EC-145, a folate-targeted Vinca alkaloid conjugate for the potential treatment of folate receptor-expressing cancers

EC-145, under development by Endocyte, is a conjugate composed of desacetylvinblastine monohydrazide linked through a peptide spacer to the targeting moiety folic acid, for the potential treatment of folate receptor-overexpressing tumors, in particular ovarian and lung cancers. The structure of EC-145 was designed to achieve selective and optimal release of the drug. In vitro studies demonstrate that EC-145 selectively binds to cells that overexpress the FR, causing cell death in at nanomolar concentrations after only a short exposure. Experiments in mouse tumor xenograft models have confirmed the potency of EC-145 and the curative effects has been confirmed on an aggressive lymphoma model. In dose-finding phase I/II clinical trials in patients with advanced ovarian and endometrial cancers, and others with advanced non-small-cell lung cancer, adverse events, though moderate, were reported: fatigue, decreased gastrointestinal motility and peripheral sensory neuropathy. Preliminary reports using EC-145 as third- to fourth-line treatment in patients with advanced ovarian cancer demonstrated better disease control than second- or third-line Doxil®. Coadministration of EC-145 and Doxil® produced a statistically significant increase in progression-free survival over standard therapy in patients with platinum-resistant ovarian cancer. Phase III trials are expected to confirm these promising results.