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AzTrials

Bladder CancerPhase 3NCT04209114

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

A Phase 3 study testing Nivolumab, Radical cystectomy (RC) and Bempegaldesleukin in people with Bladder Cancer and Bladder Tumor, run by Bristol-Myers Squibb at 116 sites in 20 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab, Radical cystectomy (RC) and Bempegaldesleukin
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
114 participants
Where
116 sitesin 20 countries
Study dates
5 Feb 2020to 7 Jun 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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).
  • CTCAE version 5, ≥ Grade 2 peripheral neuropathy.
  • Documented Left Ventricular Ejection Fraction (LVEF) more than 45%

Who cannot join

  • 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

Trial locations and contacts

116 sites in 20 countries.

116 sites in 20 countries

United States15 sites

  • Local Institution - 0005

    Allentown, Pennsylvania, 18103

  • Local Institution - 0004

    Buffalo, New York, 14263

  • Local Institution - 0007

    Charleston, South Carolina, 29425

  • Local Institution - 0122

    Gig Harbor, Washington, 98332

  • Local Institution - 0080

    Gilbert, Arizona, 85234

  • Local Institution - 0139

    Houston, Texas, 77030

  • Local Institution - 0002

    Iowa City, Iowa, 52242

  • Local Institution - 0029

    La Jolla, California, 92092-0698

  • Local Institution - 0006

    New Brunswick, New Jersey, 08903

  • Local Institution - 0015

    Orange, California, 92868

  • Local Institution

    Rochester, Minnesota, 55905

  • Local Institution - 0102

    Seattle, Washington, 98109

  • Local Institution - 0023

    Temple, Texas, 76508

  • Local Institution - 0009

    The Bronx, New York, 10461

  • Local Institution - 0136

    Tucson, Arizona, 85724

Other trials in United States

France15 sites

  • Local Institution - 0077

    Avignon, 84918

  • Local Institution - 0091

    Bordeaux, 33075

  • Local Institution - 0151

    Clermont-Ferrand, 63011

  • Local Institution - 0059

    La Roche-sur-Yon, 85000

  • Local Institution - 0071

    Lyon, 69008

  • Local Institution - 0057

    Marseille, 13273

  • Local Institution - 0075

    Montpellier, 34298

  • Local Institution - 0070

    Nice, 06189

  • Local Institution - 0062

    Paris, 75014

  • Local Institution - 0060

    Paris, 75908

  • Local Institution - 0064

    Quimper, 29000

  • Local Institution - 0161

    Reims, 51726

  • Local Institution - 0058

    Strasbourg, 67200

  • Local Institution - 0056

    Suresnes, 92151

  • Local Institution - 0074

    Tours, 37000

Other trials in France

Germany12 sites

  • Universitatsklinikum Carl Gustav Carus

    Dresden, 01307

  • Local Institution - 0117

    Düsseldorf, 40225

  • Local Institution - 0119

    Erlangen, 91054

  • Local Institution - 0050

    Essen, 45147

  • Local Institution - 0052

    Hamburg, 20246

  • Local Institution - 0051

    Hamburg, 22763

  • Local Institution - 0049

    Herne, 44625

  • Local Institution - 0045

    Jena, 07747

  • Local Institution - 0053

    Lübeck, 23538

  • Local Institution - 0113

    Münster, 48149

  • Local Institution - 0048

    Nuremberg, 90419

  • Local Institution - 0046

    Tübingen, 72076

Other trials in Germany

Spain9 sites

  • Local Institution - 0104

    A Coruña, 15006

  • Local Institution - 0106

    Badalona, 08916

  • Local Institution - 0110

    Barcelona, 08035

  • Local Institution - 0109

    Córdoba, 14004

  • Local Institution - 0105

    Madrid, 28007

  • Local Institution - 0108

    Madrid, 28034

  • Local Institution - 0103

    Madrid, 28041

  • Local Institution - 0107

    Santander, 39008

  • Local Institution - 0111

    Seville, 41013

Other trials in Spain

Brazil7 sites

  • Local Institution - 0176

    Barretos, São Paulo, 14784400

  • Local Institution - 0037

    Jaú, São Paulo, 17210-120

  • Local Institution - 0177

    Porto Alegre, Rio Grande do Sul, 90560-030

  • Local Institution - 0039

    Porto Alegre, Rio Grande do Sul, 91350-200

