Clinical trial NCT04209114: A Study of Nivolumab Plus Bempegaldesleukin (Bempeg/NKTR-214) vs Nivolumab Alone vs Standard of Care in Participants With Bladder Cancer That May Have Invaded The Muscle Wall of the Bladder and Who Cannot Get Cisplatin, A Type of Medicine Given To Treat Bladder Cancer
Official title: A Phase 3, Randomized, Study of Neoadjuvant and Adjuvant Nivolumab Plus Bempegaldesleukin (NKTR-214), Versus Nivolumab Alone Versus Standard of Care in Participants With Muscle-Invasive Bladder Cancer (MIBC) Who Are Cisplatin Ineligible
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bladder Cancer
Bladder Tumor
Muscle-Invasive Bladder Cancer
Keywords: immunotherapy
NKTR-214
nivolumab
bempeg
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Nektar Therapeutics
First posted: 2019-12-23
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to see if treatment with nivolumab plus bempegaldesleukin or nivolumab alone, before and after surgery to remove the bladder, is more effective than surgery alone in participants with high-risk urothelial cancer, including muscle-invasive bladder cancer who are not able to receive cisplatin chemotherapy.


Eligibility criteria: Inclusion Criteria:

* Urothelial carcinoma (UC) of the bladder, clinical stage T2-T4aN0, M0 or T1-T4aN1, M0, diagnosed at transurethral resection of bladder tumor (TURBT)
* Must be deemed eligible for Radical Cystectomy (RC) by urologist, and must agree to undergo RC. For arms A and B, participants must agree to undergo RC after completion of neoadjuvant therapy.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Cisplatin-ineligible participants will be defined by any one of the following criteria:

  i) Impaired renal function (glomerular filtration rate \[GFR\] ≥ 30 but \< 60 mL/min) ii) GFR should be assessed by direct measurement (ie, creatinine clearance) or, if not available, by calculation from serum/plasma creatinine (Cockcroft-Gault formula) iii) Common Terminology Criteria for Adverse Events (CTCAE) version 5, ≥ Grade 2 hearing loss (assessed per local SOC).

iv) CTCAE version 5, ≥ Grade 2 peripheral neuropathy.

* Documented Left Ventricular Ejection Fraction (LVEF) more than 45%

Exclusion Criteria:

* Clinical evidence of ≥ N2 or metastatic bladder cancer
* Prior systemic therapy, radiation therapy, or surgery for bladder cancer other than TURBT or biopsies is not permitted. Prior Bacillus Calmette-Guerin (BCG) or other intravesicular treatment of non-muscle invasive bladder cancer (NMIBC) is permitted if completed at least 6 weeks prior to initiating study treatment.
* Evidence of urothelial carcinoma (UC) in upper urinary tracts (ureters or renal pelvis) or history of previous MIBC
* History of pulmonary embolism (PE), deep vein thrombosis (DVT), or prior clinically significant venous or non-CVA(cerebrovascular accident)/TIA (Transient ischemic attack) arterial thromboembolic event
* Known cardiovascular history, including unstable or deteriorating cardiac disease within the previous 12 months (including unstable angina or myocardial infarction, congestive heart failure or uncontrolled clinically significant arrhythmias)

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Pathologic Complete Response (pCR) Rate- Nivolumab + Bempegaldesleukin Compared to Standard of Care
timeFrame: From time of radical cystectomy up to 100 days after last treatment (up to approximately 17 months)
measure: Event Free Survival (EFS) - Nivolumab + Bempegaldesleukin Compared to Standard of Care
timeFrame: From randomization up to first EFS event (up to approximately 30 months)
Secondary outcomes:
measure: Pathologic Complete Response (pCR) Rate - Nivolumab Compared to Standard of Care
timeFrame: From time of radical cystectomy up to 100 days after last treatment (up to approximately 17 months)
measure: Event Free Survival (EFS) - Nivolumab Compared to Standard of Care
timeFrame: From randomization up to first EFS event (up to approximately 30 months)
measure: Overall Survival (OS)
timeFrame: From randomization to study completion, up to approximately 40 months
measure: The Number of Participants Experiencing Adverse Events (AEs)
timeFrame: from first dose to 100 days following last dose (up to approximately 20 months)
measure: The Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: from first dose to 100 days following last dose (up to approximately 20 months)
measure: The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
timeFrame: from first dose to 100 days following last dose (up to approximately 20 months)
measure: The Number of Participants Experiencing Immune-Mediated Adverse Events (IMAEs)
timeFrame: from first dose to 100 days following last dose (up to approximately 20 months)
measure: Worst Grade Clinical Laboratory Values
timeFrame: From first dose to 100 days following last dose (up to approximately 20 months)
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Local Institution - 0080
state: Arizona
city: Tucson
country: United States
facility: Local Institution - 0136
state: Arizona
city: La Jolla
country: United States
facility: Local Institution - 0029
state: California
city: Orange
country: United States
facility: Local Institution - 0015
state: California
city: Iowa City
country: United States
facility: Local Institution - 0002
state: Iowa
city: Rochester
country: United States
facility: Local Institution
state: Minnesota
city: New Brunswick
country: United States
facility: Local Institution - 0006
state: New Jersey
city: Bronx
country: United States
facility: Local Institution - 0009
state: New York
city: Buffalo
country: United States
facility: Local Institution - 0004
state: New York
city: Allentown
country: United States
facility: Local Institution - 0005
state: Pennsylvania
city: Charleston
country: United States
facility: Local Institution - 0007
state: South Carolina
city: Houston
country: United States
facility: Local Institution - 0139
state: Texas
city: Temple
country: United States
facility: Local Institution - 0023
state: Texas
city: Gig Harbor
country: United States
facility: Local Institution - 0122
state: Washington
city: Seattle
country: United States
facility: Local Institution - 0102
state: Washington
city: Capital Federal
country: Argentina
facility: Local Institution - 0096
state: Buenos Aires
city: Ciudad Autónoma De Buenos Aires
country: Argentina
facility: Local Institution - 0028
state: Buenos Aires
city: La Plata
country: Argentina
facility: Local Institution - 0124
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution - 0027
state: Distrito Federal
city: Rosario
country: Argentina
facility: Local Institution - 0174
state: Santa FE
city: Cordoba
country: Argentina
facility: Local Institution - 0097
city: Gosford
country: Australia
facility: Local Institution - 0137
state: New South Wales
city: Ballarat
country: Australia
facility: Local Institution - 0158
state: Victoria
city: Fitzroy
country: Australia
facility: Local Institution - 0157
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution - 0011
state: Victoria
city: Murdoch
country: Australia
facility: Local Institution - 0013
state: Western Australia
city: Graz
country: Austria
facility: Local Institution - 0148
city: Vienna
country: Austria
facility: Local Institution - 0150
city: Wien
country: Austria
facility: Local Institution - 0123
city: Wilrijk
country: Belgium
facility: Local Institution - 0083
state: Antwerpen
city: Brussel
country: Belgium
facility: Local Institution - 0101
state: Brussels
city: Edegem
country: Belgium
facility: Local Institution - 0098
city: Gent
country: Belgium
facility: Local Institution - 0068
city: Liège
country: Belgium
facility: Local Institution - 0100
city: Porto Alegre
country: Brazil
facility: Local Institution - 0177
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Local Institution - 0039
state: RIO Grande DO SUL
city: Barretos
country: Brazil
facility: Local Institution - 0176
state: SAO Paulo
city: Jau
country: Brazil
facility: Local Institution - 0037
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Local Institution - 0038
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Local Institution - 0041
city: Sao Paulo
country: Brazil
facility: Local Institution - 0040
city: Oshawa
country: Canada
facility: Local Institution - 0082
