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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04700124




Registration number
NCT04700124
Ethics application status
Date submitted
5/01/2021
Date registered
7/01/2021

Titles & IDs
Public title
Perioperative Enfortumab Vedotin (EV) Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Chemotherapy for Cisplatin-eligible Muscle Invasive Bladder Cancer (MIBC) (MK-3475-B15/ KEYNOTE-B15 / EV-304)
Scientific title
A Phase 3, Randomized, Open-label Study to Evaluate Perioperative Enfortumab Vedotin Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Gemcitabine and Cisplatin in Cisplatin-eligible Participants With Muscle-invasive Bladder Cancer (KEYNOTE-B15 / EV-304)
Secondary ID [1] 0 0
MK-3475-B15
Secondary ID [2] 0 0
3475-B15
Universal Trial Number (UTN)
Trial acronym
KEYNOTE-B15
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bladder Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Other - Enfortumab vedotin (EV)
Treatment: Surgery - RC + PLND
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Cisplatin

Experimental: Arm A: Perioperative EV+ Pembrolizumab and RC + PLND - Participants receive 4 cycles (each cycle length = 21 days) of EV intravenous (IV) infusion plus pembrolizumab IV infusion preoperatively, followed by RC + PLND, followed by 5 cycles of adjuvant EV IV infusion plus 13 cycles of adjuvant pembrolizumab IV infusion postoperatively. The total treatment duration is up to approximately 1 year.

Active comparator: Arm B: Standard of Care (SOC)-Neoadjuvant chemotherapy (gemcitabine + cisplatin) and RC + PLND - Participants receive 4 cycles (each cycle length = 21 days) of standard of care (SOC) chemotherapy (gemcitabine IV infusion plus cisplatin IV infusion) preoperatively, followed by RC + PLND. The total treatment duration is up to approximately 3 months.


Treatment: Other: Pembrolizumab
200 mg of Pembrolizumab IV infusion, on Day 1 Q3W for 4 cycles (each cycle length = 21 days) in preoperative phase (up to approximately 3 months) and on Day 1 Q3W for 13 cycles in postoperative phase (up to approximately 9 months). The total duration of treatment is up to approximately 1 year.

Treatment: Other: Enfortumab vedotin (EV)
1.25 mg/kg of EV IV infusion, on Day 1 and Day 8 Q3W for 4 cycles (each cycle length = 21 days) in preoperative phase (up to approximately 3 months) and on Day 1 and Day 8 Q3W for 5 cycles (each cycle length = 21 days) in postoperative phase (up to approximately 4 months). The total duration of treatment is up to approximately 7 months.

Treatment: Surgery: RC + PLND
Curative intent RC + PLND surgery will be administered to all participants randomized to Arm A and B after completion of preoperative systemic treatment (RC + PLND to be done approximately at 15 weeks from randomization).

Treatment: Drugs: Gemcitabine
1000 mg/m\^2 of Gemcitabine IV infusion, Day 1 and Day 8 Q3W for 4 cycles in preoperative phase (up to approximately 3 months)

Treatment: Drugs: Cisplatin
70 mg/m\^2 of Cisplatin IV infusion, Day 1, Q3W for 4 cycles in preoperative phase (up to approximately 3 months)

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Surgery
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-Free Survival (EFS)
Timepoint [1] 0 0
Up to ~68 months
Secondary outcome [1] 0 0
Pathologic Complete Response (pCR) Rate
Timepoint [1] 0 0
Up to ~47 months
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to ~68 months
Secondary outcome [3] 0 0
Disease Free Survival (DFS)
Timepoint [3] 0 0
From ~12 months to up to ~68 months
Secondary outcome [4] 0 0
Pathologic Downstaging (pDS) Rate
Timepoint [4] 0 0
Up to ~47 months
Secondary outcome [5] 0 0
Number of Participants Who Experienced An Adverse Event (AE) (Arm A only)
Timepoint [5] 0 0
Up to ~68 months
Secondary outcome [6] 0 0
Number of Participants Who Discontinued Study Treatment Due to An AE (Arm A only)
Timepoint [6] 0 0
Up to ~68 months
Secondary outcome [7] 0 0
Number of Participants Experiencing Perioperative Complications
Timepoint [7] 0 0
Up to ~68 months
Secondary outcome [8] 0 0
Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score
Timepoint [8] 0 0
Baseline, Up to ~68 months
Secondary outcome [9] 0 0
Change from Baseline in EORTC QLQ-C30 Physical Functioning Scale
Timepoint [9] 0 0
Baseline, Up to ~68 months
Secondary outcome [10] 0 0
Change From Baseline in Urinary, Bowel and Sexual Domains per Bladder Cancer Index (BCI)
Timepoint [10] 0 0
Baseline, Up to ~68 months
Secondary outcome [11] 0 0
Change from Baseline in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS)
Timepoint [11] 0 0
Baseline, Up to ~68 months
Secondary outcome [12] 0 0
Change from Baseline in EORTC QLQ-C30 Role Functioning Combined Score (Items 6-7)
Timepoint [12] 0 0
Baseline, Up to ~68 months

