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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04504916
• Other study ID #: 2140-002
• Secondary ID: VLS-101-0003MK-2
• Status: Completed
• Phase: Phase 2
• Start date: October 7, 2020
• Est. completion date: June 12, 2023

Study information

• Verified date: June 2023
• Source: VelosBio Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: June 12, 2023
• Est. primary completion date: June 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• ER-negative Breast Cancer
• ER-positive Breast Cancer
• Gastric Cancer
• HER2-negative Breast Cancer
• Non-squamous Non-small-cell Lung Cancer
• NSCLC
• Pancreatic Cancer
• Platinum-resistant Ovarian Cancer
• PR-negative Breast Cancer
• PR-positive Breast Cancer
• Triple Negative Breast Neoplasms
• Triple-negative Breast Cancer

Intervention

Drug:
• Zilovertamab vedotin
Intravenous infusion

Locations

Country	Name	City	State
Canada	Cross Cancer Institute ( Site 0012)	Edmonton	Alberta
Canada	Centre intégré de cancérologie du CHUM ( Site 0016)	Montreal	Quebec
Canada	Jewish General Hospital ( Site 0013)	Montreal	Quebec
Canada	Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0006)	Toronto	Ontario
Canada	BC Cancer Vancouver ( Site 0011)	Vancouver	British Columbia
United States	Massachusetts General Hospital ( Site 0017)	Boston	Massachusetts
United States	John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0002)	Hackensack	New Jersey
United States	Memorial Regional Hospital-Memorial Cancer Institute ( Site 0005)	Hollywood	Florida
United States	MD Anderson ( Site 0001)	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center ( Site 0007)	New York	New York
United States	AdventHealth Orlando ( Site 0003)	Orlando	Florida
United States	The University of Texas Health Science Center at San Antonio ( Site 0004)	San Antonio	Texas
United States	Swedish Medical Center ( Site 0008)	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
VelosBio Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Merck Oncology Clinical Trials Information