Carcinoma, Transitional Cell, Renal Pelvis Neoplasms, Ureteral Neoplasms, Urethral Neoplasms, Urinary Bladder Neoplasms, Urologic Neoplasms, Urothelial Cancer
Conditions
Keywords
Enfortumab vedotin, Metastatic Urothelial Cancer, ASG-22CE, Locally Advanced Urothelial Cancer, Antibody-Drug Conjugate, Nectin-4, Platinum-naïve, Cisplatin-ineligible, Antineoplastic Agents, Drug Therapy, ASG-22ME
Brief summary
This is a study that will test how an experimental drug (enfortumab vedotin) affects patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other areas of the body. This clinical trial will enroll patients who were previously treated with a kind of anticancer drug called an immune checkpoint inhibitor (CPI). Some CPIs have been approved for the treatment of urothelial cancer. This study will test if the cancer shrinks with treatment. This study will also look at the side effects of the drug. A side effect is a response to a drug that is not part of the treatment effect. Patients who sign up for this trial must also fall into one of these categories: * Patients have already received treatment with platinum-containing chemotherapy * Patients have never received platinum-containing treatment and are not eligible for treatment with cisplatin.
Detailed description
Japan Pharmaceuticals and Medical Devices Agency (PMDA) has approved enfortumab vedotin (Padcev) for the treatment of advanced urothelial cancer. The study will continue as a post marketing study in Japan. This study will examine the safety and anticancer activity of enfortumab vedotin given intravenously to patients with locally advanced or metastatic urothelial cancer who previously received a CPI and either previously received platinum-containing chemotherapy (Cohort 1) or are platinum-naïve and cisplatin-ineligible (Cohort 2). Patients who received platinum in the adjuvant/neoadjuvant setting and did not progress within 12 months of completion will be considered platinum-naïve. Approximately 100 patients are expected to be enrolled in each cohort. The primary goal of the study is to determine the confirmed ORR of enfortumab vedotin.
Interventions
DRUGEnfortumab vedotin
Intravenous (IV) infusion on days 1, 8 and 15 every 28 days
Sponsors
Seagen Inc.
Astellas Pharma Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
single-arm, open-label, multi-cohort, multicenter study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically documented urothelial carcinoma (squamous differentiation or mixed cell types allowed). * Metastatic disease or locally advanced disease that is not resectable. * Must have received prior treatment with a CPI in the locally advanced or metastatic urothelial cancer setting. A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible. * Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment (Cohort 2). * Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy. * Tumor tissue samples must be available for submission to the sponsor prior to study treatment. * Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1). * An Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 for Cohort 1 or ≤2 for Cohort 2. * Anticipated life expectancy of ≥3 months as assessed by the investigator.
Exclusion criteria
* Ongoing sensory or motor neuropathy Grade ≥2. * Active central nervous system (CNS) metastases. * Immunotherapy related myocarditis, colitis, uveitis, or pneumonitis. * Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs). * Uncontrolled tumor-related pain or impending spinal cord compression.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) | 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) | ORR was defined as 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Per BICR | 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) | 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 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. |
| ORR Per Investigator Assessment | 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) | ORR was defined as the percentage of participants with confirmed CR or PR according to 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. |
| DOR Per Investigator Assessment | 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) | 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. 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. |
| PFS Per Investigator Assessment | 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) | 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 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. |
| Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | 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] | A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose. Abnormalities were graded based on National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 - Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening. |
| Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | 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] | A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose. Abnormalities were graded based NCI CTCAE version 4.03 - Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening. |
| Incidence of Antitherapeutic Antibody (ATA) | 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] | 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. |
| Disease Control Rate at 16 Weeks (DCR16) Per BICR | Up to Week 16 | Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. 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. 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. |
| DCR16 Per Investigator Assessment | Up to Week 16 | Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. 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. 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. 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. |
| Overall Survival (OS): Primary Analysis | 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] | OS is defined as the time from first dose of enfortumab vedotin to death from any cause. |
| Number of Participants With Adverse Events (AEs): Primary Analysis | 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] | AE=untoward medical occurrence associated with use of study intervention, whether or not considered related. Treatment emergent adverse event (TEAE)=newly occurring/worsening AE after first dose of study treatment, within 30 days after last dose. According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: Grade(G)3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE. Participants who discontinued treatment due to treatment related TEAEs captured under TEAEs leading to treatment discontinuation. SAE=event at any dose led to death;life-threatening;required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Treatment relatedness was judged by investigator. |
| Duration of Objective Response (DOR) Per BICR | 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) | 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 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. 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. |
| PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum) | Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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 | 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. |
| PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) | 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) | AUC was derived from the PK blood samples collected. |
| PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma) | Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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 | 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. |
| PK Parameter for Free MMAE: Tmax (Plasma) | Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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 | 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. |
| PK Parameter for Free MMAE: AUC (Plasma) | 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) | AUC was derived from the PK blood samples collected. |
| PK Parameter for Total Antibody (TAb): Cmax (Serum) | Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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 | 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. |
| PK Parameter for TAb: Tmax (Serum) | Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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 | 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. |
| PK Parameter for TAb: AUC (Serum) | 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) | AUC was derived from the PK blood samples collected. |
| Number of Participants With Adverse Events (AEs): Final Analysis | Cohort 1: median treatment duration time: 4.60 months (range 0.5, 43.0); Cohort 2: median treatment duration time: 5.98 months (range 0.3 to 25.8) | AE=untoward medical occurrence associated with use of study intervention, whether or not considered related. Treatment emergent adverse event (TEAE)=newly occurring/worsening AE after first dose of study treatment, within 30 days after last dose. According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: Grade(G)3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE. Participants who discontinued treatment due to treatment related TEAEs captured under TEAEs leading to treatment discontinuation. SAE=event at any dose led to death;life-threatening;required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Treatment relatedness was judged by investigator. |
| Overall Survival (OS): Final Analysis | Cohort 1: median follow-up: 61.0 months (range 59.63, 62.36); Cohort 2: median follow-up time: 45.8 months (range 44.91 to 48.95) | OS is defined as the time from first dose of enfortumab vedotin to death from any cause. |
| Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum) | Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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 | 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. |
Countries
France, Germany, Italy, Japan, Netherlands, South Korea, Spain, United States
Participant flow
Pre-assignment details
Eligible participants with locally advanced or metastatic urothelial cancer who have previously received systemic therapy with a programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitor and met inclusion criteria and none of the exclusion criteria were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Enfortumab Vedotin - Cohort 1 Participants in Cohort 1 had received prior treatment with platinum-containing chemotherapy. Enfortumab vedotin, at a dose of 1.25 mg/kg, was administered to participants as an IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle. | 125 |
| Enfortumab Vedotin - Cohort 2 Participants in Cohort 2 had received no platinum-containing chemotherapy were ineligible for treatment with cisplatin at the time of enrollment. Enfortumab vedotin, at a dose of 1.25 mg/kg, was administered to participants as an IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle. | 89 |
| Total | 214 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 104 | 72 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Study closed in 2023,as all milestones reached, majority of participants completed 5 years follow-up | 12 | 12 |
| Overall Study | Withdrawal by Subject | 9 | 4 |
Baseline characteristics
| Characteristic | Enfortumab Vedotin - Cohort 1 | Total | Enfortumab Vedotin - Cohort 2 |
|---|---|---|---|
| Age, Continuous | 69.0 Years | 72.0 Years | 75.0 Years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 40 Participants | 77 Participants | 37 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 85 Participants | 126 Participants | 41 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 | 0 Participants | 11 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 6 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 118 Participants | 201 Participants | 83 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 31 Participants | 20 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 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 | 6 Participants | 13 Participants | 7 Participants |
| Race (NIH/OMB) White | 106 Participants | 168 Participants | 62 Participants |
| Region of Enrollment East Asia | 8 Participants | 26 Participants | 18 Participants |
| Region of Enrollment Europe | 0 Participants | 14 Participants | 14 Participants |
| Region of Enrollment North America | 117 Participants | 174 Participants | 57 Participants |
| Sex: Female, Male Female | 37 Participants | 60 Participants | 23 Participants |
| Sex: Female, Male Male | 88 Participants | 154 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 104 / 125 | 72 / 89 |
| other Total, other adverse events | 123 / 125 | 88 / 89 |
| serious Total, serious adverse events | 59 / 125 | 35 / 89 |
Outcome results
Primary
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
ORR was defined as 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.
Time frame: 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)
Population: Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enfortumab Vedotin - Cohort 1 | Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) | 44 Percentage of Participants |
| Enfortumab Vedotin - Cohort 2 | Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) | 51.7 Percentage of Participants |
Secondary
DCR16 Per Investigator Assessment
Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. 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. 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. 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.
Time frame: Up to Week 16
Population: Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enfortumab Vedotin - Cohort 1 | DCR16 Per Investigator Assessment | 55 Percentage of Participants |
| Enfortumab Vedotin - Cohort 2 | DCR16 Per Investigator Assessment | 64.0 Percentage of Participants |
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 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. 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.
Time frame: Up to Week 16
Population: Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enfortumab Vedotin - Cohort 1 | Disease Control Rate at 16 Weeks (DCR16) Per BICR | 50 Percentage of Participants |
| Enfortumab Vedotin - Cohort 2 | Disease Control Rate at 16 Weeks (DCR16) Per BICR | 58.4 Percentage of Participants |
Secondary
DOR Per Investigator Assessment
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. 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.
Time frame: 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)
Population: Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enfortumab Vedotin - Cohort 1 | DOR Per Investigator Assessment | 7.9 Months |
| Enfortumab Vedotin - Cohort 2 | DOR Per Investigator Assessment | 10.7 Months |
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 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. 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.