  • Local Institution - 0041

    Rio de Janeiro, 20231-050

  • Local Institution - 0038

    São Paulo, São Paulo, 01509-010

  • Local Institution - 0040

    São Paulo, 01246-000

Other trials in Brazil

China7 sites

  • Local Institution

    Changsha, Hunan, 410031

  • Local Institution - 0204

    Chongqing, Chongqing Municipality, 400016

  • Local Institution

    Jinan, Shandong, 250117

  • Local Institution

    Taiyuan, Shan1xi

  • Local Institution

    Wuhan, Hubei, 430022

  • Local Institution

    Xiamen, Fujian, 361003

  • Local Institution

    Zhengzhou, Henan, 450000

Other trials in China

Italy7 sites

  • Local Institution - 0149

    Florence, 50134

  • Local Institution - 0162

    Milan, 20132

  • Local Institution - 0025

    Milan, 20133

  • Local Institution

    Pavia, 27100

  • Local Institution - 0026

    Pisa, 56126

  • Local Institution - 0065

    Roma, 00168

  • Local Institution - 0044

    Rozzano, 20089

Other trials in Italy

Argentina6 sites

  • Local Institution - 0096

    Capital Federal, Buenos Aires, 1419

  • Local Institution - 0027

    Capital Federal, Distrito Federal, C1280AEB

  • Local Institution - 0028

    Ciudad Autónoma de Buenos Aires, Buenos Aires, 1426

  • Local Institution - 0097

    Córdoba, 5000

  • Local Institution - 0124

    La Plata, Buenos Aires, 1900

  • Local Institution - 0174

    Rosario, Santa Fe Province, S2000DTC

Other trials in Argentina

Australia5 sites

  • Local Institution - 0158

    Ballarat, Victoria, 3350

  • Local Institution - 0157

    Fitzroy, Victoria, 3065

  • Local Institution - 0137

    Gosford, New South Wales, 2250

  • Local Institution - 0011

    Heidelberg, Victoria, 3084

  • Local Institution - 0013

    Murdoch, Western Australia, 6150

Other trials in Australia

Belgium5 sites

  • Local Institution - 0101

    Brussels, Brussels Capital, 1090

  • Local Institution - 0098

    Edegem, 2650

  • Local Institution - 0068

    Ghent, 9000

  • Local Institution - 0100

    Liège, 4000

  • Local Institution - 0083

    Wilrijk, Antwerpen, 2610

Other trials in Belgium

Greece4 sites

  • Local Institution - 0178

    Athens, 11528

  • Local Institution - 0088

    Athens, 15125

  • Local Institution - 0033

    Chaïdári, 12462

  • Local Institution - 0035

    Thessaloniki, 56429

Other trials in Greece

Mexico4 sites

  • Local Institution - 0154

    La Paz, BAJA Californa SUR, 23040

  • Local Institution - 0132

    Mexico City, Mexico City, 06100

  • Local Institution - 0160

    Mexico City, Mexico City, 06700

  • Local Institution - 0133

    Monterrey, Nuevo León, 64460

Other trials in Mexico

Austria3 sites

  • Local Institution - 0148

    Graz, 8036

  • Local Institution - 0123

    Vienna, 1090

  • Local Institution - 0150

    Vienna, 1160

Other trials in Austria

Canada3 sites

  • Local Institution - 0082

    Oshawa, Ontario, L1G 2B9

  • Local Institution - 0018

    Québec, Quebec, G1R3S1

  • Local Institution - 0036

    Sherbrooke, Quebec, JiH 5N4

Other trials in Canada

Czechia3 sites

  • Local Institution - 0022

    Olomouc, 77900

  • Local Institution - 0021

    Prague, 14059

  • Local Institution - 0020

    Prague, 150 06

Other trials in Czechia

Israel3 sites

  • Local Institution - 0129

    Haifa, 31096

  • Local Institution - 0131

    Tel Aviv, 6423906

  • Local Institution - 0130

    Tel HaShomer, 52621

Other trials in Israel

United Kingdom3 sites

  • Local Institution - 0085

    Leicester, LE1 5WW

  • Local Institution - 0042

    London, W6 8RF

  • Local Institution

    Stevenage, Hertfordshire, SG1 4AB

Other trials in United Kingdom

Poland2 sites

  • Local Institution - 0167

    Biała Podlaska, 21-505

  • Local Institution - 0054

    Warsaw, 02-781

Other trials in Poland

Russia2 sites

  • Local Institution

    Omsk, 644013

  • Local Institution

    Saint Petersburg, 197758

Other trials in Russia

Netherlands1 site

  • Local Institution - 0069

    Amsterdam, 1066 CX

Other trials in Netherlands

About this study

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

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.

