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
- Conditions
- Bladder TumorMuscle-Invasive Bladder CancerBladder Cancer
- Interventions
- Biological: NivolumabProcedure: Radical cystectomy (RC)Biological: Bempegaldesleukin
- Registration Number
- NCT04209114
- Lead Sponsor
- Bristol-Myers Squibb
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 114
-
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%
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Combination Therapy Radical cystectomy (RC) Neoadjuvant (pre-surgical treatment) nivolumab + bempeg, followed by radical cystectomy (RC), followed by adjuvant (post-surgical treatment) nivolumab + bempeg Arm A: Combination Therapy Bempegaldesleukin Neoadjuvant (pre-surgical treatment) nivolumab + bempeg, followed by radical cystectomy (RC), followed by adjuvant (post-surgical treatment) nivolumab + bempeg Arm A: Combination Therapy Nivolumab Neoadjuvant (pre-surgical treatment) nivolumab + bempeg, followed by radical cystectomy (RC), followed by adjuvant (post-surgical treatment) nivolumab + bempeg Arm B: Monotherapy Radical cystectomy (RC) Neoadjuvant nivolumab, followed by RC, followed by adjuvant nivolumab Arm B: Monotherapy Nivolumab Neoadjuvant nivolumab, followed by RC, followed by adjuvant nivolumab Arm C: Standard-of-care Radical cystectomy (RC) RC alone, without neoadjuvant or adjuvant therapy
- Primary Outcome Measures
Name Time Method Event Free Survival (EFS) - Nivolumab + Bempegaldesleukin Compared to Standard of Care From randomization up to first EFS event (up to approximately 30 months) Event Free Survival (EFS) is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence based on blinded independent committee review (BICR) assessments, or death due to any cause.
Participants who did not have an EFS event will be censored on the date of their last evaluable tumor assessment (imaging or biopsy) or at the date of radical surgery whichever occur last. Participants who did not have any baseline tumor assessments (imaging or biopsy) and did not undergo radical cystectomy for other reason than worsening/progression of disease will be censored on their date of randomization. Participants who did not have any on study tumor assessments (imaging or biopsy) and did not die will be censored on their date of radical cystectomy (or randomization date if no radical cystectomy performed).Pathologic Complete Response (pCR) Rate- Nivolumab + Bempegaldesleukin Compared to Standard of Care From time of radical cystectomy up to 100 days after last treatment (up to approximately 17 months) Pathologic Complete Response (pCR) is defined as the percentage of randomized participants with absence of any cancer in pathology specimens after radical cystectomy, based on blinded independent pathology review (BIPR). Participants who do not undertake surgery will be counted as non-pCR.
- Secondary Outcome Measures
Name Time Method Pathologic Complete Response (pCR) Rate - Nivolumab Compared to Standard of Care From time of radical cystectomy up to 100 days after last treatment (up to approximately 17 months) Pathologic Complete Response (pCR) is defined as the percentage of randomized participants with absence of any cancer in pathology specimens after radical cystectomy, based on blinded independent pathology review (BIPR). Participants who do not undertake surgery will be counted as non-pCR.
The Number of Participants Experiencing Adverse Events (AEs) from first dose to 100 days following last dose (up to approximately 20 months) An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.
The Number of Participants Experiencing Serious Adverse Events (SAEs) from first dose to 100 days following last dose (up to approximately 20 months) A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization.
The Number of Participants Experiencing Immune-Mediated Adverse Events (IMAEs) from first dose to 100 days following last dose (up to approximately 20 months) IMAEs are specific AEs that include pneumonitis, diarrhea/colitis, hepatitis, nephritis/renal dysfunction, rash, endocrine (adrenal insufficiency, hypothyroidism/thyroiditis, hyperthyroidism, diabetes mellitus, and hypophysitis), and other specific events, considered as potential immune-mediated events by investigator that meet the definition summarized below:
* those occurring within 100 days of the last dose,
* regardless of causality,
* treated with immune-modulating medication (of note, endocrine AEs such as adrenal insufficiency, hypothyroidism/thyroiditis, hyperthyroidism, diabetes mellitus, and hypophysitis are considered IMAEs regardless of immune-modulating medication use, since endocrine drug reactions are often managed without immune-modulating medication).
* with no clear alternate etiology based on investigator assessment, or with an immune-mediated component.Worst Grade Clinical Laboratory Values From first dose to 100 days following last dose (up to approximately 20 months) Clinical laboratory values by worst CTC grade are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.
Event Free Survival (EFS) - Nivolumab Compared to Standard of Care From randomization up to first EFS event (up to approximately 30 months) Event Free Survival (EFS) is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence based on blinded independent committee review (BICR) assessments, or death due to any cause.
Participants who did not have an EFS event will be censored on the date of their last evaluable tumor assessment (imaging or biopsy) or at the date of radical surgery whichever occur last. Participants who did not have any baseline tumor assessments (imaging or biopsy) and did not undergo radical cystectomy for other reason than worsening/progression of disease will be censored on their date of randomization. Participants who did not have any on study tumor assessments (imaging or biopsy) and did not die will be censored on their date of radical cystectomy (or randomization date if no radical cystectomy performed).Overall Survival (OS) From randomization to study completion, up to approximately 40 months Overall Survival (OS) is defined as the time between the date of randomization and the date of death. For those without documentation of death, OS will be censored on the last date the participant was known to be alive.
OS was not calculated for Arm A and Arm B because the number of events did not meet the threshold due to early study termination. In lieu of OS, time to death is reported as a Post-Hoc endpoint.The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation from first dose to 100 days following last dose (up to approximately 20 months) An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.
Trial Locations
- Locations (106)
Local Institution - 0117
🇩🇪Duesseldorf, Germany
Local Institution - 0036
🇨🇦Sherbrooke, Quebec, Canada
Local Institution - 0082
🇨🇦Oshawa, Ontario, Canada
Local Institution - 0053
🇩🇪Luebeck, Germany
Local Institution - 0013
🇦🇺Murdoch, Western Australia, Australia
Local Institution - 0028
🇦🇷Ciudad Autónoma De Buenos Aires, Buenos Aires, Argentina
Local Institution - 0160
🇲🇽Mexico, Distrito Federal, Mexico
Local Institution - 0069
🇳🇱Amsterdam, Netherlands
Local Institution - 0054
🇵🇱Warszawa, Poland
Local Institution - 0174
🇦🇷Rosario, Santa FE, Argentina
Local Institution - 0083
🇧🇪Wilrijk, Antwerpen, Belgium
Local Institution - 0035
🇬🇷Thessaloniki, Greece
Local Institution - 0158
🇦🇺Ballarat, Victoria, Australia
Local Institution - 0080
🇺🇸Gilbert, Arizona, United States
Local Institution - 0124
🇦🇷La Plata, Buenos Aires, Argentina
Local Institution - 0101
🇧🇪Brussel, Brussels, Belgium
Local Institution - 0068
🇧🇪Gent, Belgium
Local Institution - 0100
🇧🇪Liège, Belgium
Local Institution - 0033
🇬🇷Chaidari, Greece
Local Institution - 0167
🇵🇱Biala Podlaska, Poland
Local Institution - 0096
🇦🇷Capital Federal, Buenos Aires, Argentina
Local Institution
🇬🇧Stevenage, Hertfordshire, United Kingdom
Local Institution - 0027
🇦🇷Capital Federal, Distrito Federal, Argentina
Local Institution - 0097
🇦🇷Cordoba, Argentina
Local Institution - 0154
🇲🇽La Paz, BAJA Californa SUR, Mexico
Local Institution - 0006
🇺🇸New Brunswick, New Jersey, United States
Local Institution - 0123
🇦🇹Wien, Austria
Local Institution - 0098
🇧🇪Edegem, Belgium
Local Institution - 0129
🇮🇱Haifa, Israel
Local Institution - 0133
🇲🇽Monterrey, Nuevo LEON, Mexico
Local Institution - 0038
🇧🇷Sao Paulo, São Paulo, Brazil
Local Institution - 0025
🇮🇹Milano, Italy
Local Institution - 0026
🇮🇹Pisa, Italy
Local Institution - 0037
🇧🇷Jau, Sao Paulo, Brazil
Local Institution - 0065
