A Phase I/II Dose Escalation Study of the Tumor-targeting Human L19-IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Dacarbazine for Patients With Metastatic Melanoma

1. Pregnant or breastfeeding female

2. Primary ocular melanoma

3. Primary mucosal melanoma

4. Use of any investigational or other anti-cancer drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of DTIC and L19-IL2

5. Prior radiation to a target lesion, unless there has been clear progression of the lesion since radiotherapy

6. A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection

7. History or clinical evidence of brain metastases or leptomeningeal disease

8. Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix

9. Treatment with DTIC within 6 months before start of study

10. Treatment with Ipilimumab within 6 months before start of study

11. Hypersensitivity to DTIC

12. Concomitant use of drugs known to alter cardiac conduction

13. Chronic use of corticosteroids used in the management of cancer or non-cancer-related illness

14. Unstable or serious concurrent uncontrolled medical conditions

15. Inadequately controlled cardiac arrhythmias including atrial fibrillation

16. History of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris

17. Heart insufficiency \> grade II NYHA criteria

18. Uncontrolled hypertension

19. Ischemic peripheral vascular disease

20. Active infection or incomplete wound healing.

21. History or evidence of active autoimmune disease.

22. Known history of allergy to intravenously administered proteins/peptides/antibodies

23. History of organ allograft.or allogeneic peripheral blood progenitor cell or bone marrow transplantation

24. Major trauma including surgery within 4 weeks prior to entering the study.

25. Any underlying medical or psychiatric condition which in the opinion of the investigator will make administration of study drug hazardous or hinder the interpretation of study results (e.g. AE).

26. Melanoma patients with BRAF 600 E mutation who are amenable to receive approved treatments able to extend overall survival.

What this study is about