Genta Incorporated announced that the company has initiated a new phase 2b clinical trial of tesetaxel as 1st-line chemotherapy for women with metastatic breast cancer.  Tesetaxel is the leading oral taxane currently in clinical development.  The new trial will be conducted at Memorial Sloan-Kettering Cancer Center, New York, NY and at the Accelerated Community Oncology Research Network (ACORN) based in Memphis, TN.

The new trial is designed to confirm and extend the efficacy and safety results observed in a preliminary Phase 2a study of tesetaxel as 2nd-line treatment of patients with advanced breast cancer (see results below).  The new study includes women with Her2-negative breast cancer who have developed progressive disease after primary surgery but who have not previously received chemotherapy for metastatic disease.  Patients who received adjuvant post-operative chemotherapy (that may have included a taxane) are also eligible if they have been disease-free for at least 12 months since the last dose of chemotherapy.

The primary endpoint of the study is percent overall response.  Secondary endpoints include response duration, disease control at 3 months, percent progression-free survival (PFS) at 6 months, durable response > 6 months, and time-to-progression (TTP). A total of 25 patients are expected to be accrued, and enrollment should be completed in 2011.

Unlike conventional taxanes (paclitaxel [Taxol] or docetaxel [Taxotere]) that must be infused intravenously, tesetaxel is a capsule that is taken by mouth.  Compared with standard taxanes, clinical and preclinical data show that tesetaxel: Eliminates serious (occasional fatal) hypersensitivity reactions;  Eliminates requirements for premedication (e.g., steroids, antihistamines, etc.);  Reduces damage to peripheral nerves;  Is not cross-resistant with standard taxanes;  Offers flexible and convenient dosing for patients

A phase 2a, open-label, single arm, multi-center study evaluated the efficacy and safety of tesetaxel in 2 patient cohorts who received doses of 27 mg/m2 or 35 mg/m2 administered once every 3 weeks.  All patients had previously been treated and had progressed on chemotherapy that had included a minimum of 4 cycles of an anthracycline-containing regimen.  Thirty-four patients were enrolled in this trial, and 32 were evaluable for response.  Intent-to-treat analysis on all patients showed 13 patients (38%) achieved a partial response and 10 patients had stable disease for a disease control rate of 68%.  Neutropenia was the dose-limiting adverse effect.

In an ongoing trial, 8 patients with advanced breast cancer have been treated with tesetaxel once every 3 weeks after having progressed 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 prolonged stable disease while receiving oral tesetaxel (range, 14+ to 23+ treatment cycles).  Despite this extended therapy, no clinically significant neuropathy (nerve damage) has been observed in these patients.

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 premedication and careful observation.  Other prominent side-effects of this drug class include myelosuppression (low blood counts) and peripheral neuropathy (disabling nerve damage).

Tesetaxel is a novel taxane that is administered by mouth as a capsule.  The drug was developed with a goal of maintaining antitumour 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).  In experimental models, tesetaxel has demonstrated high activity against tumors that are resistant to paclitaxel and docetaxel.

Genta Incorporated is a biopharmaceutical company with a diversified product portfolio that is focused on delivering innovative products for the treatment of patients with cancer.  The company is developing tesetaxel, a novel, orally absorbed taxane that is in the same class of drugs as paclitaxel and docetaxel.