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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

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04209114
Collaborator
Nektar Therapeutics (Industry)
107
Enrollment
116
Locations
3
Arms
112.3
Anticipated Duration (Months)
0.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: Nivolumab
  • Biological: Bempegaldesleukin
  • Procedure: Radical cystectomy (RC)
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
107 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Feb 17, 2020
Anticipated Primary Completion Date :
Dec 28, 2026
Anticipated Study Completion Date :
Jun 28, 2029

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A: Combination Therapy

Neoadjuvant (pre-surgical treatment) nivolumab + bempeg, followed by radical cystectomy (RC), followed by adjuvant (post-surgical treatment) nivolumab + bempeg

Biological: Nivolumab
Specified dose on specified days
Other Names:
  • Opdivo
  • BMS-936558

    • Biological: Bempegaldesleukin
    Specified dose on specified days
    Other Names:
  • BMS-986321
  • NKTR-214
  • Bempeg

    • Procedure: Radical cystectomy (RC)
    Surgical removal of the bladder
    Experimental: Arm B: Monotherapy

    Neoadjuvant nivolumab, followed by RC, followed by adjuvant nivolumab

    Biological: Nivolumab
    Specified dose on specified days
    Other Names:
  • Opdivo
  • BMS-936558

    • Procedure: Radical cystectomy (RC)
    Surgical removal of the bladder
    Other: Arm C: Standard-of-care

    RC alone, without neoadjuvant or adjuvant therapy

    Procedure: Radical cystectomy (RC)
    Surgical removal of the bladder

    Outcome Measures

    Primary Outcome Measures

    1. Pathologic Complete Response (pCR) rate of Arm A to Arm C [Approximately 47 months]

    2. Event-Free Survival (EFS) of Arm A vs Arm C [Approximately 65 months]

    Secondary Outcome Measures

    1. pCR rate of Arm B to Arm C [Approximately 47 months]

    2. EFS of Arm B vs Arm C [Approximately 65 months]

    3. Overall Survival (OS) [Approximately 86 months]

    4. Incidence of Adverse Events (AEs) [Up to 5 years]

    5. Incidence of Serious Adverse Events (SAEs) [Up to 5 years]

    6. Incidence of AEs leading to discontinuation [Up to 5 years]

    7. Incidence of immune-mediated AEs (imAEs) [Up to 5 years]

    8. Incidence of participants with clinical laboratory abnormalities [Up to 5 years]

    9. pCR rate of Arm A to Arm B [Approximately 47 months]

