A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma
- Conditions
- Melanoma
- Interventions
- Biological: NKTR-214Biological: Nivolumab
- Registration Number
- NCT03635983
- Lead Sponsor
- Bristol-Myers Squibb
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 783
- 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
- Active brain metastases or leptomeningeal metastases
- Uveal melanoma
- Participants with an active, known or suspected autoimmune disease
Other protocol defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Combination Nivolumab NKTR-214 + Nivolumab Monotherapy Nivolumab Nivolumab Combination NKTR-214 NKTR-214 + Nivolumab
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR) From date of randomization to disease progression, or death, whichever comes first (Up to 37 months) PFS is defined as the time between the date of randomization and the first date of documented tumor progression using RECIST v 1.1 per blinded independent central review (BICR), or death due to any cause, whichever comes first. Progressive disease (PD)=At least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm.
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) From date of randomization to disease progression (Up to 37 months) ORR is defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) using RECIST v 1.1 per blinded independent central review (BICR) assessment. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.
Overall Survival (OS) From date of randomization to date of death (Up to 37 months) OS is defined as the time between the date of randomization and the date of death due to any cause. Participants who do not have a date of death will be censored on the last date for which a participant was known to be alive.
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status From date of randomization to disease progression, or death, whichever comes first (Up to 37 months) PFS by baseline PD-L1 tumor cells expression (PD-L1 negative: \<1%) vs. (PD-L1 positive: \>=1%). PFS is defined as the time between the date of randomization and the first date of documented tumor progression using RECIST v 1.1 per blinded independent central review (BICR), or death due to any cause, whichever comes first. Progressive disease (PD)=At least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm.
Number of Participants With On-Treatment Laboratory Parameters That Worsened Relative to Baseline From first dose to 100 days post last dose (Average of 10 months and a maximum up to 37 months) Number of participants with on-treatment laboratory parameters that worsened relative to baseline. Parameters include hematology, chemistry, liver function, and renal function using worst grade (grade 1-4 and grade 3-4) per national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) v5 criteria.
Grade 1=Mild event Grade 2=Moderate event Grade 3=Severe event Grade 4=Life threatening eventDuration of Response (DoR) Per Blinded Independent Central Review (BICR) From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months) DOR is defined for participants who have a confirmed complete response (CR) or partial results (PR) as the date from first documented CR or PR using RECIST v 1.1 to the date of the documentation of disease progression per blinded independent central review (BICR) assessment or death due to any cause, whichever is earlier. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.
Objective Response Rate (ORR) Per Investigator From date of randomization to disease progression (Up to 37 months) ORR is defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) using RECIST v 1.1 per investigator assessment. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.
Clinical Benefit Rate (CBR) Per Investigator From date of randomization to disease progression (Up to 37 months) CBR, or equivalently the disease control rate (DCR) is defined as the percentage of participants with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) as assessed by investigator using RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status From date of randomization to disease progression (Up to 37 months) ORR by baseline PD-L1 tumor cells expression (PD-L1 negative: \<1%) vs. (PD-L1 positive: \>=1%). ORR is defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) using RECIST v 1.1 per blinded independent central review (BICR) assessment. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.
Overall Survival (OS) by Baseline PD-L1 Status From date of randomization to date of death (Up to 37 months) OS by baseline PD-L1 tumor cells expression (PD-L1 negative: \<1%) vs. (PD-L1 positive: \>=1%). OS is defined as the time between the date of randomization and the date of death due to any cause. Participants who do not have a date of death will be censored on the last date for which a participant was known to be alive.
Time to Objective Response (TTR) Per Investigator From date of randomization to disease progression (Up to 37 months) Time to response (TTR) is defined for participants who had a confirmed complete response (CR) or partial response (PR) as the time from the date of randomization to date of first documented CR or PR per investigator assessment using RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.
Clinical Benefit Rate (CBR) Per Blinded Independent Central Review (BICR) From date of randomization to disease progression (Up to 37 months) CBR, or equivalently the disease control rate (DCR) is defined as the percentage of participants with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) as assessed by blinded independent central review (BICR) using RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
Time to Objective Response (TTR) Per Blinded Independent Central Review (BICR) From date of randomization to disease progression (Up to 37 months) Time to response (TTR) is defined for participants who had a confirmed complete response (CR) or partial response (PR) as the time from the date of randomization to date of first documented CR or PR per blinded independent central review (BICR) assessment using RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.
