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)

Last updated: March 28, 2025
Sponsor: Merck Sharp & Dohme LLC
Overall Status: Active - Recruiting

Phase

2/3

Condition

Lymphoma

Lymphoma, B-cell

Hematologic Cancer

Treatment

Gemcitabine

Granulocyte Colony-Stimulating Factor (G-CSF)

Bendamustine

Clinical Study ID

NCT05139017
2140-003
2022-502646-27-00
waveLINE-003
VLS-101
MK-2140-003
U1111-1285-0898
2022-502646-27
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Has a histologically confirmed diagnosis of Diffuse Large B-Cell Lymphoma (DLBCL).

  • Has radiographically measurable DLBCL per the Lugano Response Criteria, as assessedlocally 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 autologousstem-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 isineligible 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 havefailed at least 2 lines of prior therapy.

  • Has post-CAR-T therapy failure or is ineligible for CAR-T cell therapy.

Exclusion

Exclusion Criteria:

  • Not applicable with protocol amendment 4: Has history of transformation of indolentdisease 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 cardiacarrhythmia requiring medication.

  • Has ongoing graft-versus-host disease (GVHD) of any grade, or is receiving treatmentfor 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 beencompleted 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 notlimited to prior anaphylactic reaction.

  • Has received prior systemic anticancer therapy, including investigational agentswithin 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 requirecorticosteroids, and not have had radiation pneumonitis.

  • Has ongoing corticosteroid therapy.

  • Has received a live or live-attenuated vaccine within 30 days before the first doseof study intervention.

  • Is currently participating in or has participated in a study of an investigationalagent or has used an investigational device within 4 weeks before the first dose ofstudy intervention.

  • Has known active central nervous system (CNS) lymphoma involvement or active CNSinvolvement by lymphoma. Participants with prior CNS involvement are eligible iftheir 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 theparticipant's ability to cooperate with the requirements of the study.

Study Design

Total Participants: 290
Treatment Group(s): 6
Primary Treatment: Gemcitabine
Phase: 2/3
Study Start date:
January 14, 2022
Estimated Completion Date:
September 24, 2027

Connect with a study center

  • Hospital Aleman ( Site 2200)

    Buenos Aites, Caba C1118AAT
    Argentina

    Active - Recruiting

  • Townsville University Hospital ( Site 1800)

    Douglas, Queensland 4814
    Australia

    Active - Recruiting

  • Grampians Health ( Site 1802)

    Ballarat, Victoria 3350
    Australia

    Active - Recruiting

  • Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0200)

    Toronto, Ontario M5G 2M9
    Canada

    Completed

  • Biocenter ( Site 2401)

    Concepcion, Biobio 4070196
    Chile

    Site Not Available

  • Biocenter ( Site 2401)

    Concepcion., Biobio 4070196
    Chile

    Active - Recruiting

  • IC La Serena Research ( Site 2405)

    La Serena, Coquimbo 1720430
    Chile

    Active - Recruiting

  • Oncocentro Valdivia ( Site 2407)

    Valdivia, Los Rios 5112129
    Chile

    Site Not Available

  • Oncocentro Valdivia ( Site 2407)

    Valdivia., Los Rios 5112129
    Chile

    Active - Recruiting

  • Bradfordhill ( Site 2403)

    Santiago, Region M. De Santiago 8420383
    Chile

    Active - Recruiting

  • Clínica Inmunocel ( Site 2404)

    Santiago, Region M. De Santiago 7580206
    Chile

    Active - Recruiting

  • Clínica RedSalud Vitacura ( Site 2409)

    Santiago, Region M. De Santiago 7650018
    Chile

    Active - Recruiting

  • Beijing Cancer hospital ( Site 3000)

    Beijing, Beijing 100142
    China

    Active - Recruiting

  • Chongqing University Cancer Hospital-Medical Oncology ( Site 3025)

    Chongqing, Chongqing 400030
    China

    Active - Recruiting

  • Chongqing University Three Gorges Hospital ( Site 3026)

    Chongqing, Chongqing 404199
    China

    Active - Recruiting

  • Sun Yat-sen University Cancer Center-Internal Medicine ( Site 3001)

    Guangzhou, Guangdong 510060
    China

    Active - Recruiting

  • Zhujiang Hospital ( Site 3002)

    Guangzhou, Guangdong 510280
    China

    Active - Recruiting

  • The First Affiliated Hospital of Henan University of Science &Technology ( Site 3029)

    Luoyang, Henan 471003
    China

    Active - Recruiting

  • Henan Cancer Hospital-hematology department ( Site 3013)

    Zhengzhou, Henan 450008
    China

    Active - Recruiting

  • Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 3017)

    Wuhan, Hubei 430048
    China

    Active - Recruiting

  • Jiangxi Provincial Cancer Hospital ( Site 3005)

    Nanchang, Jiangxi 330029
    China

    Active - Recruiting

  • The First Affiliated Hospital of Nanchang University ( Site 3004)

    Nanchang, Jiangxi 330006
    China

    Active - Recruiting

  • The First Hospital of Jilin University-Hematology ( Site 3012)

