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Clinical Trial Results:
A Single-arm, Open-label, Multicenter Study of Enfortumab vedotin (ASG-22CE) for Treatment of Subjects With Locally Advanced or Metastatic Urothelial Cancer who Previously Received Immune Checkpoint Inhibitor (CPI) Therapy.

Summary
EudraCT number	2017-003479-78
Trial protocol	DE ES NL IT
Global end of trial date	28 Jul 2023

Results information
Results version number	v1(current)
This version publication date	07 Aug 2024
First version publication date	07 Aug 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

SGN22E-001

ISRCTN number

US NCT number

NCT03219333

WHO universal trial number (UTN)

Sponsor organisation name

Seagen Inc

Sponsor organisation address

21823 30th Drive S.E.,, Bothell, United States, 98021

Public contact

Chief Medical Officer, Seagen Inc.,, 1 8554732436, medinfo@seagen.com

Scientific contact

Chief Medical Officer, Seagen Inc, 1 8554732436, medinfo@seagen.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

29 Jan 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Jul 2023

Was the trial ended prematurely?

Main objective of the trial

To determine the antitumor activity of single-agent enfortumab vedotin as measured by confirmed Objective Response Rate (ORR) in participants with locally advanced or metastatic urothelial cancer who have previously received systemic therapy with a CPI and either previously received platinum-containing chemotherapy or are platinum-naïve and cisplatin ineligible.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

08 Oct 2017

Long term follow-up planned

Yes

Long term follow-up rationale

Efficacy, Safety

Long term follow-up duration

2 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 178

Country: Number of subjects enrolled

Netherlands: 5

Country: Number of subjects enrolled

France: 4

Country: Number of subjects enrolled

Spain: 1

Country: Number of subjects enrolled

Italy: 4

Country: Number of subjects enrolled

Japan: 14

Country: Number of subjects enrolled

Korea, Republic of: 13

Worldwide total number of subjects

219

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

146

85 years and over

Subject disposition

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Recruitment details

Screening 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.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Enfortumab vedotin - Cohort 1

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Enfortumab vedotin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

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.

Enfortumab vedotin - Cohort 2

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Enfortumab vedotin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

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.

Number of subjects in period 1	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Started	128	91
Treated	125	89
Completed	0	0
Not completed	128	91
Consent withdrawn by subject	9	4
Death	104	72
Unspecified	2	2
Study closed 2023,major completed 5year follow-up	12	12
Lost to follow-up	1	1

Baseline characteristics

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Reporting group title

Enfortumab vedotin - Cohort 1

Reporting group description

Reporting group title

Enfortumab vedotin - Cohort 2

Reporting group description

Reporting group values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2	Total
Number of subjects	128	91	219
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	45	16	61
From 65-84 years	83	63	146
85 years and over	0	12	12
Age Continuous
Units: Years
median (full range (min-max))	69.0 (40 to 84)	75.0 (49 to 91)	-
Sex: Female, Male
Units: Participants
Female	38	23	61
Male	90	68	158
Race Customised
Units: Subjects
Asian	12	20	32
Black or African American	2	0	2
White	108	64	172
Other	1	0	1
Not Reportable	5	7	12
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	5	1	6
Not Hispanic or Latino	121	85	206
Unknown or Not Reported	2	5	7
Region of Enrollment
Units: Subjects
North America	119	59	178
Europe	0	14	14
Asia	9	18	27
Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG performance status was used to assess participants disease progression, and ability to carry out daily living activities. 0=Normal activity; 1=Symptoms but ambulatory; 2=In bed <50% of the time; 3= In bed >50% of the time; 4=100% bedridden; 5=Dead
Units: Subjects
ECOG: 0	40	37	77
ECOG: 1	85	41	126
ECOG: 2	0	11	11
Missing	3	2	5

End points

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Reporting group title

Enfortumab vedotin - Cohort 1

Reporting group description

Reporting group title

Enfortumab vedotin - Cohort 2

Reporting group description

Primary: Objective Response Rate (ORR) per Blinded Independent Central Review (BICR)

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End point title

Objective Response Rate (ORR) per Blinded Independent Central Review (BICR) ^[1]

End point description

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. Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin.

End point type

Primary

End point timeframe

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)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	125	89
Units: Percentage of Participants
number (confidence interval 95%)	44 (35.1 to 53.2)	51.7 (40.8 to 62.4)

No statistical analyses for this end point

Secondary: Progression-Free Survival (PFS) per BICR

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End point title

Progression-Free Survival (PFS) per BICR

End point description

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. Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin.

End point type

Secondary

End point timeframe

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)

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	125	89
Units: Months
median (confidence interval 95%)	5.8 (4.93 to 7.46)	5.8 (5.03 to 8.28)

No statistical analyses for this end point

Secondary: ORR per Investigator Assessment

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End point title

ORR per Investigator Assessment

End point description

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. Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin.

