Adjuvant Nivolumab Treatment in Stage II (IIA, IIB, IIC) High-risk Melanoma

The NivoMela trial is a randomized, controlled, prospective, multi-center national phase III trial with biomarker-based risk stratification. Stage II melanoma patients having undergone surgery of the malignant melanoma will be screened using the MelaGenix GEP score to identify patients at high risk for relapse. It is expected, that 61% of screened patients will belong to this group. Patients with a risk score of \> 0.0 (HR 1.48, 1.11-1.98) corresponding to high risk of relapse will be randomized at a ratio of 2:1 to receive either nivolumab as adjuvant treatment (arm A) or observation only (arm B). Stratification factors for randomization are: 1. Tumor stage: IIA versus IIB versus IIC 2. Gender: Female versus Male 3. Site of primary tumor: extremities versus trunk versus head \&neck All screened patients with a risk score of ≤ 0.0 who are not eligible for randomization will be followed for RFS, DMFS and OS for at least 5 years according to German Follow-up guidelines (Arm C). Various factors that could potentially predict clinical response and incidence of AEs to treatment with nivolumab will be investigated in peripheral blood and tumor specimen taken at baseline. Data from these investigations will be evaluated for associations with clinical efficacy (eg, ORR, PFS, OS) and safety/toxicity (AE). The samples may also be used for exploratory analyses to assess biomarkers associated with melanoma and/or with immunotherapy treatment.