    Changchun, Jilin 130021
    China

    Active - Recruiting

  • Fudan University Shanghai Cancer Center ( Site 3009)

    Shanghai, Shanghai 200032
    China

    Active - Recruiting

  • West China Hospital of Sichuan University-Head and Neck Oncology ( Site 3016)

    Cheng Du, Sichuan 610041
    China

    Active - Recruiting

  • Sichuan Cancer hospital-Oncology ( Site 3021)

    Chengdu, Sichuan 610042
    China

    Active - Recruiting

  • Zhejiang Cancer Hospital ( Site 3014)

    Hangzhou, Zhejiang 310000
    China

    Active - Recruiting

  • FUNDACION CTIC CENTRO DE TRATAMIENTO E INVESTIGACION SOBRE CANCER LUIS CARLOS SARMIENTO ANGULO ( Sit

    Bogota, Distrito Capital De Bogota 110131
    Colombia

    Active - Recruiting

  • Fundacion Valle del Lili ( Site 0802)

    Cali, Valle Del Cauca 760032
    Colombia

    Active - Recruiting

  • Hospital Metropolitano - Sede Lindora ( Site 2500)

    Santa Ana, San Jose 10903
    Costa Rica

    Active - Recruiting

  • CIMCA ( Site 2501)

    San Jose, 10103
    Costa Rica

    Active - Recruiting

  • centre hospitalier lyon sud-Service Hématologie ( Site 0702)

    Pierre-Bénite, Rhone 69310
    France

    Site Not Available

  • Pitie Salpetriere University Hospital-Clinical haematology ( Site 0700)

    Paris, 75013
    France

    Active - Recruiting

  • University Hospital of Alexandroupolis ( Site 0903)

    Alexandroupolis, Anatoliki Makedonia Kai Thraki 681 00
    Greece

    Active - Recruiting

  • Evangelismos General Hospital of Athens ( Site 0900)

    Athens, Attiki 106 76
    Greece

    Active - Recruiting

  • Regional General Hospital of Athens "Laiko" ( Site 0901)

    Athens, Attiki 115 26
    Greece

    Active - Recruiting

  • CELAN,S.A ( Site 2603)

    Guatemala, 1010
    Guatemala

    Active - Recruiting

  • MEDI-K ( Site 2602)

    Guatemala, 01009
    Guatemala

    Active - Recruiting

  • Private Practice- Dr. Rixci Augusto Lenin Ramírez ( Site 2601)

    Guatemala, 01010
    Guatemala

    Active - Recruiting

  • Princess Margaret Hospital ( Site 3101)

    Hong Kong,
    Hong Kong

    Active - Recruiting

  • Queen Mary Hospital ( Site 3100)

    Hong Kong, 000000
    Hong Kong

    Active - Recruiting

  • Emek Medical Center-Hematology Unit ( Site 1102)

    Afula, 1834111
    Israel

    Completed

  • Carmel Hospital ( Site 1103)

    Haifa, 3436212
    Israel

    Completed

  • Hadassah Medical Center ( Site 1100)

    Jerusalem, 9112001
    Israel

    Completed

  • Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1203)

    Rozzano, Milano 20089
    Italy

    Active - Recruiting

  • IRCCS - AOU di Bologna-Istituto di Ematologia "L. e A. Seragnoli" ( Site 1200)

    Bologna, 40138
    Italy

    Completed

  • Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1202)

    Napoli, 80131
    Italy

    Active - Recruiting

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS -ISTITUTO DI EMATOLOGIA ( Site 1204)

    Roma, 00168
    Italy

    Completed

  • Samsung Medical Center ( Site 0300)

    Seoul, 06351
    Korea, Republic of

    Active - Recruiting

  • Seoul National University Hospital-Oncology ( Site 0302)

    Seoul, 03080
    Korea, Republic of

    Active - Recruiting

  • Aotearoa Clinical Trials ( Site 0501)

    Auckland, 2025
    New Zealand

    Active - Recruiting

  • Uniwersytecki Szpital Kliniczny-Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku ( Site

    Wroclaw, Dolnoslaskie 50-367
    Poland

    Completed

  • Centrum Onkologii Ziemi Lubelskiej-Oddzial Hematologiczny ( Site 1304)

    Lublin, Lubelskie 20-090
    Poland

    Active - Recruiting

  • Centrum Onkologii Ziemi Lubelskiej-Oddzial Hematologii i Transplantacji Szpiku ( Site 1304)

    Lublin, Lubelskie 20-090
    Poland

    Active - Recruiting

  • Pratia MCM Krakow ( Site 1303)

    Krakow, Malopolskie 30-727
    Poland

    Active - Recruiting

  • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chłonnego ( S

    Warszawa, Mazowieckie 02-781
    Poland

    Active - Recruiting

  • Szpitale Pomorskie Sp. z o. o.-Hematology and Bone Marrow Transplantation Department ( Site 1302)

