The goal of this clinical trial is to investigate the safety and feasibility of neoadjuvant immunotherapy for patients with high-risk uveal melanoma. The main question is:

- Is neoadjuvant treatment with nivolumab and ipilimumab safe and feasible for patientt with high-riks uveal melanoma? In addition pathological response, distant metastases-free survival, overall survival and immunological changes in the tumor microenviroenment after therapy will be assesed.

Inclusion Criteria:

• Age ≥ 18 ≤ 80
• The patient is able to read and understand Danish.
• Primary, localized and treatment-naive uveal melanoma planned for enucleation (high risk/T3-T4) and available for transvitreal biopsies. The initial diagnosis of uveal melanoma is based on ophthalmologic and clinical findings.
• ECOG performance status of 0 or 1 (appendix 2)
• The patient meets the following haematological and biochemical criteria at time of screening: a) AST and ALT ≤2,5 X ULN, b) Serum total bilirubin ≤1,5 X ULN or direct bilirubin ≤ ULN for patient with total bilirubin level > 1,5 ULN, c) Serum creatinine ≤1,5 X ULN, d) ANC (Absolute Neutrophil Count) ≥1,000/mcL, e) Platelets ≥ 75,000 /mcL, f) Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
• Signed statement of consent after receiving oral and written study information
• Willingness to participate in the planned treatment and follow-up schedule
• For women of childbearing potential (WOCBP) a negative serum pregnancy test at time of screening and the use of highly effective contraception is required. This applies from screening and until 6 months after treatment.

The following is considered highly effective methods of contraception: 1. Combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal or transdermal), 2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) 3. Intrauterine device (IUD) 4. intrauterine hormone-releasing system (IUS) 5. Bilateral tubal occlusion, 6. Vasectomised partner provided that the vasectomy is confirmed successful, 7. Sexual abstinence defined as refraining from heterosexual intercourse. WOCBP must also agree to refrain from egg donation, storage, or banking during these same time periods.

- Men with female partner of childbearing potential must: 1. Use a condom during sexual intercourse from screening and until 6 months after treatment. 2.

Ensure that their partner uses a highly effective method of contraception (as described above) 3. Agree to refrain from sperm donation, storage, or banking

Exclusion criteria

• A history of prior malignancies. Patients treated for another malignancy can participate if they are without signs of disease for a minimum of 2 years after treatment. Subjects with curatively treated ductal carcinoma in situ (DCIS or LCIS) breast cancer for which they are taking hormonal therapy is acceptable. Resectable squamous or basal cell carcinoma of the skin is acceptable.
• Requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive drugs within the last 3 weeks prior to screening
• The patient has any condition that will interfere with patient compliance or safety (including but not limited to psychiatric or substance abuse disorders)
• The patient is pregnant or breastfeeding
• The patient has an active infection requiring systemic therapy
• Significant medical disorder according to investigator; e.g severe asthma or chronic obstructive lung disease, dysregulated heart disease or dysregulated diabetes mellitus.
• Concurrent treatment with other experimental drugs
• Any significant active autoimmune disease
• Severe allergy or anaphylactic reactions earlier in life
• Known hypersensitivity to one of the active drugs or one or more of the excipients.