Clinical trial NCT03635983: A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma
Official title: A Phase 3, Randomized, Open-label Study of NKTR-214 Combined With Nivolumab Versus Nivolumab in Participants With Previously Untreated Unresectable or Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Melanoma
Keywords: NKTR-214
Nivolumab
Immunotherapy
bempegaldesleukin (BEMPEG: NKTR-214)
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Nektar Therapeutics
First posted: 2018-08-17
Enrollment: 783
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to test the effectiveness (how well the drug works), safety, and tolerability of the investigational drug called NKTR-214, when combined with nivolumab versus nivolumab given alone in participants with previously untreated melanoma skin cancer that is either unable to be surgically removed or has spread


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 (adults 18 years or older)/Lansky Performance Score ≥ 80% (minors ages 12-17 only)
* Histologically confirmed stage III (unresectable) or stage IV melanoma
* Treatment-naive participants (ie, no prior systemic anticancer therapy for unresectable or metastatic melanoma) with the exception of prior adjuvant and/or neoadjuvant treatment for melanoma with approved agents

Exclusion Criteria:

* Active brain metastases or leptomeningeal metastases
* Uveal melanoma
* Participants with an active, known or suspected autoimmune disease

Other protocol defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
timeFrame: From date of randomization to disease progression (Up to 37 months)
measure: Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR)
timeFrame: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)
measure: Overall Survival (OS)
timeFrame: From date of randomization to date of death (Up to 37 months)
Secondary outcomes:
measure: Clinical Benefit Rate (CBR) Per Blinded Independent Central Review (BICR)
timeFrame: From date of randomization to disease progression (Up to 37 months)
measure: Duration of Response (DoR) Per Blinded Independent Central Review (BICR)
timeFrame: From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months)
measure: Time to Objective Response (TTR) Per Blinded Independent Central Review (BICR)
timeFrame: From date of randomization to disease progression (Up to 37 months)
measure: Objective Response Rate (ORR) Per Investigator
timeFrame: From date of randomization to disease progression (Up to 37 months)
measure: Progression-free Survival (PFS) Per Investigator
timeFrame: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)
measure: Clinical Benefit Rate (CBR) Per Investigator
timeFrame: From date of randomization to disease progression (Up to 37 months)
measure: Duration of Response (DoR) Per Investigator
timeFrame: From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months)
measure: Time to Objective Response (TTR) Per Investigator
timeFrame: From date of randomization to disease progression (Up to 37 months)
measure: Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status
timeFrame: From date of randomization to disease progression (Up to 37 months)
measure: Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status
timeFrame: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)
measure: Overall Survival (OS) by Baseline PD-L1 Status
timeFrame: From date of randomization to date of death (Up to 37 months)
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose to 30 days post last dose (Average of 11 months and a maximum up to 26 months)
measure: Number of Participants With On-Treatment Laboratory Parameters That Worsened Relative to Baseline
timeFrame: From first dose to 100 days post last dose (Average of 13 months and a maximum up to 28 months)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Local Institution - 0187
state: Arizona
city: La Jolla
country: United States
facility: Local Institution - 0014
state: California
city: Stanford
country: United States
facility: Local Institution - 0122
state: California
city: Aurora
country: United States
facility: Local Institution - 0051
state: Colorado
city: New Haven
country: United States
facility: Local Institution - 0065
state: Connecticut
city: Miami Beach
country: United States
facility: Local Institution - 0017
state: Florida
city: Miami
country: United States
facility: Local Institution - 0153
state: Florida
city: Tampa
country: United States
facility: Local Institution - 0112
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0012
state: Georgia
city: Louisville
country: United States
facility: Local Institution - 0019
state: Kentucky
city: Boston
country: United States
facility: Local Institution - 0018
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 0188
state: Michigan
city: Fridley
country: United States
facility: Local Institution - 0186
state: Minnesota
city: Saint Louis
country: United States
facility: Local Institution - 0135
state: Missouri
city: Hackensack
country: United States
facility: Local Institution - 0016
state: New Jersey
city: New Brunswick
country: United States
facility: Local Institution - 0185
state: New Jersey
city: New York
country: United States
facility: Local Institution - 0141
state: New York
city: Cleveland
country: United States
facility: Local Institution - 0037
state: Ohio
city: Portland
country: United States
facility: Local Institution - 0011
state: Oregon
city: Portland
country: United States
facility: Local Institution - 0013
state: Oregon
city: Easton
country: United States
