Intratumoral Administration of L19IL2/L19TNF

Inclusion Criteria:

* Histologically confirmed malignant melanoma of the skin in clinical stage III or stage IV M1a
* Presence of measurable and injectable cutaneous and/or subcutaneous lesions
* Males or females, age ≥ 18 years
* ECOG Performance Status/WHO Performance Status ≤ 2
* Life expectancy of at least 12 weeks
* Absolute neutrophil count \> 1.5 x 10\^9/L
* Hemoglobin \> 9.0 g/dL
* Platelets \> 100 x 10\^9/L
* Total bilirubin ≤ 30 μmol/L (or ≤ 2.0 mg/dl)
* ALT and AST ≤ 2.5 x the upper limit of normal (ULN)
* Serum creatinine \< 1.5 x ULN
* LDH serum level within normal range
* All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.02) Grade ≤ 1 unless otherwise specified above
* Negative serum pregnancy test (for women of child-bearing potential only) at screening
* If of childbearing potential, agreement to use adequate contraceptive methods (e.g., oral contraceptives, condoms, or other adequate barrier controls, intrauterine contraceptive devices, or sterilization) beginning at the screening visit and continuing until 3 months following last treatment with study drug.
* Able to provide written Informed Consent
* Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

* Uveal melanoma and mucosal melanoma
* Evidence of visceral metastases and/or active brain metastases at screening
* Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (TA, Tis \& Ti) or any cancer curatively treated \< 5 years prior to study entry
* History of HIV infection or infectious hepatitis B or C
* Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
* History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe autoimmune disease
* History of organ allograft or stem cell transplantation
* Recovery from major trauma including surgery within 4 weeks prior to administration of study treatment.
* Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies.
* Breast feeding female
* Anti-tumor therapy within 4 weeks of the administration of study treatment (except small surgery).
* Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before administration of study treatment.
* Planned administration of growth factors or immunomodulatory agents within 7 days before the administration of study treatment
* Patients in need of systemic treatment for rapidly progressive systemic disease.
* Patient requires or is taking corticosteroids or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion.
* Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.