    Gdynia, Pomorskie 81-519
    Poland

    Completed

  • Wojewódzki Szpital Specjalistyczny im. J. Korczaka w Słupsku ( Site 1309)

    Słupsk, Pomorskie 76-200
    Poland

    Active - Recruiting

  • Pratia Onkologia Katowice ( Site 1306)

    Katowice, Slaskie 40-519
    Poland

    Active - Recruiting

  • Maharaj Nakorn Chiang Mai Hospital ( Site 0401)

    Muang, Chiang Mai 50200
    Thailand

    Site Not Available

  • Faculty of Medicine Siriraj Hospital-Division of Hematology, Department of Medicine ( Site 0400)

    Bangkok, Krung Thep Maha Nakhon 10700
    Thailand

    Active - Recruiting

  • Chulalongkorn University ( Site 0402)

    Pathumwan, Krung Thep Maha Nakhon 10330
    Thailand

    Active - Recruiting

  • Maharaj Nakorn Chiang Mai Hospital ( Site 0401)

    Chiang Mai, 50200
    Thailand

    Active - Recruiting

  • Ege University Medicine of Faculty ( Site 1902)

    Bornova, Izmir 35100
    Turkey

    Active - Recruiting

  • Ankara University Hospital Cebeci-hematology ( Site 1901)

    Ankara, 06100
    Turkey

    Active - Recruiting

  • Mega Medipol-Hematology ( Site 1909)

    Istanbul, 34214
    Turkey

    Active - Recruiting

  • Dokuz Eylül Üniversitesi-Hematology ( Site 1905)

    Izmir, 35340
    Turkey

    Active - Recruiting

  • Ondokuz Mayıs Universitesi ( Site 1907)

    Samsun, 55139
    Turkey

    Completed

  • MNPE ClinCenter of Oncology,Hematology,Transplantology and Palliative Care of CherkasyRegCouncil ( S

    Cherkasy, Cherkaska Oblast 18009
    Ukraine

    Active - Recruiting

  • Communal non-profit enterprise "Regional clinical hospital of Ivano-Frankivsk Regional Council" ( Si

    Ivano-Frankivsk, Ivano-Frankivska Oblast 76008
    Ukraine

    Active - Recruiting

  • Institute of Blood Pathology and Transfusion Medicine AMS Ukraine ( Site 2002)

    Lviv, Lvivska Oblast 79057
    Ukraine

    Active - Recruiting

  • National Research Center for Radiation Medicine of National Academy of Medical Sciences of Ukraine (

    Kyiv, 03115
    Ukraine

    Active - Recruiting

  • Public Non-Profit Enterprise Kyiv City Clinical Hospital #9 under the Executive Body of Kyiv City Co

    Kyiv, 04112
    Ukraine

    Active - Recruiting

  • State non-profit enterprise National Cancer Institute ( Site 2001)

    Kyiv, 03022
    Ukraine

    Active - Recruiting

  • Aberdeen Royal Infirmary ( Site 2104)

    Aberdeen, Aberdeen City AB25 2ZN
    United Kingdom

    Active - Recruiting

  • University College London Hospital-Cancer Clinical Trials Unit ( Site 2100)

    London-Camden, London, City Of NW1 2PG
    United Kingdom

    Active - Recruiting

  • Bass Medical Group ( Site 0166)

    Walnut Creek, California 94598
    United States

    Active - Recruiting

  • Innovative Clinical Research Institute ( Site 0122)

    Whittier, California 90603
    United States

    Completed

  • Boca Raton Regional Hospital- Lynn Cancer Institute ( Site 0163)

    Boca Raton, Florida 33486
    United States

    Active - Recruiting

  • Saint Elizabeth Medical Center Edgewood ( Site 0165)

    Edgewood, Kentucky 41017
    United States

    Active - Recruiting

  • University of Kentucky Chandler Medical Center ( Site 0158)

    Lexington, Kentucky 40536
    United States

    Active - Recruiting

  • Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0133)

    Louisville, Kentucky 40207
    United States

    Active - Recruiting

  • Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0133)

    Saint Matthews, Kentucky 40207
    United States

    Site Not Available

  • Louisiana State University Health Sciences Center New Orleans ( Site 0134)

    New Orleans, Louisiana 70112
    United States

    Completed

  • University of Maryland ( Site 0123)

    Baltimore, Maryland 21201
    United States

    Completed

  • Dana-Farber Cancer Institute-Lymphoma ( Site 0111)

    Boston, Massachusetts 02215
    United States

    Active - Recruiting

  • University of Massachusetts Medical School ( Site 0119)

    Worcester, Massachusetts 01655
    United States

    Active - Recruiting

  • St. Vincent Frontier Cancer Center-Research ( Site 0108)

    Billings, Montana 59102
    United States

    Active - Recruiting

  • Atlantic Health System ( Site 0116)

    Morristown, New Jersey 07960
    United States

    Active - Recruiting

  • New York Medical College ( Site 0113)

    Valhalla, New York 10595
    United States

    Active - Recruiting

  • Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 0156)

    Nashville, Tennessee 37232
    United States

    Active - Recruiting

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