End point type

Secondary

End point timeframe

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)

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	125	89
Units: Percentage of Participants
number (confidence interval 95%)	39 (30.6 to 48.3)	50.6 (39.8 to 61.3)

No statistical analyses for this end point

Secondary: Duration of Objective Response (DOR) per BICR

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End point title

Duration of Objective Response (DOR) per BICR

End point description

Time from first documentation of objective response(CR or PR that is subsequently confirmed) to first documentation of progressive disease(PD) or death due to any cause, whichever comes first.CR=disappearance of all target lesions, non-target lesions. Any pathological lymph nodes(whether target or non-target) reduction in short axis to <10 mm.PR = >=30% decrease in sum of diameters of target lesions,reference: baseline sum of diameters. PD=at least 20% increase in sum of diameters of target lesions, taking reference smallest sum on study(this includes baseline sum if that is smallest on study).In addition to relative increase of 20%, sum must demonstrate an absolute increase of at least 0.5 cm. Appearance of one or more new lesions=progression. DOR analyzed using Kaplan-Meier methodology. Full analysis set.‘99999’=Upper limit of 95%CI not estimated due to insufficient number of participants with events. Here, ‘Number of Participants Analyzed’=number of participants evaluable.

End point type

Secondary

End point timeframe

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)

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	55	46
Units: Months
median (confidence interval 95%)	7.6 (6.34 to 99999)	10.9 (5.78 to 99999)

No statistical analyses for this end point

Secondary: DOR per Investigator Assessment

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End point title

DOR per Investigator Assessment

End point description

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. Full analysis set. ‘99999’=Upper limit of 95%CI not estimated due to insufficient number of participants with events. Here, ‘Number of Participants Analyzed’ signifies number of participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

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)

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	49	45
Units: Months
median (confidence interval 95%)	7.9 (5.95 to 99999)	10.7 (5.85 to 16.59)

No statistical analyses for this end point

Secondary: PFS per Investigator Assessment

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End point title

PFS per Investigator Assessment

End point description

End point type

Secondary

End point timeframe

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)

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	125	89
Units: Months
median (confidence interval 95%)	5.8 (4.93 to 7.46)	7.2 (5.42 to 7.69)

No statistical analyses for this end point

Secondary: Number of Participants with Treatment-Emergent Laboratory Abnormalities (Hematology)

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End point title

Number of Participants with Treatment-Emergent Laboratory Abnormalities (Hematology)

End point description

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. 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.

End point type

Secondary

End point timeframe

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]

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	125	89
Units: Participants
Hemoglobin decreased (all grades)n=122,88	52	39
Hemoglobin decreased (grade 3-4)n=122,88	12	4
Leukocytes decreased (all grades)n=122,88	33	28
Leukocytes decreased (grade 3-4)n=122,88	5	4
Lymphocytes decreased (all grades)n=122,88	55	61
Lymphocytes decreased (grade 3-4)n=122,88	12	13
Lymphocytes increased (all grades)n=125,88	0	1
Lymphocytes increased (grade 3-4)n=125,89	0	0
Neutrophils decreased (all grades)n=122,88	28	27
Neutrophils decreased (grade 3-4)n=122,88	7	8
Platelets decreased (all grades)n=121,88	39	20
Platelets decreased (grade 3-4)n=125,89	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Treatment-Emergent Laboratory Abnormalities (Serum Chemistry)

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End point title

Number of Participants with Treatment-Emergent Laboratory Abnormalities (Serum Chemistry)

End point description

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. Safety Analysis set. ‘99999’: Fasting glucose is required for CTCAE grading of hyperglycemia grade 1-2, not grade 3-4. Since fasting glucose was not required for this study, grade 1-2 (glucose-high) could not be determined. Only grade 3-4 was determined. 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.

End point type

Secondary

End point timeframe

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]

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	125	89
Units: Participants
Alanine aminotransferase increase(all G) n=122,88	34	26
Alanine aminotransferase increase(G 3-4)n=122,89	1	0
Albumin decreased (all G)n=122,88	38	16
Albumin decreased (G 3-4)n=122,88	1	0
Alkaline phosphatase increased (all G)n=122,88	21	12
Alkaline phosphatase increased (G 3-4)n=122,88	1	0
Aspartate aminotransferase increase(all G)n=121,88	79	52
Aspartate aminotransferase increase(G 3-4)n=121,88	3	2
Bilirubin increased (all G)n=122,88	13	5
Bilirubin increased (G 3-4)n=122,89	1	0
Calcium decreased (all G)n=122,88	15	7
Calcium decreased (G 3-4)n=125,89	0	0
Calcium increased (all G)n=122,88	1	7
Calcium increased (G 3-4)n=125,88	0	3
Creatinine increased (all G)n=122,88	73	46
Creatinine increased (G 3-4)n=122,88	2	3
Glucose decreased (all G)n=122,88	32	26
Glucose decreased (G 3-4)n=125,89	0	0
Glucose increased (all G)n=125,89	99999	99999
Glucose increased (G 3-4)n=125,89	10	11
Phosphate decreased (all G)n=122,88	42	22
Phosphate decreased (G 3-4)n=122,88	12	6
Potassium decreased (all G)n=122,88	25	11
Potassium decreased (G 3-4)n=122,88	2	1
Potassium increased (all G)n=122,88	13	17
Potassium increased (G 3-4)n=125,88	0	5
Sodium decreased (all G)n=122,88	54	28
Sodium decreased (G 3-4)n=122,88	10	6
Sodium increased (all G)n=122,88	2	1
Sodium increased (G 3-4)n=125,89	0	0
Urate increased (all G)n=122,88	32	38
Urate increased (grade 3-4)n=122,88	8	8
Amylase increased (all grades)n=122,88	20	18
Amylase increased (grade 3-4)n=122,88	1	3
Lipase increased (all grades)n=122,88	37	32
Lipase increased (grade 3-4)n=122,88	12	10

No statistical analyses for this end point

Secondary: Incidence of Antitherapeutic Antibody (ATA)

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End point title

Incidence of Antitherapeutic Antibody (ATA)

End point description

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. 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.

