abstract: Vintafolide: a first-in-class small molecule drug conjugate targeting folate receptor positive tumors

 

AACR Presentation Abstract

Abstract Number:	5502
Presentation Title:	Vintafolide: a first-in-class small molecule drug conjugate targeting folate receptor positive tumors
Presentation Time:	Wednesday, Apr 10, 2013, 8:00 AM -12:00 PM
Location:	Hall A-C, Poster Section 37
Poster Board Number:	12
Author Block:	Christopher P. Leamon1, Joseph A. Reddy1, Brian B. Haines2, Isabelle Dussault2. 1Endocyte Inc, West Lafayette, IN; 2Merck & Co Inc, Boston, MA
Abstract Body:	Targeted anti-cancer therapies offer the promise of more efficacious treatments with fewer side effects. Vintafolide (also known as EC145) is a rationally designed small molecule drug conjugate consisting of one folic acid moiety which serves as a stable high affinity binding ligand for the folate receptor, and one vinca alkaloid unit (desacetylvinblastine hydrazide; DAVLBH), which serves as the cytotoxic warhead. Vintafolide is thus designed to target cancer cells by binding with high affinity to folate receptors which are more commonly expressed at high levels on tumors compared to normal tissues. Vintafolide is internalized following binding to folate receptors and is cleaved in endosomes to release DAVLBH. Like all vinca alkaloids, DAVLBH binds to tubulin and disrupts the mitotic spindle which leads to cell death. Pre-clinical in vitro and in vivo experiments show that vintafolide requires interaction with the folate receptor for its activity and that it is more efficacious and better tolerated than untargeted DAVLBH. Vintafolide is currently being investigated in clinical trials in ovarian (Phase III) and lung (Phase II) cancer patients who express folate receptors on their tumors as determined by the investigational companion imaging agent, etarfolatide. Etarfolatide is also a folate-based conjugate consisting of folic acid linked to a peptidic metal-chelating moiety labeled with 99mTechnetium. In a randomized Phase II study in patients with advanced ovarian cancer, patients treated with vintafolide had a significantly longer period of progression free survival compared with the control. This was driven by patients who were identified by etarfolatide as having tumors with functional folate receptors. Vintafolide and etarfolatide is the first pair of therapeutic and non-invasive, imaging diagnostic to be co-developed for the treatment of cancer.