Genasense Successful In Patients With Stage 4 Melanoma
Genta Incorporated announced preliminary results that have shown a high objective response rate in a pilot study that incorporates the Company's lead oncology product, Genasense (oblimersen sodium) Injection, in a chemotherapy program for patients with advanced melanoma. In this study, Genasense was used to potentially enhance the clinical activity of temozolomide, the most commonly used anticancer drug for melanoma, combined with Abraxane.
All 14 of the first cohort of patients accrued to this study had non-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 to Genasense plus chemotherapy in a recent randomized trial.) To date, 6 patients (43%) have achieved major objective responses: one with complete response (CR) after 6 cycles of treatment, and 5 with at least a partial response after only one treatment cycle. Three additional patients have maintained stable disease (SD) after at least three treatment cycles, for an overall clinical benefit response (CR+PR+SD) of 64%.
Laboratory studies showed that Genasense did not alter the expected pharmacokinetics of paclitaxel, and that clinical response was associated with alterations in Bcl-2, a protein that is the molecular target of Genasense. No dose-limiting toxicity was observed. The most commonly observed side-effects were 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 study showed that Genasense could be safely administered on a twice-weekly basis for 3 consecutive weeks at a dose of 900 mg/m2 infused intravenously (IV) over two hours. An amendment to the above pilot trial in melanoma is planned that will incorporate 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 Executive Officer. "Temozolomide is the active metabolite of dacarbazine (DTIC), which is the chemotherapy drug used in our ongoing Phase 3 AGENDA trial in patients with melanoma and low-normal LDH. We also plan that melanoma will be a target for our development program with tesetaxel, the Company's novel orally absorbed taxane, thus potentially affording patients a highly convenient treatment program for this intractable disease."