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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
21/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
23/12/2026
Actual
Sample size
Target
784
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
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United States of America
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California
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United States of America
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Colorado
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Florida
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Indiana
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Iowa
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United States of America
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Kentucky
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New York
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North Carolina
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Oregon
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Pennsylvania
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Texas
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Wisconsin
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Argentina
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Caba
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Santa Fe
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Pazardzhik
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Plovdiv
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Sofia
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Jiangsu
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Shanghai
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Antioquia
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Cordoba
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Colombia
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Distrito Capital De Bogota
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Santander
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Valle Del Cauca
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Grad Zagreb
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Osjecko-baranjska Zupanija
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Splitsko-dalmatinska Zupanija
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Jihomoravsky Kraj
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Hradec Kralove
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Olomouc
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Finistere
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Isere
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Loiret
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Nord
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Paris
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Baden-Wurttemberg
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Bayern
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Nordrhein-Westfalen
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Achaia
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Attiki
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Thessalia
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Hungary
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Csongrad
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Jasz-Nagykun-Szolnok
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Haifa
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Jerusalem
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Kfar Saba
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Petah-Tikva
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Ramat Gan
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Napoli
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Ibaraki
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Ishikawa
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Kanagawa
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Miyagi
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Shizuoka
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Gifu
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Nagasaki
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Okayama
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Osaka
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Japan
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Tokyo
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Japan
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Toyama
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Korea, Republic of
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Jeonranamdo
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Korea, Republic of
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Kyonggi-do
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Korea, Republic of
State/province [95] 0 0
Seoul
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Korea, Republic of
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Taegu-Kwangyokshi
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Korea, Republic of
State/province [97] 0 0
Incheon
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Malaysia
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Kuala Lumpur
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Malaysia
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Pulau Pinang
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Malaysia
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Sarawak
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Malaysia
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Selangor
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Philippines
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Iloilo
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Poland
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Dolnoslaskie
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Mazowieckie
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Podkarpackie
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Wielkopolskie
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Zachodniopomorskie
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Portugal
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Coimbra
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Lisboa
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Portugal
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Porto
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Romania
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Cluj
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Romania
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Dolj
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Romania
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Timis
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Romania
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Bucuresti
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Russian Federation
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Altayskiy Kray
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Russian Federation
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Kaluzskaja Oblast
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Russian Federation
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Moskva
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Russian Federation
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Nizhegorodskaya Oblast
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Russian Federation
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Sankt-Peterburg
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Russian Federation
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Sverdlovskaya Oblast
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Russian Federation
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Volgogradskaya Oblast
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Singapore
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Central Singapore
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South Africa
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Gauteng
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South Africa
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Western Cape
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Spain
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Asturias
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Spain
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Barcelona
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Spain
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Gerona
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Spain
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La Coruna
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Spain
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Las Palmas
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Spain
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Valenciana, Comunitat
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Spain
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Madrid
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Spain
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Sevilla
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Taiwan
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Kaohsiung
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Taiwan
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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.


Results not provided in https://clinicaltrials.gov/study/NCT04700124