A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)
NCT ID: NCT05458297
Last Updated: 2025-12-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
223 participants
INTERVENTIONAL
2022-07-21
2029-05-17
Brief Summary
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* Cohort A: Participants with relapsed or refractory MCL relapsed or refractory disease after at least 2 prior systemic therapies including a Bruton's tyrosine kinase inhibition/inhibitor (BTKi), and post therapy chimeric antigen receptor T (CAR-T) cell therapy or ineligible for CAR-T cell therapy
* Cohort B: Participants with relapsed or refractory RT disease after at least 1 prior systemic therapy
* Cohort C: Participants with relapsed or refractory MCL relapsed or refractory disease after at least 1 prior systemic therapy and no prior exposure to a non-covalent BTKi
* Cohort D: Participants with relapsed or refractory FL and CLL relapsed or refractory disease after at least 2 prior systemic therapies and have no other available therapy
* Cohort E: Participants with relapsed or refractory FL after at least 2 prior systemic therapies and have no other available therapy
The primary study hypothesis is that zilovertamab vedotin monotherapy has an increased Objective Response Rate (ORR) per Lugano Response Criteria as assessed by blinded independent central review (BICR).
As of Amendment 07, Cohort D is closed to enrollment of participants with CLL and enrollment of participants into Arm 2 (zilovertamab vedotin at Dose 2 on Days 1 \& 8 of each 3 Week Cycle (Q2/3W)).
Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Cohort E, Relapsed or Refractory FL with 2 Prior Lines of Therapy
Participants will receive either zilovertamab vedotin IV infuison Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
Zilovertamab vedotin
IV infusion
Cohort A, Relapsed or Refractory MCL with 2 Prior Lines of Therapy
Participants will receive zilovertamab vedotin intravenous (IV) infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
Zilovertamab vedotin
IV infusion
Cohort B, Relapsed or Refractory RT with 1 Prior Line of Therapy
Participants will receive zilovertamab vedotin IV infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
Zilovertamab vedotin
IV infusion
Cohort C, Relapsed or Refractory MCL with 1 Prior Line of Therapy
Participants will receive zilovertamab vedotin IV infusion at Dose 2 every 3 weeks (Q3W) combined with nemtabrutinib oral dose daily until disease progression or discontinuation.
Zilovertamab vedotin
IV infusion
Nemtabrutinib
Oral tablet
Cohort D, Relapsed or Refractory FL and CLL with 2 Prior Lines of Therapy
Participants will receive either zilovertamab vedotin IV infusion Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
Zilovertamab vedotin
IV infusion
Interventions
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Zilovertamab vedotin
IV infusion
Nemtabrutinib
Oral tablet
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* For aggressive B-cell malignancies MCL Cohort C: Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 1 prior systemic therapy and has no prior exposure to a non-covalent BTKi.
* For aggressive B-cell malignancies Richter transformation lymphoma (RTL): Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease.
* For indolent B-cell malignancies follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL): Has histologically confirmed biopsy and has relapsed or refractory disease after at least 2 prior systemic therapies and no other available therapy.
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization/allocation.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before cycle 1 day 1.
Exclusion Criteria
* Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina (\<6 months prior to enrollment), congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication.
* Has pericardial effusion or clinically significant pleural effusion.
* Has ongoing Grade \>1 peripheral neuropathy.
* Has a demyelinating form of Charcot-Marie-Tooth disease.
* Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
* Participants with FL who have transformed to a more aggressive type of lymphoma.
* Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibodies) or 2 weeks (if prior therapy was small molecules like kinase inhibitors) prior to the first dose of study intervention.
* Has received prior radiotherapy within 28 days of start of study intervention. Participants must have recovered from all radiation-related toxicities.
* Has ongoing corticosteroid therapy exceeding 30 mg daily of prednisone equivalent.
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma.
* Has an active infection requiring systemic therapy.