state: Ontario
city: Sherbrooke
country: Canada
facility: Local Institution - 0036
state: Quebec
city: Quebec
country: Canada
facility: Local Institution - 0018
city: Chongqing
country: China
facility: Local Institution - 0204
state: Chongqing
city: Xiamen
country: China
facility: Local Institution
state: Fujian
city: Zhengzhou
country: China
facility: Local Institution
state: Henan
city: Wuhan
country: China
facility: Local Institution
state: Hubei
city: Changsha
country: China
facility: Local Institution
state: Hunan
city: Taiyuan
country: China
facility: Local Institution
state: Shan1xi
city: Jinan
country: China
facility: Local Institution
state: Shandong
city: Olomouc
country: Czechia
facility: Local Institution - 0022
city: Praha 5
country: Czechia
facility: Local Institution - 0020
city: Praha
country: Czechia
facility: Local Institution - 0021
city: Avignon Cedex 9
country: France
facility: Local Institution - 0077
city: Bordeaux
country: France
facility: Local Institution - 0091
city: Clermont-Ferrand
country: France
facility: Local Institution - 0151
city: La Roche-sur-Yon
country: France
facility: Local Institution - 0059
city: Lyon
country: France
facility: Local Institution - 0071
city: Marseille Cedex 9
country: France
facility: Local Institution - 0057
city: Montpellier
country: France
facility: Local Institution - 0075
city: Nice
country: France
facility: Local Institution - 0070
city: Paris
country: France
facility: Local Institution - 0062
city: Paris
country: France
facility: Local Institution - 0060
city: Quimper
country: France
facility: Local Institution - 0064
city: Reims
country: France
facility: Local Institution - 0161
city: Strasbourg
country: France
facility: Local Institution - 0058
city: Suresnes
country: France
facility: Local Institution - 0056
city: Tours
country: France
facility: Local Institution - 0074
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus
city: Duesseldorf
country: Germany
facility: Local Institution - 0117
city: Erlangen
country: Germany
facility: Local Institution - 0119
city: Essen
country: Germany
facility: Local Institution - 0050
city: Hamburg
country: Germany
facility: Local Institution - 0052
city: Hamburg
country: Germany
facility: Local Institution - 0051
city: Herne
country: Germany
facility: Local Institution - 0049
city: Jena
country: Germany
facility: Local Institution - 0045
city: Luebeck
country: Germany
facility: Local Institution - 0053
city: Muenster
country: Germany
facility: Local Institution - 0113
city: Nuernberg
country: Germany
facility: Local Institution - 0048
city: Tuebingen
country: Germany
facility: Local Institution - 0046
city: Athens
country: Greece
facility: Local Institution - 0178
city: Athens
country: Greece
facility: Local Institution - 0088
city: Chaidari
country: Greece
facility: Local Institution - 0033
city: Thessaloniki
country: Greece
facility: Local Institution - 0035
city: Haifa
country: Israel
facility: Local Institution - 0129
city: Tel Aviv
country: Israel
facility: Local Institution - 0131
city: Tel Hashomer
country: Israel
facility: Local Institution - 0130
city: Firenze
country: Italy
facility: Local Institution - 0149
city: Milano
country: Italy
facility: Local Institution - 0162
city: Milano
country: Italy
facility: Local Institution - 0025
city: Pavia
country: Italy
facility: Local Institution
city: Pisa
country: Italy
facility: Local Institution - 0026
city: Roma
country: Italy
facility: Local Institution - 0065
city: Rozzano
country: Italy
facility: Local Institution - 0044
city: La Paz
country: Mexico
facility: Local Institution - 0154
state: BAJA Californa SUR
city: Ciudad de Mexico
country: Mexico
facility: Local Institution - 0132
state: Distrito Federal
city: Mexico
country: Mexico
facility: Local Institution - 0160
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Local Institution - 0133
state: Nuevo LEON
city: Amsterdam
country: Netherlands
facility: Local Institution - 0069
city: Biala Podlaska
country: Poland
facility: Local Institution - 0167
city: Warszawa
country: Poland
facility: Local Institution - 0054
city: Omsk
country: Russian Federation
facility: Local Institution
city: Saint-Petersburg
country: Russian Federation
facility: Local Institution
city: A Coruña
country: Spain
facility: Local Institution - 0104
city: Badalona
country: Spain
facility: Local Institution - 0106
city: Barcelona
country: Spain
facility: Local Institution - 0110
city: Cordoba
country: Spain
facility: Local Institution - 0109
city: Madrid
country: Spain
facility: Local Institution - 0105
city: Madrid
country: Spain
facility: Local Institution - 0108
city: Madrid
country: Spain
facility: Local Institution - 0103
city: Santander
country: Spain
facility: Local Institution - 0107
city: Sevilla
country: Spain
facility: Local Institution - 0111
city: Stevenage
country: United Kingdom
facility: Local Institution
state: Hertfordshire
city: Leicester
country: United Kingdom
facility: Local Institution - 0085
city: London
country: United Kingdom
facility: Local Institution - 0042
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: