7582 Background: NGR-hTNF is a VTA exploiting a tumor-homing peptide (NGR) that selectively binds to an aminopeptidase N (CD13) overexpressed on tumor blood vessels. In preclinical models, NGR-hTNF has shown potent anti-vascular and antitumor activity, both at low and at high doses. Methods: Patients with advanced MPM were treated with a low-dose of NGR-hTNF given intravenously at 0.8 μg/m2 as 1-hour infusion every 3 weeks (q3w). This phase II trial had a 2-stage design with 16 and a total of 27 patients to be enrolled after first and second stage, respectively. Primary endpoint was progression-free survival (PFS) with restaging performed q6w according to MPM-modified RECIST criteria. Results: From May 2007 to January 2008, forty-three patients with radiologically-documented progressive disease after a pemetrexed-based regimen were evaluated over 167 cycles (range, 1 to 17). Patient characteristics were: median age 64 years (range, 54 to 80); male/female 27/16; epithelial/non-epithelial histology 34/9; PS 0/1/2 24/10/9; EORTC score good/poor 34/9. Main grade 1–2 toxicity was chills (71%), transiently occurring after the first infusions. Only one grade 3 treatment-related toxicity was observed. One patient (2%) had a partial response lasting 7.1+ months and 17 patients (40%) maintained stable disease for a median duration of 4.4 months (range, 1.3 to 12.4+ months). The median and 3-month PFS were 2.8 months and 43%, respectively, whereas the median and 1-year overall survival were 11.6 months and 48%, respectively. In an additional 14 patients treated at same dose with a weekly schedule, there was any suggestion of toxicity exacerbation. In this cohort, the PFS rate at 6 months was 36%, with 7 patients (50%) experiencing stable disease for a median duration of 6.9 months (range, 2.4 to 9.3+ months). Conclusions: NGR-hTNF 0.8 μg/m2 weekly is well tolerated, showing prolonged disease control in previously treated MPM patients, and will be further developed in this setting. [Table: see text]