A Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Hematologic Malignancies (MK-2140-001)

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

91 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called zilovertamab vedotin, which is given through a drip. It is aimed at patients with different types of blood cancers who have already tried other treatments. The medication works by attaching to cancer cells and delivering a substance that helps to destroy them.

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.

How is the drug Zilovertamab vedotin different from other treatments?

Zilovertamab vedotin is unique because it is an antibody-drug conjugate, which means it combines an antibody with a drug to specifically target and kill cancer cells. This approach is similar to other drugs like polatuzumab vedotin and brentuximab vedotin, which also use this targeted method to treat certain types of lymphoma. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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) 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 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, 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]

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

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

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. New Zealand pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin. [2021]

5. England 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. [2018]