* Has a known history of human immunodeficiency virus (HIV) infection not well controlled on antiretroviral therapy (ART)
* Active HBV or hepatitis C virus (HCV) infection.
* For Cohort C only: has any clinically significant gastrointestinal abnormalities that might alter absorption.
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Merck Sharp & Dohme LLC
Locations
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Alaska Oncology and Hematology ( Site 0037)
Anchorage, Alaska, United States
Banner MD Anderson Cancer Center ( Site 0040)
Gilbert, Arizona, United States
Banner MD Anderson Cancer Center - University Medical Center Phoenix-Medical Oncology ( Site 0036)
Phoenix, Arizona, United States
University of Colorado Anschutz Medical Campus-The Center for Cancer and Blood Disorders ( Site 0008)
Aurora, Colorado, United States
Cancer Care Specialists of Illinois ( Site 0031)
Decatur, Illinois, United States
University of Kansas Medical Center-Division of Hematologic Malignancies and Cellular Therapeutics ( Site 0038)
Fairway, Kansas, United States
Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0007)
Saint Matthews, Kentucky, United States
Greenebaum Comprehensive Cancer Center-Hematology & Multiple Myeloma ( Site 0010)
Baltimore, Maryland, United States
Tufts Medical Center ( Site 0024)
Boston, Massachusetts, United States
Massachusetts General Hospital ( Site 0018)
Boston, Massachusetts, United States
Dana-Farber Cancer Institute-Lymphoma ( Site 0026)
Boston, Massachusetts, United States
University of Michigan ( Site 0009)
Ann Arbor, Michigan, United States
Henry Ford Hospital ( Site 0035)
Detroit, Michigan, United States
Icahn School of Medicine at Mount Sinai ( Site 0023)
New York, New York, United States
Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 0014)
Fargo, North Dakota, United States
Avera Cancer Institute- Research ( Site 0011)
Sioux Falls, South Dakota, United States
Medical Oncology Associates, PS ( Site 0005)
Spokane, Washington, United States
University of Wisconsin Hospitals and Clinics-Carbone Cancer Center ( Site 0030)
Madison, Wisconsin, United States
MEDICAL COLLEGE OF WISCONSIN ( Site 0021)
Milwaukee, Wisconsin, United States
Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 1807)
Natal, Rio Grande do Norte, Brazil
Instituto Nacional de Câncer - INCA-Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico HC1 ( Site 1809)
Rio de Janeiro, , Brazil
ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 1808)
São Paulo, , Brazil
Hospital Paulistano-Americas Oncologia ( Site 1805)
São Paulo, , Brazil
BC Cancer Vancouver-Clinical Trials Unit ( Site 0201)
Vancouver, British Columbia, Canada
The Moncton Hospital-Oncology ( Site 0211)
Moncton, New Brunswick, Canada
QEII Health Sciences Centre - Victoria General Site ( Site 0213)
Halifax, Nova Scotia, Canada
Lawson Health Research Institute - London Health Sciences Ce-London Regional Cancer Program ( Site 0203)
London, Ontario, Canada
Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0200)
Toronto, Ontario, Canada
Jewish General Hospital ( Site 0202)
Montreal, Quebec, Canada
Allan Blair Cancer Centre-Care Services ( Site 0208)
Regina, Saskatchewan, Canada
IC La Serena Research ( Site 1909)
La Serena, Coquimbo Region, Chile
Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1907)
Santiago, Region M. de Santiago, Chile
Clínica Inmunocel ( Site 1910)
Santiago, Region M. de Santiago, Chile
Clínica Alemana de Santiago ( Site 1903)
