Trial · NCT04223856

Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer

NCT04223856, Phase 3, Active not recruiting, Astellas Pharma Global Development, Inc.; results first posted 2024-09-27

3 sourcestrials-2026-11-12-0.5.0

Cite this record

ConductScience Library. Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer. Trials, record NCT04223856. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04223856

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer
NCT number: NCT04223856
Status: Active not recruiting
Phases: Phase 3
Enrollment: 886 participants, actual
Lead sponsor: Astellas Pharma Global Development, Inc.
Conditions: Urothelial Cancer
Interventions: Enfortumab vedotin, Pembrolizumab, Cisplatin, Carboplatin, Gemcitabine
First posted: 2020-01-10
Last updated: 2026-05-29
Other registries' IDs: eudract:2019-004542-15
Results first posted: 2024-09-27

Source ClinicalTrials.gov

Registered outcomes21

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Blinded Independent Central Review (BICR)	From the date of randomization to first documentation of PD or death due to any cause, whichever occurred first (maximum exposure to treatment was up to 39.2 months)	PFS was defined as the time from date of randomization to first documentation of disease progression (PD), or to death due to any cause, whichever occurred first. PD: at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). PD could also be unequivocal progression of non-target lesions or the presence of unequivocal new lesions. Kaplan-Meier method was used for analysis.
Primary	Overall Survival (OS)	From randomization to date of death due to any cause or censoring date, whichever occurred first (maximum exposure to treatment was up to 39.2 months)	OS was defined as the time from the date of randomization to the date of death from any cause. In the absence of death, OS was censored at the date the participant was last known to be alive. Kaplan-Meier method was used for analysis.
Secondary	Percentage of Participants With Objective Response Rate (ORR) Per RECIST v1.1 by BICR	From first dose till CR/PR or PD or death, whichever occurred first (maximum up to approximately 7.4 years)	ORR as per RECIST v1.1 by BICR was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) CR was defined as disappearance of all lesions including non-target lesions (not just target lesions). Any pathological lymph nodes must have reduction in short axis to\<10 mm. PR was defined as at least 30 percent \[%\] decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For a response to be considered as confirmed, the subsequent response needs to be at least 4 weeks after the initial response.
Secondary	Time to Pain Progression (TTPP)	From the date of randomization to date of pain progression (maximum up to approximately 7.4 years)	TTPP was defined as the time from the date of randomization to date of pain progression. Pain progression was defined as a participant reporting either of the following, whichever came first: 1) Increase of 2 or more points from baseline on Brief Pain Inventory - Short Form (BPI-SF) Question 3 (i.e., pain at its worst in the last 24 hours, score range 0 to 10 with higher scores associated with higher pain levels) maintained for at least two consecutive assessments. 2) Initiation of new opioid medication from baseline for pain with usage maintained for at least two consecutive assessments as recorded in BPI-SF Question 7 (i.e., What medications received for pain).
Secondary	Change From Baseline in Worst Pain Using BPI-SF at Week 26	Baseline, Week 26	Brief Pain Inventory (BPI-SF) was defined as summary of the worst, least, and average pain experienced in the last 24 hours as well as pain right now and number of pain locations were provided for each treatment arm. BPI-sf worst pain measured the severity of pain based on the pain at its worst in the last 24 hours, score range 0 to 10 with higher scores associated with higher pain levels.
Secondary	PFS Per RECIST v1.1 by Investigator Assessment	From the date of randomization to first documentation of PD or death due to any cause, whichever occurred first (maximum up to approximately 7.4 years)	PFS as per RECIST v1.1 by investigator was defined as the time from date of randomization to first documentation of PD, or to death due to any cause, whichever comes first. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PD could also be unequivocal progression of non-target lesions or the presence of unequivocal new lesions.
Secondary	ORR Per RECIST v1.1 by Investigator Assessment	From first dose till CR/PR or PD or death, whichever occurred first (maximum up to approximately 7.4 years)	ORR as per RECIST v1.1 by investigator was defined as the percentage of participants with confirmed CR or PR. CR was defined as disappearance of all lesions including non-target lesions (not just target lesions). Any pathological lymph nodes must have reduction in short axis to\<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For a response to be considered as confirmed, the subsequent response needs to be at least 4 weeks after the initial response.
Secondary	Duration of Response (DOR) Per RECIST v1.1 by BICR	From the date of first documented response of CR or PR to the first documented disease progression or to death from any cause, whichever occurred first (maximum up to approximately 7.4 years)	DOR was defined as the time from the first objective response (CR or PR that is subsequently confirmed) to the first documented PD per RECIST v1.1 per BICR or death from any cause, whichever occurs first. DOR will only include subjects with a confirmed response (CR or PR per RECIST v1.1). CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to\<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For a response to be considered as confirmed, the subsequent response needs to be at least 4 weeks after the initial response. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Secondary	DOR Per RECIST v1.1 by Investigator Assessment	From the date of first documented response of CR or PR to the first documented disease progression or to death from any cause, whichever occurred first (maximum up to approximately 7.4 years)	DOR was defined as the time from the first objective response (CR or PR that is subsequently confirmed) to the first documented PD per RECIST v1.1 per investigator or death from any cause, whichever occurs first. DOR will only include subjects with a confirmed response (CR or PR per RECIST v1.1). CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to\<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For a response to be considered as confirmed, the subsequent response needs to be at least 4 weeks after the initial response.
Secondary	Disease Control Rate (DCR) Per RECIST v1.1 by BICR	From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to approximately 7.4 years)	DCR by BICR was defined as the percentage of participants with confirmed response (CR or PR), or SD (or non-CR/non-PD), per RECIST v1.1. Subjects who have no post-baseline response assessments will be considered as non-responders for calculating the DCR. Only response assessments before the first documented PD or subsequent anticancer therapies were considered. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to\<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For a response to be considered as confirmed, the subsequent response needs to be at least 4 weeks after the initial response. SD was defined as a change in tumor size that is neither radiological response (\>30% shrinkage) nor progression (\>20% growth).

