Effectiveness Study of Nivolumab Compared to Placebo in Prevention of Recurrent Melanoma After Complete Resection of Stage IIB/C Melanoma

NCT04099251 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: CA209-76K2019-001230-34U1111-1229-8927
• Study Type: interventional
• Target: 790
• Locations: 19 countries
• Sites: 118

Brief Summary

The purpose of this study is to determine the effectiveness of nivolumab adjuvant immunotherapy compared to placebo in adults and pediatric participants after complete resection of Stage IIB/C melanoma with no evidence of disease (NED) who are at high risk for recurrence.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Recurrence Free Survival (RFS)

  Recurrence Free Survival (RFS) is defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma (including melanoma in situ), or death (whatever the cause), whichever occurs first. For participants who remain alive and whose disease has not recurred or did not die, RFS will be censored on the date of last evaluable disease assessment. For those participants who remained alive and had no recorded post-randomization tumor assessment, RFS will be censored on the day of randomization.

  From randomization up to the date of first recurrence, new primary melanoma, or death (whatever the cause), whichever occurs first (up to 32 months)

Secondary Outcomes (11)

• Distant Metastasis-Free Survival (DMFS)

  From randomization up to the date of first distant metastasis or date of death (whatever the cause), whichever occurs first (up to approximately 32 months)

• Duration of Treatment on Next Line Therapy Per Investigator Assessment

  From first dose date of next-line therapy to last dose date of next-line therapy (up to approximately 32 months)

• Progression-Free Survival Through Next-Line Therapy

  From randomization to recurrence/objective disease progression after the start of the next-line therapy, or to the start of a second next-line systemic therapy, or to death from any cause, whichever occurs first (up to approximately 32 months)

• Number of Participants Experiencing Adverse Events (AEs)

  From first dose up to 30 days post last dose of the blinded phase (up to 13 months)

• Number of Participants Experiencing Adverse Events Leading to Discontinuation

  From first dose up to 30 days post last dose of the blinded phase (up to 13 months)

Study Arms (2)

Nivolumab

EXPERIMENTAL

Biological: Nivolumab

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Placebo OTHER

Specified dose on specified days

Placebo

Nivolumab BIOLOGICAL

Specified dose on specified days

Also known as: Opdivo

Nivolumab

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:

• Had a negative sentinel lymph node biopsy
• Participant has not been previously treated for melanoma
• ECOG 0 or 1
• Participants must have been diagnosed with histologically confirmed, Resected, Stage IIB/C cutaneous melanoma

You may not qualify if:

• History of ocular or mucosal melanoma.
• Pregnant or nursing women
• Participants with active known or suspected autoimmune disease
• Known history of allergy or hypersensitivity to study drug components
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody, or agents that target IL-2 pathways, T-cell stimulators, or checkpoint pathways

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (130)

Local Institution - 0088

Birmingham, Alabama, 35294-3300, United States

Location

Local Institution - 0126

Tucson, Arizona, 85724-5024, United States

Location

Local Institution - 0087

Springdale, Arkansas, 72762, United States

Location

Local Institution - 0080

Los Angeles, California, 90025, United States

Location

Local Institution - 0077

San Francisco, California, 94115, United States

Location

Local Institution - 0119

San Francisco, California, 94115, United States

Location

Local Institution - 0122

San Jose, California, 95119, United States

Location

Local Institution - 0121

Vallejo, California, 94589-2441, United States

Location

Local Institution - 0109

Vallejo, California, 94589, United States

Location

Local Institution - 0120

Vallejo, California, 94589, United States

Location

Local Institution - 0091

Aurora, Colorado, 80045, United States

Location

Local Institution - 0089

Washington D.C., District of Columbia, 20057, United States

Location

Local Institution - 0141

Atlanta, Georgia, 30342, United States

Location

Local Institution - 0132

Chicago, Illinois, 60611, United States

Location

Local Institution - 0135

Baltimore, Maryland, 21237, United States

Location

Local Institution - 0078

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0127

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0143

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0151

Minneapolis, Minnesota, 55407, United States

Location

Local Institution - 0081

Robbinsdale, Minnesota, 55407, United States

Location

Local Institution - 0079

Omaha, Nebraska, 68130, United States

Location

Local Institution - 0093

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 0094

New York, New York, 10016, United States

Location

Local Institution - 0086

Charlotte, North Carolina, 28204, United States

Location

Local Institution - 0099

Cleveland, Ohio, 44195, United States

Location

Local Institution - 0076

Portland, Oregon, 97213, United States

Location

Local Institution - 0092

Allentown, Pennsylvania, 18103, United States

Location

Local Institution - 0031

Pittsburgh, Pennsylvania, 15232, United States

Location

Local Institution - 0148

Germantown, Tennessee, 38138, United States

Location

Local Institution - 0144

Austin, Texas, 78731, United States

Location

Local Institution - 0085

Dallas, Texas, 75246, United States

Location

Local Institution - 0090

Fairfax, Virginia, 22031, United States

Location

Local Institution - 0018

Waratah, New South Wales, 2298, Australia

Location

Local Institution - 0025

Westmead, New South Wales, 2145, Australia

Location

Local Institution - 0016

Wollstonecraft, New South Wales, 2065, Australia

Location

Local Institution - 0105

Cairns, Queensland, 4870, Australia

Location

Local Institution - 0017

Greenslopes, Queensland, 4120, Australia

Location

Local Institution - 0024

Herston, Queensland, 4029, Australia

Location

Local Institution - 0138

Southport, Queensland, 4120, Australia

Location

Local Institution - 0019

Box Hill, Victoria, 3128, Australia

Location

Local Institution - 0125

Geelong, Victoria, 3220, Australia

Location

Local Institution - 0128

Malvern, Victoria, 3144, Australia

Location

Local Institution - 0106

Melbourne, Victoria, 3004, Australia

Location

Local Institution - 0104

Nedlands, Western Australia, 6009, Australia

Location

Local Institution - 0049

Graz, 8036, Austria

Location

Local Institution - 0051

Innsbruck, 6020, Austria

Location

Local Institution - 0050

Salzburg, 5020, Austria

Location

Local Institution - 0048

Vienna, 1090, Austria

Location

Local Institution - 0028

Charleroi, 6000, Belgium

Location

Local Institution - 0011

Ghent, 9000, Belgium

Location

Local Institution - 0008

Kortrijk, 8500, Belgium

Location

Local Institution - 0010

Liège, 4000, Belgium

Location

Local Institution - 0134

Calgary, Alberta, T2N 4N2, Canada

Location

Local Institution - 0133

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Local Institution - 0131

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Local Institution - 0142

Hamilton, Ontario, L8V 5C2, Canada

Location

Local Institution - 0124

Kingston, Ontario, K7L 2V7, Canada

Location

Local Institution - 0140

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 0116

Montreal, Quebec, H2X 3E4, Canada

Location

Local Institution - 0123

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Local Institution - 0074

Prague, Praha 2, 12808, Czechia

Location

Local Institution - 0075

Ostrava-Poruba, 708 52, Czechia

Location

Local Institution - 0073

Prague, 100 34, Czechia

Location

Local Institution - 0007

Aarhus N, 8200, Denmark

Location

Local Institution - 0012

Herlev, 2730, Denmark

Location

Local Institution - 0013

Odense, 5000, Denmark

Location

Local Institution - 0014

Helsinki, Etelä-Suomen Lääni, 00290, Finland

Location

Local Institution - 0015

Tampere, Pirkanmaa, 33520, Finland

Location

Local Institution - 0110

Turku, 20251, Finland

Location

Local Institution - 0113

Brest, Finistère, 29200, France

Location

Local Institution - 0129

Besançon, 25030, France

Location

Local Institution - 0112

Bordeaux, 33075, France

Location

Local Institution - 0111

Lille, 59037, France

Location

Local Institution - 0033

Marseille, 13011, France

Location

Local Institution - 0035

Nantes, 44000, France

Location

Local Institution - 0130

Nice, 06200, France

Location

Local Institution - 0036

Paris, 75475, France

Location

Local Institution - 0032

Pierre-Bénite, 69495, France

Location

Local Institution - 0034

Villejuif, 94800, France

Location

Local Institution - 0056

München, Bavaria, 81377, Germany

Location

Local Institution - 0072

Bonn, 53127, Germany

Location

Local Institution - 0061

Buxtehude, 21614, Germany

Location

Local Institution - 0098

Dresden, 01307, Germany

Location

Local Institution - 0054

Essen, 45122, Germany

Location

Local Institution - 0062

Gera, 07548, Germany

Location

Local Institution - 0114

Göttingen, 37075, Germany

Location

Local Institution - 0060

Hanover, 30625, Germany

Location

Local Institution - 0055

Heidelberg, 69120, Germany

Location

Local Institution - 0057

Lübeck, 23538, Germany

Location

Local Institution - 0100

Mainz, 55131, Germany

Location

Local Institution - 0102

Regensburg, 93053, Germany

Location

Local Institution - 0058

Tübingen, 72076, Germany

Location

Local Institution - 0084

Athens, Attikí, 185 47, Greece

Location

Local Institution - 0082

Athens, 115 27, Greece

Location

Local Institution - 0083

Thessaloniki, 57100, Greece

Location

Local Institution - 0046

Palermo, Sicily, 90127, Italy

Location

Local Institution - 0040

Bergamo, 24127, Italy

Location

Local Institution - 0037

Milan, 20133, Italy

Location

Local Institution - 0146

Milan, 20141, Italy

Location

Local Institution - 0101

Naples, 80131, Italy

Location

Local Institution - 0039

Padova, 35128, Italy

Location

Local Institution - 0145

Perugia, 06132, Italy

Location

Local Institution - 0038

Siena, 53100, Italy

Location

Local Institution - 0107

Breda, 4819 EV, Netherlands

Location

Local Institution - 0001

Groningen, 9700RB, Netherlands

Location

Local Institution - 0030

Rotterdam, 3015 AA, Netherlands

Location

Local Institution - 0002

Utrecht, 3584 CX, Netherlands

Location

Local Institution - 0063

Bergen, 5021, Norway

Location

Local Institution - 0027

Grålum, 1714, Norway

Location

Local Institution - 0005

Oslo, 0310, Norway

Location

Local Institution - 0103

Poznan, Greater Poland Voivodeship, 60-569, Poland

Location

Local Institution - 0023

Gdansk, 80-214, Poland

Location

Local Institution - 0022

Warsaw, 02-781, Poland

Location

Local Institution - 0047

Cluj-Napoca, 400015, Romania

Location

Local Institution - 0020

Craiova, 200542, Romania

Location

Local Institution - 0021

Sector 2, 022328, Romania

Location

Local Institution - 0071

Barcelona, Barcelona [Barcelona], 08028, Spain

Location

Local Institution - 0067

A Coruña, 15006, Spain

Location

Local Institution - 0065

Badalona, 08916, Spain

Location

Local Institution - 0066

Madrid, 28034, Spain

Location

Local Institution - 0070

Madrid, 28046, Spain

Location

Local Institution - 0068

Málaga, 29010, Spain

Location

Local Institution - 0064

Santander, 39008, Spain

Location

Local Institution - 0069

Valencia, 46009, Spain

Location

Local Institution - 0026

Örebro, 701 85, Sweden

Location

Local Institution - 0003

Linköping, Östergötlands Län [se-05], 581 85, Sweden

Location

Local Institution - 0053

Lausanne, 1011, Switzerland

Location

Local Institution - 0052

Zurich, 8091, Switzerland

Location

Local Institution - 0044

Cardiff, CF14 2TL, United Kingdom

Location

Local Institution - 0095

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (2)

• Kirkwood JM, Mohr P, Hoeller C, Grob JJ, Del Vecchio M, Lord-Bessen J, Srinivasan S, Nassar A, Campigotto F, Fairbanks H, Taylor F, Lawrance R, Long GV, Weber J. Patient-reported outcomes with adjuvant nivolumab versus placebo after complete resection of stage IIB/C melanoma in the randomized phase 3 CheckMate 76 K trial. Eur J Cancer. 2025 May 2;220:115371. doi: 10.1016/j.ejca.2025.115371. Epub 2025 Mar 19.

  PMID: 40139004 DERIVED

• Kirkwood JM, Del Vecchio M, Weber J, Hoeller C, Grob JJ, Mohr P, Loquai C, Dutriaux C, Chiarion-Sileni V, Mackiewicz J, Rutkowski P, Arenberger P, Quereux G, Meniawy TM, Ascierto PA, Menzies AM, Durani P, Lobo M, Campigotto F, Gastman B, Long GV. Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial. Nat Med. 2023 Nov;29(11):2835-2843. doi: 10.1038/s41591-023-02583-2. Epub 2023 Oct 16.

  PMID: 37845511 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Melanoma

Interventions

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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 20, 2019
• First Posted: September 23, 2019
• Study Start: October 28, 2019
• Primary Completion: June 28, 2022
• Study Completion (Estimated): June 29, 2027
• Last Updated: April 9, 2026
• Results First Posted: July 27, 2023

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

PL (3); DE (13); FI (3); DK (3); CZ (3); CH (2); GR (3); US (32); IT (8); GB (2); FR (10); SE (2); RO (3); AU (4); NL (4); CA (8); ES (8); NO (3); BE (4)