Vintafolide is a water-soluble derivative of FA and the vinca alkaloid desacetylvinblastine hydrazide (DAVLBH). DAVLBH is a vinca alkaloid that disrupts the formation of the mitotic spindle, thereby inhibiting cell division and inducing cell death. FA and DAVLBH are connected through a peptide spacer and a reducible, self-immolative disulfide-linker system to form vintafolide. The disulfide linker enables the release of DAVLBH inside the cancer cell after receptor-mediated endocytosis. This is an important feature because the high affinity of FA for the FR can result in ligands remaining attached to the FR for long periods of time, which can reduce the potency of folate-targeted chemotherapeutic agents. Vintafolide was designed specifically to bind to high-affinity FR present on the surfaces of cancer cells and to release its active component, DAVLBH, once it enters the endosome of the target cell. Preclinical studies have shown that vintafolide binds to the FRα with high affinity, it has highly potent and specific antitumor activity against FRα+ tumors. The efficacy and safety of vintafolide was first assessed in 2007 in a nonrandomized trial, and a number of phase II and III clinical studies have since been conducted in patients with ovarian and lung cancer. A Marketing Authorization Application (MAA) filing for vintafolide and etarfolatide for the treatment of patients with folate receptor-positive platinum-resistant ovarian cancer in combination with doxorubicin, pegylated liposomal doxorubicin (PLD), has been accepted by the European Medicines Agency. The drug received orphan drug status in Europe in March 2012. Merck & Co. acquired the development and marketing rights to Vintafolide from Endocyte in April 2012. On 16 May 2014 Endocyte Europe B.V. officially notified the Committee for Medicinal Products for Human Use (CHMP) that it has decided to withdraw its application for a marketing authorisation for Vynfinit (Vintafolide), for the treatment of ovarian cancer which has become resistant to platinum-based cancer treatment. The preliminary data from the study could not confirm the benefit of Vynfinit in ovarian cancer patients. Endocyte and Merck are still waiting for data from a phase IIb trial of vintafolide in non-small cell lung cancer (NSCLC), called TARGET, which met its primary PFS target and is due to generate overall survival data in the coming months.