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

A Phase 2 Open-label Clinical Study to Evaluate the Efficacy and Safety of Zilovertamab Vedotin (MK-2140) in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (waveLINE-004)

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.

Study Overview

• Status: Completed
• Conditions: Relapsed or Refractory Diffuse Large B-Cell Lymphoma
• Intervention / Treatment: Biological: Zilovertamab vedotin

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0100)
• Chile
  • Araucania
    • Temuco, Araucania, Chile, 4800827
      • James Lind Centro de Investigación del Cáncer ( Site 2705)
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 7650568
      • Clínica Alemana de Santiago ( Site 2704)
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer hospital ( Site 2900)
  • Guangdong
    • Guangzhou, Guangdong, China, 510030
      • SUN YAT-SEN UNIVERSITY CANCER CENTRE-Internal Medicine ( Site 2907)
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital-hematology department ( Site 2903)
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wuhan Union Hospital ( Site 2906)
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital ( Site 2905)
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University-Hematology ( Site 2910)
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center ( Site 2908)
    • Shanghai, Shanghai Municipality, China, 200120
      • Shanghai East Hospital ( Site 2902)
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University-Head and Neck Oncology ( Site 2911)
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital-lymphoma ( Site 2901)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University-Bone marrow transplant centre ( Site 2912)
• Czechia
  • Prague, Czechia, 12808
    • Vseobecna fakultni nemocnice v Praze-I. Interní klinika - klinika hematologie ( Site 0801)
  • Brno-mesto
    • Brno, Brno-mesto, Czechia, 625 00
      • Fakultní nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0800)
• Estonia
  • Harju
    • Tallinn, Harju, Estonia, 13419
      • North Estonia Medical Centre Foundation ( Site 0900)
• France
  • Paris, France, 75013
    • Pitie Salpetriere University Hospital-Clinical haematology ( Site 1000)
  • Aquitaine
    • Bayonne, Aquitaine, France, 64109
      • Centre Hospitalier de la Côte Basque ( Site 1002)
• Greece
  • Attica
    • Athens, Attica, Greece, 106 76
      • Evangelismos General Hospital of Athens ( Site 1214)
    • Athens, Attica, Greece, 115 27
      • General Hospital of Athens "Laiko"-Hematology Department ( Site 1213)
• Israel
  • Beersheba, Israel, 8410101
    • Soroka Medical Center-Hematology Department ( Site 1403)
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center ( Site 1404)
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center ( Site 1402)
  • Tel Aviv, Israel, 64239
    • Sourasky Medical Center ( Site 1400)
• Italy
  • Bologna, Italy, 40138
    • IRCCS - AOU di Bologna-Istituto di Ematologia "L. e A. Seragnoli" ( Site 1500)
  • Naples, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1502)
  • Lombardy
    • Milan, Lombardy, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa di Ematologia ( Site 1501)
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1503)
• Norway
  • Oslo, Norway, 0310
    • Oslo universitetssykehus, Radiumhospitalet ( Site 1600)
  • Hordaland
    • Bergen, Hordaland, Norway, 5021
      • Haukeland Universitetssjukehus ( Site 1601)
• Poland
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-826
      • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie-Oncology Department ( Site 1707)
  • Lower Silesian Voivodeship
    • Wroclaw, Lower Silesian Voivodeship, Poland, 50-367
      • Uniwersytecki Szpital Kliniczny-Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku ( Site
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chłonnego ( S
  • Pomeranian Voivodeship
    • Gdynia, Pomeranian Voivodeship, Poland, 81-519
      • Szpitale Pomorskie Sp. z o. o.-Hematology and Bone Marrow Transplantation Department ( Site 1702)
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-519
      • Pratia Onkologia ( Site 1701)
• South Korea
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System-Medical oncology ( Site 0601)
  • Seoul, South Korea, 06351
    • Samsung Medical Center ( Site 0600)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron ( Site 2005)
  • Madrid, Spain, 28040
    • Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology ( Site 2000)
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca ( Site 2003)
  • Barcelona
    • L'Hospitalet Del Llobregat, Barcelona, Spain, 08908
      • Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 2002)
• Sweden
  • Skåne County
    • Lund, Skåne County, Sweden, 22185
      • Skånes Universitetssjukhus Lund ( Site 2100)
  • Stockholm County
    • Solna, Stockholm County, Sweden, 171 64
      • Karolinska Universitetssjukhuset Solna ( Site 2102)
• Thailand
  • Bangkok
    • Bangkok, Bangkok, Thailand, 10700
      • Faculty of Medicine Siriraj Hospital ( Site 0701)
  • Chiang Mai
    • Muang, Chiang Mai, Thailand, 50200
      • Maharaj Nakorn Chiang Mai Hospital ( Site 0702)
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06100
    • Ankara University Hospital Cebeci-hematology ( Site 2300)
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe Universitesi-Department of Hematology ( Site 2302)
  • Istanbul, Turkey (Türkiye), 34214
    • Mega Medipol-Hematology ( Site 2308)
  • Izmir, Turkey (Türkiye), 35340
    • Dokuz Eylül Üniversitesi-Hematology ( Site 2304)
  • Samsun, Turkey (Türkiye), 55139
    • Ondokuz Mayıs Universitesi ( Site 2306)
  • Trabzon, Turkey (Türkiye), 61080
    • Karadeniz Teknik Universitesi Tip Fakultesi-Hematology ( Site 2307)
• United States
  • California
    • Orange, California, United States, 92868
      • St. Joseph Hospital-The Center for Cancer Prevention and Treatment ( Site 0229)
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute ( Site 0202)
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University Medical Center ( Site 0204)
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital ( Site 0206)
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center ( Site 0207)
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Franciscan St. Francis Health ( Site 0225)
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 0211)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital-Cancer Center Protocol Office ( Site 0203)
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan ( Site 0200)
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute ( Site 0216)
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Saint Louis University Cancer Center ( Site 0209)
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System Morristown Medical Center ( Site 0213)
  • New York
    • Valhalla, New York, United States, 10595
      • New York Medical College ( Site 0215)
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 0217)
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center ( Site 0222)
    • Columbus, Ohio, United States, 43210
      • The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • AHN West Penn Hospital ( Site 0212)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute- Research ( Site 0233)
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • MEDICAL COLLEGE OF WISCONSIN ( Site 0234)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• 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.
• Has a known history of hepatitis B or known active hepatitis C virus (HCV).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; 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; IV infusion; Other Names: MK-2140
Experimental: Arm B; 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; IV infusion; Other Names: MK-2140

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) per Lugano Response Criteria	Duration of Response (DOR) is time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.	Up to approximately 50 months
Number of Participants Who Experience an Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented.	Up to approximately 50 months
Number of Participants Who Discontinue Study Treatment Due to an AE	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.	Up to approximately 50 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Oncology Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2022
• Primary Completion (Actual): April 21, 2026
• Study Completion (Actual): April 21, 2026

Study Registration Dates

• First Submitted: November 22, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): December 3, 2021

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: 2140-004; MK-2140-004 (Other Identifier: MSD); 2021-003397-32 (EudraCT Number); 2022-501243-33-00 (Registry Identifier: EU CT); U1111-1279-9073 (Registry Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No