Time frame: 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)
Population: Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enfortumab Vedotin - Cohort 1 | Duration of Objective Response (DOR) Per BICR | 7.6 Months |
| Enfortumab Vedotin - Cohort 2 | Duration of Objective Response (DOR) Per BICR | 10.9 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.
Time frame: 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]
Population: Safety Analysis Set: Participants who received at least one dose of enfortumab vedotin. Here, 'Overall Number of Participants Analyzed' signifies ATA subset (participants with a baseline and at least one post-baseline sample). Here, 'Number Analyzed' signifies participants evaluable for specified rows.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | Incidence of Antitherapeutic Antibody (ATA) | Baseline Negative | Transiently positive post-baseline | 2 Participants |
| Enfortumab Vedotin - Cohort 1 | Incidence of Antitherapeutic Antibody (ATA) | Baseline Positive | Negative post-baseline | 1 Participants |
| Enfortumab Vedotin - Cohort 1 | Incidence of Antitherapeutic Antibody (ATA) | Baseline Negative | Negative post-baseline | 109 Participants |
| Enfortumab Vedotin - Cohort 1 | Incidence of Antitherapeutic Antibody (ATA) | Baseline Negative | Persistently positive post-baseline | 1 Participants |
| Enfortumab Vedotin - Cohort 1 | Incidence of Antitherapeutic Antibody (ATA) | Baseline Positive | Persistently positive post-baseline | 0 Participants |
| Enfortumab Vedotin - Cohort 1 | Incidence of Antitherapeutic Antibody (ATA) | Baseline Positive | Transiently positive post-baseline | 1 Participants |
| Enfortumab Vedotin - Cohort 2 | Incidence of Antitherapeutic Antibody (ATA) | Baseline Positive | Persistently positive post-baseline | 0 Participants |
| Enfortumab Vedotin - Cohort 2 | Incidence of Antitherapeutic Antibody (ATA) | Baseline Negative | Negative post-baseline | 76 Participants |
| Enfortumab Vedotin - Cohort 2 | Incidence of Antitherapeutic Antibody (ATA) | Baseline Negative | Transiently positive post-baseline | 3 Participants |
| Enfortumab Vedotin - Cohort 2 | Incidence of Antitherapeutic Antibody (ATA) | Baseline Negative | Persistently positive post-baseline | 1 Participants |
| Enfortumab Vedotin - Cohort 2 | Incidence of Antitherapeutic Antibody (ATA) | Baseline Positive | Negative post-baseline | 1 Participants |
| Enfortumab Vedotin - Cohort 2 | Incidence of Antitherapeutic Antibody (ATA) | Baseline Positive | Transiently positive post-baseline | 0 Participants |
Secondary
Number of Participants With Adverse Events (AEs): Final Analysis
AE=untoward medical occurrence associated with use of study intervention, whether or not considered related. Treatment emergent adverse event (TEAE)=newly occurring/worsening AE after first dose of study treatment, within 30 days after last dose. According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: Grade(G)3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE. Participants who discontinued treatment due to treatment related TEAEs captured under TEAEs leading to treatment discontinuation. SAE=event at any dose led to death;life-threatening;required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Treatment relatedness was judged by investigator.
Time frame: Cohort 1: median treatment duration time: 4.60 months (range 0.5, 43.0); Cohort 2: median treatment duration time: 5.98 months (range 0.3 to 25.8)
Population: Safety Analysis Set: includes all participants who received at least one dose of enfortumab vedotin.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Final Analysis | Any treatment-emergent AEs (TEAEs) | 125 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Final Analysis | Treatment-related TEAEs | 117 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Final Analysis | Any grade 3-5 TEAEs | 93 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Final Analysis | Treatment-related grade 3-5 TEAEs | 70 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Final Analysis | Any serious TEAEs | 59 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Final Analysis | Treatment-related serious TEAEs | 24 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Final Analysis | Any TEAEs leading to treatment discontinuation | 22 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Final Analysis | Treatment-related TEAEs leading to treatment discontinuation | 16 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Final Analysis | Any TEAEs leading to death | 7 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Final Analysis | Treatment-related TEAEs leading to death | 0 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Final Analysis | Treatment-related TEAEs leading to treatment discontinuation | 17 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Final Analysis | Any treatment-emergent AEs (TEAEs) | 89 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Final Analysis | Treatment-related serious TEAEs | 15 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Final Analysis | Treatment-related TEAEs | 86 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Final Analysis | Treatment-related TEAEs leading to death | 3 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Final Analysis | Any grade 3-5 TEAEs | 62 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Final Analysis | Any TEAEs leading to treatment discontinuation | 21 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Final Analysis | Treatment-related grade 3-5 TEAEs | 49 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Final Analysis | Any TEAEs leading to death | 8 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Final Analysis | Any serious TEAEs | 35 Participants |
Secondary
Number of Participants With Adverse Events (AEs): Primary Analysis
AE=untoward medical occurrence associated with use of study intervention, whether or not considered related. Treatment emergent adverse event (TEAE)=newly occurring/worsening AE after first dose of study treatment, within 30 days after last dose. According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: Grade(G)3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE. Participants who discontinued treatment due to treatment related TEAEs captured under TEAEs leading to treatment discontinuation. SAE=event at any dose led to death;life-threatening;required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Treatment relatedness was judged by investigator.
Time frame: 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]
Population: Safety Analysis Set: includes all participants who received at least one dose of enfortumab vedotin.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Primary Analysis | Treatment-related serious TEAEs | 24 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Primary Analysis | Any treatment-emergent AEs (TEAEs) | 125 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Primary Analysis | Treatment-related TEAEs | 117 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Primary Analysis | Any grade 3-5 TEAEs | 93 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Primary Analysis | Treatment-related grade 3-5 TEAEs | 70 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Primary Analysis | Any serious TEAEs | 59 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Primary Analysis | Any TEAEs leading to treatment discontinuation | 21 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Primary Analysis | Treatment-related TEAEs leading to treatment discontinuation | 15 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Primary Analysis | Any TEAEs leading to death | 7 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Adverse Events (AEs): Primary Analysis | Treatment-related TEAEs leading to death | 0 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Primary Analysis | Treatment-related TEAEs leading to treatment discontinuation | 14 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Primary Analysis | Any TEAEs leading to treatment discontinuation | 18 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Primary Analysis | Any serious TEAEs | 35 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Primary Analysis | Any treatment-emergent AEs (TEAEs) | 89 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Primary Analysis | Treatment-related serious TEAEs | 15 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Primary Analysis | Treatment-related TEAEs | 86 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Primary Analysis | Treatment-related TEAEs leading to death | 3 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Primary Analysis | Any grade 3-5 TEAEs | 62 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Primary Analysis | Any TEAEs leading to death | 8 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Adverse Events (AEs): Primary Analysis | Treatment-related grade 3-5 TEAEs | 49 Participants |
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. Abnormalities were graded based on National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 - Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Time frame: 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]
Population: Safety Analysis set. Here 'Number Analyzed' for each laboratory parameter is based on the number of participants who received at least one dose of enfortumab vedotin and have a baseline and post-baseline laboratory value.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Lymphocytes decreased (grade 3-4) | 12 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Leukocytes decreased (all grades) | 33 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Lymphocytes increased (all grades) | 0 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Platelets decreased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Lymphocytes increased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Leukocytes decreased (grade 3-4) | 5 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Neutrophils decreased (all grades) | 28 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Hemoglobin decreased (grade 3-4) | 12 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Neutrophils decreased (grade 3-4) | 7 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Lymphocytes decreased (all grades) | 55 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Platelets decreased (all grades) | 39 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Hemoglobin decreased (all grades) | 52 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Platelets decreased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Hemoglobin decreased (all grades) | 39 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Hemoglobin decreased (grade 3-4) | 4 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Leukocytes decreased (all grades) | 28 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Leukocytes decreased (grade 3-4) | 4 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Lymphocytes decreased (all grades) | 61 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Lymphocytes decreased (grade 3-4) | 13 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Lymphocytes increased (all grades) | 1 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Lymphocytes increased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Neutrophils decreased (all grades) | 27 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Neutrophils decreased (grade 3-4) | 8 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology) | Platelets decreased (all grades) | 20 Participants |
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. Abnormalities were graded based NCI CTCAE version 4.03 - Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Time frame: 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]
Population: Safety Analysis set. Here 'Number Analyzed' for each laboratory parameter is based on the number of participants who received at least one dose of enfortumab vedotin and have a baseline and post-baseline laboratory value.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Creatinine increased (grade 3-4) | 2 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Glucose increased (all grades) | NA Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Glucose decreased (all grades) | 32 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Aspartate aminotransferase increased (all grades) | 79 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Glucose decreased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Glucose increased (grade 3-4) | 10 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Aspartate aminotransferase increased (grade 3-4) | 3 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Alanine aminotransferase increased (grade 3-4) | 1 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Phosphate decreased (grade 3-4) | 12 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Bilirubin increased (all grades) | 13 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Potassium decreased (all grades) | 25 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Phosphate decreased (all grades) | 42 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Potassium decreased (grade 3-4) | 2 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Bilirubin increased (grade 3-4) | 1 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Potassium increased (all grades) | 13 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Alkaline phosphatase increased (all grades) | 21 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Potassium increased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Calcium decreased (all grades) | 15 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Sodium decreased (all grades) | 54 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Sodium decreased (grade 3-4) | 10 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Sodium increased (all grades) | 2 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Calcium decreased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Sodium increased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Alanine aminotransferase increased (all grades) | 34 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Urate increased (all grades) | 32 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Calcium increased (all grades) | 1 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Urate increased (grade 3-4) | 8 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Albumin decreased (grade 3-4) | 1 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Amylase increased (all grades) | 20 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Calcium increased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Amylase increased (grade 3-4) | 1 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Albumin decreased (all grades) | 38 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Lipase increased (all grades) | 37 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Creatinine increased (all grades) | 73 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Lipase increased (grade 3-4) | 12 Participants |
| Enfortumab Vedotin - Cohort 1 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Alkaline phosphatase increased (grade 3-4) | 1 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Lipase increased (grade 3-4) | 10 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Albumin decreased (all grades) | 16 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Albumin decreased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Alkaline phosphatase increased (all grades) | 12 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Glucose increased (grade 3-4) | 11 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Sodium decreased (all grades) | 28 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Alanine aminotransferase increased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Alkaline phosphatase increased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Aspartate aminotransferase increased (all grades) | 52 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Aspartate aminotransferase increased (grade 3-4) | 2 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Bilirubin increased (all grades) | 5 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Bilirubin increased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Calcium decreased (all grades) | 7 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Calcium decreased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Calcium increased (all grades) | 7 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Calcium increased (grade 3-4) | 3 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Creatinine increased (all grades) | 46 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Creatinine increased (grade 3-4) | 3 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Glucose decreased (all grades) | 26 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Glucose decreased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Glucose increased (all grades) | NA Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Phosphate decreased (all grades) | 22 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Phosphate decreased (grade 3-4) | 6 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Potassium decreased (all grades) | 11 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Potassium decreased (grade 3-4) | 1 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Potassium increased (all grades) | 17 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Potassium increased (grade 3-4) | 5 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Sodium decreased (grade 3-4) | 6 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Sodium increased (all grades) | 1 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Sodium increased (grade 3-4) | 0 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Urate increased (all grades) | 38 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Urate increased (grade 3-4) | 8 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Amylase increased (all grades) | 18 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Amylase increased (grade 3-4) | 3 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Lipase increased (all grades) | 32 Participants |
| Enfortumab Vedotin - Cohort 2 | Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) | Alanine aminotransferase increased (all grades) | 26 Participants |
Secondary
ORR Per Investigator Assessment
ORR was defined as the percentage of participants with confirmed CR or PR according to 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.
Time frame: 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)
Population: Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enfortumab Vedotin - Cohort 1 | ORR Per Investigator Assessment | 39 Percentage of Participants |
| Enfortumab Vedotin - Cohort 2 | ORR Per Investigator Assessment | 50.6 Percentage of Participants |
Secondary
Overall Survival (OS): Final Analysis
OS is defined as the time from first dose of enfortumab vedotin to death from any cause.
Time frame: Cohort 1: median follow-up: 61.0 months (range 59.63, 62.36); Cohort 2: median follow-up time: 45.8 months (range 44.91 to 48.95)
Population: Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enfortumab Vedotin - Cohort 1 | Overall Survival (OS): Final Analysis | 12.4 Months |
| Enfortumab Vedotin - Cohort 2 | Overall Survival (OS): Final Analysis | 15.6 Months |
Secondary
Overall Survival (OS): Primary Analysis
OS is defined as the time from first dose of enfortumab vedotin to death from any cause.
Time frame: 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]
Population: Full analysis set: included all enrolled participants who received at least one dose of enfortumab vedotin.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enfortumab Vedotin - Cohort 1 | Overall Survival (OS): Primary Analysis | 12.4 Months |
| Enfortumab Vedotin - Cohort 2 | Overall Survival (OS): Primary Analysis | 14.7 Months |
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 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.
Time frame: 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)
Population: Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enfortumab Vedotin - Cohort 1 | PFS Per Investigator Assessment | 5.8 Months |
| Enfortumab Vedotin - Cohort 2 | PFS Per Investigator Assessment | 7.2 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.
Time frame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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
Population: PK analysis set: all participants who received enfortumab vedotin and from whom at least one blood sample was collected and assayed for enfortumab vedotin, monomethyl auristatin E (MMAE) or total antibody (Tab) concentration. Corresponding records of the time of dosing and sample collection must also be available for all enfortumab vedotin. Here, 'Number Analyzed'= participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum) | Cycle 1, Day 1 | 26.6 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 28.5 |
| Enfortumab Vedotin - Cohort 1 | Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum) | Cycle 1, Day 15 | 26.0 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 28.3 |
| Enfortumab Vedotin - Cohort 1 | Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum) | Cycle 2, Day 1 | 24.5 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 31.4 |
| Enfortumab Vedotin - Cohort 1 | Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum) | Cycle 2, Day 15 | 26.3 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 25.2 |
| Enfortumab Vedotin - Cohort 2 | Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum) | Cycle 2, Day 15 | 20.7 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 27.4 |
| Enfortumab Vedotin - Cohort 2 | Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum) | Cycle 1, Day 1 | 23.9 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 24.4 |
| Enfortumab Vedotin - Cohort 2 | Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum) | Cycle 2, Day 1 | 22.0 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 24.5 |
| Enfortumab Vedotin - Cohort 2 | Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum) | Cycle 1, Day 15 | 21.7 Microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 29.7 |
Secondary
PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum)
AUC was derived from the PK blood samples collected.
