Clinical Research Directory

Inclusion Criteria: * Histologically confirmed metastatic melanoma with radiologically verified brain metastasis * Need for systemic steroid treatment (prednisolone \> 10 mg daily; dexamethasone \> 1.6 mg daily, hydrocortisone \> 40 mg daily or equivalent) due to brain metastasis * At least one measurable lesion according to RECIST version 1.1 guidelines * Evaluable intracranial disease * 18 years of age or older * Performance status 0-2 * Able to undergo MRI with gadolinium contrast agent * Adequate hematological and organ function * No significant toxicity from previous cancer treatments (CTC\<1) * Women of childbearing potential: Negative serum pregnancy test and must use effective contraception. This applies from screening and until 6 months after treatment. Birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch are all considered effective contraceptives * Men with female partner of childbearing potential must use effective contraception from screening and until 6 months after treatment. Effective contraceptives are as described above for the female partner. In addition documented vasectomy and sterility or double barrier contraception are considered effective contraceptives * Signed statement of consent after receiving oral and written study information. * Willingness to participate in the planned treatment and follow-up and capable of handling toxicities. * For arm E specifically: Tumor cells must harbor BRAF mutation. Exclusion Criteria: * Another malignancy or concurrent malignancy unless disease-free for 3 years * Ocular melanoma * Neurological symptoms from brain metastases present at baseline despite steroid treatment, unless symptoms are related to prior surgery * Known hypersensitivity to one of the active drugs or excipients * Acute or chronic infections with HIV or hepatitis * Any medical condition that will interfere with patient compliance or safety * Prior treatment with anti-PD-1/PD-L1/PD-L2/CTLA-4 antibodies in the metastatic setting * Prior systemic treatment with anti-PD-1/PD-L1/PD-L2/CTLA-4 antibodies in the adjuvant setting, unless completed more than 6 months before enrolment in this study * Simultaneous treatment with other experimental drugs or other anti-cancer drugs * Pregnant or breastfeeding females. * For arm E specifically: Prior treatment with BRAF/MEK inhibitors.