TNFalpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 During TIL Treatment of Advanced Melanoma

Inclusion Criteria: * Signed and dated informed consent before any trial-related activities. * Male or female, between 18-75 years of age (both included). * Pathologically confirmed previously treated refractory or recurrent stage 3-4 melanoma, which cannot be treated with curative intent with available therapies. * At least one prior line of medical treatment is required (for example checkpoint inhibitors, kinase inhibitors, interleukin-2). Multiple prior therapies (e.g. surgery, checkpoint inhibitors, kinase inhibitors, interleukin-2, interferon, chemotherapy, radiation) are allowed. * A \> 9 mm tumor (in diameter, typically a minimum of 1 cm3 in volume) without signs of necrosis must be available for biopsy/operation to enable growing of TILs. * At least one additional tumor (\>14 mm in diameter) must be available for injections and biopsies for correlative analyses. The disease burden must be measurable, but does not need to fulfil RECIST 1.1. * Eligible for adoptive T-cell therapy with tumor infiltrating lymphocytes Adequate hepatic, cardiac and renal functions as following: 1. Platelets \> 75 000/mm3 2. Haemoglobin ≥ 100 g/L. 3. AST and ALT \< 3 x ULN. 4. GFR \>60 ml/min (Cockcroft-Gault formula). 5. Leukocytes (WBC) \> 3,0 6. Bilirubin \<1.5 x ULN * Men and women must be willing to use adequate forms of contraception from screening, during the trial, and for a minimum of 90 days after end of treatment, in accordance with the following: * Women of childbearing potential: Barrier contraceptive method (i.e. condom) must be used in addition to one of the following methods: Intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections). * Women not of childbearing potential: Barrier contraceptive method (i.e. condom) must be used. * Men: Barrier contraceptive method (i.e. condom) must be used. * Demonstrated WHO performance score of 0-1 at screening. * Life expectancy time longer than 3 months. * Capable of understanding and complying with parameters as outlined in the protocol. * BRAF negative or positive. Exclusion Criteria: * Use of immunosuppressive medications (corticosteroids or drugs used in treatment of autoimmune disease). Exempted are the following which can be allowed at screening and during the trial: replacement corticosteroids if e.g. the patient has adrenal insufficiency after prior immunotherapy; pulmonal and topical treatments; up to 20 mg of prednisone/prednisolone. * History of another active invasive cancer as judged by the investigator within the past 3 years except basalioma. * Treated with any anti-cancer therapy for melanoma 30 days prior to enrolment. Anti-cancer therapy for melanoma is defined as anti-cancer agents (immunotherapy, signal-transduction inhibitors \[e.g. BRAF and MEK inhibitors\], cytotoxic chemotherapy), radiotherapy and investigational agents. An investigational agent is any drug or therapy that is currently not approved for use in humans. * Uncontrolled cardiac or vascular diseases. * History of heart attack or cerebral stroke within the previous 12 months before screening or is not recovered from an older heart attack or cerebral stroke. * LDH value \> 3 x ULN. * History of hepatic dysfunction, hepatitis or HIV. * History of coagulation disorder. * Any other disease which prevent participation in the opinion of the investigator. * Female patients who are pregnant, breastfeeding or intends to become pregnant. * Untreated brain metastases. Treated brain metastases which have not progressed in 3 months prior to screening are allowed. * Previously treated with any oncolytic adenovirus that was administered intratumorally. * Previously treated with adoptive cell therapy. * Allergy to TILT-123, TIL, or ingredients present in the investigational medicinal products. * Administered an investigational medicinal product or device in another clinical trial within 30 days prior to screening