Time frame: 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)
Population: PK analysis set: all participants who received enfortumab vedotin and from whom at least one blood sample was collected and assayed for enfortumab vedotin, monomethyl auristatin E (MMAE) or total antibody (Tab) concentration. Corresponding records of the time of dosing and sample collection must also be available for all enfortumab vedotin. Here, 'Number Analyzed'= participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) | 7-day post-infusion AUC (AUC(d0-7)) - Cycle 1, Day 1 | 34.6 Day*microgram per milliliter | Geometric Coefficient of Variation 34 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) | AUC(d0-7) - Cycle 1, Day 8 | 31.3 Day*microgram per milliliter | Geometric Coefficient of Variation 43.8 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) | AUC(d0-7) - Cycle 2, Day 1 | 36.4 Day*microgram per milliliter | Geometric Coefficient of Variation 36.7 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) | AUC(d0-7) - Cycle 2, Day 8 | 35.9 Day*microgram per milliliter | Geometric Coefficient of Variation 41.2 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) | 14-day post-infusion AUC (AUC(d0-14)) - Cycle 1, Day 8 | 34.7 Day*microgram per milliliter | Geometric Coefficient of Variation 44.7 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) | AUC(d0-14) - Cycle 2, Day 15 | 41.2 Day*microgram per milliliter | Geometric Coefficient of Variation 40.4 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) | 14-day post-infusion AUC (AUC(d0-14)) - Cycle 1, Day 8 | 30.9 Day*microgram per milliliter | Geometric Coefficient of Variation 47.5 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) | 7-day post-infusion AUC (AUC(d0-7)) - Cycle 1, Day 1 | 33.5 Day*microgram per milliliter | Geometric Coefficient of Variation 41.4 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) | AUC(d0-7) - Cycle 2, Day 8 | 27.8 Day*microgram per milliliter | Geometric Coefficient of Variation 35.8 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) | AUC(d0-7) - Cycle 1, Day 8 | 26.3 Day*microgram per milliliter | Geometric Coefficient of Variation 46 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) | AUC(d0-14) - Cycle 2, Day 15 | 33.1 Day*microgram per milliliter | Geometric Coefficient of Variation 36.6 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) | AUC(d0-7) - Cycle 2, Day 1 | 32.0 Day*microgram per milliliter | Geometric Coefficient of Variation 30 |
Secondary
PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum)
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.
Time frame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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
Population: PK analysis set: all participants who received enfortumab vedotin and from whom at least one blood sample was collected and assayed for enfortumab vedotin, monomethyl auristatin E (MMAE) or total antibody (Tab) concentration. Corresponding records of the time of dosing and sample collection must also be available for all enfortumab vedotin. Here, 'Number Analyzed'= participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum) | Cycle 1, Day 1 | 0.0278 Days |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum) | Cycle 1, Day 15 | 0.0285 Days |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum) | Cycle 2, Day 1 | 0.0264 Days |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum) | Cycle 2, Day 15 | 0.0285 Days |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum) | Cycle 2, Day 15 | 0.0257 Days |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum) | Cycle 1, Day 1 | 0.0264 Days |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum) | Cycle 2, Day 1 | 0.0264 Days |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum) | Cycle 1, Day 15 | 0.0264 Days |
Secondary
PK Parameter for Free MMAE: AUC (Plasma)
AUC was derived from the PK blood samples collected.
Time frame: 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)
Population: PK analysis set: all participants who received enfortumab vedotin and from whom at least one blood sample was collected and assayed for enfortumab vedotin, MMAE or Tab concentration. Corresponding records of the time of dosing and sample collection must also be available for all enfortumab vedotin. Here, 'Overall Number of Participants Analyzed'=number of participants evaluable for this outcome measure. Here, 'Number Analyzed'= participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free MMAE: AUC (Plasma) | 7-day post-infusion AUC (AUC(d0-7)) - Cycle 1, Day 1 | 14.1 Day*nanogram per milliliter | Geometric Coefficient of Variation 81.7 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free MMAE: AUC (Plasma) | AUC(d0-7) - Cycle 1, Day 8 | 19.1 Day*nanogram per milliliter | Geometric Coefficient of Variation 79.1 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free MMAE: AUC (Plasma) | AUC(d0-7) - Cycle 2, Day 1 | 11.3 Day*nanogram per milliliter | Geometric Coefficient of Variation 58 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free MMAE: AUC (Plasma) | AUC(d0-7) - Cycle 2, Day 8 | 14.9 Day*nanogram per milliliter | Geometric Coefficient of Variation 64.7 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free MMAE: AUC (Plasma) | 14-day post-infusion AUC (AUC(d0-14)) - Cycle 1, Day 15 | 25.9 Day*nanogram per milliliter | Geometric Coefficient of Variation 74.7 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free MMAE: AUC (Plasma) | AUC(d0-14) - Cycle 2, Day 15 | 19.1 Day*nanogram per milliliter | Geometric Coefficient of Variation 61.2 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free MMAE: AUC (Plasma) | 14-day post-infusion AUC (AUC(d0-14)) - Cycle 1, Day 15 | 22.6 Day*nanogram per milliliter | Geometric Coefficient of Variation 76.4 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free MMAE: AUC (Plasma) | 7-day post-infusion AUC (AUC(d0-7)) - Cycle 1, Day 1 | 13.0 Day*nanogram per milliliter | Geometric Coefficient of Variation 64.1 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free MMAE: AUC (Plasma) | AUC(d0-7) - Cycle 2, Day 8 | 15.3 Day*nanogram per milliliter | Geometric Coefficient of Variation 60.2 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free MMAE: AUC (Plasma) | AUC(d0-7) - Cycle 1, Day 8 | 18.1 Day*nanogram per milliliter | Geometric Coefficient of Variation 65 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free MMAE: AUC (Plasma) | AUC(d0-14) - Cycle 2, Day 15 | 21.3 Day*nanogram per milliliter | Geometric Coefficient of Variation 65 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free MMAE: AUC (Plasma) | AUC(d0-7) - Cycle 2, Day 1 | 10.6 Day*nanogram per milliliter | Geometric Coefficient of Variation 65 |
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.