facility: St. Luke's Hospital & Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0015
state: Pennsylvania
city: Houston
country: United States
facility: Local Institution - 0001
state: Texas
city: Fairfax
country: United States
facility: Local Institution - 0064
state: Virginia
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Local Institution - 0109
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution - 0107
state: Ciudad Autónoma De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution - 0183
state: Distrito Federal
city: Caba
country: Argentina
facility: Local Institution - 0108
city: Cordoba
country: Argentina
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city: Coffs Harbour
country: Australia
facility: Local Institution - 0146
state: New South Wales
city: North Sydney
country: Australia
facility: Local Institution - 0053
state: New South Wales
city: Cairns
country: Australia
facility: Local Institution - 0058
state: Queensland
city: Greenslopes
country: Australia
facility: Local Institution
state: Queensland
city: Woolloongabba
country: Australia
facility: Local Institution - 0056
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Local Institution - 0172
state: South Australia
city: Melbourne
country: Australia
facility: Local Institution - 0054
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution - 0143
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution - 0057
state: Western Australia
city: Nedlands
country: Australia
facility: Local Institution - 0097
state: Western Australia
city: Graz
country: Austria
facility: Local Institution - 0034
city: Salzburg
country: Austria
facility: Local Institution - 0035
city: Wien
country: Austria
facility: Local Institution - 0033
city: Bruxelles
country: Belgium
facility: Local Institution - 0083
city: Hasselt
country: Belgium
facility: Local Institution - 0084
city: Leuven
country: Belgium
facility: Local Institution - 0085
city: Fortaleza
country: Brazil
facility: Local Institution - 0168
state: Ceara
city: Belo Horizonte
country: Brazil
facility: Local Institution - 0125
state: Minas Gerais
city: Ijui
country: Brazil
facility: Local Institution - 0124
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Local Institution - 0127
state: RIO Grande DO SUL
city: Itajai
country: Brazil
facility: Local Institution - 0171
state: Santa Catarina
city: Barretos
country: Brazil
facility: Local Institution - 0126
state: Sao Paulo
city: Rio De Janeiro
country: Brazil
facility: Local Institution - 0182
city: Sao Paulo
country: Brazil
facility: Local Institution - 0169
city: Abbotsford
country: Canada
facility: Local Institution - 0068
state: British Columbia
city: St. John's
country: Canada
facility: Local Institution - 0139
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: Local Institution - 0066
state: Ontario
city: Kitchener
country: Canada
facility: Local Institution - 0067
state: Ontario
city: Toronto
country: Canada
facility: Local Institution - 0041
state: Ontario
city: Edmonton
country: Canada
facility: Local Institution - 0121
city: Quebec
country: Canada
facility: Local Institution
city: Recoleta
country: Chile
facility: Local Institution - 0174
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 0173
state: Metropolitana
city: Brno
country: Czechia
facility: Local Institution - 0094
city: Hradec Kralove
country: Czechia
facility: Local Institution - 0093
city: Praha 10
country: Czechia
facility: Local Institution - 0091
city: Praha 2
country: Czechia
facility: Local Institution - 0092
city: Tampere
country: Finland
facility: Local Institution - 0166
state: Oulun Lääni
city: KYS
country: Finland
facility: Local Institution - 0167
city: Turku
country: Finland
facility: Local Institution - 0165
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux Hospital Saint Andre
city: Lille
country: France
facility: Hopital Claude Huriez
city: Montpellier Cedex 05
country: France
facility: Hopital Saint Eloi
city: Nantes Cedex 1
country: France
facility: Local Institution - 0003
city: Nice
country: France
facility: Local Institution - 0155
city: Paris
country: France
facility: Hopital Saint Louis
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rouen
country: France
facility: CHU Charles Nicolle
city: Saint Priest en Jarez
country: France
facility: Local Institution - 0009
city: Toulouse Cedex 9
country: France
facility: Local Institution - 0002
city: Villejuif
country: France
facility: Institute Gustave Roussy
city: Buxtehude
country: Germany
facility: Local Institution - 0031
city: Dresden
country: Germany
facility: Local Institution - 0029
city: Erfurt
country: Germany
facility: Local Institution - 0192
city: Essen
country: Germany
facility: Local Institution - 0026
city: Goettingen
country: Germany
facility: Local Institution - 0030
city: Hamburg
country: Germany
facility: Local Institution - 0023
city: Hannover
country: Germany
facility: Local Institution - 0024
city: Heidelberg
country: Germany
facility: Local Institution - 0020
city: Kiel
country: Germany
facility: Local Institution - 0028
city: Leipzig
country: Germany
facility: Local Institution - 0022
city: Muenchen
country: Germany
facility: Local Institution - 0021
city: Münster
country: Germany
facility: Local Institution - 0027
city: Regensburg
country: Germany
facility: Local Institution - 0060
city: Tuebingen
country: Germany
facility: Local Institution - 0025
city: Wuerzburg
country: Germany
facility: Local Institution - 0032
city: Athens
country: Greece