End point type

Secondary

End point timeframe

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]

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	114	81
Units: Participants
Baseline Negative\|Negative post-baseline(n=112,80)	109	76
Baseline Positive\|Negative post-baseline(n=112,80)	1	1
Baseline Negative\|Transiently P post basl(n=112,80	2	3
Baseline Positive\|Transiently P post-basl(n=2,1)	1	0
Baseline Negative\|Persistently P post-basl(n=2,1)	1	1
Baseline Positive\|Persistently P post-basl(n=2,1)	0	0

No statistical analyses for this end point

Secondary: DCR16 per Investigator Assessment

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End point title

DCR16 per Investigator Assessment

End point description

Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. CR = 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 = >=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD = 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. Appearance of one or more new lesions = considered progression. SD = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin.

End point type

Secondary

End point timeframe

Up to Week 16

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	125	89
Units: Percentage of Participants
number (confidence interval 95%)	55 (46.0 to 64.1)	64.0 (53.2 to 73.9)

No statistical analyses for this end point

Secondary: Disease Control Rate at 16 weeks (DCR16) per BICR

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End point title

Disease Control Rate at 16 weeks (DCR16) per BICR

End point description

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. Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin.

End point type

Secondary

End point timeframe

Up to Week 16

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	125	89
Units: Percentage of Participants
number (confidence interval 95%)	50 (41.3 to 59.5)	58.4 (47.5 to 68.8)

No statistical analyses for this end point

Secondary: Overall Survival (OS) at Time of Primary Analysis

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End point title

Overall Survival (OS) at Time of Primary Analysis

End point description

OS is defined as the time from first dose of enfortumab vedotin to death from any cause. Full analysis set: included all enrolled participants who received at least one dose of enfortumab vedotin.

End point type

Secondary

End point timeframe

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]

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	125	89
Units: Months
median (confidence interval 95%)	12.4 (9.46 to 15.57)	14.7 (10.51 to 18.20)

No statistical analyses for this end point

Secondary: Number of Participants with Adverse Events (AEs) at Time of Primary Analysis

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End point title

Number of Participants with Adverse Events (AEs) at Time of Primary Analysis

End point description

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, 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. Safety Analysis Set: includes all participants who received at least one dose of enfortumab vedotin.

End point type

Secondary

End point timeframe

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]

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	125	89
Units: Participants
Any treatment-emergent AEs (TEAEs)	125	89
Treatment-related TEAEs	117	86
Any grade 3-5 TEAEs	93	62
Treatment-related grade 3-5 TEAEs	70	49
Any serious TEAEs	59	35
Treatment-related serious TEAEs	24	15
Any TEAEs leading to treatment discontinuation	21	18
TR TEAEs lead to treatment discontinuation	15	14
Any TEAEs leading to death	7	8
Treatment-related TEAEs leading to death	0	3

No statistical analyses for this end point

Secondary: Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum)

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End point title

Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum)

End point description

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 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.

End point type

Secondary

End point timeframe

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

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	120	87
Units: Microgram per milliliter (µg/mL)
geometric mean (geometric coefficient of variation)
Cycle 1, Day 1 (n=120,87)	26.6 ( 28.5 )	23.9 ( 24.4 )
Cycle 1, Day 15 (n=93,64)	26.0 ( 28.3 )	21.7 ( 29.7 )
Cycle 2, Day 1 (n=105,73)	24.5 ( 31.4 )	22.0 ( 24.5 )
Cycle 2, Day 15 (n=95,62)	26.3 ( 25.2 )	20.7 ( 27.4 )

No statistical analyses for this end point

Secondary: PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum)

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End point title

PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum)

End point description

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 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.

End point type

Secondary

End point timeframe

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	120	87
Units: Days
median (full range (min-max))
Cycle 1, Day 1 (n=119,87)	0.0278 (0.010 to 0.052)	0.0264 (0.021 to 0.088)
Cycle 1, Day 15 (n=92,63)	0.0285 (0.014 to 0.054)	0.0264 (0.014 to 0.084)
Cycle 2, Day 1 (n=104,73)	0.0264 (0.011 to 0.042)	0.0264 (0.015 to 0.074)
Cycle 2, Day 15 (n=94,62)	0.0285 (0.020 to 0.115)	0.0257 (0.010 to 0.047)

No statistical analyses for this end point

Secondary: PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum)

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End point title

PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum)

End point description

AUC was derived from the PK blood samples collected. 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.

End point type

Secondary

End point timeframe

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)

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	120	87
Units: Day*microgram per milliliter
geometric mean (geometric coefficient of variation)
7-day post-inf AUC(AUC(d0-7))-Cycle 1,D1 n=115,85	34.6 ( 34.0 )	33.5 ( 41.4 )
AUC(d0-7) - Cycle 1, Day 15 n=88,63	31.3 ( 43.8 )	26.3 ( 46.0 )
AUC(d0-7) - Cycle 2, Day 1 n=104,72	36.4 ( 36.7 )	32.0 ( 30.0 )
AUC(d0-7) - Cycle 2, Day 15 n=88,56	35.9 ( 41.2 )	27.8 ( 35.8 )
14-day post-inf AUC(AUC(d0-14))Cycle1,D15 n=85,59	34.7 ( 44.7 )	30.9 ( 47.5 )
AUC(d0-14) - Cycle 2, Day 15 n=82,60	41.2 ( 40.4 )	33.1 ( 36.6 )

No statistical analyses for this end point

Secondary: PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma)

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End point title

PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma)

End point description

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 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.

