Abstract

9064 Background:L19-IL2 is a tumor targeted immunocytokine constituted by a single chain Fragment variable (scFv) format directed against the ED-B domain of fibronectin and the human cytokine interleukin-2 (IL2). The recommended dose (RD) for monotherapy of advanced solid cancer patients was established to be 22.5 Mio IU IL2 equivalent on day 1, 3, and 5 of a 21-day cycle. Here we report clinical results of the dose escalation part of a phase I/II study assessing L19-IL2 in combination with DTIC chemotherapy in metastatic melanoma patients. Methods: L19-IL2 was administered as an i.v. infusion at doses of 10 (n=3), 15 (n=3) and 22.5 MioIU IL2 equivalent dose (n=4) on days 1, 3 and 5 every 21 days in combination with DTIC 1000 mg/m2 on Day 1 for up to 6 treatment cycles. Serum samples for PK evaluation and induction of human antifusion antibodies to L19 (HAFA) were collected. Flow cytometry (T and NK/B cell panels) was performed. Data on safety and activity were evaluated using CTC v3.0 and RECIST criteria, respectively. Results: All 10 patients had progressive metastatic melanoma and the majority had already received prior systemic therapy. Median age at start of treatment was 62 years (52–74). There were no treatment related deaths and the treatment was well tolerated, details of CTC evaluation will be presented. The dose of 22.5 Mio IU day 1, 3, and 5 in combination with 1000 mg DTIC/m2 on day 1, repeated on day 22 was defined as the RD for up to 6 treatment cycles. 10 patients were evaluable for response. We observed 1 partial remission at the 15 Mio IL2 dose level after 4 treatment cycles. Immunophenotyping analysis showed transient stimulation of NK cells, T4 cells, and CTLs. Pharmacokinetic data will be presented. Conclusions: L19-IL2 at a dose of 22.5 Mio IU IL2 equivalent on days 1, 3, and 5 of a 3-weekly schedule can be safely combined with standard DTIC in metastatic melanoma patients. Toxicity was manageable and reversible. Preliminary evaluation suggests clinical activity of the L19IL2/DTIC regimen in metastatic melanoma patients. [Table: see text]

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