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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

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ClinicalTrials.gov Identifier: NCT04209114
Recruitment Status : Active, not recruiting
First Posted : December 23, 2019
Last Update Posted : January 10, 2023
Nektar Therapeutics
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Bladder Cancer Bladder Tumor Muscle-Invasive Bladder Cancer Biological: Nivolumab Procedure: Radical cystectomy (RC) Biological: Bempegaldesleukin Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 114 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 : February 5, 2020
Estimated Primary Completion Date : September 28, 2023
Estimated Study Completion Date : September 28, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer
Drug Information available for: Nivolumab

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

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

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

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

Arm C: Standard-of-care
RC alone, without neoadjuvant or adjuvant therapy
Procedure: Radical cystectomy (RC)
Surgical removal of the bladder

Primary Outcome Measures :
  1. Pathologic Complete Response (pCR) rate of Arm A to Arm C [ Time Frame: Approximately 43 months ]
  2. Event-Free Survival (EFS) of Arm A vs Arm C [ Time Frame: Approximately 43 months ]

Secondary Outcome Measures :
  1. pCR rate of Arm B to Arm C [ Time Frame: Approximately 43 months ]
  2. EFS of Arm B vs Arm C [ Time Frame: Approximately 43 months ]
  3. Overall Survival (OS) [ Time Frame: Approximately 43 months ]
  4. Incidence of Adverse Events (AEs) [ Time Frame: Up to 76.5 weeks ]
  5. Incidence of Serious Adverse Events (SAEs) [ Time Frame: Up to 76.5 weeks ]
  6. Incidence of AEs leading to discontinuation [ Time Frame: Up to 76.5 weeks ]
  7. Incidence of immune-mediated AEs (imAEs) [ Time Frame: Up to 76.5 weeks ]
  8. Incidence of participants with clinical laboratory abnormalities [ Time Frame: Up to 76.5 weeks ]
  9. pCR rate of Arm A to Arm B [ Time Frame: Approximately 43 months ]
  10. EFS of Arm A vs Arm B [ Time Frame: Approximately 43 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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:

    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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04209114

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Sponsors and Collaborators
Bristol-Myers Squibb
Nektar Therapeutics
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Additional Information:
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT04209114    
Other Study ID Numbers: CA045-009
2018-002676-40 ( EudraCT Number )
18-214-13 ( Other Identifier: Nektar Therapeutics )
First Posted: December 23, 2019    Key Record Dates
Last Update Posted: January 10, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bristol-Myers Squibb:
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action