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A dose confirmation and signal-generating study of the immunocytokine L19-IL2 in combination with dacarbazine in patients with metastatic melanoma.

2531 Background: L19-IL2 is a tumor-targeting immunocytokine composed of an antibody fragment specific to the EDB domain of fibronectin, a marker of tumor angiogenesis, and of human interleukin-2 (IL2). L19-IL2 is able to selectively deliver IL2 to tumor tissues exploiting the expression of EDB on newly formed blood vessels. The recommended monotherapy dose (RD) of 22.5 MioIU IL2 equivalents (day 1, 3, and 5) of L19-IL2 was defined earlier. In this study, we investigated L19-IL2 in combination with dacarbazine in patients with metastatic melanoma, assessing safety, tolerability, and activity.


METHODS
The study consists of a dose confirmation part, during which 10 patients with metastatic melanoma were enrolled, followed by a fixed dose part, during which 22 chemo-naive metastatic melanoma patients were treated at the RD. Patients received intravenous infusions of L19-IL2 (10, 15 and 22.5 MioIU during dose confirmation, and 22.5 MioIU in the fixed dose part of the study) on day 1, 3 and 5 in combination with 1 g/m2 of dacarbazine on day 1, every 21 days. Up to 6 treatment cycles were given, followed by a maintenance phase during which only L19-IL2 was applied biweekly. Tumor assessment was performed every 6 weeks. Data on safety and efficacy were evaluated using CTC v3.0 and RECIST criteria, respectively.


RESULTS
Median age was 55 years (30-83). The RD was confirmed to be 22.5 MioIU. Toxicity was manageable and reversible, with no treatment related deaths. Twenty-nine out of 32 patients were evaluable for efficacy according to RECIST. In a centralized radiology analysis, 8/29 patients achieved RECIST-confirmed objective responses, including a complete response, still ongoing 21 months after start of treatment. The one-year survival rate was 61.5% and median overall survival was 14.4 months for all patients treated at RD.


CONCLUSIONS
L19-IL2 combined with dacarbazine, both at RD, can be safely and repeatedly administered to patients with metastatic melanoma, and showed promising signs of clinical activity. To further evaluate this combination therapy for metastatic melanoma, a controlled randomized phase II trial is ongoing.