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History of Changes for Study: NCT04223856
Enfortumab Vedotin and Pembrolizumab, With or Without Chemotherapy, vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer (EV-302)
Latest version (submitted September 19, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 January 8, 2020 None (earliest Version on record)
2 January 15, 2020 Arms and Interventions and Study Status
3 March 20, 2020 Recruitment Status, Study Status, Contacts/Locations and Oversight
4 March 25, 2020 Contacts/Locations and Study Status
5 April 21, 2020 Study Status and Contacts/Locations
6 April 28, 2020 Contacts/Locations and Study Status
7 May 4, 2020 Study Status and Contacts/Locations
8 May 20, 2020 Contacts/Locations and Study Status
9 June 3, 2020 Study Status and Contacts/Locations
10 June 15, 2020 Contacts/Locations and Study Status
11 June 30, 2020 Study Status, Contacts/Locations and Eligibility
12 July 10, 2020 Contacts/Locations and Study Status
13 August 6, 2020 Study Status and Contacts/Locations
14 September 29, 2020 Outcome Measures, Arms and Interventions, Study Description, Study Status, Study Identification, Eligibility and Study Design
15 October 20, 2020 Study Status and Contacts/Locations
16 November 13, 2020 Study Status and Contacts/Locations
17 December 23, 2020 Study Status and Contacts/Locations
18 February 11, 2021 Contacts/Locations and Study Status
19 February 17, 2021 Contacts/Locations and Study Status
20 March 3, 2021 Study Status and Study Identification
21 March 5, 2021 Study Status and Contacts/Locations
22 March 18, 2021 Contacts/Locations and Study Status
23 March 25, 2021 Study Status
24 April 2, 2021 Study Status and Contacts/Locations
25 April 27, 2021 Contacts/Locations and Study Status
26 May 11, 2021 Study Status and Contacts/Locations
27 May 13, 2021 Contacts/Locations and Study Status
28 June 24, 2021 Study Status and Contacts/Locations
29 July 12, 2021 Study Status and Contacts/Locations
30 August 5, 2021 Study Status and Contacts/Locations
31 August 11, 2021 Contacts/Locations, Study Status and Study Identification
32 August 27, 2021 Contacts/Locations and Study Status
33 September 13, 2021 Study Status and Contacts/Locations
34 September 16, 2021 Contacts/Locations and Study Status
35 September 29, 2021 Contacts/Locations and Study Status
36 October 14, 2021 Study Status, Contacts/Locations and Study Description
37 October 28, 2021 Contacts/Locations and Study Status
38 November 3, 2021 Contacts/Locations and Study Status
39 November 29, 2021 Contacts/Locations and Study Status
40 December 21, 2021 Study Status, Contacts/Locations, Outcome Measures and Study Design
41 January 11, 2022 Contacts/Locations and Study Status
42 January 24, 2022 Contacts/Locations and Study Status
43 February 9, 2022 Study Status and Contacts/Locations
44 February 23, 2022 Outcome Measures and Study Status
45 March 8, 2022 Study Status and Contacts/Locations
46 March 21, 2022 Contacts/Locations and Study Status
47 March 24, 2022 Contacts/Locations and Study Status
48 March 28, 2022 Contacts/Locations and Study Status
49 April 8, 2022 Study Status and Contacts/Locations
50 May 18, 2022 Study Status and Contacts/Locations
51 May 27, 2022 Contacts/Locations and Study Status
52 June 13, 2022 Contacts/Locations and Study Status
53 June 28, 2022 Contacts/Locations and Study Status
54 July 20, 2022 Study Status and Study Design
55 August 1, 2022 Contacts/Locations and Study Status
56 August 9, 2022 Contacts/Locations and Study Status
57 August 24, 2022 Contacts/Locations and Study Status
58 September 19, 2022 Study Status and Contacts/Locations
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Study NCT04223856
Submitted Date:  January 8, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: SGN22E-003
Brief Title: Enfortumab Vedotin and Pembrolizumab, With or Without Chemotherapy, vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer (EV-302)
Official Title: An Open-label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination With Pembrolizumab With or Without Chemotherapy, Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer
Secondary IDs: 2019-004542-15 [EudraCT Number]
MK-3475-A39 [Merck]
Open or close this module Study Status
Record Verification: January 2020
Overall Status: Not yet recruiting
Study Start: March 2020
Primary Completion: November 2023 [Anticipated]
Study Completion: November 2023 [Anticipated]
First Submitted: January 6, 2020
First Submitted that
Met QC Criteria:
January 8, 2020
First Posted: January 10, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
January 8, 2020
Last Update Posted: January 10, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Astellas Pharma Global Development, Inc.
Responsible Party: Sponsor
Collaborators: Merck Sharp & Dohme LLC
Seagen Inc.
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab) work together alone or with platinum chemotherapy to treat patients with urothelial cancer. The study will compare these drugs to other drugs that are usually used to treat this cancer (standard of care). The patients in this study will have cancer that has spread from their urinary system to other parts of their body.
Detailed Description:

