A Study of Zilovertamab Vedotin (MK-2140/VLS-101) in Participants With Solid Tumors (MK-2140-002)

October 27, 2025 updated by: VelosBio Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

A Phase 2 Study of VLS-101 in Patients With Solid Tumors

This is a study evaluating the efficacy, safety, and pharmacokinetics of zilovertamab vedotin in participants with metastatic solid tumors including previously treated cancers of triple-negative breast cancer (TNBC), non-TNBC human epidermal growth factor receptor 2 (HER2)-negative breast cancer, non-squamous non-small-cell lung cancer (NSCLC), gastric cancer, pancreatic cancer, and platinum-resistant ovarian cancer. The study will evaluate a null hypothesis that the objective response rate (ORR) is ≤5% against the alternative hypothesis that it is ≥20%.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Participants enrolled prior to Amendment 3 will receive zilovertamab vedotin at 2.5 mg/kg given intravenously on Day 1 of repeated 21-day cycles. Participants enrolled after Amendment 3 will receive zilovertamab vedotin at 1.75 mg/kg given intravenously on Day 1 and Day 8 of repeated 21-day cycles. Treatment will continue until progressive disease or discontinuation.

Study Type

Interventional

Enrollment (Actual)

102

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute ( Site 0012)
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BC Cancer Vancouver ( Site 0011)
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre ( Site 0006)
    • Quebec
      • Montreal, Quebec, Canada, H2X 0A9
        • Centre intégré de cancérologie du CHUM ( Site 0016)
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital ( Site 0013)
      • Québec, Quebec, Canada, G1J 1Z4
        • Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
  • United States
    • Florida
      • Hollywood, Florida, United States, 33021
        • Memorial Regional Hospital-Memorial Cancer Institute ( Site 0005)
      • Orlando, Florida, United States, 32804
        • AdventHealth Orlando ( Site 0003)
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital ( Site 0017)
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0002)
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan Kettering Cancer Center ( Site 0007)
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson ( Site 0001)
      • San Antonio, Texas, United States, 78229
        • The University of Texas Health Science Center at San Antonio ( Site 0004)
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Medical Center ( Site 0008)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Has a confirmed diagnosis of solid tumor for one of the following types of cancer: previously treated cancers of triple-negative breast cancer (TNBC), non-TNBC HER2-negative breast cancer, non-squamous non-small-cell lung cancer (NSCLC), gastric cancer, pancreatic cancer, or platinum-resistant ovarian cancer.
  • Has metastatic disease that has progressed during or following previous treatment appropriate for the disease type
  • Presence of radiographically measurable disease.
  • Is willing to provide tumor tissue
  • Has adequate organ function
  • Has a negative test or adequate therapy for human immunodeficiency virus (HIV), hepatitis B, and/or hepatitis C.
  • Has completed all prior therapy.
  • Female subjects of childbearing potential must have a negative serum pregnancy test.
  • Both male and female subjects must be willing to use adequate contraception.

Exclusion Criteria:

  • Has peripheral neuropathy of Grade >1.
  • Has a malignancy involving the central nervous system.
  • Has another major cancer.
  • Has an uncontrolled ongoing infection.
  • Has significant cardiovascular disease.
  • Has a known diagnosis of liver cirrhosis.
  • Is pregnant or breastfeeding.
  • Has had major surgery within 4 weeks before the start of study therapy.
  • Has known tumor resistance or intolerance to a prior MMAE-containing drug.
  • Is concurrently participating in another therapeutic or imaging clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zilovertamab Vedotin
Participants will receive intravenous (IV) zilovertamab vedotin 2.5 mg/kg on Day 1 of each repeated 21-day cycle (Q1/3W) or 1.75 mg/kg on Day 1 and Day 8 of each 21-day cycle (Q2/3W). Treatment will continue until progressive disease or discontinuation
Drug: Zilovertamab vedotin
Intravenous infusion
Other Names:
  • MK-2140
  • VLS-101

