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RecruitingLast updated: 14 July 2026

waveLINE-003: A study recruiting people with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) to evaluate a targeted treatment called Zilovertamab vedotin when given in combination with other standard treatmentsA 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

Trial purpose

Medical clipboardCancer treatment

Tumor type

Blood Cancers Haematological

Age

People18+

Trial acronym

waveLINE-003

Clinical summary

Summary

This study is looking at a medicine called zilovertamab vedotin (ZV) for people with diffuse large B-cell lymphoma (DLBCL) that has come back or has not responded to treatment.

ZV is a type of targeted cancer treatment (called an antibody-drug conjugate) that is designed to find cancer cells and deliver treatment directly to them.

The study is testing whether adding ZV to standard cancer treatments can help control the cancer better, and delay the cancer from growing or spreading.

Who can take part?
You may be eligible to join if:

  • You are 18 years or older
  • You have DLBCL that has come back (relapsed) or not responded to treatment (refractory)
  • You have already had at least one previous treatment
  • You are not able to have, or your cancer has come back after, treatments such as a stem cell transplant or CAR T-cell therapy

You will also need to provide a tumour sample and meet general health requirements.

The study has two parts.

Part 1 - finding the right dose
The aim of this part is to find the safest and most appropriate dose of zilovertamab vedotin (ZV) when given with standard treatment.

Participants will be assigned to one of two groups (cohorts):

  • Cohort A: ZV + R-GemOx (rituximab, gemcitabine and oxaliplatin)
  • Cohort B: ZV + bendamustine and rituximab (BR)

Different dose levels of ZV are tested using a structured approach to monitor side effects and safety.

Part 2 - comparing effectiveness
This part aims to find out whether adding ZV to standard treatment helps the cancer stay under control for longer.

There are two cohorts, and within each cohort participants are randomly assigned (by chance) to receive one of two treatments:

  • Cohort A: either ZV+R-GemOx or R-GemOx alone (standard treatment)
  • Cohort B: either ZV + BR or BR alone (standard treatment).

Important note:
The Cohort B treatment groups (BR-based treatments) have been stopped. These groups are no longer enrolling participants, and their results will not be analysed.

 

Conditions

This trial is treating people with relapsed or refractory diffuse large B-cell lymphoma

Eligibility

Inclusion

  • 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

  • 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.

Inclusion

  • You have had treatment, but your cancer has come back (relapsed or recurrent).
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You have had a certain type of treatment or surgical procedure.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

Recruiting hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov, EU Clinical Trials Register *. View further details about this trial on the registry via the links below:

  • NCT05139017 *
  • 2022-502646-27-00 *
  • 2140-003; VLS-101; MK-2140-003; U1111-1285-0898; JRCT2011250068; MK2140-003

Trial sponsor

Merck Sharp & Dohme LLC

Scientific 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

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