Merck, known as MSD outside the United States and Canada, (NYSE: MRK) and Endocyte, Inc. (NASDAQ: ECYT) today announced the online publication of results from the randomized Phase II PRECEDENT trial for vintafolide (MK-8109/EC145), an investigational folate small molecule drug conjugate (SMDC), in the Journal of Clinical Oncology (JCO), the official journal of the American Society of Clinical Oncology. These trial results are the basis for the vintafolide regulatory application currently under review with the European Medicines Agency for the treatment of folate-receptor positive platinum-resistant ovarian cancer in combination with pegylated liposomal doxorubicin (PLD). Enrollment is ongoing in the pivotal Phase III PROCEED clinical trial with vintafolide, along with investigational companion imaging agent etarfolatide (EC20), in platinum-resistant ovarian cancer (Clinicaltrials.gov NCT01170650).
As reported in JCO online, results from the Phase II PRECEDENT trial showed that administration of vintafolide plus pegylated liposomal doxorubicin (PLD) versus PLD alone in women with platinum-resistant ovarian cancer resulted in a median progression-free survival (PFS) of 5.0 months compared to 2.7 months for those treated with PLD alone (HR=0.63; 95% CI 0.41--0.96; p=0.031) in the intent-to-treat (ITT) population. Those patients shown to have folate receptor-positive tumors, as defined by all selected target lesions being folate receptor-positive (FR%100) using the investigational folate receptor-targeted companion diagnostic imaging agent etarfolatide, demonstrated greater benefit, as measured by PFS, from treatment with vintafolide plus PLD versus PLD alone. Median PFS benefit in these patients was 5.5 months compared to 1.5 months for PLD alone (HR=0.38; 95% CI 0.17--0.85; p=0.013). Etarfolatide is being developed by Endocyte as a non-invasive method to identify tumors that express the folate receptor.
"The combination of vintafolide plus PLD demonstrated significant improvement in progression-free survival over standard treatment in women with folate receptor-positive platinum-resistant ovarian cancer," said R. Wendel Naumann, M.D., Associate Director, Gynecologic Oncology, Carolinas HealthCare System's Levine Cancer Institute, Charlotte, N.C., and corresponding author of the publication. "Targeting the folate receptor, which is expressed on the majority of epithelial ovarian cancers, is a potentially promising strategy, especially when combined with a companion diagnostic that is designed to identify patients who are most likely to respond to the treatment, a hallmark of personalized medicine."
The Phase II PRECEDENT trial was an international, multi-center, randomized study of 149 women with platinum-resistant ovarian cancer. Patients were randomized to receive vintafolide plus PLD or PLD alone at a standard dose, until disease progression or death. The primary endpoint of the study was PFS. Secondary endpoints included response rate and overall survival (OS). In the ITT population, no difference was observed in overall survival>
The combination of vintafolide and PLD was generally well tolerated, and no drug-related mortality or statistically significant difference in the incidence of drug-related serious treatment-emergent adverse events (TEAEs) was observed.
In the vintafolide and PLD arm vs. PLD arm, anemia, neutropenia and thrombocytopenia were reported in 16.6% vs. 10.4%, 19.1% vs. 10.4%, and 2.7% vs. 3.0% of all cycles, respectively.
Stomatitis and palmar-plantar erythrodysesthesia (hand-foot syndrome) occurred in 16.6% vs. 22.8%, and 19.1% vs.15.8% of cycles, respectively.
The frequency of fatigue was similar between arms, 15.8% of vintafolide and PLD arm cycles, and 14.9% of PLD arm cycles.