Genta Incorporated has announced that the Company will conduct a new randomized controlled Phase 3 trial of its lead anticancer product, Genasense (oblimersen sodium) Injection, in patients with advanced melanoma.
The Company has sought scientific advice on final aspects of the trial design from regulatory authorities in Europe and the U.S. The Company is actively recruiting experienced investigative sites in Europe, Australia, and North and South America, and expects to initiate patient enrollment during the summer of 2007.
The trial is designed to expand evidence for the safety and efficacy of Genasense combined with dacarbazine for patients who have not previously been treated with chemotherapy. The study will prospectively target patients using a biomarker that identified patients who derived maximal benefit in a preceding trial of Genasense, including significant increases in overall and progression-free survival. Genta expects to enroll approximately 300 subjects in this trial. Genasense in melanoma has been designated an Orphan Drug in Australia and the U.S., and the drug has Fast Track designation in the U.S.
"As the lead investigative site in the prior trial, we were highly gratified by seeing results that exceeded those from any other randomized study in patients with advanced melanoma," commented Dr. Agop Y. Bedikian, Professor of Medicine, M.D. Anderson Cancer Center. "We are very pleased to participate in this new trial of Genasense combined with chemotherapy in a biomarker-targeted population."
"The announcement of this trial reaffirms our long-standing commitment to patients afflicted with advanced melanoma," said Dr. Raymond P. Warrell, Jr., Genta's Chief Executive Officer. "The existing Genasense data derive from the largest study ever conducted in this condition. Use of a standard biomarker (serum lactate dehydrogenase [LDH]) to target specific patients should facilitate completion of this study in a considerably smaller population, and if positive, worldwide regulatory submissions."
"At the Melanoma Research Foundation, our mission is to support research that discovers and rapidly translates effective treatments for patients with melanoma," commented Linda Pilkington, Executive Director. "Advanced melanoma is a deadly disease with no satisfactory treatment options available for patients. We are extremely supportive of this new trial that offers the potential to benefit patients."
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 resistance to cancer treatment. By knocking down Bcl-2 in cancer cells, Genasense may enhance the effectiveness of chemotherapy in patients with advanced melanoma. In its initial trial, Genta performed the largest randomized controlled trial that has ever been conducted in patients with advanced melanoma. A summary of the long-term follow up data from that study, on which the design of the new trial is based, appears below.
In this trial, 771 patients from 139 sites in 9 countries were randomly assigned to receive chemotherapy with dacarbazine (DTIC) alone or in combination with Genasense. The paper includes data from a prospectively defined analysis that evaluated 24-months of minimum follow-up on all patients. Unless otherwise noted, these results were based on an intent-to- treat analysis:
Endpoint Genasense/DTIC DTIC P Overall response 13.5% 7.5% 0.007 Complete response 2.8% 0.8% 0.03 Durable response 7.3% 3.6% 0.03 Progression-free survival, median 2.6 mos. 1.6 mos. 0.0007 Overall survival, median 9.0 mos. 7.8 mos. 0.077
Prior to randomization, patients were prospectively stratified according to certain risk factors, including elevated blood levels of an enzyme known as LDH - a factor that previous clinical studies have shown is strongly associated with poor outcome. The final analysis has shown that LDH was the sole stratification factor significantly associated with a treatment interaction. When this treatment effect was evaluated, the efficacy of Genasense was significantly superior for all major efficacy outcomes in patients who had normal LDH at baseline, a group that comprised approximately two-thirds of patients in the trial (N=508). In this group, the following efficacy results were observed:
Endpoint Genasense/DTIC DTIC P Overall response 17.2% 9.3% 0.009 Complete response 3.4% 0.8% 0.04 Durable response 9.6% 4.0% 0.014 Progression-free survival, median 3.1 mos. 1.6 mos. 0.0007 Overall survival, median 11.4 mos. 9.7 mos. 0.018 Safety
The most frequent serious adverse events that occurred in greater than or equal to 5% of patients were fever and disease progression (6.2% vs. 2.8%, and 5.1% vs. 4.7%, respectively, for Genasense/DTIC compared with DTIC alone). The most frequent Grade 3 or 4 adverse events that occurred in greater than or equal to 5% of patients were neutropenia (21.3% vs. 12.5%), thrombocytopenia (15.9% vs. 6.4%), leukopenia (7.5% vs. 3.9%), anemia (7.3% vs. 4.7%), and nausea (6.7% vs. 2.5%). Although there was an increase in discontinuations due to adverse events in the Genasense arm (19% vs. 11%), there was no difference in the number of fatal, treatment-emergent adverse events (i.e., events that lead to a death on study or within 30 days from last study treatment). An abstract of the scientific article that describes these results can be accessed at: http://www.jco.org/cgi/content/abstract/JCO.2006.06.0483v1 .