Zilovertamab Vedotin for Lymphoma

Not currently recruiting at 86 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must be taking: Alkylating agents, Anthracyclines, Anti-CD20

Must not be taking: Corticosteroids, Investigational agents

Disqualifiers: PMBCL, Solid organ transplant, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Up to approximately 50 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, zilovertamab vedotin (MK-2140), to evaluate its effectiveness for individuals with Diffuse Large B-Cell Lymphoma (DLBCL), particularly after other treatments have failed. Participants will receive the drug intravenously every three weeks to assess cancer response and the duration of that response. The trial is open to those whose DLBCL has returned or not responded to at least two previous treatments and who are not eligible for or have not succeeded with stem cell transplants and CAR-T therapy. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have ongoing corticosteroid therapy exceeding 30 mg daily of prednisone equivalent, and you must not have received any systemic anticancer therapy or investigational agents within 4 weeks before starting the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that zilovertamab vedotin was safe in earlier studies. For instance, patients with relapsed or refractory lymphoma experienced ongoing tumor reduction without severe side effects. One study found a 56.3% response rate when combined with standard treatments, indicating effectiveness and general tolerability.

Regarding side effects, data from previous trials suggest they are manageable, meaning they are usually not severe and can be handled by the medical team. As this is a Phase 2 trial, some evidence already supports the treatment’s safety in humans. However, ongoing research remains important to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about zilovertamab vedotin because it offers a novel approach to treating lymphoma. Unlike standard treatments like chemotherapy and immunotherapy, zilovertamab vedotin is an antibody-drug conjugate that specifically targets and delivers a potent drug directly to cancer cells, potentially increasing effectiveness while minimizing damage to healthy cells. This targeted delivery could lead to fewer side effects compared to traditional therapies. Additionally, the treatment is administered via intravenous infusion every three weeks, which may offer convenience compared to some current regimens that require more frequent dosing.

What evidence suggests that zilovertamab vedotin could be an effective treatment for lymphoma?

Research has shown that zilovertamab vedotin may help treat certain cancers. One study found that it shrank or eliminated tumors in 56.3% of patients with relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL), meaning more than half of the patients experienced tumor reduction or disappearance. In this trial, participants will receive zilovertamab vedotin in different dosages: Arm A will receive 2.5 mg/kg, and Arm B will receive 2.25 mg/kg. The treatment is considered safe, with manageable side effects. Although more research is needed, these findings suggest that zilovertamab vedotin could be a promising option for lymphoma patients who haven't had success with other treatments. ^{1 3 4 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for people with a type of cancer called Diffuse Large B-Cell Lymphoma (DLBCL) who have tried at least two treatments and are not eligible or didn't improve after stem cell transplant or CAR-T therapy. They should be able to do daily activities, have good organ function, measurable cancer signs on scans, and confirmed DLBCL diagnosis.

Inclusion Criteria

My organs are functioning well.

My DLBCL has not responded to at least 2 treatments, including a stem cell transplant or I'm ineligible for one.

I either did not respond to CAR-T therapy or am not eligible for it.

Exclusion Criteria

I have a history of hepatitis B or active hepatitis C.

I have had an organ transplant.

I have been diagnosed with HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zilovertamab vedotin via intravenous infusion every 3 weeks until disease progression or discontinuation

Up to approximately 50 months

1 visit every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MK-2140 (zilovertamab vedotin)

Trial Overview The study tests Zilovertamab Vedotin (MK-2140) in patients with DLBCL to see how well it works and how long the effects last. It's a Phase 2 trial where everyone gets the same treatment, and doctors check if tumors shrink using special criteria while also watching for any safety issues.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 1 Intervention

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.

Group II: Arm A Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a study of 136 patients with relapsed/refractory Hodgkin lymphoma who were ineligible for autologous stem cell transplant, brentuximab vedotin (BV) showed a high overall response rate of 74%, indicating its effectiveness in this population.

The median progression-free survival (PFS) and overall survival (OS) were 15.1 months and 17.8 months, respectively, with peripheral neuropathy reported in 9.6% of patients, highlighting the treatment's safety profile in elderly or frail patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma who are Ineligible for autologous stem cell transplant: A Germany and United Kingdom retrospective study. Bröckelmann, PJ., Zagadailov, EA., Corman, SL., et al.[2019]

Brentuximab vedotin (BV) is an effective treatment for relapsed or refractory Hodgkin lymphoma (HL) and anaplastic large-cell lymphoma (ALCL), and it has recently been approved for use as a consolidation therapy after autologous stem cell transplantation in high-risk HL patients.

