A Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Solid Tumors (MK-2140-002)
Study Details
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. Treatment will continue until progressive disease or discontinuation.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Zilovertamab vedotin Participants will receive zilovertamab vedotin at 1.75 mg/kg given intravenously on Day 1 and Day 8 of repeated 21-day cycles. 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. Treatment will continue until progressive disease or discontinuation. |
Drug: Zilovertamab vedotin
Intravenous infusion of 1.75 mg/kg or 2.5 mg/kg
Other Names:
|
Outcome Measures
Primary Outcome Measures
- ORR [Up to ~18 months]
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 [Up to ~18 months]
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) [Up to ~30 months]
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) [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 will be reported.
- Progression-free survival (PFS) [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 will be reported.
- Time to treatment failure (TTF) [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 will be reported.
- 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.
- Number of participants who experienced an adverse event (AE) [Up to ~30 months]
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 [Up to ~30 months]
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 [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]
Cmax of zilovertamab vedotin determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
- Cmax of total antibody [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]
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) [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]
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 [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]
AUC of zilovertamab vedotin determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
- AUC of total antibody [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]
AUC of total antibody determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
- AUC of MMAE [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]
AUC of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Regional Hospital-Memorial Cancer Institute ( Site 0005) | Hollywood | Florida | United States | 33021 |
| 2 | AdventHealth Orlando ( Site 0003) | Orlando | Florida | United States | 32804 |
| 3 | John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0002) | Hackensack | New Jersey | United States | 07601 |
| 4 | Memorial Sloan Kettering Cancer Center ( Site 0007) | New York | New York | United States | 10021 |
| 5 | MD Anderson ( Site 0001) | Houston | Texas | United States | 77030 |
| 6 | The University of Texas Health Science Center at San Antonio ( Site 0004) | San Antonio | Texas | United States | 78229 |
| 7 | Swedish Medical Center ( Site 0008) | Seattle | Washington | United States | 98104 |
| 8 | Cross Cancer Institute ( Site 0012) | Edmonton | Alberta | Canada | T6G 1Z2 |
| 9 | BC Cancer Vancouver ( Site 0011) | Vancouver | British Columbia | Canada | V5Z 4E6 |
| 10 | Princess Margaret Cancer Centre ( Site 0006) | Toronto | Ontario | Canada | M5G 2M9 |
| 11 | Jewish General Hospital ( Site 0013) | Montreal | Quebec | Canada | H3T 1E2 |
Sponsors and Collaborators
- VelosBio Inc.
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2140-002
- VLS-101-0003
- MK-2140-002