Zilovertamab Vedotin for Lymphoma

Recruiting at 119 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Hepatitis B antivirals

Must not be taking: Corticosteroids, others

Disqualifiers: Organ transplant, Cardiovascular disease, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to approximately 57 months

223 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called zilovertamab vedotin, an experimental drug for certain B-cell lymphomas, including mantle cell lymphoma (MCL), Richter's transformation lymphoma (RTL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). The goal is to assess the treatment's safety and effectiveness both alone and in combination with other treatments. Participants should have lymphoma that has returned or not responded after at least one or two previous therapies. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot have received certain cancer therapies or radiotherapy shortly before starting the study. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that zilovertamab vedotin is likely to be safe for humans?

Research shows that zilovertamab vedotin has been tested in people with certain B-cell cancers, such as mantle cell lymphoma and follicular lymphoma. Earlier studies examined its safety and tolerability. Most patients did not experience serious side effects. Common mild to moderate side effects included tiredness, nausea, and low blood cell counts.

Since this treatment is currently in the middle phase of testing, earlier results have generally indicated safety. However, researchers continue to monitor for any rare or severe side effects as more participants join the studies. For specific concerns, discussing them with the study team or your doctor is advisable. They can provide information tailored to your health needs. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Unlike the standard treatments for lymphoma, such as chemotherapy or targeted therapies like rituximab, zilovertamab vedotin offers a novel approach by combining an antibody with a potent chemotherapy agent, allowing it to deliver the drug directly to cancer cells. This targeted delivery method aims to minimize damage to healthy cells and potentially reduce side effects. Researchers are excited because zilovertamab vedotin specifically targets a protein on the cancer cell surface, which could lead to more effective treatment outcomes. Additionally, the combination with nemtabrutinib in one of the cohorts introduces a synergistic effect that could enhance the treatment's efficacy against resistant or relapsed forms of lymphoma.

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

Research shows that zilovertamab vedotin holds promise for treating certain B-cell lymphomas, such as mantle cell lymphoma (MCL) and follicular lymphoma (FL). In this trial, participants with relapsed or refractory MCL or FL, whose cancer returned or didn't respond to other treatments, will receive zilovertamab vedotin. This treatment targets a specific pathway involved in cancer growth and has generally been found safe. Studies have reported that many patients' tumors shrank or stopped growing, which is encouraging. Although still under investigation, early results suggest zilovertamab vedotin could benefit those who haven't had success with other treatments. ^{1 2 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 adults with certain B-cell lymphomas (like MCL, RTL, FL, CLL) that have come back or didn't respond after previous treatments. They should be able to perform daily activities with minimal help and not have severe ongoing health issues like infections or heart disease. People who've had recent vaccines, live with HIV/HBV/HCV, or received cancer treatment too close to the study start are excluded.

Inclusion Criteria

I have a relapsed or unresponsive aggressive B-cell cancer as confirmed by a biopsy.

I am HBsAg positive but have been on HBV therapy for 4+ weeks with an undetectable viral load.

My B-cell cancer has returned or didn't respond after 2 treatments and no other options are available.

Exclusion Criteria

My follicular lymphoma has changed into a more aggressive form.

My lymphoma has spread to my brain or spinal cord.

Has received solid organ transplant at any time.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zilovertamab vedotin as monotherapy or in combination every 3 weeks until disease progression or discontinuation

Up to approximately 57 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Zilovertamab vedotin

Trial Overview The trial tests Zilovertamab vedotin alone and combined with Nemtabrutinib in patients divided into groups based on their specific type of lymphoma and prior treatments. The main goal is to see how well these therapies shrink the cancer as judged by independent reviewers using established criteria.

How Is the Trial Designed?

Group I: Cohort E, Relapsed or Refractory FL with 2 Prior Lines of Therapy Experimental Treatment 1 Intervention

Participants will receive either zilovertamab vedotin IV infuison Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.

Group II: Cohort D, Relapsed or Refractory FL and CLL with 2 Prior Lines of Therapy Experimental Treatment 1 Intervention

Participants will receive either zilovertamab vedotin IV infusion Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.

Group III: Cohort C, Relapsed or Refractory MCL with 1 Prior Line of Therapy Experimental Treatment 2 Interventions

Participants will receive zilovertamab vedotin IV infusion at Dose 2 every 3 weeks (Q3W) combined with nemtabrutinib oral dose daily until disease progression or discontinuation.

Group IV: Cohort B, Relapsed or Refractory RT with 1 Prior Line of Therapy Experimental Treatment 1 Intervention

Participants will receive zilovertamab vedotin IV infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.

Group V: Cohort A, Relapsed or Refractory MCL with 2 Prior Lines of Therapy Experimental Treatment 1 Intervention

Participants will receive zilovertamab vedotin intravenous (IV) infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.

Zilovertamab vedotin is already approved in European Union for the following indications:

Approved in European Union as Zilovertamab vedotin for:

• Orphan designation for hematological malignancies

Who Is Running the Clinical Trial?

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 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]

In a study involving 275 patients with various types of lymphomas treated with brentuximab vedotin (BV), CD30 expression levels did not significantly predict the clinical response to the treatment, as response rates were similar regardless of whether CD30 expression was above or below 10%.

The findings suggest that measuring CD30 expression by immunohistochemistry may not be a reliable indicator of the effectiveness of BV in treating relapsed or refractory lymphomas, indicating that other factors may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to Brentuximab Vedotin by CD30 Expression in Non-Hodgkin Lymphoma. Jagadeesh, D., Horwitz, S., Bartlett, NL., et al.[2022]

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]

Brentuximab vedotin (BV) is effective for treating CD30+ lymphomas, including classical Hodgkin lymphoma, but can cause hypersensitivity reactions in about 1.2% of patients, as seen in three reported cases of anaphylaxis.

A successful desensitization protocol allowed safe administration of BV to patients who experienced severe allergic reactions, suggesting that this approach could be a viable option for managing hypersensitivity in patients with relapsed or refractory Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Desensitization to Brentuximab Vedotin after anaphylaxis in refractory Hodgkin's lymphoma. Villarreal-González, RV., González-Díaz, SN., Santos-Fernández, WJ., et al.[2023]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05458297

NCT05458297 | A Study of Zilovertamab Vedotin (MK-2140 ... The purpose of this study is to assess the safety and tolerability of zilovertamab vedotin as monotherapy and in combination in participants with select B-cell ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS7595

waveLINE-006: A phase 2 study of the safety and efficacy ... The waveLINE-006 study (NCT05458297) is designed to investigate safety and efficacy of ZV as monotherapy or in combination with nemtabrutinib in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9429579/

P1231: ZILOVERTAMAB VEDOTIN (MK-2140) FOR THE ... Targeting the ROR1 pathway with zilovertamab vedotin is associated with a tolerable safety profile and promising antitumor activity in pts with relapsed/ ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03833180

NCT03833180 | A Study of Zilovertamab Vedotin (MK-2140 ... The purpose of this study is to evaluate the safety, pharmacokinetics, immunogenicity, and efficacy of zilovertamab vedotin given intravenously (IV) across ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-09449

A Study of Zilovertamab Vedotin (MK-2140) as ... The purpose of this study is to assess the safety and tolerability of zilovertamab vedotin as monotherapy and in combination in participants with select B-cell ...

6. merckclinicaltrials.com merckclinicaltrials.com/trial/nct05458297/

A Study of Zilovertamab Vedotin as Monotherapy and in ... The purpose of this study is to assess the safety and tolerability of zilovertamab vedotin as monotherapy and in combination in participants with select B-cell ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/hon.3164_422

A phase 2 study of zilovertamab vedotin as monotherapy or ... The waveLINE-006 study (NCT05458297) will be conducted to investigate safety and efficacy of ZV in pts with B-cell malignancies, as monotherapy ...