BV is being investigated in various new treatment settings, including as a single agent or in combination with other therapies for first-salvage HL and frontline treatment in DLBCL, showing promising results that could lead to first-line approvals if ongoing trials are successful.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New uses for brentuximab vedotin and novel antibody drug conjugates in lymphoma. Merli, M., Ferrario, A., Maffioli, M., et al.[2019]

Polatuzumab vedotin (PV) is an innovative antibody-drug conjugate that has been approved by the US FDA for treating refractory/relapsed diffuse large B-cell lymphoma, particularly in patients who are not eligible for stem cell transplants.

In a pivotal Phase II trial, PV demonstrated significant efficacy and an acceptable safety profile when used in combination with bendamustine and rituximab, highlighting its potential as a valuable treatment option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin, an anti-CD79b antibody-drug conjugate for the treatment of relapsed/refractory diffuse large B-cell lymphoma. Camus, V., Tilly, H.[2021]

Brentuximab vedotin (Bv) combined with bendamustine (B) showed a high overall response rate of 79% and a complete response rate of 49% in 47 patients with relapsed or refractory classic Hodgkin lymphoma, indicating its efficacy as a treatment option.

The treatment resulted in a median progression-free survival of 18 months and a 2-year overall survival rate of 72%, particularly benefiting patients who achieved a major clinical response and those who underwent stem cell transplantation afterward.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real-world study. Iannitto, E., Romano, A., Scalzulli, PR., et al.[2021]

Brentuximab vedotin demonstrated a clinically meaningful response in 47% of pediatric patients with relapsed or refractory classical Hodgkin's lymphoma and 53% for systemic anaplastic large-cell lymphoma, indicating its efficacy in this challenging patient population.

The treatment had a manageable safety profile, with the most common adverse events being pyrexia and nausea, and 44% of patients experiencing at least one grade 3 or worse adverse event, suggesting that while side effects occurred, they were generally tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin for paediatric relapsed or refractory Hodgkin's lymphoma and anaplastic large-cell lymphoma: a multicentre, open-label, phase 1/2 study. Locatelli, F., Mauz-Koerholz, C., Neville, K., et al.[2019]

In a study of 27 patients with refractory/relapsed peripheral T cell lymphoma (PTCL), brentuximab vedotin (Bv) demonstrated a complete response rate of 40.7%, which improved significantly when combined with chemotherapy.

The main serious side effect observed was neutropenia, particularly in patients receiving Bv with chemotherapy, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in real life, a seven year experience in patients with refractory/relapsed CD30+ T cell lymphoma. Oberic, L., Delzor, F., Protin, C., et al.[2021]

Citations

1. merck.com merck.com/news/mercks-investigational-zilovertamab-vedotin-at-1-75-mg-kg-dose-plus-standard-of-care-showed-promising-antitumor-activity-including-complete-response-rate-in-patients-with-relapsed-refractor/

Merck's Investigational Zilovertamab Vedotin at 1.75 mg/kg ... Zilovertamab vedotin 1.75 mg/kg in combination with R-GemOx achieved a 56.3% objective response rate (ORR) in patients with relapsed or refractory DLBCL.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12442023/

Phase 2 Study of Zilovertamab Vedotin in Participants with ... Zilovertamab vedotin had minimal antitumor activity and manageable safety in participants with previously treated metastatic solid tumors of ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1738/532479/Updated-Results-from-the-Phase-2-Waveline-004

Updated Results from the Phase 2 Waveline-004 Study of ... Summary/Conclusion: After additional follow-up, zilovertamab vedotin continued to demonstrate sustained antitumor activity and manageable safety ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7005

WaveLINE-003: Phase 2/3 trial of zilovertamab vedotin ... Median overall survival was 11.5 mo (ZV 1.5 mg/kg), NR (ZV 1.75 mg/kg), and 7.4 mo (ZV 2.0 mg/kg), with 6-month OS rate of 70.0%, 78.8%, and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10430974/

PHASE 2 WAVELINE-004 STUDY: ZILOVERTAMAB ... Grade 3/4 treatment-related AEs occurred in 16 pts (40%), most commonly (≥10%) neutropenia (7 [18%]), anemia (6 [15%]), and neutrophil count ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05139017

NCT05139017 | A Study of Zilovertamab Vedotin (MK-2140 ... The purpose of this Phase 2/3, randomized, multisite, open-label, dose confirmation, and expansion study is to evaluate the safety, and efficacy of ...

7. onclive.com onclive.com/view/zilovertamab-vedotin-produces-activity-in-heavily-pretreated-r-r-mantle-cell-lymphoma

Zilovertamab Vedotin Produces Activity in Heavily ... Zilovertamab vedotin showed a 40% overall response rate in relapsed/refractory mantle cell lymphoma patients, with 13% achieving complete ...