A Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Hematologic Malignancies (MK-2140-001)
A Phase 1 Dose-Escalation and Cohort-Expansion Study of VLS-101 in Subjects With Hematological Malignancies (waveLINE-001)
2 other identifiers
interventional
91
1 country
14
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2019
Longer than P75 for phase_1
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 4, 2019
CompletedFirst Posted
Study publicly available on registry
February 6, 2019
CompletedStudy Start
First participant enrolled
March 14, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 18, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 18, 2023
CompletedJanuary 12, 2024
January 1, 2024
4.8 years
February 4, 2019
January 11, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose (MTD) of zilovertamab vedotin
Participants will receive zilovertamab vedotin according to Schedule 1, 2, or 3. The MTD will be determined by the number of participants who experience a dose limiting toxicity (DLT). The MTD will be defined as the highest tested dose level at which ≥6 participants have been treated and which is associated with a Cycle 1 DLT in ≤17% of the participants.
Cycle 1 (Up to 21 Days)
Recommended Dosing Regimen (RDR)
Selection of the RDR will be based on consideration of short- and long-term safety information together with available pharmacokinetic, pharmacodynamic, and efficacy data. The RDR may be the MTD or may be a lower dose within the tolerable dose range.
Cycle 1 (Up to 21 Days)
Secondary Outcomes (37)
Average number of zilovertamab vedotin infusions administered
Up to 5 months
Number of participants with a treatment-emergent adverse event (TEAE)
Up to approximately 3.5 years
Number of participants with a DLT
Cycle 1 (Up to 21 Days)
Number of participants with a serious adverse event (SAE)
Up to approximately 3.5 years
Number of participants with an adverse event of special interest (AESI)
Up to approximately 3.5 years
- +32 more secondary outcomes
Study Arms (3)
Zilovertamab vedotin Schedule 1: Q1/3W
EXPERIMENTALParticipants 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 Schedule 2: Q2/3W
EXPERIMENTALParticipants 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).
Zilovertamab vedotin Schedule 3: Q3/4W
EXPERIMENTALParticipants 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).
Interventions
Zilovertamab vedotin administered via IV infusion per Schedule 1, 2, or 3 according to participant allocation.
Eligibility Criteria
You may qualify if:
- 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.
- +5 more criteria
You may not qualify if:
- 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.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
City of Hope ( Site 0010)
Duarte, California, 91010, United States
University of California - San Diego ( Site 0003)
La Jolla, California, 92093, United States
UCLA Hematology & Oncology ( Site 0007)
Los Angeles, California, 90095, United States
University of Nebraska Medical Center ( Site 0006)
Omaha, Nebraska, 68198-5331, United States
Northwell Health ( Site 0009)
New Hyde Park, New York, 11042, United States
Weill Cornell Medical College ( Site 0005)
New York, New York, 10021, United States
Memorial Sloan Kettering Cancer Center ( Site 0014)
New York, New York, 10065, United States
University of Rochester ( Site 0008)
Rochester, New York, 14642, United States
Memorial Sloan-Kettering Cancer Center ( Site 0019)
Uniondale, New York, 11553, United States
Oregon Health & Science University ( Site 0004)
Portland, Oregon, 97239, United States
MD Anderson Cancer Center ( Site 0001)
Houston, Texas, 77030, United States
MD Anderson Cancer Center ( Site 0011)
Houston, Texas, 77030, United States
University of Virginia Cancer Center ( Site 0012)
Charlottesville, Virginia, 22908, United States
Swedish Medical Center ( Site 0002)
Seattle, Washington, 98104, United States
Related Publications (2)
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.
PMID: 38319241RESULTKipps 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.
PMID: 34398557DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Merck Sharp & Dohme LLC
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 4, 2019
First Posted
February 6, 2019
Study Start
March 14, 2019
Primary Completion
December 18, 2023
Study Completion
December 18, 2023
Last Updated
January 12, 2024
Record last verified: 2024-01
Data Sharing
- IPD Sharing
- Will share
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf