Zilovertamab Vedotin for Pediatric and Young Adult Cancers

Recruiting at 78 trial locations

Overseen By Toll Free Number

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Corticosteroids, CYP3A4 inhibitors

Disqualifiers: Organ transplant, Cardiovascular disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to approximately 60 months

90 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 children and young adults with certain cancers that haven't responded to other treatments. The focus is on B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, Burkitt lymphoma, neuroblastoma, and Ewing sarcoma. Participants will receive this treatment through an IV once every three weeks. This trial suits those diagnosed with one of these cancers who have not had a solid organ transplant or active heart disease. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications like strong CYP3A4 inhibitors or inducers, and ongoing corticosteroid therapy must be stable and below a certain dose. 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 pediatric and young adult participants?

Research has shown that zilovertamab vedotin has undergone safety testing in several clinical trials. These studies administered the treatment to individuals with various cancers, including solid tumors and lymphoma. Most participants tolerated the treatment well, though some experienced side effects.

Common side effects included tiredness, nausea, and low blood cell counts. Serious side effects occurred less frequently and were closely monitored by doctors. The trials aim to determine the optimal dose that balances safety and effectiveness.

As this trial is in the early stages, researchers are still assessing the treatment's safety in children and young adults. However, testing in these groups suggests some confidence in its safety based on earlier studies in adults. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for pediatric and young adult cancers?

Zilovertamab vedotin is unique because it combines a targeted approach with a potent delivery system. Unlike traditional chemotherapy, which attacks both cancerous and healthy cells, zilovertamab vedotin is an antibody-drug conjugate. This means it specifically targets cancer cells with zilovertamab, delivering a powerful chemotherapy agent directly to them and minimizing damage to healthy cells. Researchers are excited about this treatment because this targeted action could potentially increase effectiveness and reduce side effects compared to standard treatments like broad-spectrum chemotherapies.

What evidence suggests that zilovertamab vedotin might be an effective treatment for pediatric and young adult cancers?

Research has shown that zilovertamab vedotin, the investigational treatment in this trial, could be promising for treating certain cancers. Studies have found that this treatment might help children with relapsed or hard-to-treat B-cell acute lymphoblastic leukemia (B-ALL) and some types of lymphoma. It targets cancer cells with a specific marker and delivers a toxin to kill them. Early results suggest that zilovertamab vedotin is generally safe and might help shrink tumors. While more research is needed, initial signs indicate it could benefit these challenging cancers. ^{1 2 3 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 young people with certain blood cancers or solid tumors, like B-cell acute lymphoblastic leukemia, Burkitt lymphoma, diffuse large B-cell lymphoma, neuroblastoma, and Ewing sarcoma. Participants must have tried other treatments that didn't work (relapsed) or didn't respond to previous treatments (refractory).

Inclusion Criteria

I have been diagnosed with a specific type of blood cancer.

My cancer is either neuroblastoma or Ewing sarcoma.

Exclusion Criteria

I have had a solid organ transplant.

I have an active heart condition.

I have been diagnosed with a demyelinating form of Charcot-Marie-Tooth disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of zilovertamab vedotin via intravenous (IV) infusion on Day 1 of each 21-day cycle

Up to approximately 60 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Zilovertamab Vedotin

Trial Overview The study tests zilovertamab vedotin's effectiveness and safety in children and young adults. It's a targeted therapy aimed at treating specific types of cancer by delivering a toxin directly to the cancer cells.

How Is the Trial Designed?

Group I: Zilovertamab vedotin Experimental Treatment 1 Intervention

Participants receive escalating doses of zilovertamab vedotin via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks).

Zilovertamab Vedotin is already approved in European Union, United States for the following indications:

Approved in European Union as Zilovertamab Vedotin for:

• Mantle-cell lymphoma

Approved in United States as Zilovertamab Vedotin for:

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 120 women with locally advanced breast cancer, adding zoledronic acid (ZOL) to neoadjuvant chemotherapy did not improve overall clinical outcomes, such as time to recurrence or survival rates, compared to chemotherapy alone.

However, younger ER+/HER2- patients treated with ZOL experienced significantly worse time to recurrence and trends towards poorer survival outcomes, indicating that ZOL may not be safe for this specific group and highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of (neo)adjuvant zoledronic acid therapy in locally advanced breast cancer. Jallouk, AP., Paravastu, S., Weilbaecher, K., et al.[2022]

In a study of 28,385 patients with solid tumors or multiple myeloma, treatment with zoledronic acid (ZOL) significantly reduced the incidence of skeletal complications, including a 24% reduction in fractures and a 45% reduction in spinal cord compression.

Patients who continued ZOL treatment for more than 180 days experienced better outcomes, including a 56% reduction in mortality risk, with the most significant benefits seen in those treated regularly for over 18 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the clinical benefit of long-term (beyond 2 years) treatment of skeletal-related events in advanced cancers with zoledronic acid. Henk, H., Teitelbaum, A., Kaura, S.[2018]

Monepantel, a veterinary drug, was tested in a Phase I trial for its potential anticancer effects in adults with hard-to-treat solid tumors, showing some preliminary signs of efficacy by reducing mTOR pathway markers in blood cells.

