What side effects are associated with this type of intervention?

Common treatments for Non-Hodgkin's Lymphoma, particularly those involving antibody-drug conjugates targeting CD20 like Zilovertamab Vedotin, often include Rituximab combined with chemotherapy agents such as Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP). Known side effects of these treatments can include infusion reactions (fever, chills, and rash), myelosuppression (leading to low blood cell counts and increased infection risk), cardiotoxicity (especially with Doxorubicin), gastrointestinal symptoms (nausea, vomiting, and diarrhea), and general fatigue. Prednisone can also cause hyperglycemia, increased appetite, and mood changes. Monitoring and managing these side effects are crucial for patient safety and treatment efficacy.

What prior FDA approvals exist?

The FDA has approved several treatments for Non-Hodgkin's Lymphoma that target CD20, similar to Zilovertamab Vedotin. Rituximab, an anti-CD20 monoclonal antibody, was one of the first and has been widely used in combination with chemotherapy. Other CD20-targeting monoclonal antibodies include Obinutuzumab and Ofatumumab. Additionally, Polatuzumab Vedotin, an antibody-drug conjugate targeting CD79b, has been approved for use in combination with bendamustine and rituximab for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). These treatments have paved the way for newer therapies like Zilovertamab Vedotin, which combines a monoclonal antibody with a cytotoxic agent to target and kill cancer cells more effectively.

What other types of research exist?

Promising novel alternatives to Zilovertamab Vedotin for Non-Hodgkin's Lymphoma patients in 2024 include: 1) Polatuzumab Vedotin, another antibody-drug conjugate targeting CD79b, which has shown efficacy in combination with bendamustine and rituximab. 2) CAR T-cell therapies such as Axicabtagene Ciloleucel and Tisagenlecleucel, which have demonstrated significant success in relapsed or refractory NHL. 3) Bispecific antibodies like Mosunetuzumab, targeting CD20 and CD3, offering a novel mechanism of action. 4) BTK inhibitors such as Acalabrutinib and Zanubrutinib, which provide targeted therapy options with favorable safety profiles.

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Chemotherapy

Zilovertamab Vedotin + R-CHP for Diffuse Large B-Cell Lymphoma (waveLINE-007 Trial)

Q: What is the mechanism of action of this treatment?

Antibody-drug conjugates (ADCs) like Zilovertamab Vedotin target CD20 on B-cells, combining the specificity of monoclonal antibodies with the cytotoxic potency of chemotherapy. The antibody binds to CD20, is internalized by the cancer cell, and releases the cytotoxic drug to induce cell death. This targeted approach minimizes damage to healthy cells, reducing side effects. Other treatments, such as Rituximab, also target CD20 but work by marking cancer cells for immune system destruction. These mechanisms are crucial for Non-Hodgkin's Lymphoma patients as they offer precision, potential efficacy, and reduced toxicity compared to traditional chemotherapy.

Phase 2

Waitlist Available

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

Has histologically confirmed diagnosis of DLBCL by prior biopsy

Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days prior to the start of study intervention

Must not have

Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL)

Has received a strong inhibitor or inducer of CYP3A4 (including itraconazole, ketoconazole, posaconazole, or voriconazole) within 7 days prior to the start of study intervention or expected requirement for chronic use of a strong CYP3A4 inhibitor until <30 days after the last dose

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 60 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug called zilovertamab vedotin combined with standard chemotherapy in patients with DLBCL who haven't been treated before. The drug targets and kills cancer cells like a guided missile, while the chemotherapy helps to further attack the cancer.

Who is the study for?

This trial is for adults with a confirmed diagnosis of Diffuse Large B-Cell Lymphoma (DLBCL) who haven't been treated before. They should have PET-positive disease and be in good physical condition, meaning they can carry out daily activities with ease or with some limitation. People with certain heart conditions, other cancers within the last 2 years, recent radiotherapy, ongoing high-dose steroids, live vaccines taken recently, strong drug interactions or active infections are excluded.

What is being tested?

The study tests Zilovertamab Vedotin combined with R-CHP (Cyclophosphamide, Doxorubicin, Prednisone plus Rituximab or its biosimilar). It has two parts: first to find a safe dose and then to see how effective this combination is at that dose for treating people newly diagnosed with DLBCL.

What are the potential side effects?

Possible side effects include reactions related to infusion of the drugs like fever and chills; low blood cell counts leading to increased infection risk; nausea; fatigue; nerve damage causing numbness or tingling; hair loss due to chemotherapy agents used.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My diagnosis of DLBCL was confirmed through a biopsy.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I have not received any treatment for DLBCL.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with primary mediastinal B-cell lymphoma.

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I haven't taken strong CYP3A4 inhibitors like itraconazole within the last week.

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I am currently being treated for an infection.

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I have an active hepatitis B infection.

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I have an active lymphoma in my brain or spinal cord.

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I am taking more than 30 mg of corticosteroids daily.

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My slow-growing cancer has changed into aggressive large B-cell lymphoma.

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I have ongoing nerve damage in my hands or feet that affects my daily activities.

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I have an active hepatitis C infection.

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I have had a serious heart condition or stroke in the last 6 months.

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I have fluid around my heart or in my chest.

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I have a type of Charcot-Marie-Tooth disease that affects the nerve covering.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 60 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 60 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 60 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

Complete Response Rate (CRR) per Lugano Response Criteria

Number of Participants Who Discontinued Study Treatment Due to an AE

Number of Participants Who Experienced At Least One AE

+1 more

Secondary study objectives

Duration of Response (DOR) per Lugano Response Criteria

Objective Response Rate (ORR) per Lugano Response Criteria

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Zilovertamab Vedotin + R-CHP: Efficacy ExpansionExperimental Treatment7 Interventions

Participants in the efficacy expansion phase receive the RP2D of zilovertamab vedotin plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months).

Group II: Zilovertamab Vedotin + R-CHP: Dose Escalation/ConfirmationExperimental Treatment7 Interventions

Participants in the dose escalation/confirmation phase receive a dose level of zilovertamab vedotin (from 1.5 mg/Kg up to 2.5 mg/Kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

2010

Completed Phase 4

~2310

Prednisone

2014

Completed Phase 4

~2500

Rituximab

1999

Completed Phase 4

~2990

Prednisolone

2005

Completed Phase 4

~3570

Doxorubicin

2012

Completed Phase 3

~8030

0 / 15Eligibility criteria met

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 target CD20 on B-cells, combining the specificity of monoclonal antibodies with the cytotoxic potency of chemotherapy. The antibody binds to CD20, is internalized by the cancer cell, and releases the cytotoxic drug to induce cell death. This targeted approach minimizes damage to healthy cells, reducing side effects. Other treatments, such as Rituximab, also target CD20 but work by marking cancer cells for immune system destruction. These mechanisms are crucial for Non-Hodgkin's Lymphoma patients as they offer precision, potential efficacy, and reduced toxicity compared to traditional chemotherapy.