End point type

Secondary

End point timeframe

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	117	84
Units: Nanogram per milliliter
geometric mean (geometric coefficient of variation)
Cycle 1, Day 1 n=117,84	3.1 ( 67.0 )	2.6 ( 57.8 )
Cycle 1, Day 15 n=93,64	3.9 ( 64.8 )	3.5 ( 51.8 )
Cycle 2, Day 1 n=106,72	2.4 ( 57.4 )	2.2 ( 60.8 )
Cycle 2, Day 15 n=90,62	3.0 ( 64.8 )	2.9 ( 59.9 )

No statistical analyses for this end point

Secondary: PK Parameter for Free MMAE: Tmax (Plasma)

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End point title

PK Parameter for Free MMAE: Tmax (Plasma)

End point description

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 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.

End point type

Secondary

End point timeframe

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	117	84
Units: Days
median (full range (min-max))
Cycle 1, Day 1 n=117,84	1.9 (1 to 5)	1.9 (1 to 4)
Cycle 1, Day 15 n=93,64	2.0 (1 to 11)	1.9 (1 to 9)
Cycle 2, Day 1 n=106,72	2.0 (1 to 5)	1.8 (1 to 5)
Cycle 2, Day 15 n=90,62	1.9 (1 to 9)	1.9 (1 to 10)

No statistical analyses for this end point

Secondary: PK Parameter for Free MMAE: AUC (Plasma)

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End point title

PK Parameter for Free MMAE: AUC (Plasma)

End point description

AUC was derived from the PK blood samples collected. 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.

End point type

Secondary

End point timeframe

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)

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	117	84
Units: Day*nanogram per milliliter
geometric mean (geometric coefficient of variation)
7-day post-inf AUC(AUC(d0-7))-Cycle1,Day1 n=115,84	14.1 ( 81.7 )	13.0 ( 64.1 )
AUC(d0-7) - Cycle 1, Day 15 n=88,66	19.1 ( 79.1 )	18.1 ( 65.0 )
AUC(d0-7) - Cycle 2, Day 1 n=104,72	11.3 ( 58.0 )	10.6 ( 65.0 )
AUC(d0-7) - Cycle 2, Day 15 n=88,57	14.9 ( 64.7 )	15.3 ( 60.2 )
14-day post-inf AUC(AUC(d0-14))-Cycle1,D15 n=91,62	25.9 ( 74.7 )	22.6 ( 76.4 )
AUC(d0-14) - Cycle 2, Day 15 n=84,63	19.1 ( 61.2 )	21.3 ( 65.0 )

No statistical analyses for this end point

Secondary: PK Parameter for Total Antibody (TAb): Cmax (Serum)

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End point title

PK Parameter for Total Antibody (TAb): Cmax (Serum)

End point description

End point type

Secondary

End point timeframe

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	120	87
Units: Microgram per milliliter
geometric mean (geometric coefficient of variation)
Cycle 1, Day 1 n=120,87	26.6 ( 30.4 )	26.4 ( 23.4 )
Cycle 1, Day 15 n=93,64	30.9 ( 22.9 )	27.3 ( 25.7 )
Cycle 2, Day 1 n=105,74	26.2 ( 30.5 )	26.3 ( 23.8 )
Cycle 2, Day 15 n=95,62	30.2 ( 22.7 )	27.1 ( 28.2 )

No statistical analyses for this end point

Secondary: PK Parameter for TAb: Tmax (Serum)

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End point title

PK Parameter for TAb: Tmax (Serum)

End point description

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 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.

End point type

Secondary

End point timeframe

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	120	87
Units: Days
median (full range (min-max))
Cycle 1, Day 1 n=119,87	0.0278 (0.010 to 0.052)	0.0264 (0.021 to 0.088)
Cycle 1, Day 15 n=92,63	0.0285 (0.014 to 0.054)	0.0264 (0.014 to 0.084)
Cycle 2, Day 1 n=104,74	0.0264 (0.011 to 0.042)	0.0264 (0.015 to 0.074)
Cycle 2, Day 15 n=94,62	0.0285 (0.020 to 0.115)	0.0257 (0.010 to 0.047)

No statistical analyses for this end point

Secondary: PK Parameter for TAb: AUC (Serum)

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End point title

PK Parameter for TAb: AUC (Serum)

End point description

End point type

Secondary

End point timeframe

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)

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	120	87
Units: Day*microgram per milliliter
geometric mean (geometric coefficient of variation)
7-day post-inf AUC(AUC(d0-7)) - Cycle1,D1 n=115,85	63.4 ( 33.6 )	66.8 ( 34.3 )
AUC(d0-7) - Cycle 1, Day 15 n=88,63	77.6 ( 35.2 )	72.3 ( 37.9 )
AUC(d0-7) - Cycle 2, Day 1 n=104,72	73.2 ( 33.5 )	72.9 ( 26.4 )
AUC(d0-7) - Cycle 2, Day 15 n=88,56	87.9 ( 30.6 )	81.0 ( 30.9 )
14-day post-inf AUC(AUC(d0-14))-Cycle1,D15 n=93,62	98.1 ( 38.8 )	91.1 ( 40.3 )
AUC(d0-14) - Cycle 2, Day 15 n=84,62	113.0 ( 33.8 )	109.7 ( 41.5 )

