The results from the randomized phase II PRECEDENT trial for Vintafolide, an investigational folate small molecule drug conjugate ( SMDC ), were published in the Journal of Clinical Oncology ( JCO ), the official journal of the American Society of Clinical Oncology ( ASCO ).
These trial results are the basis for the Vintafolide regulatory application under review with the European Medicines Agency ( EMA ) for the treatment of folate-receptor positive Platinum-resistant ovarian cancer in combination with pegylated liposomal Doxorubicin ( PLD ).
The results from PRECEDENT trial have showen that administration of Vintafolide plus pegylated liposomal Doxorubicin versus pegylated liposomal Doxorubicin alone in women with Platinum-resistant ovarian cancer resulted in a median progression-free survival of 5.0 months compared to 2.7 months for those treated with PLD alone ( hazarad ratio, HR=0.63; p=0.031 ) in the intent-to-treat ( ITT ) population.
Those patients have 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 progression-free survival, from treatment with Vintafolide plus pegylated liposomal Doxorubicin versus PLD alone.
Median progression-free survival benefit in these patients was 5.5 months compared to 1.5 months for PLD alone ( HR=0.38; p=0.013 ).
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 pegylated liposomal Doxorubicin or PLD alone at a standard dose, until disease progression or death.
The primary endpoint of the study was progression-free survival. Secondary endpoints included response rate and overall survival.
In the ITT population, no difference was observed in overall survival ( HR=1.010; p=0.957 ).
The combination of Vintafolide and pegylated liposomal Doxorubicin 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 pegylated liposomal Doxorubicin arm versus 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% vs15.8% of cycles, respectively.
The frequency of fatigue was similar between arms, 15.8% of Vintafolide and pegylated liposomal Doxorubicin arm cycles, and 14.9% of PLD arm cycles.
Vintafolide is an investigational proprietary, injectable, folate SMDC consisting of folate ( vitamin B9 ) linked to a potent vinca alkaloid chemotherapy agent, Desacetylvinblastine hydrazide ( DAVLBH ).
Vintafolide is designed to target the chemotherapy agent to rapidly growing cancer cells that actively take up folate via the folate receptor. The folate receptor is expressed in a wide variety of cancers including ovarian cancer.
Etarfolatide is an investigational folate receptor-targeted companion diagnostic imaging agent that is being developed as a non-invasive method to identify tumors that express the folate receptor. These tumors are the molecular target of Endocyte's folate receptor-targeted therapeutic compounds such as Vintafolide. Folic acid is used with Etarfolatide for the enhancement of image quality.
In 2013, it is estimated that there will be 22,240 new cases of ovarian cancer in the United States and over 40,000 new cases in the European Union.
Ovarian cancer is one of the most lethal cancers of the female reproductive system. Overall, approximately 80 percent of patients relapse after first-line Platinum-based chemotherapy. This type of cancer recurs within six months of completion with a Platinum-containing regimen, the standard of care for ovarian cancer.
Based on the phase II PRECEDENT trial data, an estimated 80% of Platinum-resistant ovarian cancer patients have been found to have folate receptor-positive disease as assessed by Etarfolatide scanning, and approximately 40% express the receptor, as detected by Etarfolatide, in all of their target tumor lesions. ( Xagena )
Source: Endocyte, 2013