Santiago, Region M. de Santiago, Chile
Beijing Cancer hospital ( Site 1200)
Beijing, Beijing Municipality, China
Zhujiang Hospital ( Site 1207)
Guangzhou, Guangdong, China
Southern Medical University Nanfang Hospital ( Site 1202)
Guangzhou, Guangdong, China
Sun Yat-sen University Cancer Center ( Site 1201)
Guangzhou, Guangdong, China
Henan Cancer Hospital-hematology department ( Site 1212)
Zhengzhou, Henan, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 1210)
Wuhan, Hubei, China
Tongji Hospital Tongji Medical,Science & Technology ( Site 1221)
Wuhan, Hubei, China
The First Affiliated Hospital of Soochow University-hematology department ( Site 1218)
Suzhou, Jiangsu, China
The Affiliated Hospital of Xuzhou Medical College ( Site 1223)
Xuzhou, Jiangsu, China
The First Affiliated Hospital of Nanchang University ( Site 1204)
Nanchang, Jiangxi, China
Jiangxi Provincial Cancer Hospital ( Site 1213)
Nanchang, Jiangxi, China
Jilin Province Tumor Hospital-oncology department ( Site 1220)
Chuangchun, Jilin, China
Fudan University Shanghai Cancer Center ( Site 1208)
Shanghai, Shanghai Municipality, China
West China Hospital of Sichuan University-Head and Neck Oncology ( Site 1206)
Chengdu, Sichuan, China
The First Affiliated Hospital, Zhejiang University ( Site 1211)
Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital ( Site 1214)
Hangzhou, Zhejiang, China
Fakultní nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0300)
Brno, Brno-mesto, Czechia
Fakultni nemocnice Ostrava-Klinika Hematoonkologie ( Site 0301)
Ostrava, Moravskoslezský kraj, Czechia
Vseobecna fakultni nemocnice v Praze-I. Interní klinika - klinika hematologie ( Site 0302)
Prague, , Czechia
North Estonia Medical Centre Foundation ( Site 0401)
Tallinn, Harju, Estonia
Universitaetsklinikum Ulm. ( Site 0502)
Ulm, Baden-Wurttemberg, Germany
Universitaetsklinikum Koeln ( Site 0506)
Cologne, North Rhine-Westphalia, Germany
St. James's Hospital ( Site 0600)
Dublin, , Ireland
Emek Medical Center-Hematology Unit ( Site 0705)
Afula, , Israel
Soroka Medical Center-Hematology Department ( Site 0707)
Beersheba, , Israel
Rambam Health Care Campus-Hematology and Bone Marrow Transplantation ( Site 0706)
Haifa, , Israel
Carmel Hospital ( Site 0709)
Haifa, , Israel
Hadassah Medical Center ( Site 0701)
Jerusalem, , Israel
Galilee Medical Center ( Site 0710)
Nahariya, , Israel
Sheba Medical Center-Hemato Oncology ( Site 0700)
Ramat Gan, , Israel
IRCCS - AOU di Bologna-SSD: Diagnosi e terapie dei linfomi e delle sindromi linfoproliferative cron ( Site 0800)
Bologna, Emilia-Romagna, Italy
Humanitas-U.O di Oncologia medica ed Ematologia ( Site 0802)
Rozzano, Milano, Italy
Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare -Azienda Ospedaliera Nazionale SS. Ant ( Site 0803)
Alessandria, , Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS -ISTITUTO DI EMATOLOGIA ( Site 0804)
Roma, , Italy
National Hospital Organization Nagoya Medical Center ( Site 1108)
Nagoya, Aichi-ken, Japan
Hokkaido University Hospital ( Site 1104)
Sapporo, Hokkaido, Japan
Tokai University Hospital ( Site 1100)
Isehara, Kanagawa, Japan
Tohoku University Hospital ( Site 1106)
Sendai, Miyagi, Japan
Kindai University Hospital ( Site 1102)
Sakai, Osaka, Japan
National Cancer Center Hospital ( Site 1103)
Chuo-ku, Tokyo, Japan
Cancer Institute Hospital of JFCR ( Site 1101)
Koto, Tokyo, Japan
Kyushu University Hospital ( Site 1105)
Fukuoka, , Japan
Okayama University Hospital ( Site 1107)
Okayama, , Japan
Centro Medico Monte Carmelo ( Site 1702)
Arequipa, Ariqipa, Peru
INSTITUTO NACIONAL DE ENFERMEDADES NEOPLASICAS ( Site 1700)
Lima, , Peru
Pratia MCM Krakow ( Site 1001)
Krakow, Lesser Poland Voivodeship, Poland
Centrum Onkologii Ziemi Lubelskiej-Oddzial Hematologiczny ( Site 1006)
Lublin, Lublin Voivodeship, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chłonnego ( Site 1002)
Warsaw, Masovian Voivodeship, Poland
Samodzielny Publiczny Zakład Opieki Zdrowotnej MSWiA w Olsztynie-Oddzial Kliniczny Hematologii ( Site 1007)
Olsztyn, Warmian-Masurian Voivodeship, Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumat-Oddiał Hematologii Ogólnej ( Site 1008)
Lodz, Łódź Voivodeship, Poland
Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakl-Klinika Hematologii i Transplantacji S ( Site 1010)
Kielce, Świętokrzyskie Voivodeship, Poland
Champalimaud Foundation ( Site 2002)
Lisbon, Lisbon District, Portugal
Unidade Local de Saude de Braga - Hospital de Braga ( Site 2001)
Braga, , Portugal
Instituto Português de Oncologia do Porto Francisco Gentil, EPE ( Site 2000)
Porto, , Portugal
National Cancer Centre Singapore ( Site 1500)
Singapore, Central Singapore, Singapore
Seoul National University Hospital ( Site 1300)
Seoul, , South Korea
Samsung Medical Center ( Site 1301)
Seoul, , South Korea
Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 4003)
L'Hospitalet Del Llobregat, Barcelona, Spain
Hospital Universitari Vall d'Hebron ( Site 4004)
Barcelona, Catalonia, Spain
MD Anderson Cancer Center ( Site 4006)
Madrid, Madrid, Comunidad de, Spain
Clinica Universidad de Navarra ( Site 4005)
Pamplona, Navarre, Spain
Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca-Hematology ( Site 4001)
Salamanca, , Spain
Skånes Universitetssjukhus Lund ( Site 5000)
Lund, Skåne County, Sweden
Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 5002)
Uppsala, Uppsala County, Sweden
Sahlgrenska Universitetssjukhuset ( Site 5003)
Gothenburg, Västra Götaland County, Sweden
Mega Medipol-Hematology ( Site 6009)
Stanbul, Istanbul, Turkey (Türkiye)
Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 6001)
Ankara, , Turkey (Türkiye)
Trakya University ( Site 6005)
Edirne, , Turkey (Türkiye)
Ege Universitesi Hastanesi ( Site 6002)
Izmir, , Turkey (Türkiye)
Ondokuz Mayıs Universitesi-Oncology department ( Site 6004)
Samsun, , Turkey (Türkiye)
The Royal Cornwall Hospital-Haematology ( Site 7006)
Truro, Cornwall, United Kingdom
University College London Hospital ( Site 7001)
London, London, City of, United Kingdom
The Churchill Hospital ( Site 7002)
Oxford, Oxfordshire, United Kingdom
The Christie NHS Foundation Trust ( Site 7007)
Manchester, , United Kingdom
Countries
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Central Contacts
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Facility Contacts
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Related Links
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Merck Clinical Trials Information
Plain Language Summary
Other Identifiers
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MK-2140-006
Identifier Type: OTHER
Identifier Source: secondary_id
jRCT2011230019
Identifier Type: REGISTRY
Identifier Source: secondary_id
2022-501374-19-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
U1111-1280-1849
Identifier Type: REGISTRY
Identifier Source: secondary_id
2021-004450-36
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2140-006
Identifier Type: -
Identifier Source: org_study_id