Progression-free Survival (PFS) Per Investigator From date of randomization to disease progression, or death, whichever comes first (Up to 37 months) PFS is defined as the time between the date of randomization and the first date of documented tumor progression using RECIST v 1.1 per investigator, or death due to any cause, whichever comes first. Progressive disease (PD)=At least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm.
Duration of Response (DoR) Per Investigator From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months) DOR is defined for participants who have a confirmed complete response (CR) or partial results (PR) as the date from first documented CR or PR using RECIST v 1.1 to the date of the documentation of disease progression per investigator assessment or death due to any cause, whichever is earlier. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.
Number of Participants With Adverse Events (AEs) From first dose to 30 days post last dose (Average of 8 months and a maximum up to 35 months) Number of participants with any grade adverse events (AEs) including treatment-related AEs, AEs leading to discontinuation of any drug, serious adverse events (SAEs), treatment-related SAEs, and deaths from first dose to 30 days post last dose. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Trial Locations
- Locations (164)
Local Institution - 0146
🇦🇺Coffs Harbour, New South Wales, Australia
Local Institution - 0037
🇺🇸Cleveland, Ohio, United States
Local Institution - 0135
🇺🇸Saint Louis, Missouri, United States
Local Institution - 0109
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Local Institution - 0172
🇦🇺Elizabeth Vale, South Australia, Australia
Local Institution - 0143
🇦🇺Melbourne, Victoria, Australia
Local Institution - 0034
🇦🇹Graz, Austria
Local Institution - 0091
🇨🇿Praha 10, Czechia
Local Institution - 0192
🇩🇪Erfurt, Germany
Local Institution - 0117
🇪🇸Valencia, Spain
Local Institution - 0163
🇸🇪Gothenburg, Sweden
Local Institution - 0104
🇨🇭Bern, Switzerland
Local Institution - 0131
🇬🇧Sutton., Surrey, United Kingdom
Local Institution - 0105
🇨🇭Lausanne, Switzerland
Local Institution - 0079
🇬🇧Cottingham, United Kingdom
Local Institution - 0074
🇬🇧London, United Kingdom
Local Institution - 0001
🇺🇸Houston, Texas, United States
Local Institution - 0153
🇺🇸Miami, Florida, United States
Local Institution - 0097
🇦🇺Nedlands, Western Australia, Australia
Local Institution - 0129
🇮🇪Dublin 7, Dublin, Ireland
Local Institution - 0186
🇺🇸Fridley, Minnesota, United States
Local Institution - 0125
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Local Institution - 0124
🇧🇷Ijui, RIO Grande DO SUL, Brazil
Local Institution - 0127
🇧🇷Porto Alegre, RIO Grande DO SUL, Brazil
Local Institution - 0187
🇺🇸Tucson, Arizona, United States
Local Institution - 0041
🇨🇦Toronto, Ontario, Canada
Local Institution - 0017
🇺🇸Miami Beach, Florida, United States
Local Institution - 0183
🇦🇷Buenos Aires, Distrito Federal, Argentina
Local Institution - 0018
🇺🇸Boston, Massachusetts, United States
Local Institution - 0107
🇦🇷Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina
Centre Hospitalier Universitaire de Bordeaux Hospital Saint Andre
🇫🇷Bordeaux, France
Local Institution - 0027
🇩🇪Münster, Germany
Local Institution - 0025
🇩🇪Tuebingen, Germany
Istituto Oncologico Veneto IOV
🇮🇹Padova, Italy
