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

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)

Phase2; Phase3 Interventional Merck Sharp & Dohme LLC · NCT05139017

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
Enrollment290 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC Industry-sponsored
Drugs / interventionsZilovertamab, Rituximab, CAR-T, chimeric antigen receptor, radiation
Locations124 sites (Glendale, Arizona and 123 other locations)
Trial IDNCT05139017 on ClinicalTrials.gov

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.

Who should consider this trial

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

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.

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

Eligibility criteria

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 this trial is running

Glendale, Arizona and 123 other locations

+74 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions DLBCLDiffuse Large B-Cell Lymphoma
Last reviewed 2026-06-09 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.