No statistical analyses for this end point

Secondary: Number of Subjects With Adverse Events (AEs): Final Analysis

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End point title

Number of Subjects With Adverse Events (AEs): Final Analysis

End point description

End point type

Secondary

End point timeframe

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)

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	125	89
Units: Participants
Any treatment-emergent AEs (TEAEs)	125	89
Treatment-related TEAEs	117	86
Any grade 3-5 TEAEs	93	62
Treatment-related grade 3-5 TEAEs	70	49
Any serious TEAEs	59	35
Treatment-related serious TEAEs	24	15
Any TEAEs leading to treatment discontinuation	22	21
TR TEAEs leading to treatment discontinuation	16	17
Any TEAEs leading to death	7	8
Treatment-related TEAEs leading to death	0	3

No statistical analyses for this end point

Secondary: Overall Survival (OS): Final Analysis

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End point title

Overall Survival (OS): Final Analysis

End point description

OS is defined as the time from first dose of enfortumab vedotin to death from any cause. Full analysis set: includes all enrolled participants who received at least one dose of enfortumab vedotin.

End point type

Secondary

End point timeframe

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)

End point values	Enfortumab vedotin - Cohort 1	Enfortumab vedotin - Cohort 2
Number of subjects analysed	125	89
Units: Months
median (confidence interval 95%)	12.4 (9.46 to 15.57)	15.6 (11.24 to 20.37)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Cohort 1: maximum up to 43.0 months of treatment; Cohort 2: maximum up to 25.8 months of treatment

