Genta Incorporated (OTCBB: GETA.OB) announced today the presentation of results from two dose-ranging trials of tesetaxel, the Company’s novel oral tubulin inhibitor. Results showed potential activity in patients with taxane-resistant cancers, along with no evidence of hypersensitivity and a low incidence of nerve damage, both of which are common side effects of standard taxanes. Tesetaxel — a late Phase 2 oncology product — is the leading oral taxane in clinical development. The data were presented on Sunday at the 2010 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL.
“Taxanes have been effectively used in ‘dose-dense’ chemotherapy programs, and these schedules appear to be compellingly superior in women with advanced breast cancer”
In these studies, two dosing schedules were evaluated: a single dose administered once every 3 weeks; and one dose administered once weekly for 3 consecutive weeks, followed by one week off treatment. Evaluation of the initial schedule was completed with accrual of 27 patients. A single oral 40 mg dose was established for ongoing and future studies, with incremental escalation depending on individual tolerance. Accrual to the weekly schedule is ongoing, and final determination of a maximally tolerable weekly dose is pending. Pharmacokinetic studies have not shown significant drug accumulation on either dosing schedule. As in prior studies, neutropenia was the dose-limiting adverse event. No hypersensitivity reactions were observed.
These trials were also the first studies to evaluate tesetaxel in patients who had progressed on other taxane-containing regimens. Tesetaxel was previously tested in women with 2nd and 3rd-line breast cancer (see below), and the drug showed clinical activity in patients who had not previously received a taxane. In the current trial, 8 patients with advanced breast cancer were treated with tesetaxel after progression on a median of 5 prior chemotherapy regimens. Seven of the 8 patients had progressed after receiving either 1 or 2 taxane-containing regimens. Four patients (50%), 3 of whom had progressed on docetaxel or paclitaxel, achieved and are currently maintaining prolonged stable disease while receiving oral tesetaxel (range, 9+ to 18+ treatment cycles). Other diseases associated with extended stable disease included one patient each with melanoma (12 cycles), nasopharyngeal cancer (10 cycles), and non small cell lung cancer (10 cycles). Despite this extended therapy, no clinically significant neuropathy (nerve damage) has been observed on either schedule.
“Taxanes have been effectively used in ‘dose-dense’ chemotherapy programs, and these schedules appear to be compellingly superior in women with advanced breast cancer,” said Dr. Raymond P. Warrell, Jr., Genta’s Chief Executive Officer. “Our prior Phase 2a study in patients with 2nd-and 3rd-line breast cancer yielded a 38% major objective response rate. The new clinical results suggest confirmation of preclinical data that tesetaxel can overcome standard mechanisms of clinically acquired resistance to standard taxanes. The lack of hypersensitivity reactions and significant nerve damage — coupled with dosing flexibility, elimination of requirements for premedications, and a high level of patient convenience — offer important advantages for tesetaxel that we are exploring in ongoing clinical trials.”