Zilovertamab Vedotin for Lymphoma

No longer recruiting at 25 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: VelosBio Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Must not be taking: Corticosteroids, CYP3A4 inhibitors

Disqualifiers: CNS malignancy, Cardiovascular disease, Infections, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 3.5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, zilovertamab vedotin (also known as VLS-101 or MK-2140), to determine its safety and effectiveness for people with certain blood cancers that have returned or worsened after treatment. The researchers aim to understand how the body processes the drug and any potential immune reactions. The study includes various blood cancer types, such as leukemia and lymphoma, and participants will receive the drug through an IV. Individuals with these cancers, whose conditions have not responded well to other treatments, might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use certain drugs like strong CYP3A4 inhibitors or inducers, or drugs that prolong the QT interval within 7 days before starting the study. If you're on corticosteroids, the dose must be stable or adjusted as specified.

Is there any evidence suggesting that zilovertamab vedotin is likely to be safe for humans?

Research has shown that zilovertamab vedotin is generally safe for patients, with most tolerating the treatment well. In one study, patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) had a 56.3% positive response rate when treated with zilovertamab vedotin alongside other standard treatments. This indicates the treatment can be effective without causing serious side effects. Although these results are promising, the current study is in an early phase, primarily testing safety at different doses. More detailed safety information will emerge as the study progresses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about zilovertamab vedotin because it introduces a novel approach to treating hematologic malignancies. Unlike standard therapies that often target broader cell types, zilovertamab vedotin is an antibody-drug conjugate designed to specifically target a protein called ROR1, which is commonly found on the surface of cancer cells. This targeted mechanism aims to deliver chemotherapy directly to cancer cells, potentially reducing harm to healthy cells and minimizing side effects. Additionally, the drug's ability to be administered in different dosing schedules offers flexibility that could improve patient outcomes and quality of life.

What evidence suggests that zilovertamab vedotin might be an effective treatment for hematological cancers?

Research has shown that zilovertamab vedotin yields promising results for treating certain blood cancers. In patients with relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL), the treatment proved effective in 56.3% of cases when combined with a standard therapy. For mantle cell lymphoma, 40% of patients responded to the treatment, with 13% experiencing a complete disappearance of cancer. Early findings also suggest it may benefit those unable to undergo intense treatments like stem cell transplants. This trial will explore different dosing schedules of zilovertamab vedotin, offering hope for addressing these challenging conditions. ^{1 2 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

Adults (≥18 years) with certain types of blood cancers that have progressed after treatment can join this trial. They must have measurable cancer, resolved side effects from previous treatments, and proper organ function. Pregnant or breastfeeding individuals, those with significant heart disease, CNS malignancies, uncontrolled infections, liver cirrhosis, or recent major surgery cannot participate.

Inclusion Criteria

You have a type of blood cancer that has been treated in the past but has gotten worse or come back after treatment.

You currently need medical treatment because of symptoms or complications caused by your disease, low blood cell counts, enlarged lymph nodes or organs, involvement of organs outside of lymph nodes, or your disease is getting worse over time.

Presence of measurable cancer including CLL/SLL, MCL, FL, MZL, DLBCL, RTL, BL, LPL/WM, T-cell NHL, ALL, and AML

Exclusion Criteria

You have had a serious heart condition in the last 3 months before starting the study treatment.

Presence of malignancy involving the central nervous system

Significant screening electrocardiogram (ECG) abnormalities

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 intravenously on a schedule of repeated 21-day cycles

Up to 3.5 years

Day 1, 8, 15 of each cycle

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 is testing Zilovertamab vedotin given intravenously to people with various hematological cancers like leukemia and lymphoma. It aims to assess the drug's safety and effectiveness at different doses in patients who've had prior treatments but need more due to progressing disease.

How Is the Trial Designed?

Group I: Zilovertamab vedotin Schedule 3: Q3/4W Experimental Treatment 1 Intervention

Participants will be administered escalating doses of zilovertamab vedotin at 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, and 2.25 mg/kg IV on Day 1, 8, and 15 of repeated 21-day cycles (Q3/4W).