This study is being conducted to evaluate the combination of enfortumab vedotin + pembrolizumab, with or without platinum-containing chemotherapy, versus standard of care gemcitabine + platinum-containing chemotherapy, in subjects with previously untreated locally advanced or metastatic urothelial cancer.

Enfortumab vedotin may be administered for an unlimited number of cycles until a protocol defined reason for study discontinuation occurs. Pembrolizumab may be administered for a maximum of 35 cycles or a protocol-defined reason for study discontinuation occurs, whichever is first. Cisplatin, carboplatin, and/or gemcitabine may be administered for a maximum of 6 cycles or a protocol-defined reason for study discontinuation occurs, whichever is first.

Open or close this module Conditions
Conditions: Urothelial Cancer
Keywords: Urothelial Cancer
Enfortumab vedotin
metastatic urothelial cancer
pembrolizumab
locally advanced urothelial cancer
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 3
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 1095 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Arm A
Enfortumab vedotin + pembrolizumab
Drug: Enfortumab vedotin
Enfortumab vedotin administered as an IV infusion on Days 1 and 8 of every 3-week cycle
Other Names:
  • ASG-22CE
  • ASG-22ME
  • PADCEV
Drug: Pembrolizumab
IV infusion on Day 1 of every 3-week cycle
Other Names:
  • Keytruda
Active Comparator: Arm B
Gemcitabine + cisplatin or carboplatin
Drug: Cisplatin
administered as IV infusion on Day 1 of each 3-week cycle
Drug: Carboplatin
Dosed according to local will be administered as IV infusion on Day 1 of each 3-week cycle
Drug: Gemcitabine
IV infusion on Days 1 and 8 of every 3 week cycle
Experimental: Arm C
Enfortumab vedotin + pembrolizumab + Cisplatin or carboplatin
Drug: Enfortumab vedotin
Enfortumab vedotin administered as an IV infusion on Days 1 and 8 of every 3-week cycle
Other Names:
  • ASG-22CE
  • ASG-22ME
  • PADCEV
Drug: Pembrolizumab
IV infusion on Day 1 of every 3-week cycle
Other Names:
  • Keytruda
Drug: Cisplatin
administered as IV infusion on Day 1 of each 3-week cycle
Drug: Carboplatin
Dosed according to local will be administered as IV infusion on Day 1 of each 3-week cycle
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Duration of progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review (BICR)
[ Time Frame: Up to approximately 5 years ]

Defined as the time from randomization to first documentation of disease progression per RECIST v1.1 by BICR, or to death due to any cause, whichever comes first.
2. Duration of Overall survival (OS)
[ Time Frame: Up to approximately 5 years ]

OS is defined as the time from date of randomization to date of death due to any cause.
Secondary Outcome Measures:
1. Duration of PFS per RECIST v1.1 by investigator assessment
[ Time Frame: Up to approximately 5 years ]

Defined as the time from randomization to first documentation of disease progression per RECIST v1.1, or to death due to any cause, whichever comes first
2. Overall response rate (ORR) per RECIST v1.1 by BICR
[ Time Frame: Up to approximately 5 years ]

Defined as the proportion of subjects with confirmed CR or PR according to RECIST v1.1
3. ORR per RECIST v1.1 by investigator assessment
[ Time Frame: Up to approximately 5 years ]

Defined as the proportion of subjects with confirmed CR or PR according to RECIST v1.1
4. Duration of response (DOR) per RECIST v1.1 by BICR
[ Time Frame: Up to approximately 5 years ]

Defined as the time from first documented response of CR or PR (that is subsequently confirmed) to the first documented disease progression per RECIST v1.1, or to death due to any cause, whichever comes first
5. DOR per RECIST v1.1 by investigator assessment
[ Time Frame: Up to approximately 5 years ]

