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
Conditions
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.
Interventions
Intravenous infusion
Sponsors
VelosBio Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR)- Blinded Independent Central Review (BICR) | Up to ~18 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response (TTR)- BICR | Up to ~30 months | 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. |
| Duration of Response (DOR)- BICR | 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 per RECIST, Version 1.1 by BICR was reported. |
| Progression-free Survival (PFS)- BICR | 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 per RECIST, Version 1.1 by BICR was reported. |
| Time to Treatment Failure (TTF)- BICR | 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 per RECIST, Version 1.1 by BICR was 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 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. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to ~11 months | 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. |
| Maximum Plasma Concentration (Cmax) of Zilovertamab Vedotin-Q1/3W Dosing Schedule | 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 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. |
| Cmax of Total Antibody-Q1/3W Dosing Schedule | 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 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. |
| Cmax of MMAE-Q1/3W Dosing Schedule | 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 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. |
| Area Under the Plasma Concentration-time Curve (AUC) 0-504hrs of Zilovertamab Vedotin- Q1/3W Dosing Schedule | 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 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. |
| AUC0-504hrs of Total Antibodies-Q1/3W Dosing Schedule | 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 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. |
| ORR- Investigator Assessed | Up to ~18 months | 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. |
| Cmax of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 1 | Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days | 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. |
| Cmax of Total Antibody-Q2/3W Dosing Schedule: Day 1 | Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days | 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. |
| Cmax of MMAE-Q2/3W Dosing Schedule: Day 1 | Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days | 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. |
| Cmax of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 8 | Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days | 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. |
| Cmax of Total Antibody-Q2/3W Dosing Schedule: Day 8 | Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days | 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. |
| Cmax of MMAE-Q2/3W Dosing Schedule: Day 8 | Day 8 [(predose; end of infusion (EOI)], Day 15 (168 hr), Cycle 2 Day 1 Predose; each cycle=21 days | 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. |
| AUC0-168hrs of Zilovertamab Vedotin -Q2/3W Dosing Schedule: Day 1 | Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days | 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. |
| AUC0-168hrs of Total Antibody-Q2/3W Dosing Schedule: Day 1 | Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days | 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. |
| AUC0-168 hr of MMAE-Q2/3W Dosing Schedule: Day 1 | Day 1 [(predose; end of infusion (EOI)], Day 8 (predose); each cycle=21 days | 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. |
| AUC168-336hrs of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 8 | Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days | 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. |
| AUC168-336 Hrs of Total Antibody-Q2/3W Dosing Schedule: Day 8 | Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days | 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. |
| AUC168-336 hr of MMAE-Q2/3W Dosing Schedule: Day 8 | Day 8 [(predose; end of infusion (EOI)], Day 15 (168hr), Cycle 2 Day 1 Predose; each cycle=21 days | AUC168-336 of MMAE determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported. |
| AUC0-504hrs of MMAE-Q1/3W Dosing Schedule | 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 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. |
Countries
Canada, United States
Participant flow
Pre-assignment details
Participants enrolled prior to Amendment 3 received intravenous (IV) zilovertamab vedotin 2.5 mg/kg on Day 1 of each repeated 21-day cycle (Q1/3W). Participants enrolled after Amendment 3 received IV zilovertamab vedotin 1.75 mg/kg on Day 1 and Day 8 (Q2/3W) of each repeated 21-day cycle.
Participants by arm
| Arm | Count |
|---|---|
| Zilovertamab Vedotin Q1/3W Participants received IV zilovertamab vedotin 2.5 mg/kg on Day 1 of each repeated 21-day cycle (Q1/3W). Treatment continued until progressive disease or discontinuation. | 70 |
| Zilovertamab Vedotin Q2/3W Participants received IV zilovertamab vedotin 1.75 mg/kg on Day 1 and Day 8 of each repeated 21-day cycle (Q2/3W). Treatment continued until progressive disease or discontinuation. | 32 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 54 | 18 |
| Overall Study | Did not agree to follow-up | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Study terminated | 7 | 8 |
| Overall Study | Withdrawal by Subject | 8 | 4 |
Baseline characteristics
| Characteristic | Zilovertamab Vedotin Q2/3W | Total | Zilovertamab Vedotin Q1/3W |
|---|---|---|---|
| Age, Continuous | 62.7 Years STANDARD_DEVIATION 11.62 | 60.0 Years STANDARD_DEVIATION 11.82 | 58.7 Years STANDARD_DEVIATION 11.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 7 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 92 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 12 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 8 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) White | 29 Participants | 75 Participants | 46 Participants |
| Sex: Female, Male Female | 24 Participants | 88 Participants | 64 Participants |
| Sex: Female, Male Male | 8 Participants | 14 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 54 / 70 | 18 / 32 |
| other Total, other adverse events | 66 / 70 | 30 / 32 |
| serious Total, serious adverse events | 29 / 70 | 16 / 32 |
Outcome results
Primary
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
