A phase I safety and PK study of the novel vascular targeting agent (VTA), Exherin, in patients with refractory solid tumors stratified according to N-cadherin expression

Abstract

3078 Background: Exherin is a novel angiolytic VTA which specifically targets existing tumor vessels. Exherin is a cyclic pentapeptide (CHAVC) which competitively inhibits N-cadherin mediated endothelial cell, pericyte and tumor cell binding. Exherin caused highly-specific tumor angiolysis in multiple murine and xenograft tumor models. We report here preliminary data from the first human safety and pharmacokinetics (PK) study on Exherin. Methods: 13 patients (pts) with refractory solid tumors received 24 cycles of Exherin by bolus injection at 4 dose levels from 50 to 225 mg/m2to define the toxicities (AE) and maximum tolerated dose (MTD) for patients with N-cadherin positive or negative tumors. Dynamic MRI was performed in cohorts 3 to 5 where feasible to assess for changes in tumor perfusion and intra-tumoral hemorrhage. Results: Dose escalation has proceeded without reaching MTD. AE > grade 2 considered possibly drug related include tumor pain (n=3) and 1 coronary syndrome in a patient with a previousl...