Abstract
e13054 Background: The human recombinant antibody L19 selectively binds to the angiogenesis-related and tumor stroma-associated antigen extradomain B (ED-B) fibronectin. 131I-L19SIP is being investigated in a clinical trial in pts with solid cancer to define the maximum tolerated dose for a single application. Methods: All pts had failed multiple therapies and had recurrent and progressive disease at enrollment. A tracer amount of 131I-L19SIP (185 MBq or 5 mCi) was administered for biodistribution and dosimetry evaluation. Whole-body, spot, and SPECT/CT images were acquired at different time points after 131I-L19SIP injection. Three cohorts of pts were scheduled to receive 4107 MBq/m2(111 mCi/m2), 5143 MBq/m2 (139 mCi/m2), and 6167 MBq/m2 (167 mCi/m2) of 131I-L19SIP. Post-therapy planar whole-body and SPECT/CT images were obtained 8–12 days post- administration of the therapeutic dose to confirm specific tumor targeting. Results: 12 pts (7 men, 5 women; mean age 58.1±7.2 yr) were enrolled: NSCLC (4), mesothelioma (3), thymoma (2), head and neck cancer (1), uveal melanoma (1), ovarian adenocarcinoma (1). Based on selective uptake into tumor lesions (lesion/background ratio ≥4) 10 pts were eligible for the therapeutic 131I-L19SIP dose and 7 pts have received treatment (2 pts excluded because of disease progression between the diagnostic and therapeutic phase; 1 pt awaiting therapy). No dose-limiting toxicity observed so far, with the first dose cohort closed and the second actively recruiting. Transient grade 1–4 thrombocytopenia and grade 2–4 lymphocytopenia were observed in all the cases between weeks 1 and 5, with spontaneous recovery; no other systemic or organ-specific toxicity was observed. Sequential [18F]FDG-PET/CT at 2 months after therapy demonstrated significant reduction in size and intensity of [18F]FDG uptake in 1 pt, stable disease in 5 pts, and progressive disease in 1 pt. Conclusions: Preliminary data indicate that ED-B fibronectin is a promising target for the antibody-based delivery of therapeutic agents in pts with solid cancer. A single 131I-L19SIP administration of up to 5143 MBq/m2 is well tolerated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Schering Pharma, Philogen SpA Philogen SpA Bayer Schering Pharma, Philogen SpA Philogen SpA Bayer Schering Pharma
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