Group II: Zilovertamab vedotin Schedule 2: Q2/3W Experimental Treatment 1 Intervention

Participants will be administered escalating doses of zilovertamab vedotin at 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, and 2.25 mg/kg IV on Day 1 and 8 of repeated 21-day cycles (Q2/3W).

Group III: Zilovertamab vedotin Schedule 1: Q1/3W Experimental Treatment 1 Intervention

Participants will be administered escalating doses of zilovertamab vedotin at 0.50, 1.00, 1.50, 2.25, 2.50, 2.75, and 3.00 mg/kg IV on Day 1 of repeated 21-day cycles (Q1/3W).

Zilovertamab vedotin is already approved in European Union for the following indications:

Approved in European Union as Zilovertamab vedotin for:

• Orphan designation for hematological malignancies

Who Is Running the Clinical Trial?

VelosBio Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Lead Sponsor

Trials

2

Recruited

190+

VelosBio Inc.

Lead Sponsor

Trials

2

Recruited

190+

Published Research Related to This Trial

Polatuzumab vedotin, an antibody-drug conjugate, demonstrated an acceptable safety profile in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL), with a recommended phase 2 dose of 2.4 mg/kg showing objective responses in 23 out of 42 evaluable patients.

In contrast, the treatment was not effective for patients with chronic lymphocytic leukaemia (CLL), as no objective responses were observed, highlighting the need for further assessment of polatuzumab vedotin specifically in NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Palanca-Wessels, MC., Czuczman, M., Salles, G., et al.[2018]

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 is an antibody-drug conjugate that combines an anti-CD30 antibody with a powerful cytotoxic agent, showing promise in treating Hodgkin lymphoma and anaplastic large cell lymphoma.

The drug is currently under investigation in North America and Europe, highlighting its potential as a targeted therapy for specific types of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin. [2021]

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) 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40762544/

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 ...

2. merck.com merck.com/news/mercks-investigational-zilovertamab-vedotin-at-1-75-mg-kg-dose-plus-standard-of-care-showed-promising-antitumor-activity-including-complete-response-rate-in-patients-with-relapsed-refractor/

Merck's Investigational Zilovertamab Vedotin at 1.75 mg/kg ... Zilovertamab vedotin 1.75 mg/kg in combination with R-GemOx achieved a 56.3% objective response rate (ORR) in patients with relapsed or refractory DLBCL.

3. 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 ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.7531

Zilovertamab vedotin (MK 2140) in relapsed/refractory (R/R ... Early results show that ZV had clinically meaningful antitumor activity in pts with R/R DLBCL who progressed after or have been ineligible for ASCT and/or CAR- ...

5. onclive.com onclive.com/view/zilovertamab-vedotin-produces-activity-in-heavily-pretreated-r-r-mantle-cell-lymphoma

Zilovertamab Vedotin Produces Activity in Heavily ... Zilovertamab vedotin showed a 40% overall response rate in relapsed/refractory mantle cell lymphoma patients, with 13% achieving complete ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9429579/

P1231: ZILOVERTAMAB VEDOTIN (MK-2140) FOR THE ... Targeting the ROR1 pathway with zilovertamab vedotin is associated with a tolerable safety profile and promising antitumor activity in pts with relapsed/ ...

7. medchemexpress.com medchemexpress.com/zilovertamab-vedotin.html?srsltid=AfmBOoqEsgTchi8y5mYWl7OutT0IhYXWTcE3nwUIktN4ZFyc8okES6By

Zilovertamab vedotin (VLS-101) | Antibody-Drug Conjugate Zilovertamab vedotin. Inquiry Online. Your information is safe with us. ... SAFETY DATA SHEET (SDS). English - EN (251 KB) Français - FR (251 KB) Deutsch ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS7592

Open-label, active-control, phase 2/3 study of zilovertamab ... Open-label, active-control, phase 2/3 study of zilovertamab vedotin plus standard of care in patients with relapsed or refractory diffuse large ...