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%.
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
102
Intravenous infusion
Memorial Regional Hospital-Memorial Cancer Institute ( Site 0005)
Hollywood, Florida, United States
AdventHealth Orlando ( Site 0003)
Orlando, Florida, 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 Sloan Kettering Cancer Center ( Site 0007)
New York, New York, United States
MD Anderson ( Site 0001)
Houston, Texas, 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, United States
Cross Cancer Institute ( Site 0012)
Edmonton, Alberta, Canada
BC Cancer Vancouver ( Site 0011)
Vancouver, British Columbia, Canada
...and 4 more locations
Objective Response Rate (ORR)- Blinded Independent Central Review (BICR)
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.
Time frame: Up to ~18 months
ORR- Investigator Assessed
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.
Time frame: Up to ~18 months
Time to Response (TTR)- BICR
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.
Time frame: Up to ~30 months
Duration of Response (DOR)- BICR
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.
Time frame: Up to ~30 months
Progression-free Survival (PFS)- BICR
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.
Time frame: Up to ~30 months
Time to Treatment Failure (TTF)- BICR
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.
Time frame: 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.
Time frame: Up to ~30 months
Number of Participants Who Experienced an Adverse Event (AE)
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.
Time frame: Up to ~30 months
Number of Participants Who Discontinued Study Treatment Due to an AE
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.
Time frame: Up to ~11 months
Maximum Plasma Concentration (Cmax) of Zilovertamab Vedotin-Q1/3W Dosing Schedule
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.
Time frame: 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-Q1/3W Dosing Schedule
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.
Time frame: 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-Q1/3W Dosing Schedule
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.
Time frame: 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
Area Under the Plasma Concentration-time Curve (AUC) 0-504hrs of Zilovertamab Vedotin- Q1/3W Dosing Schedule
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.
Time frame: 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 Antibodies-Q1/3W Dosing Schedule
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.
Time frame: 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-Q1/3W Dosing Schedule
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.
Time frame: 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-Q2/3W Dosing Schedule: Day 1
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.
Time frame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
Cmax of Total Antibody-Q2/3W Dosing Schedule: Day 1
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.
Time frame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
Cmax of MMAE-Q2/3W Dosing Schedule: Day 1
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.
Time frame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
Cmax of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 8
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.
Time frame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days
Cmax of Total Antibody-Q2/3W Dosing Schedule: Day 8
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.
Time frame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days
Cmax of MMAE-Q2/3W Dosing Schedule: Day 8
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.
Time frame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days
AUC0-168hrs of Zilovertamab Vedotin -Q2/3W Dosing Schedule: Day 1
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.
Time frame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
AUC0-168hrs of Total Antibody-Q2/3W Dosing Schedule: Day 1
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.
Time frame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
AUC0-168 hr of MMAE-Q2/3W Dosing Schedule: Day 1
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.
Time frame: Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days
AUC168-336hrs of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 8
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.
Time frame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days
AUC168-336 Hrs of Total Antibody-Q2/3W Dosing Schedule: Day 8
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 frame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days
AUC168-336 hr of MMAE-Q2/3W Dosing Schedule: Day 8
AUC168-336 of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
Time frame: Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days
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