Zilovertamab Vedotin for Lymphoma

Recruiting at 71 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

140 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate zilovertamab vedotin with respect to objective response rate and duration of response per Lugano Response Criteria as assessed by blinded independent central review (BICR). Safety and tolerability will also be evaluated in this Phase 2, single arm, interventional study.

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.

What data supports the effectiveness of the drug zilovertamab vedotin for lymphoma?

Zilovertamab vedotin is similar to other drugs like polatuzumab vedotin and brentuximab vedotin, which have shown effectiveness in treating certain types of lymphoma. These drugs work by targeting specific proteins on cancer cells and delivering a toxic substance to kill them, and have been effective in treating relapsed or refractory lymphomas. ^{1 2 3 4 5}

What makes the drug zilovertamab vedotin unique for treating lymphoma?

Zilovertamab vedotin is unique because it is an antibody-drug conjugate (ADC) that targets specific proteins on lymphoma cells, similar to other ADCs like polatuzumab vedotin and brentuximab vedotin, but it may target different proteins or use a different mechanism to deliver its cancer-killing agent. This targeted approach can potentially offer more effective treatment with fewer side effects compared to traditional chemotherapy. ^{1 3 6 7 8}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real-world study. [2021]

3. 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]

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

Brentuximab vedotin in CD30+ primary cutaneous T-cell lymphomas: a review and analysis of existing data. [2019]

5. England 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. [2019]

6. England pubmed.ncbi.nlm.nih.gov

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

7. 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]

8. France pubmed.ncbi.nlm.nih.gov

[Brentuximab vedotin: new treatment for CD30+ lymphomas]. [2019]