TIL and Anti-PD1 in Metastatic Melanoma

Inclusion Criteria: 1. Age ≥ 18 years 2. Histologically or cytologically proven metastatic skin melanoma 3. Melanoma must be at one of the following AJCC 2009 stages: * Unresectable (or residual) regional metastatic melanoma, i.e. in terms of AJCC 2009 classification unresectable stage III melanoma, or * Stage IV melanoma, i.e. distant metastatic disease (any T, any N, M1a, M1b or M1c), and normal LDH * Patients have failed on standard treatment options 4. Patients with brain metastases have to be neurologically stable for at least 2 months and should not use dexamethasone 5. Presence of measurable progressive disease according to RECIST version 1.1 6. Expected survival of at least 3 months 7. WHO performance status ≤1 8. Within the last 2 weeks prior to study day 1, vital laboratory parameters should be within normal range, except for the following laboratory parameters, which should be within the ranges specified: Lab Parameter Range Hemoglobin ≥ 6,0 mmol/l Granulocytes ≥ 1,500/µl Lymphocytes ≥ 700/µl Platelets ≥ 100,000/µl Creatinine clearance ≥ 60 min/ml Serum bilirubin ≤ 40 µmol/l ASAT and ALAT ≤ 5 x the normal upper limit LDH ≤ 2 x the normal upper limit 9. Viral tests must be performed at least 30 days before surgery: * Negative for HIV type 1/2, HTLV and TPHA * No HBV (hepatitis B virus) antigen or antibodies against HBc in the serum * No antibodies against HCV (hepatitis C virus) in the serum 10. Able and willing to give valid written informed consent. 11. Progressive disease on prior treatment with f.e. BRAF-inhibitors, MEK-inhibitors or immunotherapy, including anti-PD1 treatment. Systemic therapy must have been discontinued for at least four weeks before start of study treatment. Exclusion Criteria: 1. Patients with brain metastases who are neurologically unstable and/or use dexamethasone 2. Clinically significant heart disease (NYHA Class III or IV) 3. Other serious acute or chronic illnesses, e.g. active infections requiring antibiotics, bleeding disorders, or other conditions requiring concurrent medications not allowed during this study 4. Active immunodeficiency disease, autoimmune disease requiring immune suppressive drugs or autoimmune adverse events following treatment with checkpoint inhibitors. Vitiligo is not an exclusion criterion 5. Subjects with a condition requiring systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any immunosuppressive therapy within 14 days prior to planned date for first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids, and adrenal replacement therapy are allowed. 6. Other malignancy within 2 years prior to entry into the study, except for treated non-melanoma skin cancer and in situ cervical carcinoma 7. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study 8. Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the associated with the participation, study drug administration, or would impair the ability of the patient to receive protocol therapy 9. Lack of availability for follow-up assessments 10. Pregnancy or breastfeeding 11. Known allergy to penicillin or streptomycin (used during the culturing of T cells)