Nivolumab +/- Ipilimumab Immunomonitoring in Metastatic Melanoma

Study Overview
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Brief Summary
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This is an open bi-centric prospective non-randomized study in patients with metastatic melanoma treated with a first line treatment of Nivolumab +/- Ipilimumab. The aim of the study is to characterize the immune cells modulations under anti-PD-1 +/- anti-CTLA4 and identify the differences between responder and non-responder patients.

Official Title
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Immune Modulation Study in Patients With Metastatic Melanoma Treated With a First Line Therapy of Nivolumab +/- Ipilimumab (IMMUNONIVO/MelpredictPD1).

Conditions
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Metastatic Melanoma

Intervention / Treatment
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* Biological: Blood and biopsy sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged ≥ 18 years of age. Patient with metastatic or unresectable melanoma Nivolumab or Nivolumab + Ipilimumab treatment indication Skin biopsies available Patient affiliated to or a beneficiary of a social security category. Signed Written Informed Consent. Patient who agrees to the storage of his biological samples Exclusion Criteria: Treated haematological malignancies Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications Patients with autoimmune disease. Ocular melanoma

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Nivolumab<br>Previous untreated patient with metastatic melanoma eligible for a Nivolumab treatment. 30 patients will be included in the arm. | Biological: Blood and biopsy sampling<br>* Blood samples (52mL) will be taken at week 1, week 3, week 7, week 13, week 53 or at the progression. Skin biopsies will be taken at week 1, week 7, week 53 or at the progression.<br>|
| Other: Nivolumab + Ipilimumab<br>Previous untreated patient with metastatic melanoma eligible for a Nivolumab + Ipilimumab treatment. 30 patients will be included in the arm. | Biological: Blood and biopsy sampling<br>* Blood samples (52mL) will be taken at week 1, week 3, week 7, week 13, week 53 or at the progression. Skin biopsies will be taken at week 1, week 7, week 53 or at the progression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change description of biological characteristics of immune cells of the blood by immunomonitoring. | Biological characteristics description of monocytes, dendritic cell and T cells subpopulations including different circulating suppressive subpopulations by immunomonitoring | Week 1 (baseline, before the 1st injection), week 3 (before the 2d injection treatment), week 7 (before the 4th) , week 13 (before the 5th), week 53 (before the 26th or during radiological evaluation) or at the progression | 
| Change in the immune response by skin biopsy. |  | Week 1 (Baseline), week 7, week 53 or at the progression. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression free survival (PFS) will be calculated as the period of time from the immunotherapy first administration to the first RECIST 1.1 disease progression | Week1 , every radiological assessments defined by standard care (not by specific time frame) | 
| Overall survival | Overall survival (OS) will be calculated as the period of time from the immunotherapy first administration to the patient's death. | week 1, date of patient death | 
| Auto-immune adverse event frequency | Immune adverse event description by clinical examination and correlation with biological characteristics of immune cells | baseline, week 53 or at the progression | 
| Subtype of melanoma correlated with biological characteristics of immune cells | Subtype of melanoma defined by histological analysis correlated with biological characteristics of immune cells | baseline | 
| Immunity gene polymorphism correlated with biological characteristics of immune cells | Immunity gene polymorphism defined by RNA sequencing correlated with biological characteristics of immune cells immune cells | Week 1, week 3, week 7, week 13, week 53 or at the progression. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Nivolumab, Ipilimumab, Immune modulation