A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma

NCT03635983 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: CA045-0012018-001423-4017-214-08
• Study Type: interventional
• Target: 783
• Locations: 26 countries
• Sites: 164

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

Conditions

Melanoma

Keywords

NKTR-214; Nivolumab; Immunotherapy; bempegaldesleukin (BEMPEG: NKTR-214)

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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)

  From date of randomization to disease progression (Up to 37 months)

• Duration 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)

• Time to Objective Response (TTR) Per Blinded Independent Central Review (BICR)

  From date of randomization to disease progression (Up to 37 months)

• Objective Response Rate (ORR) Per Investigator

  From date of randomization to disease progression (Up to 37 months)

• Progression-free Survival (PFS) Per Investigator

  From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)

Study Arms (2)

Combination

EXPERIMENTAL

NKTR-214 + Nivolumab

Biological: NKTR-214; Biological: Nivolumab

Monotherapy

EXPERIMENTAL

Nivolumab

Biological: Nivolumab

Interventions

NKTR-214 BIOLOGICAL

Specified dose on specified days

Also known as: Bempegaldesleukin, BMS-986321

Combination

Nivolumab BIOLOGICAL

Specified dose on specified days

Also known as: Opdivo, BMS-936558

Combination; Monotherapy

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Nektar Therapeutics: collaborator

Study Sites (167)

