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Phase 3 Safety and Efficacy Trial Initiated for Oblimersen
AGENDA is designed to confirm the safety and efficacy of Genasense when combined with DTIC in patients who have not previously received chemotherapy. Genta's prior Phase 3 trial of this drug combination had shown that maximal benefit occurred in patients with normal baseline LDH, a blood enzyme that strongly correlates with outcome. The AGENDA study is limited to patients whose baseline LDH is less than 0.8 times the upper limit of normal. Analysis of that trial suggested that patients in this group achieved a significantly superior outcome (see table below).
"Genasense plus dacarbazine yielded superior results in a large randomized trial," said Dr. Agop Bedikian, Professor of Medicine at the M.D. Anderson Cancer Center, Houston, TX, who was the lead author on the publication of the previous Genasense trial. "Our center is pleased to have entered the first patient onto this important new study that seeks to extend those initial results using a biomarker to target novel therapies for melanoma."
"I am pleased that the European Association of Dermato-Oncology (EADO) will be the lead international cooperative group for AGENDA," said Dr. Claus Garbe, Professor of Dermatology and Head of the Division of Dermatooncology, Department of Dermatology, University Medical Center, Tubingen, Germany. "The use of LDH to pre-select individuals who are disproportionately likely to benefit represents an important innovation for patient treatment."
"The Genasense/dacarbazine trial represents our highest treatment priority for patients with advanced melanoma," said Dr. Sanjiv Agarwala, Chief of Medical Oncology, St. Luke's Hospital and Health Network, Allentown, PA. "With our center now actively enrolling patients, we look forward to rapidly confirming the exciting results previously obtained in individuals with low- normal LDH."
About Genasense in Advanced Melanoma
Genasense, Genta's lead anticancer drug, is a novel targeted therapy that blocks the production of Bcl-2, a protein that appears to be a fundamental cause of cancer treatment resistance. By knocking down Bcl-2, Genasense may enhance the effectiveness of chemotherapy in patients with advanced melanoma. Genasense in melanoma has Orphan Drug designations in Australia and the U.S., along with Fast Track designation in the U.S.
In its initial Phase 3 trial, Genta performed the largest randomized controlled trial that has ever been conducted in patients with advanced melanoma. In that trial, 771 patients were randomly assigned to receive chemotherapy with DTIC alone or in combination with Genasense. A scientific article that describes efficacy and safety results from this study can be accessed at: http://jco.ascopubs.org/lookup/resid/JCO.2006.06.0483v1?view=abstract&uritype=cgi.
In that trial, patients were also prospectively stratified according to blood levels LDH. Further analysis of this study suggested that maximum benefit accrued to patients whose LDH did not exceed 80% of the upper limit of normal for LDH. Efficacy results in this group of 274 patients (who are the focus of the new AGENDA trial) are displayed in the table below. The hazard ratios indicate that the addition of Genasense to DTIC was associated with a 42% reduction in the risk of disease progression and a 36% reduction in risk of death.
|Progression-free survival, median||3.6 mos.||1.6 mos.||0.58|
|Overall surivival, median||12.3 mos.||9.9 mos.||0.64||0.0009|
Malignant melanoma is the most deadly form of skin cancer. The incidence of this disease is increasing by approximately 4% annually in the US. In 2004, the American Cancer Society estimates more than 55,000 cases of malignant melanoma will have been diagnosed. Melanoma is the number one cause of cancer death in women aged 25 to 29. More information about melanoma can be accessed at the Melanoma Research Foundation. The EADO is an international cooperative group dedicated to promote, coordinate and improve clinical and laboratory research activities in skin cancer. Further information about the EADO can be viewed at: http://www.eado.org/.