A Study to Assess Adjuvant Immunotherapy With Nivolumab Plus Relatlimab Versus Nivolumab Alone After Complete Resection of Stage III-IV Melanoma

NCT ID: NCT05002569

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1093 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-19
• Study Completion Date: 2025-04-02

Brief Summary

The purpose of this study is to assess nivolumab plus relatlimab fixed-dose combination (FDC) versus nivolumab alone in participants with completely resected stage III-IV melanoma.

Conditions

Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm A: Nivolumab Plus Relatlimab

Combination

Group Type: EXPERIMENTAL

Nivolumab + Relatlimab Fixed Dose Combination

Intervention Type: BIOLOGICAL

Specified dose on specified days

Arm B: Nivolumab

Monotherapy

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

Specified dose on specified days

Interventions

Nivolumab

Specified dose on specified days

Intervention Type: BIOLOGICAL

Nivolumab + Relatlimab Fixed Dose Combination

Specified dose on specified days

Intervention Type: BIOLOGICAL

Other Intervention Names

Opdivo; BMS-936558; BMS-986213; Opdualag

Eligibility Criteria

Inclusion Criteria

• Must have been diagnosed with either Stage IIIA (> 1 mm tumor in lymph node)/B/C/D or Stage IV melanoma by American Joint Committee on Cancer (AJCC) v8 and have histologically confirmed melanoma that is completely surgically resected (free of disease) with negative margins in order to be eligible
• Participants ≥ 18 years of age must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1. Adolescent participants between 12 and < 18 years of age must have a Lansky/Karnofsky performance score ≥ 80%
• Complete resection must be performed within 90 days prior to randomization
• All participants must have disease-free status documented by a complete physical examination within 14 days prior to randomization and imaging studies within 35 days prior to randomization
• Tumor tissue must be provided for biomarker analyses

Exclusion Criteria

• History of ocular melanoma
• Untreated/unresected CNS metastases or leptomeningeal metastases
• Active, known, or suspected autoimmune disease
• Participants with serious or uncontrolled medical disorder
• Prior immunotherapy treatment for any prior malignancy: No prior immunotherapies are permitted
• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 4 weeks prior to screening
• History of myocarditis, regardless of etiology.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution - 0176

Birmingham, Alabama, United States

Local Institution - 0164

Springdale, Arkansas, United States

Local Institution - 0200

Los Angeles, California, United States

Local Institution - 0185

Palo Alto, California, United States

Local Institution - 0162

San Francisco, California, United States

Saint John's Cancer Institute

Santa Monica, California, United States

Local Institution - 0138

Aurora, Colorado, United States

Local Institution - 0166

Washington D.C., District of Columbia, United States

Local Institution - 0243

Miami, Florida, United States

Washington University School Of Medicine

Miami, Florida, United States

Local Institution - 0179

Pensacola, Florida, United States

Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center

Tampa, Florida, United States

Local Institution - 0191

Atlanta, Georgia, United States

Local Institution - 0148

Atlanta, Georgia, United States

Local Institution - 0202

Chicago, Illinois, United States

Local Institution - 0177

Peoria, Illinois, United States

Local Institution - 0223

Fort Wayne, Indiana, United States

University of Iowa-Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Local Institution - 0178

Westwood, Kansas, United States

Dana-Farber Cancer Institute-Melanoma

Boston, Massachusetts, United States

Local Institution - 0258

Ann Arbor, Michigan, United States

Local Institution

Grand Rapids, Michigan, United States

Local Institution - 0133

Minneapolis, Minnesota, United States

Local Institution - 0139

Hackensack, New Jersey, United States

Local Institution - 0206

Morristown, New Jersey, United States

Local Institution - 0140

New York, New York, United States

Icahn School Of Medicine At Mount Sinai

New York, New York, United States

Local Institution - 0210

New York, New York, United States

Local Institution - 0130

Charlotte, North Carolina, United States

Local Institution - 0145

Durham, North Carolina, United States

MetroHealth Medical Center

Cleveland, Ohio, United States

Local Institution - 0141

Cleveland, Ohio, United States

The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C

Columbus, Ohio, United States

Local Institution - 0267

Allentown, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Local Institution - 0125

