo ( Site 2803) — Chiclayo, Lambayeque, Peru
INSTITUTO NACIONAL DE ENFERMEDADES NEOPLASICAS ( Site 2800) — Surquillo, Muni Metro de Lima, Peru
Clínica San Felipe ( Site 2805) — Lima, Peru
Hospital Nacional Edgardo Rebagliati Martins ( Site 2802) — Lima, Peru
Hospital Nacional Dos De Mayo ( Site 2804) — Lima, Peru
Pratia MCM Krakow ( Site 1303) — Krakow, Lesser Poland Voivodeship, Poland
Specjalistyczny Szpital im. Dr Alfreda Sokolowskiego w Walbrzychu ( Site 1305) — Wałbrzych, Lower Silesian Voivodeship, Poland
Uniwersytecki Szpital Kliniczny-Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku ( Site 1301) — Wroclaw, Lower Silesian Voivodeship, Poland
Centrum Onkologii Ziemi Lubelskiej-Oddzial Hematologii i Transplantacji Szpiku ( Site 1304) — Lublin, Lublin Voivodeship, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chłonnego ( Site 1300) — Warsaw, Masovian Voivodeship, Poland
Szpitale Pomorskie Sp. z o. o.-Hematology and Bone Marrow Transplantation Department ( Site 1302) — Gdynia, Pomeranian Voivodeship, Poland
Wojewódzki Szpital Specjalistyczny im. J. Korczaka w Słupsku ( Site 1309) — Słupsk, Pomeranian Voivodeship, Poland
Pratia Onkologia Katowice ( Site 1306) — Katowice, Silesian Voivodeship, Poland
Seoul National University Hospital-Oncology ( Site 0302) — Seoul, South Korea
Samsung Medical Center ( Site 0300) — Seoul, South Korea
Faculty of Medicine Siriraj Hospital-Division of Hematology, Department of Medicine ( Site 0400) — Bangkok, Bangkok, Thailand
Chulalongkorn University ( Site 0402) — Pathumwan, Bangkok, Thailand
Maharaj Nakorn Chiang Mai Hospital ( Site 0401) — Muang, Chiang Mai, Thailand
Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastırma Hastanesi ( Site 1912) — Yenimahalle, Ankara, Turkey (Türkiye)
Ege University Medicine of Faculty ( Site 1902) — Bornova, İzmir, Turkey (Türkiye)
Ankara University Hospital Cebeci-hematology ( Site 1901) — Ankara, Turkey (Türkiye)
Mega Medipol-Hematology ( Site 1909) — Istanbul, Turkey (Türkiye)
Dokuz Eylül Üniversitesi-Hematology ( Site 1905) — Izmir, Turkey (Türkiye)
Ondokuz Mayıs Universitesi ( Site 1907) — Samsun, Turkey (Türkiye)
MNPE ClinCenter of Oncology,Hematology,Transplantology and Palliative Care of CherkasyRegCouncil ( Site 2000) — Cherkasy, Cherkasy Oblast, Ukraine
Communal non-profit enterprise "Regional clinical hospital of Ivano-Frankivsk Regional Council" ( Site 2004) — Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine
Institute of Blood Pathology and Transfusion Medicine AMS Ukraine ( Site 2002) — Lviv, Lviv Oblast, Ukraine
State non-profit enterprise National Cancer Institute ( Site 2001) — Kyiv, Ukraine
National Research Center for Radiation Medicine of National Academy of Medical Sciences of Ukraine ( Site 2005) — Kyiv, Ukraine
Aberdeen Royal Infirmary ( Site 2104) — Aberdeen, Aberdeen City, United Kingdom
The Royal Cornwall Hospital ( Site 2103) — Truro, England, United Kingdom
University College London Hospital-Cancer Clinical Trials Unit ( Site 2100) — London-Camden, London, City of, United Kingdom

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Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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