Defined as the time from first documented response of CR or PR (that is subsequently confirmed) to the first documented disease progression per RECIST v1.1, or to death due to any cause, whichever comes first
6. Disease control rate (DCR) per RECIST v1.1 by BICR
[ Time Frame: Up to approximately 5 years ]

Defined as the proportion of subjects with confirmed CR, PR, or SD according to RECIST v1.1
7. DCR per RECIST v1.1 by investigator assessment
[ Time Frame: Up to approximately 5 years ]

Defined as the proportion of subjects with confirmed CR, PR, or SD according to RECIST v1.1
8. Change from baseline in patient reported outcome assessment measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) questionnaire
[ Time Frame: Up to approximately 5 years ]

The EQ-5D-5L is a standardized instrument developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. The EQ-5D-5L is a 5-item self-reported measure of functioning and wellbeing, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale.
9. Change from baseline in patient reported outcome assessment measured by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)
[ Time Frame: Up to approximately 5 years ]

EORTC-QLQ-C30 is a cancer-specific 30-item questionnaire. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
10. Change from baseline in patient reported outcome assessment measured by Brief Pain Inventory - Short Form (BPI-SF)
[ Time Frame: Up to approximately 5 years ]

The Short Form is a single assessment of overall pain where 0 equals no pain and 10 equals extreme pain. Low pain scores are considered a better outcome than a high pain score.
11. Incidence of adverse events (AEs)
[ Time Frame: Up to approximately 5 years ]

Descriptive statistics will be used to summarize results
12. Incidence of laboratory abnormalities
[ Time Frame: Up to approximately 5 years ]

Descriptive statistics will be used to summarize results
13. Treatment discontinuation rate due to AEs
[ Time Frame: Up to approximately 5 years ]

Descriptive statistics will be used to summarize results
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Histologically documented, unresectable locally advanced or metastatic urothelial carcinoma
  • Measurable disease by investigator assessment according to RECIST v1.1
    • Participants with prior definitive radiation therapy must have measurable disease per RECIST v1.1 that is outside the radiation field or has demonstrated unequivocal progression since completion of radiation therapy
  • Participants must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:
    • Participants that received neoadjuvant chemotherapy with recurrence >12 months from completion of therapy are permitted
    • Participants that received adjuvant chemotherapy following cystectomy with recurrence >12 months from completion of therapy are permitted
  • Must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy, in the investigator's judgement
  • Archival tumor tissue comprising muscle-invasive urothelial carcinoma or a biopsy of metastatic urothelial carcinoma must be provided for PD-L1 testing prior to randomization
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
  • Adequate hematologic and organ function

Exclusion Criteria

  • Previously received enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugate (ADCs)
  • Received prior treatment with a programmed cell death ligand-1 (PD-(L)-1) inhibitor for any malignancy, including earlier stage urothelial cancer (UC), defined as a PD-1 inhibitor or PD-L1 inhibitor
  • Received prior treatment with an agent directed to another stimulatory or co inhibitory T-cell receptor
  • Received anti-cancer treatment with chemotherapy, biologics, or investigational agents not otherwise prohibited by exclusion criterion 1-3 that is not completed 4 weeks prior to first dose of study treatment
  • Uncontrolled diabetes
  • Estimated life expectancy of less than 12 weeks
  • Active central nervous system (CNS) metastases
  • Ongoing clinically significant toxicity associated with prior treatment that has not resolved to ≤ Grade 1 or returned to baseline
  • Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted.
  • Known history of hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
  • History of another invasive malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy
  • Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class IV within 6 months prior to randomization
  • Receipt of radiotherapy within 2 weeks prior to randomization
  • Received major surgery (defined as requiring general anesthesia and >24 hour inpatient hospitalization) within 3 weeks prior to randomization
  • Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin
  • Active keratitis or corneal ulcerations
  • History of autoimmune disease that has required systemic treatment in the past 2 years
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Prior allogeneic stem cell or solid organ transplant
  • Received a live attenuated vaccine within 30 days prior to randomization
Open or close this module Contacts/Locations
Central Contact Person: Seattle Genetics Trial Information Support
Telephone: 866-333-7436
Email: clinicaltrials@seagen.com
Study Officials: Christina Derleth, MD, MSCI
Study Director
Seagen Inc.
Locations:
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Links:
Available IPD/Information:

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