Local Institution - 0016
🇺🇸Hackensack, New Jersey, United States
Local Institution - 0185
🇺🇸New Brunswick, New Jersey, United States
Local Institution - 0067
🇨🇦Kitchener, Ontario, Canada
Local Institution - 0070
🇷🇴Cluj-Napoca, Romania
Local Institution - 0108
🇦🇷Caba, Argentina
Local Institution - 0157
🇦🇷Cordoba, Argentina
Local Institution - 0036
🇨🇭Zuerich, Switzerland
Local Institution - 0023
🇩🇪Hamburg, Germany
Local Institution - 0171
🇧🇷Itajai, Santa Catarina, Brazil
Local Institution - 0126
🇧🇷Barretos, Sao Paulo, Brazil
Local Institution - 0173
🇨🇱Santiago, Metropolitana, Chile
Institute Gustave Roussy
🇫🇷Villejuif, France
Local Institution - 0024
🇩🇪Hannover, Germany
Local Institution - 0022
🇩🇪Leipzig, Germany
Local Institution - 0060
🇩🇪Regensburg, Germany
Local Institution - 0039
🇬🇷Neo Faliro, Greece
Istituto Europeo di Oncologia IRCCS
🇮🇹Milan, Lombardia, Italy
IRCCS Istituto Nazionale Tumori Milano
🇮🇹Milano, Italy
Local Institution - 0042
🇮🇹Siena, Italy
Local Institution - 0162
🇷🇴Bucharest, Romania
Local Institution - 0132
🇬🇧Southampton, Hampshire, United Kingdom
Local Institution - 0174
🇨🇱Recoleta, Metropolitana, Chile
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite, France
Local Institution - 0026
🇩🇪Essen, Germany
Local Institution - 0088
🇮🇱Jerusalem, Israel
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
🇮🇹Torino, Piemonte, Italy
Instituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Napoli, Italy
Local Institution - 0179
🇲🇽Puebla, Mexico
Local Institution - 0031
🇩🇪Buxtehude, Germany
Local Institution - 0058
🇦🇺Cairns, Queensland, Australia
Local Institution - 0056
🇦🇺Woolloongabba, Queensland, Australia
Local Institution - 0029
🇩🇪Dresden, Germany
Local Institution - 0030
🇩🇪Goettingen, Germany
Local Institution - 0020
🇩🇪Heidelberg, Germany
Local Institution - 0028
🇩🇪Kiel, Germany
Local Institution - 0032
🇩🇪Wuerzburg, Germany
Hotel Dieu - Chu De Nantes
🇫🇷Nantes Cedex 1, France
Local Institution - 0051
🇺🇸Aurora, Colorado, United States
Local Institution - 0112
🇺🇸Tampa, Florida, United States
Local Institution - 0188
🇺🇸Ann Arbor, Michigan, United States
Local Institution - 0011
🇺🇸Portland, Oregon, United States
Local Institution - 0013
🇺🇸Portland, Oregon, United States
Local Institution - 0065
🇺🇸New Haven, Connecticut, United States
Local Institution - 0019
🇺🇸Louisville, Kentucky, United States
Local Institution - 0118
🇪🇸Jaén, Spain
Local Institution - 0014
🇺🇸La Jolla, California, United States
Local Institution - 0122
🇺🇸Stanford, California, United States
Local Institution - 0012
🇺🇸Atlanta, Georgia, United States
Local Institution - 0141
🇺🇸New York, New York, United States
St. Luke's Hospital & Health Network
🇺🇸Easton, Pennsylvania, United States
Local Institution - 0015
🇺🇸Philadelphia, Pennsylvania, United States
Local Institution - 0064
🇺🇸Fairfax, Virginia, United States
Local Institution - 0053
🇦🇺North Sydney, New South Wales, Australia
Local Institution
🇬🇧Edinburgh, Midlothian, United Kingdom
Local Institution - 0057
🇦🇺Nedlands, Western Australia, Australia
Local Institution - 0035
🇦🇹Salzburg, Austria
Local Institution - 0033
🇦🇹Wien, Austria
Local Institution - 0083
🇧🇪Bruxelles, Belgium
Local Institution - 0085
🇧🇪Leuven, Belgium
Local Institution - 0084
🇧🇪Hasselt, Belgium
Local Institution - 0168
🇧🇷Fortaleza, Ceara, Brazil
Local Institution - 0068
🇨🇦Abbotsford, British Columbia, Canada
Local Institution - 0182
🇧🇷Rio De Janeiro, Brazil
Local Institution - 0169
🇧🇷Sao Paulo, Brazil
Local Institution - 0139
🇨🇦St. John's, Newfoundland and Labrador, Canada
Local Institution - 0066
🇨🇦Hamilton, Ontario, Canada
Local Institution - 0121
🇨🇦Edmonton, Canada
Local Institution - 0094
🇨🇿Brno, Czechia
Local Institution - 0093
🇨🇿Hradec Kralove, Czechia
Local Institution - 0092
🇨🇿Praha 2, Czechia
Local Institution - 0167
🇫🇮KYS, Finland
Local Institution - 0166
🇫🇮Tampere, Oulun Lääni, Finland
Local Institution - 0165
🇫🇮Turku, Finland
Hopital Claude Huriez
🇫🇷Lille, France
Hopital Saint Eloi
🇫🇷Montpellier Cedex 05, France
Chu De Nice Hopital De Cimiez
🇫🇷Nice, France
CHU Charles Nicolle
🇫🇷Rouen, France
Hopital Nord - CHU de Saint-Etienne
🇫🇷Saint Priest en Jarez, France
Institut Claudius Regaud
🇫🇷Toulouse Cedex 9, France
Local Institution - 0021
🇩🇪Muenchen, Germany
Local Institution - 0038
🇬🇷Athens, Greece
Local Institution - 0136
🇮🇪Wilton, Cork, Ireland
Local Institution - 0040
🇬🇷Thessaloniki, Greece
Local Institution - 0130
🇮🇪Dublin, Ireland
Local Institution - 0128
🇮🇪Dublin, Ireland
Local Institution - 0098
🇮🇱Beer Sheva, Israel
Local Institution - 0089
🇮🇱Ramat-gan, Israel
IRCCS Giovanni Paolo II Istituto Oncologico
🇮🇹Bari, Italy
ASST Papa Giovanni XXIII
🇮🇹Bergamo, Italy
IRST Meldola
🇮🇹Meldola (fc), Italy
Local Institution - 0175
🇲🇽Ciudad de Mexico, Distrito Federal, Mexico
Local Institution - 0176
🇲🇽Zapopan, Jalisco, Mexico
Local Institution - 0133
🇵🇹Porto, Portugal
Local Institution - 0180
🇲🇽Monterrey, Nuevo LEON, Mexico
Local Institution - 0177
🇲🇽Monterrey, Nuevo LEON, Mexico
Local Institution - 0181
🇲🇽San Luis Potosi, Mexico
Local Institution - 0101
🇳🇱Amsterdam, Netherlands
Local Institution - 0102
🇳🇱Amsterdam, Netherlands
Local Institution - 0099
🇳🇱Leiden, Netherlands
Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
🇮🇹Torino, Italy
Local Institution - 0147
🇳🇱Untrecht, Netherlands
Local Institution - 0100
🇳🇱Nijmegen, Netherlands
Local Institution - 0159
🇳🇿Auckland, New Zealand
Local Institution - 0062
🇳🇿Wellington, New Zealand
Local Institution - 0063
🇳🇿Christchurch, New Zealand
Local Institution - 0152
🇵🇱Bydgoszcz, Poland
Local Institution - 0090
🇵🇱Warszawa, Poland
Local Institution - 0134
🇵🇹Lisboa, Portugal
Local Institution - 0071
🇷🇴Craiova, Romania
Local Institution - 0086
🇷🇺Moscow, Russian Federation
Local Institution - 0111
🇷🇺Moscow, Russian Federation
Local Institution - 0120
🇷🇴Floresti, Romania
Local Institution - 0149
🇷🇺Krasnoyarsk, Russian Federation
Local Institution - 0148
🇷🇺Moscow, Russian Federation
Local Institution - 0123
🇪🇸Cordoba, Spain
Local Institution - 0116
🇪🇸Barcelona, Spain
Local Institution - 0115
🇪🇸Barcelona, Spain
Local Institution - 0190
🇪🇸Doniostia - San Sebastian, Spain
Local Institution - 0114
🇪🇸Madrid, Spain
Local Institution - 0119
🇪🇸Santiago Compostela, Spain
Local Institution - 0164
🇸🇪Lund, Sweden
Local Institution - 0078
🇬🇧Belfast, United Kingdom
Local Institution - 0076
🇬🇧Cambridge, United Kingdom
Local Institution - 0137
🇬🇧Liverpool, United Kingdom
Local Institution - 0077
🇬🇧London, United Kingdom
Local Institution - 0075
🇬🇧Manchester, United Kingdom
Local Institution - 0142
🇬🇧Tauton, United Kingdom
Local Institution - 0054
🇦🇺Melbourne, Victoria, Australia
Hopital Saint Louis
🇫🇷Paris, France
Local Institution - 0178
🇲🇽Cancún, Quintana Roo, Mexico