    10. EFS of Arm A vs Arm B [Approximately 65 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

    1. 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).
    1. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Local Institution - 0080 Gilbert Arizona United States 85234
    2 Local Institution - 0136 Tucson Arizona United States 85724
    3 Local Institution - 0029 La Jolla California United States 92092-0698
    4 Local Institution - 0015 Orange California United States 92868
    5 Local Institution - 0002 Iowa City Iowa United States 52242
    6 Local Institution Rochester Minnesota United States 55905
    7 Local Institution - 0006 New Brunswick New Jersey United States 08903
    8 Local Institution - 0009 Bronx New York United States 10461
    9 Roswell Park Cancer Institute Buffalo New York United States 14263
    10 Local Institution - 0005 Allentown Pennsylvania United States 18103
    11 Medical University Of South Carolina Charleston South Carolina United States 29425
    12 Local Institution - 0139 Houston Texas United States 77030
    13 Local Institution - 0023 Temple Texas United States 76508
    14 Local Institution - 0122 Gig Harbor Washington United States 98332
    15 Local Institution - 0102 Seattle Washington United States 98109
    16 Local Institution - 0096 Capital Federal Buenos Aires Argentina 1419
    17 Local Institution - 0028 Ciudad Autónoma De Buenos Aires Buenos Aires Argentina 1426
    18 Local Institution - 0124 La Plata Buenos Aires Argentina 1900
    19 Local Institution - 0027 Capital Federal Distrito Federal Argentina C1280AEB
    20 Local Institution - 0174 Rosario Santa FE Argentina S2000DTC
    21 Local Institution - 0097 Cordoba Argentina 5000
    22 Local Institution - 0137 Gosford New South Wales Australia 2250
    23 Local Institution - 0158 Ballarat Victoria Australia 3350
    24 Local Institution - 0157 Fitzroy Victoria Australia 3065
    25 Local Institution - 0011 Heidelberg Victoria Australia 3084
    26 Local Institution - 0013 Murdoch Western Australia Australia 6150
    27 Local Institution - 0148 Graz Austria 8036
    28 Local Institution - 0150 Vienna Austria 1160
    29 Local Institution - 0123 Wien Austria 1090
    30 Local Institution - 0083 Wilrijk Antwerpen Belgium 2610
    31 Local Institution - 0101 Brussel Brussels Belgium 1090
    32 Local Institution - 0098 Edegem Belgium 2650
    33 Local Institution - 0068 Gent Belgium 9000
    34 Local Institution - 0100 Liège Belgium 4000
    35 Local Institution - 0177 Porto Alegre RIO Grande DO SUL Brazil 90560-030
    36 Local Institution - 0039 Porto Alegre RIO Grande DO SUL Brazil 91350-200
    37 Local Institution - 0176 Barretos SAO Paulo Brazil 14784400
    38 Local Institution - 0037 Jau Sao Paulo Brazil 17210-120
    39 Local Institution - 0038 Sao Paulo São Paulo Brazil 01509-010
    40 Local Institution - 0041 Rio de Janeiro Brazil 20230-130
    41 Local Institution - 0040 Sao Paulo Brazil 01246-000
    42 Local Institution - 0082 Oshawa Ontario Canada L1G 2B9
    43 Local Institution - 0036 Sherbrooke Quebec Canada JiH 5N4
    44 Local Institution - 0018 Quebec Canada G1R3S1
    45 Local Institution - 0204 Chongqing Chongqing China 400016
    46 Local Institution Xiamen Fujian China 361003
    47 Local Institution Zhengzhou Henan China 450000
    48 Local Institution Wuhan Hubei China 430022
    49 Local Institution Changsha Hunan China 410031
    50 Local Institution Taiyuan Shan1xi China
    51 Local Institution Jinan Shandong China 250117
    52 Local Institution - 0022 Olomouc Czechia 77900
    53 Local Institution - 0020 Praha 5 Czechia 150 06
    54 Local Institution - 0021 Praha Czechia 14059
    55 Local Institution - 0064 Quimper Bretagne France 29000
    56 Local Institution - 0077 Avignon Cedex 9 France 84918
    57 Local Institution - 0091 Bordeaux France 33075
    58 Local Institution - 0151 Clermont-Ferrand France 63011
    59 Local Institution - 0059 La Roche-sur-Yon France 85000
    60 Local Institution - 0071 Lyon France 69008
    61 Local Institution - 0057 Marseille Cedex 9 France 13273
    62 Local Institution - 0075 Montpellier France 34298
    63 Local Institution - 0070 Nice France 06189
    64 Local Institution - 0062 Paris France 75014
    65 Local Institution - 0060 Paris France 75908
    66 Local Institution - 0161 Reims France 51726
    67 Local Institution - 0058 Strasbourg France 67200
    68 Local Institution - 0056 Suresnes France 92151
    69 Local Institution - 0074 Tours France 37000
    70 Universitatsklinikum Carl Gustav Carus Dresden Germany 01307
    71 Local Institution - 0117 Duesseldorf Germany 40225
    72 Local Institution - 0119 Erlangen Germany 91054
    73 Local Institution - 0050 Essen Germany 45147
    74 Local Institution - 0052 Hamburg Germany 20246
    75 Local Institution - 0051 Hamburg Germany 22763
    76 Local Institution - 0049 Herne Germany 44625
    77 Local Institution - 0045 Jena Germany 07747
    78 Local Institution - 0053 Luebeck Germany 23538
    79 Local Institution - 0113 Muenster Germany 48149
    80 Local Institution - 0048 Nuernberg Germany 90419
    81 Local Institution - 0046 Tuebingen Germany 72076
    82 Local Institution - 0178 Athens Greece 11528
    83 Local Institution - 0088 Athens Greece 15125
    84 Local Institution - 0033 Chaidari Greece 12462
    85 Local Institution - 0035 Thessaloniki Greece 56429
    86 Local Institution - 0129 Haifa Israel 31096
    87 Local Institution - 0131 Tel Aviv Israel 6423906
    88 Local Institution - 0130 Tel Hashomer Israel 52621
    89 Local Institution - 0149 Firenze Italy 50134
    90 Local Institution - 0162 Milano Italy 20132
    91 Local Institution - 0025 Milano Italy 20133
    92 Local Institution Pavia Italy 27100
    93 Local Institution - 0026 Pisa Italy 56126
    94 Local Institution - 0065 Roma Italy 00168
    95 Local Institution - 0044 Rozzano Italy 20089
    96 Local Institution - 0154 La Paz BAJA Californa SUR Mexico 23040
    97 Local Institution - 0132 Ciudad de Mexico Distrito Federal Mexico 06100
    98 Local Institution - 0160 Mexico Distrito Federal Mexico 06700
    99 Local Institution - 0133 Monterrey Nuevo LEON Mexico 64460
    100 Local Institution - 0069 Amsterdam Netherlands 1066 CX
    101 Local Institution - 0167 Biala Podlaska Poland 21-505
    102 Local Institution - 0054 Warszawa Poland 02-781
    103 Local Institution Omsk Russian Federation 644013
    104 Local Institution Saint-Petersburg Russian Federation 197758
    105 Local Institution - 0104 A Coruña Spain 15006
    106 Local Institution - 0106 Badalona Spain 08916
    107 Local Institution - 0110 Barcelona Spain 08035
    108 Local Institution - 0109 Cordoba Spain 14004
    109 Local Institution - 0105 Madrid Spain 28007
    110 Local Institution - 0108 Madrid Spain 28034
    111 Local Institution - 0103 Madrid Spain 28041
    112 Local Institution - 0107 Santander Spain 39008
    113 Local Institution - 0111 Sevilla Spain 41013
    114 Local Institution Stevenage Hertfordshire United Kingdom SG1 4AB
    115 Local Institution - 0085 Leicester United Kingdom LE1 5WW
    116 Local Institution - 0042 London United Kingdom W6 8RF

    Sponsors and Collaborators

    • Bristol-Myers Squibb
    • Nektar Therapeutics

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT04209114
    Other Study ID Numbers:
    • CA045-009
    • 2018-002676-40
    • 18-214-13
    First Posted:
    Dec 23, 2019
    Last Update Posted:
    Aug 1, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Bristol-Myers Squibb
    immunotherapy
    NKTR-214
    nivolumab
    bempeg
    Additional relevant MeSH terms:
    Urinary Bladder Neoplasms
    Nivolumab

    Study Results

    No Results Posted as of Aug 1, 2022