Back to resultsA Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Solid Tumors (MK-2140-002)
Primary Purpose
Triple-negative Breast Cancer, Non-squamous Non-small-cell Lung Cancer, NSCLC
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Zilovertamab vedotin
Sponsored by
About this trial
This is an interventional treatment trial for Triple-negative Breast Cancer
Eligibility Criteria
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.
Sites / Locations
- Memorial Regional Hospital-Memorial Cancer Institute ( Site 0005)
- AdventHealth Orlando ( Site 0003)
- Massachusetts General Hospital ( Site 0017)
- John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0002)
- Memorial Sloan Kettering Cancer Center ( Site 0007)
- MD Anderson ( Site 0001)
- The University of Texas Health Science Center at San Antonio ( Site 0004)
- Swedish Medical Center ( Site 0008)
- Cross Cancer Institute ( Site 0012)
- BC Cancer Vancouver ( Site 0011)
- Princess Margaret Cancer Centre ( Site 0006)
- Centre intégré de cancérologie du CHUM ( Site 0016)
- Jewish General Hospital ( Site 0013)
- Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Zilovertamab vedotin
Arm Description
Participants will receive zilovertamab vedotin at 2.0 mg/kg given intravenously on Day 1 and Day 8 of repeated 21-day cycles. Treatment will continue until progressive disease or discontinuation.
Outcomes
Primary Outcome Measures
ORR
The percentage of participants who achieve a complete response (CR) or partial response (PR) using per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 by Blinded Independent Central Review (BICR) will be reported.
Secondary Outcome Measures
ORR
The percentage of participants who achieve a complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 by investigator will be reported.
Time to response (TTR)
TTR, defined as the time from the start of study treatment to the first documentation of objective tumor response will be reported.
Duration of response (DOR)
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 will be reported.
Progression-free survival (PFS)
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 will be reported.
Time to treatment failure (TTF)
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 will be reported.
Overall survival (OS)
OS, defined as the interval from the start of study treatment to death from any cause will be reported.
Number of participants who experienced an adverse event (AE)
An AE is 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 is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experienced an AE will be reported.
Number of participants who discontinued study treatment due to an AE
An AE is 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 is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinued study treatment due to an AE will be reported.
Maximum plasma concentration (Cmax) of zilovertamab vedotin
Cmax of zilovertamab vedotin determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Cmax of total antibody
Cmax of total antibody determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Cmax of monomethyl auristatin E (MMAE)
Cmax of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Area under the plasma concentration-time curve (AUC) of zilovertamab vedotin
AUC of zilovertamab vedotin determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
AUC of total antibody
AUC of total antibody determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
AUC of MMAE
AUC of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04504916
Brief Title
A Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Solid Tumors (MK-2140-002)
Official Title
A Phase 2 Study of VLS-101 in Patients With Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
October 7, 2020 (Actual)
Primary Completion Date
June 12, 2023 (Actual)
Study Completion Date
June 12, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VelosBio Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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 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%.
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. Participants enrolled after Amendment 4 will receive zilovertamab vedotin at 2.0 mg/kg given intravenously on Day 1 and Day 8 of repeated 21-day cycles. Treatment will continue until progressive disease or discontinuation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Triple-negative Breast Cancer, Non-squamous Non-small-cell Lung Cancer, NSCLC, Estrogen-receptor-positive Breast Cancer, Progesterone-receptor-positive Breast Cancer, Estrogen-receptor-negative Breast Cancer, ER-negative Breast Cancer, Progesterone-receptor Negative Breast Cancer, PR-negative Breast Cancer, HER2-negative Breast Cancer, ER-positive Breast Cancer, PR-positive Breast Cancer, Platinum-resistant Ovarian Cancer, Gastric Cancer, Pancreatic Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
102 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Zilovertamab vedotin
Arm Type
Experimental
Arm Description
Participants will receive zilovertamab vedotin at 2.0 mg/kg given intravenously on Day 1 and Day 8 of repeated 21-day cycles. Treatment will continue until progressive disease or discontinuation.
Intervention Type
Drug
Intervention Name(s)
Zilovertamab vedotin
Other Intervention Name(s)
MK-2140, VLS-101
Intervention Description
Intravenous infusion
Primary Outcome Measure Information:
Title
ORR
Description
The percentage of participants who achieve a complete response (CR) or partial response (PR) using per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 by Blinded Independent Central Review (BICR) will be reported.
