Clinical Study Phase II of L19IL2 in Combination With Dacarbazine in Patients With Metastatic Melanoma

This Phase II clinical study is an open-label, multicenter study of L19IL2 in combination with Dacarbazine in patients with metastatic melanoma. The study is divided in two parts: a phase IIa part, designed to establish the recommended dose (RD) of L19IL2 when administered in combination with a fixed dose of Dacarbazine, as well as to determine the preliminary tolerability profile; the second phase IIb part evaluates the objective response rate (ORR) including a randomized study with a fixed dose of Dacarbazine with or without L19IL2, dosed at the RD determined in phase IIa.

Dose limiting toxicity will be assessed during the dose-escalation part of Phase IIa from day 1 through day 21 of the first cycle. Response will be measured using RECIST criteria every 6 weeks (after every 2 cycles of treatment). Patients with stable or responding disease at each assessment may receive additional treatment for a maximum of 6 cycles of induction. Patients with stable or responding disease after induction may receive L19IL2 (without dacarbazine) every 2 weeks as maintenance therapy. Tumor expression of ED-B FN and tumor uptake of L19IL2 and of Dacarbazine will be assessed via immunohistochemistry and/or other methods deemed appropriate on tumor tissue biopsies. Tumor biopsy will be performed on superficial accessible cutaneous and/or subcutaneous lesions only. Tumor biopsy will be considered optional and will not preclude patient entry on to study should the patient refuse. Pharmacokinetics of L19IL2, Dacarbazine and AIC will be assessed from serial blood samples using standard methods. Overall response rate, PFS, survival rate at 6 and 12 months, and overall survival time for all patients and separately for the patients in the Phase IIb part will be assessed using standard methods.