The goal of this observational study is to assess whether the IOpener® melanoma test can assist treating physicians in deciding which therapy is most suitable for patients with skin cancer (advanced cutaneous melanoma). For this purpose it is evaluated how well the IOpener-melanoma test can predict the result of cancer treatment in the treatment groups (standard of care anti-PD1 mono-therapy and standard of care anti-PD1 + anti-CTLA-4 therapy).

Participants will be asked to provide blood sample for analysis using IOpener®-melanoma test. Patients will receive regular medical care, the test results will not be used to make any treatment decisions. The patients will visit the clinic for treatment administration and clinical evaluation as part of their regular medical care.

Inclusion Criteria:

• First line treatment for unresectable stage III or IV cutaneous melanoma (according to AJCC version 8) with anti-PD1 monotherapy (nivolumab or pembrolizumab) or anti-PD1 + anti-CTL4A combination therapy (nivolumab and ipilimumab).
• Anticipated life expectancy exceeding 3 months.
• Aged 18 years or older and able to provide written informed consent.

Patients who have completed adjuvant treatment with anti-PD1 immunotherapy at least 6 months ago can be included.

Exclusion Criteria:

• Prior treatment for irresectable stage III or stage IV melanoma with BRAF/MEK inhibitors.
• Presence of progressive/symptomatic brain metastases at baseline.
• WHO performance score ≥ 2.
• Adjuvant treatment with anti-PD1 immunotherapy received within the last 6 months.
• Patients undergoing experimental treatments or therapies.
• Presence of any medical or other condition that in the opinion of the investigator(s) would preclude the participation in a clinical study.
• Unwillingness or inability to comply with study and follow-up procedures.

Patients with advanced-stage melanoma who will receive standard-of-care treatment with immune checkpoint inhibitors (ICIs).