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

v26.0

Reporting group title

Enfortumab vedotin - Cohort 2

Reporting group description

Reporting group title

Enfortumab vedotin - Cohort 1

Reporting group description

Serious adverse events	Enfortumab vedotin - Cohort 2	Enfortumab vedotin - Cohort 1
Total subjects affected by serious adverse events
subjects affected / exposed	35 / 89 (39.33%)	59 / 125 (47.20%)
number of deaths (all causes)	72	104
number of deaths resulting from adverse events	8	7
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cancer pain
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colon cancer
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transitional cell carcinoma metastatic
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	3 / 89 (3.37%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 3	0 / 2
Transitional cell carcinoma
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Vascular disorders
Embolism
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertension
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypotension
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	2 / 89 (2.25%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	2 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic stenosis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Deep vein thrombosis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Shock
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Chills
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Asthenia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Fatigue
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	3 / 125 (2.40%)
occurrences causally related to treatment / all	0 / 0	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Incarcerated hernia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infusion site extravasation
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple organ dysfunction syndrome
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Non-cardiac chest pain
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Aspiration
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic obstructive pulmonary disease
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cough
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspnoea
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	4 / 125 (3.20%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoxia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	3 / 125 (2.40%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Interstitial lung disease
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural effusion
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonitis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Delirium
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Confusional state
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Amylase increased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic enzyme increased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lipase increased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neutrophil count decreased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urine output decreased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
White blood cell count decreased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Compression fracture
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fall
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Wound
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Myocardial infarction
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorder
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Atrial thrombosis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial fibrillation
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	2 / 89 (2.25%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acute myocardial infarction
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Spinal cord compression
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral motor neuropathy
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Paraplegia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Encephalopathy
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Demyelinating polyneuropathy
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Neutropenia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	2 / 89 (2.25%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	2 / 2	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile neutropenia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	5 / 125 (4.00%)
occurrences causally related to treatment / all	1 / 1	5 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Cataract
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Nausea
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	2 / 89 (2.25%)	3 / 125 (2.40%)
occurrences causally related to treatment / all	1 / 2	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Odynophagia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestinal obstruction
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal haemorrhage
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enterocolitis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	3 / 89 (3.37%)	3 / 125 (2.40%)
occurrences causally related to treatment / all	2 / 3	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	0 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	3 / 125 (2.40%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Small intestinal obstruction
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	3 / 125 (2.40%)
occurrences causally related to treatment / all	2 / 2	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Stomatitis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Bile duct stone
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash vesicular
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Rash maculo-papular
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rash
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Drug eruption
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dermatitis bullous
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Stevens-Johnson syndrome
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	9 / 89 (10.11%)	4 / 125 (3.20%)
occurrences causally related to treatment / all	3 / 10	1 / 4
deaths causally related to treatment / all	1 / 2	0 / 0
Urinary tract obstruction
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Ureterolithiasis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal impairment
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematuria
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	3 / 125 (2.40%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Adrenal insufficiency
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bone pain
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Muscular weakness
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myositis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Pneumonia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	3 / 89 (3.37%)	3 / 125 (2.40%)
occurrences causally related to treatment / all	1 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Bacteraemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Kidney infection
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Joint abscess
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infection
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Device related infection
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	6 / 125 (4.80%)
occurrences causally related to treatment / all	0 / 0	2 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia aspiration
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Pneumonia bacterial
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	4 / 89 (4.49%)	4 / 125 (3.20%)
occurrences causally related to treatment / all	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 1
Urinary tract infection
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	3 / 89 (3.37%)	6 / 125 (4.80%)
occurrences causally related to treatment / all	0 / 4	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection staphylococcal
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Metabolic acidosis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Hypomagnesaemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoglycaemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperuricaemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	0 / 89 (0.00%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperkalaemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	0 / 125 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperglycaemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	2 / 89 (2.25%)	2 / 125 (1.60%)
occurrences causally related to treatment / all	2 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Dehydration
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	2 / 89 (2.25%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	1 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Decreased appetite
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	2 / 89 (2.25%)	1 / 125 (0.80%)
occurrences causally related to treatment / all	2 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hyponatraemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	3 / 125 (2.40%)
occurrences causally related to treatment / all	0 / 1	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Enfortumab vedotin - Cohort 2	Enfortumab vedotin - Cohort 1
Total subjects affected by non serious adverse events
subjects affected / exposed	88 / 89 (98.88%)	123 / 125 (98.40%)
Vascular disorders
Hypertension
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	4 / 89 (4.49%)	7 / 125 (5.60%)
occurrences all number	5	12
Hypotension
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	4 / 89 (4.49%)	9 / 125 (7.20%)
occurrences all number	5	10
General disorders and administration site conditions
Asthenia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	7 / 89 (7.87%)	7 / 125 (5.60%)
occurrences all number	15	7
Chills
