Clinical trial Recruiting at 43 sites Phase2; Phase3 Interventional Ages 18 and up

Treatment for relapsed or refractory diffuse large B-cell lymphoma using zilovertamab vedotin

Official title: A Phase 2/3 Multicenter, Open-label, Randomized, Active-Control Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (waveLINE-003)

Run by Merck Sharp & Dohme LLC · NCT05139017 · Data updated 2026-11-12

This study is testing a new treatment called zilovertamab vedotin for adults with relapsed or refractory diffuse large B-cell lymphoma to see if it works better than standard care.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment290 (estimated)
SponsorMerck Sharp & Dohme LLC
Industry-sponsored
Drugs / interventionsZilovertamab, Rituximab, CAR-T, chimeric antigen receptor, radiation
Locations135 sites (Glendale, Arizona and 134 other locations)
StatusRecruiting
StartedJanuary 14, 2022
Main results expectedSeptember 24, 2027
Study endsSeptember 24, 2027
Registry record updatedNovember 3, 2026
Trial IDNCT05139017 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Ideal candidates are adults aged 18 and older with histologically confirmed rrDLBCL who have failed at least one prior therapy.

Probably not a fit

Patients who have not been diagnosed with DLBCL or those who are not relapsed or refractory may not benefit from this study.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial evaluates the safety and efficacy of zilovertamab vedotin (ZV) in combination with standard care treatments for patients with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL). The study is divided into two parts: a dose confirmation phase and an efficacy expansion phase. Participants will receive either ZV with rituximab, gemcitabine, and oxaliplatin or ZV with bendamustine and rituximab, with the aim of improving progression-free survival compared to standard treatments. The trial will enroll adults aged 18 and older who meet specific eligibility criteria.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with rrDLBCL who have limited treatment alternatives.

How similar studies have gone: Other studies have shown promising results with similar combination therapies in treating DLBCL, indicating potential for success in this approach.

Who can join: the full rules

Show full inclusion / exclusion 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.

