Effectiveness Study of Nivolumab Compared to Placebo in Prevention of Recurrent Melanoma After Complete Resection of Stage IIB/C Melanoma (CheckMate76K)

A Phase 3, Randomized, Double-Blind Study of Adjuvant Immunotherapy With Nivolumab Versus Placebo After Complete Resection of Stage IIB/C Melanoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma
• Intervention / Treatment: Other: Placebo; Biological: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 790
• Phase: Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Local Institution - 0018
    • Westmead, New South Wales, Australia, 2145
      • Local Institution - 0025
    • Wollstonecraft, New South Wales, Australia, 2065
      • Local Institution - 0016
  • Queensland
    • Cairns, Queensland, Australia, 4870
      • Local Institution - 0105
    • Greenslopes, Queensland, Australia, 4120
      • Local Institution - 0017
    • Herston, Queensland, Australia, 4029
      • Local Institution - 0024
    • Southport, Queensland, Australia, 4120
      • Local Institution - 0138
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Local Institution - 0019
    • Geelong, Victoria, Australia, 3220
      • Local Institution - 0125
    • Malvern, Victoria, Australia, 3144
      • Local Institution - 0128
    • Melbourne, Victoria, Australia, 3004
      • Local Institution - 0106
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Local Institution - 0104
• Austria
  • Graz, Austria, 8036
    • Local Institution - 0049
  • Innsbruck, Austria, 6020
    • Local Institution - 0051
  • Salzburg, Austria, 5020
    • Local Institution - 0050
  • Wien, Austria, 1090
    • Local Institution - 0048
• Belgium
  • Charleroi, Belgium, 6000
    • Local Institution - 0028
  • Gent, Belgium, 9000
    • Local Institution - 0011
  • Kortrijk, Belgium, 8500
    • Local Institution - 0008
  • Liège, Belgium, 4000
    • Local Institution - 0010
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Local Institution - 0134
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Local Institution - 0133
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Local Institution - 0131
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Local Institution - 0142
    • Kingston, Ontario, Canada, K7L 2V7
      • Local Institution - 0124
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0140
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Local Institution - 0116
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Local Institution - 0123
• Czechia
  • Ostrava-Poruba, Czechia, 708 52
    • Local Institution - 0075
  • Praha 10, Czechia, 100 34
    • Local Institution - 0073
  • Praha 2
    • Prague, Praha 2, Czechia, 12808
      • Local Institution - 0074
• Denmark
  • Aarhus N, Denmark, 8200
    • Local Institution - 0007
  • Herlev, Denmark, 2730
    • Local Institution - 0012
  • Odense, Denmark, 5000
    • Local Institution - 0013
• Finland
  • Turku, Finland, 20251
    • Local Institution - 0110
  • Etelä-Suomen Lääni
    • Helsinki, Etelä-Suomen Lääni, Finland, 00290
      • Local Institution - 0014
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland, 33520
      • Local Institution - 0015
• France
  • Besancon Cedex, France, 25030
    • Local Institution - 0129
  • Bordeaux, France, 33075
    • Local Institution - 0112
  • Lille, France, 59037
    • Local Institution - 0111
  • Marseille, France, 13011
    • Local Institution - 0033
  • Nantes, France, 44000
    • Local Institution - 0035
  • Nice, France, 06200
    • Local Institution - 0130
  • Paris, France, 75475
    • Local Institution - 0036
  • Pierre Benite Cedex, France, 69495
    • Local Institution - 0032
  • Villejuif, France, 94800
    • Local Institution - 0034
  • Finistère
    • Brest, Finistère, France, 29200
      • Local Institution - 0113
• Germany
  • Bonn, Germany, 53127
    • Local Institution - 0072
  • Buxtehude, Germany, 21614
    • Local Institution - 0061
  • Dresden, Germany, 01307
    • Local Institution - 0098
  • Essen, Germany, 45122
    • Local Institution - 0054
  • Gera, Germany, 07548
    • Local Institution - 0062
  • Goettingen, Germany, 37075
    • Local Institution - 0114
  • Hannover, Germany, 30625
    • Local Institution - 0060
  • Heidelberg, Germany, 69120
    • Local Institution - 0055
  • Lubeck, Germany, 23538
    • Local Institution - 0057
  • Mainz, Germany, 55131
    • Local Institution - 0100
  • Regensburg, Germany, 93053
    • Local Institution - 0102
  • Tuebingen, Germany, 72076
    • Local Institution - 0058
  • Bayern
    • München, Bayern, Germany, 81377
      • Local Institution - 0056
• Greece
  • Athina, Greece, 115 27
    • Local Institution - 0082
  • Piraeus, Greece, 185 47
    • Local Institution - 0084
  • Thessaloniki, Greece, 57100
    • Local Institution - 0083
• Italy
  • Bergamo, Italy, 24127
    • ASST Papa Giovanni XXIII
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia IRCCS
  • Milano, Italy, 20133
    • IRCCS Istituto Nazionale Tumori Milano
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori Fondazione Pascale
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto IOV
  • Perugia, Italy, 06132
    • Azienda Ospedaliera di Perugia
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese
  • Sicilia
    • Palermo, Sicilia, Italy, 90127
      • A.O.U. Policlinico Paolo Giaccone
• Netherlands
  • Breda, Netherlands, 4819 EV
    • Local Institution - 0107
  • Groningen, Netherlands, 9700RB
    • Local Institution - 0001
  • Rotterdam, Netherlands, 3015 AA
    • Local Institution - 0030
  • Utrecht, Netherlands, 3584 CX
    • Local Institution - 0002
• Norway
  • Bergen, Norway, 5021
    • Local Institution - 0063
  • Gralum, Norway, 1714
    • Local Institution - 0027
  • Oslo, Norway, 0310
    • Local Institution - 0005
• Poland
  • Gdansk, Poland, 80-214
    • Local Institution - 0023
  • Warszawa, Poland, 02-781
    • Local Institution - 0022
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-780
      • Local Institution - 0103
• Romania
  • Cluj-Napoca, Romania, 400015
    • Local Institution - 0047
  • Craiova, Romania, 200542
    • Local Institution - 0020
  • Sector 2, Romania, 022328
    • Local Institution - 0021
• Spain
  • A Coruña, Spain, 15006
    • Local Institution - 0067
  • Badalona, Spain, 08916
    • Local Institution - 0065
  • Barcelona, Spain, 08028
    • Local Institution - 0071
  • Madrid, Spain, 28034
    • Local Institution - 0066
  • Madrid, Spain, 28046
    • Local Institution - 0070
  • Malaga, Spain, 29010
    • Local Institution - 0068
  • Santander, Spain, 39008
    • Local Institution - 0064
  • Valencia, Spain, 46009
    • Local Institution - 0069
• Sweden
  • Orebro, Sweden, 701 85
    • Local Institution - 0026
  • Östergötlands Län [se-05]
    • Linköping, Östergötlands Län [se-05], Sweden, 581 85
      • Local Institution - 0003
• Switzerland
  • Lausanne, Switzerland, 1011
    • Local Institution - 0053
  • Zuerich, Switzerland, 8091
    • Local Institution - 0052
• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
    • Local Institution - 0044
  • Southampton, United Kingdom, SO16 6YD
    • Local Institution - 0095
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • Local Institution - 0088
  • Arizona
    • Tucson, Arizona, United States, 85724-5024
      • Local Institution - 0126
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Local Institution - 0087
  • California
    • Los Angeles, California, United States, 90025
      • Local Institution - 0080
    • San Francisco, California, United States, 94115
      • Local Institution - 0077
    • San Francisco, California, United States, 94115
      • Local Institution - 0119
    • San Jose, California, United States, 95119
      • Local Institution - 0122
    • Vallejo, California, United States, 94589-2441
      • Local Institution - 0109
    • Vallejo, California, United States, 94589
      • Local Institution - 0120
    • Vallejo, California, United States, 94589
      • Local Institution - 0121
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Local Institution - 0091
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Local Institution - 0089
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Local Institution - 0141
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Local Institution - 0132
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Local Institution - 0135
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0078
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0127
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0143
  • Minnesota
    • Robbinsdale, Minnesota, United States, 55407
      • Local Institution - 0081
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Local Institution - 0079
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 0093
  • New York
    • New York, New York, United States, 10016
      • Local Institution - 0094
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 0086
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Local Institution - 0099
  • Oregon
    • Portland, Oregon, United States, 97213
      • Local Institution - 0076
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18105
      • Local Institution - 0092
    • Pittsburgh, Pennsylvania, United States, 15232
      • Local Institution - 0031
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Local Institution - 0148
  • Texas
    • Austin, Texas, United States, 78731
      • Local Institution - 0144
    • Dallas, Texas, United States, 75246
      • Local Institution - 0085
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Local Institution - 0090

