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.