Clinical trial NCT03785925: A Single-Arm Study of Bempegaldesleukin (NKTR-214) Plus Nivolumab in Cisplatin Ineligible Patients Who Have Locally Advanced or Metastatic Urothelial Cancer
Official title: A Phase 2, Single-Arm Study of Bempegaldesleukin (NKTR-214) in Combination With Nivolumab in Cisplatin Ineligible, Locally Advanced or Metastatic Urothelial Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urinary Bladder Neoplasm
Neoplasm Metastasis
Keywords: Bladder
Bladder Cancer
CD122
Cisplatin Ineligible
Immuno-oncology
Immunotherapy
Locally Advanced Urothelial Cancer
Metastatic Urothelial Cancer
mUC
Natural Killer Cells
Nivolumab
NKTR-214
Opdivo®
PD-L1
Urothelial Cancer
Urothelial
Metastatic Urothelial Carcinoma
Urothelial Carcinoma
Bempegaldesleukin
BEMPEG
CPI Combination
IL-2
Lead sponsor: Nektar Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-12-24
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the anti-tumor activity of bempegaldesleukin (NKTR-214) in combination with nivolumab by assessing the objective response rate (ORR) in cisplatin ineligible, locally advanced or metastatic urothelial cancer patients.


Eligibility criteria: Key Inclusion Criteria:

* Provide written, informed consent to participate in the study and follow the study procedures
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Measurable disease per RECIST 1.1 criteria
* Histologically or cytologically documented inoperable, locally advanced or metastatic urothelial cell carcinoma (also termed TCC)
* Fresh biopsy or archival tissue
* No prior systemic chemotherapy or investigational agent for inoperable locally advanced or mUC
* Ineligible for cisplatin

Key Exclusion Criteria:

* Patients who have an active, known or suspected autoimmune disease
* Patients must not have received prior IL-2 therapy
* Prior treatment with an anti PD-1, anti PD-L1, or anti cytotoxic T lymphocyte associated protein 4 (anti CTLA-4) antibody, agents that target IL-2 pathway, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
* Patients with hypertension must be on a stable antihypertensive regimen for the 14 days prior to Cycle 1 Day 1

Additional protocol-defined inclusion/exclusion criteria applied

Primary outcomes:
measure: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Per Blinded Independent Central Review (BICR) in Patients Whose Tumors Have Low Programmed Cell Death Ligand (PD-L1) Expression
timeFrame: Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months
Secondary outcomes:
measure: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Per Blinded Independent Central Review (BICR) in All Treated Patients
timeFrame: Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months.
measure: Duration of Response (DOR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Per Blinded Independent Central Review (BICR) in in All Treated Patients and Patients Whose Tumors Have Low Programmed Cell Death Ligand (PD-L1) Expression
timeFrame: Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months.
measure: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator in All Treated Patients and Patients Whose Tumors Have Low Programmed Cell Death Ligand (PD-L1) Expression
timeFrame: Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months.
measure: Duration of Response (DOR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator in All Treated Patients and Patients Whose Tumors Have Low Programmed Cell Death Ligand (PD-L1) Expression
timeFrame: Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months.
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco VA Medical Center - NAVREF - PPDS
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute, LLC
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Newnan
country: United States
facility: Southeastern Regional Medical Center - CTCA - PPDS
state: Georgia
city: Peoria
country: United States
facility: Investigator Site - Peoria
state: Illinois
city: New York
country: United States
facility: Laura And Isaac Perlmutter Cancer Center
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Viedma
country: Argentina
facility: Centro de Investigación Clínica - Clínica Viedma
state: Rio Negro
city: Rosario
country: Argentina
facility: Instituto de Oncologia de Rosario
state: Santa Fe
city: San Miguel De Tucumán
country: Argentina
facility: CAIPO Centro para la atención integral del paciente oncológico
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Hospital Alemán
city: Buenos Aires
country: Argentina
facility: Instituto Médico Especializado Alexander Fleming
city: Córdoba
country: Argentina
facility: Centro Médico Privado CEMAIC
city: Córdoba
country: Argentina
facility: Sanatorio Privado Duarte Quirós, de Clínica Colombo S.A.
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Southport
country: Australia
facility: Tasman Health Care
state: Queensland
city: Kurralta Park
country: Australia
facility: Adelaide Cancer Centre
state: South Australia
city: Bentleigh East
country: Australia
facility: Monash Health, Monash Medical Centre
state: Victoria
city: Nedlands
country: Australia
facility: St John of God Murdoch Hospital
state: Western Australia
city: Brasschaat
country: Belgium
facility: Algemeen Ziekenhuis Klina
state: Antwerpen
city: Wilrijk
country: Belgium
facility: GasthuisZusters Antwerpen
state: Antwerpen
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Helsinki
country: Finland
facility: Helsingin Yliopistollinen Keskussairaala - PPDS
city: Caen
country: France
facility: Centre François Baclesse
state: Calvados
city: Hyères
country: France
facility: Hôpital Privé TOULON/HYERES Sainte Marguerite
city: Le Mans
country: France
facility: Centre Jean Bernard Clinique Victor Hugo
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Saint-Herblain
country: France
facility: Edog Ico - Ppds
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Nürtingen
country: Germany
facility: Studienpraxis Urologie
state: Baden-Württemberg
city: Weiden
country: Germany
facility: Kliniken Nordoberpfalz AG
state: Bavaria
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der TU Dresden
city: Athens
country: Greece
facility: Alexandra Hospital
state: Attiki
city: Maroúsi
country: Greece
facility: Medical Center of Athens
state: Attiki
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Thessaloníki
country: Greece
facility: Euromedica - PPDS
city: Zerifin
country: Israel
facility: Shamir Medical Center Assaf Harofeh
state: HaMerkaz
city: Haifa
country: Israel
facility: Rambam Medical Center - PPDS
city: Kefar Saba
country: Israel
facility: Meir Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center - PPDS
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center PPDS
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS
state: Emilia-Romagna
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico
state: Pordenone
city: Milano
country: Italy
facility: Istituto Nazionale Dei Tumori
city: Ciudad de mexico
country: Mexico
facility: Health Pharma Professional Research S.A de C.V.
state: Distrito Federal
city: Cuautitlán Izcalli
country: Mexico
facility: Phylasis Clinicas Research S. de R.L. de C.V.
city: Amsterdam
country: Netherlands
facility: Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
city: Coimbra
country: Portugal
facility: Centro Hospitalar E Universitário de Coimbra EPE
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Oncology Hospital
state: Yaroslavskaya Oblast
city: Obninsk
country: Russian Federation
facility: Federal State Institution Medical Radiology Research Center
city: Omsk
country: Russian Federation
facility: Clinical Oncology Dispensary
city: Pushkin
country: Russian Federation
facility: PMI Euromedservice
city: Saint Petersburg
country: Russian Federation
facility: Railway Clinical Hospital JSC RZhD
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
state: Catalonia
city: Pozuelo De Alarcón
country: Spain
facility: Hospital Universitario Ramon y Cajal
state: Madrid
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro - CIOCC
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio - PPDS
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncologia
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty - PPDS
city: İzmir
country: Turkey
facility: Izmir Medicalpark Hospital
city: Malatya
country: Turkey
facility: Inonu University Faculty of Medicine Turgut Ozal Medical Center
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital - Surrey
state: Surrey
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Barts Health NHS Trust
Study officials:
affiliation: Nektar Therapeutics
name: Study Director
role: STUDY_DIRECTOR
References: