A Study to Assess Adjuvant Immunotherapy With Nivolumab Plus Relatlimab Versus Nivolumab Alone After Complete Resection of Stage III-IV Melanoma (RELATIVITY-098)

A Phase 3, Randomized, Double-blind Study of Adjuvant Immunotherapy With Nivolumab + Relatlimab Fixed-dose Combination Versus Nivolumab Monotherapy After Complete Resection of Stage III-IV Melanoma

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.

Study Overview

• Status: Terminated
• Conditions: Melanoma
• Intervention / Treatment: Biological: Nivolumab; Biological: Nivolumab + Relatlimab Fixed Dose Combination

• Study Type: Interventional
• Enrollment (Actual): 1093
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina, X5002HWE
    • Local Institution - 0004
  • Buenos Aires
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1426ABP
      • Local Institution - 0003
  • Distrito Federal
    • Buenos Aires, Distrito Federal, Argentina, 1426
      • Local Institution - 0005
    • CABA, Distrito Federal, Argentina, C1430
      • Local Institution - 0001
    • Ciudad de Buenos Aires, Distrito Federal, Argentina, C1121ABE
      • Local Institution - 0002
• Australia
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Local Institution - 0030
    • Westmead, New South Wales, Australia, 2145
      • Local Institution - 0252
    • Wollstonecraft, New South Wales, Australia, 2065
      • Local Institution - 0032
  • Northern Territory
    • Tiwi, Northern Territory, Australia, 0810
      • Local Institution - 0254
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Local Institution - 0028
    • Southport, Queensland, Australia, 4215
      • Local Institution - 0027
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • Local Institution - 0250
  • Victoria
    • Ballarat, Victoria, Australia, 3350
      • Local Institution - 0035
    • Heidelberg, Victoria, Australia, 3084
      • Local Institution - 0253
    • Melbourne, Victoria, Australia, 3000
      • Local Institution - 0031
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Local Institution - 0251
    • Perth, Western Australia, Australia, 6009
      • Local Institution - 0029
• Austria
  • Salzburg, Austria, 5020
    • Local Institution - 0086
  • Vienna, Austria, 1090
    • Local Institution - 0084
  • Styria
    • Graz, Styria, Austria, 8036
      • Local Institution - 0082
• Belgium
  • Brussels, Belgium, 1090
    • Local Institution - 0110
  • Brussels, Belgium, 1200
    • Local Institution - 0105
  • Liège, Belgium, 4000
    • Local Institution - 0109
  • Wilrijk, Belgium, 2610
    • Local Institution - 0106
• Brazil
  • Rio de Janeiro, Brazil, 20220-410
    • Local Institution - 0058
  • Ceará
    • Fortaleza, Ceará, Brazil, 60135237
      • Local Institution - 0072
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil, 29055450
      • Local Institution - 0068
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 40170-070
      • Local Institution - 0071
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-090
      • Local Institution - 0047
  • Rio Grande do Sul
    • Ijuí, Rio Grande do Sul, Brazil, 98700-000
      • Local Institution - 0056
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Local Institution - 0257
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
      • Local Institution - 0049
    • Santa Cruz do Sul, Rio Grande do Sul, Brazil, 96830-180
      • Local Institution - 0048
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784400
      • Local Institution - 0070
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6X 1E8
      • Local Institution - 0155
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Local Institution - 0175
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Local Institution - 0197
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Local Institution - 0158
    • Montreal, Quebec, Canada, H2X 1P1
      • Local Institution - 0159
    • Québec, Quebec, Canada, G1J 1Z4
      • Local Institution - 0160
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Local Institution - 0198
• Chile
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 7510032
      • Local Institution - 0013
    • Santiago, Santiago Metropolitan, Chile, 8420383
      • Local Institution - 0006
    • Santiago, Santiago Metropolitan, Chile
      • Local Institution - 0014
• China
  • Taiyuan, China, 030032
    • Local Institution - 0244
  • Anhui
    • Hefei, Anhui, China, 230022
      • Local Institution - 0221
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100034
      • Local Institution - 0259
    • Beijing, Beijing Municipality, China, 100035
      • Local Institution - 0261
    • Beijing, Beijing Municipality, China, 100142
      • Local Institution - 0214
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400030
      • Local Institution - 0241
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Local Institution - 0245
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Local Institution - 0217
  • Henan
    • Zhengzhou, Henan, China, 450001
      • Local Institution - 0226
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Local Institution - 0237
    • Wuhan, Hubei, China, 430030
      • Local Institution - 0239
  • Hunan
    • Changsha Shi, Hunan, China, 410013
      • Local Institution - 0234
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Local Institution - 0215
    • Nanjing, Jiangsu, China, 210029
      • Local Institution - 0225
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Local Institution - 0224
  • Jilin
    • Changchun, Jilin, China, 130021
      • Local Institution - 0219
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • Local Institution - 0242
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Local Institution - 0230
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Local Institution - 0263
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830000
      • Local Institution - 0228
  • Yunnan
    • Kunming, Yunnan, China, 650106
      • Local Institution - 0222
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Local Institution - 0216
    • Hangzhou, Zhejiang, China, 310016
      • Local Institution - 0220
• Czechia
  • Brno, Czechia, 65653
    • Local Institution - 0156
  • Hradec Králové, Czechia, 50005
    • Local Institution - 0091
  • Ostrava, Czechia, 708 52
    • Local Institution - 0026
  • Prague, Czechia, 12808
    • Local Institution - 0062
• Denmark
  • Aalborg, Denmark, 9100
    • Local Institution - 0022
  • Copenhagen, Denmark, 2730
    • Local Institution - 0018
  • Odense, Denmark, 5000
    • Local Institution - 0020
  • Central Jutland
    • Aarhus, Central Jutland, Denmark, 8200
      • Local Institution - 0016
• Finland
  • Helsinki, Finland, 00290
    • Helsinki University Hospital Adult ICU PPDS
  • Tampere, Finland, 33520
    • Local Institution - 0019
  • Turku, Finland, 20521
    • Local Institution - 0015
• France
  • Dijon, France, 21000
    • Local Institution - 0043
  • Marseille, France, 13385
    • Local Institution - 0044
  • Nantes, France, 44093
    • Local Institution - 0039
  • Paris, France, 75010
    • Local Institution - 0042
  • Pierre-Bénite, France, 69310
    • Local Institution - 0041
  • Toulouse, France, 31100
    • Local Institution - 0046
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94800
      • Local Institution - 0040
• Germany
  • Buxtehude, Germany, 21614
    • Local Institution - 0073
  • Dresden, Germany, 01307
    • Local Institution - 0077
  • Erlangen, Germany, 91054
    • Local Institution - 0074
  • Essen, Germany, 45147
    • Local Institution - 0131
  • Gera, Germany, 07548
    • Local Institution - 0081
  • Heidelberg, Germany, D-69120
    • Local Institution - 0075
  • Lübeck, Germany, 23538
    • Local Institution - 0078
  • Minden, Germany, 32429
    • Local Institution - 0083
  • Munich, Germany, 80337
    • Local Institution - 0076
  • Würzburg, Germany, 97080
    • Local Institution - 0080
  • Baden-Wurttemberg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Local Institution - 0092
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Local Institution - 0079
• Greece
  • Athens, Greece, 11527
    • Local Institution - 0114
  • Neo Faliro, Greece, 185 47
    • Local Institution - 0113
  • Thessaloniki, Greece, 540 07
    • Local Institution - 0112
• Israel
  • Afula, Israel, 1834111
    • Local Institution - 0116
  • Ramat Gan, Israel, 5262100
    • Local Institution - 0117
  • Central District
    • Petah Tikva, Central District, Israel, 4941492
      • Local Institution - 0199
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 9112001
      • Local Institution - 0118
• Italy
  • Milan, Italy, 20133
    • Local Institution - 0115
  • Milan, Italy, 20133
    • Local Institution - 0268
  • Milan, Italy, 20141
    • Local Institution - 0123
  • Napoli, Italy, 80131
    • Local Institution - 0119
  • Padua, Italy, 35128
    • Local Institution - 0120
  • Perugia, Italy, 06132
    • Local Institution - 0122
  • Siena, Italy, 53100
    • Local Institution - 0121
• Mexico
  • Oaxaca City, Mexico, 68020
    • Local Institution - 0098
  • Jalisco
    • Zapopan, Jalisco, Mexico, 45070
      • Local Institution - 0021
  • Mexico City
    • Benito Juárez, Mexico City, Mexico, 03240
      • Local Institution - 0100
  • Nuevo León
    • México, Nuevo León, Mexico, 64320
      • Local Institution - 0093
• Norway
  • Oslo, Norway, 0310
    • Local Institution - 0017
  • Akershus
    • Lørenskog, Akershus, Norway, 1478
      • Local Institution - 0009
  • Rogaland
    • Stavanger, Rogaland, Norway, 4011
      • Local Institution - 0023
• Portugal
  • Coimbra, Portugal, 3000-075
    • Local Institution - 0249
• Romania
  • Brasov, Romania, 500283
    • Local Institution - 0170
  • Cluj-Napoca, Romania, 400015
    • Local Institution - 0065
  • Craiova, Romania, 200542
    • Local Institution - 0066
  • Floresti/ Cluj, Romania, 407280
    • Local Institution - 0064
• Spain
  • Badajoz, Spain, 06071
    • Local Institution - 0188
  • Barcelona, Spain, 08035
    • Local Institution - 0201
  • Donostia / San Sebastian, Spain, 20014
    • Local Institution - 0151
  • Granada, Spain, 18012
    • Local Institution - 0153
  • Madrid, Spain, 28009
    • Local Institution - 0150
  • Valencia, Spain, 46026
    • Local Institution - 0152
• Sweden
  • Gothenburg, Sweden, 41345
    • Local Institution - 0010
  • Lund, Sweden, 221 85
    • Local Institution - 0011
  • Solna, Sweden, 171 64
    • Local Institution - 0012
• Switzerland
  • Basel, Switzerland, 4031
    • Local Institution - 0085
  • Chur, Switzerland, 7000
    • Local Institution - 0087
  • Zurich, Switzerland, 8091
    • Local Institution - 0090
• United Kingdom
  • Bristol, United Kingdom, BS2 8ED
    • Local Institution - 0102
  • Glasgow, United Kingdom, G12 0YN
    • Local Institution - 0187
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Local Institution - 0154
  • Oxford, United Kingdom, OX3 7LE
    • Local Institution - 0232
  • Southampton, United Kingdom, SO16 0YD
    • Local Institution - 0127
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Local Institution - 0101
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Local Institution - 0176
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Local Institution - 0164
  • California
    • Los Angeles, California, United States, 90025
      • Local Institution - 0200
    • Palo Alto, California, United States, 94304
      • Local Institution - 0185
    • San Francisco, California, United States, 94115
      • Local Institution - 0162
    • Santa Monica, California, United States, 90404
      • Saint John's Cancer Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Local Institution - 0138
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Local Institution - 0166
  • Florida
    • Miami, Florida, United States, 33136
      • Local Institution - 0243
    • Miami, Florida, United States, 33136
      • Washington University School of Medicine
    • Pensacola, Florida, United States, 32504
      • Local Institution - 0179
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Local Institution - 0191
    • Atlanta, Georgia, United States, 30342
      • Local Institution - 0148
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Local Institution - 0202
    • Peoria, Illinois, United States, 61615
      • Local Institution - 0177
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Local Institution - 0223
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa-Holden Comprehensive Cancer Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Local Institution - 0178
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute-Melanoma
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Local Institution - 0258
    • Grand Rapids, Michigan, United States, 49503
      • Local Institution
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Local Institution - 0133
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 0139
    • Morristown, New Jersey, United States, 07960
      • Local Institution - 0206
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10016
      • Local Institution - 0140
    • New York, New York, United States, 10065
      • Local Institution - 0210
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 0130
    • Durham, North Carolina, United States, 27710
      • Local Institution - 0145
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44195
      • Local Institution - 0141
    • Columbus, Ohio, United States, 43210
      • The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Local Institution - 0267
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • Local Institution - 0125
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Local Institution - 0171
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Local Institution - 0147
    • Nashville, Tennessee, United States, 37232
      • Local Institution - 0183
  • Texas
    • Austin, Texas, United States, 78731
      • Local Institution - 0146
    • Dallas, Texas, United States, 75246
      • Local Institution - 0163
    • Houston, Texas, United States, 77030
      • Local Institution - 0172
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Local Institution - 0137