Time frame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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
Population: PK analysis set: all participants who received enfortumab vedotin and from whom at least one blood sample was collected and assayed for enfortumab vedotin, MMAE or Tab concentration. Corresponding records of the time of dosing and sample collection must also be available for all enfortumab vedotin. Here, 'Overall Number of Participants Analyzed'=number of participants evaluable for this outcome measure. Here, 'Number Analyzed'= participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free MMAE: Tmax (Plasma) | Cycle 1, Day 15 | 2.0 Days |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free MMAE: Tmax (Plasma) | Cycle 2, Day 1 | 2.0 Days |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free MMAE: Tmax (Plasma) | Cycle 2, Day 15 | 1.9 Days |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free MMAE: Tmax (Plasma) | Cycle 1, Day 1 | 1.9 Days |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free MMAE: Tmax (Plasma) | Cycle 1, Day 1 | 1.9 Days |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free MMAE: Tmax (Plasma) | Cycle 1, Day 15 | 1.9 Days |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free MMAE: Tmax (Plasma) | Cycle 2, Day 15 | 1.9 Days |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free MMAE: Tmax (Plasma) | Cycle 2, Day 1 | 1.8 Days |
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.
Time frame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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
Population: PK analysis set: all participants who received enfortumab vedotin and from whom at least one blood sample was collected and assayed for enfortumab vedotin, MMAE or Tab concentration. Corresponding records of the time of dosing and sample collection must also be available for all enfortumab vedotin. Here, 'Overall Number of Participants Analyzed'=number of participants evaluable for this outcome measure. Here, 'Number Analyzed'= participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma) | Cycle 1, Day 1 | 3.1 Nanogram per milliliter | Geometric Coefficient of Variation 67 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma) | Cycle 1, Day 15 | 3.9 Nanogram per milliliter | Geometric Coefficient of Variation 64.8 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma) | Cycle 2, Day 1 | 2.4 Nanogram per milliliter | Geometric Coefficient of Variation 57.4 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma) | Cycle 2, Day 15 | 3.0 Nanogram per milliliter | Geometric Coefficient of Variation 64.8 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma) | Cycle 2, Day 15 | 2.9 Nanogram per milliliter | Geometric Coefficient of Variation 59.9 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma) | Cycle 1, Day 1 | 2.6 Nanogram per milliliter | Geometric Coefficient of Variation 57.8 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma) | Cycle 2, Day 1 | 2.2 Nanogram per milliliter | Geometric Coefficient of Variation 60.8 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma) | Cycle 1, Day 15 | 3.5 Nanogram per milliliter | Geometric Coefficient of Variation 51.8 |
Secondary
PK Parameter for TAb: AUC (Serum)
AUC was derived from the PK blood samples collected.