Local Institution - 0187

Tucson, Arizona, 85724, United States

Location

Local Institution - 0014

La Jolla, California, 92093, United States

Location

Local Institution - 0122

Stanford, California, 94305, United States

Location

Local Institution - 0051

Aurora, Colorado, 80045, United States

Location

Local Institution - 0065

New Haven, Connecticut, 06510, United States

Location

Local Institution - 0153

Miami, Florida, 33136, United States

Location

Local Institution - 0017

Miami Beach, Florida, 33140, United States

Location

Local Institution - 0112

Tampa, Florida, 33612, United States

Location

Local Institution - 0012

Atlanta, Georgia, 30322-1013, United States

Location

Local Institution - 0019

Louisville, Kentucky, 40202, United States

Location

Local Institution - 0018

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0188

Ann Arbor, Michigan, 48109, United States

Location

Local Institution - 0186

Fridley, Minnesota, 55432, United States

Location

Local Institution - 0135

St Louis, Missouri, 63110, United States

Location

Local Institution - 0016

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 0185

New Brunswick, New Jersey, 08903, United States

Location

Local Institution - 0141

New York, New York, 10065, United States

Location

Local Institution - 0037

Cleveland, Ohio, 44195, United States

Location

Local Institution - 0011

Portland, Oregon, 97213, United States

Location

Local Institution - 0013

Portland, Oregon, 97239, United States

Location

St. Luke's Hospital & Health Network

Easton, Pennsylvania, 18045, United States

Location

Local Institution - 0015

Philadelphia, Pennsylvania, 19111, United States

Location

Local Institution - 0001

Houston, Texas, 77030, United States

Location

Local Institution - 0064

Fairfax, Virginia, 22031, United States

Location

Local Institution - 0109

Ciudad Autonoma de Buenos Aires, Buenos Aires, 1430, Argentina

Location

Local Institution - 0107

Buenos Aires, Buenos Aires F.D., C1118AAT, Argentina

Location

Local Institution - 0183

Buenos Aires, Distrito Federal, C1017, Argentina

Location

Local Institution - 0108

CABA, 1426, Argentina

Location

Local Institution - 0157

Córdoba, 5000, Argentina

Location

Local Institution - 0146

Coffs Harbour, New South Wales, 2450, Australia

Location

Local Institution - 0053

North Sydney, New South Wales, 2060, Australia

Location

Local Institution - 0058

Cairns, Queensland, 4870, Australia

Location

Local Institution

Greenslopes, Queensland, 4120, Australia

Location

Local Institution - 0056

Woolloongabba, Queensland, 4102, Australia

Location

Local Institution - 0172

Elizabeth Vale, South Australia, 5112, Australia

Location

Local Institution - 0054

Melbourne, Victoria, 3000, Australia

Location

Local Institution - 0143

Melbourne, Victoria, 3004, Australia

Location

Local Institution - 0057

Nedlands, Western Australia, 6009, Australia

Location

Local Institution - 0097

Nedlands, Western Australia, 6009, Australia

Location

Local Institution - 0034

Graz, 8036, Austria

Location

Local Institution - 0035

Salzburg, 5020, Austria

Location

Local Institution - 0033

Vienna, 1090, Austria

Location

Local Institution - 0083

Brussels, 1000, Belgium

Location

Local Institution - 0084

Hasselt, 3500, Belgium

Location

Local Institution - 0085

Leuven, B-3000, Belgium

Location

Local Institution - 0168

Fortaleza, Ceará, 60130-241, Brazil

Location

Local Institution - 0125

Belo Horizonte, Minas Gerais, 30130-090, Brazil

Location

Local Institution - 0124

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Local Institution - 0127

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Local Institution - 0171

Itajaí, Santa Catarina, 88301-220, Brazil

Location

Local Institution - 0126

Barretos, São Paulo, 14780-070, Brazil

Location

Local Institution - 0182

Rio de Janeiro, 20231-050, Brazil

Location

Local Institution - 0169

São Paulo, 01509-010, Brazil

Location

Local Institution - 0068

Abbotsford, British Columbia, V2S 0C2, Canada

Location

Local Institution - 0139

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Local Institution - 0066

Hamilton, Ontario, L8V 5C2, Canada

Location

Local Institution - 0067

Kitchener, Ontario, N2G 1G3, Canada

Location

Local Institution - 0041

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution

Québec, Quebec, G1R 2J6, Canada

Location

Local Institution - 0121

Edmonton, T6X 1E8, Canada

Location

Local Institution - 0174

Recoleta, Santiago Metropolitan, 0, Chile

Location

Local Institution - 0173

Santiago, Santiago Metropolitan, 8330024, Chile

Location

Local Institution - 0094

Brno, 656 53, Czechia

Location

Local Institution - 0093

Hradec Králové, 500 05, Czechia

Location

Local Institution - 0091

Prague, 100 34, Czechia

Location

Local Institution - 0092

Prague, 128 08, Czechia

Location

Local Institution - 0166

Tampere, Oulun Lääni, FI-33520, Finland

Location

Local Institution - 0167

KYS, 70029, Finland

Location

Local Institution - 0165

Turku, 20520, Finland

Location

Centre Hospitalier Universitaire de Bordeaux Hospital Saint Andre

Bordeaux, 33075, France

Location

Hopital Claude Huriez

Lille, 59000, France

Location

Hopital Saint Eloi

Montpellier, 34295, France

Location

Local Institution - 0003

Nantes, 44093, France

Location

Local Institution - 0155

Nice, 06200, France

Location

Hopital Saint Louis

Paris, 75475, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69310, France

Location

CHU Charles Nicolle

Rouen, 76000, France

Location

Local Institution - 0009

Saint-Priest-en-Jarez, 42270, France

Location

Local Institution - 0002

Toulouse, 31059, France

Location

Institute Gustave Roussy

Villejuif, 94805, France

Location

Local Institution - 0031

Buxtehude, 21614, Germany

Location

Local Institution - 0029

Dresden, 01307, Germany

Location

Local Institution - 0192

Erfurt, 99089, Germany

Location

Local Institution - 0026

Essen, 45147, Germany

Location

Local Institution - 0030

Göttingen, 37075, Germany

Location

Local Institution - 0023

Hamburg, 20251, Germany

Location

Local Institution - 0024

Hanover, D30625, Germany

Location

Local Institution - 0020

Heidelberg, 69120, Germany

Location

Local Institution - 0028

Kiel, 24105, Germany

Location

Local Institution - 0022

Leipzig, 04103, Germany

Location

Local Institution - 0021

München, 80337, Germany

Location

Local Institution - 0027

Münster, 48157, Germany

Location

Local Institution - 0060

Regensburg, 93053, Germany

Location

Local Institution - 0025

Tübingen, 72076, Germany

Location

Local Institution - 0032

Würzburg, 97080, Germany

Location

Local Institution - 0038

Athens, 11526, Greece

Location

Local Institution - 0039

Neo Faliro, 18547, Greece

Location

Local Institution - 0040

Thessaloniki, 57001, Greece

Location

Local Institution - 0136

Wilton, CORK, 0, Ireland

Location

Local Institution - 0129

Dublin, Dublin, 0, Ireland

Location

Local Institution - 0128

Dublin, 4, Ireland

Location

Local Institution - 0130

Dublin, Dublin 7, Ireland

Location

Local Institution - 0098

Beersheba, 84101, Israel

Location

Local Institution - 0088

Jerusalem, 91120, Israel

Location

Local Institution - 0089

Ramat Gan, 52621, Israel

Location

Local Institution - 0045

Milan, Lombardy, 20141, Italy

Location

Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino

Turin, Piedmont, 10126, Italy

Location

Local Institution - 0044

Bari, 70124, Italy

Location

ASST Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Local Institution - 0113

