MelanomaPhase 3NCT03635983
A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma
A Phase 3 study testing NKTR-214 and Nivolumab in people with Melanoma, run by Bristol-Myers Squibb at 167 sites in 27 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- NKTR-214 and Nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 783 participants
- Where
- 167 sitesin 27 countries
- Study dates
- 21 Sep 2018to 19 Mar 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Active brain metastases or leptomeningeal metastases
- Uveal melanoma
- Participants with an active, known or suspected autoimmune disease
- Other protocol defined inclusion/exclusion criteria apply
Trial locations and contacts
167 sites in 27 countries.
167 sites in 27 countries
United States24 sites
Local Institution - 0188
Ann Arbor, Michigan, 48109
Local Institution - 0012
Atlanta, Georgia, 30322-1013
Local Institution - 0051
Aurora, Colorado, 80045
Local Institution - 0018
Boston, Massachusetts, 02215
Local Institution - 0037
Cleveland, Ohio, 44195
St. Luke's Hospital & Health Network
Easton, Pennsylvania, 18045
Local Institution - 0064
Fairfax, Virginia, 22031
Local Institution - 0186
Fridley, Minnesota, 55432
Local Institution - 0016
Hackensack, New Jersey, 07601
Local Institution - 0001
Houston, Texas, 77030
Local Institution - 0014
La Jolla, California, 92093
Local Institution - 0019
Louisville, Kentucky, 40202
Local Institution - 0153
Miami, Florida, 33136
Local Institution - 0017
Miami Beach, Florida, 33140
Local Institution - 0185
New Brunswick, New Jersey, 08903
Local Institution - 0065
New Haven, Connecticut, 06510
Local Institution - 0141
New York, New York, 10065
Local Institution - 0015
Philadelphia, Pennsylvania, 19111
Local Institution - 0011
Portland, Oregon, 97213
Local Institution - 0013
Portland, Oregon, 97239
Local Institution - 0135
St Louis, Missouri, 63110
Local Institution - 0122
Stanford, California, 94305
Local Institution - 0112
Tampa, Florida, 33612
Local Institution - 0187
Tucson, Arizona, 85724
Germany15 sites
Local Institution - 0031
Buxtehude, 21614
Local Institution - 0029
Dresden, 01307
Local Institution - 0192
Erfurt, 99089
Local Institution - 0026
Essen, 45147
Local Institution - 0030
Göttingen, 37075
Local Institution - 0023
Hamburg, 20251
Local Institution - 0024
Hanover, D30625
Local Institution - 0020
Heidelberg, 69120
Local Institution - 0028
Kiel, 24105
Local Institution - 0022
Leipzig, 04103
Local Institution - 0021
München, 80337
Local Institution - 0027
Münster, 48157
Local Institution - 0060
Regensburg, 93053
Local Institution - 0025
Tübingen, 72076
Local Institution - 0032
Würzburg, 97080
France11 sites
Centre Hospitalier Universitaire de Bordeaux Hospital Saint Andre
Bordeaux, 33075
Hopital Claude Huriez
Lille, 59000
Hopital Saint Eloi
Montpellier, 34295
Local Institution - 0003
Nantes, 44093
Local Institution - 0155
Nice, 06200
Hopital Saint Louis
Paris, 75475
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69310
CHU Charles Nicolle
Rouen, 76000
Local Institution - 0009
Saint-Priest-en-Jarez, 42270
Local Institution - 0002
Toulouse, 31059
Institute Gustave Roussy
Villejuif, 94805
United Kingdom11 sites
Local Institution - 0078
Belfast, BT9 7AB
Local Institution - 0076
Cambridge, CB2 0QQ
Local Institution - 0079
Cottingham, HU16 5JQ
Local Institution
Edinburgh, Midlothian, EH16 4SB
Local Institution - 0137
Liverpool, L7 8YA
Local Institution - 0077
London, SW17 0RE
Local Institution - 0074
London, SW36JJ
Local Institution - 0075
Manchester, M20 4BX
Local Institution - 0132
Southampton, Hampshire, SO16 6YD
Local Institution - 0131
Sutton, Surrey, SM25PT
Local Institution - 0142
Tauton, TA1 5DA
Australia10 sites
Local Institution - 0058
Cairns, Queensland, 4870
Local Institution - 0146
Coffs Harbour, New South Wales, 2450
Local Institution - 0172
Elizabeth Vale, South Australia, 5112
Local Institution
Greenslopes, Queensland, 4120
Local Institution - 0054
Melbourne, Victoria, 3000
Local Institution - 0143
Melbourne, Victoria, 3004
Local Institution - 0057
Nedlands, Western Australia, 6009
Local Institution - 0097
Nedlands, Western Australia, 6009
Local Institution - 0053
North Sydney, New South Wales, 2060
Local Institution - 0056
Woolloongabba, Queensland, 4102
Italy10 sites
Local Institution - 0044
Bari, 70124
ASST Papa Giovanni XXIII
Bergamo, 24127
Local Institution - 0113
Meldola (FC), 47014
Local Institution - 0045
Milan, Lombardy, 20141
IRCCS Istituto Nazionale Tumori Milano
Milan, 20133
Local Institution - 0043
Naples, 80131
Istituto Oncologico Veneto IOV
Padova, 35128
Local Institution - 0042
Siena, 53100
Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
Torino, 10060
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
Turin, Piedmont, 10126
Spain9 sites
Local Institution - 0116
Barcelona, 08035
Local Institution - 0115
Barcelona, 08036
Local Institution - 0123
Córdoba, 14004
Local Institution - 0190
Doniostia - San Sebastian, 20014
Local Institution
Donostia / San Sebastian, 20014
Local Institution - 0118
Jaén, 23007
Local Institution - 0114
Madrid, 28007
Local Institution - 0119
Santiago Compostela, 15706
Local Institution - 0117
Valencia, 46014
Brazil8 sites
Local Institution - 0126
Barretos, São Paulo, 14780-070
Local Institution - 0125
Belo Horizonte, Minas Gerais, 30130-090
Local Institution - 0168
Fortaleza, Ceará, 60130-241
Local Institution - 0124
Ijuí, Rio Grande do Sul, 98700-000
Local Institution - 0171
Itajaí, Santa Catarina, 88301-220
Local Institution - 0127
Porto Alegre, Rio Grande do Sul, 90610-000
Local Institution - 0182
Rio de Janeiro, 20231-050
Local Institution - 0169
São Paulo, 01509-010
Canada7 sites
Local Institution - 0068
Abbotsford British Columbia, British Columbia, V2S 0C2
Local Institution - 0121
Edmonton, T6X 1E8
Local Institution - 0066
Hamilton, Ontario, L8V 5C2
Local Institution - 0067
Kitchener, Ontario, N2G 1G3
Local Institution
Québec, Quebec, G1R 2J6
Local Institution - 0139
St. John's, Newfoundland and Labrador, A1B 3V6
Local Institution - 0041
Toronto, Ontario, M5G 2M9
Mexico7 sites
Local Institution - 0178
Cancún, Quintana Roo, 77500
Local Institution - 0175
Mexico City, Mexico City, 03100
Local Institution - 0177
Monterrey, Nuevo León, 64460
Local Institution - 0180
Monterrey, Nuevo León, 64710
Local Institution - 0179
Puebla City, 72424
Local Institution - 0181
San Luis Potosí City, 78200
Local Institution - 0176
Zapopan, Jalisco, 45070
Argentina5 sites
Local Institution - 0107
Buenos Aires, Buenos Aires F.D., C1118AAT
Local Institution - 0183
Buenos Aires, Distrito Federal, C1017
Local Institution - 0108
CABA, 1426
Local Institution - 0109
Ciudad Autonoma de Buenos Aires, Buenos Aires, 1430
Local Institution - 0157
Córdoba, 5000
Netherlands5 sites
Local Institution - 0101
Amsterdam, 1066CX
Local Institution - 0102
Amsterdam, 1081 HV
Local Institution - 0099
Leiden, 2333 ZA
Local Institution - 0100
Nijmegen, 6525 GA
Local Institution - 0147
Untrecht, 3584CX
Czechia4 sites
Local Institution - 0094
Brno, 656 53
Local Institution - 0093
Hradec Králové, 500 05
Local Institution - 0091
Prague, 100 34
Local Institution - 0092
Prague, 128 08
Ireland4 sites
Local Institution - 0129
Dublin, Dublin, 0
Local Institution - 0128
Dublin, 4
Local Institution - 0130
Dublin, Dublin 7
Local Institution - 0136
Wilton, CORK, 0
Romania4 sites
Local Institution - 0162
Bucharest, 022328
Local Institution - 0070
Cluj-Napoca, 400015
Local Institution - 0071
Craiova, 200542
Local Institution - 0120
Floreşti, 407280
Russia4 sites
Local Institution - 0149
Krasnoyarsk, 660133
Local Institution - 0086
Moscow, 105229
Local Institution - 0111
Moscow, 115478
Local Institution - 0148
Moscow, 121309
Austria3 sites
Local Institution - 0034
Graz, 8036
Local Institution - 0035
Salzburg, 5020
Local Institution - 0033
Vienna, 1090
Belgium3 sites
Local Institution - 0083
Brussels, 1000
Local Institution - 0084
Hasselt, 3500
Local Institution - 0085
Leuven, B-3000
Finland3 sites
Local Institution - 0167
KYS, 70029
Local Institution - 0166
Tampere, Oulun Lääni, FI-33520
Local Institution - 0165
Turku, 20520
Greece3 sites
Local Institution - 0038
Athens, 11526
Local Institution - 0039
Neo Faliro, 18547
Local Institution - 0040