facility: Local Institution - 0038
city: Neo Faliro
country: Greece
facility: Local Institution - 0039
city: Thessaloniki
country: Greece
facility: Local Institution - 0040
city: Wilton
country: Ireland
facility: Local Institution - 0136
state: Cork
city: Dublin 7
country: Ireland
facility: Local Institution - 0129
state: Dublin
city: Dublin
country: Ireland
facility: Local Institution - 0128
city: Dublin
country: Ireland
facility: Local Institution - 0130
city: Beer Sheva
country: Israel
facility: Local Institution - 0098
city: Jerusalem
country: Israel
facility: Local Institution - 0088
city: Ramat-gan
country: Israel
facility: Local Institution - 0089
city: Milan
country: Italy
facility: Local Institution - 0045
state: Lombardia
city: Torino
country: Italy
facility: Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
state: Piemonte
city: Bari
country: Italy
facility: Local Institution - 0044
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
city: Meldola (fc)
country: Italy
facility: Local Institution - 0113
city: Milano
country: Italy
facility: IRCCS Istituto Nazionale Tumori Milano
city: Napoli
country: Italy
facility: Local Institution - 0043
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IOV
city: Siena
country: Italy
facility: Local Institution - 0042
city: Torino
country: Italy
facility: Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
city: Ciudad de Mexico
country: Mexico
facility: Local Institution - 0175
state: Distrito Federal
city: Zapopan
country: Mexico
facility: Local Institution - 0176
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution - 0177
state: Nuevo LEON
city: Monterrey
country: Mexico
facility: Local Institution - 0180
state: Nuevo LEON
city: Cancún
country: Mexico
facility: Local Institution - 0178
state: Quintana Roo
city: Puebla
country: Mexico
facility: Local Institution - 0179
city: San Luis Potosi
country: Mexico
facility: Local Institution - 0181
city: Amsterdam
country: Netherlands
facility: Local Institution - 0101
city: Amsterdam
country: Netherlands
facility: Local Institution - 0102
city: Leiden
country: Netherlands
facility: Local Institution - 0099
city: Nijmegen
country: Netherlands
facility: Local Institution - 0100
city: Untrecht
country: Netherlands
facility: Local Institution - 0147
city: Auckland
country: New Zealand
facility: Local Institution - 0159
city: Christchurch
country: New Zealand
facility: Local Institution - 0063
city: Wellington
country: New Zealand
facility: Local Institution - 0062
city: Bydgoszcz
country: Poland
facility: Local Institution - 0152
city: Warszawa
country: Poland
facility: Local Institution - 0090
city: Lisboa
country: Portugal
facility: Local Institution - 0134
city: Porto
country: Portugal
facility: Local Institution - 0133
city: Bucharest
country: Romania
facility: Local Institution - 0162
city: Cluj-Napoca
country: Romania
facility: Local Institution - 0070
city: Craiova
country: Romania
facility: Local Institution - 0071
city: Floresti
country: Romania
facility: Local Institution - 0120
city: Krasnoyarsk
country: Russian Federation
facility: Local Institution - 0149
city: Moscow
country: Russian Federation
facility: Local Institution - 0086
city: Moscow
country: Russian Federation
facility: Local Institution - 0111
city: Moscow
country: Russian Federation
facility: Local Institution - 0148
city: Barcelona
country: Spain
facility: Local Institution - 0116
city: Barcelona
country: Spain
facility: Local Institution - 0115
city: Cordoba
country: Spain
facility: Local Institution - 0123
city: Doniostia - San Sebastian
country: Spain
facility: Local Institution - 0190
city: Donostia
country: Spain
facility: Local Institution
city: Jaén
country: Spain
facility: Local Institution - 0118
city: Madrid
country: Spain
facility: Local Institution - 0114
city: Santiago Compostela
country: Spain
facility: Local Institution - 0119
city: Valencia
country: Spain
facility: Local Institution - 0117
city: Gothenburg
country: Sweden
facility: Local Institution - 0163
city: Lund
country: Sweden
facility: Local Institution - 0164
city: Bern
country: Switzerland
facility: Local Institution - 0104
city: Lausanne
country: Switzerland
facility: Local Institution - 0105
city: Zuerich
country: Switzerland
facility: Local Institution - 0036
city: Southampton
country: United Kingdom
facility: Local Institution - 0132
state: Hampshire
city: Edinburgh
country: United Kingdom
facility: Local Institution
state: Midlothian
city: Sutton.
country: United Kingdom
facility: Local Institution - 0131
state: Surrey
city: Belfast
country: United Kingdom
facility: Local Institution - 0078
city: Cambridge
country: United Kingdom
facility: Local Institution - 0076
city: Cottingham
country: United Kingdom
facility: Local Institution - 0079
city: Liverpool
country: United Kingdom
facility: Local Institution - 0137
city: London
country: United Kingdom
facility: Local Institution - 0077
city: London
country: United Kingdom
facility: Local Institution - 0074
city: Manchester
country: United Kingdom
facility: Local Institution - 0075
city: Tauton
country: United Kingdom
facility: Local Institution - 0142
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Khushalani NI, Diab A, Ascierto PA, Larkin J, Sandhu S, Sznol M, Koon HB, Jarkowski A, Zhou M, Statkevich P, Geese WJ, Long GV. Bempegaldesleukin plus nivolumab in untreated, unresectable or metastatic melanoma: Phase III PIVOT IO 001 study design. Future Oncol. 2020 Oct;16(28):2165-2175. doi: 10.2217/fon-2020-0351. Epub 2020 Jul 29.