An Investigational Immuno-therapy Study of Nivolumab Combined With Ipilimumab Compared to Nivolumab by Itself After Complete Surgical Removal of Stage IIIb/c/d or Stage IV Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether an investigational immunotherapy Nivolumab, when combined with Ipilimumab, is more effective than Nivolumab by itself, in delaying the return of cancer in patients who have had a complete surgical removal of stage IIIb/c/d or stage IV Melanoma

Official Title
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A Phase 3, Randomized Study of Adjuvant Immunotherapy With Nivolumab Combined With Ipilimumab Versus Nivolumab Monotherapy After Complete Resection of Stage IIIb/c/d or Stage IV Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Biological: nivolumab
* Biological: ipilimumab


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Completely surgically resected stage IIIb/c/d or stage IV melanoma within 12 weeks of participation in study. Must have full activity or, if limited, must be able to walk and carry out activities such as light house work or office work No prior anti-cancer treatment for melanoma (except surgery for the melanoma lesion(s) and/or except for adjuvant radiation therapy (RT) after neurosurgical resection for central nervous system (CNS) lesions) Exclusion Criteria: History of uveal melanoma Patients with active, known or suspected autoimmune disease Prior treatment with interferon (if complete < 6 months prior to participation in study), anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Other protocol defined inclusion/exclusion criteria could 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nivolumab + ipilimumab<br>Specified Dose on Specified Days | Biological: nivolumab<br>* Specified Dose on Specified Days<br>* Other names: BMS-936558;Biological: ipilimumab<br>* Specified Dose on Specified Days<br>* Other names: BMS-734016;|
| Experimental: nivolumab<br>Specified Dose on Specified Days | Biological: nivolumab<br>* Specified Dose on Specified Days<br>* Other names: BMS-936558;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free Survival (RFS) - All Randomized Participants | RFS was 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 (from any cause), whichever occurred first. Median values based on Kaplan-Meier Estimates. | From randomization to Primary Completion Date (up to approximately 3 years) | 
| Recurrence-free Survival (RFS) - All Randomized Participants With PD-L1 Expression Level < 1% | RFS was 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 (from any cause), whichever occurred first. Median based on Kaplan-Meier Estimates. | From randomization to Primary Completion Date (up to approximately 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) - All Randomized Participants | OS is defined as the time between the date of randomization and the date of death. Median based on Kaplan-Meier Estimates. | From randomization to date of death (up to approximately 45 months) | 
| Overall Survival (OS) - All Randomized Participants With PD-L1 Expression Level < 1% | OS is defined as the time between the date of randomization and the date of death. Median based on Kaplan-Meier Estimates. | From randomization to date of death (up to approximately 45 months) | 
| Recurrence-free Survival (RFS) by Baseline Tumor PD-L1 Expression | RFS was 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 (from any cause), whichever occurred first. Median based on Kaplan-Meier Estimates. | From randomization to Study Completion Date (up to approximately 45 months) | 
| Time to Next-Line Therapies - All Randomized Participants | Time to next therapy was defined as the time from the date of randomization to the start date of next systemic therapy. Participants who did not receive next treatment were censored at the last known alive date. Time to second next therapy was defined as the time from the date of randomization to the start date of second next systemic therapy. Participants who did not receive second next treatment were censored at the last known alive date. | From randomization to start of next therapy or second next therapy (up to approximately 45 months) | 
| Time to Next-Line Therapies - All Randomized Participants With PD-L1 Expression Level < 1% | Time to next therapy was defined as the time from the date of randomization to the start date of next systemic therapy. Participants who did not receive next treatment were censored at the last known alive date. Time to second next therapy was defined as the time from the date of randomization to the start date of second next systemic therapy. Participants who did not receive second next treatment were censored at the last known alive date | From randomization to start of next therapy or second next therapy (up to approximately 45 months) | 
| Time From Next Therapy to Second Next Therapy - All Randomized Participants | Time from next treatment to second next treatment was defined as the time from the start date of next systemic therapy to start date of second next systemic therapy. No censoring rules were applied here as analysis was only performed for the subset of participants who received second next treatment. | From start of first next systemic therapy to start of second next systemic therapy (up to approximately 28 months) | 
| Time From Next Therapy to Second Next Therapy - All Randomized Participants With PD-L1 Expression Level < 1% | Time from next treatment to second next treatment was defined as the time from the start date of next systemic therapy to start date of second next systemic therapy. No censoring rules were applied here as analysis was only performed for the subset of participants who received second next treatment. | From start of first next systemic therapy to start of second next systemic therapy (up to approximately 28 months) | 
| Progression-free Survival (PFS) on Next-line Therapy - All Randomized Participants | PFS2 was defined as the time from randomization to the progression date on next-line systemic therapy or the end date of next-line systemic therapy (if progression date not available) or death from any cause (if both progression date and end date not available), and to last known alive date in case of no event (ie, censoring), meaning either (1) no subsequent systemic therapy and no death OR (2) subsequent systemic therapy but no progression date nor end date available and no death. | From randomization to progression event (up to approximately 45 months) | 
| Progression-free Survival (PFS) on Next-line Therapy - All Randomized Participants With PD-L1 Expression Level < 1% | PFS2 was defined as the time from randomization to the progression date on next-line systemic therapy or the end date of next-line systemic therapy (if progression date not available) or death from any cause (if both progression date and end date not available), and to last known alive date in case of no event (ie, censoring), meaning either (1) no subsequent systemic therapy and no death OR (2) subsequent systemic therapy but no progression date nor end date available and no death. | From randomization to progression event (up to approximately 45 months) |