Eligibility
Key inclusion criteria
* Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (=50%) urothelial histology.
* Have clinically non-metastatic bladder cancer (N=1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis
* Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND)
* Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Have adequate organ function.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has a known additional malignancy that is progressing or has required active anti-cancer treatment =3 years of study randomization with certain exceptions
* Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
* Has =N2 disease or metastatic disease (M1) as identified by imaging
* Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol
* Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder
* Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC
* Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
* Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection. Hepatitis B infection or known active Hepatitis C infection
* Has a known psychiatric or substance abuse disorder
* Has had an allogenic tissue/solid organ transplant
* Has ongoing sensory or motor neuropathy Grade 2 or higher
* Has active keratitis (superficial punctate keratitis) or corneal ulcerations
* Has a history of uncontrolled diabetes defined as hemoglobin A1c (HbA1c) =8% or HbA1c 7% to <8% with associated diabetes symptoms

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Macquarie University-MQ Health Clinical Trials Unit ( Site 1259) - Macquarie University
Recruitment hospital [2] 0 0
Mater Hospital Brisbane ( Site 1257) - South Brisbane
Recruitment hospital [3] 0 0
Lyell McEwin Hospital ( Site 1252) - Elizabeth Vale
Recruitment hospital [4] 0 0
Frankston Hospital-Oncology and Haematology ( Site 1258) - Frankston
Recruitment postcode(s) [1] 0 0
2109 - Macquarie University
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
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Oregon
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United States of America
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Pennsylvania
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United States of America
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South Carolina
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Tennessee
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United States of America
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Texas
Country [15] 0 0
United States of America
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Wisconsin
Country [16] 0 0
Argentina
State/province [16] 0 0
Buenos Aires
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Argentina
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Caba
Country [18] 0 0
Argentina
State/province [18] 0 0
Santa Fe
Country [19] 0 0
Bulgaria
State/province [19] 0 0
Pazardzhik
Country [20] 0 0
Bulgaria
State/province [20] 0 0
Plovdiv
Country [21] 0 0
Bulgaria
State/province [21] 0 0
Sofia
Country [22] 0 0
Canada
State/province [22] 0 0
British Columbia
Country [23] 0 0
Canada
State/province [23] 0 0
Manitoba
Country [24] 0 0
Canada
State/province [24] 0 0
New Brunswick
Country [25] 0 0
Canada
State/province [25] 0 0
Ontario
Country [26] 0 0
Canada
State/province [26] 0 0
Quebec
Country [27] 0 0
China
State/province [27] 0 0
Guangdong
Country [28] 0 0
China
State/province [28] 0 0
Hunan
Country [29] 0 0
China
State/province [29] 0 0
Jiangsu
Country [30] 0 0
China
State/province [30] 0 0
Shanghai