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)- Blinded Independent Central Review (BICR)
Time Frame: Up to ~18 months
The percentage of participants who achieved a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: a ≥30% decrease in the sum of diameters [SOD] of target lesions) using per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 by BICR was reported.
Up to ~18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR- Investigator Assessed
Time Frame: Up to ~18 months
The percentage of participants who achieved a CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters [SOD] of target lesions) per RECIST, Version 1.1 by investigator was reported.
Up to ~18 months
Time to Response (TTR)- BICR
Time Frame: Up to ~30 months
TTR, defined as the time from the start of study treatment to the first documentation of objective tumor response per RECIST, Version 1.1 by BICR was reported.
Up to ~30 months
Duration of Response (DOR)- BICR
Time Frame: Up to ~30 months
DOR, defined as the interval from the first documentation of objective tumor response to the earlier of the first documentation of disease progression or death from any cause per RECIST, Version 1.1 by BICR was reported.
Up to ~30 months
Progression-free Survival (PFS)- BICR
Time Frame: Up to ~30 months
PFS, defined as the interval from the start of study treatment to the earlier of the first documentation of disease progression or death from any cause per RECIST, Version 1.1 by BICR was reported.
Up to ~30 months
Time to Treatment Failure (TTF)- BICR
Time Frame: Up to ~30 months
TTF, defined as the time from the start of study treatment to the earliest of the first documentation of disease progression, the permanent cessation of study drug due to an AE, or death from any cause per RECIST, Version 1.1 by BICR was reported.
Up to ~30 months
Overall Survival (OS)
Time Frame: Up to ~30 months
OS, defined as the interval from the start of study treatment to death from any cause will be reported.
Up to ~30 months
Number of Participants Who Experienced an Adverse Event (AE)
Time Frame: Up to ~30 months
An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an AE. The number of participants who experienced an AE was reported.
Up to ~30 months
Number of Participants Who Discontinued Study Treatment Due to an AE
Time Frame: Up to ~11 months
An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an AE. The number of participants who discontinued study treatment due to an AE was reported.
Up to ~11 months
Maximum Plasma Concentration (Cmax) of Zilovertamab Vedotin-Q1/3W Dosing Schedule
Time Frame: Day 1 [(predose; end of infusion (EOI); and 2 and 4 hours after EOI)], Day 8 (168 hr), Day 15 (336 hr), and Cycle 2 Day 1 (predose); each cycle=21 days
Cmax of zilovertamab vedotin determined by blood samples collected pre-dose and at designated timepoints post-dose were reported. Per protocol the Zilovertamab vedotin Q2/3W Dosing Group was not included in this analysis.
Day 1 [(predose; end of infusion (EOI); and 2 and 4 hours after EOI)], Day 8 (168 hr), Day 15 (336 hr), and Cycle 2 Day 1 (predose); each cycle=21 days
Cmax of Total Antibody-Q1/3W Dosing Schedule
Time Frame: Day 1 [(predose; end of infusion (EOI); and 2 and 4 hours after EOI)], Day 8 (168 hr), Day 15 (336 hr), and Cycle 2 Day 1 (predose); each cycle=21 days
Cmax of total antibody determined by blood samples collected pre-dose and at designated timepoints post-dose was reported. Total Antibody was defined as total zilovertamab vedotin plus any antibody that was not conjugated to monomethyl auristatin E (MMAE). Per protocol the Zilovertamab vedotin Q2/3W Dosing Group was not included in this analysis.
Day 1 [(predose; end of infusion (EOI); and 2 and 4 hours after EOI)], Day 8 (168 hr), Day 15 (336 hr), and Cycle 2 Day 1 (predose); each cycle=21 days
Cmax of MMAE-Q1/3W Dosing Schedule
Time Frame: Day 1 [(predose; end of infusion (EOI); and 2 and 4 hours after EOI)], Day 8 (168 hr), Day 15 (336 hr), and Cycle 2 Day 1 (predose); each cycle=21 days
Cmax of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose was reported. Per protocol the Zilovertamab vedotin Q2/3W Dosing Group was not included in this analysis.
Day 1 [(predose; end of infusion (EOI); and 2 and 4 hours after EOI)], Day 8 (168 hr), Day 15 (336 hr), and Cycle 2 Day 1 (predose); each cycle=21 days
Area Under the Plasma Concentration-time Curve (AUC) 0-504hrs of Zilovertamab Vedotin- Q1/3W Dosing Schedule
Time Frame: Day 1 [(predose; end of infusion (EOI); and 2 and 4 hours after EOI)], Day 8 (168 hr), Day 15 (336 hr), and Cycle 2 Day 1 (predose); each cycle=21 days
AUC0-504hrs of Zilovertamab Vedotin determined by blood samples collected pre-dose and at designated timepoints post-dose was reported. Per protocol the Zilovertamab vedotin Q2/3W Dosing Group was not included in this analysis.
Day 1 [(predose; end of infusion (EOI); and 2 and 4 hours after EOI)], Day 8 (168 hr), Day 15 (336 hr), and Cycle 2 Day 1 (predose); each cycle=21 days
AUC0-504hrs of Total Antibodies-Q1/3W Dosing Schedule
Time Frame: Day 1 [(predose; end of infusion (EOI); and 2 and 4 hours after EOI)], Day 8 (168 hr), Day 15 (336 hr), and Cycle 2 Day 1 (predose); each cycle=21 days
AUC0-504hrs of total antibody determined by blood samples collected pre-dose and at designated timepoints post-dose was reported. Total Antibody was defined as total zilovertamab vedotin plus any antibody that was not conjugated to monomethyl auristatin E (MMAE). Per protocol the Zilovertamab vedotin Q2/3W Dosing Group was not included in this analysis.
Day 1 [(predose; end of infusion (EOI); and 2 and 4 hours after EOI)], Day 8 (168 hr), Day 15 (336 hr), and Cycle 2 Day 1 (predose); each cycle=21 days
AUC0-504hrs of MMAE-Q1/3W Dosing Schedule
Time Frame: Day 1 [(predose; end of infusion (EOI); and 2 and 4 hours after EOI)], Day 8 (168 hr), Day 15 (336 hr), and Cycle 2 Day 1 (predose); each cycle=21 days
