Clinical Trial Finder

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

The primary objective of the trial is to evaluate the safety of TILT-123. The approach has the potential to a) increase the efficacy of adoptive T-cell therapy, b) remove the need for toxic pre- and post-conditioning regimens, c) yield the combined anti-tumor benefits of armed oncolytic viruses and T-cell therapy. Dose escalation of TILT-123 injection will take place between cohorts not intra-patient and will be determined based on Dose Limiting Toxicities (DLTs).

Arms

Experimental: TILT-123

Patients will receive administrations of TILT-123. Patients will also receive Tumor Infiltrating Lymphocytes (TILs) during the treatment phase. Escalation to the next dose of TILT-123 level will occur when the safety data has been evaluated for all patients in the preceding dose level.

Interventions

Biological: - TILT-123

TNFalpha and IL-2 coding oncolytic adenovirus TILT-123