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

Bladder Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04209114
• Other study ID #: CA045-009
• Secondary ID: 2018-002676-4018
• Status: Completed
• Phase: Phase 3
• Start date: February 5, 2020
• Est. completion date: June 7, 2023

Study information

• Verified date: September 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 chemotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: June 7, 2023
• Est. primary completion date: June 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Bladder Tumor
• Muscle-Invasive Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Biological:
• Nivolumab
Specified dose on specified days

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

Biological:
• Bempegaldesleukin
Specified dose on specified days

Locations

Country	Name	City	State
Argentina	Local Institution - 0027	Capital Federal	Distrito Federal
Argentina	Local Institution - 0096	Capital Federal	Buenos Aires
Argentina	Local Institution - 0028	Ciudad Autónoma De Buenos Aires	Buenos Aires
Argentina	Local Institution - 0097	Cordoba
Argentina	Local Institution - 0124	La Plata	Buenos Aires
Argentina	Local Institution - 0174	Rosario	Santa FE
Australia	Local Institution - 0158	Ballarat	Victoria
Australia	Local Institution - 0157	Fitzroy	Victoria
Australia	Local Institution - 0137	Gosford	New South Wales
Australia	Local Institution - 0011	Heidelberg	Victoria
Australia	Local Institution - 0013	Murdoch	Western Australia
Austria	Local Institution - 0148	Graz
Austria	Local Institution - 0150	Vienna
Austria	Local Institution - 0123	Wien
Belgium	Local Institution - 0101	Brussel	Brussels
Belgium	Local Institution - 0098	Edegem
Belgium	Local Institution - 0068	Gent
Belgium	Local Institution - 0100	Liège
Belgium	Local Institution - 0083	Wilrijk	Antwerpen
Brazil	Local Institution - 0176	Barretos	SAO Paulo
Brazil	Local Institution - 0037	Jau	Sao Paulo
Brazil	Local Institution - 0039	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution - 0177	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution - 0041	Rio de Janeiro
Brazil	Local Institution - 0038	Sao Paulo	São Paulo
Brazil	Local Institution - 0040	Sao Paulo
Canada	Local Institution - 0082	Oshawa	Ontario
Canada	Local Institution - 0018	Quebec
Canada	Local Institution - 0036	Sherbrooke	Quebec
China	Local Institution	Changsha	Hunan
China	Local Institution - 0204	Chongqing	Chongqing
China	Local Institution	Jinan	Shandong
China	Local Institution	Taiyuan	Shan1xi
China	Local Institution	Wuhan	Hubei
China	Local Institution	Xiamen	Fujian
China	Local Institution	Zhengzhou	Henan
Czechia	Local Institution - 0022	Olomouc
Czechia	Local Institution - 0021	Praha
Czechia	Local Institution - 0020	Praha 5
France	Local Institution - 0077	Avignon Cedex 9
France	Local Institution - 0091	Bordeaux
France	Local Institution - 0151	Clermont-Ferrand
France	Local Institution - 0059	La Roche-sur-Yon
France	Local Institution - 0071	Lyon
France	Local Institution - 0057	Marseille Cedex 9
France	Local Institution - 0075	Montpellier
France	Local Institution - 0070	Nice
France	Local Institution - 0060	Paris
France	Local Institution - 0062	Paris
France	Local Institution - 0064	Quimper
France	Local Institution - 0161	Reims
France	Local Institution - 0058	Strasbourg
France	Local Institution - 0056	Suresnes
France	Local Institution - 0074	Tours
Germany	Universitatsklinikum Carl Gustav Carus	Dresden
Germany	Local Institution - 0117	Duesseldorf
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 - 0053	Luebeck
Germany	Local Institution - 0113	Muenster
Germany	Local Institution - 0048	Nuernberg
Germany	Local Institution - 0046	Tuebingen
Greece	Local Institution - 0088	Athens
Greece	Local Institution - 0178	Athens
Greece	Local Institution - 0033	Chaidari
Greece	Local Institution - 0035	Thessaloniki
Israel	Local Institution - 0129	Haifa
Israel	Local Institution - 0131	Tel Aviv
Israel	Local Institution - 0130	Tel Hashomer
Italy	Local Institution - 0149	Firenze
Italy	Local Institution - 0025	Milano
Italy	Local Institution - 0162	Milano
Italy	Local Institution	Pavia
Italy	Local Institution - 0026	Pisa
Italy	Local Institution - 0065	Roma
Italy	Local Institution - 0044	Rozzano
Mexico	Local Institution - 0132	Ciudad de Mexico	Distrito Federal
Mexico	Local Institution - 0154	La Paz	BAJA Californa SUR
Mexico	Local Institution - 0160	Mexico	Distrito Federal
Mexico	Local Institution - 0133	Monterrey	Nuevo LEON
Netherlands	Local Institution - 0069	Amsterdam
Poland	Local Institution - 0167	Biala Podlaska
Poland	Local Institution - 0054	Warszawa
Russian Federation	Local Institution	Omsk
Russian Federation	Local Institution	Saint-Petersburg
Spain	Local Institution - 0104	A Coruña
Spain	Local Institution - 0106	Badalona
Spain	Local Institution - 0110	Barcelona
Spain	Local Institution - 0109	Cordoba
Spain	Local Institution - 0103	Madrid
Spain	Local Institution - 0105	Madrid
Spain	Local Institution - 0108	Madrid
Spain	Local Institution - 0107	Santander
Spain	Local Institution - 0111	Sevilla
United Kingdom	Local Institution - 0085	Leicester
United Kingdom	Local Institution - 0042	London
United Kingdom	Local Institution	Stevenage	Hertfordshire
United States	Local Institution - 0005	Allentown	Pennsylvania
United States	Local Institution - 0009	Bronx	New York
United States	Local Institution - 0004	Buffalo	New York
United States	Local Institution - 0007	Charleston	South Carolina
United States	Local Institution - 0122	Gig Harbor	Washington
United States	Local Institution - 0080	Gilbert	Arizona
United States	Local Institution - 0139	Houston	Texas
United States	Local Institution - 0002	Iowa City	Iowa
United States	Local Institution - 0029	La Jolla	California
United States	Local Institution - 0006	New Brunswick	New Jersey
United States	Local Institution - 0015	Orange	California
United States	Local Institution	Rochester	Minnesota
United States	Local Institution - 0102	Seattle	Washington
United States	Local Institution - 0023	Temple	Texas
United States	Local Institution - 0136	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Nektar Therapeutics

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Czechia,  France,  Germany,  Greece,  Israel,  Italy,  Mexico,  Netherlands,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Complete Response (pCR) rate of Arm A to Arm C		Approximately 43 months
Primary	Event-Free Survival (EFS) of Arm A vs Arm C		Approximately 43 months
Secondary	pCR rate of Arm B to Arm C		Approximately 43 months
Secondary	EFS of Arm B vs Arm C		Approximately 43 months
Secondary	Overall Survival (OS)		Approximately 43 months
Secondary	Incidence of Adverse Events (AEs)		Up to 76.5 weeks
Secondary	Incidence of Serious Adverse Events (SAEs)		Up to 76.5 weeks
Secondary	Incidence of AEs leading to discontinuation		Up to 76.5 weeks
Secondary	Incidence of immune-mediated AEs (imAEs)		Up to 76.5 weeks
Secondary	Incidence of participants with clinical laboratory abnormalities		Up to 76.5 weeks
Secondary	pCR rate of Arm A to Arm B		Approximately 43 months
Secondary	EFS of Arm A vs Arm B		Approximately 43 months

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls