The chemotherapeutic component of vintafolide is a type of vinca alkaloid taken up only by cancer cells. For the treatment of patients with platinum-resistant ovarian cancer, vintafolide is combined with Doxil® (pegylated liposomal doxorubicin). The firm says the drug combination increases the likelihood of killing cancer cells, since treating tumors with more than one drug makes it harder for cancer cells to develop resistance.
“Vintafolide’s toxicity profile gives us great flexibility to combine it with other drugs,” says Ellis. Many other drugs cannot be combined because their additive toxicities are too dangerous for clinical use.
Vintafolide was tested in an international, multicenter Phase II trial of 149 women with platinum-resistant ovarian cancer. Patients received vintafolide plus Doxil or Doxil alone until either disease progression or death. The primary endpoint was progression-free survival. Patients taking vintafolide plus Doxil had a median progression free survival of 5 months, compared to 2.7 months for patients receiving Doxil alone.
However, in patients who tested the most positive for a specific folate receptor, the delayed progression-free survival increased from 1.5 months to 5.5, or 260%. “If you don’t have the receptor, the drug doesn’t work as well. That’s a remarkable result,” says Ellis. A Phase III trial of vintafolide in platinum-resistant ovarian cancer is under way, as well as a Phase II/III trial of vintafolide in non-small-cell lung cancer.
The folate receptor that predicted patient response to vintafolide was identified with etarfolatide, the companion molecular imaging agent designed to screen patients who are likely to respond. “Our development strategy is to start with a diagnostic to assess quickly and easily which tissues and organs a chemotherapy drug will target,” says Ellis.
More importantly, tumors in patients are assessed to see if they contain the folate receptor. Tumor cells that highly express the folate receptor are more likely to be killed by the targeted therapy.
The EMA granted vintafolide the equivalence of orphan drug status in March 2012, because the drug shows exciting early results in patient populations that do not have effective treatments. “There’s probably no other cancer more in need of an effective treatment than platinum-resistant ovarian cancer,” says Ellis.