Country [31] 0 0
Colombia
State/province [31] 0 0
Antioquia
Country [32] 0 0
Colombia
State/province [32] 0 0
Cordoba
Country [33] 0 0
Colombia
State/province [33] 0 0
Distrito Capital De Bogota
Country [34] 0 0
Colombia
State/province [34] 0 0
Santander
Country [35] 0 0
Colombia
State/province [35] 0 0
Valle Del Cauca
Country [36] 0 0
Croatia
State/province [36] 0 0
Grad Zagreb
Country [37] 0 0
Croatia
State/province [37] 0 0
Osjecko-baranjska Zupanija
Country [38] 0 0
Croatia
State/province [38] 0 0
Splitsko-dalmatinska Zupanija
Country [39] 0 0
Czechia
State/province [39] 0 0
Jihomoravsky Kraj
Country [40] 0 0
Czechia
State/province [40] 0 0
Hradec Kralove
Country [41] 0 0
Czechia
State/province [41] 0 0
Olomouc
Country [42] 0 0
Czechia
State/province [42] 0 0
Praha 4
Country [43] 0 0
France
State/province [43] 0 0
Bouches-du-Rhone
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France
State/province [44] 0 0
Doubs
Country [45] 0 0
France
State/province [45] 0 0
Finistere
Country [46] 0 0
France
State/province [46] 0 0
Haute-Garonne
Country [47] 0 0
France
State/province [47] 0 0
Haute-Vienne
Country [48] 0 0
France
State/province [48] 0 0
Ile-de-France
Country [49] 0 0
France
State/province [49] 0 0
Isere
Country [50] 0 0
France
State/province [50] 0 0
Loiret
Country [51] 0 0
France
State/province [51] 0 0
Nord
Country [52] 0 0
France
State/province [52] 0 0
Paris
Country [53] 0 0
Germany
State/province [53] 0 0
Baden-Wurttemberg
Country [54] 0 0
Germany
State/province [54] 0 0
Bayern
Country [55] 0 0
Germany
State/province [55] 0 0
Nordrhein-Westfalen
Country [56] 0 0
Germany
State/province [56] 0 0
Sachsen-Anhalt
Country [57] 0 0
Germany
State/province [57] 0 0
Sachsen
Country [58] 0 0
Germany
State/province [58] 0 0
Berlin
Country [59] 0 0
Greece
State/province [59] 0 0
Achaia
Country [60] 0 0
Greece
State/province [60] 0 0
Attiki
Country [61] 0 0
Greece
State/province [61] 0 0
Thessalia
Country [62] 0 0
Hungary
State/province [62] 0 0
Csongrad
Country [63] 0 0
Hungary
State/province [63] 0 0
Jasz-Nagykun-Szolnok
Country [64] 0 0
Hungary
State/province [64] 0 0
Debrecen
Country [65] 0 0
Israel
State/province [65] 0 0
Haifa
Country [66] 0 0
Israel
State/province [66] 0 0
Jerusalem
Country [67] 0 0
Israel
State/province [67] 0 0
Kfar Saba
Country [68] 0 0
Israel
State/province [68] 0 0
Petah-Tikva
Country [69] 0 0
Israel
State/province [69] 0 0
Ramat Gan
Country [70] 0 0
Israel
State/province [70] 0 0
Tel Aviv
Country [71] 0 0
Israel
State/province [71] 0 0
Zerifin
Country [72] 0 0
Italy
State/province [72] 0 0
Lombardia
Country [73] 0 0
Italy
State/province [73] 0 0
Napoli
Country [74] 0 0
Italy
State/province [74] 0 0
Torino
Country [75] 0 0
Italy
State/province [75] 0 0
Veneto
Country [76] 0 0
Italy
State/province [76] 0 0
Ancona
Country [77] 0 0
Italy
State/province [77] 0 0
Catania
Country [78] 0 0
Italy
State/province [78] 0 0
Milano
Country [79] 0 0
Italy
State/province [79] 0 0
Padova
Country [80] 0 0
Japan
State/province [80] 0 0
Aichi
Country [81] 0 0
Japan
State/province [81] 0 0
Aomori
Country [82] 0 0
Japan
State/province [82] 0 0
Ibaraki
Country [83] 0 0
Japan
State/province [83] 0 0
Ishikawa
Country [84] 0 0
Japan
State/province [84] 0 0
Kanagawa
Country [85] 0 0
Japan
State/province [85] 0 0
Miyagi
Country [86] 0 0
Japan
State/province [86] 0 0
Shizuoka
Country [87] 0 0
Japan
State/province [87] 0 0
Gifu
Country [88] 0 0
Japan
State/province [88] 0 0
Nagasaki
Country [89] 0 0
Japan
State/province [89] 0 0
Okayama
Country [90] 0 0
Japan