🇮🇹Roma, Italy
Local Institution - 0064
🇫🇷Quimper, France
Local Institution - 0029
🇺🇸La Jolla, California, United States
Local Institution - 0015
🇺🇸Orange, California, United States
Local Institution - 0002
🇺🇸Iowa City, Iowa, United States
Local Institution - 0004
🇺🇸Buffalo, New York, United States
Local Institution - 0005
🇺🇸Allentown, Pennsylvania, United States
Local Institution - 0023
🇺🇸Temple, Texas, United States
Local Institution - 0122
🇺🇸Gig Harbor, Washington, United States
Local Institution - 0137
🇦🇺Gosford, New South Wales, Australia
Local Institution - 0148
🇦🇹Graz, Austria
Local Institution - 0157
🇦🇺Fitzroy, Victoria, Australia
Local Institution - 0011
🇦🇺Heidelberg, Victoria, Australia
Local Institution - 0150
🇦🇹Vienna, Austria
Local Institution - 0177
🇧🇷Porto Alegre, RIO Grande DO SUL, Brazil
Local Institution - 0176
🇧🇷Barretos, SAO Paulo, Brazil
Local Institution - 0039
🇧🇷Porto Alegre, RIO Grande DO SUL, Brazil
Local Institution - 0040
🇧🇷Sao Paulo, Brazil
Local Institution - 0041
🇧🇷Rio de Janeiro, Brazil
Local Institution - 0018
🇨🇦Quebec, Canada
Local Institution - 0020
🇨🇿Praha 5, Czechia
Local Institution - 0204
🇨🇳Chongqing, Chongqing, China
Local Institution - 0022
🇨🇿Olomouc, Czechia
Local Institution - 0077
🇫🇷Avignon Cedex 9, France
Local Institution - 0021
🇨🇿Praha, Czechia
Local Institution - 0091
🇫🇷Bordeaux, France
Local Institution - 0151
🇫🇷Clermont-Ferrand, France
Local Institution - 0057
🇫🇷Marseille Cedex 9, France
Local Institution - 0071
🇫🇷Lyon, France
Local Institution - 0059
🇫🇷La Roche-sur-Yon, France
Local Institution - 0075
🇫🇷Montpellier, France
Local Institution - 0070
🇫🇷Nice, France
Local Institution - 0060
🇫🇷Paris, France
Local Institution - 0062
🇫🇷Paris, France
Local Institution - 0161
🇫🇷Reims, France
Local Institution - 0074
🇫🇷Tours, France
Local Institution - 0058
🇫🇷Strasbourg, France
Local Institution - 0056
🇫🇷Suresnes, France
Universitatsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Local Institution - 0119
🇩🇪Erlangen, Germany
Local Institution - 0050
🇩🇪Essen, Germany
Local Institution - 0051
🇩🇪Hamburg, Germany
Local Institution - 0052
🇩🇪Hamburg, Germany
Local Institution - 0049
🇩🇪Herne, Germany
Local Institution - 0045
🇩🇪Jena, Germany
Local Institution - 0113
🇩🇪Muenster, Germany
Local Institution - 0048
🇩🇪Nuernberg, Germany
Local Institution - 0178
🇬🇷Athens, Greece
Local Institution - 0046
🇩🇪Tuebingen, Germany
Local Institution - 0088
🇬🇷Athens, Greece
Local Institution - 0131
🇮🇱Tel Aviv, Israel
Local Institution - 0130
🇮🇱Tel Hashomer, Israel
Local Institution - 0149
🇮🇹Firenze, Italy
Local Institution - 0162
🇮🇹Milano, Italy
Local Institution - 0044
🇮🇹Rozzano, Italy
Local Institution - 0132
🇲🇽Ciudad de Mexico, Distrito Federal, Mexico
Local Institution - 0110
🇪🇸Barcelona, Spain
Local Institution - 0104
🇪🇸A Coruña, Spain
Local Institution - 0106
🇪🇸Badalona, Spain
Local Institution - 0109
🇪🇸Cordoba, Spain
Local Institution - 0105
🇪🇸Madrid, Spain
Local Institution - 0111
🇪🇸Sevilla, Spain
Local Institution - 0107
🇪🇸Santander, Spain
Local Institution - 0103
🇪🇸Madrid, Spain
Local Institution - 0085
🇬🇧Leicester, United Kingdom
Local Institution - 0042
🇬🇧London, United Kingdom
Local Institution - 0108
🇪🇸Madrid, Spain
Local Institution - 0009
🇺🇸Bronx, New York, United States
Local Institution - 0007
🇺🇸Charleston, South Carolina, United States
Local Institution - 0139
🇺🇸Houston, Texas, United States
Local Institution - 0102
🇺🇸Seattle, Washington, United States
Local Institution - 0136
🇺🇸Tucson, Arizona, United States