Where it's running

  • Palo Verde Hematology/ Oncology Center, Ltd. ( Site 0175)
    Glendale, Arizona, United States
    Recruiting
  • Bass Medical Group ( Site 0166)
    Walnut Creek, California, United States
    Recruiting
  • Boca Raton Regional Hospital- Lynn Cancer Institute ( Site 0163)
    Boca Raton, Florida, United States
    Recruiting
  • Clermont Oncology Center ( Site 0174)
    Clermont, Florida, United States
    Recruiting
  • BRP-Hialeah Hospital ( Site 0182)
    Hialeah, Florida, United States
    Recruiting
  • Illinois Cancer Specialists ( Site 8000)
    Niles, Illinois, United States
    Recruiting
Show 44 more locations
  • Saint Elizabeth Medical Center Edgewood ( Site 0165)
    Edgewood, Kentucky, United States
    Recruiting
  • Corewell Health ( Site 0162)
    Grand Rapids, Michigan, United States
    Recruiting
  • Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0188)
    Grand Island, Nebraska, United States
    Recruiting
  • Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0177)
    Omaha, Nebraska, United States
    Recruiting
  • Comprehensive Cancer Centers of Nevada ( Site 0168)
    Las Vegas, Nevada, United States
    Recruiting
  • Alliance Cancer Specialists (ACS) ( Site 8001)
    Horsham, Pennsylvania, United States
    Recruiting
  • Tennessee Cancer Specialists ( Site 7000)
    Knoxville, Tennessee, United States
    Recruiting
  • Grampians Health ( Site 1802)
    Ballarat, Victoria, Australia
    Recruiting
  • Royal Perth Hospital-Haematology ( Site 1801)
    Perth, Western Australia, Australia
    Recruiting
  • Hospital Erasto Gaertner ( Site 2302)
    Curitiba, Paraná, Brazil
    Recruiting
  • Liga Norte Riograndense Contra o Câncer ( Site 2305)
    Natal, Rio Grande do Norte, Brazil
    Recruiting
  • Clínica Inmunocel ( Site 2404)
    Santiago, Region M. de Santiago, Chile
    Recruiting
  • Clínica RedSalud Vitacura ( Site 2409)
    Santiago, Region M. de Santiago, Chile
    Recruiting
  • Henan Cancer Hospital-hematology department ( Site 3013)
    Zhengzhou, Henan, China
    Recruiting
  • Fudan University Shanghai Cancer Center ( Site 3009)
    Shanghai, Shanghai Municipality, China
    Recruiting
  • Zhejiang Cancer Hospital ( Site 3014)
    Hangzhou, Zhejiang, China
    Recruiting
  • The First Affiliated Hospital Zhejiang University School of Medicine ( Site 3027)
    Hangzhou, Zhejiang, China
    Recruiting
  • Hokkaido University Hospital ( Site 3202)
    Sapporo, Hokkaido, Japan
    Recruiting
  • Tokai University Hospital ( Site 3212)
    Isehara, Kanagawa, Japan
    Recruiting
  • Mie University Hospital ( Site 3210)
    Tsu, Mie-ken, Japan
    Recruiting
  • Kansai Medical University Hospital ( Site 3203)
    Hirakata, Osaka, Japan
    Recruiting
  • Tokyo Metropolitan Komagome Hospital ( Site 3200)
    Bunkyo, Tokyo, Japan
    Recruiting
  • The Jikei University Hospital ( Site 3208)
    Minato, Tokyo, Japan
    Recruiting
  • University of Yamanashi Hospital ( Site 3201)
    Chūō, Yamanashi, Japan
    Recruiting
  • National Hospital Organization Kyushu Cancer Center ( Site 3204)
    Fukuoka, Japan
    Recruiting
  • Fukushima Medical University Hospital ( Site 3207)
    Fukushima, Japan
    Recruiting
  • University Hospital,Kyoto Prefectural University of Medicine ( Site 3209)
    Kyoto, Japan
    Recruiting
  • University of Miyazaki Hospital ( Site 3211)
    Miyazaki, Japan
    Recruiting
  • Osaka Metropolitan University Hospital ( Site 3205)
    Osaka, Japan
    Recruiting
  • Yamagata University Hospital ( Site 3206)
    Yamagata, Japan
    Recruiting
  • Hospital Nacional Dos De Mayo ( Site 2804)
    Lima, Peru
    Recruiting
  • Wojewódzki Szpital Specjalistyczny im. J. Korczaka w Słupsku ( Site 1309)
    Słupsk, Pomeranian Voivodeship, Poland
    Recruiting
  • Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastırma Hastanesi ( Site 1912)
    Yenimahalle, Ankara, Turkey (Türkiye)
    Recruiting
  • Ege University Medicine of Faculty ( Site 1902)
    Bornova, İzmir, Turkey (Türkiye)
    Recruiting
  • Ankara University Hospital Cebeci-hematology ( Site 1901)
    Ankara, Turkey (Türkiye)
    Recruiting
  • Mega Medipol-Hematology ( Site 1909)
    Istanbul, Turkey (Türkiye)
    Recruiting
  • Dokuz Eylül Üniversitesi-Hematology ( Site 1905)
    Izmir, Turkey (Türkiye)
    Recruiting
  • Beverly Hills Cancer Center ( Site 0184)
    Beverly Hills, California, United States
    Active not recruiting
  • Innovative Clinical Research Institute ( Site 0122)
    Whittier, California, United States
    Completed
  • University of Kentucky Chandler Medical Center ( Site 0158)
    Lexington, Kentucky, United States
    Active not recruiting
  • Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0133)
    Louisville, Kentucky, United States
    Active not recruiting
  • University of Maryland ( Site 0123)
    Baltimore, Maryland, United States
    Active not recruiting
  • Dana-Farber Cancer Institute-Lymphoma ( Site 0111)
    Boston, Massachusetts, United States
    Active not recruiting
  • University of Massachusetts Medical School ( Site 0119)
    Worcester, Massachusetts, United States
    Active not recruiting

+85 more sites. See ClinicalTrials.gov for the full list.

Study contacts

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.