Meldola (FC), 47014, Italy

Location

IRCCS Istituto Nazionale Tumori Milano

Milan, 20133, Italy

Location

Local Institution - 0043

Napoli, 80131, Italy

Location

Istituto Oncologico Veneto IOV

Padua, 35128, Italy

Location

Local Institution - 0042

Siena, 53100, Italy

Location

Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia

Torino, 10060, Italy

Location

Local Institution - 0176

Zapopan, Jalisco, 45070, Mexico

Location

Local Institution - 0175

Mexico City, Mexico City, 03100, Mexico

Location

Local Institution - 0177

Monterrey, Nuevo León, 64460, Mexico

Location

Local Institution - 0180

Monterrey, Nuevo León, 64710, Mexico

Location

Local Institution - 0178

Cancún, Quintana Roo, 77500, Mexico

Location

Local Institution - 0179

Puebla City, 72424, Mexico

Location

Local Institution - 0181

San Luis Potosí City, 78200, Mexico

Location

Local Institution - 0101

Amsterdam, 1066CX, Netherlands

Location

Local Institution - 0102

Amsterdam, 1081 HV, Netherlands

Location

Local Institution - 0099

Leiden, 2333 ZA, Netherlands

Location

Local Institution - 0100

Nijmegen, 6525 GA, Netherlands

Location

Local Institution - 0147

Untrecht, 3584CX, Netherlands

Location

Local Institution - 0159

Auckland, 1142, New Zealand

Location

Local Institution - 0063

Christchurch, 8011, New Zealand

Location

Local Institution - 0062

Wellington, 6021, New Zealand

Location

Local Institution - 0152

Bydgoszcz, 85-796, Poland

Location

Local Institution - 0090

Warsaw, 02-781, Poland

Location

Local Institution - 0134

Lisbon, 1649-035, Portugal

Location

Local Institution - 0133

Porto, 4200-072, Portugal

Location

Local Institution - 0162

Bucharest, 022328, Romania

Location

Local Institution - 0070

Cluj-Napoca, 400015, Romania

Location

Local Institution - 0071

Craiova, 200542, Romania

Location

Local Institution - 0120

Floreşti, 407280, Romania

Location

Local Institution - 0149

Krasnoyarsk, 660133, Russia

Location

Local Institution - 0086

Moscow, 105229, Russia

Location

Local Institution - 0111

Moscow, 115478, Russia

Location

Local Institution - 0148

Moscow, 121309, Russia

Location

Local Institution - 0116

Barcelona, 08035, Spain

Location

Local Institution - 0115

Barcelona, 08036, Spain

Location

Local Institution - 0123

Córdoba, 14004, Spain

Location

Local Institution - 0190

Doniostia - San Sebastian, 20014, Spain

Location

Local Institution

Donostia / San Sebastian, 20014, Spain

Location

Local Institution - 0118

Jaén, 23007, Spain

Location

Local Institution - 0114

Madrid, 28007, Spain

Location

Local Institution - 0119

Santiago Compostela, 15706, Spain

Location

Local Institution - 0117

Valencia, 46014, Spain

Location

Local Institution - 0163

Gothenburg, 413 45, Sweden

Location

Local Institution - 0164

Lund, 222 42, Sweden

Location

Local Institution - 0104

Bern, 3010, Switzerland

Location

Local Institution - 0105

Lausanne, 1011, Switzerland

Location

Local Institution - 0036

Zurich, 8091, Switzerland

Location

Local Institution - 0132

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Local Institution

Edinburgh, Midlothian, EH16 4SB, United Kingdom

Location

Local Institution - 0131

Sutton, Surrey, SM25PT, United Kingdom

Location

Local Institution - 0078

Belfast, BT9 7AB, United Kingdom

Location

Local Institution - 0076

Cambridge, CB2 0QQ, United Kingdom

Location

Local Institution - 0079

Cottingham, HU16 5JQ, United Kingdom

Location

Local Institution - 0137

Liverpool, L7 8YA, United Kingdom

Location

Local Institution - 0077

London, SW17 0RE, United Kingdom

Location

Local Institution - 0074

London, SW36JJ, United Kingdom

Location

Local Institution - 0075

Manchester, M20 4BX, United Kingdom

Location

Local Institution - 0142

Tauton, TA1 5DA, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 37651676 DERIVED

• 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.

  PMID: 32723187 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Melanoma

Interventions

bempegaldesleukin; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2018
• First Posted: August 17, 2018
• Study Start: September 21, 2018
• Primary Completion: November 19, 2021
• Study Completion: March 19, 2024
• Last Updated: April 1, 2025
• Results First Posted: December 19, 2022

Record last verified: 2025-03

Locations

BR (8); CA (7); CL (2); FR (11); RU (4); BE (3); IT (10); NL (5); PL (2); RO (4); DE (15); CH (3); GB (11); IL (3); AU (10); SE (2); AR (5); ME (7); FI (3); IE (4); PT (2); US (24); CZ (4); ES (9); NZ (3); GR (3)