Thessaloniki, 57001
Israel3 sites
Local Institution - 0098
Beersheba, 84101
Local Institution - 0088
Jerusalem, 91120
Local Institution - 0089
Ramat Gan, 52621
New Zealand3 sites
Local Institution - 0159
Auckland, 1142
Local Institution - 0063
Christchurch, 8011
Local Institution - 0062
Wellington, 6021
Switzerland3 sites
Local Institution - 0104
Bern, 3010
Local Institution - 0105
Lausanne, 1011
Local Institution - 0036
Zurich, 8091
Chile2 sites
Local Institution - 0174
Recoleta, Santiago Metropolitan, 0
Local Institution - 0173
Santiago, Santiago Metropolitan, 8330024
Poland2 sites
Local Institution - 0152
Bydgoszcz, 85-796
Local Institution - 0090
Warsaw, 02-781
Portugal2 sites
Local Institution - 0134
Lisbon, 1649-035
Local Institution - 0133
Porto, 4200-072
Sweden2 sites
Local Institution - 0163
Gothenburg, 413 45
Local Institution - 0164
Lund, 222 42
About this study
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
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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NKTR-214Biological
Also called Bempegaldesleukin, BMS-986321
Specified dose on specified days
NivolumabBiological
Also called Opdivo, BMS-936558
Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Combination | Experimental | NKTR-214 + Nivolumab Receives: Biological: NKTR-214; Biological: Nivolumab |
| Monotherapy | Experimental | Nivolumab Receives: Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
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.
Measured: From date of randomization to disease progression (Up to 37 months)
Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR)
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.
Measured: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)
Overall Survival (OS)
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.
Measured: From date of randomization to date of death (Up to 37 months)
Secondary outcomes (13)
Clinical Benefit Rate (CBR) Per Blinded Independent Central Review (BICR)
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.
Measured: From date of randomization to disease progression (Up to 37 months)
Duration of Response (DoR) Per Blinded Independent Central Review (BICR)
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.
Measured: From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months)
Time to Objective Response (TTR) Per Blinded Independent Central Review (BICR)
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.
Measured: From date of randomization to disease progression (Up to 37 months)
Objective Response Rate (ORR) Per Investigator
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.
Measured: From date of randomization to disease progression (Up to 37 months)
Progression-free Survival (PFS) Per Investigator
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.
Measured: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)
Clinical Benefit Rate (CBR) Per Investigator
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.
Measured: From date of randomization to disease progression (Up to 37 months)
Duration of Response (DoR) Per Investigator
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.
Measured: From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months)
Time to Objective Response (TTR) Per Investigator
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.
Measured: From date of randomization to disease progression (Up to 37 months)
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status
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.
Measured: From date of randomization to disease progression (Up to 37 months)
Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status
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.
Measured: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)
Overall Survival (OS) by Baseline PD-L1 Status
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.
Measured: From date of randomization to date of death (Up to 37 months)
Number of Participants With Adverse Events (AEs)
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.
