Tesetaxel, an oral therapy against advanced gastric cancer, will soon undergo safety studies in humans.
Genta Incorporated has initiated a confirmatory Phase 2b trial of tesetaxel in patients with advanced gastric cancer, the company announced.
Tesetaxel is the company’s newest clinical-stage small molecule. As a late Phase 2 oncology product, tesetaxel is the leading oral taxane currently in clinical development.
Tesetaxel is a novel taxane that is administered by mouth as a capsule.
The drug was developed with a goal of maintaining the high antitumor activity while eliminating infusion reactions, reducing neuropathy, and increasing patient convenience.
The oral route also enables the development of novel schedules that may expand dosing options when tesetaxel is combined with other anticancer drugs (such as “all oral” chemotherapy programs).
Tesetaxel has demonstrated high activity against cell lines that were resistant to paclitaxel and docetaxel.
The trial is currently open to enrollment at Northwestern University, Chicago, IL, which will be joined by M.D. Anderson Cancer Center in Houston, TX and several additional sites, Genta said in a press release.
The new trial is designed to confirm the efficacy results observed in a preliminary Phase 2a study of tesetaxel as 2nd-line treatment of patients with advanced gastric cancer and will enroll patients who have progressed on a single 1st-line chemotherapy regimen.
Unlike conventional taxanes (paclitaxel [Taxol] or docetaxel [Taxotere]) that must be infused intravenously, tesetaxel is a capsule that is taken by mouth.
The dose for the new trial was determined from Genta’s recently completed dose-ranging and pharmacokinetic study, whose results have been accepted for presentation at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO) in June 2010.
“While several taxanes are approved as agents for 1st-line treatment of gastric cancer, most actual use in practice is as 2nd- or 3rd- line therapy due to their toxicity,” stated Dr. Raymond P. Warrell, Jr., Genta’s chairman and chief executive officer.
Taxanes (including paclitaxel and docetaxel) are the most widely used chemotherapy drug class in cancer medicine. However, these agents are associated with serious safety issues, particularly hypersensitivity reactions related to intravenous infusions that are occasionally fatal and that require careful premedication and observation. Other prominent side-effects of this drug class include myelosuppression (low blood counts) and peripheral neuropathy (disabling nerve damage).
As a late Phase 2 oncology product, tesetaxel has demonstrated anticancer activity in its initial clinical trials, and the drug has not been associated with the severe infusion reactions that are linked with other taxanes.
Moreover, unlike other oral taxanes that have been developed, nerve damage has not been a prominent side effect of tesetaxel.
Thus, the drug offers substantial opportunities to improve patient convenience, safety, and anticancer activity.
More than 280 patients worldwide have been treated with oral tesetaxel in Phase 1 and Phase 2 clinical trials.
In the Phase 2 study, 35 patients with advanced gastric cancer were treated with tesetaxel at doses ranging from 27 to 35 mg/m(2) once every three weeks.
All patients had received extensive prior treatment, having failed a combination regimen that included cisplatin plus 5-fluorouracil or capecitabine (Xeloda); Hoffmann-La Roche, Inc.).
All but 2 of these patients had also received a third chemotherapy drug along with this regimen. Final intent-to-treat analysis, including all patients enrolled in the study, showed that 5 patients achieved a partial response, 2 patients achieved a partial response unconfirmed by CT scan, and 14 patients achieved stable disease, for an overall major response rate of 20% and a disease-control rate of 60%.
Genta Incorporated is a biopharmaceutical company.
Two major programs anchor the company’s research platform: DNA/RNA-based Medicines and Small Molecules.
Genasense (oblimersen sodium) Injection is the Company’s lead compound from its DNA/RNA Medicines program.
Genasense is being developed as an agent that may enhance the effectiveness of anticancer therapy.
The company is currently collecting long-term followup data on durable response and overall survival from the recently completed randomized Phase 3 study of Genasense in patients with advanced melanoma (the AGENDA trial).
The company is also developing tesetaxel, a novel, orally absorbed, semi-synthetic taxane that is in the same class of drugs as paclitaxel and docetaxel.
In the U.S., Genta is exclusively marketing Ganite (gallium nitrate injection), which is indicated for treatment of symptomatic patients with cancer-related hypercalcemia that is resistant to hydration.
The company has developed proprietary oral formulations of the active ingredient in Ganite that are being evaluated as potential treatments for diseases associated with accelerated bone loss.