Time Frame
Up to ~18 months
Secondary Outcome Measure Information:
Title
ORR
Description
The percentage of participants who achieve a complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 by investigator will be reported.
Time Frame
Up to ~18 months
Title
Time to response (TTR)
Description
TTR, defined as the time from the start of study treatment to the first documentation of objective tumor response will be reported.
Time Frame
Up to ~30 months
Title
Duration of response (DOR)
Description
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 will be reported.
Time Frame
Up to ~30 months
Title
Progression-free survival (PFS)
Description
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 will be reported.
Time Frame
Up to ~30 months
Title
Time to treatment failure (TTF)
Description
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 will be reported.
Time Frame
Up to ~30 months
Title
Overall survival (OS)
Description
OS, defined as the interval from the start of study treatment to death from any cause will be reported.
Time Frame
Up to ~30 months
Title
Number of participants who experienced an adverse event (AE)
Description
An AE is 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 is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experienced an AE will be reported.
Time Frame
Up to ~30 months
Title
Number of participants who discontinued study treatment due to an AE
Description
An AE is 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 is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinued study treatment due to an AE will be reported.
Time Frame
Up to ~30 months
Title
Maximum plasma concentration (Cmax) of zilovertamab vedotin
Description
Cmax of zilovertamab vedotin determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Time Frame
Pre-dose and post-dose on Day 1 and Day 8 of Cycle 1, and each subsequent cycle (up to ~30 months); Non-dose day samples on Day 15 of Cycle 1, Cycle 3, and at the end of treatment (up to ~30 months); each cycle = 21 days
Title
Cmax of total antibody
Description
Cmax of total antibody determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Time Frame
Pre-dose and post-dose on Day 1 and Day 8 of Cycle 1, and each subsequent cycle (up to ~30 months); Non-dose day samples on Day 15 of Cycle 1, Cycle 3, and at the end of treatment (up to ~30 months); each cycle = 21 days
Title
Cmax of monomethyl auristatin E (MMAE)
Description
Cmax of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Time Frame
Pre-dose and post-dose on Day 1 and Day 8 of Cycle 1, and each subsequent cycle (up to ~30 months); Non-dose day samples on Day 15 of Cycle 1, Cycle 3, and at the end of treatment (up to ~30 months); each cycle = 21 days
Title
Area under the plasma concentration-time curve (AUC) of zilovertamab vedotin
Description
AUC of zilovertamab vedotin determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Time Frame
Pre-dose and post-dose on Day 1 and Day 8 of Cycle 1, and each subsequent cycle (up to ~30 months); Non-dose day samples on Day 15 of Cycle 1, Cycle 3, and at the end of treatment (up to ~30 months); each cycle = 21 days
Title
AUC of total antibody
Description
AUC of total antibody determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Time Frame
Pre-dose and post-dose on Day 1 and Day 8 of Cycle 1, and each subsequent cycle (up to ~30 months); Non-dose day samples on Day 15 of Cycle 1, Cycle 3, and at the end of treatment (up to ~30 months); each cycle = 21 days
Title
AUC of MMAE
Description
AUC of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Time Frame
Pre-dose and post-dose on Day 1 and Day 8 of Cycle 1, and each subsequent cycle (up to ~30 months); Non-dose day samples on Day 15 of Cycle 1, Cycle 3, and at the end of treatment (up to ~30 months); each cycle = 21 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Memorial Regional Hospital-Memorial Cancer Institute ( Site 0005)
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
AdventHealth Orlando ( Site 0003)
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Massachusetts General Hospital ( Site 0017)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0002)
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center ( Site 0007)
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
MD Anderson ( Site 0001)
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The University of Texas Health Science Center at San Antonio ( Site 0004)
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Swedish Medical Center ( Site 0008)
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Cross Cancer Institute ( Site 0012)
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
BC Cancer Vancouver ( Site 0011)
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Princess Margaret Cancer Centre ( Site 0006)
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Centre intégré de cancérologie du CHUM ( Site 0016)
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 0A9
Country
Canada
Facility Name
Jewish General Hospital ( Site 0013)
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
City
Quebec
ZIP/Postal Code
G1J 1Z4
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pd
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
34398557
Citation
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.
Results Reference
derived
Links:
URL
http://merckoncologyclinicaltrials.com
Description
Merck Oncology Clinical Trials Information
Learn more about this trial
A Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Solid Tumors (MK-2140-002)
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