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

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: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Specified dose on specified days
Experimental: Nivolumab	Biological: Nivolumab; Specified dose on specified days; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distant Metastasis-Free Survival (DMFS)	Investigator-assessed distant metastasis-free survival (DMFS) is defined as the time between the date of randomization and the date of first distant metastasis or date of death (whatever the cause), whichever occurs first. Participants with no baseline disease assessment, no on-study disease assessments and no death, and no distant metastasis and no death will be censored. Participants with no baseline disease assessment and no on-study disease assessments and death are censored on the date of randomization. Participants with no recurrence and no death will be censored on the date of their last evaluable disease assessment.	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	Duration of treatment is an investigator-assessed outcome of next-line therapy (NLT) defined as the time from first dose date of NLT to last dose date of NLT. Participants who did not stop the NLT were censored.	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	Progression-free survival through next-line therapy (PFS2) is defined as the time from randomization to recurrence/objective disease progression after the start of the next-line of systemic anti-cancer therapy, or to the start of a second next-line systemic therapy, or to death from any cause, whichever occurs first. Participants who did not receive subsequent systemic anti-cancer therapy who died will be considered as having the event on the date of death. Participants who received subsequent systemic anti-cancer therapy who had a disease progression after the start of therapy will be considered as having the event on the date of disease progression. Participants who died or started second next-line therapy, the date of death or start date of second next-line therapy will be the event date, whichever is earlier. Participants who did not experience disease progression, death, or second next-line therapy will be censored on the last known alive date.	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)	An Adverse Event (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 and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.	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	An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
Number of Participants Experiencing Select Adverse Events	The number of participants experiencing all-cause select adverse events (AEs). An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
Number of Participants Experiencing Serious Adverse Events (SAEs)	A Serious Adverse Events (SAE) is defined as any untoward or unfavorable medical occurrence in a participants that results in death, is life threatening, or places the participant at immediate risk of death from the event as it occurred, requires or prolongs hospitalization, causes persistent or significant disability or incapacity, results in congenital anomalies or birth defects, and is another condition which investigators judge to represent significant hazards.	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
Number of Participants Experiencing Death	All study participants who died during the blinded phase of the study following treatment.	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
Number of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities in Selected Hematology Parameters	The number of participants experiencing Grade 3 or 4 laboratory abnormalities in the specific pre-determined hematology tests.	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
Number of Participants Experiencing Laboratory Abnormalities in Selected Liver Parameters	The number of participants experiencing laboratory abnormalities in the specific pre-determined liver tests.	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
Overall Survival (OS)	OS is defined as the time between the date of randomization and the date of death. For those without documentation of death, OS will be censored on the last date the participant was known to be alive.	From randomization up to the date of death or the last date the participant was known to be alive

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2019
• Primary Completion (Actual): June 28, 2022
• Study Completion (Estimated): June 29, 2027

Study Registration Dates

• First Submitted: September 20, 2019
• First Submitted That Met QC Criteria: September 20, 2019
• First Posted (Actual): September 23, 2019

Study Record Updates

• Last Update Posted (Actual): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 9, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA209-76K; 2019-001230-34 (EudraCT Number); U1111-1229-8927 (Other Identifier: UTN 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