Genta Incorporated announced updated interim results from a trial of tesetaxel used as 2nd-line treatment in patients with advanced gastric cancer. The ongoing trial is lead by the M.D. Anderson Cancer Center in Houston, TX. The data are presented in conjunction with the 2011 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL. Tesetaxel is the leading oral taxane in clinical development.
The trial is evaluating 3 cohorts of patients, all of whom had failed one prior chemotherapy regimen that must have included a platinum-containing compound (cisplatin, oxaliplatin, or carboplatin) and a fluoropyrimidine compound (5-fluorouracil [5-FU] or capecitabine [Xeloda(R); Hofmann LaRoche, Inc.]). Two patient cohorts were treated over a range of “fixed” (as opposed to “weight-based”) doses starting at 40-45 mg (Cohort 1) and 50-60 mg (Cohort 2), whereas Cohort 3 is using conventional weight-based dosing at the previously identified maximally tolerable dose (MTD).
In Cohorts 1 and 2, wide variations in body weight were observed. By example, body surface area (BSA, a composite measure of weight and height), of an average U.S. adult male approximates 1.7 m2, whereas the median BSA for patients in the first 2 study cohorts was 1.9 and 2.0 m2, respectively. One major response was observed in each of 11 and 13 patients in the first 2 cohorts, respectively; however, no episodes of > Grade 3 neutropenia were observed in either fixed-dose cohort,
suggesting that patients had been substantially under-dosed. Accordingly, Cohort 3 — which is currently open to accrual — employs a starting dose of 27 mg/m2 with escalation to 35 mg/m2 as tolerated in subsequent cycles. Data from this cohort are too early to evaluate.
Since overall survival (OS) is the primary endpoint in planned Phase 3 studies, an analysis of OS was conducted across all 3 cohorts in which any patient’s actual starting dose converted to a weight-based dose of > 26 mg/m2. With early followup, median OS in this group of 12 patients has not been reached, but currently exceeds a median of 7.5+ months.
For context, docetaxel (Taxotere(R); Sanofi, Inc.), a standard taxane, is approved for 1st-line treatment of gastric cancer. Four publications have reported the use of docetaxel as 2nd-line therapy in gastric cancer that show response rates ranging from 5% to 19% and median OS ranging from 3.5 to 8.4 months.
“While fixed dosing is convenient, the extremes of body weight observed in Western subjects has lead to substantial under-dosing, which in a global study would greatly increase the risk of under-treatment in seriously ill patients,” said Dr. Raymond P. Warrell, Jr., Genta’s Chief Executive Officer. “We now have a broadening experience in 1st and 2nd-line gastric cancer in both Western and Asian patients, both alone and in combination with other agents. Consequently, we have high confidence that safe and potentially effective dosing schedules of tesetaxel have been identified for these disparate populations.”
Date: June 3, 2011
Source: Genta Incorporated
Filed Under: Drug Discovery
