Abstract
16032 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). We carried out a phase I/II study in patients with solid tumors to assess safety, pharmacokinetics (PK), and early signs of activity of L19-IL2 monotherapy. Methods: L19-IL2 was administered as an i.v. infusion at doses of 5 (n=1), 10 (n=1), 22.5 (n=15) and 30 MioIU IL2 equivalent dose (n=1) on days 1, 3 and 5 every 21 days. Serum samples for PK assessment were collected on day 1, 3, 5 and 10 of each cycle. Flow cytometry (marker panels: T-cells CD71/CD8/CD3/CD4; NK/B-cells CD71/CD19/CD3/CD56; IL-2R-positive T-cells CD25/-CD122/CD3/CD4) and assessment of human antifusion protein antibodies to L19 (HAFA) were performed at screening and on day 1, 3, 5 and 10 of each cycle. Data on safety and activity were evaluated using CTC v3.0 and RECIST criteria, respectively. Results: Among the total 33 patients,18 had progressive advanced renal clear-cell carcinoma (RCC). Of these, 6 were treated in the phase I and a further 12 planned patients with RCC in the phase II part of the study. The 30 MiU IL2 equivalent dose was considered toxic. The 22.5 MiU dose was determined to be the MTD, which was selected to be the RD. Total/median number of cycles was 62/4 (2–6). Median age was 62 years (52–74). 15 of 18 patients had received prior systemic therapy. We recorded three grade 3 toxicities: 1 hypertension and hypoxia, 1 dyspnoea, and 1 renal failure. All other toxicities were moderate and transient. There were no treatment-related deaths. 16 patients are evaluable for response. We observed stable disease in 13 patients (81%) and progressive disease in 3 (19%) after six infusions of L19-IL2. Immunophenotyping analysis showed stimulation of NK cells being by far the strongest, followed by T4 cells and CTLs. Pharmacokinetic analysis and HAFA development data will be shown. Conclusions: The part II of this study confirms that L19-IL2 can be safely administered repeatedly in patients with advanced RCC at 22.5 Mio IU IL2 equivalent dose. Preliminary evaluation suggests clinical activity in these mostly pretreated patients. Toxicity was manageable and reversible. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Philogen, Philogen SPA Philogen SPA Bayer, Schering AG Philogen SPA
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