Vintafolide is a water-soluble molecule designed to target the toxic vinblastine to the folate receptor, overexpressed in the case of certain cancers, including the ovarian one.
DAVLBH is a derivative of the generated by plants vinblastine - vinca alkaloid, a chemical analogue of vincristine. Its action on the cells involves inhibition of assembling of microtubules, hindering the proper formation of the mitotic spindle and the kinetochore, necessary for mitosis process. Depending on the concentration it can suppress microtubule dynamics or polymer mass. Vintafolide utilizes the method of the Folate targeting to deliver the drug to cancer cells.
The Phase II PRECEDENT trial involved the international study of 149 women with platinum-resistant ovarian cancer. Patients were receiving vintafolide plus pegylated liposomal doxorubicin (PLD) or PLD alone at a standard dose until the disease progression or death. The combination was well tolerated, no drug-related mortality was observed and the median progression-free survival (PFS) increased from 2.7 months to 5.0 months comparing to the PLD-alone treatment in the intent-to-treat (ITT) population.
MK-8109 is investigated in companion with diagnostic imaging agent etarfolatide (EC20), folate-receptor targeted. It allows identification of patients expressing the folate receptor and possibly responding to the vintafolide therapy.
Currently, it is being evaluated in a Phase III PROCEED clinical trial for platinum-resistant ovarian cancer. Moreover, Phase IIb TARGET trial for non-small cell lung cancer (NSCLC) is being executed. There are going to be performed also Phase II tests of vintafolide in folate receptor-positive triple negative breast cancer soon. Vintafolide along with PLD is under review of European Medicines Agency (EMA) and has already been granted orphan drug status in Europe in March 2012.
by Piotr Kołata
2018-02-24 19:03:54 +0100
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