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All 14 of the first cohort of patients accrued to this study hadnon-resectable stage 4 melanoma. None had previously received chemotherapy,and their baseline LDH did not exceed 1.1 times the upper limit of normal.(LDH is a tumor-derived blood marker that was shown to affect the response toGenasense plus chemotherapy in a recent randomized trial.) To date, 6patients (43%) have achieved major objective responses: one with completeresponse (CR) after 6 cycles of treatment, and 5 with at least a partialresponse after only one treatment cycle. Three additional patients havemaintained stable disease (SD) after at least three treatment cycles, for anoverall clinical benefit response (CR+PR+SD) of 64%.
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Laboratory studies showed that Genasense did not alter the expectedpharmacokinetics of paclitaxel, and that clinical response was associated withalterations in Bcl-2, a protein that is the molecular target of Genasense. Nodose-limiting toxicity was observed. The most commonly observed side-effectswere similar to those encountered with the chemotherapy drugs used alone,including leukopenia, thrombocytopenia, and hair loss.
In a related study accepted for publication at ASCO, a Phase 1 studyshowed that Genasense could be safely administered on a twice-weekly basis for3 consecutive weeks at a dose of 900 mg/m2 infused intravenously (IV) over twohours. An amendment to the above pilot trial in melanoma is planned that willincorporate this more convenient treatment schedule.
"While preliminary, we believe these initial data are very promising,"said Dr. Raymond P. Warrell, Jr., Genta's Chairman and Chief ExecutiveOfficer. "Temozolomide is the active metabolite of dacarbazine (DTIC), whichis the chemotherapy drug used in our ongoing Phase 3 AGENDA trial in patientswith melanoma and low-normal LDH. We also plan that melanoma will be a targetfor our development program with tesetaxel, the Company's novel orallyabsorbed taxane, thus potentially affording patients a highly convenienttreatment program for this intractable disease."
About AGENDA
AGENDA is a Phase 3, randomized, double-blind, placebo-controlled trialthat is intended to support global registration of Genasense for patients withadvanced melanoma. The study is designed to confirm certain safety andefficacy results from Genta's prior randomized trial of Genasense combinedwith dacarbazine (DTIC) in patients identified by a biomarker who have notpreviously received chemotherapy. The co-primary endpoints of AGENDA areprogression-free survival and overall survival.
About Melanoma
Malignant melanoma is the most deadly form of skin cancer. The incidenceof this disease is increasing by approximately 4% annually in the US. In2004, the American Cancer Society estimates more than 55,000 cases ofmalignant melanoma will have been diagnosed. Melanoma is the number one causeof cancer death in women aged 25 to 29. More information about melanoma canbe accessed at the Melanoma Research Foundation: http://www.melanoma.org.The EADO is an international cooperative group dedicated to promote,coordinate and impro
