Neoadjuvant Nivolumab+Ipilimumab Followed by Adjuvant Nivolumab or Neoadjuvant Nivolumab+Ipilimumab Followed by Adjuvant Observation Compared With Adjuvant Nivolumab in Treatment-Naive High-risk Melanoma Participants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the role of neoadjuvant immunotherapy and to demonstrate high pathologic complete response (pCR) and near pCR rates in melanoma participants with clinically detectable nodal disease and a high risk of recurrence. Neoadjuvant immunotherapy aims to enhance the systemic T-cell response to tumor antigens while detectable tumor is still present, inducing a stronger and broader tumor-specific immune response. Of the neoadjuvant approaches studied within melanoma, the neoadjuvant combination of nivolumab and ipilimumab has demonstrated high pCR and near pCR rates that may translate to prolonged clinical benefit.

Official Title
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A Phase 2, Randomized Study of Neoadjuvant Nivolumab Plus Ipilimumab Followed by Adjuvant Nivolumab or Neoadjuvant Nivolumab Plus Ipilimumab Followed by Either Adjuvant Nivolumab or Postsurgical Observation Depending on Pathologic Response Compared With Adjuvant Nivolumab in Treatment-Naive Patients With Resectable Clinically Detectable Stage III 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: Males and females, ≥ 12 years of age [Except: where local regulations and/or institutional policies do not allow for participants < 18 years of age (adolescent population) to participate. For those sites, the eligible participant population is 18 years of age or local age of majority, inclusive] Diagnosed with cytologically or histologically confirmed Stage IIIB, IIIC, or IIID cutaneous melanoma as per American Joint Committee on Cancer (AJCC) staging system, with ≥ 1 clinically detectable lymph node metastases (N1b, N2b, N3b), which are measurable according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) Adult participants and adolescents 16 to 18 years old must have an Eastern Cooperative Oncology Group (ECOG) scale performance status of 0 or 1. Adolescents < 16 years old must have Lanksky Play-Performance Status scale performance of ≥ 60 Must be treatment-naïve (ie, no prior systemic anticancer therapy as adjuvant therapy for melanoma or unresectable/metastatic melanoma) Women and men must agree to follow specific methods of contraception, if applicable, while participating in the trial Exclusion Criteria: Women who are breastfeeding Patients with serious or uncontrolled medical disorders Prior treatment with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti-programmed death-ligand 2 (PD-L2), or anti cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant treatment + Adjuvant treatment<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: Yervoy;|
| Experimental: Adjuvant treatment<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Neo treat with patho response-driven Adju treat or observation<br>Neoadjuvant treatment with pathologic response-driven Adjuvant treatment or observation | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: Yervoy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival (EFS) |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free survival (RFS) Time from Surgery |  | Up to 5 years | 
| RFS Time from Adjuvant Therapy |  | Up to 5 years | 
| Pathologic response rate (pRR) by immune-related pathologic response (irPR) |  | Up to 5 years | 
| Concordance major pathologic response (MPR) by local and central pathology Review | MPR is defined as participants achieving either pathologic complete response (pCR) or near pCR | Up to 5 years | 
| RFS by MPR |  | Up to 5 years | 
| Incidence of Adverse Events (AEs) |  | Up to 5 years | 
| Incidence of Serious Adverse Events (SAEs) |  | Up to 5 years | 
| Incidence of deaths |  | Up to 5 years | 
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests |  | Up to 5 years | 
| Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests |  | Up to 5 years | 
| Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests |  | Up to 5 years | 
| Change from baseline in Health-related quality of life (HRQoL) by the Trial Outcome Index (TOI) and Melanoma Subscale (MS) |  | Up to 5 years |