What is the mechanism of action of this treatment?

Antibody-drug conjugates (ADCs) like zilovertamab vedotin, which targets ROR1, are designed to deliver cytotoxic agents directly to lymphoma cells, thereby increasing treatment efficacy and minimizing damage to healthy cells. This targeted approach is crucial for lymphoma patients as it aims to reduce side effects while effectively killing cancer cells. Other common treatments include Bruton's tyrosine kinase inhibitors (BTKis) that block growth-promoting signals in cancer cells, and chimeric antigen receptor T-cell (CAR-T) therapy, which modifies a patient's T-cells to specifically attack cancer cells. These therapies offer more personalized and potentially more effective treatment options for lymphoma patients.

What side effects are associated with this type of intervention?

Common treatments for lymphoma, particularly those involving antibody-drug conjugates like Zilovertamab Vedotin, often have side effects such as neutropenia, peripheral neuropathy, fatigue, and gastrointestinal issues (e.g., nausea, diarrhea). Other targeted therapies for B-cell malignancies, such as Bruton's tyrosine kinase inhibitors (BTKi) and CAR-T cell therapies, can also cause infections, cytopenias, and infusion-related reactions. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

Several antibody-drug conjugates (ADCs) have been approved by the FDA for the treatment of lymphoma. Notably, Polatuzumab Vedotin, an ADC targeting CD79B, has been approved for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Another example is Brentuximab Vedotin, which targets CD30 and is approved for Hodgkin lymphoma and systemic anaplastic large cell lymphoma. These ADCs, like Zilovertamab Vedotin targeting ROR1, combine the specificity of monoclonal antibodies with the cytotoxic potency of chemotherapy, offering targeted treatment options for lymphoma patients.

What other types of research exist?

Promising novel alternatives to Zilovertamab Vedotin for lymphoma patients in 2024 include: 1) BTK inhibitors like Acalabrutinib and Zanubrutinib, which have shown efficacy and better tolerability in CLL and MCL. 2) Venetoclax, particularly in combination with Obinutuzumab, which has demonstrated significant improvements in progression-free survival in CLL. 3) RET inhibitors such as Selpercatinib and Pralsetinib, which are being explored for their efficacy in various malignancies, including lymphomas. 4) Anti-CD20 monoclonal antibodies like Rituximab, often used in combination with other agents for enhanced efficacy. These alternatives offer different mechanisms of action and have shown promising results in clinical trials.

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Monoclonal Antibodies

Zilovertamab Vedotin for Lymphoma

Phase 2

Recruiting

Research Sponsored by Merck Sharp & Dohme LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 57 months

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While not all side effects are listed here, participants may experience symptoms related to nerve damage (like numbness), reactions at the infusion site, fatigue, digestive problems such as nausea or diarrhea, blood disorders including low counts leading to increased infection risk.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 57 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 57 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 57 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

ORR per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as Assessed by Investigator in Participants with CLL

ORR per Lugano Response Criteria as Assessed by Investigator in Participants with MCL (Cohort C)

Objective Response Rate (ORR) per Lugano Response Criteria as Assessed by Blinded Independent Central Review (BICR) in Participants with MCL (Cohort A), RT, and FL (Cohorts D & E)

+3 more

Secondary study objectives

DOR per Lugano Response Criteria as Assessed by Investigator in Participants with MCL (Cohort C)

DOR per iwCLL Criteria as Assessed by Investigator in Participants with CLL

Duration of Response (DOR) per Lugano Response Criteria as Assessed by BICR in Participants with MCL (Cohort A), RT, and FL (Cohorts D & E)

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: Cohort E, Relapsed or Refractory FL with 2 Prior Lines of TherapyExperimental Treatment1 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 TherapyExperimental Treatment1 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 TherapyExperimental Treatment2 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 TherapyExperimental Treatment1 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 TherapyExperimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Zilovertamab vedotin

2019

Completed Phase 1

~100

Nemtabrutinib

2023

Completed Phase 1

~100

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Antibody-drug conjugates (ADCs) like zilovertamab vedotin, which targets ROR1, are designed to deliver cytotoxic agents directly to lymphoma cells, thereby increasing treatment efficacy and minimizing damage to healthy cells. This targeted approach is crucial for lymphoma patients as it aims to reduce side effects while effectively killing cancer cells. Other common treatments include Bruton's tyrosine kinase inhibitors (BTKis) that block growth-promoting signals in cancer cells, and chimeric antigen receptor T-cell (CAR-T) therapy, which modifies a patient's T-cells to specifically attack cancer cells. These therapies offer more personalized and potentially more effective treatment options for lymphoma patients.

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Who is running the clinical trial?

Merck Sharp & Dohme LLCLead Sponsor

4,015 Previous Clinical Trials

5,186,110 Total Patients Enrolled

Medical DirectorStudy DirectorMerck Sharp & Dohme LLC

2,889 Previous Clinical Trials

8,088,970 Total Patients Enrolled

Media Library

Zilovertamab vedotin (Monoclonal Antibodies) Clinical Trial Eligibility Overview. Trial Name: NCT05458297 — Phase 2

$Chronic Lymphocytic Leukemia Research Study Groups: Cohort A, Relapsed or Refractory MCL with 2 Prior Lines of Therapy, Cohort B, Relapsed or Refractory RT with 1 Prior Line of Therapy, Cohort C, Relapsed or Refractory MCL with 1 Prior Line of Therapy, Cohort D, Relapsed or Refractory FL and CLL with 2 Prior Lines of Therapy, Cohort E, Relapsed or Refractory FL with 2 Prior Lines of Therapy$