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

NCT ID: NCT03833180

Last Updated: 2024-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

91 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-14

Study Completion Date

2023-12-18

Brief Summary

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The purpose of this study is to evaluate the safety, pharmacokinetics, immunogenicity, and efficacy of zilovertamab vedotin given intravenously (IV) across a range of dose levels in participants with previously treated hematological cancers including acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), Burkitt lymphoma (BL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), Richter transformation lymphoma (RTL), and T-cell non-Hodgkin lymphoma (NHL).

Detailed Description

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Conditions

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Chronic Lymphocytic Leukemia Mantle Cell Lymphoma Follicular Lymphoma Marginal Zone Lymphoma Diffuse Large B-cell Lymphoma Richter Transformation Lymphoma Burkitt Lymphoma Lymphoplasmacytoid Lymphoma T-cell Non-Hodgkin Lymphoma Acute Lymphoid Leukemia Acute Myeloid Leukemia Waldenstrom Macroglobulinemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels within each dose schedule of zilovertamab vedotin using a 3+3 dose-escalation design.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Zilovertamab vedotin Schedule 1: Q1/3W

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).

Group Type EXPERIMENTAL

Zilovertamab vedotin

Intervention Type DRUG

Zilovertamab vedotin administered via IV infusion per Schedule 1, 2, or 3 according to participant allocation.

Zilovertamab vedotin Schedule 2: Q2/3W

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 Type EXPERIMENTAL

Zilovertamab vedotin

Intervention Type DRUG

Zilovertamab vedotin administered via IV infusion per Schedule 1, 2, or 3 according to participant allocation.

Zilovertamab vedotin Schedule 3: Q3/4W

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 Type EXPERIMENTAL

Zilovertamab vedotin

Intervention Type DRUG

Zilovertamab vedotin administered via IV infusion per Schedule 1, 2, or 3 according to participant allocation.

Interventions

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Zilovertamab vedotin

Zilovertamab vedotin administered via IV infusion per Schedule 1, 2, or 3 according to participant allocation.

Intervention Type DRUG

Other Intervention Names

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VLS-101 MK-2140

Eligibility Criteria

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Inclusion Criteria

* Men or women of age ≥18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
* Histological diagnosis of CLL/SLL, MCL, FL, MZL, DLBCL, RTL, BL, LPL/WM, T-cell NHL, ALL, or AML as documented in medical records.
* Hematological cancer under study has been previously treated and has progressed during or relapsed after prior systemic therapy.
* Hematological cancer is unlikely to be responsive to established therapies known to provide clinical benefit or the study candidate has developed an intolerance to established therapies known to provide clinical benefit.
* Presence of measurable cancer including CLL/SLL, MCL, FL, MZL, DLBCL, RTL, BL, LPL/WM, T-cell NHL, ALL, and AML.
* Current medical need for therapy due to disease-related symptoms or complications, cytopenias, lymphadenopathy, organomegaly, extranodal organ involvement, or progressive disease.
* Availability of pretreatment tumor tissue.
* Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥1 week before the start of study therapy.
* All acute toxic effects of any prior antitumor therapy (not including hydroxyurea, cytarabine, and/or cyclophosphamide used in subjects with acute leukemia) resolved to ≤Grade 1 before the start of study therapy (with the exception of alopecia \[Grade 1 or 2 permitted\] or selected laboratory parameters \[Grade 1 or Grade 2 permitted with exceptions.
* Adequate bone marrow function.
* Adequate hepatic profile.
* Adequate renal function.
* Adequate coagulation profile.
* Negative antiviral serology.
* For female participants of childbearing potential, a negative serum pregnancy test.
* For both male and female participants, willingness to use protocol-recommended method of contraception from the start of the screening period until ≥6 months after the final dose of study therapy.
* Willingness and ability of the participant to comply with study activities.
* Evidence of a personally signed informed consent document.
* Previous treatment with an MMAE-containing drug is allowed.

