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

Study Overview
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Brief Summary
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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.

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

Conditions
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Melanoma

Intervention / Treatment
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* Biological: Nivolumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Specified dose on specified days<br>|

What is the study measuring?
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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 |