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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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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

Intervention / Treatment
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* Drug: Zilovertamab vedotin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zilovertamab vedotin<br>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. | Drug: Zilovertamab vedotin<br>* Intravenous infusion<br>* Other names: VLS-101;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to  18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to  18 months | 
| 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. | Up to  30 months | 
| 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. | Up to  30 months | 
| 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. | Up to  30 months | 
| 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. | Up to  30 months | 
| Overall survival (OS) | 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) | 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. | Up to  30 months | 
| 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. | Up to  30 months | 
| 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. | 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 | Cmax of total antibody determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported. | 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 monomethyl auristatin E (MMAE) | Cmax of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported. | 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 | 
| 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. | 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 | AUC of total antibody determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported. | 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 | AUC of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported. | 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 |