Zilovertamab Vedotin for Lymphoma

Recruiting at 104 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called zilovertamab vedotin to see if it can help treat certain blood cancers that have not responded to other treatments. The drug works by targeting and killing cancer cells using a combination of an antibody and a drug.

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.

What makes the drug Zilovertamab vedotin unique for treating lymphoma?

Zilovertamab vedotin is unique because it combines an antibody that targets specific cancer cells with a drug that kills those cells, similar to brentuximab vedotin, but it targets a different protein on the cancer cells, potentially offering a new option for patients who do not respond to other treatments. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Zilovertamab vedotin (Monoclonal Antibodies)

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.

Participant Groups

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.

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

Findings from Research

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 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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in real life, a seven year experience in patients with refractory/relapsed CD30+ T cell lymphoma. [2021]

2. England 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. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Response to Brentuximab Vedotin by CD30 Expression in Non-Hodgkin Lymphoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Desensitization to Brentuximab Vedotin after anaphylaxis in refractory Hodgkin's lymphoma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

New uses for brentuximab vedotin and novel antibody drug conjugates in lymphoma. [2019]