AUC0-504hrs of MMAE by blood collected pre-dose and at designated timepoints post-dose was reported. Per protocol the Zilovertamab vedotin Q2/3W Dosing Group was not included in this analysis.
Day 1 [(predose; end of infusion (EOI); and 2 and 4 hours after EOI)], Day 8 (168 hr), Day 15 (336 hr), and Cycle 2 Day 1 (predose); each cycle=21 days
Cmax of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 1
Time Frame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
Cmax of zilovertamab vedotin determined by blood samples collected pre-dose and at designated timepoints post-dose were reported. Per protocol the Zilovertamab vedotin Q1/3W Dosing Group was not included in this analysis.
Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
Cmax of Total Antibody-Q2/3W Dosing Schedule: Day 1
Time Frame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
Cmax of total antibody determined by blood samples collected pre-dose and at designated timepoints post-dose was reported. Total Antibody was defined as total zilovertamab vedotin plus any antibody that was not conjugated to monomethyl auristatin E (MMAE). Per protocol the Zilovertamab vedotin Q1/3W Dosing Group was not included in this analysis.
Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
Cmax of MMAE-Q2/3W Dosing Schedule: Day 1
Time Frame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
Cmax of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose were reported. Per protocol the Zilovertamab vedotin Q1/3W Dosing Group was not included in this analysis.
Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
Cmax of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 8
Time Frame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days
Cmax of zilovertamab vedotin determined by blood samples collected pre-dose and at designated timepoints post-dose were reported. Per protocol the Zilovertamab vedotin Q1/3W Dosing Group was not included in this analysis.
Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days
Cmax of Total Antibody-Q2/3W Dosing Schedule: Day 8
Time Frame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days
Cmax of total antibody determined by blood samples collected pre-dose and at designated timepoints post-dose was reported. Total Antibody was defined as total zilovertamab vedotin plus any antibody that was not conjugated to monomethyl auristatin E (MMAE). Per protocol the Zilovertamab vedotin Q1/3W Dosing Group was not included in this analysis.
Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days
Cmax of MMAE-Q2/3W Dosing Schedule: Day 8
Time Frame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days
Cmax of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose were reported. Per protocol the Zilovertamab vedotin Q1/3W Dosing Group was not included in this analysis.
Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days
AUC0-168hrs of Zilovertamab Vedotin -Q2/3W Dosing Schedule: Day 1
Time Frame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
AUC0-168hrs of zilovertamab vedotin determined by blood samples collected pre-dose and at designated timepoints post-dose was reported. Per protocol the Zilovertamab vedotin Q1/3W Dosing Group was not included in this analysis.
Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
AUC0-168hrs of Total Antibody-Q2/3W Dosing Schedule: Day 1
Time Frame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
AUC0-168hrs of total antibody determined by blood samples collected pre-dose and at designated timepoints post-dose was reported. Total Antibody was defined as total zilovertamab vedotin plus any antibody that is not conjugated to monomethyl auristatin E (MMAE). Per protocol the Zilovertamab vedotin Q1/3W Dosing Group was not included in this analysis.
Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
AUC0-168 hr of MMAE-Q2/3W Dosing Schedule: Day 1
Time Frame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
AUC0-168hrs of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose were reported. Per protocol the Zilovertamab vedotin Q1/3W Dosing Group was not included in this analysis.
Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
AUC168-336hrs of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 8
Time Frame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days
AUC168-336 hrs of zilovertamab vedotin determined by blood samples collected pre-dose and at designated timepoints post-dose was reported. Per protocol the Zilovertamab vedotin Q1/3W Dosing Group was not included in this analysis.
Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days
AUC168-336 Hrs of Total Antibody-Q2/3W Dosing Schedule: Day 8
Time Frame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days
AUC168-336hrs of total antibody determined by blood samples collected pre-dose and at designated timepoints post-dose was reported. Total Antibody was defined as total zilovertamab vedotin plus any antibody that was not conjugated to MMAE. Per protocol the Zilovertamab vedotin Q1/3W Dosing Group was not included in this analysis.
Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days
AUC168-336 hr of MMAE-Q2/3W Dosing Schedule: Day 8
Time Frame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days
AUC168-336 of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 7, 2020

Primary Completion (Actual)

June 12, 2023

Study Completion (Actual)

June 12, 2023

Study Registration Dates

First Submitted

August 4, 2020

First Submitted That Met QC Criteria

August 6, 2020

First Posted (Actual)

August 7, 2020

Study Record Updates

Last Update Posted (Estimated)

November 7, 2025

Last Update Submitted That Met QC Criteria

October 27, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2140-002
  • VLS-101-0003 (Other Identifier: VelosBio)
  • MK-2140-002 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pd

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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