Genta Incorporated, a biopharmaceutical company, has enrolled its first patient to a new randomized trial of tesetaxel as initial chemotherapy for women with advanced or recurrent breast cancer. This trial will be conducted approximately at 15 sites in the US and Western Europe.

The trial -- a randomized, three-arm, phase II b study that is expected to accrue approximately 220 patients. Accrual is projected to take approximately 12 months, with approximately 12 months of followup. Tesetaxel is the leading oral taxane in clinical development.

The trial will enroll women who have not previously received chemotherapy for metastatic or recurrent disease. Eligible patients who are HER2-negative (including so-called “triple negative” patients) may have received adjuvant chemotherapy and hormonal therapy. In this study, which compares two oral chemotherapy agents, patients will be randomized to one of three treatment groups: tesetaxel administered once every three weeks; tesetaxel administered once weekly for three consecutive weeks; or capecitabine (Xeloda; Hoffmann La Roche, Inc.) administered twice per day for 14 consecutive days. The primary endpoint of the trial is overall response rate; secondary endpoints include progression-free survival and safety.

“Our preliminary results suggest that tesetaxel may compare favorably with capecitabine across a number of parameters, including response, safety, convenience, and compliance,” said Dr Loretta M Itri, president and chief medical officer, Genta. “Genta has now completed two, non-randomized, phase II a studies comprised of more than 80 patients. The company has been engaged in extended discussions with regulatory authorities in the US and EU regarding potential registration strategies for tesetaxel in breast cancer. We believe this new study will provide a firm basis for a phase III trial design as first-line chemotherapy in this patient population.”

Two phase II a studies have explored the activity and safety of tesetaxel in patients with breast cancer who received the drug once every three weeks. One study evaluated patients who had progressed on 1st-line chemotherapy that had included an anthracycline. Thirteen of 34 patients (38) achieved a major objective response, and 11 patients achieved stable disease, for a disease control rate of 70 per cent. A second, confirmatory trial evaluated tesetaxel as 1st-line chemotherapy for locally advanced or metastatic HER2-negative breast cancer (as described above). In results that will be presented next week at the annual meeting of the American Society of Clinical Oncology (ASCO), 20 of 44 patients (45 per cent) achieved major objective responses with a disease-control rate of 82 per cent.

In both studies, tesetaxel was generally well-tolerated. Neutropenia was the most common Grade three-four adverse event. Consistent with prior studies, no hypersensitivity reactions were observed.