Clinical trial NCT04504916: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: VelosBio Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2020-08-07
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Objective Response Rate (ORR)- Blinded Independent Central Review (BICR)
timeFrame: Up to ~18 months
Secondary outcomes:
measure: ORR- Investigator Assessed
timeFrame: Up to ~18 months
measure: Time to Response (TTR)- BICR
timeFrame: Up to ~30 months
measure: Duration of Response (DOR)- BICR
timeFrame: Up to ~30 months
measure: Progression-free Survival (PFS)- BICR
timeFrame: Up to ~30 months
measure: Time to Treatment Failure (TTF)- BICR
timeFrame: Up to ~30 months
measure: Overall Survival (OS)
timeFrame: Up to ~30 months
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to ~30 months
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to ~11 months
measure: Maximum Plasma Concentration (Cmax) of Zilovertamab Vedotin-Q1/3W Dosing Schedule
timeFrame: 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
measure: Cmax of Total Antibody-Q1/3W Dosing Schedule
timeFrame: 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
measure: Cmax of MMAE-Q1/3W Dosing Schedule
timeFrame: 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
measure: Area Under the Plasma Concentration-time Curve (AUC) 0-504hrs of Zilovertamab Vedotin- Q1/3W Dosing Schedule
timeFrame: 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
measure: AUC0-504hrs of Total Antibodies-Q1/3W Dosing Schedule
timeFrame: 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
measure: AUC0-504hrs of MMAE-Q1/3W Dosing Schedule
timeFrame: 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
measure: Cmax of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 1
timeFrame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
measure: Cmax of Total Antibody-Q2/3W Dosing Schedule: Day 1
timeFrame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
measure: Cmax of MMAE-Q2/3W Dosing Schedule: Day 1
timeFrame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
measure: Cmax of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 8
timeFrame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days
measure: Cmax of Total Antibody-Q2/3W Dosing Schedule: Day 8
timeFrame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days
measure: Cmax of MMAE-Q2/3W Dosing Schedule: Day 8
timeFrame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days
measure: AUC0-168hrs of Zilovertamab Vedotin -Q2/3W Dosing Schedule: Day 1
timeFrame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
measure: AUC0-168hrs of Total Antibody-Q2/3W Dosing Schedule: Day 1
timeFrame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
measure: AUC0-168 hr of MMAE-Q2/3W Dosing Schedule: Day 1
timeFrame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
measure: AUC168-336hrs of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 8
timeFrame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days
measure: AUC168-336 Hrs of Total Antibody-Q2/3W Dosing Schedule: Day 8
timeFrame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days
measure: AUC168-336 hr of MMAE-Q2/3W Dosing Schedule: Day 8
timeFrame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days
Other outcomes:
Locations:
city: Hollywood
country: United States
facility: Memorial Regional Hospital-Memorial Cancer Institute ( Site 0005)
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando ( Site 0003)
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital ( Site 0017)
state: Massachusetts
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0002)
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center ( Site 0007)
state: New York
city: Houston
country: United States
facility: MD Anderson ( Site 0001)
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio ( Site 0004)
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center ( Site 0008)
state: Washington
city: Edmonton
country: Canada
facility: Cross Cancer Institute ( Site 0012)
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer Vancouver ( Site 0011)
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre ( Site 0006)
state: Ontario
city: Montreal
country: Canada
facility: Centre intégré de cancérologie du CHUM ( Site 0016)
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 0013)
state: Quebec
city: Quebec
country: Canada
facility: Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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.