Measured: From first dose to 30 days post last dose (Average of 11 months and a maximum up to 26 months)
Number of Participants With On-Treatment Laboratory Parameters That Worsened Relative to Baseline
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 event
Measured: From first dose to 100 days post last dose (Average of 13 months and a maximum up to 28 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2018
- Study start21 Sep 2018
- Primary completion19 Nov 2021
- Study completion19 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 783 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Nektar Therapeutics
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03635983
- Sponsor's protocol ID
- CA045-001
- Other IDs
- 2018-001423-40, 17-214-08, 2018
- Status last verified
- Mar 2025
- First submitted
- 16 Aug 2018
- Last updated
- 1 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Diab A, Gogas H, Sandhu S, Long GV, Ascierto PA, Larkin J, Sznol M, Franke F, Ciuleanu TE, Pereira C, Munoz Couselo E, Bronzon Damian F, Schenker M, Perfetti A, Lebbe C, Quereux G, Meier F, Curti BD, Rojas C, Arriaga Y, Yang H, Zhou M, Ravimohan S, Statkevich P, Tagliaferri MA, Khushalani NI. Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results. J Clin Oncol. 2023 Oct 20;41(30):4756-4767. doi: 10.1200/JCO.23.00172. Epub 2023 Aug 31.
PubMed 37651676Khushalani 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.
PubMed 32723187
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03635983
- Acronym / sponsor ID
- CA045-001
- Conditions
- Melanoma
- Keywords
- NKTR-214, Nivolumab, Immunotherapy, bempegaldesleukin (BEMPEG: NKTR-214)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 783 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Collaborators
- Nektar Therapeutics
- Study start
- 21 Sep 2018 (actual)
- Primary completion
- 19 Nov 2021 (actual)
- Study completion
- 19 Mar 2024 (actual)
- First posted
- 17 Aug 2018 (actual)
- Results
- Posted 19 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Combination | Experimental | Biological: NKTR-214, Biological: NivolumabNKTR-214 + Nivolumab |
| Monotherapy | Experimental | Biological: NivolumabNivolumab |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- Active brain metastases or leptomeningeal metastases
- Uveal melanoma
- Participants with an active, known or suspected autoimmune disease
- Other protocol defined inclusion/exclusion criteria apply
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NKTR-214Also: Bempegaldesleukin, BMS-986321Specified dose on specified days | Biological | Combination |
| NivolumabAlso: Opdivo, BMS-936558Specified dose on specified days | Biological | Combination, Monotherapy |
Primary outcome
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
Time frame: 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.
Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR)
Time frame: 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.
Overall Survival (OS)
Time frame: 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.
13 secondary outcomes
Clinical Benefit Rate (CBR) Per Blinded Independent Central Review (BICR)
Time frame: From date of randomization to disease progression (Up to 37 months)
Duration of Response (DoR) Per Blinded Independent Central Review (BICR)
Time frame: From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months)
Time to Objective Response (TTR) Per Blinded Independent Central Review (BICR)
Time frame: From date of randomization to disease progression (Up to 37 months)
Objective Response Rate (ORR) Per Investigator
Time frame: From date of randomization to disease progression (Up to 37 months)
Progression-free Survival (PFS) Per Investigator
Time frame: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)
Clinical Benefit Rate (CBR) Per Investigator
Time frame: From date of randomization to disease progression (Up to 37 months)
Duration of Response (DoR) Per Investigator
Time frame: From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months)
Time to Objective Response (TTR) Per Investigator
Time frame: From date of randomization to disease progression (Up to 37 months)
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status
Time frame: From date of randomization to disease progression (Up to 37 months)
Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status
Time frame: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)
Overall Survival (OS) by Baseline PD-L1 Status
Time frame: From date of randomization to date of death (Up to 37 months)
Number of Participants With Adverse Events (AEs)
Time frame: From first dose to 30 days post last dose (Average of 11 months and a maximum up to 26 months)
Number of Participants With On-Treatment Laboratory Parameters That Worsened Relative to Baseline
Time frame: From first dose to 100 days post last dose (Average of 13 months and a maximum up to 28 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37651676Diab A, Gogas H, Sandhu S, Long GV, Ascierto PA, Larkin J, Sznol M, Franke F, Ciuleanu TE, Pereira C, Munoz Couselo E, Bronzon Damian F, Schenker M, Perfetti A, Lebbe C, Quereux G, Meier F, Curti BD, Rojas C, Arriaga Y, Yang H, Zhou M, Ravimohan S, Statkevich P, Tagliaferri MA, Khushalani NI. Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results. J Clin Oncol. 2023 Oct 20;41(30):4756-4767. doi: 10.1200/JCO.23.00172. Epub 2023 Aug 31.
- Derived from this study: PubMed 32723187Khushalani 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.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
167 sites in 27 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NKTR-214 and Nivolumab in people with Melanoma, run by Bristol-Myers Squibb at 167 sites in 27 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 167 sites in United States, Germany, France, United Kingdom, Australia and 22 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) (time frame: From date of randomization to disease progression (Up to 37 months)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03635983, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2025.