1 to 10 of 21Source ClinicalTrials.gov

See all 21 registered outcomes

Outcomes21

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Blinded Independent Central Review (BICR)	From the date of randomization to first documentation of PD or death due to any cause, whichever occurred first (maximum exposure to treatment was up to 39.2 months)	ITT analysis set included all randomized participants. Participants were analyzed according to the treatment arm assigned at randomization regardless of the actual treatment received.	Months	MEDIAN
PRIMARY	Overall Survival (OS)	From randomization to date of death due to any cause or censoring date, whichever occurred first (maximum exposure to treatment was up to 39.2 months)	ITT analysis set included all randomized participants. Participants were analyzed according to the treatment arm assigned at randomization regardless of the actual treatment received.	Months	MEDIAN
SECONDARY	Percentage of Participants With Objective Response Rate (ORR) Per RECIST v1.1 by BICR	From first dose till CR/PR or PD or death, whichever occurred first (maximum up to approximately 7.4 years)
SECONDARY	Time to Pain Progression (TTPP)	From the date of randomization to date of pain progression (maximum up to approximately 7.4 years)
SECONDARY	Change From Baseline in Worst Pain Using BPI-SF at Week 26	Baseline, Week 26
SECONDARY	PFS Per RECIST v1.1 by Investigator Assessment	From the date of randomization to first documentation of PD or death due to any cause, whichever occurred first (maximum up to approximately 7.4 years)
SECONDARY	ORR Per RECIST v1.1 by Investigator Assessment	From first dose till CR/PR or PD or death, whichever occurred first (maximum up to approximately 7.4 years)
SECONDARY	Duration of Response (DOR) Per RECIST v1.1 by BICR	From the date of first documented response of CR or PR to the first documented disease progression or to death from any cause, whichever occurred first (maximum up to approximately 7.4 years)
SECONDARY	DOR Per RECIST v1.1 by Investigator Assessment	From the date of first documented response of CR or PR to the first documented disease progression or to death from any cause, whichever occurred first (maximum up to approximately 7.4 years)
SECONDARY	Disease Control Rate (DCR) Per RECIST v1.1 by BICR	From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to approximately 7.4 years)

