• All the criteria listed in the following need to be met before patient inclusion.

∙ Histologically confirmed inoperable or metastatic melanoma (stage IIIc or IV).

‣ Progressive disease after standard treatment with PD-1 check-point inhibition or combination of aforementioned with CTLA-4 check-point inhibition.

‣ Age: 18 - 75 years at time of signed Informed consent.

‣ ECOG performance status of ≤ 1 (Appendix 2).

‣ Is fit for tumor resection and has at least one lesion (\> 1 cm3) available for surgical resection for manufacture of TIL.

‣ At least one measurable parameter in accordance with RECIST 1.1 -criteria (excluding lesion to be resected).

‣ LVEF assessment with documented LVEF ≥50% by either TTE (transthoracic echocardiography) or MUGA (multigated acquisition scan).

‣ Sufficient organ function, including:

⁃ Absolute neutrophil count (ANC) ≥ 1.500 /µl

• Leucocyte count ≥ lower normal limit

• Platelets ≥ 100.000 /µl and \<700.000 /µl

• Hemoglobin ≥ 6.0 mmol/l

• eGFR \> 70 ml/min\*

• S-bilirubin ≤ 1.5 times upper normal limit (Exception: Subjects with liver metastasis ≤ 2.5 × ULN)

• ASAT/ALAT ≤ 2.5 times upper normal limit (Exception: Subjects with liver metastasis ≤ 5.0 × ULN)

• Alkaline phosphatase ≤ 5 times upper normal limit

• Lactate dehydrogenase ≤ 5 times upper normal limit

• Sufficient coagulation: APPT\<40 and INR\<1.5

• \* In selected cases it can be decided to include a patient with an eGFR \< 70 ml/min with the use of a reduced dose of chemotherapy.

• 9\. Signed statement of consent after receiving oral and written study information 10. Willingness to participate in the planned controls and capable of handling toxicities.

• 11\. Subject must receive T-cell therapy as the next therapy following tumor resection, unless bridging therapy is administered:

⁃ Bridging therapy is discouraged. However, if in the opinion of the Investigator, the subject requires immediate therapy after tumor resection, the subject may receive bridging therapy for the period during which the subject is awaiting the manufacture of TIL-infusion product. Bridging therapy may be a continuation of the therapy the subject was receiving prior to tumor resection or may be a new therapy.

⁃ Following this bridging therapy, the subject must adhere to the mandatory washout periods (exclusion criterion 1) and must continue to have measurable disease prior to receiving T-cell therapy.

‣ 12\. Age and Reproductive Status:

⁃ Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test AND must agree to use an effective method of contraception starting at the first dose of chemotherapy for at least 12 months. WOCBP must also agree to refrain from egg donation, storage, or banking during these same time periods. The following are considered safe methods of contraception:

• Hormonal anticonception (birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch)

• Intrauterine device

• Surgical sterilization

• Surgical sterilization of male partner with verification of no sperm after the procedure

• Menopause (for more than 12 months) o Male subjects must be surgically sterile or agree to use a double-barrier contraception method or abstain from sexual activity with an WOCBP starting at the first dose of chemotherapy and for 6 months thereafter. Male subjects must also agree to refrain from sperm donation, storage, or banking.