Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) |
The percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR is defined as disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as a =30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. |
Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]). |
|
| Secondary |
Duration of Objective Response (DOR) Per BICR |
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or to death due to any cause, whichever comes first. CR and PR are defined in ORR per BICR endpoint. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. The appearance of one or more new lesions is also considered progression. DOR was analyzed using Kaplan-Meier methodology. |
Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]). |
|
| Secondary |
Progression-Free Survival (PFS) Per BICR |
The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first. PD is defined in the DOR per BICR endpoint. |
Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]). |
|
| Secondary |
ORR Per Investigator Assessment |
The percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR and PR are defined in the ORR per BICR endpoint. |
Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]). |
|
| Secondary |
DOR Per Investigator Assessment |
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD or to death due to any cause, whichever comes first. CR and PR are defined in ORR per BICR endpoint. PD is defined in the DOR per BICR endpoint. |
Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]). |
|
| Secondary |
PFS Per Investigator Assessment |
The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first. PD is defined in the DOR per BICR endpoint. |
Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]). |
|
| Secondary |
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) |
A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose. |
Up to data cut-off date of 08 Sept 2020 (The median duration of treatment was 4.60 months for Cohort 1 [range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [range: 0.3, 24.6 months]). |
|
| Secondary |
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) |
A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose. |
Up to data cut-off date of 08 Sept 2020 (The median duration of treatment was 4.60 months for Cohort 1 [full range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [full range: 0.3, 24.6 months]). |
|
| Secondary |
Incidence of Antitherapeutic Antibody (ATA) |
Participants who were tested positive for ATA at any time post-baseline were considered to be transiently positive or persistently positive if >=2 consecutive samples were confirmed as positive. |
Up to data cut-off date of 08 Sept 2020 (The median duration of treatment was 4.60 months for Cohort 1 [full range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [full range: 0.3, 24.6 months]). |
|
| Secondary |
Disease Control Rate at 16 Weeks (DCR16) Per BICR |
Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. CR and PR are defined in ORR per BICR endpoint. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
Up to Week 16. Data cut-off date 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2. |
|
| Secondary |
DCR16 Per Investigator Assessment |
Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. CR and PR are defined in ORR per BICR endpoint. SD is defined in DCR16 per BICR endpoint. |
Up to Week 16. Data cut-off date 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2. |
|
| Secondary |
Overall Survival (OS) at Time of Primary Analysis |
OS is defined as the time from first dose of enfortumab vedotin to death from any cause. This data is part of a pre-specified primary analysis. Updated data will be provided in a separate outcome measure upon study completion. |
Up to data cut-off date of 08 Sept 2020 (Cohort 1 median follow-up time: 28.4 months [range 0.49, 32.62]. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]). |
|
| Secondary |
Number of Participants With Adverse Events (AEs) at Time of Primary Analysis |
An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A treatment emergent adverse event (TEAE) was defined as a newly occurring or worsening AE after the first dose of study treatment and within 30 days after the last dose of study treatment. This data is part of a pre-specified primary analysis. Updated data will be provided in a separate outcome measure upon study completion. |
Up to data cut-off date of 08 Sept 2020 (The median duration of treatment was 4.60 months for Cohort 1 [range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [range: 0.3, 24.6 months]). |
|
| Secondary |
Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum) |
Cmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22. |
Up to data cut-off date of 08 Sept 2020. Collected during cycle 1 and 2 of treatment (approximately 2 months) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22. |
|
| Secondary |
PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum) |
Tmax was derived from the PK blood samples collected. Time of maximum concentration corresponds to the end of infusion sample time. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22. |
Up to data cut-off date of 08 Sept 2020. Collected during cycle 1 and 2 of treatment (approximately 2 months) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22. |
|
| Secondary |
PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) |
AUC was derived from the PK blood samples collected. |
Up to data cut-off date of 08 Sept 2020. AUC0-7 was assessed (in cycles 1 and 2) based on concentration data from Day 1 to Day 8 (pre dose) and AUC0-14 was assessed based on data from D15 (pre dose) to D29 (pre-dose). |
|
| Secondary |
PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma) |
Cmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22. |
Up to data cut-off date of 08 Sept 2020. Collected during cycle 1 and 2 of treatment (approximately 2 months) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22. |
|
| Secondary |
PK Parameter for Free MMAE: Tmax (Plasma) |
Tmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22. |
Up to data cut-off date of 08 Sept 2020. Collected during cycle 1 and 2 of treatment (approximately 2 months) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22. |
|
| Secondary |
PK Parameter for Free MMAE: AUC (Plasma) |
AUC was derived from the PK blood samples collected. |
Up to data cut-off date of 08 Sept 2020. AUC0-7 was assessed (in cycles 1 and 2) based on concentration data from Day 1 to Day 8 (pre dose) and AUC0-14 was assessed based on data from D15 (pre dose) to D29 (pre-dose). |
|
| Secondary |
PK Parameter for Total Antibody (TAb): Cmax (Serum) |
Cmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22. |
Up to data cut-off date of 08 Sept 2020. Collected during cycle 1 and 2 of treatment (approximately 2 months) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22. |
|
| Secondary |
PK Parameter for TAb: Tmax (Serum) |
Tmax was derived from the PK blood samples collected. Time of maximum concentration corresponds to the end of infusion sample time. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22. |
Up to data cut-off date of 08 Sept 2020. Collected during cycle 1 and 2 of treatment (approximately 2 months) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22. |
|
| Secondary |
PK Parameter for TAb: AUC (Serum) |
AUC was derived from the PK blood samples collected. |
Up to data cut-off date of 08 Sept 2020. AUC0-7 was assessed (in cycles 1 and 2) based on concentration data from Day 1 to Day 8 (pre dose) and AUC0-14 was assessed based on data from D15 (pre dose) to D29 (pre-dose). |
|
| Secondary |
Overall Survival (OS) |
|
Updated Time Frame description will be provided at study completion. |
|
| Secondary |
Number of Participants With Adverse Events (AEs) |
An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A treatment emergent adverse event (TEAE) was defined as a newly occurring or worsening AE after the first dose of study treatment and within 30 days after the last dose of study treatment. |
Updated Time Frame description will be provided at study completion. |
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