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Nivolumab Plus Relatlimab; Combination	Biological: Nivolumab + Relatlimab Fixed Dose Combination; Specified dose on specified days; Other Names: BMS-986213; Opdualag
Experimental: Arm B: Nivolumab; Monotherapy	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence Free Survival (RFS)	RFS is defined as the time between the date of randomization and the first date of documented recurrence (local, regional, distant, new primary melanoma) or death due to any cause, whichever occurs first.	Approximately 27.5 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time between the date of randomization and the date of death due to any cause.	Approximately 27.5 Months
Distant Metastasis Free Survival (DMFS)	DMFS is defined as the time between the date of randomization and the date of first distant metastasis or date of death due to any cause, whichever occurs first.	Approximately 27.5 Months
Progression Free Survival on Next-Line Systemic Therapy (PFS2)	PFS2 defined as time from randomization to second recurrence/objective disease progression on next-line systemic therapy per investigator, or death from any cause, whichever occurs first.	Approximately 27.5 Months
Number of Participants With Safety Related Events	Safety related events encompass the following measures: Adverse events (AEs), Serious AEs, AEs leading to discontinuation, Drug-Related AEs and Deaths. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment that does not necessarily have a causal relationship with this treatment. An SAE is an AE which: Results in death; Is life threatening; Requires hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Is an important medical event	Approximately 27.5 Months
Number of Participants With Select AEs	Select AEs will be reported as AEs per organ class. Organ classes which will be reported: Gastrointestinal; Hepatic; Pulmonary; Renal; Skin; Hypersensitivity/Infusion reaction	Approximately 27.5 Months
Number of Participants With Endocrine Related Immune Mediated AEs	Immune-mediated adverse events are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity.	Approximately 27.5 Months
Number of Participants With Non-endocrine Related Immune Mediated AEs	Immune-mediated adverse events are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity.	Approximately 27.5 Months
Laboratory Abnormalities for Specific Thyroid Tests	Number of participants with laboratory abnormalities in specific thyroid tests.	Approximately 27.5 Months

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2021
• Primary Completion (Actual): December 16, 2024
• Study Completion (Actual): April 2, 2025

Study Registration Dates

• First Submitted: August 4, 2021
• First Submitted That Met QC Criteria: August 4, 2021
• First Posted (Actual): August 12, 2021

Study Record Updates

• Last Update Posted (Estimated): January 8, 2026
• Last Update Submitted That Met QC Criteria: December 29, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Nivolumab; Melanoma; Relatlimab; Opdivo
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; relatlimab; Opdualag
• Other Study ID Numbers: CA224-098; 2021-001641-13 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No