Time frame: 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)
Population: PK analysis set: all participants who received enfortumab vedotin and from whom at least one blood sample was collected and assayed for enfortumab vedotin, monomethyl auristatin E (MMAE) or total antibody (Tab) concentration. Corresponding records of the time of dosing and sample collection must also be available for all enfortumab vedotin. Here, 'Number Analyzed'= participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | PK Parameter for TAb: AUC (Serum) | AUC(d0-7) - Cycle 2, Day 8 | 87.9 Day*microgram per milliliter | Geometric Coefficient of Variation 30.6 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for TAb: AUC (Serum) | 14-day post-infusion AUC (AUC(d0-14)) - Cycle 1, Day 15 | 98.1 Day*microgram per milliliter | Geometric Coefficient of Variation 38.8 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for TAb: AUC (Serum) | AUC(d0-14) - Cycle 2, Day 15 | 113.0 Day*microgram per milliliter | Geometric Coefficient of Variation 33.8 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for TAb: AUC (Serum) | 7-day post-infusion AUC (AUC(d0-7)) - Cycle 1, Day 1 | 63.4 Day*microgram per milliliter | Geometric Coefficient of Variation 33.6 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for TAb: AUC (Serum) | AUC(d0-7) - Cycle 1, Day 8 | 77.6 Day*microgram per milliliter | Geometric Coefficient of Variation 35.2 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for TAb: AUC (Serum) | AUC(d0-7) - Cycle 2, Day 1 | 73.2 Day*microgram per milliliter | Geometric Coefficient of Variation 33.5 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for TAb: AUC (Serum) | AUC(d0-7) - Cycle 1, Day 8 | 72.3 Day*microgram per milliliter | Geometric Coefficient of Variation 37.9 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for TAb: AUC (Serum) | AUC(d0-7) - Cycle 2, Day 8 | 81.0 Day*microgram per milliliter | Geometric Coefficient of Variation 30.9 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for TAb: AUC (Serum) | 7-day post-infusion AUC (AUC(d0-7)) - Cycle 1, Day 1 | 66.8 Day*microgram per milliliter | Geometric Coefficient of Variation 34.3 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for TAb: AUC (Serum) | 14-day post-infusion AUC (AUC(d0-14)) - Cycle 1, Day 15 | 91.1 Day*microgram per milliliter | Geometric Coefficient of Variation 40.3 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for TAb: AUC (Serum) | AUC(d0-7) - Cycle 2, Day 1 | 72.9 Day*microgram per milliliter | Geometric Coefficient of Variation 26.4 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for TAb: AUC (Serum) | AUC(d0-14) - Cycle 2, Day 15 | 109.7 Day*microgram per milliliter | Geometric Coefficient of Variation 41.5 |
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.
Time frame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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
Population: PK analysis set: all participants who received enfortumab vedotin and from whom at least one blood sample was collected and assayed for enfortumab vedotin, monomethyl auristatin E (MMAE) or total antibody (Tab) concentration. Corresponding records of the time of dosing and sample collection must also be available for all enfortumab vedotin. Here, 'Number Analyzed'= participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | PK Parameter for TAb: Tmax (Serum) | Cycle 1, Day 1 | 0.0278 Days |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for TAb: Tmax (Serum) | Cycle 1, Day 15 | 0.0285 Days |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for TAb: Tmax (Serum) | Cycle 2, Day 1 | 0.0264 Days |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for TAb: Tmax (Serum) | Cycle 2, Day 15 | 0.0285 Days |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for TAb: Tmax (Serum) | Cycle 2, Day 15 | 0.0257 Days |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for TAb: Tmax (Serum) | Cycle 1, Day 1 | 0.0264 Days |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for TAb: Tmax (Serum) | Cycle 2, Day 1 | 0.0264 Days |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for TAb: Tmax (Serum) | Cycle 1, Day 15 | 0.0264 Days |
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.
Time frame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) 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
Population: PK analysis set: all participants who received enfortumab vedotin and from whom at least one blood sample was collected and assayed for enfortumab vedotin, monomethyl auristatin E (MMAE) or total antibody (Tab) concentration. Corresponding records of the time of dosing and sample collection must also be available for all enfortumab vedotin. Here, 'Number Analyzed'= participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Total Antibody (TAb): Cmax (Serum) | Cycle 1, Day 1 | 26.6 Microgram per milliliter | Geometric Coefficient of Variation 30.4 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Total Antibody (TAb): Cmax (Serum) | Cycle 1, Day 15 | 30.9 Microgram per milliliter | Geometric Coefficient of Variation 22.9 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Total Antibody (TAb): Cmax (Serum) | Cycle 2, Day 1 | 26.2 Microgram per milliliter | Geometric Coefficient of Variation 30.5 |
| Enfortumab Vedotin - Cohort 1 | PK Parameter for Total Antibody (TAb): Cmax (Serum) | Cycle 2, Day 15 | 30.2 Microgram per milliliter | Geometric Coefficient of Variation 22.7 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Total Antibody (TAb): Cmax (Serum) | Cycle 2, Day 15 | 27.1 Microgram per milliliter | Geometric Coefficient of Variation 28.2 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Total Antibody (TAb): Cmax (Serum) | Cycle 1, Day 1 | 26.4 Microgram per milliliter | Geometric Coefficient of Variation 23.4 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Total Antibody (TAb): Cmax (Serum) | Cycle 2, Day 1 | 26.3 Microgram per milliliter | Geometric Coefficient of Variation 23.8 |
| Enfortumab Vedotin - Cohort 2 | PK Parameter for Total Antibody (TAb): Cmax (Serum) | Cycle 1, Day 15 | 27.3 Microgram per milliliter | Geometric Coefficient of Variation 25.7 |
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 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.
Time frame: 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)
Population: Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enfortumab Vedotin - Cohort 1 | Progression-Free Survival (PFS) Per BICR | 5.8 Months |
| Enfortumab Vedotin - Cohort 2 | Progression-Free Survival (PFS) Per BICR | 5.8 Months |