Pittsburgh, Pennsylvania, United States

Local Institution - 0171

Charleston, South Carolina, United States

Local Institution - 0147

Germantown, Tennessee, United States

Local Institution - 0183

Nashville, Tennessee, United States

Local Institution - 0146

Austin, Texas, United States

Local Institution - 0163

Dallas, Texas, United States

Local Institution - 0172

Houston, Texas, United States

Local Institution - 0137

Fairfax, Virginia, United States

Local Institution - 0003

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Local Institution - 0005

Buenos Aires, Distrito Federal, Argentina

Local Institution - 0001

CABA, Distrito Federal, Argentina

Local Institution - 0002

Ciudad de Buenos Aires, Distrito Federal, Argentina

Local Institution - 0004

Córdoba, , Argentina

Local Institution - 0030

Waratah, New South Wales, Australia

Local Institution - 0252

Westmead, New South Wales, Australia

Local Institution - 0032

Wollstonecraft, New South Wales, Australia

Local Institution - 0254

Tiwi, Northern Territory, Australia

Local Institution - 0028

Brisbane, Queensland, Australia

Local Institution - 0027

Southport, Queensland, Australia

Local Institution - 0250

Woodville, South Australia, Australia

Local Institution - 0035

Ballarat, Victoria, Australia

Local Institution - 0253

Heidelberg, Victoria, Australia

Local Institution - 0031

Melbourne, Victoria, Australia

Local Institution - 0251

Murdoch, Western Australia, Australia

Local Institution - 0029

Perth, Western Australia, Australia

Local Institution - 0082

Graz, Styria, Austria

Local Institution - 0086

Salzburg, , Austria

Local Institution - 0084

Vienna, , Austria

Local Institution - 0110

Brussels, , Belgium

Local Institution - 0105

Brussels, , Belgium

Local Institution - 0109

Liège, , Belgium

Local Institution - 0106

Wilrijk, , Belgium

Local Institution - 0072

Fortaleza, Ceará, Brazil

Local Institution - 0068

Vitória, Espírito Santo, Brazil

Local Institution - 0071

Salvador, Estado de Bahia, Brazil

Local Institution - 0047

Belo Horizonte, Minas Gerais, Brazil

Local Institution - 0056

Ijuí, Rio Grande do Sul, Brazil

Local Institution - 0257

Porto Alegre, Rio Grande do Sul, Brazil

Local Institution - 0049

Porto Alegre, Rio Grande do Sul, Brazil

Local Institution - 0048

Santa Cruz do Sul, Rio Grande do Sul, Brazil

Local Institution - 0070

Barretos, São Paulo, Brazil

Local Institution - 0058

Rio de Janeiro, , Brazil

Local Institution - 0155

Edmonton, Alberta, Canada

Local Institution - 0175

Vancouver, British Columbia, Canada

Local Institution - 0197

Halifax, Nova Scotia, Canada

Local Institution - 0159

Montreal, Quebec, Canada

Local Institution - 0158

Montreal, Quebec, Canada

Local Institution - 0160

Québec, Quebec, Canada

Local Institution - 0198

Sherbrooke, Quebec, Canada

Local Institution - 0013

Santiago, Santiago Metropolitan, Chile

Local Institution - 0006

Santiago, Santiago Metropolitan, Chile

Local Institution - 0014

Santiago, Santiago Metropolitan, Chile

Local Institution - 0221

Hefei, Anhui, China

Local Institution - 0259

Beijing, Beijing Municipality, China

Local Institution - 0261

Beijing, Beijing Municipality, China

Local Institution - 0214

Beijing, Beijing Municipality, China

Local Institution - 0241

Chongqing, Chongqing Municipality, China

Local Institution - 0245

Fuzhou, Fujian, China

Local Institution - 0217

Guangzhou, Guangdong, China

Local Institution - 0226

Zhengzhou, Henan, China

Local Institution - 0237

Wuhan, Hubei, China

Local Institution - 0239

Wuhan, Hubei, China

Local Institution - 0234

Changsha Shi, Hunan, China

Local Institution - 0215

Nanjing, Jiangsu, China

Local Institution - 0225

Nanjing, Jiangsu, China

Local Institution - 0224

Nanchang, Jiangxi, China

Local Institution - 0219

Changchun, Jilin, China

Local Institution - 0242

Shenyang, Liaoning, China

Local Institution - 0230

Chengdu, Sichuan, China

Local Institution - 0263

Tianjin, Tianjin Municipality, China

Local Institution - 0228

Ürümqi, Xinjiang, China

Local Institution - 0222

Kunming, Yunnan, China

Local Institution - 0220

Hangzhou, Zhejiang, China

Local Institution - 0216

Hangzhou, Zhejiang, China

Local Institution - 0244

Taiyuan, , China

Local Institution - 0156

Brno, , Czechia

Local Institution - 0091

Hradec Králové, , Czechia

Local Institution - 0026

Ostrava, , Czechia

Local Institution - 0062