Population: Full Analysis Set (FAS) which included all participants who received ≥1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zilovertamab Vedotin Q1/3W | Objective Response Rate (ORR)- Blinded Independent Central Review (BICR) | 1.4 Percentage of Participants |
| Zilovertamab Vedotin Q2/3W | Objective Response Rate (ORR)- Blinded Independent Central Review (BICR) | 0.0 Percentage of Participants |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | Area Under the Plasma Concentration-time Curve (AUC) 0-504hrs of Zilovertamab Vedotin- Q1/3W Dosing Schedule | 4030 hr*μg/mL | Geometric Coefficient of Variation 27.3 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | AUC0-168 hr of MMAE-Q2/3W Dosing Schedule: Day 1 | 0.202 hr*μg/mL | Geometric Coefficient of Variation 101.2 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | AUC0-168hrs of Total Antibody-Q2/3W Dosing Schedule: Day 1 | 2730 hr*μg/mL | Geometric Coefficient of Variation 25 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | AUC0-168hrs of Zilovertamab Vedotin -Q2/3W Dosing Schedule: Day 1 | 2070 hr*μg/mL | Geometric Coefficient of Variation 26.1 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | AUC0-504hrs of MMAE-Q1/3W Dosing Schedule | 0.828 hr*μg/mL | Geometric Coefficient of Variation 58.1 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | AUC0-504hrs of Total Antibodies-Q1/3W Dosing Schedule | 6720 hr*μg/mL | Geometric Coefficient of Variation 28.6 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | AUC168-336 hr of MMAE-Q2/3W Dosing Schedule: Day 8 | 0.596 hr*μg/mL | Geometric Coefficient of Variation 103.3 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | AUC168-336 Hrs of Total Antibody-Q2/3W Dosing Schedule: Day 8 | 5890 hr*μg/mL | Geometric Coefficient of Variation 48.1 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | AUC168-336hrs of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 8 | 2900 hr*μg/mL | Geometric Coefficient of Variation 66 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | Cmax of MMAE-Q1/3W Dosing Schedule | 0.00393 μg/mL | Geometric Coefficient of Variation 65.7 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | Cmax of MMAE-Q2/3W Dosing Schedule: Day 1 | .00121 μg/mL | Geometric Coefficient of Variation 332.3 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | Cmax of MMAE-Q2/3W Dosing Schedule: Day 8 | 0.00289 μg/mL | Geometric Coefficient of Variation 90.9 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | Cmax of Total Antibody-Q1/3W Dosing Schedule | 51.2 μg/mL | Geometric Coefficient of Variation 23.3 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | Cmax of Total Antibody-Q2/3W Dosing Schedule: Day 1 | 26.2 μg/mL | Geometric Coefficient of Variation 39.8 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | Cmax of Total Antibody-Q2/3W Dosing Schedule: Day 8 | 39.1 μg/mL | Geometric Coefficient of Variation 73.7 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | Cmax of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 1 | 28.6 μg/mL | Geometric Coefficient of Variation 40.8 |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | Cmax of Zilovertamab Vedotin-Q2/3W Dosing Schedule: Day 8 | 35.0 μg/mL | Geometric Coefficient of Variation 90.3 |
Secondary
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
Population: Responding Analysis Set which included data from participants in the FAS who had measurable disease, who could be evaluated for tumor response with both baseline and on-study tumor evaluations, and who achieved an objective response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Zilovertamab Vedotin Q1/3W | Duration of Response (DOR)- BICR | 1 Months |
Secondary
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
Population: Evaluable Analysis Set which included participants in the FAS who had the necessary baseline and on-study measurements to provide interpretable results for specific parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zilovertamab Vedotin Q1/3W | Maximum Plasma Concentration (Cmax) of Zilovertamab Vedotin-Q1/3W Dosing Schedule | 53.4 μg/mL | Geometric Coefficient of Variation 20.5 |
Secondary
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
Population: FAS which included all participants who received ≥1 dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zilovertamab Vedotin Q1/3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 7 Participants |
| Zilovertamab Vedotin Q2/3W | Number of Participants Who Discontinued Study Treatment Due to an AE | 6 Participants |
Secondary
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
Population: FAS which included all participants who received ≥1 dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zilovertamab Vedotin Q1/3W | Number of Participants Who Experienced an Adverse Event (AE) | 70 Participants |
| Zilovertamab Vedotin Q2/3W | Number of Participants Who Experienced an Adverse Event (AE) | 32 Participants |
Secondary
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
Population: FAS which included all participants who received ≥1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zilovertamab Vedotin Q1/3W | ORR- Investigator Assessed | 1.4 Percentage of Participants |
| Zilovertamab Vedotin Q2/3W | ORR- Investigator Assessed | 0.0 Percentage of Participants |
Secondary
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
Population: FAS which included all participants who received ≥1 dose of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Zilovertamab Vedotin Q1/3W | Overall Survival (OS) | 8.3 Months |
| Zilovertamab Vedotin Q2/3W | Overall Survival (OS) | 5.5 Months |
Secondary
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
Population: FAS which included all participants who received ≥1 dose of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Zilovertamab Vedotin Q1/3W | Progression-free Survival (PFS)- BICR | 2.3 Months |
| Zilovertamab Vedotin Q2/3W | Progression-free Survival (PFS)- BICR | 1.9 Months |
Secondary
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
Population: Responding Analysis Set which included data from participants in the FAS who had measurable disease, who could be evaluated for tumor response with both baseline and on-study tumor evaluations, and who achieved an objective response.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zilovertamab Vedotin Q1/3W | Time to Response (TTR)- BICR | 1.9 Months |
Secondary
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
Population: FAS which included all participants who received ≥1 dose of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Zilovertamab Vedotin Q1/3W | Time to Treatment Failure (TTF)- BICR | 2.2 Months |
| Zilovertamab Vedotin Q2/3W | Time to Treatment Failure (TTF)- BICR | 1.9 Months |