NCT04099251 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-08-07

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Recurrence Free Survival (RFS)

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outcome · POSTED

Distant Metastasis-Free Survival (DMFS)

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outcome · POSTED

Duration of Treatment on Next Line Therapy Per Investigator Assessment

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outcome · POSTED

Progression-Free Survival Through Next-Line Therapy

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outcome · POSTED

Number of Participants Experiencing Adverse Events (AEs)

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outcome · POSTED

Number of Participants Experiencing Adverse Events Leading to Discontinuation

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outcome · POSTED

Number of Participants Experiencing Select Adverse Events

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outcome · POSTED

Number of Participants Experiencing Serious Adverse Events (SAEs)

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outcome · POSTED

Number of Participants Experiencing Death

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outcome · POSTED

Number of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities in Selected Hematology Parameters

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outcome · POSTED

Number of Participants Experiencing Laboratory Abnormalities in Selected Liver Parameters

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outcome · NOT POSTED

Overall Survival (OS)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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.
healthy Volunteers: false
minimum Age: 12 Years
sex: ALL
std Ages: CHILD
ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

intervention Names
Biological: Nivolumab
label
Nivolumab
type
EXPERIMENTAL
intervention Names
Other: Placebo
label
Placebo
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Nivolumab
description
Specified dose on specified days
name
Nivolumab
other Names
Opdivo
type
BIOLOGICAL
arm Group Labels
Placebo
description
Specified dose on specified days
name
Placebo
type
OTHER

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: TRIPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 790
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Recurrence Free Survival (RFS)
time Frame
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

description
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.
measure
Distant Metastasis-Free Survival (DMFS)
time Frame
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)
description
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.
measure
Duration of Treatment on Next Line Therapy Per Investigator Assessment
time Frame
From first dose date of next-line therapy to last dose date of next-line therapy (up to approximately 32 months)
description
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.
measure
Progression-Free Survival Through Next-Line Therapy
time Frame
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)
description
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.
measure
Number of Participants Experiencing Adverse Events (AEs)
time Frame
From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
description
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.
measure
Number of Participants Experiencing Adverse Events Leading to Discontinuation
time Frame
From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
description
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.
measure
Number of Participants Experiencing Select Adverse Events
time Frame
From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
description
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.
measure
Number of Participants Experiencing Serious Adverse Events (SAEs)
time Frame
From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
description
All study participants who died during the blinded phase of the study following treatment.
measure
Number of Participants Experiencing Death
time Frame
From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
description
The number of participants experiencing Grade 3 or 4 laboratory abnormalities in the specific pre-determined hematology tests.
measure
Number of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities in Selected Hematology Parameters
time Frame
From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
description
The number of participants experiencing laboratory abnormalities in the specific pre-determined liver tests.
measure
Number of Participants Experiencing Laboratory Abnormalities in Selected Liver Parameters
time Frame
From first dose up to 30 days post last dose of the blinded phase (up to 13 months)
description
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.
measure
Overall Survival (OS)
time Frame
From randomization up to the date of death or the last date the participant was known to be alive

Full study description

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.

Source references

references

citation
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
type
DERIVED
citation
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
type
DERIVED