A Study to Evaluate Zilovertamab Vedotin (MK-2140) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (MK-2140-004)

NCT05144841 | Active Not Recruiting Phase 2 FDA Drug

• 5 other identifiers: 2140-004MK-2140-0042022-501243-33-00U1111-1279-90732021-003397-32
• Study Type: interventional
• Target: 140
• Locations: 16 countries
• Sites: 70

Brief Summary

The purpose of this study is to evaluate zilovertamab vedotin with respect to objective response rate and duration of response per Lugano Response Criteria as assessed by blinded independent central review (BICR). Safety and tolerability will also be evaluated in this Phase 2, single arm, interventional study.

Conditions

Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) per Lugano Response Criteria

  ORR is percentage of participants with complete response (CR) or partial response (PR). ORR by cohort, relapsed or refractory (rr) DLBCL as assessed by BICR according to Lugano Response Criteria 2014 in participants treated with zilovertamab vedotin Q3W. CR is the complete radiologic response. PR is a partial response, \>=50% decrease in sum of the product of the perpendicular diameters for multiple lesions for up to 6 target measurable nodes and extranodal sites.

  Up to approximately 50 months

Secondary Outcomes (3)

• Duration of Response (DOR) per Lugano Response Criteria

  Up to approximately 50 months

• Number of Participants Who Experience an Adverse Event (AE)

  Up to approximately 50 months

• Number of Participants Who Discontinue Study Treatment Due to an AE

  Up to approximately 50 months

Study Arms (2)

Arm A

EXPERIMENTAL

Participants will receive treatment with zilovertamab vedotin 2.5 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks (Q3W)) until documented disease progression or any other discontinuation criterion is met.

Biological: Zilovertamab vedotin

Arm B

EXPERIMENTAL

Participants will receive treatment with zilovertamab vedotin 2.25 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks (Q3W)) until documented disease progression or any other discontinuation criterion is met.

Biological: Zilovertamab vedotin

Interventions

Zilovertamab vedotin BIOLOGICAL

IV infusion

Also known as: MK-2140

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has relapsed or refractory (rr) DLBCL; has progressed after at least 2 lines of prior therapy; and has progressed after auto- stem cell transplant (SCT) or are auto-SCT ineligible. Must have received prior multiagent regimen that includes an alkylating agent. anthracycline, and anti-CD20 (cluster of differentiation 20) monoclonal antibody.
• Has histologically confirmed diagnosis of DLBCL.
• Has radiographically measurable DLBCL per the Lugano Response Criteria.
• Should either be post- chimeric antigen receptor T cell therapy (CAR-T) failure or ineligible for CAR-T (for any reason).
• Life expectancy of at least 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before time of enrollment.
• Has adequate organ function.

You may not qualify if:

• Has received a diagnosis of Primary mediastinal B-cell lymphoma (PMBCL).
• Has undergone solid organ transplant at any time.
• Has a history of any clinically significant cardiovascular conditions within 6 months of screening or serious cardiac arrhythmia requiring medication.
• Has known history of liver cirrhosis.
• Has pericardial effusion or clinically significant 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.
• Transformed DLBCL from indolent lymphoma.
• In participants with prior allo-SCT, acute graft versus host disease (GVHD) or ongoing evidence of chronic GVHD.
• 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 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.
• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (71)

St. Joseph Hospital-The Center for Cancer Prevention and Treatment ( Site 0229)

Orange, California, 92868, United States

Location

Innovative Clinical Research Institute ( Site 0202)

Whittier, California, 90603, United States

Location

Georgetown University Medical Center ( Site 0204)

Washington D.C., District of Columbia, 20007, United States

Location

Northside Hospital ( Site 0206)

Atlanta, Georgia, 30342, United States

Location

University of Chicago Medical Center ( Site 0207)

Chicago, Illinois, 60637, United States

Location

Franciscan St. Francis Health ( Site 0225)

Indianapolis, Indiana, 46237, United States

Location

University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 0211)

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital-Cancer Center Protocol Office ( Site 0203)

Boston, Massachusetts, 02114, United States

Location

University of Michigan ( Site 0200)

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute ( Site 0216)

Detroit, Michigan, 48201, United States

Location

Saint Louis University Cancer Center ( Site 0209)

St Louis, Missouri, 63110, United States

Location

Atlantic Health System Morristown Medical Center ( Site 0213)

Morristown, New Jersey, 07960, United States

Location

New York Medical College ( Site 0215)

Valhalla, New York, 10595, United States

Location

University of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 0217)

Cincinnati, Ohio, 45219, United States

Location

University Hospitals Cleveland Medical Center ( Site 0222)

Cleveland, Ohio, 44106, United States

Location

The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C

Columbus, Ohio, 43210, United States

Location

AHN West Penn Hospital ( Site 0212)

Pittsburgh, Pennsylvania, 15224, United States

Location

Avera Cancer Institute- Research ( Site 0233)

Sioux Falls, South Dakota, 57105, United States

Location

MEDICAL COLLEGE OF WISCONSIN ( Site 0234)

Milwaukee, Wisconsin, 53226, United States

Location

Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0100)

Toronto, Ontario, M5G 2M9, Canada

Location

Clínica Alemana de Santiago ( Site 2704)

Santiago, Region M. de Santiago, 7650568, Chile

Location

James Lind Centro de Investigación del Cáncer ( Site 2705)

Temuco, Región de la Araucanía, 4800827, Chile

Location

Beijing Cancer hospital ( Site 2900)

Beijing, Beijing Municipality, 100142, China

Location

SUN YAT-SEN UNIVERSITY CANCER CENTRE-Internal Medicine ( Site 2907)