State/province [90] 0 0
Osaka
Country [91] 0 0
Japan
State/province [91] 0 0
Tokyo
Country [92] 0 0
Japan
State/province [92] 0 0
Toyama
Country [93] 0 0
Korea, Republic of
State/province [93] 0 0
Jeonranamdo
Country [94] 0 0
Korea, Republic of
State/province [94] 0 0
Kyonggi-do
Country [95] 0 0
Korea, Republic of
State/province [95] 0 0
Seoul
Country [96] 0 0
Korea, Republic of
State/province [96] 0 0
Taegu-Kwangyokshi
Country [97] 0 0
Korea, Republic of
State/province [97] 0 0
Incheon
Country [98] 0 0
Malaysia
State/province [98] 0 0
Kuala Lumpur
Country [99] 0 0
Malaysia
State/province [99] 0 0
Pulau Pinang
Country [100] 0 0
Malaysia
State/province [100] 0 0
Sarawak
Country [101] 0 0
Malaysia
State/province [101] 0 0
Selangor
Country [102] 0 0
Philippines
State/province [102] 0 0
Iloilo
Country [103] 0 0
Poland
State/province [103] 0 0
Dolnoslaskie
Country [104] 0 0
Poland
State/province [104] 0 0
Mazowieckie
Country [105] 0 0
Poland
State/province [105] 0 0
Podkarpackie
Country [106] 0 0
Poland
State/province [106] 0 0
Wielkopolskie
Country [107] 0 0
Poland
State/province [107] 0 0
Zachodniopomorskie
Country [108] 0 0
Portugal
State/province [108] 0 0
Coimbra
Country [109] 0 0
Portugal
State/province [109] 0 0
Lisboa
Country [110] 0 0
Portugal
State/province [110] 0 0
Porto
Country [111] 0 0
Romania
State/province [111] 0 0
Cluj
Country [112] 0 0
Romania
State/province [112] 0 0
Dolj
Country [113] 0 0
Romania
State/province [113] 0 0
Timis
Country [114] 0 0
Romania
State/province [114] 0 0
Bucuresti
Country [115] 0 0
Russian Federation
State/province [115] 0 0
Altayskiy Kray
Country [116] 0 0
Russian Federation
State/province [116] 0 0
Kaluzskaja Oblast
Country [117] 0 0
Russian Federation
State/province [117] 0 0
Moskva
Country [118] 0 0
Russian Federation
State/province [118] 0 0
Nizhegorodskaya Oblast
Country [119] 0 0
Russian Federation
State/province [119] 0 0
Sankt-Peterburg
Country [120] 0 0
Russian Federation
State/province [120] 0 0
Sverdlovskaya Oblast
Country [121] 0 0
Russian Federation
State/province [121] 0 0
Volgogradskaya Oblast
Country [122] 0 0
Singapore
State/province [122] 0 0
Central Singapore
Country [123] 0 0
South Africa
State/province [123] 0 0
Gauteng
Country [124] 0 0
South Africa
State/province [124] 0 0
Western Cape
Country [125] 0 0
Spain
State/province [125] 0 0
Asturias
Country [126] 0 0
Spain
State/province [126] 0 0
Barcelona
Country [127] 0 0
Spain
State/province [127] 0 0
Gerona
Country [128] 0 0
Spain
State/province [128] 0 0
La Coruna
Country [129] 0 0
Spain
State/province [129] 0 0
Las Palmas
Country [130] 0 0
Spain
State/province [130] 0 0
Valenciana, Comunitat
Country [131] 0 0
Spain
State/province [131] 0 0
Madrid
Country [132] 0 0
Spain
State/province [132] 0 0
Sevilla
Country [133] 0 0
Taiwan
State/province [133] 0 0
Kaohsiung
Country [134] 0 0
Taiwan
State/province [134] 0 0
Taichung
Country [135] 0 0
Taiwan
State/province [135] 0 0
Taipei
Country [136] 0 0
Ukraine
State/province [136] 0 0
Dnipropetrovska Oblast
Country [137] 0 0
Ukraine
State/province [137] 0 0
Kharkivska Oblast
Country [138] 0 0
Ukraine
State/province [138] 0 0
Lvivska Oblast
Country [139] 0 0
Ukraine
State/province [139] 0 0
Zhytomyrska Oblast
Country [140] 0 0
United Kingdom
State/province [140] 0 0
Devon
Country [141] 0 0
United Kingdom
State/province [141] 0 0
London, City Of

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Seagen Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Astellas Pharma Inc
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.