1 to 10 of 21Source ClinicalTrials.gov

See all 21 outcomes

Results by group4

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Spread	Units
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Blinded Independent Central Review (BICR)	Enfortumab Vedotin + Pembrolizumab	12.5	95% Confidence Interval 10.4 to 16.6	Months
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Blinded Independent Central Review (BICR)	Standard of Care	6.3	95% Confidence Interval 6.2 to 6.5	Months
Overall Survival (OS)	Enfortumab Vedotin + Pembrolizumab	31.5	95% Confidence Interval 25.4 to NA	Months
Overall Survival (OS)	Standard of Care	16.1	95% Confidence Interval 13.9 to 18.3	Months

Source ClinicalTrials.gov

Participant flow8

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Enfortumab Vedotin + Pembrolizumab	442
Overall Study	STARTED	Standard of Care	444
Overall Study	Treated	Enfortumab Vedotin + Pembrolizumab	440
Overall Study	Treated	Standard of Care	433
Overall Study	COMPLETED	Enfortumab Vedotin + Pembrolizumab	8
Overall Study	COMPLETED	Standard of Care	244
Overall Study	NOT COMPLETED	Enfortumab Vedotin + Pembrolizumab	434
Overall Study	NOT COMPLETED	Standard of Care	200

Source ClinicalTrials.gov

Adverse events620

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Anaemia	Blood and lymphatic system disorders	Enfortumab Vedotin + Pembrolizumab	106	440	168
other	Anaemia	Blood and lymphatic system disorders	Standard of Care	255	433	362
other	Leukopenia	Blood and lymphatic system disorders	Enfortumab Vedotin + Pembrolizumab	16	440	25
other	Leukopenia	Blood and lymphatic system disorders	Standard of Care	47	433	91
other	Neutropenia	Blood and lymphatic system disorders	Enfortumab Vedotin + Pembrolizumab	43	440	70
other	Neutropenia	Blood and lymphatic system disorders	Standard of Care	178	433	360
other	Thrombocytopenia	Blood and lymphatic system disorders	Enfortumab Vedotin + Pembrolizumab	19	440	21
other	Thrombocytopenia	Blood and lymphatic system disorders	Standard of Care	147	433	266
other	Tinnitus	Ear and labyrinth disorders	Enfortumab Vedotin + Pembrolizumab	6	440	6
other	Tinnitus	Ear and labyrinth disorders	Standard of Care	29	433	31

1 to 10 of 620Source ClinicalTrials.gov

See all 620 adverse events

Adverse event totals6

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Enfortumab Vedotin + Pembrolizumab	133	442
Total, all-cause mortality	Standard of Care	226	444
Total, other adverse events	Enfortumab Vedotin + Pembrolizumab	435	440
Total, other adverse events	Standard of Care	418	433
Total, serious adverse events	Enfortumab Vedotin + Pembrolizumab	220	440
Total, serious adverse events	Standard of Care	169	433

Source ClinicalTrials.gov

Papers8

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
36041086	DERIVED	PubMed
38446675	DERIVED	PubMed
38446680	DERIVED	PubMed
38485615	DERIVED	PubMed
40449498	DERIVED	PubMed
41039930	DERIVED	PubMed
41563650	DERIVED	PubMed
41925239	DERIVED	PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons2

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison	Source
Enfortumab Vedotin + Pembrolizumab vs Standard of Care: deaths from any cause	Trial comparisons
Enfortumab Vedotin + Pembrolizumab vs Standard of Care: serious adverse events	Trial comparisons

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

For software

Read this trial from software.

The record and each of its lists are JSON, twenty rows a page. No key.

GET https://conductscience.org/api/trials/v1/NCT04223856

GET https://conductscience.org/api/trials/v1/NCT04223856/registered?page=2

API reference For AI assistants