A Study of Zilovertamab Vedotin (MK-2140/VLS-101) in Participants With Solid Tumors (MK-2140-002)
- Conditions
- Triple-negative Breast CancerNSCLCNon-squamous Non-small-cell Lung CancerEstrogen-receptor-positive Breast CancerGastric CancerProgesterone-receptor-positive Breast CancerEstrogen-receptor-negative Breast CancerER-negative Breast CancerProgesterone-receptor Negative Breast CancerPR-negative Breast Cancer
- Interventions
- Registration Number
- NCT04504916
- Lead Sponsor
- VelosBio Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- 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 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%.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 102
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Zilovertamab Vedotin 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
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR)- Blinded Independent Central Review (BICR) 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.
- Secondary Outcome Measures
Name Time Method Time to Treatment Failure (TTF)- BICR 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.
AUC0-168 hr of MMAE-Q2/3W Dosing Schedule: Day 1 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.
Progression-free Survival (PFS)- BICR 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.
Number of Participants Who Discontinued Study Treatment Due to an AE 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.
ORR- Investigator Assessed 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.
AUC168-336hrs of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 8 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.
AUC168-336 Hrs of Total Antibody-Q2/3W Dosing Schedule: Day 8 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.
Time to Response (TTR)- BICR 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.
Duration of Response (DOR)- BICR 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.
Number of Participants Who Experienced an Adverse Event (AE) 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.
Cmax of Total Antibody-Q2/3W Dosing Schedule: Day 8 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.
Cmax of MMAE-Q2/3W Dosing Schedule: Day 8 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.
AUC0-168hrs of Zilovertamab Vedotin -Q2/3W Dosing Schedule: Day 1 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.
AUC0-168hrs of Total Antibody-Q2/3W Dosing Schedule: Day 1 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.
AUC168-336 hr of MMAE-Q2/3W Dosing Schedule: Day 8 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.
Cmax of Total Antibody-Q1/3W Dosing Schedule 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.
Overall Survival (OS) Up to ~30 months OS, defined as the interval from the start of study treatment to death from any cause will be reported.
Maximum Plasma Concentration (Cmax) of Zilovertamab Vedotin-Q1/3W Dosing Schedule 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.
Cmax of MMAE-Q1/3W Dosing Schedule 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.
Area Under the Plasma Concentration-time Curve (AUC) 0-504hrs of Zilovertamab Vedotin- Q1/3W Dosing Schedule 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.
AUC0-504hrs of Total Antibodies-Q1/3W Dosing Schedule 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.
AUC0-504hrs of MMAE-Q1/3W Dosing Schedule 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.
Cmax of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 1 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.
Cmax of Total Antibody-Q2/3W Dosing Schedule: Day 1 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.
Cmax of MMAE-Q2/3W Dosing Schedule: Day 1 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.
Cmax of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 8 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.
Trial Locations
- Locations (14)
Memorial Regional Hospital-Memorial Cancer Institute ( Site 0005)
🇺🇸Hollywood, Florida, United States
John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0002)
🇺🇸Hackensack, New Jersey, United States
Memorial Sloan Kettering Cancer Center ( Site 0007)
🇺🇸New York, New York, United States
Cross Cancer Institute ( Site 0012)
🇨🇦Edmonton, Alberta, Canada
Massachusetts General Hospital ( Site 0017)
🇺🇸Boston, Massachusetts, United States
Jewish General Hospital ( Site 0013)
🇨🇦Montreal, Quebec, Canada
Princess Margaret Cancer Centre ( Site 0006)
🇨🇦Toronto, Ontario, Canada
Swedish Medical Center ( Site 0008)
🇺🇸Seattle, Washington, United States
The University of Texas Health Science Center at San Antonio ( Site 0004)
🇺🇸San Antonio, Texas, United States
Centre intégré de cancérologie du CHUM ( Site 0016)
🇨🇦Montreal, Quebec, Canada
MD Anderson ( Site 0001)
🇺🇸Houston, Texas, United States
BC Cancer Vancouver ( Site 0011)
🇨🇦Vancouver, British Columbia, Canada
Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
🇨🇦Quebec, Canada
AdventHealth Orlando ( Site 0003)
🇺🇸Orlando, Florida, United States