Tumor-targeting human L19IL2 monoclonal antibody-cytokine fusion protein in combination with DTIC in chemotherapy-naïve stage IV melanoma patients.

Abstract

8555 Background: L19IL2 is a tumor targeted immunocytokine constituted by a single chain Fragment variable (scFv) format directed against the extradomain-B of fibronectin and the human cytokine interleukin-2 (IL2). The recommended dose for monotherapy of advanced solid cancer patients was established to be 22.5 Mio IU L19IL2 on days 1, 3, and 5 of a 21-day cycle in a previous dose escalation study. Methods: Chemotherapy-naive patients with advanced melanoma and normal LDH were treated with L19IL2 as an i.v. infusion at a dosage of 22.5 Mio IU L19IL2 on days 1, 3 and 5 every 21 days in combination with DTIC 1,000 mg/m2 on day 1 for up to 6 treatment cycles. In the subsequent maintenance phase 22.5 Mio IU L19IL2 was applied biweekly, while DTIC was omitted. Tumor assessment was performed every 6 weeks. Data on safety and efficacy were evaluated using CTC v3.0 and RECIST criteria, respectively. Results: 22 patients were evaluable. Median age was 54.5 years (20-83). Treatment was well tolerated. There were no treatment related deaths; details of CTC evaluation will be presented. Median number of applied induction cycles was 6 (range 2-6), 6/22 patients entered the maintenance phase. Several RECIST-confirmed tumor responses and durable disease stabilizations were observed. Updated efficacy data will be available for presentation. Conclusions: L19IL2 at a dose of 22.5 Mio IU L19IL2 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. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Philogen Philogen, Bayer Philogen