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	7 / 89 (7.87%)	5 / 125 (4.00%)
occurrences all number	8	9
Fatigue
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	40 / 89 (44.94%)	66 / 125 (52.80%)
occurrences all number	41	71
Gait disturbance
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	9 / 89 (10.11%)	7 / 125 (5.60%)
occurrences all number	9	7
Malaise
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	2 / 89 (2.25%)	10 / 125 (8.00%)
occurrences all number	3	10
Oedema peripheral
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	20 / 89 (22.47%)	31 / 125 (24.80%)
occurrences all number	22	45
Pyrexia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	14 / 89 (15.73%)	15 / 125 (12.00%)
occurrences all number	16	17
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	9 / 89 (10.11%)	7 / 125 (5.60%)
occurrences all number	9	8
Dyspnoea
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	14 / 89 (15.73%)	15 / 125 (12.00%)
occurrences all number	16	19
Dysphonia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	7 / 125 (5.60%)
occurrences all number	5	7
Cough
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	12 / 89 (13.48%)	20 / 125 (16.00%)
occurrences all number	15	25
Psychiatric disorders
Anxiety
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	4 / 125 (3.20%)
occurrences all number	5	5
Insomnia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	13 / 89 (14.61%)	18 / 125 (14.40%)
occurrences all number	13	18
Investigations
Amylase increased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	15 / 89 (16.85%)	13 / 125 (10.40%)
occurrences all number	19	17
Aspartate aminotransferase increased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	11 / 89 (12.36%)	19 / 125 (15.20%)
occurrences all number	15	27
Blood alkaline phosphatase increased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	7 / 125 (5.60%)
occurrences all number	1	7
Blood creatinine increased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	11 / 125 (8.80%)
occurrences all number	10	17
Lipase increased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	9 / 89 (10.11%)	16 / 125 (12.80%)
occurrences all number	15	27
Lymphocyte count decreased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	2 / 89 (2.25%)	9 / 125 (7.20%)
occurrences all number	5	9
Weight decreased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	31 / 89 (34.83%)	40 / 125 (32.00%)
occurrences all number	33	41
Alanine aminotransferase increased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	9 / 89 (10.11%)	15 / 125 (12.00%)
occurrences all number	11	16
Injury, poisoning and procedural complications
Fall
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	9 / 89 (10.11%)	14 / 125 (11.20%)
occurrences all number	12	18
Infusion related reaction
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	4 / 125 (3.20%)
occurrences all number	6	5
Cardiac disorders
Palpitations
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	1 / 125 (0.80%)
occurrences all number	7	1
Tachycardia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	1 / 89 (1.12%)	9 / 125 (7.20%)
occurrences all number	1	10
Nervous system disorders
Dizziness
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	10 / 89 (11.24%)	20 / 125 (16.00%)
occurrences all number	12	23
Dysgeusia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	27 / 89 (30.34%)	49 / 125 (39.20%)
occurrences all number	28	53
Headache
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	6 / 125 (4.80%)
occurrences all number	6	6
Paraesthesia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	6 / 89 (6.74%)	4 / 125 (3.20%)
occurrences all number	7	4
Peripheral motor neuropathy
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	9 / 89 (10.11%)	14 / 125 (11.20%)
occurrences all number	9	16
Peripheral sensory neuropathy
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	47 / 89 (52.81%)	54 / 125 (43.20%)
occurrences all number	53	59
Blood and lymphatic system disorders
Anaemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	34 / 89 (38.20%)	44 / 125 (35.20%)
occurrences all number	42	62
Neutropenia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	10 / 89 (11.24%)	13 / 125 (10.40%)
occurrences all number	12	22
Eye disorders
Dry eye
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	17 / 89 (19.10%)	30 / 125 (24.00%)
occurrences all number	19	32
Lacrimation increased
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	12 / 89 (13.48%)	21 / 125 (16.80%)
occurrences all number	14	25
Punctate keratitis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	3 / 89 (3.37%)	9 / 125 (7.20%)
occurrences all number	3	9
Vision blurred
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	9 / 89 (10.11%)	20 / 125 (16.00%)
occurrences all number	10	25
Blepharitis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	3 / 89 (3.37%)	8 / 125 (6.40%)
occurrences all number	3	9
Gastrointestinal disorders
Abdominal distension
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	7 / 89 (7.87%)	4 / 125 (3.20%)
occurrences all number	8	4
Abdominal pain
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	6 / 89 (6.74%)	23 / 125 (18.40%)
occurrences all number	8	26
Abdominal pain upper
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	6 / 125 (4.80%)
occurrences all number	7	6
Constipation
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	19 / 89 (21.35%)	35 / 125 (28.00%)
occurrences all number	26	41
Diarrhoea
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	30 / 89 (33.71%)	52 / 125 (41.60%)
occurrences all number	52	73
Dry mouth
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	8 / 89 (8.99%)	11 / 125 (8.80%)
occurrences all number	10	11
Dysphagia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	2 / 89 (2.25%)	7 / 125 (5.60%)
occurrences all number	3	7
Gastrooesophageal reflux disease
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	9 / 125 (7.20%)
occurrences all number	5	9
Nausea
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	26 / 89 (29.21%)	56 / 125 (44.80%)
occurrences all number	35	68
Stomatitis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	6 / 89 (6.74%)	10 / 125 (8.00%)
occurrences all number	7	11
Vomiting
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	11 / 89 (12.36%)	24 / 125 (19.20%)
occurrences all number	13	36
Skin and subcutaneous tissue disorders
Dry skin
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	18 / 89 (20.22%)	35 / 125 (28.00%)
occurrences all number	20	38
Alopecia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	48 / 89 (53.93%)	64 / 125 (51.20%)
occurrences all number	49	67
Rash maculo-papular
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	28 / 89 (31.46%)	29 / 125 (23.20%)
occurrences all number	40	45
Rash macular
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	6 / 89 (6.74%)	6 / 125 (4.80%)
occurrences all number	8	7
Rash erythematous
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	6 / 89 (6.74%)	15 / 125 (12.00%)
occurrences all number	10	16
Pruritus
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	31 / 89 (34.83%)	34 / 125 (27.20%)
occurrences all number	37	41
Skin hyperpigmentation
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	4 / 89 (4.49%)	13 / 125 (10.40%)
occurrences all number	4	14
Skin exfoliation
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	3 / 89 (3.37%)	7 / 125 (5.60%)
occurrences all number	4	10
Renal and urinary disorders
Pollakiuria
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	4 / 125 (3.20%)
occurrences all number	5	4
Acute kidney injury
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	6 / 89 (6.74%)	4 / 125 (3.20%)
occurrences all number	6	4
Dysuria
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	6 / 125 (4.80%)
occurrences all number	6	6
Haematuria
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	10 / 89 (11.24%)	10 / 125 (8.00%)
occurrences all number	11	13
Musculoskeletal and connective tissue disorders
Back pain
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	4 / 89 (4.49%)	21 / 125 (16.80%)
occurrences all number	4	22
Arthralgia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	8 / 89 (8.99%)	14 / 125 (11.20%)
occurrences all number	10	16
Pain in extremity
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	10 / 89 (11.24%)	14 / 125 (11.20%)
occurrences all number	10	16
Myalgia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	6 / 89 (6.74%)	9 / 125 (7.20%)
occurrences all number	6	11
Muscular weakness
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	8 / 89 (8.99%)	10 / 125 (8.00%)
occurrences all number	10	12
Infections and infestations
Oral candidiasis
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	7 / 125 (5.60%)
occurrences all number	5	7
Urinary tract infection
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	13 / 89 (14.61%)	18 / 125 (14.40%)
occurrences all number	17	23
Metabolism and nutrition disorders
Decreased appetite
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	35 / 89 (39.33%)	64 / 125 (51.20%)
occurrences all number	43	81
Dehydration
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	10 / 89 (11.24%)	12 / 125 (9.60%)
occurrences all number	11	14
Hypercalcaemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	6 / 89 (6.74%)	2 / 125 (1.60%)
occurrences all number	6	2
Hyperglycaemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	12 / 89 (13.48%)	17 / 125 (13.60%)
occurrences all number	13	20
Hyperkalaemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	2 / 125 (1.60%)
occurrences all number	8	2
Hyperuricaemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	4 / 89 (4.49%)	8 / 125 (6.40%)
occurrences all number	4	14
Hypoalbuminaemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	4 / 125 (3.20%)
occurrences all number	6	4
Hypokalaemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	6 / 89 (6.74%)	16 / 125 (12.80%)
occurrences all number	7	20
Hyponatraemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	9 / 89 (10.11%)	15 / 125 (12.00%)
occurrences all number	12	17
Hypophosphataemia
alternative dictionary used: MedDRA 26.0
subjects affected / exposed	5 / 89 (5.62%)	8 / 125 (6.40%)
occurrences all number	5	11

