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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 Has Invaded the Muscle Wall of the Bladder and Who Cannot Get Cisplatin, a Type of Medicine Given to Treat Bladder Cancer.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04209114
Recruitment Status : Recruiting
First Posted : December 23, 2019
Last Update Posted : December 2, 2021
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 bempeg or nivolumab alone, before and after surgery to remove the bladder, is more effective than surgery alone in participants with 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 Biological: Bempeg Procedure: Radical cystectomy (RC) Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 540 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 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 : August 28, 2023
Estimated Study Completion Date : September 5, 2024

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: Combination
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 Name: Opdivo

Biological: Bempeg
Specified dose on specified days
Other Name: BMS-986321, NKTR-214

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

Experimental: Monotherapy
Neoadjuvant nivolumab, followed by RC, followed by adjuvant nivolumab
Biological: Nivolumab
Specified dose on specified days
Other Name: Opdivo

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

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 neoadjuvant nivolumab + bempeg to Standard of Care (SOC) in all randomized participants [ Time Frame: Approximately 36 months ]
  2. Event-free survival (EFS) of neoadjuvant nivolumab + bempeg followed by adjuvant nivolumab + bempeg after RC vs. SOC [ Time Frame: Approximately 54 months ]

Secondary Outcome Measures :
  1. pCR rate of neoadjuvant nivolumab monotherapy to SOC at the time of surgery in all randomized participants [ Time Frame: Approximately 36 months ]
  2. EFS of neoadjuvant nivolumab followed by adjuvant nivolumab vs. SOC [ Time Frame: Approximately 54 months ]
  3. Overall survival [ Time Frame: Approximately 74 months ]
  4. Incidence of adverse events (AEs) [ Time Frame: Up to 5 years ]
  5. Incidence of serious adverse events (SAEs) [ Time Frame: Up to 5 years ]
  6. Incidence of AEs leading to discontinuation [ Time Frame: Up to 5 years ]
  7. Incidence of immune-mediated AEs (imAEs) [ Time Frame: Up to 5 years ]
  8. Incidence of laboratory abnormalities [ Time Frame: Up to 5 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit

Inclusion Criteria:

  • MIBC, clinical stage T2-T4a, N0, M0, diagnosed at transurethral resection of bladder tumor (TURBT) and confirmed by radiographic imaging.
  • 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%
  • Women and men must agree to follow specific methods of contraception, if applicable

Exclusion Criteria:

  • Clinical evidence of pathologic lymph node (LN) 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

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 identifier (NCT number): NCT04209114

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Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email:
Contact: First line of the email MUST contain NCT # and Site #.

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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 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: December 2, 2021
Last Verified: December 2021
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

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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