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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04700124




Registration number
NCT04700124
Ethics application status
Date submitted
5/01/2021
Date registered
7/01/2021
Date last updated
26/01/2024

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
Other interventions - Pembrolizumab
Other interventions - 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.


Other interventions: 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.

Other interventions: 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
Other interventions
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
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Timis
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Bucuresti
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Russian Federation
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Altayskiy Kray
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Kaluzskaja Oblast
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Moskva
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Sverdlovskaya Oblast
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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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Gerona
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La Coruna
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Las Palmas
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Valenciana, Comunitat
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Spain
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Madrid
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Sevilla
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Taiwan
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Kaohsiung
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Taichung
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Taiwan
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Taipei
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Ukraine
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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
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Zhytomyrska Oblast
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United Kingdom
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Devon
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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
The purpose of this study is to assess the antitumor efficacy and safety of perioperative
enfortumab vedotin (EV) plus pembrolizumab and radical cystectomy (RC) + pelvic lymph node
dissection (PLND) compared with the current standard of care (neoadjuvant chemotherapy
[gemcitabine plus cisplatin] and RC + PLND) for participants with MIBC who are
cisplatin-eligible. The primary hypothesis is perioperative EV and pembrolizumab and RC +
PLND (Arm A) will achieve superior event free survival (EFS) compared with neoadjuvant
gemcitabine + cisplatin and RC + PLND (Arm B).
Trial website
https://clinicaltrials.gov/ct2/show/NCT04700124
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