Prague, , Czechia

Local Institution - 0016

Aarhus, Central Jutland, Denmark

Local Institution - 0022

Aalborg, , Denmark

Local Institution - 0018

Copenhagen, , Denmark

Local Institution - 0020

Odense, , Denmark

Helsinki University Hospital Adult ICU PPDS

Helsinki, , Finland

Local Institution - 0019

Tampere, , Finland

Local Institution - 0015

Turku, , Finland

Local Institution - 0040

Villejuif, Val-de-Marne, France

Local Institution - 0043

Dijon, , France

Local Institution - 0044

Marseille, , France

Local Institution - 0039

Nantes, , France

Local Institution - 0042

Paris, , France

Local Institution - 0041

Pierre-Bénite, , France

Local Institution - 0046

Toulouse, , France

Local Institution - 0092

Tübingen, Baden-Wurttemberg, Germany

Local Institution - 0079

Hanover, Lower Saxony, Germany

Local Institution - 0073

Buxtehude, , Germany

Local Institution - 0077

Dresden, , Germany

Local Institution - 0074

Erlangen, , Germany

Local Institution - 0131

Essen, , Germany

Local Institution - 0081

Gera, , Germany

Local Institution - 0075

Heidelberg, , Germany

Local Institution - 0078

Lübeck, , Germany

Local Institution - 0083

Minden, , Germany

Local Institution - 0076

Munich, , Germany

Local Institution - 0080

Würzburg, , Germany

Local Institution - 0114

Athens, , Greece

Local Institution - 0113

Neo Faliro, , Greece

Local Institution - 0112

Thessaloniki, , Greece

Local Institution - 0199

Petah Tikva, Central District, Israel

Local Institution - 0118

Jerusalem, Jerusalem, Israel

Local Institution - 0116

Afula, , Israel

Local Institution - 0117

Ramat Gan, , Israel

Local Institution - 0115

Milan, , Italy

Local Institution - 0268

Milan, , Italy

Local Institution - 0123

Milan, , Italy

Local Institution - 0119

Napoli, , Italy

Local Institution - 0120

Padua, , Italy

Local Institution - 0122

Perugia, , Italy

Local Institution - 0121

Siena, , Italy

Local Institution - 0021

Zapopan, Jalisco, Mexico

Local Institution - 0100

Benito Juárez, Mexico City, Mexico

Local Institution - 0093

México, Nuevo León, Mexico

Local Institution - 0098

Oaxaca City, , Mexico

Local Institution - 0009

Lørenskog, Akershus, Norway

Local Institution - 0023

Stavanger, Rogaland, Norway

Local Institution - 0017

Oslo, , Norway

Local Institution - 0249

Coimbra, , Portugal

Local Institution - 0170

Brasov, , Romania

Local Institution - 0065

Cluj-Napoca, , Romania

Local Institution - 0066

Craiova, , Romania

Local Institution - 0064

Floresti/ Cluj, , Romania

Local Institution - 0188

Badajoz, , Spain

Local Institution - 0201

Barcelona, , Spain

Local Institution - 0151

Donostia / San Sebastian, , Spain

Local Institution - 0153

Granada, , Spain

Local Institution - 0150

Madrid, , Spain

Local Institution - 0152

Valencia, , Spain

Local Institution - 0010

Gothenburg, , Sweden

Local Institution - 0011

Lund, , Sweden

Local Institution - 0012

Solna, , Sweden

Local Institution - 0085

Basel, , Switzerland

Local Institution - 0087

Chur, , Switzerland

Local Institution - 0090

Zurich, , Switzerland

Local Institution - 0101

Nottingham, Nottinghamshire, United Kingdom

Local Institution - 0102

Bristol, , United Kingdom

Local Institution - 0187

Glasgow, , United Kingdom

Local Institution - 0154

Newcastle upon Tyne, , United Kingdom

Local Institution - 0232

Oxford, , United Kingdom

Local Institution - 0127

Southampton, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Canada; Chile; China; Czechia; Denmark; Finland; France; Germany; Greece; Israel; Italy; Mexico; Norway; Portugal; Romania; Spain; Sweden; Switzerland; United Kingdom

References

Long GV, Garnett-Benson C, Dolfi S, Ascierto PA, Guo J, Tarhini AA, Chandra S, Munoz-Couselo E, Del Vecchio M, de Melo AC, Callahan M, Gogas H, Dummer R, Schadendorf D, Koelblinger P, Quereux G, Thomas I, Yu JX, Fisher A, Wang B, Djidel P, Chouzy A, Semaan M, Chen B, Cheong AMY, Tawbi HA. Adjuvant nivolumab and relatlimab in stage III/IV melanoma: the randomized phase 3 RELATIVITY-098 trial. Nat Med. 2025 Dec;31(12):4301-4309. doi: 10.1038/s41591-025-04032-8. Epub 2025 Oct 18.

Reference Type: DERIVED

PMID: 41109920 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

http://www.BMSClinicalTrials.com

BMS Clinical Trial Patient Recruiting

Other Identifiers

2021-001641-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA224-098

Identifier Type: -

Identifier Source: org_study_id