While the drug was generally well-tolerated at the lowest dose of 5 mg/kg, gastrointestinal side effects were common, leading to concerns about its palatability and suggesting the need for reformulation to improve patient experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preliminary assessment of oral monepantel's tolerability and pharmacokinetics in individuals with treatment-refractory solid tumors. Mislang, A., Mollard, R., Tapia Rico, G., et al.[2021]

The study established a safe dose recommendation (SDR) of 130 mg/m2/day for vorinostat in children with relapsed or therapy-refractory malignancies, with a maximum tolerated dose (MTD) reaching up to 580 mg/m2/day.

Higher doses of vorinostat were associated with better treatment responses and prolonged disease control, while most treatment-related side effects were manageable and reversible, indicating a potential for effective use in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma, or leukemia. van Tilburg, CM., Milde, T., Witt, R., et al.[2020]

In a study of 16 pediatric patients with Hodgkin lymphoma, brentuximab vedotin showed significant pharmacokinetic variability primarily influenced by the patients' weight, accounting for over 60% of the variability.

The drug's exposure levels (AUC and C max) were lower in children compared to adults, but the treatment was found to be safe and tolerable, with no development of anti-therapeutic antibodies during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, immunogenicity, and safety of weekly dosing of brentuximab vedotin in pediatric patients with Hodgkin lymphoma. Flerlage, JE., Metzger, ML., Wu, J., et al.[2019]

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]

The antibody-drug conjugate tisotumab vedotin (TV) has been shown to significantly increase the probability of objective response in patients with recurrent or metastatic cervical cancer as the maximum serum concentration (Cmax) increases, indicating its efficacy in treatment.

However, higher exposure levels of TV are also associated with an increased risk of treatment-related adverse events, particularly ocular side effects, suggesting a need for careful monitoring of dosage to balance efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-safety and exposure-efficacy analyses for tisotumab vedotin for patients with locally advanced or metastatic solid tumors. Passey, C., Voellinger, J., Gibiansky, L., et al.[2023]

Zoledronic acid (ZOL) has shown potential anticancer activity across various cancer types, with evidence from clinical trials indicating survival benefits for patients with advanced cancers.

In early breast cancer patients, ZOL not only improves disease-free survival but also reduces the presence of tumor cells and decreases the size of residual invasive tumors, suggesting it may have significant clinical benefits beyond its role in preventing skeletal-related events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticancer evidence for zoledronic acid across the cancer continuum. Costa, L., Harper, P., Coleman, RE., et al.[2018]

Zoledronic acid (ZOL) significantly inhibits the growth of non-small-cell lung cancer (NSCLC) cells in vitro and in vivo, demonstrating a dose-dependent effect that prolongs survival in treated mice.

ZOL induces cell-cycle arrest at the S/G2/M-phase without causing apoptosis, suggesting it may be a promising therapeutic strategy when combined with chemotherapy or radiotherapy for treating NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zoledronic acid is unable to induce apoptosis, but slows tumor growth and prolongs survival for non-small-cell lung cancers. Li, YY., Chang, JW., Chou, WC., et al.[2021]

In a study of 39 patients treated with brentuximab vedotin (BV) at a French university hospital, over half (51.3%) experienced significant adverse drug reactions (ADRs), with 50% of these being severe.

The most common ADRs included peripheral sensory neuropathy and CMV reactivation, leading to drug discontinuation in 4 patients and dose reductions in 6, highlighting the need for better monitoring of BV's safety in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions related to brentuximab vedotin use: A real-life retrospective study. Clarivet, B., Vincent, L., Vergely, L., et al.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS10075

Phase 1/2 study of zilovertamab vedotin in pediatric and ... The study consists of 2 parts: dose escalation and confirmation (part 1) and efficacy expansion (part 2). Part 1 will enroll 3-12 pts per dose ...

2. 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 ...

3. merckclinicaltrials.com merckclinicaltrials.com/trial/nct06395103/

Substudy 01A: Zilovertamab Vedotin in Pediatric and Young ... The purpose of this study is to assess the efficacy and safety of zilovertamab vedotin in pediatric participants with relapsed or refractory B-cell acute ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04504916

A Study of Zilovertamab Vedotin (MK-2140/VLS-101) in ... This is a study evaluating the efficacy, safety, and pharmacokinetics of zilovertamab vedotin in participants with metastatic solid tumors including ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12442023/

Phase 2 Study of Zilovertamab Vedotin in Participants with ... Zilovertamab vedotin had minimal antitumor activity and manageable safety in participants with previously treated metastatic solid tumors of ...

6. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT119/761484/Abstract-CT119-Zilovertamab-vedotin-in-pediatric

Abstract CT119: Zilovertamab vedotin in pediatric and young ... A single-arm, open-label, phase 1/2 basket study designed to determine the preliminary recommended phase 2 dose (RP2D), safety, and antitumor activity of ZV in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06890884

NCT06890884 | A Clinical Study of Zilovertamab Vedotin ... GCB is a type of DLBCL that affects young B-cells that are still maturing. The goal of this study is to learn if more people who receive zilovertamab vedotin ( ...