Exclusion Criteria

* Presence of malignancy involving the central nervous system.
* Presence of another cancer with disease manifestations or therapy that could adversely affect participant safety or longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results.
* Significant cardiovascular disease within 3 months prior to start of study therapy.
* Significant screening electrocardiogram (ECG) abnormalities.
* Uncontrolled ongoing systemic bacterial, fungal, or viral infection.
* Known diagnosis of liver cirrhosis.
* Pregnancy or breastfeeding.
* Candidacy for hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor (CAR)-T-cell therapy with access to HSCT or CAR-T cells and a willingness to undergo such therapy.
* In participants with prior HSCT, evidence of graft-versus-host disease (GVHD) with Grade ≥2 serum bilirubin, Grade ≥3 skin involvement, or Grade ≥3 diarrhea.
* Prior solid organ transplantation.
* Major surgery within 4 weeks before the start of study therapy.
* Prior therapy with a receptor tyrosine kinase-like orphan receptor 1 (ROR1)-directed therapy.
* Has ongoing corticosteroid therapy (exceeding 30 mg daily of prednisone equivalent). Prednisone equivalent dosing must have been stable for at least 4 weeks prior to Cycle 1 Day 1 (C1D1). If corticosteroid treatment is required for lymphoma symptom control prior to C1D1, up to 100 mg per day of prednisone equivalent can be given for up to 5 days. In that case, all tumor assessments must have been completed prior to the start of corticosteroid treatment.
* Use of a strong inhibitor or inducer of cytochrome P450 (CYP) 3A4.
* Use within 7 days prior to the start of study therapy of a drug known to prolong the QT interval.
* Concurrent participation in another therapeutic or imaging clinical trial.
* Presence of a medical condition that (in the judgement of the investigator) interferes with the ability of the participant to participate in the study.
* Has baseline peripheral neuropathy \>Grade 1.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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City of Hope ( Site 0010)

Duarte, California, United States

Site Status

University of California - San Diego ( Site 0003)

La Jolla, California, United States

Site Status

UCLA Hematology & Oncology ( Site 0007)

Los Angeles, California, United States

Site Status

University of Nebraska Medical Center ( Site 0006)

Omaha, Nebraska, United States

Site Status

Northwell Health ( Site 0009)

New Hyde Park, New York, United States

Site Status

Weill Cornell Medical College ( Site 0005)

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center ( Site 0014)

New York, New York, United States

Site Status

University of Rochester ( Site 0008)

Rochester, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center ( Site 0019)

Uniondale, New York, United States

Site Status

Oregon Health & Science University ( Site 0004)

Portland, Oregon, United States

Site Status

MD Anderson Cancer Center ( Site 0001)

Houston, Texas, United States

Site Status

MD Anderson Cancer Center ( Site 0011)

Houston, Texas, United States

Site Status

University of Virginia Cancer Center ( Site 0012)

Charlottesville, Virginia, United States

Site Status

Swedish Medical Center ( Site 0002)

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Wang ML, Barrientos JC, Furman RR, Mei M, Barr PM, Choi MY, de Vos S, Kallam A, Patel K, Kipps TJ, Rule S, Flanders K, Jessen KA, Ren H, Riebling PC, Graham P, King L, Thurston AW, Sun M, Schmidt EM, Lannutti BJ, Johnson DM, Miller LL, Spurgeon SE. Zilovertamab Vedotin Targeting of ROR1 as Therapy for Lymphoid Cancers. NEJM Evid. 2022 Jan;1(1):EVIDoa2100001. doi: 10.1056/EVIDoa2100001. Epub 2021 Oct 12.

Reference Type RESULT
PMID: 38319241 (View on PubMed)

Kipps TJ. Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia. Cancer J. 2021 Jul-Aug 01;27(4):306-313. doi: 10.1097/PPO.0000000000000536.

Reference Type DERIVED
PMID: 34398557 (View on PubMed)

Related Links

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https://merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

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VLS-101-0001

Identifier Type: OTHER

Identifier Source: secondary_id

2140-001

Identifier Type: -

Identifier Source: org_study_id

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