Being tested
Nivolumab, Radical cystectomy (RC), Bempegaldesleukin
Keywords
immunotherapy, NKTR-214, nivolumab, bempeg
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabBiological

    Also called Opdivo, BMS-936558

    Specified dose on specified days

  • Radical cystectomy (RC)Procedure or surgery

    Surgical removal of the bladder

  • BempegaldesleukinBiological

    Also called BMS-986321, NKTR-214, Bempeg

    Specified dose on specified days

Study groups in NCT04209114
Study groupRoleWhat they receive
Arm A: Combination TherapyExperimentalNeoadjuvant (pre-surgical treatment) nivolumab + bempeg, followed by radical cystectomy (RC), followed by adjuvant (post-surgical treatment) nivolumab + bempeg
Receives: Biological: Nivolumab; Procedure: Radical cystectomy (RC); Biological: Bempegaldesleukin
Arm B: MonotherapyExperimentalNeoadjuvant nivolumab, followed by RC, followed by adjuvant nivolumab
Receives: Biological: Nivolumab; Procedure: Radical cystectomy (RC)
Arm C: Standard-of-careOtherRC alone, without neoadjuvant or adjuvant therapy
Receives: Procedure: Radical cystectomy (RC)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathologic Complete Response (pCR) Rate- Nivolumab + Bempegaldesleukin Compared to Standard of Care

    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.

    Measured: From time of radical cystectomy up to 100 days after last treatment (up to approximately 17 months)

  2. Event Free Survival (EFS) - Nivolumab + Bempegaldesleukin Compared to Standard of Care

    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).

    Measured: From randomization up to first EFS event (up to approximately 30 months)

Secondary outcomes (8)

  1. Pathologic Complete Response (pCR) Rate - Nivolumab Compared to Standard of Care

    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.

    Measured: From time of radical cystectomy up to 100 days after last treatment (up to approximately 17 months)

  2. Event Free Survival (EFS) - Nivolumab Compared to Standard of Care

    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).

    Measured: From randomization up to first EFS event (up to approximately 30 months)

  3. Overall Survival (OS)

    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.

    Measured: From randomization to study completion, up to approximately 40 months

  4. The Number of Participants Experiencing Adverse Events (AEs)

    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.

    Measured: from first dose to 100 days following last dose (up to approximately 20 months)

  5. The Number of Participants Experiencing Serious Adverse Events (SAEs)

    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.

    Measured: from first dose to 100 days following last dose (up to approximately 20 months)

  6. The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation

    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.

    Measured: from first dose to 100 days following last dose (up to approximately 20 months)

  7. The Number of Participants Experiencing Immune-Mediated Adverse Events (IMAEs)

    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.

    Measured: from first dose to 100 days following last dose (up to approximately 20 months)

  8. Worst Grade Clinical Laboratory Values

    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.

    Measured: From first dose to 100 days following last dose (up to approximately 20 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2019
  2. Study start5 Feb 2020
  3. Primary completion7 Jun 2023
  4. Study completion7 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
114 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04209114
Sponsor's protocol ID
CA045-009
Other IDs
2018-002676-40, 18-214-13, 2018
Status last verified
Jun 2024
First submitted
20 Dec 2019
Last updated
27 Jun 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual patient level data from this study may be shared with qualified researchers, upon request, following the timelines and process detailed on https://www.bms.com/researchers-and-partners/independent-research/data-sharing-request-process.html

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nivolumab, Radical cystectomy (RC) and Bempegaldesleukin in people with Bladder Cancer and Bladder Tumor, run by Bristol-Myers Squibb at 116 sites in 20 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 116 sites in United States, France, Germany, Spain, Brazil and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologic Complete Response (pCR) Rate- Nivolumab + Bempegaldesleukin Compared to Standard of Care (time frame: From time of radical cystectomy up to 100 days after last treatment (up to approximately 17 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04209114.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2024.

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