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

NCT04209114 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: CA045-0092018-002676-4018-214-13
• Study Type: interventional
• Target: 114
• Locations: 19 countries
• Sites: 111

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.

Conditions

Bladder Cancer; Bladder Tumor; Muscle-Invasive Bladder Cancer

Keywords

immunotherapy; NKTR-214; nivolumab; bempeg

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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).

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

Secondary Outcomes (8)

• 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)

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

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

• Overall Survival (OS)

  From randomization to study completion, up to approximately 40 months

• The Number of Participants Experiencing Adverse Events (AEs)

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

• The Number of Participants Experiencing Serious Adverse Events (SAEs)

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

Study Arms (3)

Arm A: Combination Therapy

EXPERIMENTAL

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

Biological: Nivolumab; Procedure: Radical cystectomy (RC); Biological: Bempegaldesleukin

Arm B: Monotherapy

EXPERIMENTAL

Neoadjuvant nivolumab, followed by RC, followed by adjuvant nivolumab

Biological: Nivolumab; Procedure: Radical cystectomy (RC)

Arm C: Standard-of-care

OTHER

RC alone, without neoadjuvant or adjuvant therapy

Procedure: Radical cystectomy (RC)

Interventions

Nivolumab BIOLOGICAL

Specified dose on specified days

Also known as: Opdivo, BMS-936558

Arm A: Combination Therapy; Arm B: Monotherapy

Radical cystectomy (RC) PROCEDURE

Surgical removal of the bladder

Arm A: Combination Therapy; Arm B: Monotherapy; Arm C: Standard-of-care

Bempegaldesleukin BIOLOGICAL

Specified dose on specified days

Also known as: BMS-986321, NKTR-214, Bempeg

Arm A: Combination Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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)

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Nektar Therapeutics: collaborator

Study Sites (116)