Guangzhou, Guangdong, 510030, China

Location

Henan Cancer Hospital-hematology department ( Site 2903)

Zhengzhou, Henan, 450008, China

Location

Wuhan Union Hospital ( Site 2906)

Wuhan, Hubei, 430022, China

Location

Hunan Cancer Hospital ( Site 2905)

Changsha, Hunan, 410013, China

Location

The First Hospital of Jilin University-Hematology ( Site 2910)

Changchun, Jilin, 130021, China

Location

Fudan University Shanghai Cancer Center ( Site 2908)

Shanghai, Shanghai Municipality, 200032, China

Location

Shanghai East Hospital ( Site 2902)

Shanghai, Shanghai Municipality, 200120, China

Location

West China Hospital of Sichuan University-Head and Neck Oncology ( Site 2911)

Chengdu, Sichuan, 610041, China

Location

Tianjin Medical University Cancer Institute and Hospital-lymphoma ( Site 2901)

Tianjin, Tianjin Municipality, 300060, China

Location

The First Affiliated Hospital, Zhejiang University-Bone marrow transplant centre ( Site 2912)

Hangzhou, Zhejiang, 310003, China

Location

Fakultní nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0800)

Brno, Brno-mesto, 625 00, Czechia

Location

Vseobecna fakultni nemocnice v Praze-I. Interní klinika - klinika hematologie ( Site 0801)

Prague, 12808, Czechia

Location

North Estonia Medical Centre Foundation ( Site 0900)

Tallinn, Harju, 13419, Estonia

Location

Centre Hospitalier de la Côte Basque ( Site 1002)

Bayonne, Aquitaine, 64109, France

Location

Pitie Salpetriere University Hospital-Clinical haematology ( Site 1000)

Paris, 75013, France

Location

Evangelismos General Hospital of Athens ( Site 1214)

Athens, Attica, 106 76, Greece

Location

General Hospital of Athens "Laiko"-Hematology Department ( Site 1213)

Athens, Attica, 115 27, Greece

Location

Soroka Medical Center-Hematology Department ( Site 1403)

Beersheba, 8410101, Israel

Location

Shaare Zedek Medical Center ( Site 1404)

Jerusalem, 9103102, Israel

Location

Hadassah Medical Center ( Site 1402)

Jerusalem, 9112001, Israel

Location

Sourasky Medical Center ( Site 1400)

Tel Aviv, 64239, Israel

Location

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa di Ematologia ( Site 1501)

Milan, Lombardy, 20133, Italy

Location

Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1503)

Rozzano, Milano, 20089, Italy

Location

IRCCS - AOU di Bologna-Istituto di Ematologia "L. e A. Seragnoli" ( Site 1500)

Bologna, 40138, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1502)

Naples, 80131, Italy

Location

Haukeland Universitetssjukehus ( Site 1601)

Bergen, Hordaland, 5021, Norway

Location

Oslo universitetssykehus, Radiumhospitalet ( Site 1600)

Oslo, 0310, Norway

Location

Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie-Oncology Department ( Site 1707)

Krakow, Lesser Poland Voivodeship, 31-826, Poland

Location

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

Wroclaw, Lower Silesian Voivodeship, 50-367, Poland

Location

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

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Szpitale Pomorskie Sp. z o. o.-Hematology and Bone Marrow Transplantation Department ( Site 1702)

Gdynia, Pomeranian Voivodeship, 81-519, Poland

Location

Pratia Onkologia ( Site 1701)

Katowice, Silesian Voivodeship, 40-519, Poland

Location

Severance Hospital, Yonsei University Health System-Medical oncology ( Site 0601)

Seoul, 03722, South Korea

Location

Samsung Medical Center ( Site 0600)

Seoul, 06351, South Korea

Location

Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 2002)

L'Hospitalet Del Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitari Vall d'Hebron ( Site 2005)

Barcelona, 08035, Spain

Location

Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology ( Site 2000)

Madrid, 28040, Spain

Location

Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca ( Site 2003)

Salamanca, 37007, Spain

Location

Skånes Universitetssjukhus Lund ( Site 2100)

Lund, Skåne County, 22185, Sweden

Location

Karolinska Universitetssjukhuset Solna ( Site 2102)

Solna, Stockholm County, 171 64, Sweden

Location

Faculty of Medicine Siriraj Hospital ( Site 0701)

Bangkok, Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital ( Site 0702)

Muang, Chiang Mai, 50200, Thailand

Location

Ankara University Hospital Cebeci-hematology ( Site 2300)

Ankara, 06100, Turkey (Türkiye)

Location

Hacettepe Universitesi-Department of Hematology ( Site 2302)

Ankara, 06230, Turkey (Türkiye)

Location

Mega Medipol-Hematology ( Site 2308)

Istanbul, 34214, Turkey (Türkiye)

Location

Dokuz Eylül Üniversitesi-Hematology ( Site 2304)

Izmir, 35340, Turkey (Türkiye)

Location

Ondokuz Mayıs Universitesi ( Site 2306)

Samsun, 55139, Turkey (Türkiye)

Location

Karadeniz Teknik Universitesi Tip Fakultesi-Hematology ( Site 2307)

Trabzon, 61080, Turkey (Türkiye)

Location

Related Links

• Merck Oncology Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Recurrence; Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: December 3, 2021
• Study Start: January 8, 2022
• Primary Completion: April 22, 2026
• Study Completion: April 22, 2026
• Last Updated: February 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

GR (2); NO (2); CL (2); ES (4); SE (2); CN (11); CZ (2); CA (1); IT (4); IL (4); US (19); FR (2); PL (5); TU (6); KR (2); TH (2)