More information

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Were there any global substantial amendments to the protocol? Yes

14 Nov 2017

Amendment 1: Added Management of Hyperglycemia section as follows: Investigators should monitor blood glucose levels and are advised to perform additional assessments if any symptoms of hyperglycemia are observed, including a thorough evaluation for infection. In addition, if steroids are used to treat any other condition, blood glucose levels may require additional monitoring. If elevated blood glucose levels are observed, patients should be treated according to local standard of care and referral to endocrinology may be considered. Patients, especially those with a history of or ongoing diabetes mellitus or hyperglycemia, should be advised to immediately notify their physician if their glucose level becomes difficult to control or if they experience symptoms suggestive of hyperglycemia such as frequent urination, increased thirst, blurred vision, fatigue, and headache. Patients who enter the study with an elevated HbA1c (≥6.5%) at baseline should be referred to an appropriate provider during Cycle 1 for glucose management. Blood glucose should be checked prior to each dosing and dose should be withheld for blood glucose >250 ml/dL (Grade 3 or higher). Dosing may continue once the patient’s blood glucose has improved to ≤ Grade 2 and patient is clinically and metabolically stable.

13 Feb 2018

Amendment 2: Added Cycle 6 (±1 week) slit lamp examinations for at least the first 60 enrolled patients. Clarified that end of treatment (EOT) slit lamp exams will be performed for all patients who experience a corneal adverse event on study.

13 Apr 2018

Amendment 3: Added text regarding drug administration setting as follows: The patient should be observed during administration of enfortumab vedotin and for at least 60 minutes following the infusion during the first 3 cycles. All supportive measures consistent with optimal subject care should be given throughout the study according to institutional standards.

16 Apr 2018

Amendment 4: Revised primary objective as follows: To determine the antitumor activity of singleagent enfortumab vedotin as measured by confirmed objective response rate (ORR) in patients with locally advanced or metastatic urothelial cancer who tohave previously received systemic therapy with a CPI and either previously received platinum-containing chemotherapy or are platinum-naïve and cisplatin-ineligible

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Single-arm, Open-label, Multicenter Study of Enfortumab vedotin (ASG-22CE) for Treatment of Subjects With Locally Advanced or Metastatic Urothelial Cancer who Previously Received Immune Checkpoint Inhibitor (CPI) Therapy.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Objective Response Rate (ORR) per Blinded Independent Central Review (BICR)

Primary: Objective Response Rate (ORR) per Blinded Independent Central Review (BICR)

Secondary: Progression-Free Survival (PFS) per BICR

Secondary: Progression-Free Survival (PFS) per BICR

Secondary: ORR per Investigator Assessment

Secondary: ORR per Investigator Assessment

Secondary: Duration of Objective Response (DOR) per BICR

Secondary: Duration of Objective Response (DOR) per BICR

Secondary: DOR per Investigator Assessment

Secondary: DOR per Investigator Assessment

Secondary: PFS per Investigator Assessment

Secondary: PFS per Investigator Assessment

Secondary: Number of Participants with Treatment-Emergent Laboratory Abnormalities (Hematology)

Secondary: Number of Participants with Treatment-Emergent Laboratory Abnormalities (Hematology)

Secondary: Number of Participants with Treatment-Emergent Laboratory Abnormalities (Serum Chemistry)

Secondary: Number of Participants with Treatment-Emergent Laboratory Abnormalities (Serum Chemistry)

Secondary: Incidence of Antitherapeutic Antibody (ATA)

Secondary: Incidence of Antitherapeutic Antibody (ATA)

Secondary: DCR16 per Investigator Assessment

Secondary: DCR16 per Investigator Assessment

Secondary: Disease Control Rate at 16 weeks (DCR16) per BICR

Secondary: Disease Control Rate at 16 weeks (DCR16) per BICR

Secondary: Overall Survival (OS) at Time of Primary Analysis

Secondary: Overall Survival (OS) at Time of Primary Analysis

Secondary: Number of Participants with Adverse Events (AEs) at Time of Primary Analysis

Secondary: Number of Participants with Adverse Events (AEs) at Time of Primary Analysis

Secondary: Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum)

Secondary: Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum)

Secondary: PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum)

Secondary: PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum)

Secondary: PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum)

Secondary: PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum)

Secondary: PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma)

Secondary: PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma)

Secondary: PK Parameter for Free MMAE: Tmax (Plasma)

Secondary: PK Parameter for Free MMAE: Tmax (Plasma)

Secondary: PK Parameter for Free MMAE: AUC (Plasma)

Secondary: PK Parameter for Free MMAE: AUC (Plasma)

Secondary: PK Parameter for Total Antibody (TAb): Cmax (Serum)

Secondary: PK Parameter for Total Antibody (TAb): Cmax (Serum)

Secondary: PK Parameter for TAb: Tmax (Serum)

Secondary: PK Parameter for TAb: Tmax (Serum)

Secondary: PK Parameter for TAb: AUC (Serum)

Secondary: PK Parameter for TAb: AUC (Serum)

Secondary: Number of Subjects With Adverse Events (AEs): Final Analysis

Secondary: Number of Subjects With Adverse Events (AEs): Final Analysis

Secondary: Overall Survival (OS): Final Analysis

Secondary: Overall Survival (OS): Final Analysis

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Single-arm, Open-label, Multicenter Study of Enfortumab vedotin (ASG-22CE) for Treatment of Subjects With Locally Advanced or Metastatic Urothelial Cancer who Previously Received Immune Checkpoint Inhibitor (CPI) Therapy.