Local Institution - 0080

Gilbert, Arizona, 85234, United States

Location

Local Institution - 0136

Tucson, Arizona, 85724, United States

Location

Local Institution - 0029

La Jolla, California, 92092-0698, United States

Location

Local Institution - 0015

Orange, California, 92868, United States

Location

Local Institution - 0002

Iowa City, Iowa, 52242, United States

Location

Local Institution

Rochester, Minnesota, 55905, United States

Location

Local Institution - 0006

New Brunswick, New Jersey, 08903, United States

Location

Local Institution - 0004

Buffalo, New York, 14263, United States

Location

Local Institution - 0009

The Bronx, New York, 10461, United States

Location

Local Institution - 0005

Allentown, Pennsylvania, 18103, United States

Location

Local Institution - 0007

Charleston, South Carolina, 29425, United States

Location

Local Institution - 0139

Houston, Texas, 77030, United States

Location

Local Institution - 0023

Temple, Texas, 76508, United States

Location

Local Institution - 0122

Gig Harbor, Washington, 98332, United States

Location

Local Institution - 0102

Seattle, Washington, 98109, United States

Location

Local Institution - 0096

Capital Federal, Buenos Aires, 1419, Argentina

Location

Local Institution - 0028

Ciudad Autónoma de Buenos Aires, Buenos Aires, 1426, Argentina

Location

Local Institution - 0124

La Plata, Buenos Aires, 1900, Argentina

Location

Local Institution - 0027

Capital Federal, Distrito Federal, C1280AEB, Argentina

Location

Local Institution - 0174

Rosario, Santa Fe Province, S2000DTC, Argentina

Location

Local Institution - 0097

Córdoba, 5000, Argentina

Location

Local Institution - 0137

Gosford, New South Wales, 2250, Australia

Location

Local Institution - 0158

Ballarat, Victoria, 3350, Australia

Location

Local Institution - 0157

Fitzroy, Victoria, 3065, Australia

Location

Local Institution - 0011

Heidelberg, Victoria, 3084, Australia

Location

Local Institution - 0013

Murdoch, Western Australia, 6150, Australia

Location

Local Institution - 0148

Graz, 8036, Austria

Location

Local Institution - 0123

Vienna, 1090, Austria

Location

Local Institution - 0150

Vienna, 1160, Austria

Location

Local Institution - 0083

Wilrijk, Antwerpen, 2610, Belgium

Location

Local Institution - 0101

Brussels, Brussels Capital, 1090, Belgium

Location

Local Institution - 0098

Edegem, 2650, Belgium

Location

Local Institution - 0068

Ghent, 9000, Belgium

Location

Local Institution - 0100

Liège, 4000, Belgium

Location

Local Institution - 0177

Porto Alegre, Rio Grande do Sul, 90560-030, Brazil

Location

Local Institution - 0039

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

Local Institution - 0176

Barretos, São Paulo, 14784400, Brazil

Location

Local Institution - 0037

Jaú, São Paulo, 17210-120, Brazil

Location

Local Institution - 0038

São Paulo, São Paulo, 01509-010, Brazil

Location

Local Institution - 0041

Rio de Janeiro, 20231-050, Brazil

Location

Local Institution - 0040

São Paulo, 01246-000, Brazil

Location

Local Institution - 0082

Oshawa, Ontario, L1G 2B9, Canada

Location

Local Institution - 0018

Québec, Quebec, G1R3S1, Canada

Location

Local Institution - 0036

Sherbrooke, Quebec, JiH 5N4, Canada

Location

Local Institution - 0204

Chongqing, Chongqing Municipality, 400016, China

Location

Local Institution

Xiamen, Fujian, 361003, China

Location

Local Institution

Zhengzhou, Henan, 450000, China

Location

Local Institution

Wuhan, Hubei, 430022, China

Location

Local Institution

Changsha, Hunan, 410031, China

Location

Local Institution

Taiyuan, Shan1xi, China

Location

Local Institution

Jinan, Shandong, 250117, China

Location

Local Institution - 0022

Olomouc, 77900, Czechia

Location

Local Institution - 0021

Prague, 14059, Czechia

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Local Institution - 0020

Prague, 150 06, Czechia

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Local Institution - 0077

Avignon, 84918, France

Location

Local Institution - 0091

Bordeaux, 33075, France

Location

Local Institution - 0151

Clermont-Ferrand, 63011, France

Location

Local Institution - 0059

La Roche-sur-Yon, 85000, France

Location

Local Institution - 0071

Lyon, 69008, France

Location

Local Institution - 0057

Marseille, 13273, France

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Local Institution - 0075

Montpellier, 34298, France

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Local Institution - 0070

Nice, 06189, France

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Local Institution - 0062

Paris, 75014, France

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Local Institution - 0060

Paris, 75908, France

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Local Institution - 0064

Quimper, 29000, France

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Local Institution - 0161

Reims, 51726, France

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Local Institution - 0058

Strasbourg, 67200, France

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Local Institution - 0056

Suresnes, 92151, France

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Local Institution - 0074

Tours, 37000, France

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Universitatsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Local Institution - 0117

Düsseldorf, 40225, Germany

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Local Institution - 0119

Erlangen, 91054, Germany

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Local Institution - 0050

Essen, 45147, Germany

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Local Institution - 0052

Hamburg, 20246, Germany

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Local Institution - 0051

Hamburg, 22763, Germany

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Local Institution - 0049

Herne, 44625, Germany

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Local Institution - 0045

Jena, 07747, Germany

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Local Institution - 0053

Lübeck, 23538, Germany

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Local Institution - 0113

Münster, 48149, Germany

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Local Institution - 0048

Nuremberg, 90419, Germany

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Local Institution - 0046

Tübingen, 72076, Germany

Location

Local Institution - 0178

Athens, 11528, Greece

Location

Local Institution - 0088

Athens, 15125, Greece

Location

Local Institution - 0033

Chaïdári, 12462, Greece

Location

Local Institution - 0035

Thessaloniki, 56429, Greece

Location

Local Institution - 0129

Haifa, 31096, Israel

Location

Local Institution - 0131

Tel Aviv, 6423906, Israel

Location

Local Institution - 0130

Tel Litwinsky, 52621, Israel

Location

Local Institution - 0149

Florence, 50134, Italy

Location

Local Institution - 0162

Milan, 20132, Italy

Location

Local Institution - 0025

Milan, 20133, Italy

Location

Local Institution

Pavia, 27100, Italy

Location

Local Institution - 0026

Pisa, 56126, Italy

Location

Local Institution - 0065

Roma, 00168, Italy

Location

Local Institution - 0044

Rozzano, 20089, Italy

Location

Local Institution - 0154

La Paz, BAJA Californa SUR, 23040, Mexico

Location

Local Institution - 0132

Mexico City, Mexico City, 06100, Mexico

Location

Local Institution - 0160

Mexico City, Mexico City, 06700, Mexico

Location

Local Institution - 0133

Monterrey, Nuevo León, 64460, Mexico

Location

Local Institution - 0069

Amsterdam, 1066 CX, Netherlands

Location

Local Institution - 0167

Biała Podlaska, 21-505, Poland

Location

Local Institution - 0054

Warsaw, 02-781, Poland

Location

Local Institution

Omsk, 644013, Russia

Location

Local Institution

Saint Petersburg, 197758, Russia

Location

Local Institution - 0104

A Coruña, 15006, Spain

Location

Local Institution - 0106

Badalona, 08916, Spain

Location

Local Institution - 0110

Barcelona, 08035, Spain

Location

Local Institution - 0109

Córdoba, 14004, Spain

Location

Local Institution - 0105

Madrid, 28007, Spain

Location

Local Institution - 0108

Madrid, 28034, Spain

Location

Local Institution - 0103

Madrid, 28041, Spain

Location

Local Institution - 0107

Santander, 39008, Spain

Location

Local Institution - 0111

Seville, 41013, Spain

Location

Local Institution

Stevenage, Hertfordshire, SG1 4AB, United Kingdom

Location

Local Institution - 0085

Leicester, LE1 5WW, United Kingdom

Location

Local Institution - 0042

London, W6 8RF, United Kingdom

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Nivolumab; Cystectomy; bempegaldesleukin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Limitations and Caveats

BMS and Nektar Therapeutics jointly decided to terminate the clinical development program for bempegaldesleukin (NKTR-214) in combination with nivolumab. Discontinued survival follow-up and the stopping of submission of local labs to vendors, imaging to the BICR vendor, and PROs have resulted in confounded and incomplete trial results.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trails@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: December 23, 2019
• Study Start: February 5, 2020
• Primary Completion: June 7, 2023
• Study Completion: June 7, 2023
• Last Updated: June 27, 2024
• Results First Posted: June 27, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

DE (12); BR (7); CA (3); IL (3); US (15); BE (5); IT (7); CN (7); AU (3); FR (15); CZ (3); GR (4); PL (2); NL (1); ES (9); ME (4); RU (2); GB (3); AR (6)